ascorbic-acid and Ascorbic-Acid-Deficiency

The maternal diet during pregnancy is a key determinant of offspring health. Early studies have linked poor maternal nutrition during gestation with a propensity for the development of chronic conditions in offspring. These conditions include cardiovascular disease, type 2 diabetes and even compromised mental health. While multiple factors may contribute to these outcomes, disturbed epigenetic programming during early development is one potential biological mechanism. The epigenome is programmed primarily in utero, and during this time, the developing fetus is highly susceptible to environmental factors such as nutritional insults. During neurodevelopment, epigenetic programming coordinates the formation of primitive central nervous system structures, neurogenesis, and neuroplasticity. Dysregulated epigenetic programming has been implicated in the aetiology of several neurodevelopmental disorders such as Tatton-Brown-Rahman syndrome. Accordingly, there is great interest in determining how maternal nutrient availability in pregnancy might affect the epigenetic status of offspring, and how such influences may present phenotypically. In recent years, a number of epigenetic enzymes that are active during embryonic development have been found to require vitamin C as a cofactor. These enzymes include the ten-eleven translocation methylcytosine dioxygenases (TETs) and the Jumonji C domain-containing histone lysine demethylases that catalyse the oxidative removal of methyl groups on cytosines and histone lysine residues, respectively. These enzymes are integral to epigenetic regulation and have fundamental roles in cellular differentiation, the maintenance of pluripotency and development. The dependence of these enzymes on vitamin C for optimal catalytic activity illustrates a potentially critical contribution of the nutrient during mammalian development. These insights also highlight a potential risk associated with vitamin C insufficiency during pregnancy. The link between vitamin C insufficiency and development is particularly apparent in the context of neurodevelopment and high vitamin C concentrations in the brain are indicative of important functional requirements in this organ. Accordingly, this review considers the evidence for the potential impact of maternal vitamin C status on neurodevelopmental epigenetics.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Epigenesis, Genetic; Female; Gene Expression Regulation, Developmental; Humans; Maternal Nutritional Physiological Phenomena; Neurodevelopmental Disorders; Neurogenesis; Pregnancy

Scurvy is a well-known clinical condition caused by vitamin C deficiency. Although considered a rare disease in high-income countries, it has been recently increasingly reported in children, especially in those with abnormal dietary habits, mental or physical disabilities. We performed an extensive review of the literature analyzing studies published in the last 20 years focusing on clinical features, differential diagnosis and diagnostic delay. Fifteen articles were selected, collectively reporting a total of 166 children. Because of the wide clinical spectrum (musculoskeletal complaints and/or mucocutaneous lesions or systemic symptoms), scurvy can mimic several conditions, including autoimmune diseases, infections, and neoplasia. In addition, frequent findings such as normal nutritional status, anemia or elevated inflammatory markers may guide clinicians towards the abovementioned misdiagnoses. Scurvy should be considered in patients presenting with musculoskeletal complaints, not only in those with risk factors but also in healthy children. A focused dietary history and a careful physical examination, assessing other signs of vitamin C deficiency, are mandatory in these patients. When suspected, the dosage of serum vitamin C is the diagnostic gold standard; furthermore, imaging studies, performed by an expert radiologist, can reveal the typical features of scurvy. Only early diagnosis can avoid unnecessary investigations and potentially fatal complications of the disease.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Delayed Diagnosis; Diagnosis, Differential; Humans; Scurvy

Ascorbate has many biological activities that involve fundamental cellular functions such as gene expression, differentiation, and redox homeostasis. Biochemically, it serves as a cofactor for a large family of dioxygenases (> 60 members) which control transcription, formation of extracellular matrix, and epigenetic processes of histone and DNA demethylation. Ascorbate is also a major antioxidant acting as a very effective scavenger of primary reactive oxygen species. Reduction of Fe(III) by ascorbate is important for cellular uptake of iron via DMT1. Cell culture models are extensively used in toxicology and pharmacology for mechanistic studies of nutrients, drugs and other xenobiotics. High-throughput screens in vitro, such as a large-scale Tox21 program in the US, offers opportunities to assess hazardous properties of a vast and growing number of industrial chemicals. However, cells in typical cultures are severely deficient in ascorbate, raising concerns about their ability to accurately recapitulate toxic and other responses in vivo. Scarcity of ascorbate and a frequently unrecognized use of media with its thiol substitute alters stress sensitivity of cells in different directions. Remediation of ascorbate deficiency in tissue culture restores the physiological state of many cellular processes and it should improve a currently limited toxicity predictability of in vitro bioassays.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Cells, Cultured; High-Throughput Screening Assays; Humans; In Vitro Techniques; Toxicity Tests

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence-scurvy. The only clinically well-documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is relatively safe, but caution should be given to the administration of high doses, which can cause overt side effects in some susceptible patients (e.g., oxalate renal stones). Lastly, analytical methods for its determination with advantages and pitfalls are also discussed in this review.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Kinetics

Severe and long-term vitamin C deficiency can lead to fatal scurvy, which is fortunately considered rare today. However, a moderate state of vitamin C (vitC) deficiency (hypovitaminosis C)-defined as a plasma concentration below 23 μM-is estimated to affect up to 10% of the population in the Western world, albeit clinical hallmarks in addition to scurvy have not been linked to vitC deficiency. The brain maintains a high vitC content and uniquely high levels during deficiency, supporting vitC's importance in the brain. Actions include both antioxidant and co-factor functions, rendering vitamin C deficiency likely to affect several targets in the brain, and it could be particularly significant during development where a high cellular metabolism and an immature antioxidant system might increase sensitivity. However, investigations of a non-scorbutic state of vitC deficiency and effects on the developing young brain are scarce. This narrative review provides a comprehensive overview of the complex mechanisms that regulate vitC homeostasis in vivo and in the brain in particular. Functions of vitC in the brain and the potential consequences of deficiency during brain development are highlighted, based primarily on findings from experimental animal models. Perspectives for future investigations of vitC are outlined.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Carnitine; Fatty Acids, Unsaturated; Homeostasis; Humans; Mice, Knockout; Models, Animal; Neuroglia; Neurons; Scurvy; Sodium-Coupled Vitamin C Transporters

Vitamins and minerals are essential to humans as they play essential roles in a variety of basic metabolic pathways that support fundamental cellular functions. In particular, their involvement in energy-yielding metabolism, DNA synthesis, oxygen transport, and neuronal functions makes them critical for brain and muscular function. These, in turn, translate into effects on cognitive and psychological processes, including mental and physical fatigue. This review is focused on B vitamins (B1, B2, B3, B5, B6, B8, B9 and B12), vitamin C, iron, magnesium and zinc, which have recognized roles in these outcomes. It summarizes the biochemical bases and actions of these micronutrients at both the molecular and cellular levels and connects them with cognitive and psychological symptoms, as well as manifestations of fatigue that may occur when status or supplies of these micronutrients are not adequate.

Topics: Affect; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cognition; Cognition Disorders; Energy Metabolism; Fatigue; Humans; Iron; Magnesium; Minerals; Nutritional Status; Vitamin B Complex; Vitamin B Deficiency; Vitamins; Zinc

The administration of ascorbic acid (vitamin C) alone or in combination with thiamine (vitamin B1) and corticosteroids (VCTS) has recently been hypothesized to improve hemodynamics, end-organ function, and may even increase survival in critically ill patients. There are several clinical studies that have investigated the use of vitamin C alone or VCTS in patients with sepsis and septic shock or are ongoing. Some of these studies have demonstrated its safety and potential benefit in septic patients. However, many questions remain regarding the optimal dosing regimens and plasma concentrations, timing of administration, and adverse effects of vitamin C and thiamine. These questions exist because the bulk of research regarding the efficacy of vitamin C alone or in combination with thiamine and corticosteroids in sepsis is limited to a few randomized controlled trials, retrospective before-and-after studies, and case reports. Thus, although the underlying rationale and mechanistic pathways of vitamin C and thiamine in sepsis have been well described, the clinical impact of the VCTS regimen is complex and remains to be determined. This review aims to explore the current evidence and potential benefits and adverse effects of the VCTS regimen for the treatment of sepsis.

Topics: Adrenal Cortex Hormones; Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Protocols; Critical Illness; Dietary Supplements; Hemodynamics; Humans; Hydrocortisone; Intestines; Patient Safety; Randomized Controlled Trials as Topic; Retrospective Studies; Sepsis; Shock, Septic; Thiamine; Vitamins

Vitamin C deficiency may be more common than is generally assumed, and the association between vitamin C deficiency and adverse psychiatric effects has been known for centuries. This paper aims to systematically review the evidence base for the neuropsychiatric effects of vitamin C deficiency.. Relevant studies were identified via systematic literature review.. Nine studies of vitamin C deficiency, including subjects both with and without the associated physical manifestations of scurvy, were included in this review. Vitamin C deficiency, including scurvy, has been linked to depression and cognitive impairment. No effect on affective or non-affective psychosis was identified.. Disparate measurement techniques for vitamin C, and differing definitions of vitamin C deficiency were apparent, complicating comparisons between studies. However, there is evidence suggesting that vitamin C deficiency is related to adverse mood and cognitive effects. The vitamin C blood levels associated with depression and cognitive impairment are higher than those implicated in clinical manifestations of scurvy. While laboratory testing for ascorbic acid can be practically difficult, these findings nonetheless suggest that mental health clinicians should be alerted to the possibility of vitamin C deficiency in patients with depression or cognitive impairment. Vitamin C replacement is inexpensive and easy to deliver, although as of yet there are no outcome studies investigating the neuropsychiatric impact of vitamin C replacement in those who are deficient.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cognitive Dysfunction; Depression; Humans; Scurvy; Vitamins

A recent review of global vitamin C status has indicated a high prevalence of deficiency, particularly in low- and middle-income countries, as well as in specific subgroups within high-income countries. Here, we provide a narrative review of potential factors influencing vitamin C status globally. The in vivo status of vitamin C is primarily affected by dietary intake and supplement use, with those who supplement having a higher mean status and a lower prevalence of deficiency. Dietary intake can be influenced by cultural aspects such as traditional cooking practices and staple foods, with many staple foods, such as grains, contributing negligible vitamin C to the diet. Environmental factors can also affect vitamin C intake and status; these include geographic region, season, and climate, as well as pollution, the latter partly due to enhanced oxidative stress. Demographic factors such as sex, age, and race are known to affect vitamin C status, as do socioeconomic factors such as deprivation, education and social class, and institutionalization. Various health aspects can affect vitamin C status; these include body weight, pregnancy and lactation, genetic variants, smoking, and disease states, including severe infections as well as various noncommunicable diseases such as cardiovascular disease and cancer. Some of these factors have changed over time; therefore, we also explore if vitamin C status has shown temporal changes. Overall, there are numerous factors that can affect vitamin C status to different extents in various regions of the world. Many of these factors are not taken into consideration during the setting of global dietary intake recommendations for vitamin C.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cooking; Culture; Diet; Dietary Supplements; Environment; Female; Global Health; Health Status; Humans; Male; Nutritional Requirements; Nutritional Status; Pregnancy; Socioeconomic Factors

Vitamin C is an essential nutrient that must be obtained through the diet in adequate amounts to prevent hypovitaminosis C, deficiency and its consequences-including the potentially fatal deficiency disease scurvy. Global vitamin C status and prevalence of deficiency has not previously been reported, despite vitamin C's pleiotropic roles in both non-communicable and communicable disease. This review highlights the global literature on vitamin C status and the prevalence of hypovitaminosis C and deficiency. Related dietary intake is reported if assessed in the studies. Overall, the review illustrates the shortage of high quality epidemiological studies of vitamin C status in many countries, particularly low- and middle-income countries. The available evidence indicates that vitamin C hypovitaminosis and deficiency is common in low- and middle-income countries and not uncommon in high income settings. Further epidemiological studies are required to confirm these findings, to fully assess the extent of global vitamin C insufficiency, and to understand associations with a range of disease processes. Our findings suggest a need for interventions to prevent deficiency in a range of at risk groups and regions of the world.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Developed Countries; Developing Countries; Diet; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Pregnancy; Prevalence; Risk Factors; Young Adult

Vitamin C serves as a cofactor for Fe(II) and 2-oxoglutarate-dependent dioxygenases including TET family enzymes, which catalyze the oxidation of 5-methylcytosine into 5-hydroxymethylcytosine and further oxidize methylcytosines. Loss-of-function mutations in epigenetic regulators such as TET genes are prevalent in hematopoietic malignancies. Vitamin C deficiency is frequently observed in cancer patients. In this review, we discuss the role of vitamin C and TET proteins in cancer, with a focus on hematopoietic malignancies, T regulatory cells, and other immune system cells.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dioxygenases; Humans; Immunity; Ketoglutaric Acids; Leukopoiesis; Neoplasms; T-Lymphocytes, Regulatory

Recent research studies have shown that vitamin C (ascorbic acid) may affect bone mineral density and that a deficiency of ascorbic acid leads to the development of osteoporosis. Patients suffering from an inflammatory bowel disease are at a risk of low bone mineral density. It is vital to notice that patients with Crohn's disease and ulcerative colitis also are at risk of vitamin C deficiency which is due to factors such as reduced consumption of fresh vegetables and fruits, i.e., the main sources of ascorbic acid. Additionally, some patients follow diets which may provide an insufficient amount of vitamin C. Moreover, serum vitamin C level also is dependent on genetic factors, such as

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Bone Density; Colitis, Ulcerative; Crohn Disease; Diet; Female; Gastrointestinal Microbiome; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Inflammatory Bowel Diseases; Male; Osteoporosis; Risk Factors; Sodium-Coupled Vitamin C Transporters

There are limited proven therapies for COVID-19. Vitamin C's antioxidant, anti-inflammatory and immunomodulating effects make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19. This literature review focuses on vitamin C deficiency in respiratory infections, including COVID-19, and the mechanisms of action in infectious disease, including support of the stress response, its role in preventing and treating colds and pneumonia, and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8 g/day) may reduce the incidence and duration of respiratory infections and intravenous vitamin C (6-24 g/day) has been shown to reduce mortality, intensive care unit (ICU) and hospital stays, and time on mechanical ventilation for severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and the frequency of vitamin C deficiency in respiratory infections, it may be worthwhile testing patients' vitamin C status and treating them accordingly with intravenous administration within ICUs and oral administration in hospitalised persons with COVID-19.

Topics: Administration, Intravenous; Administration, Oral; Anti-Inflammatory Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Chemotherapy, Adjuvant; COVID-19; COVID-19 Drug Treatment; Critical Care; Hospitalization; Humans; Immunologic Factors; Intensive Care Units; Nutritional Status; Pandemics; Respiration, Artificial; Respiratory Tract Infections; SARS-CoV-2; Sepsis; Vitamins

The pharmacokinetics of vitamin C (vitC) is indeed complex. Regulated primarily by a family of saturable sodium dependent vitC transporters (SVCTs), the absorption and elimination are highly dose-dependent. Moreover, the tissue specific expression levels and subtypes of these SVCTs result in a compartmentalized distribution pattern with a diverse range of organ concentrations of vitC at homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. The homeostasis of vitC is influenced by several factors, including genetic polymorphisms and environmental and lifestyle factors such as smoking and diet, as well as diseases. Going from physiological to pharmacological doses, vitC pharmacokinetics change from zero to first order, rendering the precise calculation of dosing regimens in, for example, cancer and sepsis treatment possible. Unfortunately, the complex pharmacokinetics of vitC has often been overlooked in the design of intervention studies, giving rise to misinterpretations and erroneous conclusions. The present review outlines the diverse aspects of vitC pharmacokinetics and examines how they affect vitC homeostasis under a variety of conditions.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Diffusion; Female; Homeostasis; Humans; Intestinal Absorption; Nutritional Requirements; Pregnancy; Smoking; Sodium-Coupled Vitamin C Transporters; Tissue Distribution

Vitamin C exhibits interesting properties in the context of critical illness, with benefits described in neurologic, cardiovascular, renal, and hematologic systems, both in in vitro and in animal models. Through direct effects on bacterial replication, immunomodulation, and antioxidant reserve of the organism, vitamin C directly affects the pathophysiological process of sepsis, trauma, burn, and systemic inflammation. Even if several observational trials have linked vitamin C deficiency to worse outcomes, the evidence is not such as to provide us with a distinction between causality effects or simple epiphenomenon, and the current focus is on interventional trials. Pharmacokinetic data suggest that a minimal supplementation of 3 g/d intravenously is required to restore normal serum values in critically ill patients with known deficiency. According to these data, only five trials, including a retrospective analysis, studied pharmacologic dose: three as an antioxidant cocktail and two as monotherapy. The largest trial, conducted in 2002, reported reduced incidence of multiorgan failure and duration of mechanical ventilation. Recently a retrospective analysis reported impressive results after administration of vitamin C, thiamine, and hydrocortisone. The two most recent trials reported improved clinical outcomes, including improved mortality, but contained significant methodological limitations. A recent systematic review did not find clinical benefits with the most-studied low-dose oral supplementation, potentially because of suboptimal or insufficient repletion. Current guidelines do not support the administration of high-dose vitamin C in critically ill patients. Future larger trials are required to support any therapy, but the low cost and safety profile can justify supplementation in the meantime. Metabolomics study will further help understand biological effect.

Topics: Administration, Intravenous; Ascorbic Acid; Ascorbic Acid Deficiency; Critical Illness; Dietary Supplements; Humans; Severity of Illness Index; Treatment Outcome; Vitamins

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Topics: Acute Coronary Syndrome; Administration, Intravenous; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Reperfusion Injury; Time Factors; Vitamins

Hypovitaminosis C and vitamin C deficiency are very common in critically ill patients due to increased needs and decreased intake. Because vitamin C has pleiotropic functions, deficiency can aggravate the severity of illness and hamper recovery.. Vitamin C is a key circulating antioxidant with anti-inflammatory and immune-supporting effects, and a cofactor for important mono and dioxygenase enzymes. An increasing number of preclinical studies in trauma, ischemia/reperfusion, and sepsis models show that vitamin C administered at pharmacological doses attenuates oxidative stress and inflammation, and restores endothelial and organ function. Older studies showed less organ dysfunction when vitamin C was administered in repletion dose (2-3 g intravenous vitamin C/day). Recent small controlled studies using pharmacological doses (6-16 g/day) suggest that vitamin C reduces vasopressor support and organ dysfunction, and may even decrease mortality.. A short course of intravenous vitamin C in pharmacological dose seems a promising, well tolerated, and cheap adjuvant therapy to modulate the overwhelming oxidative stress in severe sepsis, trauma, and reperfusion after ischemia. Large randomized controlled trials are necessary to provide more evidence before wide-scale implementation can be recommended.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Critical Care; Critical Illness; Humans; Nutritional Requirements; Organ Dysfunction Scores; Oxidative Stress; Treatment Outcome

In the early literature, vitamin C deficiency was associated with pneumonia. After its identification, a number of studies investigated the effects of vitamin C on diverse infections. A total of 148 animal studies indicated that vitamin C may alleviate or prevent infections caused by bacteria, viruses, and protozoa. The most extensively studied human infection is the common cold. Vitamin C administration does not decrease the average incidence of colds in the general population, yet it halved the number of colds in physically active people. Regularly administered vitamin C has shortened the duration of colds, indicating a biological effect. However, the role of vitamin C in common cold treatment is unclear. Two controlled trials found a statistically significant dose-response, for the duration of common cold symptoms, with up to 6-8 g/day of vitamin C. Thus, the negative findings of some therapeutic common cold studies might be explained by the low doses of 3-4 g/day of vitamin C. Three controlled trials found that vitamin C prevented pneumonia. Two controlled trials found a treatment benefit of vitamin C for pneumonia patients. One controlled trial reported treatment benefits for tetanus patients. The effects of vitamin C against infections should be investigated further.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Common Cold; Humans; Pneumonia; Tetanus; Vitamins

The vitamin C deficiency disease scurvy is characterised by musculoskeletal pain and recent epidemiological evidence has indicated an association between suboptimal vitamin C status and spinal pain. Furthermore, accumulating evidence indicates that vitamin C administration can exhibit analgesic properties in some clinical conditions. The prevalence of hypovitaminosis C and vitamin C deficiency is high in various patient groups, such as surgical/trauma, infectious diseases and cancer patients. A number of recent clinical studies have shown that vitamin C administration to patients with chronic regional pain syndrome decreases their symptoms. Acute herpetic and post-herpetic neuralgia is also diminished with high dose vitamin C administration. Furthermore, cancer-related pain is decreased with high dose vitamin C, contributing to enhanced patient quality of life. A number of mechanisms have been proposed for vitamin C's analgesic properties. Herein we propose a novel analgesic mechanism for vitamin C; as a cofactor for the biosynthesis of amidated opioid peptides. It is well established that vitamin C participates in the amidation of peptides, through acting as a cofactor for peptidyl-glycine α-amidating monooxygenase, the only enzyme known to amidate the carboxy terminal residue of neuropeptides and peptide hormones. Support for our proposed mechanism comes from studies which show a decreased requirement for opioid analgesics in surgical and cancer patients administered high dose vitamin C. Overall, vitamin C appears to be a safe and effective adjunctive therapy for acute and chronic pain relief in specific patient groups.

Topics: Analgesics; Analgesics, Opioid; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Pain

Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons. It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system. Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. It is also needed for apoptosis and clearance of the spent neutrophils from sites of infection by macrophages, thereby decreasing necrosis/NETosis and potential tissue damage. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects. Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements. Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels (i.e., 100-200 mg/day), which optimize cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand.

Topics: Adaptive Immunity; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Communicable Diseases; Dietary Supplements; Humans; Immune System; Immunity, Innate; Leukocytes; Wound Healing

Randomised controlled trials (RCTs) in humans revealed contradictory results regarding the effect of vitamin C supplementation on blood lipids. We aimed to conduct a systematic review and meta-analysis of RCTs investigating the effect of vitamin C supplementation on total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides and to determine whether the effects are modified by the participants' or intervention characteristics.. Four databases (PubMed, Embase, Scopus and Cochrane Library) were searched from inception until August 2014 for RCTs supplementing adult participants with vitamin C for ≥ 2 weeks and reporting changes in blood lipids.. Overall, vitamin C supplementation did not change blood lipids concentration significantly. However, supplementation reduced total cholesterol in younger participants (≤52 years age) (-0.26 mmol/L, 95% CI: -0.45, -0.07) and LDL-C in healthy participants (-0.32 mmol/L, 95% CI: -0.57, -0.07). In diabetics, vitamin C supplementation reduced triglycerides significantly (-0.15 mmol/L, 95% CI: -0.30, -0.002) and increased HDL-C significantly (0.06 mmol/L, 95% CI: 0.02, 0.11). Meta-regression analyses showed the changes in total cholesterol (β: -0.24, CI: -0.36, -0.11) and in triglycerides (β: -0.17, CI: -0.30, -0.05) following vitamin C supplementation were greater in those with higher concentrations of these lipids at baseline. Greater increase in HDL-C was observed in participants with lower baseline plasma concentrations of vitamin C (β: -0.002, CI: -0.003, -0.0001).. Overall, vitamin C supplementation had no significant effect on lipid profile. However, subgroup and sensitivity analyses showed significant reductions in blood lipids following supplementation in sub-populations with dyslipidaemia or low vitamin C status at baseline. PROSPERO Database registration: CRD42014013487, http://www.crd.york.ac.uk/prospero/.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Agents; Cardiovascular Diseases; Dyslipidemias; Humans; Hyperlipidemias; Hypolipidemic Agents; Oxidative Stress; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk

Recent advances have uncovered a previously unknown function of vitamin C in epigenetic regulation. Vitamin C exists predominantly as an ascorbate anion under physiological pH conditions. Ascorbate was discovered as a cofactor for methylcytosine dioxygenases that are responsible for DNA demethylation, and also as a likely cofactor for some JmjC domain-containing histone demethylases that catalyze histone demethylation. Variation in ascorbate bioavailability thus can influence the demethylation of both DNA and histone, further leading to different phenotypic presentations. Ascorbate deficiency can be presented systematically, spatially and temporally in different tissues at the different stages of development and aging. Here, we review how ascorbate deficiency could potentially be involved in embryonic and postnatal development, and plays a role in various diseases such as neurodegeneration and cancer through epigenetic dysregulation.

Topics: Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Dioxygenases; DNA Methylation; Embryonic Development; Epigenesis, Genetic; F-Box Proteins; Histones; Humans; Jumonji Domain-Containing Histone Demethylases; Neoplasms; Neurodegenerative Diseases; Scurvy

Vitamin C has been suggested as beneficial in preventing and curing the common cold, decreasing the incidence of preterm delivery and preeclampsia, decreasing risk of cancer and cardiovascular disease, and improving the quality of life by inhibiting blindness and dementia. In this article, we review the hypothesized mechanisms of these purported health benefits and the evidence behind such claims.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Common Cold; Dementia; Female; Humans; Neoplasms; Obstetric Labor, Premature; Pre-Eclampsia; Pregnancy; Vision Disorders; Vitamins

Epidemiology of bronchial asthma (BA) indicates a marked paradox: rapid rise in the prevalence.Simultaneous decline in mortality is mostly related to improvement in the diagnosis and therapy. In many economically developed countries the BA affects more than 10 per cent of the population, while mortality related to this respiratory disorder is below 1/100,000. Factors favorably influencing mortality of BA include new more effective medications, decline in smoking and also improved nutrition, based on awareness of protective role of vitamins. Vitamin D deficiency has a number of biological effects that are potentially instrumental in the pathogenesis and severity of BA. Increased number of randomized, controlled, interventional studies is showing positive effects of vitamin D supplementation in pediatric and in adult BA. Oxidative stress is potentially an important pathogenic factor in the progression of BA. Vitamin C (ascorbic acid) belongs to the most effective nutritional antioxidants. By counteracting oxidants, reducing generation of reactive oxygen species, vitamin C may inhibit external attacks in the respiratory tract, thus modulating the development of BA (Fig. 2, Ref. 15).

Topics: Adult; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Asthma; Child; Dietary Supplements; Humans; Oxidative Stress; Smoking; Vitamin D; Vitamin D Deficiency; Vitamins

Vitamin C is not only an essential nutrient involved in many anabolic pathways, but also an important player of the endogenous antioxidant defense. Low plasma levels are very common in critical care patients and may reflect severe deficiency states.. Vitamin C scavenges reactive oxygen species such as superoxide and peroxynitrite in plasma and cells (preventing damage to proteins, lipids and DNA), prevents occludin dephosphorylation and loosening of the tight junctions. Ascorbate improves microcirculatory flow impairment by inhibiting tumor-necrosis-factor-induced intracellular adhesion molecule expression, which triggers leukocyte stickiness and slugging. Clinical trials in sepsis, trauma and major burns testing high-dose vitamin C show clinical benefit. Restoration of normal plasma levels in inflammatory patients requires the administration of 3 g/day for several days, which is 30 times the daily recommended dose.. The recent research on the modulation of oxidative stress and endothelial protection offer interesting therapeutic perspectives, based on the biochemical evidence, with limited or even absent side-effects.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Burns; Critical Care; Critical Illness; Dietary Supplements; Humans; Nutrition Therapy; Oxidative Stress; Reactive Oxygen Species; Vitamins; Wounds and Injuries

Vitamin C is an important antioxidant and cofactor that is involved in the regulation of development, function, and maintenance of several cell types in the body. Deficiencies in vitamin C can lead to conditions such as scurvy, which, among other ailments, causes gingivia, bone pain, and impaired wound healing. This review examines the functional importance of vitamin C as it relates to the development and maintenance of bone tissues. Analysis of several epidemiological studies and genetic mouse models regarding the effect of vitamin C shows a positive effect on bone health. Overall, vitamin C exerts a positive effect on trabecular bone formation by influencing expression of bone matrix genes in osteoblasts. Recent studies on the molecular pathway for vitamin C actions that include direct effects of vitamin C on transcriptional regulation of target genes by influencing the activity of transcription factors and by epigenetic modification of key genes involved in skeletal development and maintenance are discussed. With an understanding of mechanisms involved in the uptake and metabolism of vitamin C and knowledge of precise molecular pathways for vitamin C actions in bone cells, it is possible that novel therapeutic strategies can be developed or existing therapies can be modified for the treatment of osteoporotic fractures.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone and Bones; Cartilage; Disease Models, Animal; Humans; Models, Biological

Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Cognition; Cognition Disorders; Female; Humans; Pregnancy; Prenatal Nutritional Physiological Phenomena; Stroke; Vitamins

The aim of this review was to evaluate recently published review articles which examine the use of nutritional supplements to prevent preterm birth (PTB) by modifying vaginal bacteria.. Probiotics, vitamin D and vitamin C were all identified as nutritional supplements that have the potential to alter bacterial flora and consequently reduce PTB and treat or prevent genital infections. Evidence shows that probiotics may reduce the incidence of PTB as well as being effective at treating bacterial vaginosis, a known cause for PTB. Low vitamin D levels may be associated with bacterial vaginosis, although no evidence was identified which demonstrated that vitamin D supplementation reduced the risk of having bacterial vaginosis or PTB.There is little evidence regarding vitamin C supplementation, although it does suggest a possible benefit with regard to preterm rupture of membranes; however, this did not appear to reduce rates of PTB.. Although there is evidence that taking probiotics in pregnancy may reduce the incidence of PTB, it is mainly derived from small, poor quality studies. Vitamin D and vitamin C may have potential benefits, but these remain to be proven. Large randomized controlled trials are needed to more accurately evaluate the potential benefits of these low-cost interventions for reducing PTB and its consequences.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Evidence-Based Medicine; Female; Fetal Membranes, Premature Rupture; Humans; Obstetric Labor, Premature; Pregnancy; Prenatal Nutritional Physiological Phenomena; Probiotics; Risk; Vagina; Vaginosis, Bacterial; Vitamin D; Vitamin D Deficiency

Obesity and the subsequent reprogramming of the white adipose tissue are linked to human disease-complexes including metabolic syndrome and concurrent non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The dietary imposed dyslipidemia promotes redox imbalance by the generation of excess levels of reactive oxygen species and induces adipocyte dysfunction and reprogramming, leading to a low grade systemic inflammation and ectopic lipid deposition, e.g., in the liver, hereby promoting a vicious circle in which dietary factors initiate a metabolic change that further exacerbates the negative consequences of an adverse life-style. Large epidemiological studies and findings from controlled in vivo animal studies have provided evidence supporting an association between poor vitamin C (VitC) status and propagation of life-style associated diseases. In addition, overweight per se has been shown to result in reduced plasma VitC, and the distribution of body fat in obesity has been shown to have an inverse relationship with VitC plasma levels. Recently, a number of epidemiological studies have indicated a VitC intake below the recommended daily allowance (RDA) in NAFLD-patients, suggesting an association between dietary habits, disease and VitC deficiency. In the general population, VitC deficiency (defined as a plasma concentration below 23 μM) affects around 10% of adults, however, this prevalence is increased by an adverse life-style, deficiency potentially playing a broader role in disease progression in specific subgroups. This review discusses the currently available data from human surveys and experimental models in search of a putative role of VitC deficiency in the development of NAFLD and NASH.

Topics: Adiposity; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Comorbidity; Humans; Inflammation; Life Style; Non-alcoholic Fatty Liver Disease; Nutritional Status; Obesity; Prevalence; Prognosis; Risk Assessment; Risk Factors

Despite continuous advances in the prevention of cardiovascular disease (CVD), critical issues associated with an unhealthy lifestyle remain an increasing cause of morbidity and mortality in industrialized countries.. A growing body of literature supports a specific role for vitamin C in a number of reactions that are associated with vascular function and control including, for example, nitric oxide bioavailability, lipid metabolism, and vascular integrity.. A large body of epidemiological evidence supports a relationship between poor vitamin C status and increased risk of developing CVD, and the prevalence of deficiency continues to be around 10%-20% of the general Western population although this problem could easily and cheaply be solved by supplementation. However, large intervention studies using vitamin C have not found a beneficial effect of supplementation. This review outlines the proposed mechanism by which vitamin C deficiency worsens CVD progression. In addition, it discusses problems with the currently available literature, including the discrepancies between the large intervention studies and the experimental and epidemiological literature.. Increased insights into vitamin C deficiency-mediated CVD progression will enable the design of future randomized controlled trials that are better suited to test the efficacy of vitamin C in disease prevention as well as the identification of high-risk individuals which could possibly benefit from supplementation.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Disease Progression; Humans; Life Style; Obesity; Oxidation-Reduction; Randomized Controlled Trials as Topic; Smoking

Large cross-sectional population studies confirm that vitamin C deficiency is common in humans, affecting 5%-10% of adults in the industrialized world. Moreover, significant associations between poor vitamin C status and increased morbidity and mortality have consistently been observed. However, the absorption, distribution and elimination kinetics of vitamin C in vivo are highly complex, due to dose-dependent non-linearity, and the specific regulatory mechanisms are not fully understood. Particularly, little is known about how adaptive mechanisms during states of deficiency affect the overall regulation of vitamin C transport in the body. This review discusses mechanisms of vitamin C transport and potential means of regulation with special emphasis on capacity and functional properties, such as differences in the K(m) of vitamin C transporters in different target tissues, in some instances demonstrating a tissue-specific distribution.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Transport; Homeostasis; Humans; Hydrogen-Ion Concentration; Nutritional Status

Though vitamin C supplementation has shown no observed effects on stroke prevention in several clinical trials, uncertainty remains as to whether long-term, low-dose intake influences the development of stroke among general populations. Furthermore, the association between circulating vitamin C and the risk of stroke is also unclear. For further clarification of these issues, we conducted a meta-analysis of prospective studies.. PubMed and EMBASE databases were searched, and the bibliographies of the retrieved articles were also reviewed to identify eligible studies. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were computed with a random-effects model. The summary RR for the high-versus-low categories was 0.81 (95% CI: 0.74 to 0.90) for dietary vitamin C intake (11 studies), and 0.62 (95% CI: 0.49 to 0.79) for circulating vitamin C (6 studies). The summary RR for each 100 mg/day increment in dietary vitamin C was 0.83 (95% CI: 0.75 to 0.93) (10 studies), and for each 20 μmol/L increment in circulating vitamin C was 0.81 (95% CI: 0.75 to 0.88) (5 studies). Few studies reported results for vitamin C supplements (RR for high-versus-low intake=0.83, 95% CI: 0.62 to 1.10, 3 studies).. This meta-analysis suggests significant inverse relationships between dietary vitamin C intake, circulating vitamin C, and risk of stroke.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Dietary Supplements; Humans; Prognosis; Prospective Studies; Risk Factors; Stroke; Time Factors

Vitamin C is a water soluble vitamin which is mainly fresh fruits and vegetables foodborne. Vitamin C deficiency is most often due to a lack of daily amount. Scurvy is characterized by the occurrence of fatigue, myalgia, arthralgia, purpura, bleeding disorders, and later by dental manifestations. Biological signs are nonspecific: anemia, hypocholesterolemia, hypoalbuminemia. Clinical suspicion is confirmed by the decrease in ascorbic acid level (< 2 mg/L). It must be interpreted in light of the acute phase reactants. The treatment is the administration of 1 g of vitamin C per day for 15 days. Vitamin C depletion (ascorbic acid: 2 to 5 mg/L) could induce long-term complications. The recommended dietary allowance of vitamin C protect from these risks.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Disease Progression; Humans; Neoplasms; Prevalence; Scurvy

Research progress to understand the role of vitamin C (ascorbic acid) in human health has been slow in coming. This is predominantly the result of several flawed approaches to study design, often lacking a full appreciation of the redox chemistry and biology of ascorbic acid. In this review, we summarize our knowledge surrounding the limitations of common approaches used in vitamin C research. In human cell culture, the primary issues are the high oxygen environment, presence of redox-active transition metal ions in culture media, and the use of immortalized cell lines grown in the absence of supplemental ascorbic acid. Studies in animal models are also limited due to the presence of endogenous ascorbic acid synthesis. Despite the use of genetically altered rodent strains lacking synthesis capacity, there are additional concerns that these models do not adequately recapitulate the effects of vitamin C deprivation and supplementation observed in humans. Lastly, several flaws in study design endemic to randomized controlled trials and other human studies greatly limit their conclusions and impact. There also is anecdotal evidence of positive and negative health effects of vitamin C that are widely accepted but have not been substantiated. Only with careful attention to study design and experimental detail can we further our understanding of the possible roles of vitamin C in promoting human health and preventing or treating disease.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Disease Models, Animal; Humans; Randomized Controlled Trials as Topic

Vitamin C, also known as ascorbic acid (AA), is involved in all phases of wound healing. In the inflammatory phase it is required for neutrophil apoptosis and clearance. During the proliferative phase, AA contributes towards synthesis, maturation, secretion and degradation of collagen. Deficiencies affect the maturation phase by altering collagen production and scar formation. The body strives to maintain homeostasis of AA, thereby ensuring availability for collagen synthesis. After wounding, plasma and tissue levels of AA diminish and, as a consequence, supplements may be useful for healing, although levels beyond saturation are excreted Clinicians need to be aware of both the nutritional status of patients with either acute or chronic wounds and the possibility of any AA deficiency which may hinder healing.

Topics: Apoptosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cicatrix; Collagen; Humans; Wound Healing

Bacterial bloodstream infection causes septic syndromes that range from systemic inflammatory response syndrome (SIRS) and encephalopathy to severe sepsis and septic shock. Microvascular dysfunction, comprising impaired capillary blood flow and arteriolar responsiveness, precedes multiple organ failure. Vitamin C (ascorbate) levels are low in critically ill patients. The impact of ascorbate administered orally is moderate because of its limited bioavailability. However, intravenous injection of ascorbate raises plasma and tissue concentrations of the vitamin and may decrease morbidity. In animal models of polymicrobial sepsis, intravenous ascorbate injection restores microvascular function and increases survival. The protection of capillary blood flow and arteriolar responsiveness by ascorbate may be mediated by inhibition of oxidative stress, modulation of intracellular signaling pathways, and maintenance of homeostatic levels of nitric oxide. Ascorbate scavenges reactive oxygen species (ROS) and also inhibits the NADPH oxidase that synthesizes superoxide in microvascular endothelial cells. The resulting changes in redox-sensitive signaling pathways may diminish endothelial expression of inducible nitric oxide synthase (iNOS), tissue factor and adhesion molecules. Ascorbate also regulates nitric oxide concentration by releasing nitric oxide from adducts and by acting through tetrahydrobiopterin (BH4) to stimulate endothelial nitric oxide synthase (eNOS). Therefore, it may be possible to improve microvascular function in sepsis by using intravenous vitamin C as an adjunct therapy.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain Diseases; Humans; Hypotension; Regional Blood Flow; Sepsis

The discovery of Helicobacter pylori as the cause of gastritis and peptic ulcers ushered in the modern era of research into gastritis and into acid-peptic diseases and rekindled interest in the role of ascorbic acid in the pathophysiology and treatment of gastritis and peptic ulcer disease. Here, we review historic and modern studies on ascorbic acid and gastric diseases with an emphasis on H. pylori gastritis and its sequelae. The relationship of ascorbic acid and gastritis and peptic ulcer and its complications was extensively studied during the 1930s through the 1950s. Much of this extensive literature has been effectively "lost." Ascorbic acid deficiency was associated with all forms of gastritis (e.g., autoimmune, chemical, and infectious) due in varying degrees to insufficient intake, increased metabolic requirements, and destruction within the GI tract. Importantly, gastritis-associated abnormalities in gastric ascorbic acid metabolism are reversed by H. pylori-eradication and potentially worsened by proton pump inhibitor therapy. Diets rich in naturally occurring ascorbic acid are associated with protection of the gastric corpus from atrophy and a reduction in the incidence of gastric cancer possibly through the ability of ascorbic acid to reduce oxidative damage to the gastric mucosa by scavenging carcinogenic N-nitroso compounds and free radicals and attenuating the H. pylori-induced inflammatory cascade. Ascorbic acid supplementation was possibly associated with a decreased incidence of bleeding from peptic ulcer disease. Pharmacologic doses of ascorbic acid also may improve the effectiveness of H. pylori-eradication therapy. Occasionally, looking back can help plot the way forward.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Diseases

The recommended dietary allowance (RDA) of vitamin C has traditionally been based on the prevention of the vitamin C deficiency disease, scurvy. While higher intakes of vitamin C may exert additional health benefits, the limited Phase III randomized placebo-controlled trials (RCTs) of vitamin C supplementation have not found consistent benefit with respect to chronic disease prevention. To date, this has precluded upward adjustments of the current RDA. Here we argue that Phase III RCTs-designed principally to test the safety and efficacy of pharmaceutical drugs-are ill suited to assess the health benefits of essential nutrients; and the currently available scientific evidence is sufficient to determine the optimum intake of vitamin C in humans. This evidence establishes biological plausibility and mechanisms of action for vitamin C in the primary prevention of coronary heart disease, stroke, and cancer; and is buttressed by consistent data from prospective cohort studies based on blood analysis or dietary intake and well-designed Phase II RCTs. These RCTs show that vitamin C supplementation lowers hypertension, endothelial dysfunction, chronic inflammation, and Helicobacter pylori infection, which are independent risk factors of cardiovascular diseases and certain cancers. Furthermore, vitamin C acts as a biological antioxidant that can lower elevated levels of oxidative stress, which also may contribute to chronic disease prevention. Based on the combined evidence from human metabolic, pharmacokinetic, and observational studies and Phase II RCTs, we conclude that 200 mg per day is the optimum dietary intake of vitamin C for the majority of the adult population to maximize the vitamin's potential health benefits with the least risk of inadequacy or adverse health effects.

Topics: Adult; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dietary Supplements; Health Promotion; Humans; Nutrition Policy; Nutritional Requirements; Oxidative Stress; Randomized Controlled Trials as Topic

The water-soluble vitamins B6, B12 and C play important roles in maternal health as well as fetal development and physiology during gestation. This systematic review evaluates the risks and benefits of interventions with vitamins B6, B12 and C during pregnancy on maternal, neonatal and child health and nutrition outcomes. Relevant publications were identified by searching PubMed, Popline and Web of Science databases. Meta-analyses were conducted for outcomes where results from at least three controlled trials were available. Potential benefits of vitamin B6 supplementation were reduction in nausea and vomiting, improvement in dental health, and treatment of some cases of anaemia. In meta-analysis based on three small studies, vitamin B6 supplementation had a significant positive effect on birthweight (d = 217 g [95% confidence interval (CI) 130, 304]). Interventions with vitamin C alone or combined with vitamin E did not systematically reduce the incidence of pre-eclampsia, premature rupture of membranes, or other adverse pregnancy outcomes. In meta-analyses, vitamins C and E increased the risk of pregnancy-related hypertension (relative risk 1.10 [95% CI 1.02, 1.19]). Effects of vitamin B6 or C intervention on other neonatal outcomes, including preterm birth, low birthweight, and perinatal morbidity and mortality, were not significant. Data on child health outcomes were lacking. Despite the prevalence of vitamin B12 deficiency amongst populations with limited intake of animal source foods, no intervention trials have evaluated vitamin B12 supplementation before or during pregnancy. In conclusion, existing evidence does not justify vitamin C supplementation during pregnancy. Additional studies are needed to confirm positive effects of vitamin B6 supplementation on infant birthweight and other outcomes. While vitamin B12 supplementation may reduce the incidence of neural tube defects in the offspring based on theoretical considerations, research is needed to support this hypothesis.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Birth Weight; Child Welfare; Child, Preschool; Dietary Supplements; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Maternal Nutritional Physiological Phenomena; Maternal Welfare; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Vitamin B 6 Deficiency

As elements of the antioxidant system, cofactors of enzymes, components of transcription factors, and epigenetic modulators, micronutrients, such as vitamins and trace elements, influence various metabolic processes that are directly associated with immune functions. Specifically, the vitamins C and D have been shown to have significance immune function. Therefore, the objective of this review is to elucidate interactions between micronutrients and the immune system. In the initial section of this review, we present a general overview of interactions between the immune system and micronutrients, with a focus on the immunobiologically relevant functions of vitamin C. Immune competent cells accumulate vitamin C against a concentration gradient, with a close relationship between vitamin C supply and immune cell activity, especially phagocytosis activity and T-cell function. Accordingly, one of the consequences of vitamin C deficiency is impaired resistance to various pathogens, while an enhanced supply increases antibody activity and infection resistance.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Communicable Diseases; Dietary Supplements; Ergocalciferols; Humans; Immune System; Inflammation; Inflammation Mediators; Signal Transduction

In contrast to the promised 'antioxidant miracle' of the 1980s, several randomised controlled trials have shown no effect of antioxidant supplements on hard endpoints such as morbidity and mortality. The former over-optimistic attitude has clearly called for a more realistic assessment of the benefit:harm ratio of antioxidant supplements. We have examined the literature on vitamin C intervention with the intention of drawing a conclusion on its possible beneficial or deleterious effect on health and the result is discouraging. One of several important issues is that vitamin C uptake is tightly controlled, resulting in a wide-ranging bioavailability depending on the current vitamin C status. Lack of proper selection criteria dominates the currently available literature. Thus, while supplementation with vitamin C is likely to be without effect for the majority of the Western population due to saturation through their normal diet, there could be a large subpopulation with a potential health problem that remains uninvestigated. The present review discusses the relevance of the available literature on vitamin C supplementation and proposes guidelines for future randomised intervention trials.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Humans; Public Health

Senescence Marker Protein-30 (SMP30) was originally identified as a novel protein in the rat liver, the expression of which decreases with aging. Recently, we identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonases (GNL) of animal species. GNL was a key enzyme which involved in vitamin C biosynthesis, and the essential role of SMP30 in this synthetic process was verified by a nutritional study. SMP30 knockout mice developed symptoms of scurvy when fed a vitamin C-deficient diet, verifying the pivotal role of SMP30 in vitamin C biosynthesis. Moreover, SMP30 knockout mice were shorter in life span than the wild type when fed autoclaved mouse chow contained approximately 55 mg/kg of vitamin C, which we now know contains too little vitamin C to maintain normal levels of vitamin C in tissues. These results demonstrate that vitamin C deficiency shortens longevity, that is, vitamin C deficiency accelerates aging.

Topics: Aging; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Carboxylic Ester Hydrolases; Humans; Intracellular Signaling Peptides and Proteins; Mice; Mice, Knockout

To summarize recent findings on vitamin C status and assess the requirement and optimal dose of supplementation in surgical patients.. Blood vitamin C concentration falls after uncomplicated surgery and further decreases in surgical intensive care unit patients. The decline may be owing to increased demand caused by increased oxidative stress. To normalize plasma vitamin C concentration, much higher doses than the recommended daily allowance or doses recommended in parenteral nutrition guidelines are needed in these patients. In uncomplicated surgical patients, more than 500 mg/day of vitamin C may be required, with much higher doses in surgical intensive care unit patients. In uncomplicated gastrointestinal surgery, continuous parenteral administration of 500 mg/day of vitamin C reduced postoperative oxidative stress as manifested by reduced urinary excretion of isoprostane. In some studies, postoperative atrial fibrillation was prevented after cardiac surgery by perioperative vitamin C supplementation. In critically ill patients, some prospective randomized controlled trials support parenteral supplementation of high doses of vitamin C, E and trace elements.. Vitamin C requirement is increased in surgical patients, and the potential advantage of supplementation is to increase the plasma and tissue levels of vitamin C and thereby reduce oxidative stress. Although some clinical benefits of high-dose vitamin C supplementation have been shown in the critically ill, the optimal dose for supplementation and the clinical benefits remain to be investigated in surgical patients.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Critical Illness; Dietary Supplements; Humans; Nutrition Policy; Oxidative Stress; Parenteral Nutrition; Postoperative Care; Postoperative Complications

Vitamin C is a pivotal redox modulater in many biological reactions of which several remain poorly understood. Naturally, vitamin C has been the subject of many investigations over the past decades in relation to its possible beneficial effects on cardiovascular disease primarily based on its powerful yet general antioxidant properties. However, growing epidemiological, clinical and experimental evidence now suggests a more specific role of ascorbate in vasomotion and in the prevention of atherosclerosis. For example, in contrast to most other biological antioxidants, administration of vitamin C can apparently induce vasodilation. Millions of people worldwide can be diagnosed with vitamin C deficiency according to accepted definitions. In this perspective, the present review examines the evidence for a specific link between vitamin C deficiency and increased risk of atherosclerosis as well as the possible mechanisms by which vitamin C may exert its protective function.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Atherosclerosis; Coenzymes; Disease Models, Animal; Dyslipidemias; Endothelium, Vascular; Humans; Lipid Metabolism; Lipids; Nitric Oxide; Nitric Oxide Synthase; Scurvy; Vasodilation

Vitamin C and a vitamin B are essential nutrients to maintain bone density and bone quality. Recent literature clearly shows that vitamin C and B affect bone quality determinant "collagen cross-link formation" . Mildly elevated plasma homocysteine levels induced by vitamin B insufficiency and methylenetetrahydrofolate reductase (MTHFR) deteriorate normal collagen cross-link formation (Saito M, Osteoporos Int 2009 May 30. [Epub ahead of print] , Shiraki M and Saito M, J Bone Miner Metab [6] 2008) . In this review, we describe the effects of vitamin C and vitamin B insufficiency and hyperhomocysteinemia on bone quality in terms of collagen cross-link formation in bone that have been reported in the literature.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Bone Density; Collagen; Homocysteine; Humans; Hyperhomocysteinemia; Vitamin B Complex; Vitamin B Deficiency

The analysis of the literature on communication of a hemostasis and vitamin C has allowed to assert, that its deficiency accelerates lipid peroxidation and reduces potential at porpoises, and it conducts to activation platelets, to acceleration of continuous intravascular blood coagulation of and to reduction in tolerance to thrombin. High dozes of vitamin C influences a hemostasis strengthens lipid peroxidation similarly to prooxidizers. Entering high dozes of vitamin C at the statuses menacing weith thromboses, it is desirable to supervise a level of markers of intravascular blood coagulation in plasma.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Coagulation; Blood Platelets; Disseminated Intravascular Coagulation; Homeostasis; Humans; Lipid Peroxidation; Platelet Activation; Thrombin; Thrombosis

Parenteral ascorbic acid has been frequently used to overcome problems of vitamin C deficiency in haemodialysis patients. The benefits of vitamin C supplementation in clinical studies have been controversial and did not consider toxicological aspects. The review summarizes recent findings of the effects of parenteral ascorbic acid and discusses toxicological effects.. Vitamin C deficiency in haemodialysis patients, which has been frequently described, cannot be improved with oral supplementation due to limited absorption of high dosages. To avoid consequences of vitamin C deficiency, parenteral vitamin C solutions should be administered because this intervention is the only way to guarantee a sufficient supply to the cells. A beneficial consequence of parenteral vitamin C on the recombinant human erythropoietin resistance is an additional therapeutic effect, which contributes to the prevention of iron deficiency anaemia in haemodialysis patients. Thus, large amount of supplemental vitamin C are required for extended periods of time (up to 500 mg 3 times a week). To avoid hyperoxaluria, plasma oxalate levels should be monitored on a regular basis, for example, once a week.. Parenteral administration of ascorbic acid may be an approach that can overcome problems of vitamin C deficiency in haemodialysis patients - in particular problems of iron overload, erythropoetin resistance, and chronic inflammation.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Drug Resistance; Erythropoietin; Hemosiderosis; Humans; Inflammation; Infusions, Parenteral; Renal Dialysis

Consumption of vitamin C is essential for life in humans because the body does not synthesize it. Numerous studies have demonstrated that supplementation with vitamin C enhances the immune system, avoids DNA damage, and significantly decreases the risk of a wide range of pathologies, such as cancers, and degenerative and chronic diseases. Moreover, it has been demonstrated that modern crop production, transport, and food storage severely impair the quality of food and provoke a loss in micronutrients, such as vitamin C.. In this paper, we report that the Recommended Daily Allowance (RDA) in vitamin C is lower than the bodily needs. In fact, it does not seem to ensure true health protection and it appears difficult to reach an effective dose of vitamin C only through food consumption. Furthermore, the literature shows that vitamin C intake higher than the RDA is safe. Therefore, in order to achieve optimal health and avoid a number of diseases, we suggest that, in the present situation, vitamin C supplementation is required.. According to the current literature, we would like to emphasize that to ensure an optimal allowance of vitamin C, we advise 1 g daily intake of vitamin C supplementation, accompanied by a diet rich in fruits and vegetables.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Chronic Disease; Fruit; Health Education; Health Promotion; Humans; Nutrition Policy; Nutritional Requirements; Vegetables

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Erythropoiesis; Humans; Kidney Failure, Chronic; Prognosis; Renal Replacement Therapy; Vitamins

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Asthma; Cardiovascular Diseases; Cataract; Common Cold; Humans; Nutrition Policy; Nutritional Requirements

Dialogues in Dermatology, a monthly audio program from the American Academy of Dermatology, contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editor-in-Chief Warren R. Heymann, MD, are provided after each discussion as a topic summary and are provided here as a special service to readers of the Journal of the American Academy of Dermatology.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Diagnosis, Differential; Humans; Scurvy

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Cohort Studies; Controlled Clinical Trials as Topic; Dietary Supplements; Female; Humans; Male; Middle Aged; Pneumonia

Anemia prevention for hemodialysis relies primarily on supplemental erythropoietin (EPO) and intravenous iron (IV-iron). The doses of EPO utilized are somewhat higher than normal endogenous rates of EPO production in healthy subjects, and the amount of IV-iron used to boost red blood cell (RBC) production may be greater than the amounts used for erythropoiesis. EPO and IV-iron might be used more efficiently if two fundamental problems were solved in the management of dialysis patients: better vitamin C status, and avoidance of chronic inflammation. The low levels of plasma vitamin C commonly observed in dialysis patients restrict mobilization of stored iron from the reticuloendothelial system (RES), and inflammation has a very similar effect. The impact of low vitamin C levels and concurrent inflammation causes a large amount of iron to be stored, with relatively inefficient utilization for erythropoiesis. Vitamin C intake for dialysis patients is often restricted because of avoidance of vitamin C-rich foods, and because of concerns about oxalosis. Inflammation is a chronic feature of renal disease, which is compounded by infections from use of catheters. Research strategies to improve vitamin C status and to decrease inflammation would lead to better utilization of iron and EPO, and could have parallel benefits for the long-term health of patients on hemodialysis.

Topics: Anemia; Ascorbic Acid; Ascorbic Acid Deficiency; Hematopoiesis; Humans; Kidney Failure, Chronic; Renal Dialysis

The studies on experimental animals (guinea pigs, monkeys, fish) have confirmed the important role of ascorbic acid deficiency in the development of hypercholesterolemia and atherosclerosis, but the clinical experience is not quite uniform. Metaanalyses of randomized controlled trials performed on subjects without established vitamin C-deficiency conclud that the evidence of the presence or absence of benefits derived from the ability of ascorbic acid to prevent cardiovascular diseases is not sufficient. This review is an outline of numerous clinical, epidemiological and prospective studies that have found a positive role of vitamin C in the prevention of atherosclerosis. If we admit the possibility that vitamin C deficiency is a significant risk factor of atherogenesis, due to ethical reasons it is impossible to perform long-term controlled trials on subjects with proved vitamin C deficiency, to recommend them not to change their nutrition and lifestyle, and to administer placebo to the control group. Therefore the proof of atherogenic effect of chronic vitamin C deficiency is limited to indirect evidence only. In this review many new data on the positive effects of ascorbic acid on human cardiovascular system are summarized and the mechanisms of its protective influence on blood vessels are discussed (Fig.5, Ref. 45). Full Text (Free, PDF) www.bmj.sk.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Atherosclerosis; Cardiovascular Diseases; Humans; Risk Factors

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Breast Feeding; Child, Preschool; Cystic Fibrosis; Female; Humans; Hypervitaminosis A; Infant; Infant, Newborn; Male; Rickets; Vitamin A; Vitamin A Deficiency; Vitamin B Complex; Vitamin D; Vitamin E; Vitamin K; Vitamins

For more than 50 years, the Food and Nutrition Board of the National Academy of Sciences has been reviewing nutrition research and defining nutrient requirements for healthy people, referred to as the Recommended Dietary Allowances (RDA). As new nutrition research is published, the importance of vitamins as vital nutrients is underscored, and new physiologic roles and applications to human health are examined and considered with regard to updating the RDA. Each year a substantial amount of new research is published on vitamins. This review examines recent research published on the importance of vitamin C with regard to general health.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Asthma; Cardiovascular Diseases; Diabetes Mellitus; Exercise; Humans; Hypersensitivity; Neoplasms

Vitamin C (ASC) is well known as an outstanding antioxidant in animal tissues. This concept is reviewed from a chemical standpoint, starting from a chemical view of radical reactions in the cell. ASC, vitamin E, and lipid hydroperoxide were selected as key molecules involved in radical reactions in the cell, and their efficiencies as an index of oxidative stress were evaluated. At first, methods for specific and sensitive determination of ASC and lipid hydroperoxide were developed. Based on comparisons of these indices during oxidative stress in typical pathological conditions, such as diabetes and liver damage by toxicants, ASC concentration was found to be the most sensitive index in animal tissues. Antioxidative effect of food factors in vivo can be evaluated on the basis of these indices. Analysis of oxidation of low-density lipoprotein (LDL) revealed that degradation and cross-link of apolipoprotein B-100 (apoB) are extremely facile processes. Fragmented and conjugated apoB proteins are present in normal human serum, and tend to increase with age based on immunoblot analysis. Estimation of these products allows us a mechanism-based diagnosis of atherosclerosis. A significant relationship between plasma ASC level and the sum of these apoB products was found. In conclusion, specifically determined ASC concentration sensitively reflects oxidative stress in tissues.

Topics: Animals; Apoptosis; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Dehydroascorbic Acid; Food; Humans; In Vitro Techniques; Lipid Peroxides; Mice; Molecular Structure; Organ Specificity; Oxidative Stress; Rats; Reactive Oxygen Species; Vitamin E

Vitamins are essential to maintain normal metabolic processes and homeostasis within the body. The amount of a specific vitamin required by an individual varies considerably and it is influenced by such factors as body size, growth rate, physical activity, and pregnancy. Most vitamins are stored minimally in human cells, but some are stored in liver cells to a greater extent. Vitamins A and D, for example, may be stored in sufficient amounts to maintain an individual without any intake for 5 to 10 months and 2 to 4 months, respectively. However, a deficiency of vitamin B compounds (except vitamin B12) may be noted within days, and the lack of vitamin C will manifest within weeks and may result in death in 5 to 6 months. The current recommended dietary allowance (RDA) of vitamin C is 75 mg for woman and 90 mg for men, based on the vitamin's role as an antioxidant as well as protection from deficiency. High intakes of the vitamin are generally well tolerated, however, a Tolerable Upper Level (TUL) was recently set at 2 g based on gastrointestinal upset that sometimes accompanies excessive dosages. Several populations warrant special attention with respect to vitamin C requirements. These include patients with periodontal disease, smokers, pregnant and lactating women, and the elderly.

Topics: Alzheimer Disease; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Regeneration; Cardiovascular Diseases; Chondrogenesis; Diabetes Mellitus; Female; Humans; Male; Maximum Tolerated Dose; Nutrition Policy; Periodontal Diseases; Pregnancy; Virus Diseases

Topics: Aged; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Combined Modality Therapy; Female; Humans; Nutrition Policy; Nutritional Requirements; Pressure Ulcer; Skin Care; Wound Healing

Hypovitaminosis C is frequent in populations at risk (men who live alone, old people, homelessness, patients with psychiatric diseases, foodfaddists,...) and is underestimated in the general population.. Scurvy occurs after 3 months without consumption of ascorbic acid, and is due to lack of consumption fresh fruits and vegetables. Clinical manifestations are weakness, myalgia and arthralgia, vascular purpura and hemorrhagic syndrome, and later the stomatologic manifestations: gingivorragia and loss of teeth. Biological signs are nonspecific: anemia, hypocholesterolemia, hypoalbuminemia. Clinical suspicion must be confirmed by a low level of ascorbic acid (<2.5 mg/l), but this value needs to be interpretated according to the presence of an acute phase response. Leucocyte ascorbic acid level reflects total body store and is more reliable, but not available in practice. Treatment consists in administration of 1 g vitamin C per day during 15 days.. Vitamin C depletion (serum ascorbic acid level between 2 and 5 mg/l) may occur long-term complications such as increase cardiovascular and neoplasic risks or cataract. The new recommended dietary allowance of vitamin C (110 mg per day for an adult) takes into account of these risks.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Prevalence

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Blood Chemical Analysis; Humans; Reference Values

Vitamin C is an essential micronutrient. Absence from the diet will result in the deficiency disease scurvy, typically characterised by weakening of collagenous structures. High intakes of vitamin C have been associated with decreased incidence or severity of a number of diseases, including cancer and cardiovascular disease. These beneficial effects may be attributed to its antioxidant properties, although the exact mechanisms of action remain elusive. It is also unclear what intake levels are required for optimal health benefits. The task of defining optimal intakes is hindered by the lack of a reliable functional marker of tissue vitamin C status in man. Many different pathways have been investigated, but none of them have measurable outcome variables relating directly to scorbutic changes. The bone-collagen formation pathway has the potential to provide a functional index of tissue vitamin C adequacy. Vitamin C acts as a cofactor for the enzyme lysyl hydroxylase, which is required for the hydroxylation of lysine residues in procollagen chains. Pyridinoline is a mature collagen cross-link formed from three hydroxylysine residues, deoxypyridinoline is formed from two hydroxylysine and one lysine residue. Guinea-pig studies have shown an alteration in the pyridinium cross-link ratios in response to graded vitamin C intakes (Tsuchiya & Bates, 1998). In order to investigate whether these changes can be seen in a human population group, a study was carried out in rural Gambia, where there is a marked seasonal variation in dietary vitamin C. The present review discusses the rationale behind the study and presents some preliminary results.

Topics: Amino Acids; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Bone and Bones; Collagen; Humans; Hydroxylation; Seasons

Dehydroascorbic acid, the oxidized form of vitamin C, is transported into mammalian cells via facilitative glucose transporters and hyperglycemia inhibits this process by competitive inhibition. This inhibited transport may promote oxidative stress and contribute to the increase in atherosclerotic cardiovascular disease observed in patients with diabetes mellitus. This review explores the importance of this proposed mechanism in light of current research. For example, recent reports suggest that administration of antioxidants, such as vitamin C, may slow atherogenesis by improving endothelium-dependent vasodilation in individuals with abnormal glucose and lipid metabolism, perhaps by preventing the oxidation of nitric oxide, an important regulator of vasomotor tone. Endothelial dysfunction plays a key role in the development of atherosclerosis and endothelial cells may be particularly affected by hyperglycemia-induced ascorbic acid deficiency as they line the interior of blood vessels. In addition, we discuss evidence of several other mechanisms by which vitamin C status may affect the development of atherosclerotic cardiovascular disease, particularly its inverse relationship to multiple cardiovascular disease risk factors and indicators. Given these factors, vitamin C administration is recommended during periods of both acute and chronic hyperglycemia to help preserve endothelial function.

Topics: Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Endothelium, Vascular; Humans; Hyperglycemia

Vitamin C functions in a human organism have been discussed. Connection with many diseases and its systemic deficiency has been emphasized. A review of current application of this vitamin in medicine has been made. Problems accompanying the use of reference sources of vitamin C "normal concentrations" in blood plasma have been characterised. 10 ranges of concentrations given by medical handbooks and textbooks have been compared in detail with 15 parallel ranges taken from scientific papers, paying attention to their significant discrepancies. Basing on source values, performing basic statistical calculations, a reliable mean range of vitamin C "normal concentrations" in blood plasma has been obtained: 36.1-79.4 mumol/l.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Diagnosis, Differential; Humans; Infant; Prognosis; Purpura; Scurvy

There is substantial evidence for a role of dietary antioxidants in the prevention of cardiovascular disease, but evidence for a protective effect of vitamin C is inconclusive. Two recent reports add to the supporting evidence and provide some new observations. The first study, a 5-year prospective population study of Finnish men, suggests that vitamin C-deficient men may be at increased risk of myocardial infarction. The second study suggests that vitamin C may play a role in preventing manifestations of existing coronary artery disease, rather than in limiting disease progression. Although these results suffer from the limitations of observational studies, they provide impetus for further investigation.

Topics: Antioxidants; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Male; Nutritional Physiological Phenomena; Prospective Studies; Risk Factors

Although gingival bleeding is a manifestation of both scurvy and inflammatory periodontal disease, the two conditions are distinctly separate entities. The defective collagen synthesis associated with scurvy also manifests many of the same symptoms as deficient vitamin C physiology, but neither condition is associated with periodontal disease. Unlike scurvy, the various periodontal diseases are caused by oral plaque microorganisms. The body's reaction to these microorganisms is strongly influenced by the compromised functioning of leucocytes and monocytes. Although certain infections and systemic diseases cause gingival bleeding, avitaminosis-C does not cause commonly encountered periodontitis. Vitamin C should not be used for the prophylaxis or cure of periodontal disease in otherwise healthy, well-nourished individuals. A patient with bleeding gingivae warrants referral to a periodontist, oral medicine specialist, or appropriately qualified dentist for examination and treatment.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Dental Plaque; Diagnosis, Differential; Gingival Hemorrhage; Humans; Leukocytes; Monocytes; Mouth Diseases; Periodontal Diseases; Periodontitis; Scurvy

The recent scientific literature indicates that beyond merely protecting against scurvy vitamin C contributes to many aspects of human health. The main areas of research reviewed include: 1. Vitamin C requirements of smokers. The data indicate that the vitamin C requirement of smokers is higher by at least 60 mg per day (up to 140 mg per day) than that of nonsmokers. 2. Important functions of the body, such as immune response, pulmonary function, and iron absorption are related to vitamin C intakes. Daily vitamin C intake of at least 150-200 mg per day enhance these functions. 3. Vitamin C may play critical roles in the prevention of CHD, cancer and cataract. Based on the available data, vitamin C intakes of at least 80-120 mg per day are associated with lowering the risk of these chronic diseases. 4. The literature documents that these and much higher intake levels of vitamin C are safe.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Cataract; Diet; Health Status; Humans; Neoplasms; Nutrition Policy; Nutritional Requirements

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Connective Tissue; Elastin; Extracellular Matrix Proteins; Gene Expression; Humans; Hydroxylation; Wound Healing

Senile cataract indicates the opacity of ocular lenses occurring in old and especially in very old people. Lens proteins are extremely long-living and often show oxidative damages. Aging and smoking appear to be the greatest risk factors for the development of lens opacities. The sufficient antioxidant protection of young lenses decreases with the aging process. Consequently, the importance of other protective factors increases. Nutritional factors, particularly vitamins with antioxidant properties, may influence the development of senile cataracts in the ocular lens. Meanwhile an association between the supply with vitamin C, E and beta-carotene and the risk of cataract development was demonstrated in animal studies and also in an increasing number of epidemiological studies. These epidemiological studies mainly support the hypothesis that higher vitamin intakes reduce the risk of developing cataracts in old age. The antioxidant properties of the named nutrients give a plausible explanation for the mechanism of cataractogenesis. On the basis of the present data definitive recommendation, necessary for cataract prevention can not yet be established. Some results seem to support higher recommendations. At the moment several large human intervention trials are carried out. Form these studies a further confirmation of the antioxidant hypothesis and of a dose-response-relationship are expected.

Topics: Adult; Aged; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; beta Carotene; Carotenoids; Cataract; Child; Humans; Risk Factors; Vitamin E; Vitamin E Deficiency

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cadmium; Cataract; Humans; Lens, Crystalline; Risk Factors; Smoking

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans

This article reviews the chemistry, functions, and toxicity of vitamin C, as well as its food sources, recommended daily allowance, and laboratory biochemical findings, to help clinicians understand and recognize its systemic and oral deficiency manifestations. An understanding of these topics will help the general dentist, periodontist, and oral surgeon appropriately prescribe vitamin C for their patients.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dentinogenesis; Humans; Periodontal Diseases

One of the vital roles of ascorbic acid (vitamin C) is to act as an antioxidant to protect cellular components from free radical damage. Ascorbic acid has been shown to scavenge free radicals directly in the aqueous phases of cells and the circulatory system. Ascorbic acid has also been proven to protect membrane and other hydrophobic compartments from such damage by regenerating the antioxidant form of vitamin E. In addition, reduced coenzyme Q, also a resident of hydrophobic compartments, interacts with vitamin E to regenerate its antioxidant form. The mechanism of vitamin C antioxidant function, the myriad of pathologies resulting from its clinical deficiency, and the many health benefits it provides, are reviewed.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Membrane; Free Radical Scavengers; Humans; Oxidation-Reduction; Oxidative Stress; Oxidoreductases; Ubiquinone; Vitamin E

The transport systems of animal and human tissues for vitamin C are reviewed with respect to their properties. It emerges that pure diffusion plays only a very minor role while a variety of more or less specific transporters is found on cellular membranes. Although most tissues prefer the reduced ascorbate over the oxidized dehydroascorbic acid and have high-affinity transporters for it, there are several examples for the reversed situation. Special attention is given to similarity or identity with glucose transporters, especially the GLUT-1 and the sodium-dependent intestinal and renal transporters, and to the very widespread dependence of ascorbate transport on sodium ions. The significance of ascorbate transport for vitamin C-requiring and nonrequiring species as well as alterations in states of disease can be seen from ample experimental evidence.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Transport; Carrier Proteins; Dehydroascorbic Acid; Diffusion; Glucose; Glucose Transporter Type 1; Humans; Monosaccharide Transport Proteins; Nutritional Requirements; Organ Specificity; Oxidation-Reduction; Sodium; Species Specificity; Stereoisomerism

A better understanding of the functions of ascorbic acid would help clarify the magnitude of the influence of this vitamin on health-related conditions. Many of the purported benefits require confirmation as well as a knowledge of the mechanism of action. The majority of investigations of the association of vitamin C with various types of cancer, with cardiovascular risk, and with cataract formation were epidemiologic studies. Often it was not possible to discern whether the apparent protective effect was due to vitamin C, vitamin E, or carotene, or to a combined effect of these nutrients or of additional factors. Human intervention trials may provide definitive and quantitative assessments of the role of vitamin C in health maintenance. We need to gain a more thorough understanding of the interactions of vitamin C with other nutrients, such as vitamin E and carotenoids, in order to appreciate the role of vitamin C in disease prevention. Investigators are increasingly recognizing the diverse functions of vitamin C in the body in addition to its role in collagen synthesis. However, the functional consequences of these many important roles of vitamin C remain essentially unknown. Excluding scurvy, the health consequences of inadequate vitamin C status are not well characterized. Nonetheless, epidemiologic evidence suggests a role for vitamin C in cancer and heart disease as well as in a number of other diseases.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Availability; Humans

Topics: Animals; Animals, Newborn; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Glutathione; Guinea Pigs; Mice; Rats

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Nutritional Status

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Nutritional Requirements

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Humans; Nutritional Physiological Phenomena

Topics: Amino Acid Sequence; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Dehydroascorbic Acid; Glutathione; Humans; Molecular Sequence Data; Oxidation-Reduction

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Evolution; Free Radical Scavengers; Humans; Lipid Peroxidation; Superoxides

It has been suggested that early features of scurvy (fatigue and weakness) may be attributed to carnitine deficiency. Ascorbate is a cofactor for two alpha-ketoglutarate-requiring dioxygenase reactions (epsilon-N-trimethyllysine hydroxylase and gamma-butyrobetaine hydroxylase) in the pathway of carnitine biosynthesis. Carnitine concentrations are variably low in some tissues of scorbutic guinea pigs. Ascorbic acid deficiency in guinea pigs resulted in decreased activity of hepatic gamma-butyrobetaine hydroxylase and renal but not hepatic epsilon-N-trimethyllsine hydroxylase when exogenous substrates were provided. It remains unclear whether vitamin C deficiency has a significant impact on the overall rate of carnitine synthesis from endogenous substrates. Nevertheless, results of studies of enzyme preparations and perfused liver in vitro and of scorbutic guinea pigs in vivo provide compelling evidence for participation of ascorbic acid in carnitine biosynthesis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carnitine; gamma-Butyrobetaine Dioxygenase; Humans; Hydroxylation; Mixed Function Oxygenases

Scurvy-like symptoms have been seen in experimental copper deficiency. This forecasts a role for the vitamin in copper metabolism. Ascorbate has been known to antagonize the intestinal absorption of copper. More recent studies have characterized a postabsorption role for ascorbate in the transfer of copper ions into cells. The vitamin reacts directly or indirectly with ceruloplasmin, a serum copper protein, specifically labilizing the bound copper atoms and facilitating their cross-membrane transport. Ascorbate at physiological levels and above impedes the intracellular binding of copper to Cu,Zn superoxide dismutase. The mechanism is unclear but nonetheless suggests both positive and negative regulatory functions for ascorbate in copper metabolism.

Topics: Absorption; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Transport; Ceruloplasmin; Copper; Humans; Intracellular Membranes

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Smoking

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Common Cold; Humans; Oxidants

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Diabetes Mellitus; Drug Synergism; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Free Radicals; Humans; Intestinal Absorption; Oxidation-Reduction

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Guinea Pigs; Hypercholesterolemia

Maintaining natural dentition is a realistic goal given today's improved caries control and attention to good oral hygiene. Expanding knowledge in the area of periodontal diseases provides further insight into health promotion practices which can be effective in preventing tooth loss. Vitamin C's role in maintaining the health of teeth and gingivae remains unchallenged. Now clinical evidence indicates that vitamin C functions in improving host defence mechanisms and is thereby implicated in preserving periodontal health. Common sense tells us that the monitoring of the vitamin C status of individuals, especially those at high risk (e.g., diabetics, smokers, elderly, etc.) for inadequate intakes, will yield positive results for periodontal health. Patient education programs that stress the importance of good nutrition, while at the same time providing practical information for the selection of a well balanced diet, are simple measures that will benefit many.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Oral Health; Periodontal Diseases

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cocarcinogenesis; Humans; Neoplasms; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamin E Deficiency

The list of vitamins recognized as essential in human nutrition is extensive. Only some of them, however, are attributed an important role in public health. The present paper deals with three of these selected because their deficiencies still prevail in important sectors of population in the Latin American Region: vitamin A, vitamin C and vitamin D. For each vitamin the paper discusses the scientific bases for their requirements, as well as pragmatic considerations to be taken into account for the derivation of recommended dietary intakes. Reference is made to the logic of applying the concepts of nutrient density when developing guidelines for the design of diets for the family and the community. Adequate nutrient density means that when a diet is consumed in sufficient amounts to satisfy energy requirements, the needs for essential nutrients are also being met. For the above reasons, the principle of expressing the recommended levels of intake of vitamin A and C per 1,000 kilocalories has been followed. This is not the case with vitamin D which, in view of its special feature of being synthesized endogenously, is not really a vitamin in the strict sense of the term and, therefore, a rational and consistent relationship with the energy of the diet cannot be established.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Diet; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Latin America; Male; Nutritional Requirements; Pregnancy; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency

Topics: 4-Hydroxyphenylpyruvate Dioxygenase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carnitine; Cell Line; Chemical Phenomena; Chemistry; Collagen; Complement Activating Enzymes; Complement C1q; Dopamine beta-Hydroxylase; Elastin; Fibroblasts; Free Radicals; Humans; Hydroxylation; Mixed Function Oxygenases; Multienzyme Complexes; Nucleosides; Nutritional Requirements; Oxidation-Reduction; Oxidoreductases Acting on CH-NH Group Donors; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; Procollagen-Proline Dioxygenase; Pyrimidines

The data on the influence of antioxidant vitamins (E and C) on the growth of induced and transplantable tumours in animals and on the development of cancer process in man as well as on the course of chemo- and radiotherapy are analyzed; a degree of vitamin provision of the tumour-bearing organism is discussed. Special attention is paid to optimal doses of the above mentioned vitamins. The necessity of combined application of antioxidant vitamins in cancer therapy is established.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Transformation, Neoplastic; Dose-Response Relationship, Drug; Drug Evaluation; Drug Synergism; Humans; Lipid Metabolism; Lipid Peroxides; Mice; Neoplasms; Neoplasms, Experimental; Nitrosamines; Oxidation-Reduction; Oxidative Phosphorylation; Rabbits; Rats; Tissue Distribution; Vitamin E; Vitamin E Deficiency

The various roles of the water-soluble vitamins (including choline and vitamin C) in diseases of swine are outlined. The most important role is in the prevention of deficiency disease; another important role is in relation to the immune response. Deficiency signs relating to each vitamin are described and the metabolism of each vitamin is outlined. Recent estimates of requirements are set out, together with suggestions on supplementation of practical diets for swine.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biotin; Choline; Choline Deficiency; Folic Acid; Folic Acid Deficiency; Niacin; Nutritional Requirements; Pantothenic Acid; Pyridoxine; Riboflavin; Riboflavin Deficiency; Solubility; Swine; Swine Diseases; Thiamine; Thiamine Deficiency; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency; Vitamins; Water

Topics: Adolescent; Adult; Aged; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Eating; Female; Humans; Intestinal Absorption; Male; Middle Aged; Nutrition Surveys; Nutritional Requirements; Risk; Smoking

Topics: Anticonvulsants; Ascorbic Acid; Ascorbic Acid Deficiency; Aspirin; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Folic Acid; Folic Acid Deficiency; Humans; Nutritional Requirements; Risk; Vitamins

Topics: Acetyltransferases; Adrenocorticotropic Hormone; Amides; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cells, Cultured; Copper; Cytoplasmic Granules; Endorphins; Humans; Mixed Function Oxygenases; Multienzyme Complexes; N-Terminal Acetyltransferases; Nerve Tissue Proteins; Oxygenases; Pro-Opiomelanocortin; Protein Precursors; Protein Processing, Post-Translational; Species Specificity

The ascorbic acid plays an important part by activation of hydroxylation reactions in various biosyntheses, such as in that of tropocollagen, bile acids and carnitine. It also considerably participates in the detoxication of compounds by hydroxylation and in the maintenance of the cytochrome P 450 contents in the liver. A sufficient supply is of importance for the absorption and accumulation of iron as well as for the efficiency of the immune system. After application of 14C-labelled ascorbic acid the compound is retained mainly in the brain, the salivary glands, the adrenal glands, the testes and in the eye lens. The largest contents of ascorbic acid lies in the pituitary gland, in the adrenal glands and in the eye lens. The need of ascorbic acid varies in man in dependence upon the state of development and the loads between 30 and 60 mg/die. In great smokers, after operations and traumas as well as when infections are present the intake of 100 to 200 mg a day are recommended. When more 1 g a day are taken the utilization decreases, the decomposition and the excretion, respectively, increase. A dose of more than 2 g a day inhibits the phagocytosis activity of leucocytes.

Topics: Age Factors; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carnitine; Collagen; Glycosaminoglycans; Humans; Immunoglobulins; Iron; Leukocytes; Lymphocytes; Nutritional Requirements; Phagocytosis; Smoking; Triglycerides

Scurvy and periodontitis both manifest gingival bleeding but constitute separate entities. Defective collagen in scurvy reflects many symptoms emanating from deficient vitamin C physiology. The various periodontal diseases are caused by oral plaque micro-organisms, the body's reaction to which is strongly influenced by inadequate functioning of leucocytes and monocytes. Although certain infections and systemic diseases cause gingival bleeding, avitaminosis C does not cause commonly encountered periodontal disease, but will aggravate established periodontitis. Vitamin C should not be used for prophylaxis or cure of periodontitis in healthy well-nourished individuals. A patient with bleeding gingivae warrants referral to oral medicine and periodontics specialists for examination and treatment.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Chronic Disease; Humans; Male; Periodontal Diseases; Periodontitis; Scurvy

Topics: Aminopyrine N-Demethylase; Aniline Hydroxylase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bromobenzenes; Cytochrome P-450 Enzyme System; Electron Transport; Epoxide Hydrolases; Ethanol; Glutathione Transferase; Heme; Humans; Kinetics; Liver; Methanol; Microsomes, Liver; Models, Biological; NADPH-Ferrihemoprotein Reductase; Nitroanisole O-Demethylase; Oxidation-Reduction; Pharmaceutical Preparations

Vitamin C (ascorbic acid) has been known to prevent scurvy for many years. Recent research has shown its importance in lipid and iron metabolism. Vitamin C may also have some effect on the immune system. There is not as yet conclusive evidence that ascorbic acid may cure or prevent colds or cancer. The vitamin has few side effects even when ingested in large quantities. Several methods for analysis of ascorbic acid have been developed. These include titration and fluorometric methods, a ferrozine technique automated for centrifugal analyzers, a high performance liquid chromatography method, and a dip-stick for urine ascorbic acid.

Topics: Aged; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Chemical Phenomena; Chemistry; Child; Common Cold; Female; Guinea Pigs; Humans; Infant; Lipid Metabolism; Male; Mice; Rabbits; Scurvy

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Drug Evaluation; Drug Therapy, Combination; Humans; Skin Diseases

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Leukocytes; Male; Middle Aged; Nutritional Requirements; Scurvy; Seasons

Topics: Anemia; Animal Feed; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Caniformia; Deficiency Diseases; Dolphins; Fishes, Poisonous; Histamine; Hyponatremia; Lactose Intolerance; Seals, Earless; Thiamine Deficiency; Vitamin E Deficiency

Topics: Adult; Alveolar Process; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Collagen; Epidemiologic Methods; Humans; Leukocytes; Mouth Mucosa; Nutritional Physiological Phenomena; Periodontal Diseases; Periodontium; Permeability; Tooth Mobility

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Corneal Diseases; Diabetic Retinopathy; Drug Therapy, Combination; Eye; Eye Burns; Eye Diseases; Humans; Tuberculosis, Ocular; Vision, Ocular

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Mice; Neoplasms; Neoplasms, Experimental

This article is an attempt to study the metabolic functions of vitamin C and E together. Such a study must necessarily be imcomplete owing to the extreme richness of the literature. The increasing importance of the work on free radical reactions, their toxicity and carcinogenic action, and also their relation to the metabolism of metals, particularly iron, copper, selenium, and zinc, shows a number of metabolic pathways with which both vitamins interact. It is hoped that this article will indicate future research possibilities.

Topics: Adolescent; Adult; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Chemical Phenomena; Chemistry; Dehydroascorbic Acid; Fatty Acids, Unsaturated; Female; Fertility; Food Analysis; Food Handling; Free Radicals; Hot Temperature; Humans; Inactivation, Metabolic; Leukocytes; Male; Nutritional Requirements; Pregnancy; Sex Factors; Species Specificity; Structure-Activity Relationship; Trace Elements; Vitamin E; Vitamin E Deficiency

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cholelithiasis; Cholesterol; Diet; Disease Models, Animal; Guinea Pigs; Humans; Lipids; Liver; Rats; Triglycerides

The high concentration of ascorbate in leucocytes and its rapid expenditure during infection and phagocytosis suggests a role for the vitamin in the immune process. Evidence published to date shows an involvement in the migration and phagocytosis by macrophages and leucocytes, as well as the induction and expression of delayed hypersensitivity. Its effect on antibody production and complement levels is controversial but probably minimal. This study suggests there is room for further investigation into the effect of ascorbate on immunity, particularly with defined populations, but cautions the use of megadose therapy.

Topics: Antibody Formation; Ascorbic Acid; Ascorbic Acid Deficiency; Complement System Proteins; Female; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Interferons; Leukocytes; Male; Phagocytosis; Pregnancy

Topics: Acute Disease; Animals; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Chronic Disease; Fatty Liver; Humans; Hypercholesterolemia; Lipid Metabolism; Liver Cirrhosis; Scurvy

Topics: Adolescent; Adult; Aged; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Capillary Fragility; Child; Child, Preschool; Environment; Female; Hormones; Humans; Hypersensitivity; Infant; Infant, Newborn; Infant, Premature; Infections; Lactation; Male; Mental Health; Middle Aged; Nutritional Requirements; Physical Exertion; Pregnancy; Wound Healing

Topics: Adrenal Cortex Hormones; Adrenal Gland Diseases; Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Male; Rats; Vitamin A; Vitamin A Deficiency

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Nutrition Disorders; Periodontitis; Proteins; Vitamins

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Cholesterol, Dietary; Cholic Acids; Humans; Hypercholesterolemia; Scurvy

Topics: Adult; Age Factors; Anemia; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Diseases, Developmental; Capillaries; Child; Collagen Diseases; Connective Tissue; Creatinine; Dentin; Gingival Hemorrhage; Hemorrhage; Humans; Hydroxyproline; Infant; Scurvy; Skin Diseases; Species Specificity

Plasma, leukocyte, and platelet ascorbic acid levels are decreased in women ingesting oral contraceptive steroids. Studies have shown that it is the estrogenic component of the oral contraceptive agents that is associated with the decresased ascorbic acid concentrations. Urinary excretion of ascorbic acid does not appear to be increased by the steroids. Although serum levels of copper are increased by estrogens and oral contraceptives, ascorbic acid catabolism does not appear to be increased (unpublished). Our preliminary data on tissue uptake of ascorbic acid suggest that changes in tissue distribution are one possible answer for the observed effects of the steroids on blood levels of ascorbic acid.. Plasma, leukocyte and platelet ascorbic acid levels have been shown to decrease in in women using oral contraceptives (OC). Supplemental ascorbic acid therapy ranging from 50-200 mg/day showed no difference between the values for supplemented and nonsupplemented OC use. Measurement of plasma ascorbic acid after supplementation with 500 mg ascorbic acid/day for 14 days showed that adequate supplementation to reach tissue saturation and maximum fasting plasma levels occurred in control subjects but not in OC users. Other studies indicated that when women were maintained for 75 days on high ascorbic acid intake, the plasma levels in OC users were lower than in controls. Studies in humans and animals suggest that the estrogen in OCs cause decreased plasma and tissue levels of ascorbic acid. Women taking oral progestin (.35 mg daily norethisterone) and depot progestin (150 mg medroxyprogesterone acetate im every 3 months) had similar leukocyte plasma and platelet levels of ascorbic acid to controls. 625 mg daily of conjugated estrogens showed lower plasma and leukocyte levels than controls. Whereas increase of urinary excretion of ascorbic acid during OC therapy has not been shown, an increase in serum copper levels has been shown under OC use and estrogen influence. It is suggested that an increased catabolism of ascorbic acid accounts for the decreased plasma and tissue levels in humans and animals with estrogen or OC steroids. Other unconfirmed or disputed suggestions include decreased absorption, changes in tissue distribution and decreased levels of reducing compounds. Tissue uptake patterns in steroid-treated animals appear altered suggesting that changes in tissue distribution may be associated with observed changes in ascorbic acid blood levels in OC users.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Platelets; Blood Vessels; Contraceptives, Oral; Contraceptives, Oral, Hormonal; Copper; Estradiol; Estrogens; Female; Humans; Leukocytes; Mestranol; Progestins

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Chlorine; Erythrocyte Aging; Erythrocytes; Glucosephosphate Dehydrogenase Deficiency; Hexosephosphates; Humans; Minnesota; Pentosephosphates; Renal Dialysis; Uremia; Water

Topics: Acyltransferases; Adult; Animals; Arteries; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Disease Models, Animal; Evaluation Studies as Topic; Forecasting; Humans; Phosphatidylcholines; Self Medication

Topics: Absorption; Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Circadian Rhythm; Dose-Response Relationship, Drug; Erythrocyte Count; Hemoglobins; Humans; Infant; Leukocytes; Methods; Nutritional Requirements

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Carbon Dioxide; Carbon Isotopes; Cholesterol; Chronic Disease; Disease Models, Animal; Feces; Guinea Pigs; Kinetics; Liver; Skin; Spleen

Topics: Aminopyrine N-Demethylase; Aniline Compounds; Animals; Anisoles; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Cytochrome Reductases; Electron Transport; Guinea Pigs; Kinetics; Liver; Methyltransferases; Microsomes, Liver; Mixed Function Oxygenases; Oxidation-Reduction; Pentobarbital; Pharmaceutical Preparations; Sleep; Time Factors; Zoxazolamine

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Birds; Guinea Pigs; Half-Life; Hominidae; Humans; Liver; Rats

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Common Cold; Depression; Guinea Pigs; Humans; Male; Miliaria; Nutritional Requirements; Scurvy; Sjogren's Syndrome; Skin Manifestations; Urinary Bladder Neoplasms

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Development; Collagen; Growth; Guinea Pigs; Nutritional Requirements; Primates; Salmon; Salmonidae; Species Specificity; Spinal Diseases; Wound Healing

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Diet; Guinea Pigs; Humans; Nutritional Requirements; Wound Healing; Wounds and Injuries

Topics: Animals; Arteries; Ascorbic Acid; Ascorbic Acid Deficiency; Chick Embryo; Collagen; Elastin; Guinea Pigs; Humans; Hydroxyproline; Proline; Protein Binding; Skin

Topics: Acidosis; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Deoxyribonucleases; Glycogen; Guinea Pigs; Hydrogen-Ion Concentration; Iron; Lysosomes; Male; Membranes; Mitochondria; Muscles; Oxidation-Reduction; Testis

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Humans

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Guinea Pigs; Humans; Rabbits

Topics: Adult; Anemia, Hemolytic; Anemia, Macrocytic; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Cell Count; Bone Marrow Cells; Erythrocytes; Erythropoiesis; FIGLU Test; Folic Acid; Folic Acid Deficiency; Hemolysis; Hemorrhagic Disorders; Humans; Iron; Leukocytes; Liver; Reticulocytes; Scurvy; Tissue Extracts; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma 256, Walker; Guinea Pigs; Leukemia; Neoplasms; Neoplasms, Experimental; Rats; Research; Sarcoma; Sarcoma, Experimental; Sarcoma, Yoshida

Consumption of vitamin C-rich fruits and vegetables has been associated with greater feelings of vitality. However, these associations have rarely been tested in experimental trials. The aim of the current study was to test the effects of eating a vitamin C-rich food (kiwifruit) on subjective vitality and whether effects are driven by vitamin C. Young adults (n = 167, 61.1% female, aged 18–35 years) with plasma vitamin C < 40 µmol/L were allocated to three intervention conditions: kiwifruit (2 SunGold™ kiwifruit/day), vitamin C (250 mg tablet/day), placebo (1 tablet/day). The trial consisted of a two-week lead-in, four-week intervention, and two-week washout. Plasma vitamin C and vitality questionnaires (total mood disturbance, fatigue, and well-being) were measured fortnightly. Self-reported sleep quality and physical activity were measured every second day through smartphone surveys. Nutritional confounds were assessed using a three-day food diary during each study phase. Plasma vitamin C reached saturation levels within two weeks for the kiwifruit and vitamin C groups. Participants consuming kiwifruit showed a trend of improvement in mood disturbance, significantly decreased fatigue, and significantly improved well-being after two weeks of the intervention. Improvements in well-being remained elevated through washout. Consumption of vitamin C tablets alone was associated with improved well-being after two weeks, and additionally improved mood and fatigue for participants with consistently low vitamin C levels during lead-in. Diet records showed that participants consuming kiwifruit reduced their fat intake during the intervention period. Intervention effects remained significant when adjusting for condition allocation groupings, age, and ethnicity, and were not explained by sleep quality, physical activity, BMI, or other dietary patterns, including fat intake. There were no changes in plasma vitamin C status or vitality in the placebo group. Whole-food consumption of kiwifruit was associated with improved subjective vitality in adults with low vitamin C status. Similar, but not identical changes were found for vitamin C tablets, suggesting that additional properties of kiwifruit may contribute to improved vitality.

Topics: Actinidia; Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Australia; Fatigue; Female; Fruit; Humans; Male; Mood Disorders; New Zealand; Phytotherapy; Placebos; Surveys and Questionnaires; Young Adult

To study vitamin C pharmacokinetics in septic shock.. Prospective pharmacokinetic study.. Two intensive care units.. Twenty-one patients with septic shock enrolled in a randomised trial of high dose vitamin C therapy in septic shock.. Patients received 1.5 g intravenous vitamin C every 6 hours. Plasma samples were obtained before and at 1, 4 and 6 hours after drug administration, and vitamin C concentrations were measured by high performance liquid chromatography.. Clearance, volume of distribution, and half-life were calculated using noncompartmental analysis. Data are presented as median (interquartile range [IQR]).. Of the 11 participants who had plasma collected before any intravenous vitamin C administration, two (18%) were deficient (concentrations < 11 μmol/L) and three (27%) had hypovitaminosis C (concentrations between 11 and 23 μmol/L), with a median concentration 28 μmol/L (IQR, 11-44 μmol/L). Volume of distribution was 23.3 L (IQR, 21.9-27.8 L), clearance 5.2 L/h (IQR, 3.3-5.4 L/h), and half-life 4.3 h (IQR, 2.6-7.5 h). For the participants who had received at least one dose of intravenous vitamin C before sampling, T0 concentration was 258 μmol/L (IQR, 162- 301 μmol/L). Pharmacokinetic parameters for subsequent doses were a median volume of distribution 39.9 L (IQR, 31.4-44.4 L), clearance 3.6 L/h (IQR, 2.6-6.5 L/h), and half-life 6.9 h (IQR, 5.7-8.5 h).. Intravenous vitamin C (1.5 g every 6 hours) corrects vitamin C deficiency and hypovitaminosis C and provides an appropriate dosing schedule to achieve and maintain normal or elevated vitamin C levels in septic shock.

Topics: Administration, Intravenous; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Chromatography, High Pressure Liquid; Critical Illness; Dose-Response Relationship, Drug; Humans; Prospective Studies; Shock, Septic; Vitamins

Bateman purpura is characterized by diffuse senile skin atrophy, senile purpura and spontaneous stellar pseudocicatrices. Cutaneous changes in the course of ageing have been related to lower levels of ascorbic acid into the dermis of elderly people.. In this study, we postulate that senile purpura could be linked to dermal vitamin C deficiency and could be corrected by topical administration of this vitamin.. A 12-weeks, hemi-member (forearm or leg), randomized double-blind comparative study was conducted in 18 patients with Bateman purpura aged over than 60 years. At each visit, clinical assessment and biometrological measurements were performed. Clinical examination and scoring by experts showed a significant improvement on the vitamin C-treated side compared with the control, with reduction of haemorrhage areas, increase of dermal thickness.. Twice-daily application of 5% topical vitamin C led to a clinically apparent improvement of the skin symptoms and allows beneficial effects on skin elasticity and thickness. Bateman purpura, a classical sign of photoaging whose origin has not clearly been recognized could be improved by vitamin C applied on to the skin.. These results confirm the hypothesis of the underlying role of vitamin C deficiency in the determinism of Bateman purpura.

Topics: Administration, Cutaneous; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Colorimetry; Double-Blind Method; Elasticity; Humans; Purpura; Skin; Skin Aging; Skin Cream; Skinfold Thickness; Vitamins

Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO).. To investigate the effects of vitamin C as an adjuvant therapy to the three used iron chelators in moderately iron-overloaded young vitamin C-deficient patients with β-thalassemia major (β-TM) in relation to tissue iron overload.. This randomized prospective trial that included 180 β-TM vitamin C-deficient patients were equally divided into three groups (n = 60) and received DFO, deferiprone (DFP), and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin C supplementation (100 mg daily) or not (n = 30). All patients received vitamin C (group A) or no vitamin C (group B) were followed up for 1 yr with assessment of transfusion index, hemoglobin, iron profile, liver iron concentration (LIC) and cardiac magnetic resonance imaging (MRI) T2*.. Baseline vitamin C was negatively correlated with transfusion index, serum ferritin (SF), and LIC. After vitamin C therapy, transfusion index, serum iron, SF, transferrin saturation (Tsat), and LIC were significantly decreased in group A patients, while hemoglobin and cardiac MRI T2* were elevated compared with baseline levels or those in group B without vitamin C. The same improvement was found among DFO-treated patients post-vitamin C compared with baseline data. DFO-treated patients had the highest hemoglobin with the lowest iron, SF, and Tsat compared with DFP or DFX subgroups.. Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with β-TM, with no adverse events.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; beta-Thalassemia; Biomarkers; Dietary Supplements; Drug Therapy, Combination; Female; Humans; Iron; Iron Chelating Agents; Iron Overload; Liver; Magnetic Resonance Imaging; Male; Treatment Outcome

The early indications of vitamin C deficiency are unremarkable (fatigue, malaise, depression) and may manifest as a reduced desire to be physically active; moreover, hypovitaminosis C may be associated with increased cold duration and severity. This study examined the impact of vitamin C on physical activity and respiratory tract infections during the peak of the cold season. Healthy non-smoking adult men (18-35 years; BMI < 34 kg/m2; plasma vitamin C < 45 µmol/L) received either 1000 mg of vitamin C daily (n = 15) or placebo (n = 13) in a randomized, double-blind, eight-week trial. All participants completed the Wisconsin Upper Respiratory Symptom Survey-21 daily and the Godin Leisure-Time Exercise Questionnaire weekly. In the final two weeks of the trial, the physical activity score rose modestly for the vitamin C group vs. placebo after adjusting for baseline values: +39.6% (95% CI [-4.5,83.7]; p = 0.10). The number of participants reporting cold episodes was 7 and 11 for the vitamin C and placebo groups respectively during the eight-week trial (RR = 0.55; 95% CI [0.33,0.94]; p = 0.04) and cold duration was reduced 59% in the vitamin C versus placebo groups (-3.2 days; 95% CI [-7.0,0.6]; p = 0.06). These data suggest measurable health advantages associated with vitamin C supplementation in a population with adequate-to-low vitamin C status.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Body Mass Index; Common Cold; Dietary Supplements; Double-Blind Method; Health Surveys; Healthy Volunteers; Humans; Incidence; Male; Motor Activity; Nutritional Status; Surveys and Questionnaires; Wisconsin; Young Adult

Vitamin C has important physical and mental health benefits and plasma concentrations reflect recent intakes. Inflammation associated with any acute illness can lead to poor appetite and low food intake in older people. The aims of this report were to assess the prevalence and clinical significance of vitamin C deficiency among hospitalized acutely-ill older patients.. Three hundred and twenty two patients (152 [47%] female), aged 65 yrs. and over who took part in a randomized, double blind, placebo-controlled trial had their nutritional status assessed from anthropometric, hematological and biochemical data at baseline, and after 6 weeks and 6 months. Vitamin C was measured using a fluorimetric technique and logistic regression analysis was performed to determine the influence of a number of clinical indicators, including tissue inflammation measured using C-reactive protein on vitamin C concentrations. Clinical outcome measures including symptoms of depression were also compared between patients with vitamin C deficiency and those with normal levels.. At baseline, 116 (36%) patients had a vitamin C concentration below 11 µmol/L indicating biochemical depletion. The figures at 6 weeks and 6 months were 28 (22%) and 44 (28%) patients, respectively. Older age, male gender, smoking, increased dependency and tissue inflammation were associated with lower vitamin C concentrations. Patients with vitamin C biochemical depletion had significantly increased symptoms of depression compared with those with higher concentrations at baseline (p=0.035) and at 6 weeks (p=0.028).. A high proportion of older patients had sub-optimal vitamin C status and this was associated with increased symptoms of depression.

Topics: Acute Disease; Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; C-Reactive Protein; Depression; Double-Blind Method; Female; Hospitalization; Humans; Inflammation; Male; Nutritional Status; Placebos; Prognosis; Sex Factors; Smoking

Deficient ascorbic acid levels (AALs) and Type 2 diabetes mellitus (T2DM) are associated with periodontal disease. This study evaluated the relationship between plasma AAL and periodontitis in systemically healthy and T2DM subjects, which to the best of our knowledge is being reported for the first time.. One hundred twenty subjects were categorized into four groups of 30 each as group 1: without periodontal disease; group 2: chronic gingivitis; group 3: chronic periodontitis, and group 4: chronic periodontitis and freshly diagnosed T2DM. Plaque index (PlI), sulcus bleeding index (SBI), and probing pocket depths (PPDs) were evaluated. Venous blood was evaluated for plasma AAL spectrophotometrically. Randomized subjects were subgrouped within groups 2-4, to receive either scaling and root planing (SRP) with dietary supplementation (450 mg) of ascorbic acid (AA) for two weeks or only SRP. After two weeks, the clinical parameters were reassessed. Tukey's multiple post hoc procedures and paired t test were used with the level of statistical significance adjusted to p ≤ .05.. AAL plasma levels were significantly greater in group 1 than in group 2 (p = .0007) and in group 4 (p = .0003). A significant reduction in the SBI was seen in the subgroups that received dietary supplementation of vitamin C within group 2 (p = .0012) and group 4 (p = .036).. Plasma AAL is below the normal range in systemically healthy subjects with gingivitis and diabetics with periodontitis. Dietary AA supplementation with SRP improves the SBI in subjects with gingivitis and diabetics with periodontitis.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Dental Plaque Index; Dental Scaling; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Gingival Pocket; Gingivitis; Humans; India; Middle Aged; Periodontal Index; Periodontitis; Root Planing

We previously reported that asthmatic children with GSTM1 null genotype may be more susceptible to the acute effect of ozone on the small airways and might benefit from antioxidant supplementation. This study aims to assess the acute effect of ozone on lung function (FEF(25-75)) in asthmatic children according to dietary intake of vitamin C and the number of putative risk alleles in three antioxidant genes: GSTM1, GSTP1 (rs1695), and NQO1 (rs1800566).. 257 asthmatic children from two cohort studies conducted in Mexico City were included. Stratified linear mixed models with random intercepts and random slopes on ozone were used. Potential confounding by ethnicity was assessed. Analyses were conducted under single gene and genotype score approaches.. The change in FEF(25-75) per interquartile range (60 ppb) of ozone in persistent asthmatic children with low vitamin C intake and GSTM1 null was -91.2 ml/s (p = 0.06). Persistent asthmatic children with 4 to 6 risk alleles and low vitamin C intake showed an average decrement in FEF(25-75) of 97.2 ml/s per 60 ppb of ozone (p = 0.03). In contrast in children with 1 to 3 risk alleles, acute effects of ozone on FEF25-75 did not differ by vitamin C intake.. Our results provide further evidence that asthmatic children predicted to have compromised antioxidant defense by virtue of genetic susceptibility combined with deficient antioxidant intake may be at increased risk of adverse effects of ozone on pulmonary function.

Topics: Age Factors; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Asthma; Child; Cohort Studies; Dietary Supplements; Double-Blind Method; Environmental Exposure; Enzymes; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Linear Models; Lung; Male; Maximal Midexpiratory Flow Rate; Mexico; NAD(P)H Dehydrogenase (Quinone); Ozone; Phenotype; Polymorphism, Genetic; Risk Assessment; Risk Factors; Urban Health

Vitamin C (ascorbate) deficiency and symptoms consistent with deficiency (fatigue, myalgia, dyspnoea, gingivitis, cardiovascular instability and depression) are common in patients with renal failure. This study aimed to determine if supplementation with ascorbate in patients with severe renal failure improved symptoms or cardiovascular stability, or was associated with adverse effects.. The study was a 3-month, double-blind, randomized trial of ascorbic acid 250 mg or matching placebo given thrice weekly. Subjects were clinically stable and either received conventional dialysis or had an estimated glomerular filtration rate of <20 mL/min. Symptoms were measured using the Kidney Dialysis Quality of Life-Short Form (KDQOL-SF™) symptom subscale, and the study was 80% powered to detect a change of 10 in the KDQOL-SF™.. Ninety-nine subjects were randomized, and ascorbate deficiency was present in 40% at baseline. Mean symptom scores at follow-up were similar in the two groups (P-value=0.19). There was a trend to slightly worse nausea scores in the ascorbate group after controlling for the level of baseline nausea (P=0.09), and there was no impact on cardiovascular stability. Compliance appeared adequate at 91%, and deficiency was corrected in most (85%) of the subjects in the active treatment group.. This study indicates that ascorbate supplementation does not improve symptoms or cardiovascular stability in those with severe renal impairment, but is associated with a trend towards worse nausea.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Double-Blind Method; Humans; Prospective Studies; Renal Insufficiency; Uremia

Hypovitaminosis C and D are highly prevalent in acutely hospitalized patients, but the clinical significance of these biochemical abnormalities is not known. Because deficiencies of vitamin C and D have been linked to psychologic abnormalities, vitamin C or D provision could improve the mood state of acutely hospitalized patients.. Double-blind clinical trial of the effect of vitamin C (500 mg twice daily) or vitamin D (1000 IU twice daily) on mood, as assessed with a validated instrument, the Profile of Mood States.. Vitamin C therapy increased plasma (P < 0.0001) and mononuclear leukocyte (P = 0.014) vitamin C concentrations and was associated with a 34% reduction in mood disturbance (P = 0.013). Vitamin D therapy increased plasma 25-hydroxyvitamin D concentrations (P = 0.0004), but had no significant effect on mood.. Treatment of hypovitaminosis C improves the mood state of acutely hospitalized patients.

Topics: Acute Disease; Affect; Ascorbic Acid; Ascorbic Acid Deficiency; Double-Blind Method; Female; Hospitalization; Humans; Leukocytes, Mononuclear; Male; Prevalence; Psychological Tests; Vitamin D; Vitamin D Deficiency

Vitamin C levels decrease during hemodialysis (HD), which deteriorates antioxidant defense. Vitamin C may also act pro-oxidatively, via reduction in Fe(III). We sought to determine whether intravenous iron (Fe(iv))-induced oxidative stress differs in HD patients with low and physiological vitamin C levels and whether intravenous vitamin C (C(iv)) administration during HD would change the response to Fe(iv).. Twenty patients with vitamin C deficiency (median 15.7 micromol/l, range 8.0-22.7) received Fe(iv) (100 mg iron sucrose between 150 and 180 min of HD). After 4 weeks of oral supplementation, the levels of vitamin C were comparable with those of controls (60.1 micromol/l, range 47.4-70.9). Patients were subsequently treated with (1) Fe(iv), (2) Fe(iv) and continuous 2 mg/min C(iv) throughout HD, (3) saline (S), and (4) S+C(iv). Plasma thiobarbituric acid reacting substances (TBARS) and vitamin C were assessed before, during and after FE(iv)(S), and 15, 30 and 60 min after infusion.. Fe(iv) induced a comparable rise in TBARS in patients with vitamin C deficiency (before Fe(iv), 1.9 micromol/l, range 1.4-1.9; after Fe(iv), 2.6 micromol/l, range 2.3-2.9; p < 0.01) and in those with normal vitamin C (before Fe(iv), 1.9 micromol/l, range 1.7-2.1; after Fe(iv), 2.6 micromol/l, range 2.5-2.9; p < 0.01). Fe(iv)+C(iv) resulted in a greater increase in TBARS (after Fe(iv), 3.1 micromol/l, range 2.8-3.2) compared with Fe(iv) (p < 0.01).. Iron sucrose-induced oxidative stress is comparable in HD patients with vitamin C deficiency and in those with normal vitamin C. We documented a pro-oxidative effect of vitamin C during Fe(iv)+C(iv) administration.

Topics: Administration, Oral; Aged; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Thiobarbituric Acid Reactive Substances

Ascorbate supplementation for patients on regular dialysis treatment (RDT) is advised to obviate deficiency and improve epoetin response in those with functional iron deficiency. However, clear-cut safety concerns regarding hyperoxalemia are still poorly understood. This study tries to establish safety/efficacy profiles of ascorbate and oxalate during long-term intravenous ascorbate supplementation.. A prospective study was performed in 30 patients on RDT showing ascorbate deficiency (plasma ascorbate < 2.6 mg/L [<15 micromol/L]): 18 patients were administered intravenous ascorbate during 18 months (250 mg/wk, subsequently increased to 500 mg), and 12 patients were taken as reference untreated cases. Plasma ascorbate and oxalate assays and dialytic balance determinations were performed (ion chromatography and reverse-phase high-performance liquid chromatography, respectively) at baseline, during treatment, and 12 months after withdrawal.. Plasma ascorbate levels increased dose dependently with supplementation (1.6 +/- 0.8 mg/L [9.1 +/- 4.6 mumol/L] at baseline, 2.8 +/- 1.8 mg/L [15.9 +/- 10.1 micromol/L]) with 250 mg of ascorbate, and 6.6 +/- 2.8 mg/L [37.5 +/- 16.0 micromol/L] with 500 mg/wk of ascorbate), but only normalized with greater dosages for several months in 94% of patients. Baseline plasma oxalate levels increased from 3.2 +/- 0.8 mg/L (35.8 +/- 8.8 micromol/L) to 3.6 +/- 0.8 mg/L (39.5 +/- 9.1 micromol/L) and 4.5 +/- 0.9 mg/L (50.3 +/- 10.4 micromol/L) with 250 and 500 mg, respectively ( P < 0.001). The calcium oxalate saturation threshold was exceeded by 7 of 18 patients (40%) during 6 months therapy with 500 mg/wk. Ascorbate dialysis removal increased from 37.8 +/- 23.2 mg (215 +/- 132 micromol) to 99.6 +/- 51.7 mg (566 +/- 294 micromol) during supplementation (P < 0.001), with corresponding increases in oxalate removal from 82.5 +/- 33.2 mg (917 +/- 369 micromol) to 111.2 +/- 32.6 mg/L (1,236 +/- 362 micromol; P < 0.01). Withdrawal reverted plasma levels and dialysis removal to initial values. Values for untreated patients did not change during 1 year of follow-up.. Patients on RDT may resolve ascorbate deficiency with intravenous supplementation of 500 mg/wk, but this implies a significant risk for oxalate supersaturation. Oxalate measurements are strongly recommended during long-term ascorbate therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium Oxalate; Drug Resistance; Erythropoietin; Female; Humans; Hyperoxaluria; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Ascorbate and glutathione play central roles in the defense against free radicals and oxidants that are implicated in chronic diseases.. The objective was to determine the ability of vitamin C supplements to modulate the concentration of glutathione in human lymphocytes.. The effect of vitamin C supplements was determined in a sequential study with time points before supplementation, after 13 wk of vitamin C supplements (500 or 1000 mg/d), and after 13 wk of matching placebo. The supplementation group was selected on the basis of low plasma ascorbate (<33 mmol/L) and consisted of 48 healthy men and women, smokers and nonsmokers, aged 25-64 y. Ascorbate and glutathione were measured in purified lymphocytes.. At baseline, the mean (+/-SD) concentration of plasma ascorbate was 19.5 +/- 7.2 micro mol/L, 22.5 micro mol/L below the median of normal distribution. The ascorbate concentration in plasma was linearly associated with that in lymphocytes (r = 0.53, P < 0.001). On supplementation with vitamin C, lymphocyte ascorbate increased by 51% (from 16.7 +/- 4.9 to 25.3 +/- 6.9 nmol/mg protein; P < 0.001) and was accompanied by an increase of lymphocyte glutathione by 18% (from 22.5 +/- 4.5 to 26.6 +/- 6.5 nmol/mg protein; P < 0.001). After placebo, the ascorbate and glutathione concentrations fell to near baseline concentrations (17.1 +/- 5.4 and 23.5 +/- 6.4 nmol/mg protein, respectively). No significant interaction was observed for sex and smoking status. Finally, the changes in lymphocyte ascorbate after supplementation were strongly associated with changes in lymphocyte glutathione (r = 0.71, P < 0.001). The association suggests that every 1-mol change in ascorbate is accompanied by a change of approximately 0.5 mol in glutathione.. Vitamin C supplements increase glutathione in human lymphocytes.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Chromatography, High Pressure Liquid; Female; Glutathione; Humans; Lymphocytes; Male; Middle Aged

The young people of draft age often have breach of a the dietary, that guite often is accompanied by decrease resistance and adaptation of opportunities. Application vegetative BAS to food (the beet with selderej) separately or especially together with liquid biphidiumbacterin gives good therapeutic effect.

Topics: Adaptation, Physiological; Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Deficiency Diseases; Dietary Supplements; Feces; Humans; Male; Military Personnel; Nutrition Disorders; Vegetables

Lack of reliable dietary data has hampered the ability to effectively distinguish between effects of smoking and diet on plasma antioxidant status. As confirmed by analyses of comprehensive food-frequency questionnaires, the total dietary intakes of fruit and vegetables and of dietary antioxidants were not significantly different between the study groups in the present study, thereby enabling isolation of the effect of smoking.. Our objective was to investigate the effect of smoking on plasma antioxidant status by measuring ascorbic acid, alpha-tocopherol, gamma-tocopherol, beta-carotene, and lycopene, and subsequently, to test the effect of a 3-mo dietary supplementation with a moderate-dose vitamin cocktail.. In a double-blind, placebo-controlled design, the effect of a vitamin cocktail containing 272 mg vitamin C, 31 mg all-rac-alpha-tocopheryl acetate, and 400 microg folic acid on plasma antioxidants was determined in a population of smokers (n = 37) and nonsmokers (n = 38). The population was selected for a low intake of fruit and vegetables and recruited from the San Francisco Bay area.. Only ascorbic acid was significantly depleted by smoking per se (P < 0.01). After the 3-mo supplementation period, ascorbic acid was efficiently repleted in smokers (P < 0.001). Plasma alpha-tocopherol and the ratio of alpha- to gamma-tocopherol increased significantly in both supplemented groups (P < 0.05).. Our data suggest that previous reports of lower concentrations of plasma vitamin E and carotenoids in smokers than in nonsmokers may primarily have been caused by differences in dietary habits between study groups. Plasma ascorbic acid was depleted by smoking and repleted by moderate supplementation.

Topics: Adult; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Dietary Supplements; Fruit; Humans; Male; Middle Aged; Smoking; Vegetables; Vitamin E

A placebo-controlled, depletion-repletion protocol was utilized to examine the effect of vitamin C status on substrate utilization during a 90 min walk at 50% maximal oxygen consumption (VO2max). Nine vitamin C depleted subjects (plasma vitamin C < 28 mumol/L) agreed to participate in the 5-week study (aged, 27.6 +/- 2.5 years, mean +/- SE; 5 females, 4 males). Subjects were apparently healthy but unaware of their vitamin C status. Prior to the experimental period, VO2max was measured using open-circuit spirometry during a graded walking protocol. Subjects ingested a placebo capsule daily during weeks 1-3 and a 500 mg vitamin C capsule daily during weeks 4-5 of the experimental study. Mean plasma vitamin C rose nearly 3-fold and mean plasma carnitine fell by nearly 20% at repletion (week 5) versus depletion (week 3). At the end of weeks 3 and 5, subjects completed a 90 minute treadmill walk at an exercise intensity of 50% VO2max. The relative contribution of fat utilized for energy during walking did not differ in the vitamin C depleted versus repleted states. However, work performed by subjects and gross efficiency during exercise increased significantly at repletion versus depletion (10% and 15%, respectively). These data indicate that vitamin C depletion is associated with reduced work efficiency during submaximal exercise.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Energy Metabolism; Exercise; Female; Humans; Lipid Metabolism; Male; Nutritional Status; Oxygen Consumption; Placebos

To evaluate the role of factors that may affect the level of plasma ascorbic acid (AA), including age, body weight, physical activity, minor illness and the impact of prior depletion and repletion.. After one month of stabilization on 60 mg vitamin C/day, subjects underwent two complete depletion-repletion cycles (one cycle=one month of vitamin C depletion with nine mg/day, followed by one month of repletion with 117 mg per day). Subjects (68 men, ages 30 to 59 years) did not smoke or drink alcohol during the study. All food was provided by the study.. There was extreme individual variability in the plasma AA level achieved on an identical repletion dose: after four weeks at 117 mg/day of vitamin C, AA ranged from 26.8 micromol/L to 85.8 micromol/L. Body weight was inversely associated with plasma AA attained (p<0.0001). Regression analysis indicated that, compared to a 130-lb man, a 200-lb man reached 10 micromol/L lower AA after the first repletion and 18 micromol/L lower AA after the second repletion. One-third of the subjects did not reach a plasma plateau after the first repletion. Prior depletion and apparent repletion also had a major impact, and only 10% of subjects reached the same plasma AA on the second repletion as on the first repletion.. Plasma AA attained on a given dose depends on body weight (or dose per kg of body weight) and on whether or not any prior depletions had been repleted adequately. The results have implications for nutrition recommendations and research design.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Diet; Exercise; Humans; Male; Middle Aged; Regression Analysis

To conduct an inpatient study on the recommended dietary allowance (RDA) for vitamin C, we developed a unique vitamin C-deficient diet using a nutrient database and selective menus. Fourteen different menus were developed offering > 300 items with 0-2.4 mg vitamin C per serving. During the 4-6 mo volunteers were hospitalized, daily dietary vitamin C was restricted to < or = 5.0 mg. The mean daily dietary vitamin C intake was < 3.9 mg for the seven study subjects. With concurrent supplementation, the diet provided > or = 85% of the RDA for 17 essential nutrients. Within 3 wk of admission the diet induced vitamin C deficiency as indicated by plasma concentrations, which decreased from 23 +/- 6.9 to 6.9 +/- 2.0 mumol/L. Daily intake of vitamin C and five other nutrients was determined by nutrient database analyses. Mean energy, protein, the iron were 105-185% of the RDA and total and saturated fat were 32% and 10% of energy, respectively. Weight and nutritionally relevant indexes remained normal. Dietary adherence, calculated by the number of days with < or = 5.0 mg vitamin C per total study days, was 88-98% per repletion dose. Computer analyses of menu selections permitted individual preferences to be met while restricting vitamin C intake to < or = 5.0 mg/d. There were no complications from the diet during the depletion and repletion phase. With this diet, ascorbic acid pharmacokinetics for escalating doses could be determined in healthy volunteers.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Dietary Fats; Dietary Proteins; Energy Intake; Humans; Iron; Lipids; Male; Minerals; Nutrition Policy; Nutritional Physiological Phenomena; Vitamins

To determine the plasma ascorbic acid concentrations among men in North Karelia (Finland) and in Pitkäranta (Republic of Karelia) and to test how a short intervention would affect the plasma concentrations.. The baseline survey was done as a cross-sectional population survey. A subsample was selected to the intervention study and randomised to treatment and control groups.. North Karelia province in Finland and the Pitkäranta area in the Republic of Karelia.. In the cross-section population survey the stratified random sample of men between 25 and 64 years of age was 1000 in North Karelia and 500 in Pitkäranta. Participation rates were 68% and 77%, respectively. Plasma ascorbic acid measurements were made in one-third of the sample. In Pitkäranta 60 men, having very low plasma ascorbic acid concentrations, were invited to the intervention study.. A controlled intervention study was made with blackcurrant-strawberry nectar in which vitamin C content was approximately 70 mg/100 g. The treatment group drank two times daily 200 ml nectar for 4-5 weeks. After intervention plasma ascorbic acid concentration was measured from both treatment and control groups.. Plasma ascorbic acid concentrations were very different in the two areas. In Pitkäranta 93% of the men and in North Karelia only 2% of the men had plasma levels suggesting severe vitamin C deficiency. After intervention 46% of the men in the experimental group compared with 5% in the control group had plasma ascorbic acid concentrations exceeding 23 mumol/l (4.0 mg/l).. In addition to a high smoking prevalence the very low ascorbic acid concentration among men in the Republic Karelia can have an effect on the high cardiovascular disease mortality.

Topics: Administration, Oral; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Cross-Sectional Studies; Finland; Humans; Male; Middle Aged; Prevalence; Russia; Smoking

Thirty elderly long-stay patients were randomly allocated to receive either placebo or dietary supplementation with vitamins A, C and E for 28 days. Nutritional status and cell-mediated immune function were assessed before and after the period of supplementation. Following vitamin supplementation, cell-mediated immune function improved as indicated by a significant increase in the absolute number of T cells (p less than 0.05), T4 subsets (p less than 0.05), T4 to T8 ratio (p less than 0.01) and the proliferation of lymphocytes in response to phytohaemagglutinin (p less than 0.01). In contrast, no significant changes were noted in the immune function of the placebo group. We conclude that supplementation with the dietary antioxidants vitamins A, C and E can improve aspects of cell-mediated immune function in elderly long-stay patients.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Geriatric Assessment; Geriatrics; Humans; Immunity, Cellular; Institutionalization; Leukocyte Count; Nutritional Status; Placebos; T-Lymphocytes; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamin E Deficiency

The relationship between ascorbic acid status and the urinary excretion of hydroxyproline was examined in 11 healthy male subjects fed an ascorbic acid-deficient diet for 14 wk while in a metabolic unit. The diet provided 5 mg ascorbic acid/d and was supplemented with ascorbic acid to give intakes of 65 mg/d (2 wk), 5 mg/d (4 wk), 605 mg/d (3 wk), 5 mg/d (4 wk), and an average 375 mg/d (1 wk). The urinary excretion of hydroxyproline increased by an average of 16% and 30% after the first and second depletion periods, respectively, and decreased to baseline values after supplementation with normal or high doses of vitamin C. Significant (p less than 0.05) inverse correlations were found between urinary hydroxyproline and plasma, red cell, and leukocyte ascorbic acid. These results show that urinary hydroxyproline excretion increases during human vitamin C deficiency but that this effect is not strong enough to provide a reliable marker of mild vitamin C deficiency.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Dose-Response Relationship, Drug; Erythrocytes; Humans; Hydroxyproline; Leukocytes; Male; Nutritional Status

The interaction between dietary ascorbic acid at extremes of ascorbic acid intake and selenium in young adult male humans was investigated with a stable-isotope approach using 74Se-selenite. Measurements were made of 74Se in plasma, urine, and feces with neutron-activation analysis after oral administration of 74SeO3(2-). Urine excretion and total body retention of isotope and the selenite-exchangeable metabolic pool (Se-EMP) were calculated. Limiting dietary ascorbic acid to about 20 mg/d appeared to reduce the time-related retention of absorbed selenite and the size of Se-EMP. Compared with a diet providing 1 g ascorbic acid/d the low ascorbic acid intake was associated with a lower fractional absorption of the isotope, a reduced retention of the label, and a smaller Se-EMP. These data and those previously obtained in subjects with more usual ascorbic acid intakes point to a possible important role for ascorbic acid in the maintenance of Se homeostasis.

Topics: Absorption; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Humans; Isotopes; Male; Selenious Acid; Selenium; Selenium Compounds; Selenium Oxides

The influence of dietary supplementation with moderate (200 mg/day) and high (2,000 mg/day) doses of vitamin C on serum lipid levels was studied in 27 female long-stay hospital patients characterized by low plasma ascorbic acid levels during the preceding year. The two doses of vitamin C were compared with placebo in a double-blind, cross-over design during randomly determined 6-week periods followed by 2-week washout intervals. No effect was observed on serum cholesterol, HDL cholesterol, and triglyceride levels. Plasma ascorbic acid levels were highly significantly increased (p less than 0.001) by both doses of vitamin C. It is concluded that dietary supplementation with moderate or high doses of vitamin C does not affect serum lipids of persons who have low plasma ascorbic acid levels suggestive of possible marginal deficiency of vitamin C.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cholesterol; Cholesterol, HDL; Female; Humans; Lipids; Triglycerides

This study sought to determine whether the lingual ascorbic acid test (LAAT) and measurement of salivary ascorbate reflect plasma and leukocyte ascorbate levels during controlled periods of ascorbic acid depletion and supplementation. Eleven healthy non-smoking men, aged 19-28 years, ate a diet that was repeated every seven days and was adequate in all nutrients except ascorbic acid (AA). This basal diet, which provided less than 5 mg of AA per day, was supplemented with 60 mg of AA per day for two weeks, 0 mg (placebo) per day for four weeks, 600 mg per day for three weeks, and 0 mg per day for four weeks. Oral examinations, the lingual ascorbic acid test, and measurement of salivary, plasma, and leukocyte ascorbate concentrations were conducted throughout the study. Ascorbic acid concentrations in plasma and leukocytes responded rapidly to changes in vitamin C intake. LAAT-derived ascorbate values were unrelated to ascorbic acid intake and plasma and leukocyte ascorbate concentrations. Salivary ascorbate levels approached the lower limits of detection of the assay and remained constant throughout the investigation. Oral hygiene was consistently excellent, and no severe mucosal or periodontal changes were observed. It was concluded that lingual ascorbic acid test values and salivary ascorbate levels are not related to changes in ascorbic acid intake and are not consistent with plasma or leukocyte ascorbate concentrations.

Topics: 2,6-Dichloroindophenol; Administration, Oral; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Leukocytes; Male; Placebos; Saliva; Time Factors; Tongue

Forty boys and girls between 11 and 14.5 years with evidence of subclinical vitamin deficiencies were allocated to two groups to receive, twice weekly, either a placebo or a multivitamin and iron supplement. Prior to supplementation and on two subsequent occasions about 5 weeks apart, the children performed an exercise regimen on a treadmill during which expired air was collected and heart rate monitored. The supplement resulted in marked improvements in riboflavin and vitamin C status and checked the decline in iron stores seen in the unsupplemented children. During the study the running performance of unsupplemented children deteriorated, and markedly so in a subgroup with initially poor nutrient status. The vitamin and iron supplement prevented this deterioration so as to produce a significant reduction in the energy cost of treadmill running in the more malnourished subgroup, relative to the changes seen in children receiving no supplement.

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Double-Blind Method; Female; Ferritins; Gambia; Heart Rate; Hematocrit; Hemoglobins; Humans; Iron; Iron Deficiencies; Male; Oxygen Consumption; Physical Exertion; Radioimmunoassay; Riboflavin; Riboflavin Deficiency; Rural Population; Thiamine; Thiamine Deficiency

Serum presupplementation ascorbic acid levels were subnormal in 8 out of 10 patients undergoing chronic hemodialysis with capillary film and capillary flow dialyzers, the mean duration of treatment being 11 months. Supplementation with 100 mg ascorbic acid daily for two weeks raised the ascorbic acid values to normal in 9 out of 10 patients. After supplementation with 500 mg daily, all patients had ascorbic acid levels exceeding the normal upper limit, and 3 of them had gastrointestinal side-effects. The mean blood pH value, measured in 24 patients on chronic hemodialysis, showed a significant, though slight, decrease during supplementation with 500 mg daily as compared with the mean presupplementation value, but no statistically significant changes were observed in blood bicarbonate, base excess or PCO2 values.

Topics: Acid-Base Equilibrium; Adolescent; Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Renal Dialysis

In a population of schoolchildren aged 12-15 years in which biochemical deficiencies of vitamin C, riboflavin and pyridoxine affected 30.0, 33.9 and 17.2 per cent of subjects respectively, a small but statistically significant correlation was found between VO2max and vitamin C, riboflavin, vitamin A, and parameters of iron nutrition status. The administration of tablets containing 70.0 mg ascorbic acid, 2.0 mg riboflavin and 2.0 mg pyridoxine resulted in a statistically significant reduction in prevalence of vitamin deficiency, and in a small but statistically significant increase in VO2max. No such changes were observed in the untreated control groups. When data from both the experimental and control groups were pooled and analysed together, the results showed that the increase in VO2max was associated with an increase in plasma vitamin C level, in erythrocyte riboflavin content and in blood haemoglobin level. On the basis of presented data, it is not possible to conclude whether the increase in VO2max was the result of correction of vitamin deficiency per se or was due to its effect on resorption and utilization of dietary iron.

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Child; Health Status; Humans; Iron; Male; Nutritional Physiological Phenomena; Oxygen Consumption; Physical Exertion; Pyridoxine; Riboflavin; Riboflavin Deficiency; Vitamin B 6 Deficiency

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Mice; Neoplasms; Neoplasms, Experimental

The effect of oral vitamin C has been examined in elderly long-stay inpatients known to have low levels of vitamin C in their plasma and leucocytes. 1 g of vitamin C given daily for 28 days was shown to be associated with slight, but significant, clinical improvement and weight-gain when compared with placebo therapy.

Topics: Activities of Daily Living; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Clinical Trials as Topic; Double-Blind Method; Follow-Up Studies; Humans; Length of Stay; Leukocytes; Long-Term Care; Middle Aged; Placebos; Time Factors

A significantly lower vitamin C concentration has been found in the blood and particularly in the leukocytes of hypercholesterolemic diabetic patients than of healthy blood donors. Ascorbic acid administered in a dose of 500 mg per day for 12 months to metabolically stabilized hypercholesterolemic subjects with maturity-onset diabetes mellitus (diabetic diet without insulin or diabetic drugs) brought about a striking decline of cholesterolemia and a moderate decline of triglyceridemia. The serum lipid level in the control group given placebo remained unaltered. A daily administration of 500 mg of ascorbic acid for six months failed to affect the fasting level of serum immunoreactive insulin. It is assumed that the long-term administration of ascorbic acid to maturity-onset diabetics removed the tissue ascorbate deficiency and improved the liver ability to compensate the increased endogenous synthesis of cholesterol by its enhanced transformation to bile acids.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Leukocytes; Male; Middle Aged; Placebos; Triglycerides

Topics: Age Factors; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Trials as Topic; Homes for the Aged; Humans

In a prospective double-blind controlled trial the effect of large doses of ascorbic acid on the healing of pressure-sores has been assessed. 20 surgical patients were studied, the pressure areas being assessed by serial photography and ulcer tracings. The mean ascorbic-acid levels in treated and non-treated groups one month after the start of treatment were 65.6 and 25.8 mug per 10-8 white blood-cells. In the group treated with ascorbic acid there was a mean reduction in pressure-sore area of 84% after one month compared with 42.7% in the placebo group. These findings are statistically significant (P less than 0.005) and suggest that ascorbic acid may accelerate the healing of pressure-sores.

Topics: Aged; Arthritis, Rheumatoid; Ascorbic Acid; Ascorbic Acid Deficiency; Cerebrovascular Disorders; Clinical Trials as Topic; Female; Fractures, Bone; Humans; Leukocytes; Male; Middle Aged; Paraplegia; Postoperative Complications; Pressure Ulcer; Prospective Studies; Vascular Diseases; Wound Healing

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Trials as Topic; Humans; Nutritional Requirements; Schizophrenia

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Trials as Topic; Female; Hospitalization; Humans; Leukocytes; Male; Middle Aged

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Trials as Topic; Female; Humans; Male; Vitamin B Complex; Vitamin B Deficiency

Symptomatic vitamin C deficiency, scurvy, is a relatively rare disease in developed countries, but it has been reported in patients with autism spectrum disorder or developmental delay who tend to have selective diets. Patients with scurvy often demonstrate musculoskeletal manifestations with unknown pathophysiology. Herein, we report a case of scurvy in an 11-year-old boy who presented with iron-deficiency anaemia, systemic osteomyelitis, myositis predominantly in the lower extremities, and right ventricular volume overload with mild pulmonary hypertension and was diagnosed with scurvy. He had a mild developmental disorder and a selective diet, which resulted in severe vitamin C deficiency. He received intravenous and oral vitamin C supplementation, which relieved his arthralgia and muscle pain in a week. Following 4 months of vitamin C supplementation, he demonstrated no abnormal manifestations on laboratory or imaging examination and recovered without sequelae. Inflammatory cytokine and chemokine evaluations demonstrated elevated levels of interleukin (IL)-6, IL-17A, and IL-23, which are associated with T-helper (Th) 17 cell activation. This study is the first to suggest the association between the inflammation seen in scurvy, rheumatic manifestations in the patient, and Th17 cell activation. Further analysis of the association between the inflammation and vitamin C supplementation may contribute to new insights for the comprehension and treatment of other inflammatory diseases, such as rheumatic diseases.

Topics: Arthritis, Rheumatoid; Ascorbic Acid; Ascorbic Acid Deficiency; Autism Spectrum Disorder; Child; Humans; Inflammation; Interleukin-17; Interleukin-23; Interleukin-6; Male; Scurvy

Vitamin C is an essential dietary nutrient important for collagen synthesis, including within the gastrointestinal tract.. We aimed to document the prevalence of Vitamin C deficiency (VCD) in patients who present with upper gastrointestinal bleeding (UGIB) and its association with clinical outcomes.. We conducted a prospective cohort study of patients presenting with UGIB. Fasting Vitamin C levels were collected at admission. Primary outcomes were the prevalence of VCD (Vitamin C level <23 μmol/L, severe VCD < 12 μmol/L) and a composite outcome of adverse events, stratified by VCD status. Secondary outcomes were prolonged hospitalisation and the need for ICU admission.. A total of 227 patients were included (mean age 64.5 years, males 63.9%). VCD was identified in 74 (32.6%) and severe deficiency in 32 (14.1%) patients. VCD was associated with a higher composite endpoint of AE (45.9% vs 24.8%, p < 0.01), higher in-hospital mortality (9.5% vs 1.3%, p < 0.01), increased prolonged admissions (62.2% versus 47.1%, p = 0.03) and increased rebleeding (17.6% vs 7.8%, p = 0.03), compared with patients with normal Vitamin C levels. Multivariate logistic regression models showed that VCD was independently associated with the composite endpoint of AE.. VCD is highly prevalent in patients with UGIB and associated with poorer outcomes, including higher mortality, rebleeding and length of stay. Interventional studies are required to determine the impact of early Vitamin C supplementation on clinical outcomes.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Prevalence; Prognosis; Prospective Studies

Vitamin C is an essential vitamin that acts as a co-factor for many enzymes involved in epigenetic regulation in humans. Low vitamin C levels in hematopoietic stem cells (HSC) promote self-renewal and vitamin C supplementation retards leukaemogenesis in vitamin C-deficient mouse models. Studies on vitamin C levels in patients with myeloid malignancies are limited. We thus conducted a retrospective analysis on a prospective cohort of patients with myeloid malignancies on whom plasma vitamin C levels were measured serially at diagnosis and during treatment. Baseline characteristics including hematological indices, cytogenetics, and molecular mutations are described in this cohort. Among 64 patients included in our study, 11 patients (17%) had low vitamin C levels. We noted a younger age at diagnosis for patients with myeloid malignancies who had low plasma vitamin C levels. Patients with low plasma vitamin C levels were more likely to have acute myeloid leukemia compared to other myeloid malignancies. Low vitamin C levels were associated with ASXL1 mutations. Our study calls for further multi-institutional studies to understand the relevance of low plasma vitamin C level in myeloid neoplasms, the role of vitamin C deficiency in leukemogenesis, and the potential benefit of vitamin C supplementation.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Epigenesis, Genetic; Humans; Leukemia, Myeloid, Acute; Mice; Mutation; Myeloproliferative Disorders; Prospective Studies; Retrospective Studies

Animals use sour taste to avoid spoiled food and to choose foods containing vitamins and minerals. To investigate the response to sour taste substances during vitamin C (ascorbic acid; AA) deficiency, we conducted behavioral, neural, anatomical, and molecular biological experiments with osteogenic disorder Shionogi/Shi Jcl-od/od rats, which lack the ability to synthesize AA. Rats had higher 3 mM citric acid and 10 mM AA preference scores when AA-deficient than when replete. Licking rates for sour taste solutions [AA, citric acid, acetic acid, tartaric acid, and HCl] were significantly increased during AA deficiency relative to pre- and postdeficiency. Chorda tympani nerve recordings were conducted to evaluate organic acid taste responses in the AA-deficient and replete rats. Nerve responses to citric acid, acetic acid, and tartaric acid were significantly diminished in AA-deficient rats relative to replete controls. There was no significant difference in the number of fungiform papillae taste buds per unit area in the AA-deficient rats relative to the replete rats. However, mRNA expression levels of Gnat3 (NM_173139.1), Trpm5 (NM_001191896.1), Tas1r1 (NM_053305.1), Car4 (NM_019174.3), and Gad1 (NM_017007.1) in fungiform papillae taste bud cells from AA-deficient rats were significantly lower than those in replete rats. Our data suggest that AA deficiency decreases avoidance of acids and reduces chorda tympani nerve responses to acids. AA deficiency downregulates some taste-related genes in fungiform papillae taste bud cells. However, the results also reveal that the mRNA expression of some putative sour taste receptors in fungiform papillae taste bud cells is not affected by AA deficiency.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Chorda Tympani Nerve; Rats; RNA, Messenger; Taste; Taste Buds

Scurvy is taught in history class and most doctors consider it a disease of the past. However, several studies show that vitamin C deficiency is highly prevalent among alcoholics, but also in elderly, people with low socioeconomic status, mental disorders or a restricted diet (7.1 - 25%). Besides the classical signs of scurvy, individuals exhibit a wide variety of symptoms. We present three recent cases of patients with vitamin C deficiency, with symptoms of bleeding, lethargy and edema, in whom supplementation greatly improved symptoms. As our cases illustrate having a high suspicion of scurvy and starting ascorbic acid might be a low cost and very effective intervention.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Mental Disorders; Scurvy

Vitamin C (VC) is implicated in many physiological pathways. Vitamin C deficiency (VCD) can compromise the health of patients with metabolic and bariatric surgery (patients). As symptoms of VCD are elusive and data on VCD in patients is scarce, we aim to characterize patients with measured VC levels, investigate the association of VCD with other lab abnormalities, and create predictive models of VCD using machine learning (ML).. A retrospective chart review of patients seen from 2017 to 2021 at a tertiary care center in Northeastern USA was conducted. A 1:4 case mix of patients with VC measured to a random sample of patients without VC measured was created for comparative purposes. ML models (BayesNet and random forest) were used to create predictive models and estimate the prevalence of VCD patients.. Of 5946 patients reviewed, 187 (3.1%) had VC measures, and 73 (39%) of these patients had VC<23 μmol/L(VCD. When comparing patients with VCD to patients without VCD, the ML algorithms identified a higher risk of VCD in patients deficient in vitamin B1, D, calcium, potassium, iron, and blood indices. ML models reached 70% accuracy. Applied to the testing sample, a "true" VCD prevalence of ~20% was predicted, among whom ~33% had scurvy levels (VC<11 μmol/L).. Our models suggest a much higher level of patients have VCD than is reflected in the literature. This indicates a high proportion of patients remain potentially undiagnosed for VCD and are thus at risk for postoperative morbidity and mortality.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Bariatric Surgery; Humans; Machine Learning; Obesity, Morbid; Retrospective Studies; Scurvy; Vitamins

Severe vitamin C deficiency, or scurvy, presents as a syndrome of multisystem abnormalities associated with defective collagen synthesis and antioxidative functions. The many clinical features of scurvy lead to frequent misdiagnoses, as they can often point to other diseases, such as vasculitis, venous thrombosis and musculoskeletal disorders. As such, an extensive workup is recommended in cases in which scurvy is suspected.. A 21-month-old male patient and a 36-month-old female patient presented with difficulty in walking, painful joint movements, irritability, gingival hypertrophy and bleeding. After exhaustive investigations and risky invasive procedures, vitamin C deficiency was diagnosed in both cases, and the symptoms improved dramatically with vitamin C treatment.. The importance of taking a dietary history in pediatric patients is highly recommended. In cases where scurvy is considered, serum ascorbic acid levels should be checked to confirm the diagnosis prior to conducting invasive tests.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Female; Humans; Infant; Male; Scurvy; Vitamins

Reduced plasma vitamin C (vitC) concentrations in human immunodeficiency virus (HIV) may result from abnormal urinary excretion: a renal leak. VitC renal leak indicates underlying nutritional dysregulation independent of diet. We hypothesized that increased renal leak prevalence in HIV would be associated with deficient vitC concentrations.. We conducted an outpatient cross-sectional study of 96 women (40 HIV [PWH] and 56 without HIV [PWOH]) at the National Institutes of Health and Georgetown University. Renal leak was defined as abnormal urinary vitC excretion at fasting plasma concentrations <43.2µM, 2 SDs below vitC renal threshold in healthy women. To determine the primary outcome of renal leak prevalence, matched urine and plasma samples were collected the morning after overnight fast. Secondary outcomes assessed group differences in mean plasma vitC concentrations and prevalence of vitC deficiency. Exploratory outcomes assessed clinical parameters associated with renal leak. VitC was measured by high-performance liquid chromatography with coulometric electrochemical detection.. PWH had significantly higher renal leak prevalence (73%vs14%; OR (odds ratio):16; P<.001), lower mean plasma vitC concentrations (14µMvs50µM; P<.001), and higher prevalence of vitC deficiency (43%vs7%; OR:10; P<.001) compared with PWOH, unchanged by adjustments for confounding factors. Significant predictors of renal leak included antiretroviral therapy (ART), Black race, older age, and metabolic comorbidities but not viral load or CD4 count. When compared with other chronic disease cohorts, PWH had the highest prevalence of renal leak and vitC deficiency (P<.001).. High prevalence of vitC renal leak in HIV was associated with vitC deficiency, ART use, and race/ethnicity differences.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Comorbidity; Cross-Sectional Studies; Female; HIV; HIV Infections; Humans

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Bayes Theorem; Folic Acid; Folic Acid Deficiency; Humans; Inpatients; Vitamin B 12 Deficiency; Vitamin D

Vitamin C (VitC) is essential for bone health, and low VitC serum levels increase the risk for skeletal fractures. If and how VitC affects bone mineralization is unclear. Using micro-computed tomography (μCT), histologic staining, as well as quantitative backscattered electron imaging (qBEI), we assessed the effects of VitC on femoral structure and microarchitecture, bone formation, and bone mineralization density distribution (BMDD) in the VitC incompetent Gulo

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone and Bones; Bone Density; Calcification, Physiologic; Calcium; Female; Male; Mice; Mustelidae; X-Ray Microtomography

Vitamin C levels are known rapidly decrease in adult critical illness. Vitamin C scavenges free radicals, provides critical protection of the endothelial barrier, and improves endothelial responsiveness to catecholamines. Children with congenital heart disease and undergoing cardiac surgery might be at increased risk for low circulating vitamin C levels. A prospective single-center observational study investigated perioperative changes in vitamin C levels in critically ill Children who underwent congenital heart surgery using CPB. Vitamin C serum levels were collected preoperatively and postoperatively (upon admission to the ICU, 24 and 72 h). Linear mixed-effect model was used to estimate mean circulating concentration of vitamin C and to estimate changes in concentration over time. Primary outcome was change in circulating levels of vitamin C before and after CPB. Secondary outcomes were hospital length of stay (LOS), acute kidney injury (AKI), and illness severity. Forty-one patients with a median age of 4.5 [interquartile range (IQR) 2.6-65.6] months at the time of surgery were consented and enrolled. Median CPB duration was 130 [90-175] minutes, and hospital LOS was 9.1 [5.2-19] days. Mean vitamin C levels (μmol/L) before CPB, at PICU admission, 24 h, and 72 h were 82.0 (95% CI 73.4-90.7), 53.4 (95% CI 44.6,62.0), 55.1 (95% CI 46.3,63.8), and 59.2 (95% CI 50.3,68.1), respectively. Upon postoperative admission to the PICU, vitamin C levels decreased by 28.7 (95% CI 20.6-36.8; p < 0.001) μmol/L, whereas levels at 24 and 72 h recovered and did not differ substantially from concentrations reported upon PICU admission (p > 0.15). Changes in vitamin C concentration were not associated with CPB time, STAT mortality category, age, or PIM3. Three patients had post-CPB hypovitaminosis C or vitamin C deficiency. Reduction in vitamin C levels was not associated with hospital LOS (p = 0.673). A 25 μmol/L decrease in vitamin C levels upon PICU admission was associated with developing AKI (aOR = 3.65; 95% CI 1.01-18.0, p = 0.049). Pediatric patients undergoing cardiac surgery with CPB showed decreased vitamin C levels during the immediate postoperative period. Effects of hypovitaminosis C and vitamin C deficiency in this population remain unclear.

Topics: Acute Kidney Injury; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiopulmonary Bypass; Child; Child, Preschool; Humans; Infant; Prospective Studies; Risk Factors

Vitamin C deficiency is common in patients with chronic intestinal failure. Risk factors are poorly understood and guidelines for monitoring largely based on expert opinion. The aim of this study was to describe patterns of vitamin C deficiency in patients on long-term home parenteral support (HPS).. A retrospective review of a prospectively collated database for 236 HPS patients cared for in Glasgow, from 1998 to 2023, was interrogated for subjects with paired CRP and vitamin C measurements. Following analysis of the impact of CRP on vitamin C levels, further review of associated clinical, micronutrient and dietetic details in those with a paired CRP <5 mg L. 1527 recorded episodes with paired CRP and vitamin C measurements were analysed. Period prevalence of hypoascorbataemia was between 29.3 and 52.5%, depending on choice of the lower reference range for vitamin C as either 15 μmol L. Vitamin C may present differently in long term HPS patients in comparison to those in the acute phase of illness. An evidence based approach to guideline development should be promoted to reduce morbidity.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Databases, Factual; Dietetics; Humans; Vitamins

We present a 17-month-old girl with postencephalitic sequelae only on high-calorie cereal milk through a nasogastric tube. She presented with a 3-week history of swelling and decreased lower limb movements. Synovial fluid analysis ruled out septic arthritis. Plain radiograph and magnetic resonance imaging (MRI) were suggestive of scurvy. She was diagnosed to have pseudoparalysis secondary to scurvy. She was started on vitamin C supplements, after which she showed good clinical improvement.. This case report is to re-emphasize the need for awareness of the possibility of scurvy in children with poor nutritional status due to feeding difficulties.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child, Preschool; Female; Humans; Infant; Magnetic Resonance Imaging; Radiography; Scurvy

The 1st millennium BCE in Italy was a time of agricultural intensification of staple cereal production which shaped sociocultural, political, and economic spheres of pre-Roman groups. The lifeways and foodways of the Etruscans, the greatest civilization in western Europe before Roman hegemony, are traditionally inferred from secondary written sources, funerary archaeology, archaeobotany, and zooarchaeology. However, no direct data extrapolated from the study of human skeletal remains are available to evaluate the extent to which agricultural intensification and decreased dietary diversity impacted health and the expression of skeletal indicators of metabolic disease. Macroscopic and radiological analyses were conducted on an archaeological skeletal sample of non-adults (n = 29) recovered from Pontecagnano (southern Italy) dating to the Orientalizing period (730-580 BCE). This allowed us to identify five cases of scorbutic non-adults and to assign diagnostic values to skeletal lesions of scurvy that have not been previously described in the literature. The onset of scurvy in the examined sample is related to the increased reliance of Etruscans on crops lacking vitamin C in this period of agricultural intensification. The skeletal expression of scurvy varied among the non-adults, with differences in location and disease severity; these were interpreted considering the age-at-death of the individuals coupled with feeding behaviors and interindividual variability.

Topics: Archaeology; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Europe; Humans; Scurvy

Vitamin C (ascorbic acid) is an essential water-soluble antioxidant, and deficiency (ie, plasma level <11 μmol/L) can result in scurvy. People at the highest risk for vitamin C deficiency (ie, scurvy) are those with inadequate intake, such as patients with alcohol abuse disorder, malnutrition, psychiatric disorders, restrictive eating habits, and food insecurity, as well as those with malabsorptive syndromes. We present a case of a 26-year-old woman with Crohn's colitis, myasthenia gravis, and juvenile rheumatoid arthritis who presented with frequent bruising, epistaxis, and excessive bleeding from small cuts and who was found to be deficient in vitamin C. Plasma levels initially normalized with oral vitamin C supplementation, but bleeding symptoms eventually returned despite high-dose oral supplementation with 2000 mg daily. She ultimately required routine intravenous supplementation in the home setting for the normalization of levels and the resolution of symptoms. Case reports of vitamin C deficiency typically involve patients with an inadequate intake of vitamin C-containing foods or inadequate absorption. In contrast, our patient reported a regular intake of vitamin C-containing foods, in addition to oral supplementation, but continued to have difficulty maintaining normal vitamin C levels. Scurvy should be considered for any patient with symptoms of bleeding, petechiae, or ecchymosis and, although it can typically be treated with oral vitamin C, intravenous repletion may be necessary in some cases.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Crohn Disease; Female; Humans; Myasthenia Gravis; Scurvy; Vitamins

Vitamin C deficiency is found in patients with variable kidney diseases. However, the role of vitamin C as an epigenetic regulator in renal homeostasis and pathogenesis remains largely unknown.. Integrated evidence suggested that epigenetic modifications affected the proximal tubule cells and fenestrated endothelial cells, leading to tubule injury and hypoxia through transcriptional regulation. Strikingly, loss of DNA hydroxymethylation and DNA hypermethylation in vitamin C-deficient kidneys preceded the histologic sign of tubule necrosis, indicating the causality of vitamin C-induced epigenetic modification in ATN. Consistently, prophylactic supplementation of an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, promoted DNA demethylation and prevented the progression of cisplatin-induced ATN.. Vitamin C played a critical role in renal homeostasis and pathogenesis in a mouse model, suggesting vitamin supplementation may be an approach to lower the risk of kidney injury.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Endothelial Cells; Epigenesis, Genetic; Female; Humans; Kidney Tubular Necrosis, Acute; Male; Mice; Necrosis; RNA

To evaluate the presence of vitamin C deficiency in critically ill children admitted to the PICU.. Single-center prospective observational cohort study.. A 28-bed PICU and a pediatric outpatient sedation room of a tertiary-care teaching hospital.. Two pediatric patient groups 0-21 years old were studied: a PICU group and a group receiving deep sedation for elective outpatient procedures (noncritical care group).. Vitamin C level was drawn for the PICU group within 24 hours of admission. Vitamin C level was drawn prior to start of deep sedation for the noncritical group.. Vitamin C deficiency was present in 11/60 (18%) in the PICU group and 0/21 (0%) of the noncritical group (p < 0.05).. Vitamin C deficiency was prevalent in our patients admitted to PICU.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Critical Illness; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Prospective Studies; Young Adult

Vitamin C deficiency, historically known as scurvy, was associated with sailors in the Victorian times, however, a global review in 2020 suggests it still exists in certain at-risk groups.A case is presented of a young non-verbal child with learning difficulties and on a restricted diet, in which the primary symptom was gingival inflammation. It posed a diagnostic dilemma due to the non-specific symptoms, and a delay in the diagnosis, until vitamin C deficiency was confirmed.Gingival inflammation is one of the common findings in vitamin C deficiency and dental professionals may be the first point of contact. The importance of dietary evaluation, identifying and looking for other signs and liaising with the medical colleagues are discussed.This case highlights the role of the dentist in identifying latent cases of vitamin C deficiency and to consider this as a differential diagnosis especially in certain at-risk groups.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Diagnosis, Differential; Humans; Inflammation; Scurvy

To investigate the effects of vitamin C on central retinal thickness and choroidal thickness.. A total of 69 patients diagnosed with vitamin C deficiency and 1:1 age- and gender-matched 69 healthy individuals with normal serum vitamin C were included in this study. Demographic characteristics of the individuals were collected. All patients underwent a comprehensive ophthalmic examination. Subfoveal choroidal thickness and retinal thickness were measured using a swept-source optical coherence tomography (SS-OCT).. The average retinal thickness was 269.07 ± 13.51 μm in the vitamin C deficiency group and 276.92 ± 13.51 μm in the control group. The average choroidal thickness was 195.62 ± 66.40 μm in the in the vitamin C deficiency group and 238.86 ± 55.08 μm in the control group. There was a significant decrease in both average choroidal thickness and retinal thickness in vitamin C deficiency group compared with normal individuals (p < 0.001, and = 0.001 respectively).. The central retinal and choroidal thickness were thinner in vitamin C deficiency group compared with normal individuals. These findings suggested that vitamin C deficiency might play an important role in retinal and choroidal diseases.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Choroid; Humans; Retina; Tomography, Optical Coherence

Vitamin C (VC, l-ascorbic acid) is an essential nutrient that plays a key role in metabolism and functions as a potent antioxidant in regulating the S-nitrosylation and denitrosylation of target proteins. The precise function of VC deprivation in glucose homeostasis is still unknown. In the absence of L-gulono-1,4-lactone oxidoreductase, an essential enzyme for the last step of VC synthesis, VC deprivation resulted in persistent hypoglycemia and subsequent impairment of cognitive functions in female but not male mouse pups. The cognitive disorders caused by VC deprivation were largely reversed when these female pups were given glucose. VC deprivation-induced S-nitrosylation of glycogen synthase kinase 3β (GSK3β) at Cys14, which activated GSK3β and inactivated glycogen synthase to decrease glycogen synthesis and storage under the feeding condition, while VC deprivation inactivated glycogen phosphorylase to decrease glycogenolysis under the fasting condition, ultimately leading to hypoglycemia and cognitive disorders. Treatment with Nω-Nitro-l-arginine methyl ester (l-NAME), a specific inhibitor of nitric oxide synthase, on the other hand, effectively prevented S-nitrosylation and activation of GSK3β in female pups in response to the VC deprivation and reversed hypoglycemia and cognitive disorders. Overall, this research identifies S-nitrosylation of GSK3β and subsequent GSK3β activation as a previously unknown mechanism controlling glucose homeostasis in female pups in response to VC deprivation, implying that VC supplementation in the prevention of hypoglycemia and cognitive disorders should be considered in the certain groups of people, particularly young females.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Cognition; Female; Glucose; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Glycogen Synthase Kinase 3 beta; Humans; Hypoglycemia; Lactones; Mice; Neurocognitive Disorders; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase

Dear Editor, Scurvy is a nutritional disorder which can develop after prolonged (>1-3 months) severe vitamin C deficiency. Vitamin C is a cofactor in several enzyme reactions involved in collagen synthesis. The defect in collagen causes blood vessel fragility, poor wound healing, mucocutaneous bleedings, hair abnormalities, bone pains, and joint contractures due to periosteal and intraarticular bleeding (1,2). Risk factors for scurvy development are undernutrition, low socioeconomic status, older age, male sex, alcoholism, tobacco smoking, and severe psychiatric illnesses (1-3). The required daily intake for vitamin C is ~60 mg, and this amount of vitamin C can be found in only one medium-sized orange. For this reason, the disease is rarely encountered in developed countries and is often underrecognized by healthcare personnel. Herein, we present an illustrative case of scurvy in order to raise the awareness of this disorder. A 61-year-old Caucasian man was admitted to hospital due to fatigue, hypotension (80/50 mmHg), severe normocytic anemia (hemoglobin 76 g/L), kidney failure (estimated glomerular filtration rate of 6 mL/min/1.73m2) and mild elevation in C-reactive protein (30.9 mg/L). Prior medical history included radical cystoprostatectomy with an ileal conduit performed eight years ago due to a bladder tumor and moderate chronic kidney disease with recurrent urinary tract infections. The patient was also an alcoholic and tobacco smoker, with a very low-income and a poor diet. He did not use any medications. Heteroanamnestically, the current clinical state had developed slowly over several weeks. At admission, the patient was afebrile, lethargic, malnourished, and immobile due to generalized weakness, bone pains, and hip and knee contractures. He had generalized edema, mostly related to kidney failure, as well as severe hypoalbuminemia (serum albumin 19 g/L). There were multiple ecchymoses (Figure 1, a) and perifollicular bleedings (Figure 1, b) in the skin. The teeth were defective, and the patient's facial hair had a "corkscrew" appearance (Figure 1, c). The platelet count was normal, as was the serum fibrinogen level and the prothrombin- and activated partial thromboplastin times. Vancomycin-resistant Enterococcus faecium and multi-drug-resistant Acinetobacter baumanii were isolated from the urine. Therefore, hemodialysis, linezolid, and colistin were started. However, the patient continued to be lethargic, immobile, and with prominent skin bleed

Topics: Anemia; Anticoagulants; Ascorbic Acid; Ascorbic Acid Deficiency; C-Reactive Protein; Colistin; Contracture; Fatigue; Fibrinogen; Humans; Linezolid; Male; Middle Aged; Prothrombin; Renal Insufficiency; Scurvy; Serum Albumin; Thromboplastin; Vancomycin; Vitamins

Patients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn's disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency.. To determine proportions and factors associated with vitamin C deficiency in CD and UC patients.. In this retrospective study, we obtained clinical, laboratory and endoscopic data from CD and UC patients presenting to the IBD clinic at a single tertiary care center from 2014 to 2019. All patients had an available plasma vitamin C level. Of 353 subjects who met initial search criteria using a cohort discovery tool, 301 ultimately met criteria for inclusion in the study. The primary aim described vitamin C deficiency (≤ 11.4 μmol/L) rates in IBD. Secondary analyses compared proportions with deficiency between active and inactive IBD. Multivariate logistic regression analysis evaluated factors associated with deficiency.. Of 301 IBD patients, 21.6% had deficiency, including 24.4% of CD patients and 16.0% of UC patients. Patients with elevated C-reactive protein (CRP) (39.1%. Vitamin C deficiency was common in IBD. Patients with elevated inflammatory markers and penetrating disease had higher rates of vitamin C deficiency.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Biological Products; Biomarkers; C-Reactive Protein; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Humans; Inflammatory Bowel Diseases; Leukocyte L1 Antigen Complex; Prevalence; Retrospective Studies; Scurvy; Vitamin D Deficiency

Vitamin C deficiency disrupts the integrity of connective tissues including bone. For decades this function has been primarily attributed to Vitamin C as a cofactor for collagen maturation. Here, we demonstrate that Vitamin C epigenetically orchestrates osteogenic differentiation and function by modulating chromatin accessibility and priming transcriptional activity. Vitamin C regulates histone demethylation (H3K9me3 and H3K27me3) and promotes TET-mediated 5hmC DNA hydroxymethylation at promoters, enhancers and super-enhancers near bone-specific genes. This epigenetic circuit licenses osteoblastogenesis by permitting the expression of all major pro-osteogenic genes. Osteogenic cell differentiation is strictly and continuously dependent on Vitamin C, whereas Vitamin C is dispensable for adipogenesis. Importantly, deletion of 5hmC-writers, Tet1 and Tet2, in Vitamin C-sufficient murine bone causes severe skeletal defects which mimic bone phenotypes of Vitamin C-insufficient Gulo knockout mice, a model of Vitamin C deficiency and scurvy. Thus, Vitamin C's epigenetic functions are central to osteoblastogenesis and bone formation and may be leveraged to prevent common bone-degenerating conditions.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcification, Physiologic; Cell Differentiation; Chromatin; DNA; DNA Methylation; Histones; Mice; Osteogenesis

We previously demonstrated that ascorbic acid (AsA) deficiency, caused by an AsA-free diet, induces inflammatory changes in the liver and intestine of osteogenic disorder Shionogi (ODS) rats that cannot synthesize AsA. However, whether low AsA intake induces inflammatory changes remains unknown. Here, we assessed the inflammatory changes in ODS rats caused by low AsA intake and compared them to ODS rats that were fed a diet supplemented with sufficient amounts of AsA (300 mg/kg). Male ODS rats (12-wk-old) were fed an AsA-free diet (0 ppm group), AsA 20 mg/kg diet (20 ppm group), AsA 40 mg/kg diet (40 ppm group) or AsA 300 mg/kg diet (300 ppm group) for 22 d. The hepatic mRNA levels of acute phase proteins, including C-reactive protein (CRP) and haptoglobin, were higher in the 0 and 20 ppm groups, than in the 300 and 40 ppm groups, but were not significantly higher in the 20 ppm group. Serum CRP concentrations were significantly higher in the 0 and 20 ppm groups than in the 300 and 40 ppm groups. Jejunal and ileal interleukin-1β (IL-1β) mRNA levels were higher in the 0 and 20 ppm groups than in the 300 ppm group. Jejunal and ileal IL-6 mRNA levels tended to be higher in the 0 and 20 ppm groups than in the 300 ppm group. Furthermore, the portal IL-6 concentration gradually increased with decrease in the AsA intake. Thus, inflammatory changes could occur in both AsA-deficient ODS rats and ODS rats with low AsA intake.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Interleukin-6; Intestines; Liver; Male; Rats; RNA, Messenger

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Scurvy

While the use of vitamin C as a therapeutic agent has been investigated since the 1950s, there has been substantial recent interest in the role of vitamin C supplementation in critical illness and particularly, sepsis and septic shock. Humans cannot synthesize vitamin C and rely on exogenous intake to maintain a plasma concentration of approximately 70 to 80 μmol/L. Vitamin C, in healthy humans, is involved with antioxidant function, wound healing, endothelial function, and catecholamine synthesis. Its function in the human body informs the theoretical basis for why vitamin C supplementation may be beneficial in sepsis/septic shock.Critically ill patients can be vitamin C deficient due to low dietary intake, increased metabolic demands, inefficient recycling of vitamin C metabolites, and loss due to renal replacement therapy. Intravenous supplementation is required to achieve supraphysiologic serum levels of vitamin C. While some clinical studies of intravenous vitamin C supplementation in sepsis have shown improvements in secondary outcome measures, none of the randomized clinical trials have shown differences between vitamin C supplementation and standard of care and/or placebo in the primary outcome measures of the trials. There are some ongoing studies of high-dose vitamin C administration in patients with sepsis and coronavirus disease 2019; the majority of evidence so far does not support the routine supplementation of vitamin C in patients with sepsis or septic shock.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Clinical Trials as Topic; Critical Illness; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Inflammation Mediators; Shock, Septic; Vasoconstrictor Agents; Vitamins

Vitamin C, well-established in immune function and a key factor in epigenetic inflammatory modifications, is only obtained through consistent dietary intake. Identifying individuals at risk for Vitamin C insufficiency may guide prevention and treatment, however, national surveillance has not been evaluated in the United States since 2006. A descriptive, cross-sectional secondary analysis was performed utilizing data from the 2003-2006 National Health and Nutrition Examination Surveys (NHANES) assessing non-institutionalized adults. Five categories of plasma Vitamin C were delineated: deficiency (<11 μmol/L), hypovitaminosis (11-23 μmol/L), inadequate (23-49 μmol/L), adequate (50-69 μmol/L), and saturating (≥70 μmol/L). Results indicated 41.8% of the population possessed insufficient levels (deficiency, hypovitaminosis, and inadequate) of Vitamin C. Males, adults aged 20-59, Black and Mexican Americans, smokers, individuals with increased BMI, middle and high poverty to income ratio and food insecurity were significantly associated with insufficient Vitamin C plasma levels. Plasma Vitamin C levels reveal a large proportion of the population still at risk for inflammatory driven disease with little to no symptoms of Vitamin C hypovitaminosis. Recognition and regulation of the health impact of Vitamin C support the goal of Nutrition and Healthy Eating as part of the Healthy People 2030.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Black or African American; Body Mass Index; Cross-Sectional Studies; Diet; Female; Food Insecurity; Humans; Male; Mexican Americans; Middle Aged; Nutrition Surveys; Poverty; Sex Factors; Smoking; Vitamins; Young Adult

Ascorbic acid (vitamin C) is critical for Schwann cells to myelinate peripheral nerve axons during development and remyelination after injury. However, its exact mechanism remains elusive. Vitamin C is a dietary nutrient that was recently discovered to promote active DNA demethylation. Schwann cell myelination is characterized by global DNA demethylation in vivo and may therefore be regulated by vitamin C. We found that vitamin C induces a massive transcriptomic shift (n = 3,848 genes) in primary cultured Schwann cells while simultaneously producing a global increase in genomic 5-hydroxymethylcytosine (5hmC), a DNA demethylation intermediate which regulates transcription. Vitamin C up-regulates 10 pro-myelinating genes which exhibit elevated 5hmC content in both the promoter and gene body regions of these loci following treatment. Using a mouse model of human vitamin C metabolism, we found that maternal dietary vitamin C deficiency causes peripheral nerve hypomyelination throughout early development in resulting offspring. Additionally, dietary vitamin C intake regulates the expression of myelin-related proteins such as periaxin (PRX) and myelin basic protein (MBP) during development and remyelination after injury in mice. Taken together, these results suggest that vitamin C cooperatively promotes myelination through 1) increased DNA demethylation and transcription of pro-myelinating genes, and 2) its known role in stabilizing collagen helices to form the basal lamina that is necessary for myelination.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cells, Cultured; DNA Demethylation; Female; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myelin Proteins; Myelin Sheath; Rats, Inbred F344; Schwann Cells; Sciatic Neuropathy

Vitamin C deficiency is common in chronic kidney disease (CKD) due to losses through dialysis and dietary intake below requirement. We investigated prevalence of vitamin C deficiency and impact of vitamin C treatment in deficient/insufficient patients.. A prospective cohort study in patients aged 1-18 years with CKD stages 4 and 5D collected demographic data including underlying disease, treatment, and anthropometric assessment. Vitamin C intake was assessed using 24-h dietary recall. Hemoglobin, iron status, serum vitamin C, and serum oxalate were measured at baseline and after treatment. Vitamin C (250 mg/day) was given orally for 3 months to deficient/insufficient patients.. Nineteen patients (mean age 12.00 ± 4.1 years) showed prevalence of 10.6% vitamin C insufficiency and 78.9% deficiency. There were no associations between vitamin C level and daily vitamin C intake (p = 0.64) or nutritional status (p = 0.87). Median serum vitamin C was 1.51 (0.30-1.90) mg/L. In 16 patients receiving treatment, median serum vitamin C increased from 1.30 (0.23-1.78) to 3.22 (1.77-5.96) mg/L (p = 0.008) without increasing serum oxalate (79.92 (56.6-106.84) vs. 80.47 (56.88-102.95) μmol/L, p = 0.82). However, 62.5% failed to achieve normal vitamin C levels. Ordinal regression analysis revealed patients with non-oligoanuric CKD were less likely to achieve normal vitamin C levels (β = - 3.41, p = 0.03).. We describe high prevalence of vitamin C insufficiency/deficiency among pediatric CKD patients. Vitamin C levels could not be solely predicted by nutritional status or daily intake. The treatment regimen raised serum vitamin C without increasing serum oxalate; however, it was largely insufficient to normalize levels, particularly in non-oligoanuric CKD. Graphical abstract .

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Humans; Oxalates; Prevalence; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

Accidental exposure to high-dose radiation causes life-threatening acute radiation syndrome, features that include gastrointestinal syndrome (GIS) and hematopoietic syndrome (HS). Administration of vitamin C (VC), a free radical scavenger, has been reported to increase survival of mice in GIS and HS models. The effect of nutritional VC status on radiation injury remains unknown because, unlike humans, mice can synthesize VC. The aim of this study was to investigate the effect of VC insufficiency on acute radiation syndrome using senescence marker protein 30 (SMP30)/gluconolactonase knockout (SMP30-KO) mice.. SMP30-KO mice, which cannot synthesize VC, were given water with or without sufficient VC supplementation, and were analyzed in GIS and HS models.. In the GIS model, in which bone marrow failure is rescued by bone marrow transplantation, VC-insufficient mice had a lower survival rate than VC-sufficient mice. The intestine of VC-insufficient GIS mice showed epithelial cell atrophy, inflammatory cell infiltration, and decreased crypt cell proliferation. We observed rapid VC oxidation after total body irradiation in the intestine of mice supplemented with VC-sufficient water. In the HS model, which was not combined with bone marrow transplantation, there was no difference in survival between VC-insufficient and -sufficient mice.. The results of this study demonstrated that nutritionally sufficient VC exerts a radioprotective effect against radiation-induced GIS.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Intracellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Radiation Injuries

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a median survival of 14.6 months. GBM is highly resistant to radio- and chemotherapy, and remains without a cure; hence, new treatment strategies are constantly sought. Vitamin C, an essential micronutrient and antioxidant, was initially described as an antitumor molecule; however, several studies have shown that it can promote tumor progression and angiogenesis. Thus, considering the high concentrations of vitamin C present in the brain, our aim was to study the effect of vitamin C deficiency on the progression of GBM using a GBM model generated by the stereotactic injection of human GBM cells (U87-MG or HSVT-C3 cells) in the subventricular zone of guinea pig brain. Initial characterization of U87-MG and HSVT-C3 cells showed that HSVT-C3 are highly proliferative, overexpress p53, and are resistant to ferroptosis. To induce intraperiventricular tumors, animals received control or a vitamin C-deficient diet for 3 weeks, after which histopathological and confocal microscopy analyses were performed. We demonstrated that the vitamin C-deficient condition reduced the glomeruloid vasculature and microglia/macrophage infiltration in U87-MG tumors. Furthermore, tumor size, proliferation, glomeruloid vasculature, microglia/macrophage infiltration, and invasion were reduced in C3 tumors carried by vitamin C-deficient guinea pigs. In conclusion, the effect of the vitamin C deficiency was dependent on the tumor cell used for GBM induction. HSVT-C3 cells, a cell line with stem cell features isolated from a human subventricular GBM, showed higher sensitivity to the deficient condition; however, vitamin C deficiency displayed an antitumor effect in both GBM models analyzed.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glioblastoma; Guinea Pigs; Humans; Neoplastic Stem Cells; Xenograft Model Antitumor Assays

Foxp3 stability of vitamin C-treated induced-regulatory T cells (V-iTregs) is superior to that of conventional iTregs (C-iTregs). However, the role of V-iTregs in allograft rejection under vitamin C-deficient conditions, such as those seen in humans, remains unclear. We aimed to elucidate the role of vitamin C treatment on generation and maintenance of iTregs from gulo knockout (Gulo-KO) mice as well as wild type (WT) mice, and in vitro and in vivo suppressive effects of V-iTregs on heart allograft rejection in either Gulo-KO or WT recipient mice. Conversion efficiency of iTregs was similar between C- and V-iTregs in both WT and Gulo-KO mice. V-iTregs from WT or Gulo-KO mice showed better in vitro Foxp3 stability than C-iTregs, although there was no difference between WT V-iTregs and Gulo-KO V-iTregs. Furthermore, V-iTregs from WT or Gulo-KO mice suppressed in vitro T cell proliferation better than C-iTregs. Heterotrophic heart transplantation from BALB/c mice to WT or vitamin C-deficient Gulo-KO C57BL/6J mice was performed following adoptive transfer of C- or V-iTregs. V-iTregs as well as C-iTregs prolonged heart allograft survival in WT and Gulo-KO mice. However, there was no difference between the C- and V-iTreg groups. Supplementation of low- or high-dose vitamin C did not induce significant changes in heart allograft survival in Gulo-KO recipients that had received V-iTregs. In conclusion, V-iTregs do not exert better suppressive effects on heart allograft survival than C-iTregs in either WT or vitamin C-deficient recipients.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Graft Rejection; Heart Transplantation; Mice, Inbred BALB C; Mice, Inbred C57BL; T-Lymphocytes, Regulatory; Vitamins

Chronic respiratory disease (CRD) is an airflow limitation that represents a wide array of serious diseases. The aim of this study is to examine the influence of vitamin C deficiency on metabolic health-related quality in individuals with and without chronic respiratory disease in the Gaza Strip.. A matched case-control study including 52 cases of CRD and 52 controls of healthy participants were matched by age, sex, body mass index (BMI) and waist circumferences (WC). The study was conducted at the Ministry of Health secondary health-care centers in Gaza strip, Palestine. The biochemical data included Protein Carbonyl (PC), high sensitivity C reactive protein (CRP), vitamin C, fasting blood glucose (FBG) and markers of the lipid profile.. By the qualitative estimation of vitamin C consumption, there was a significantly lower consumption of foods that are rich in vitamin C by CRD patients than the matched controls. By comparing the results between both groups, CRD patients had significantly lower plasma concentrations of vitamins C than the control group (18.43 ± 11.93 μgm/ml vs. 24.06 ± 11.19 μgm/ml, P = 0.025), but significantly higher in PC (3.86 ± 4.21 μgm/ml vs. 2.11 ± 0.97 μgm/ml, P = 0.005), CRP (5.98 ± 8.84 mg/l vs. 1.87 ± 1.96 mg/l, P = 0.001), and FBG (102.46 ± 15.09 mg/dl vs. 95.92 ± 10.88 mg/dl, P = 0.017). The results revealed that CRD patients had significantly lower blood oxygen saturation than the control group (96.36 ± 3.81 vs. 98.51 ± 0.75, P < 0.001), whereas no significant differences were observed regarding the lipid profiles markers.. CRD patients have lower levels of vitamin C in their plasma and their diet than do healthy matched people; they also have higher oxidative stress and inflammatory markers than healthy people, which are risk factors for predicting metabolic complications.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; C-Reactive Protein; Case-Control Studies; Humans; Israel; Waist Circumference

Although the symptoms related to vitamin C deficiency were known in ancient Egypt and eighteenth century Scottish surgeon James Lind found that scurvy (a disease resulting from insufficient dietary ingestion of vitamin C) could be effectively treated with citrus fruit, this vitamin was discovered only in the year 1912 and then after 21 years it was chemically synthetized and introduced to the market as the first vitamin supplement [...].

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Citrus; Diet; Dietary Supplements; Humans; Scurvy; Vitamins

The impact of vitamin C supplementation on the risk of cardiovascular diseases (CVDs) remains uncertain with inconsistent evidence obtained from observational studies and randomized clinical trials (RCTs). We aimed to assess possible causal associations of vitamin C with major CVD events as well as their risk factors using Mendelian randomization (MR) design.. Nine genetic variants associated with vitamin C at genome-wide significance (p < 5 × 10. This MR study does not support a causal protective role to circulate vitamin C levels on various types of CVD events. In combination with previous RCT results, our findings suggest that vitamin C supplementation to increase circulating vitamin C levels may not help in CVD prevention.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Body Composition; Cardiovascular Diseases; Genetic Predisposition to Disease; Heart Disease Risk Factors; Humans; Lipids; Mendelian Randomization Analysis; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment

Topics: Animals; Animals, Zoo; Ascorbic Acid; Ascorbic Acid Deficiency; Chiroptera; Dietary Supplements; Vitamins

Scurvy is a disease caused by chronic vitamin C deficiency. The greater prevalence was found in the paediatric population with neurodevelopmental disorders such as autism spectrum disorders due to their restricted dietary intake. Our case reported a child with autism who presented with arthralgia and anaemia. Systemic lupus erythematosus was the first diagnostic impression, resulting in over investigation and delayed diagnosis of vitamin C deficiency. After the child was treated with ascorbic acid, the child's symptoms resolved. This case highlighted the importance of developmental and nutritional history taking in the paediatric population. Furthermore, parents and physicians should be concerned about nutritional status, especially in children with restrictive dietary intake.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Autism Spectrum Disorder; Child; Humans; Lupus Erythematosus, Systemic; Scurvy

Lipoprotein (a) deposition in coronary vascular plaques and cerebral vessels is a recognized risk factor for cardiovascular disease, and research supports its role as a "repair factor" in vascular walls weakened by vitamin C deficiency.. Humans depend on dietary vitamin C as an important antioxidant and as a cofactor in collagen synthesis, yet are prone to vitamin C deficiency. The brain is the one with the highest vitamin C content, owing to its high oxygen consumption and oxidative stress. It has been shown that brain aging is accompanied by accumulated oxidative damage, which can lead to memory decline and neurological diseases.. Our transgenic mouse, Gulo (-/-); Lp(a)+, presents a unique model for the study of key aspects of human metabolism with respect to a lack of internal vitamin C synthesis and the production of human lipoprotein(a).. This mouse model was used in our study to investigate the effects of prolonged intake of low and high levels of vitamin C, at different ages, on oxidative damage, cholesterol levels and lipoprotein( a) deposition in the brain.. The results show that a long-term high vitamin C intake is important in maintaining brain cholesterol homeostasis and preventing oxidative damage in Gulo(-/-);Lp(a)+ mice as they age. Moreover, we observed that the formation of brain lipoprotein(a) deposits was negatively correlated with brain level of vitamin C, thereby confirming its role as a stability factor for an impaired extracellular matrix.. Our study emphasizes the critical role of vitamin C in protecting brain health as we age. Other: Our findings show that optimal vitamin C intake from early life to old age is important for brain health as it prevents oxidative stress damage and maintains cholesterol homeostasis in the brain. More importantly, the negative correlation between brain ascorbic levels and the formation of Lp(a) deposit on the choroid plexus further emphasizes the critical role of vitamin C in protecting brain health throughout the normal aging process.

Topics: Age Factors; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Humans; Lipoprotein(a); Mice; Mice, Transgenic

Scurvy is seldom encountered in modern day clinical practice. Children can present with nonspecific features which can mimic several other common conditions. We describe here a four-year-old child who presented with severe pain and weakness of bilateral lower limbs and found to be severely malnourished. The diagnosis of scurvy was suspected in the context of underlying malnutrition after excluding other ominous pathologies. Pathognomic radiological changes clinched the diagnosis, and the best supportive evidence was the dramatic response to vitamin C supplementation.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child, Preschool; Dietary Supplements; Humans; Leg; Male; Malnutrition; Pain; Radiography; Scurvy; Treatment Outcome; Vitamins

Ten patients with scurvy were evaluated by rheumatology; we review their clinical, laboratory, and dietary presentations. Eight patients had developmental delay or autism. All had elevated inflammatory markers. These clinical and laboratory features with imaging findings can mimic rheumatic conditions such as arthritis, vasculitis, and chronic nonbacterial osteomyelitis (CNO).

Topics: Adolescent; Arthritis, Juvenile; Ascorbic Acid; Ascorbic Acid Deficiency; Autistic Disorder; Child; Child Nutritional Physiological Phenomena; Child, Preschool; Diagnosis, Differential; Diet; Female; Humans; Inflammation; Male; Musculoskeletal Pain; Osteomyelitis; Rheumatology; Scurvy; Vasculitis; Young Adult

A female patient presented with exertional dyspnea, myalgia, a petechial rash of the lower extremities and pronounced gingivitis. The biochemical test results showed the presence of anemia. The patient had a known eating disorder and on questioning about eating habits admitted that she did not eat any fruit or vegetables. This led to the suspicion of a vitamin C deficiency, which was confirmed by high-pressure liquid chromatography. The patient was subsequently treated with 1000 mg ascorbic acid daily for 1 month whereby the clinical symptoms and anemia improved within a few weeks.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Dyspnea; Female; Gingivitis; Humans; Lower Extremity; Middle Aged; Myalgia; Purpura

We report a case of a man in his 60s who developed pulmonary arterial hypertension (PAH) in association with profound vitamin C deficiency. Decreased availability of endothelial nitric oxide and activation of the hypoxia-inducible family of transcription factors, both consequences of vitamin C deficiency, are believed to be mechanisms contributing to the pathogenesis of the pulmonary hypertension. The PAH resolved following vitamin C supplementation. The current case highlights the importance of testing for vitamin C deficiency in patients with PAH in the proper clinical setting.

Topics: Aged; Anemia; Arthralgia; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiac Catheterization; Echocardiography; Endothelium, Vascular; Exanthema; Humans; Hypoxia; Male; Nitric Oxide; Pulmonary Arterial Hypertension; Transcription Factors; Vitamins

Using rats, we previously found that vitamin C deficiency increases serum levels of interleukin-6 (IL-6) and glucocorticoid, and changes the gene expression of acute phase proteins (APP) in the liver. However, it remains unclear how vitamin C deficiency causes these inflammation-like responses. In this study, we investigated the possibility that changes in gut microbiota are involved in the induction of APP gene expression by vitamin C deficiency. ODS rats that cannot genetically synthesize vitamin C were divided into 4 groups based on the presence or absence of vitamin C or antibiotics and were raised for 15 d. Neomycin, vancomycin, and ampicillin were used as antibiotics, and 300 mg L-ascorbic acid/kg was added to the AIN93G diet. Vitamin C deficiency affected neither the wet tissue weights nor relative abundance of bacteria in the cecal contents. Antibiotic administration increased wet weights of the cecum, cecal contents, and colon, changed the relative abundance of some bacteria in the cecal contents, and decreased serum IL-6 level. However, antibiotic administration had no effect on serum concentrations of corticosterone and α1-acid glycoprotein (AGP), vitamin C concentration in the liver, and mRNA levels of haptoglobin and AGP in the liver. Therefore, disturbance of gut microbiota did not attenuate the increase in glucocorticoid level and induction of APP gene expression due to vitamin C deficiency. This suggests that gut microbiota is not involved in the inflammation-like responses caused by vitamin C deficiency.

Topics: Acute-Phase Proteins; Animals; Anti-Bacterial Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Corticosterone; Gastrointestinal Microbiome; Inflammation; Interleukin-6; Liver; Male; Rats; RNA, Messenger

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Betacoronavirus; Coronavirus Infections; COVID-19; Critical Illness; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2

Arterial tortuosity syndrome (ATS) is a recessively inherited connective tissue disorder, mainly characterized by tortuosity and aneurysm formation of the major arteries. ATS is caused by loss-of-function mutations in SLC2A10, encoding the facilitative glucose transporter GLUT10. Former studies implicated GLUT10 in the transport of dehydroascorbic acid, the oxidized form of ascorbic acid (AA). Mouse models carrying homozygous Slc2a10 missense mutations did not recapitulate the human phenotype. Since mice, in contrast to humans, are able to intracellularly synthesize AA, we generated a novel ATS mouse model, deficient for Slc2a10 as well as Gulo, which encodes for L-gulonolactone oxidase, an enzyme catalyzing the final step in AA biosynthesis in mouse. Gulo;Slc2a10 double knock-out mice showed mild phenotypic anomalies, which were absent in single knock-out controls. While Gulo;Slc2a10 double knock-out mice did not fully phenocopy human ATS, histological and immunocytochemical analysis revealed compromised extracellular matrix formation. Transforming growth factor beta signaling remained unaltered, while mitochondrial function was compromised in smooth muscle cells derived from Gulo;Slc2a10 double knock-out mice. Altogether, our data add evidence that ATS is an ascorbate compartmentalization disorder, but additional factors underlying the observed phenotype in humans remain to be determined.

Topics: Animals; Arteries; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Glucose Transport Proteins, Facilitative; Homozygote; Humans; Joint Instability; L-Gulonolactone Oxidase; Mice; Mice, Knockout; Mitochondria; Respiration; Signal Transduction; Skin Diseases, Genetic; Vascular Malformations

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Humans; Male; Pain; Treatment Outcome; Vitamins

To date, there are no recommendations about screening plasma vitamin C concentration and adjust its supplementation in patients on long-term home parenteral nutrition (HPN). The aim of this study was to evaluate vitamin C status and determine if a commercial multivitamin preparation (CMVP) containing 125 mg of vitamin C is sufficient in stable patients on HPN. All clinically stable patients receiving HPN or an intravenous fluid infusion at least two times per week for at least 6 months, hospitalized for nutritional assessment, were retrospectively included, for a total of 186 patients. We found that 29% of the patients had vitamin C insufficiency (i.e., <25 µmol/L). In univariate analysis, C-reactive protein (CRP) (

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Eating; Female; Humans; Inflammation; Male; Middle Aged; Monitoring, Physiologic; Nutrition Assessment; Nutritional Physiological Phenomena; Nutritional Status; Parenteral Nutrition, Home Total; Retrospective Studies

Vitamin C (ascorbate) acts as an antioxidant and enzyme cofactor, and plays a vital role in human health. Vitamin C status can be affected by illness, with low levels being associated with disease due to accelerated turnover. However, robust data on the ascorbate status of patients with cancer are sparse. This study aimed to accurately measure ascorbate concentrations in plasma from patients with cancer, and determine associations with patient or tumor characteristics. We recruited 150 fasting patients with cancer (of 199 total recruited) from two cohorts, either prior to cancer surgery or during cancer chemo- or immunotherapy. A significant number of patients with cancer had inadequate plasma ascorbate concentrations. Low plasma status was more prevalent in patients undergoing cancer therapy. Ascorbate status was higher in women than in men, and exercising patients had higher levels than sedentary patients. Our study may prompt increased vigilance of ascorbate status in cancer patients.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Breast Neoplasms; Colonic Neoplasms; Exercise; Female; Health Surveys; Humans; Male; Middle Aged; Neoplasms; Nutritional Status; Risk Factors; Sedentary Behavior; Vitamins

Vitamin C deficiency increases the risk of postherpetic neuralgia (PHN). In this cross-sectional study, the relationships among plasma vitamin C concentrations, pain and Leeds assessment of neuropathic symptoms and signs (LANSS) items were investigated during their first pain clinic visit of 120 PHN patients. The factors associated with vitamin C deficiency were determined. Independent predictors of vitamin C deficiency were presented as adjusted odds ratios (AOR) and 95% confidence intervals (CI). The patients had a high prevalence (52.5%) of vitamin C deficiency. Their plasma vitamin C concentrations were negatively associated with spontaneous pain and tingling, prickling or pins and needles sensation according to the LANSS questionnaire. Based on the receiver operator characteristic curve, the cutoffs for plasma vitamin C to predict moderate-to-severe and severe symptoms of sharp sensation were <7.05 and <5.68 mg/L, respectively. By comparison, the patients well-nourished with vitamin C had lower incidences of sharp sensations, sharp pain, and reddish skin. Multivariate analyses revealed that vitamin C deficiency was associated with the low intake of fruit/vegetables (AOR 2.66, 95% CI 1.09-6.48,

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Cross-Sectional Studies; Diet; Diet Surveys; Female; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Neuralgia, Postherpetic; Odds Ratio; Pain Measurement; Paresthesia; Prevalence; Prospective Studies; Risk Factors; ROC Curve; Surveys and Questionnaires; Young Adult

Investigation into the role of vitamin C in the prevention and treatment of pneumonia and sepsis has been underway for many decades. This research has laid a strong foundation for translation of these findings into patients with severe coronavirus disease (COVID-19). Research has indicated that patients with pneumonia and sepsis have low vitamin C status and elevated oxidative stress. Administration of vitamin C to patients with pneumonia can decrease the severity and duration of the disease. Critically ill patients with sepsis require intravenous administration of gram amounts of the vitamin to normalize plasma levels, an intervention that some studies suggest reduces mortality. The vitamin has pleiotropic physiological functions, many of which are relevant to COVID-19. These include its antioxidant, anti-inflammatory, antithrombotic and immuno-modulatory functions. Preliminary observational studies indicate low vitamin C status in critically ill patients with COVID-19. There are currently a number of randomized controlled trials (RCTs) registered globally that are assessing intravenous vitamin C monotherapy in patients with COVID-19. Since hypovitaminosis C and deficiency are common in low-middle-income settings, and many of the risk factors for vitamin C deficiency overlap with COVID-19 risk factors, it is possible that trials carried out in populations with chronic hypovitaminosis C may show greater efficacy. This is particularly relevant for the global research effort since COVID-19 is disproportionately affecting low-middle-income countries and low-income groups globally. One small trial from China has finished early and the findings are currently under peer review. There was significantly decreased mortality in the more severely ill patients who received vitamin C intervention. The upcoming findings from the larger RCTs currently underway will provide more definitive evidence. Optimization of the intervention protocols in future trials, e.g., earlier and sustained administration, is warranted to potentially improve its efficacy. Due to the excellent safety profile, low cost, and potential for rapid upscaling of production, administration of vitamin C to patients with hypovitaminosis C and severe respiratory infections, e.g., COVID-19, appears warranted.

Topics: Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Betacoronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Critical Illness; Humans; Nutritional Status; Pandemics; Pneumonia, Viral; SARS-CoV-2; Severe Acute Respiratory Syndrome; Vitamins

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Hypotension, Orthostatic; Norepinephrine

Plaque-induced gingivitis, a common condition in children, responds well to proper oral hygiene practices. Persistent severe gingivitis, on the other hand, should prompt investigation of etiological factors. Nutritional elements are implicated in periodontal health. This case report describes a pediatric patient with severe persistent gingivitis caused by vitamin C deficiency. The events that led to a diagnosis of scurvy and a resolution of the systemic and localized manifestations of the disease, after vitamin C administration, are presented. It is recommended that vitamin C deficiency be considered in cases of refractory gingivitis, especially in pediatric patients with special health care needs who have aversion to foods rich in ascorbic acid.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Dental Plaque; Gingivitis; Humans; Scurvy

Development is often assumed to be hardwired in the genome, but several lines of evidence indicate that it is susceptible to environmental modulation with potential long-term consequences, including in mammals

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Count; DNA Methylation; DNA-Binding Proteins; Epigenomics; Female; Germ Cells; Loss of Function Mutation; Meiosis; Mice; Models, Animal; Pregnancy; Proto-Oncogene Proteins; Transcriptome

Vitamin C has anti-oxidant properties and acts as a cofactor for several enzymes. Hypovitaminosis C has been associated with bleeding, endothelial dysfunction and death. The prevalence of hypovitaminosis C is unknown in Australian hospitalised patients, and its clinical relevance is uncertain.. To determine the prevalence, characteristics and clinical outcomes of hospitalised patients with hypovitaminosis C.. This observational study included general-medical inpatients in a tertiary-level hospital in Australia. High-performance liquid chromatography (HPLC) was used to determine plasma vitamin C levels. As per Johnston's criteria, vitamin C levels of ≥28 μmol/L were classified as normal and <28 μmol/L as low. Clinical outcomes determined included length of hospital stay (LOS), nosocomial complications, intensive care unit admission and in-hospital mortality.. A total of 200 patients participated in this study, and vitamin C levels were available for 149 patients, of whom 35 (23.5%) had normal vitamin C levels, and 114 (76.5%) had hypovitaminosis C. Patients with hypovitaminosis C were older and had higher C-reactive protein (CRP) levels. Median LOS was 2 days longer in patients with hypovitaminosis C (6 days (interquartile range (IQR) 4, 8) vs 4 days (IQR 3, 6), P = 0.02), and they had fourfold higher odds of staying in hospital for >5 days than those with normal vitamin C levels. Other clinical outcomes were similar between the two groups.. Hypovitaminosis C is common in hospitalised patients and is associated with prolonged LOS. Further research is needed to ascertain the benefits of vitamin C supplementation in vitamin C-depleted patients.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Australia; C-Reactive Protein; Female; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Logistic Models; Male; Middle Aged; Prevalence; Risk Factors

Autism spectrum disorder is a heterogenous neurodevelopmental condition accompanied by a variety of associated features. Case reports suggest one such associated feature, food selectivity, increases risk for nutritional deficiencies; however, little attention has been given to prevent and treat nutritional deficiencies in youth with autism spectrum disorder.. Single case report.. This single case report presents a child with autism spectrum disorder and food selectivity difficulties that resulted in severe vitamin C deficiency. Although eventually corrected, the nutritional deficiency was debilitating, required invasive interventions, and resulted in significant social/emotional and economic costs.. We review the course of treatment and highlight strategies to prevent and more effectively treat nutritional deficiencies in youth with autism spectrum disorder.

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Autism Spectrum Disorder; Diet Therapy; Early Diagnosis; Food Preferences; Humans; Male; Malnutrition; Patient Care Management; Risk Assessment; Vitamins

Vitamin C (l-ascorbic acid, VC) and vitamin E (α-tocopherol, VE) play important physiological roles as endogenous antioxidants in many tissues and organs. However, their roles in the brain remain entirely elusive. We established senescence marker protein 30 (SMP30)/α-tocopherol transfer protein (αTTP) double knockout (DKO) mice as a novel VC and VE double-deficiency model and examined the effect of VC and VE double-deficiency on brain functions.. DKO and wild-type (WT) mice were divided into the following two groups: mice in the CE (+) group were supplied with sufficient amounts of VC and VE and mice in the CE (-) group were deficient in both VC and VE. After 8 weeks of CE (+) or CE (-) treatments, a battery of behavioral experiments was conducted to analyze cognitive functions, including memory, through the Morris water maze and Pavlovian fear conditioning tasks.. The plasma VC and VE levels in DKO-CE (-) mice and VE level in WT-CE (-) mice were almost completely depleted after 8 weeks of the deficient treatment. The behavioral study revealed that the general behaviors, including locomotor activity and anxiety level, were not influenced by the CE (-) treatment in DKO and WT mice. However, in the Pavlovian fear conditioning task, DKO-CE (-) mice showed impaired conditioned fear memory compared with that of DKO-CE (+) mice. Furthermore, increased mRNA expression was observed in inflammatory-related genes, such as IL-6, TNFα, F4/80, and Mcp-1, in the hippocampus of DKO-CE (-) mice.. The findings of this study provide evidence that VC and VE deficiency led to impaired conditioned fear memory possibly caused by neuroinflammation in the brain.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Calcium-Binding Proteins; Carrier Proteins; Conditioning, Classical; Fear; Inflammation; Intracellular Signaling Peptides and Proteins; Maze Learning; Memory; Mice; Mice, Knockout; Vitamin E; Vitamin E Deficiency

Historically known to be a disease of sailors and soldiers in the seventeenth and eighteenth century, scurvy is a rare nutritional deficiency in the developed world, but it can still be seen among the alcoholics and the malnourished. We present a case of a 39-year-old alcoholic male who presented with progressive fatigue and diffuse purpuric rash with scattered ecchymosis for 2 months. Blood work was remarkable for hemoglobin of 9.1 g/dl, which further dropped to 7 g/dl over the next few days. He was then found to have hemolysis on lab work. After an extensive workup, the common causes of hemolytic anemia were ruled out, vitamin C level was checked, which interestingly resulted as 0 mg/dl. Supplementation with oral vitamin C resulted in the gradual resolution of hemolytic anemia and rash. Hemoglobin improved to 15 g/dl in 4 weeks, with normalization of vitamin C level. The clinical features of scurvy can easily be confused with conditions such as vasculitis, deep venous thrombosis, and systemic bleeding disorders. Therefore, comprehensive workup up is required prior to the diagnosis. Although rare, being a reversible condition, early diagnosis and treatment of scurvy in high-risk populations cannot be stressed enough.

Topics: Administration, Oral; Adult; Alcoholism; Anemia, Hemolytic; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Male

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Critical Illness; Guinea Pigs; Humans; Primates; Scurvy

L-Ascorbic acid (AsA) is a water-soluble antioxidant. We examined the effect of AsA deficiency on skeletal muscle using senescence marker protein-30 (SMP30)-knockout (KO) mice that are defective in AsA biosynthesis, which makes this mouse model similar to humans, to clarify the function of AsA in skeletal muscle. Eight-week-old female SMP30-KO mice were divided into the following two groups: an AsA-sufficient group [AsA(+)] that was administered 1.5 g/L AsA and an AsA-deficient group [AsA(-)] that was administered tap (AsA-free) water. At 4 weeks, the AsA content in the gastrocnemius muscle of AsA(-) mice was 0.7% compared to that in the gastrocnemius muscle of AsA(+) mice. Significantly lower weights of all muscles were observed in AsA(-) mice than those in AsA(+) mice at 12 and 16 weeks. The cross-sectional area of the soleus was significantly smaller in AsA(-) mice at 16 weeks than that in AsA(+) mice. The physical performance of AsA(-) mice was significantly less than that of AsA(+) mice at 12 weeks. Following AsA deficiency for 12 weeks, the expression of ubiquitin ligases, such as atrogin1/muscle atrophy F-box (MAFbx) and muscle RING-finger protein 1 (MuRF1), was upregulated. Furthermore, all detected effects of AsA deficiency on muscles of the AsA(-) group at 12 weeks were restored following AsA supplementation for 12 weeks. Thus, longer-term AsA deficiency is associated with muscle wasting, that this can be reversed by restoring AsA levels.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Mice; Mice, Knockout; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Ubiquitin; Ubiquitin-Protein Ligases; Up-Regulation

To investigate the appetite for vitamin C (VC), we conducted behavioral and neural experiments using osteogenic disorder Shionogi/Shi Jcl-od/od (od/od) rats, which lack the ability to synthesize VC, and their wild-type controls osteogenic disorder Shionogi/Shi Jcl- +/+ (+/+) rats. In the behavioral study, rats were deprived of VC for 25 days and then received two-bottle preference tests with a choice between water and 10 mM VC. The preference for 10 mM VC solution of od/od rats was significantly greater than that of +/+ rats. In the neural study, the relative magnitudes of the whole chorda tympani nerve (CTN) responses to 100-1000 mM VC, 3-10 mM HCl, 100-1000 mM NaCl, and 20 mM quinine▪HCl in the VC-deficient rats were significantly smaller than those in the nondeficient ones. Further, we conducted additional behavioral experiments to investigate the appetite for sour and salty taste solutions of VC-deficient od/od rats. Preference scores for 3 mM citric acid increased in od/od rats after VC removal, compared with before, whereas preference scores for 100 and 150 mM NaCl were decreased in VC-deficient od/od rats. The preference for 300 mM NaCl was not changed. Hence, our results suggest that the reduction of the aversive taste of VC during VC deficiency may have involved the reduction of CTN responses to acids. Overall, our results indicate that VC-deficient rats ingest sufficient VC to relieve their deficiency and that VC deficiency causes changes in peripheral sensitivity to acids, but nongustatory factors may also affect VC intake and choice.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Behavior, Animal; Bone Diseases; Chorda Tympani Nerve; Dose-Response Relationship, Drug; Rats; Rats, Inbred Strains; Solutions

Topics: Abscess; Adult; Aged; Ankle Joint; Arthralgia; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Hematoma; Humans; Knee Joint; Male; Middle Aged; Postoperative Complications; Scurvy

We have previously shown that ascorbic acid (AsA) deficiency elevates hepatic expression of acute phase proteins (APPs), inflammatory markers, in Osteogenic Disorder Shionogi (ODS) rats, which are unable to synthesize AsA. However, the precise mechanisms of this elevation are unknown. Signal transducer and activator of transcription 3 (STAT3) is one of the transcription factors inducing the expression of APPs and is activated by several cytokines including interleukin-6 (IL-6). The aim of this study was to determine whether AsA deficiency stimulates hepatic STAT3 activation and increases intestinal production of proinflammatory cytokines such as IL-6. Male ODS rats (6 weeks old) were fed either a basal diet containing 300 mg AsA/kg (control group) or an AsA-free diet (AsA-deficient group) for 18 days. AsA deficiency gradually and simultaneously elevated both mRNA levels of APPs (haptoglobin, α1-acid glycoprotein, C-reactive protein and α2-macroglobulin) and nuclear level of phosphorylated STAT3 (activated STAT3) in the liver. These results showed that the AsA-deficiency-induced expression of hepatic APPs is stimulated by proinflammatory cytokines activating STAT3. On day 14, AsA deficiency significantly elevated IL-6 mRNA level in the ileum and the concentration of IL-6 in portal blood. Furthermore, the portal concentration of IL-6 positively correlated with hepatic mRNA levels of STAT3-regulated genes. These findings suggest that IL-6, produced in the intestine as a result of AsA deficiency, is recruited to the liver via the portal vein and contributes to hepatic STAT3 activation and the elevated expression of APPs.

Topics: Acute-Phase Proteins; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Nucleus; Cytosol; Duodenum; Gene Expression Profiling; Inflammation; Interleukin-6; Liver; Male; Osteogenesis; Phosphorylation; Rats; STAT3 Transcription Factor

In this study, we aimed to clarify the role of ascorbic acid in collagen synthesis in periodontal ligaments using osteogenic disorder Shionogi (ODS)/ShiJcl-od/od rats lacking L-gulonolactone oxidase. These rats cannot synthesize ascorbic acid in vivo. Eight-week-old ODS/ShiJcl-od/od male rats were administered ascorbic acid solution at a concentration of 200 mg/dL (control group, n = 6) or ascorbic acid solution at concentration of 0.3 mg/dL (insufficient group, n = 12). Six rats of the insufficient group were then given with ascorbic acid solution at concentration of 200 mg/dL for additional 3 weeks (rescued group, n = 6), and then, their mandibles were histochemically examined. Consequently, the insufficient group specimens were seen to possess fewer collagen fibers, and silver impregnation revealed numerous fine, reticular fiber-like fibrils branching off from collagen in the periodontal ligaments. In control group, faint immunoreactivities for matrix metalloproteinase (MMP)2 and cathepsin H were seen in the periphery of blood vessels and throughout the ligament, respectively. In contrast, in the insufficient group, intense MMP2-immunoreactivity was observed to be associated with collagen fibrils in the periodontal ligaments, and cathepsin H-immunopositivity was seen in ligamentous cells. The rescued group showed abundant collagen fibers filling the periodontal ligament space. Under transmission electron microscopy, ligamentous fibroblasts incorporated collagen fibrils into tubular endosomes/lysosomes while simultaneously synthesizing collagen fibril bundles. Thus, ascorbic acid insufficiency affected the immunolocalization of cathepsin H and MMP2; however, ligamentous fibroblasts appear to possess the potential to synthesize collagen fibers when supplied with ascorbic acid.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Immunohistochemistry; Male; Microscopy, Electron, Transmission; Periodontal Ligament; Rats

To investigate the demographic and lifestyles factors associated with vitamin C deficiency and to examine the association between plasma vitamin C level and self-reported physical functional health.. A population-based cross-sectional study using the European Prospective Investigation into Cancer-Norfolk study. Plasma vitamin C level < 11 µmol/L indicated vitamin C deficiency. Unconditional logistic regression models assessed the association between vitamin C deficiency and potential risk factors. Associations between quartiles of vitamin C and self-reported functional health measured by the 36-item short-form questionnaire (SF-36) were assessed.. After adjustment, vitamin C deficiency was associated with older age, being male, lower physical activity, smoking, more socially deprived area (Townsend index) and a lower educational attainment. Compared to the highest, those in the lowest quartile of vitamin C were more likely to score in the lowest decile of physical function (adjusted odds ratio (aOR): 1.43 (95%CI: 1.21-1.70)), bodily pain (aOR: 1.29 (95% CI: 1.07-1.56)), general health (aOR: 1.4 (95%CI: 1.18-1.66)), and vitality (aOR: 1.23 (95%CI: 1.04-1.45)) SF-36 scores.. Simple public health interventions should be aimed at populations with risk factors for vitamin C deficiency. Poor self-reported functional health was associated with lower plasma vitamin C levels, which may reflect symptoms of latent scurvy.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Europe; Female; Humans; Life Style; Male; Middle Aged; Neoplasms; Risk Factors; Self Report; Socioeconomic Factors; United Kingdom

Objectives Vitamin C deficiency is considered extremely rare in modern industrialized countries. This study was performed to assess vitamin C concentrations in the German population. Methods As part of a consultant-patient seminar on nutrition and food intolerances, patients were asked to participate in this study on a voluntary basis. Blood samples were taken for analysis of serum vitamin C concentrations, and all patients were asked to complete a questionnaire. The vitamin C concentration was determined by high-performance liquid chromatography. Results Of approximately 300 patients attending the seminar, 188 (62.6%) consented to vitamin C blood sample analysis and 178 (59.3%) answered the questionnaire. The mean vitamin C concentration was 7.98 mg/L (range, 0.50-17.40; reference range, 5-15 mg/L). A low plasma level with vitamin C insufficiency (<5 mg/L) was found in 31 patients (17.4%), and a potential scorbutogenic deficiency (<1.5 mg/L) was found in 6 (3.3%). Conclusions Potential vitamin C insufficiency and deficiency is common. It is therefore possible, even in modern developed populations, that certain individuals may require a higher intake of vitamin C.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Body Mass Index; Cross-Sectional Studies; Female; Germany; Humans; Incidence; Male; Middle Aged; Sex Factors; Surveys and Questionnaires

A nationwide cross-sectional study.. To measure the associations between cigarette smoking (defined as serum cotinine concentration >15 ng/mL) and the 3-month prevalence of spinal pain (neck pain, low back pain, low back pain with pain below knee, and self-reported diagnosis of arthritis/rheumatism) and related limitations, and to verify whether these associations are mediated by serum concentrations of vitamin C.. Cigarette smoking has been consistently associated with back pain, but this association has never been explained. Because vitamin C has recently been reported to be associated with spinal pain and related functional limitations, and the metabolism of vitamin C differs between smokers and nonsmokers, we hypothesized that the prevalence of spinal pain and related limitations might be greater among smokers because they are more susceptible to be in a state of hypovitaminosis C.. We conducted secondary analyses of National Health and Nutrition Examination Survey (NHANES) 2003 to 2004 data on 4438 individuals aged ≥20 years.. Serum concentrations of vitamin C and cotinine were strongly and inversely correlated (r = -0.35, P < 0.0001). Smoking was statistically associated with the prevalence of neck pain [adjusted odds ratio: aOR: 1.25; 95% confidence interval (95% CI): 1.06-1.47], low back pain (aOR: 1.20; 95% CI: 1.04-1.39), and low back pain with pain below knee (aOR: 1.58; 95% CI: 1.13-2.22) and related limitations, with a dose-response relationship (P < 0.05). However, the associations between smoking and spinal pain were not mediated by concentrations of vitamin C.. These results confirm the relationship between smoking and spinal pain, but they do not support a mediating effect of vitamin C on this relationship.. 2.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Back Pain; Cigarette Smoking; Cotinine; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Neck Pain; Nutrition Surveys; Prevalence

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Atrophy; Humans; Hyaluronan Receptors; Hyaluronic Acid; Mice; Signal Transduction; Skin; Skin Aging; Skin Diseases; Vitamins

Topics: Adolescent; Adult; Aged; Anthropometry; Ascorbic Acid; Ascorbic Acid Deficiency; Asian People; China; Cohort Studies; Cross-Sectional Studies; Diet; Female; Fruit; Humans; Logistic Models; Male; Middle Aged; Nutrition Assessment; Nutritional Requirements; Nutritional Status; Prevalence; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires; Vegetables; Young Adult

Topics: Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Double-Blind Method; Humans; Purpura; Scurvy

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Double-Blind Method; Humans; Purpura; Scurvy

Topics: Abdomen; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Lower Extremity; Middle Aged; Purpura; Skin

Topics: Anemia; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Diet, Healthy; Humans; Male; Middle Aged; Scurvy

The aim of this study was to verify the protective effects of ascorbic acid (AsA) against lipopolysaccharide (LPS)-induced sepsis. The study was conducted using osteogenic disorder Shionogi (ODS) rats, which are unable to synthesize AsA. Male ODS rats (6 wk old) were fed either an AsA-free diet (AsA-deficient group), a diet supplemented with 300 mg/kg AsA (control group), or a diet supplemented with 3,000 mg/kg AsA (high-AsA group) for 8 d. On day 8, all the rats were intraperitoneally injected with LPS (15 mg/kg body weight). Forty-eight hours after the injection, the survival rates of the rats in the control (39%) and the high-AsA (61%) groups were significantly higher than that in the AsA-deficient group (5.5%). Next, we measured several inflammatory parameters during 10 h after administering LPS. At 6 h, elevated serum levels of markers for hepatic and systemic injuries were suppressed in rats fed AsA. Similarly, 10 h after LPS injection, the elevation in the serum levels of markers for renal injury were also suppressed proportionally to the amount of AsA in the diet. The elevated serum concentrations of TNFα and IL-1β by LPS in the AsA-deficient group decreased in groups fed AsA. Hematic TNFα mRNA levels at 6 h after the LPS injection were also lowered by feeding AsA. These results demonstrated that the dietary intake of AsA improved the survival rates and suppressed the inflammatory damage, in a dose-dependent manner, caused during sepsis induced by LPS in ODS rats.

Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Dietary Supplements; Inflammation; Interleukin-1beta; Kidney; Kidney Diseases; Lipopolysaccharides; Liver; Liver Diseases; Male; Nutritional Status; Osteogenesis; Rats; Rats, Inbred Strains; Sepsis; Tumor Necrosis Factor-alpha; Vitamins

Recent studies have highlighted the role of oxidative stress in the pathogenesis of lichen planus (LP). In the present study, the interest of the authors is focused on the investigation of ascorbic acid status in patients with LP and identification of parameters that might influence the level of this vitamin.. We analyzed the level of urinary ascorbic acid (reflectometric method) in 77 patients with LP (cutaneous LP (CLP)-49 cases; oral LP (OLP)-28 cases) and 50 control subjects. The evaluation of all participants included clinical examination and laboratory and imaging tests.. Compared to the control group (19.82 mg/dl) the level of ascorbic acid was significantly lower both in patients with CLP (8.47 mg/dl, p = 0.001) and in those with OLP (8.04 mg/dl, p = 0.001). In patients with LP it was found that the deficiency of ascorbic acid increases with age (r = -0.318, p = 0.032). The urinary concentrations of ascorbic acid were significantly lower in patients with LP associated with infections compared to patients with LP without infections.. The urinary ascorbic acid level may be a useful parameter in identifying patients with LP who are at risk of developing viral or bacterial infections.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Lichen Planus; Male; Middle Aged

Senescence marker protein-30 (SMP30) decreases androgen-independently with aging and is a lactone-hydrolyzing enzyme gluconolactonase (GNL) that is involved in vitamin C biosynthesis. In the present study, bone properties of SMP30/GNL knockout (KO) mice with deficiency in vitamin C synthesis were investigated to reveal the effects of SMP30/GNL and exogenous vitamin C supplementation on bone formation. Mineral content (BMC) and mineral density (BMD) of the mandible and femur of SMP30/GNL KO and wild-type mice at 2 and 3 months of age with or without vitamin C supplementation were measured by dual-energy X-ray absorptiometry. Body and bone weight of both age groups decreased and became significantly lower than those of wild-type mice. The bones of SMP30/GNL KO mice were rough and porous, with BMC and BMD significantly below wild-type. Oral supplementation with vitamin C eliminated differences in body weight, bone weight, BMC, and BMD between SMP30/GNL KO and wild-type mice at each age. These results indicate that bone degeneration in SMP30/GNL KO mice was caused by lack of vitamin C, and that this mouse strain is an appropriate model for bone metabolism in humans, which have no ability to synthesize vitamin C.

Topics: Absorptiometry, Photon; Aging; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Bone Density; Bone Diseases, Metabolic; Calcium-Binding Proteins; Carboxylic Ester Hydrolases; Dietary Supplements; Disease Models, Animal; Female; Femur; Intracellular Signaling Peptides and Proteins; Male; Mandible; Mice, Inbred C57BL; Mice, Knockout; Osteoporosis

Vitamin C may reduce inflammation and is inversely associated with mortality in the general population. We investigated the association of plasma vitamin C with all-cause mortality in renal transplant recipients (RTR); and whether this association would be mediated by inflammatory biomarkers. Vitamin C, high sensitive C-reactive protein (hs-CRP), soluble intercellular cell adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured in a cohort of 598 RTR. Cox regression analyses were used to analyze the association between vitamin C depletion (≤28 µmol/L; 22% of RTR) and mortality. Mediation analyses were performed according to Preacher and Hayes's procedure. At a median follow-up of 7.0 (6.2-7.5) years, 131 (21%) patients died. Vitamin C depletion was univariately associated with almost two-fold higher risk of mortality (Hazard ratio (HR) 1.95; 95% confidence interval (95%CI) 1.35-2.81,

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Body Composition; Body Mass Index; C-Reactive Protein; Creatinine; Dietary Supplements; Endpoint Determination; Female; Follow-Up Studies; Humans; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Mortality; Proportional Hazards Models; Prospective Studies; Proteinuria; Vascular Cell Adhesion Molecule-1

The increasing incidence of metabolic diseases such as obesity or diabetes have made them a major public health problem. Increasing oxidative stress induced by reactive oxygen species, which initiate the oxidative adverse changes in the cell, is mentioned, among other risk factors, to underlie these diseases. Vitamin A, C and E are listed among the non-enzymatic mechanisms counteracting this phenomenon. Vitamin D deficiency is also associated with cardiovascular diseases.. The aim of the study was to assess the risk of vitamin A, C, E and D deficit in the plasma of metabolic syndrome (MS) patients.. The study included 191 patients with MS and 98 subjects without MS. Loglinear analysis was used in the assessment of mutual interactions between the vitamin concentration and the analysis of classification by ROC curves to predict the frequency of vitamin deficiency in MS patients.. A correlation was found between the plasma level of vitamins in the group of MS patients. Vitamin A concentration correlated with that of vitamin C (r = 0.51, p = 0.0000), vitamin D (r = 0.49, p = 0.0000) and E (r = 0.32, p = 0.0001). The plasma level of vitamin D correlated with the level of vitamin E (r = 0.46, p = 0.00000) and vitamin C (r = 0.37, p = 0.0000). Regression analysis showed a correlation between the concentration of the tested vitamins in patients with MS. Interactions were observed between vitamins C and A and between C and D. HDL cholesterol level was lower in patients with vitamin A deficiency compared to patients with its normal level.. The plasma levels of vitamin A, C, E and D were significantly lower in patients with MS than in healthy subjects and they mutually correlated with each other. The normalization of glucose and HDL level may contribute to the regulation of the concentration of vitamin A in patients with MS.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Case-Control Studies; Cholesterol, HDL; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Reactive Oxygen Species; Risk; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency

Topics: Age Factors; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Cognition; Cognitive Aging; Cognitive Dysfunction; Female; Health Status; Healthy Aging; Humans; Longitudinal Studies; Male; Mental Health; Middle Aged; New Zealand; Prevalence; Prospective Studies; Recommended Dietary Allowances; Risk Factors; Socioeconomic Factors

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Obsessive-Compulsive Disorder; Psychotic Disorders

Stem-cell fate can be influenced by metabolite levels in culture, but it is not known whether physiological variations in metabolite levels in normal tissues regulate stem-cell function in vivo. Here we describe a metabolomics method for the analysis of rare cell populations isolated directly from tissues and use it to compare mouse haematopoietic stem cells (HSCs) to restricted haematopoietic progenitors. Each haematopoietic cell type had a distinct metabolic signature. Human and mouse HSCs had unusually high levels of ascorbate, which decreased with differentiation. Systemic ascorbate depletion in mice increased HSC frequency and function, in part by reducing the function of Tet2, a dioxygenase tumour suppressor. Ascorbate depletion cooperated with Flt3 internal tandem duplication (Flt3

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinogenesis; Dioxygenases; DNA-Binding Proteins; Female; fms-Like Tyrosine Kinase 3; Hematopoietic Stem Cells; Humans; Leukemia; Male; Metabolomics; Mice; Myelopoiesis; Proto-Oncogene Proteins

Plant GDP-D-mannose epimerase (GME) converts GDP-D-mannose to GDP-L-galactose, a precursor of both L-ascorbate (vitamin C) and cell wall polysaccharides. However, the genetic functions of GME in Arabidopsis are unclear. In this study, we found that mutations in Arabidopsis GME affect pollen germination, pollen tube elongation, and transmission and development of the male gametophyte through analysis of the heterozygous GME/gme plants and the homozygous gme plants. Arabidopsis gme mutants also exhibit severe growth defects and early leaf senescence. Surprisingly, the defects in male gametophyte in the gme plants are not restored by L-ascorbate, boric acid or GDP-L-galactose, though boric acid rescues the growth defects of the mutants, indicating that GME may regulate male gametophyte development independent of L-ascorbate and GDP-L-galactose. These results reveal key roles for Arabidopsis GME in reproductive development, vegetative growth and leaf senescence, and suggest that GME regulates plant growth and controls male gametophyte development in different manners.

Topics: Arabidopsis; Arabidopsis Proteins; Ascorbic Acid; Ascorbic Acid Deficiency; Carbohydrate Epimerases; Cellular Senescence; Genes, Plant; Germ Cells, Plant; Germination; Mannose; Mutation; Phenotype; Plant Development; Plant Leaves; Pollen; Pollen Tube

Vitamin C is an essential water-soluble nutrient which cannot be synthesised or stored by humans. It is a potent antioxidant with anti-inflammatory and immune-supportive roles. Previous research has indicated that vitamin C levels are depleted in critically ill patients. In this study we have assessed plasma vitamin C concentrations in critically ill patients relative to infection status (septic shock or non-septic) and level of inflammation (C-reactive protein concentrations). Vitamin C status was also assessed relative to daily enteral and parenteral intakes to determine if standard intensive care unit (ICU) nutritional support is adequate to meet the vitamin C needs of critically ill patients.. Forty-four critically ill patients (24 with septic shock, 17 non-septic, 3 uncategorised) were recruited from the Christchurch Hospital Intensive Care Unit. We measured concentrations of plasma vitamin C and a pro-inflammatory biomarker (C-reactive protein) daily over 4 days and calculated patients' daily vitamin C intake from the enteral or total parenteral nutrition they received. We compared plasma vitamin C and C-reactive protein concentrations between septic shock and non-septic patients over 4 days using a mixed effects statistical model, and we compared the vitamin C status of the critically ill patients with known vitamin C bioavailability data using a four-parameter log-logistic response model.. Overall, the critically ill patients exhibited hypovitaminosis C (i.e., < 23 μmol/L), with a mean plasma vitamin C concentration of 17.8 ± 8.7 μmol/L; of these, one-third had vitamin C deficiency (i.e., < 11 μmol/L). Patients with hypovitaminosis C had elevated inflammation (C-reactive protein levels; P < 0.05). The patients with septic shock had lower vitamin C concentrations and higher C-reactive protein concentrations than the non-septic patients (P < 0.05). Nearly 40% of the septic shock patients were deficient in vitamin C, compared with 25% of the non-septic patients. These low vitamin C levels were apparent despite receiving recommended intakes via enteral and/or parenteral nutritional therapy (mean 125 mg/d).. Critically ill patients have low vitamin C concentrations despite receiving standard ICU nutrition. Septic shock patients have significantly depleted vitamin C levels compared with non-septic patients, likely resulting from increased metabolism due to the enhanced inflammatory response observed in septic shock.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; C-Reactive Protein; Critical Illness; Enteral Nutrition; Female; Humans; Intensive Care Units; Male; Middle Aged; New Zealand; Nutritional Requirements; Organ Dysfunction Scores; Parenteral Nutrition; Shock, Septic

The AKR1A1 protein is a member of the aldo-keto reductase superfamily that is responsible for the conversion of D-glucuronate to L-gulonate in the ascorbic acid (vitamin C) synthesis pathway. In a pCAG-eGFP transgenic mouse line that was produced by pronuclear microinjection, the integration of the transgene resulted in a 30-kb genomic DNA deletion, including the Akr1A1 gene, and thus caused the knockout (KO) of the Akr1A1 gene and targeting of the eGFP gene. The Akr1A1 KO mice (Akr1A1eGFP/eGFP) exhibited insufficient serum ascorbic acid levels, abnormal bone development and osteoporosis. Using micro-CT analysis, the results showed that the microarchitecture of the 12-week-old Akr1A1eGFP/eGFP mouse femur was shorter in length and exhibited less cortical bone thickness, enlargement of the bone marrow cavity and a complete loss of the trabecular bone in the distal femur. The femoral head and neck of the proximal femur also showed a severe loss of bone mass. Based on the decreased levels of serum osteocalcin and osteoblast activity in the Akr1A1eGFP/eGFP mice, the osteoporosis might be caused by impaired bone formation. In addition, administration of ascorbic acid to the Akr1A1eGFP/eGFP mice significantly prevented the condition of osteoporotic femurs and increased bone formation. Therefore, through ascorbic acid administration, the Akr1A1 KO mice exhibited controllable osteoporosis and may serve as a novel model for osteoporotic research.

Topics: Aldehyde Reductase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Female; Femur; Gene Knockout Techniques; Genetic Predisposition to Disease; Mice, Knockout; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis; Phenotype; Time Factors; X-Ray Microtomography

Vitamin C deficiency globally affects several hundred million people and has been associated with increased morbidity and mortality in numerous studies. In this study, bioavailability of the oxidized form of vitamin C (l-dehydroascorbic acid or DHA)-commonly found in vitamin C containing food products prone to oxidation-was studied. Our aim was to compare tissue accumulation of vitamin C in guinea pigs receiving different oral doses of either ascorbate or DHA. In all tissues tested (plasma, liver, spleen, lung, adrenal glands, kidney, muscle, heart, and brain), only sporadic differences in vitamin C accumulation from ascorbate or DHA were observed except for the lowest dose of DHA (0.25mg/ml in the drinking water), where approximately half of the tissues had slightly yet significantly less vitamin C accumulation than from the ascorbate source. As these results contradicted data from rats, we continued to explore the ability to recycle DHA in blood, liver and intestine in guinea pigs, rats and mice. These investigations revealed that guinea pigs have similar recycling capacity in red blood cells as observed in humans, while rats and mice do not have near the same ability to reduce DHA in erythrocytes. In liver and intestinal homogenates, guinea pigs also showed a significantly higher ability to recycle DHA compared to rats and mice. These data demonstrate that DHA in guinea pigs-as in humans-is almost as effective as ascorbate as vitamin C source when it comes to taking up and storing vitamin C and further suggest that the guinea pig is superior to other rodents in modeling human vitamin C homeostasis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dehydroascorbic Acid; Dietary Supplements; Dose-Response Relationship, Drug; Erythrocytes; Guinea Pigs; Humans; Intestines; Liver; Mice; Rats; Tissue Distribution; Vitamins

A 10-year-old boy developed a perifollicular rash during interim maintenance of T-Cell acute lymphoblastic leukaemia. Differential diagnoses included drug reaction and inflammatory process. Before diagnosis, the patient had a limited diet--low in vegetables and fruits--due to selective eating, with later anorexia and taste aversions due to chemotherapy treatment. Despite nutritional counselling and starting a multivitamin, the patient incurred severe weight loss (18.5% of his usual body weight). Serum levels of ascorbic acid were non-detectable, at <5 μmol/L, indicative of vitamin C deficiency. The patient began vitamin C supplementation containing 125 mg ascorbic acid three times a day for 7 days, then 125 mg once daily for 3 months to normalise serum vitamin C. After ascorbic acid treatment was completed, the patient started a complete multivitamin and made efforts to eat fruits and vegetables rich in vitamin C. His serum ascorbic acid concentrations normalised to 52 μmol/L 3 months after receiving supplementation.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Dietary Supplements; Directive Counseling; Energy Intake; Feeding and Eating Disorders; Fruit; Humans; Male; Patient Compliance; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome; Vegetables; Vitamins; Weight Loss

Suboptimal intake of dietary vitamin C (ascorbate) increases the risk of several chronic diseases but the exact metabolic pathways affected are still unknown. In this study, we examined the metabolic profile of mice lacking the enzyme gulonolactone oxidase (Gulo) required for the biosynthesis of ascorbate. Gulo-/- mice were supplemented with 0%, 0.01%, and 0.4% ascorbate (w/v) in drinking water and serum was collected for metabolite measurements by targeted mass spectrometry. We also quantified 42 serum cytokines and examined the levels of different stress markers in liver. The metabolic profiles of Gulo-/- mice treated with ascorbate were different from untreated Gulo-/- and normal wild type mice. The cytokine profiles of Gulo-/-mice, in return, overlapped the profile of wild type animals upon 0.01% or 0.4% vitamin C supplementation. The life span of Gulo-/- mice increased with the amount of ascorbate in drinking water. It also correlated significantly with the ratios of serum arginine/lysine, tyrosine/phenylalanine, and the ratio of specific species of saturated/unsaturated phosphatidylcholines. Finally, levels of hepatic phosphorylated endoplasmic reticulum associated stress markers IRE1α and eIF2α correlated inversely with serum ascorbate and life span suggesting that vitamin C modulates endoplasmic reticulum stress response and longevity in Gulo-/- mice.

Topics: Amino Acids; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cytokines; DNA-Binding Proteins; Endoplasmic Reticulum Stress; Endoribonucleases; Hormones; L-Gulonolactone Oxidase; Longevity; Male; Membrane Lipids; Metabolome; Mice; Mice, Knockout; Mitochondria, Liver; Protein Serine-Threonine Kinases; Transcription Factors

This study investigated the effects of dietary vitamin C on the growth, and head kidney, spleen and skin immunity, structural integrity and related signaling molecules mRNA expression levels of young grass carp (Ctenopharyngodon idella). A total of 540 grass carp (264.37 ± 0.66 g) were fed six diets with graded levels of vitamin C (2.9, 44.2, 89.1, 133.8, 179.4 and 224.5 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila and the survival rate recorded for 14 days. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) decreased lysozyme (LA) and acid phosphatase (ACP) activities, and complement 3 and complement 4 (C4) contents (P < 0.05), down-regulated the mRNA levels of antimicrobial peptides [liver expressed antimicrobial peptide (LEAP) 2A, LEAP-2B, hepcidin, β-defensin] and anti-inflammatory cytokines-related factors, interleukin (IL) 4/13A, IL-4/13B (only in head kidney), IL-10, IL-11, transforming growth factor (TGF) β1, TGF-β2, inhibitor of κBα and eIF4E-binding protein 1 (P < 0.05), and up-regulated pro-inflammatory cytokines-related factors, tumor necrosis factor α, interferon γ2, IL-1β, IL-6, IL-8, IL-12 P35 (only in spleen), IL-12 P40, IL-15, IL-17D, nuclear factor κB p65, IκB kinases (IKKα, IKKβ, IKKγ), target of rapamycin and ribosomal protein S6 kinase 1 mRNA levels (P < 0.05) in the head kidney and spleen under injection fish of A. hydrophila, suggesting that vitamin C deficiency could decrease fish head kidney and spleen immunity and cause inflammation. Meanwhile, compared with optimal vitamin C supplementation, vitamin C deficiency decreased the activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase, glutathione S-transferases and glutathione reductase (P < 0.05), and down-regulated zonula occludens (ZO) 1, ZO-2, Claudin-b, -c, -3c, -7a, -7b, B-cell lymphoma-2, inhibitor of apoptosis protein, NF-E2-related factor 2 mRNA levels (P < 0.05), increased reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl contents (P < 0.05), and up-regulated Claudin-12, 15a, -15b, Fas ligand, mitogen-activated protein kinase kinase 6, p38 mitogen-activated protein kinase, B-cell lymphoma protein 2 associated X protein, apoptotic protease activating factor-1, caspase-3, -7, -8, -9, Kelch-like ECH-associating protein (Keap) 1a and Keap 1b mRNA le

Topics: Aeromonas hydrophila; Animal Feed; Animals; Apoptosis; Ascorbic Acid; Ascorbic Acid Deficiency; Carps; Diet; Dietary Supplements; Dose-Response Relationship, Drug; Fish Diseases; Fish Proteins; Gram-Negative Bacterial Infections; Head Kidney; Immunity, Innate; Random Allocation; Signal Transduction; Spleen

Scurvy results from a deficiency of vitamin C, a nutrient otherwise known as ascorbic acid. Today, scurvy is rare yet emerges in select patients. The patient reported herein developed scurvy secondary to deliberate avoidance of vitamin C-rich foods. Classic cutaneous manifestations of scurvy include follicular hyperkeratosis and perifollicular hemorrhage encompassing coiled "corkscrew" hairs and hairs bent into "swan-neck" deformities. Ecchymoses, purpura, and petechiae are also characteristically prominent. Classic oral abnormalities include erythematous, swollen gingivae that hemorrhage from subtle microtrauma.Subungual linear splinter hemorrhages may also manifest as a sign of the disease. To establish the diagnosis requirements include characteristic physical exam findings, evidence of inadequate dietary intake, and rapid reversal of symptoms upon supplementation. Although unnecessary for diagnosis, histological findings demonstrate perifollicular inflammation and hemorrhage, fibrosis, and hyperkeratosis, amongst dilated hair follicles and keratin plugging. Although citrus fruit allergies have been historically documented, ascorbic acid has not been previously reported as an allergen. Although lacking absolute certainty, this report suggests a presumed case of ascorbic acid allergy based on patient history and favorable response to ascorbic acid desensitization therapy.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Diagnosis, Differential; Drug Eruptions; Fast Foods; Humans; Male; Middle Aged; Scurvy; Skin; Vitamins

In Switzerland, vitamin C deficiency is a rare condition. Nonetheless, in clinical practice, there are some patients exhibiting a vitamin C deficiency as a result of an unbalanced diet or intestinal malabsorption. We report the clinical history of a 55-year-old man known for alcoholism and insufficient intake of fresh fruits and vegetables. He was admitted to the intensive care unit, for haemodynamic instability caused by blood loss due to fragile vessels (skin, gastrointestinal). Further analyses revealed a severe lack of vitamin C. The patient received a high dose of intravenous substitutive treatment, leading to a favourable clinical outcome.

Topics: Alcoholism; Anemia; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Hemodynamics; Humans; Male; Malnutrition; Middle Aged; Purpura; Switzerland

Although vitamin C is not produced in the body, it is important for many biochemical and physiological functions. Little is known about the current vitamin C status of Canadians. This study describes the correlates of vitamin C status in a nationally representative sample of adults.. Data are from the 2012/2013 Canadian Health Measures Survey. Plasma vitamin C (L-ascorbic acid) concentrations were measured among a fasting subsample of respondents aged 20 to 79 (n = 1,615). Vitamin C status, prevalence of deficiency (plasma vitamin C < 11 μmol/L), and use of vitamin C-containing supplements were estimated. Multivariate regression models were used to examine associations between vitamin C status and sociodemographic characteristics, smoking, body mass index, supplement use, and consumption of fruit juice and citrus fruit.. The mean plasma vitamin C concentration of adults aged 20 to 79 was 53 μmol/L; fewer than 3% were vitamin C-deficient. Almost 22% took a vitamin C-containing supplement. Concentrations were lower among smokers and people who were obese, and higher among vitamin C supplement users and fruit juice and citrus fruit consumers. Multivariate models showed that supplement use was the strongest and most consistent predictor of vitamin C status; fruit juice and citrus fruit consumption were predictors only among populations with lower vitamin C concentrations (for example, smokers, obese).. Few Canadians were vitamin C-deficient. Smokers and people with a higher BMI were most at risk of lower vitamin C concentrations; concentrations were higher among supplement users and consumers of fruit juice and citrus fruit.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Canada; Female; Health Surveys; Humans; Male; Middle Aged

A Japanese-style diet consists of meals that include grain (shushoku), fish and meat (shusai), and vegetable dishes (fukusai). Little is known about the association of such meals (designated well-balanced meals hereafter) with nutrient intake. We therefore examined the frequency of well-balanced meals required to prevent nutrient deficiency. Participants were Japanese people, ages 40 to 59 y, from Toyama, recruited for INTERMAP, in an international population-based study. Each person provided 4 in-depth 24-h dietary recalls (149 men, 150 women). The prevalence of risk ratios of not meeting the Dietary Reference Intakes for Japanese (2015) was calculated. Well-balanced diets were assessed by the Japanese Food Guide Spinning Top. We counted the frequencies of meals in which participants consumed 1.0 or more servings of all 3 dishes categories. We divided the frequency of consumption of well-balanced meals into the following 4 groups: <1.00 time/d, 1.00-1.49 times/d, 1.50-1.74 times/d, and ≥1.75 times/d. Compared with participants in the highest frequency group for well-balanced meals, those who consumed well-balanced meals less than once a day had a higher risk of not meeting the adequate intake for potassium and the recommended dietary allowance for vitamin A. Those who consumed well-balanced meals on average less than 1.50 times per day had a higher risk of not meeting the recommended dietary allowance for calcium and vitamin C. Our results suggest that individuals should on average consume well-balanced meals more than 1.5 times per day to prevent calcium and vitamin C deficiencies.

Topics: Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Asian People; Body Mass Index; Body Weight; Calcium, Dietary; Diet, Healthy; Energy Intake; Female; Fishes; Humans; Japan; Male; Malnutrition; Meat; Mental Recall; Micronutrients; Middle Aged; Nutrition Assessment; Recommended Dietary Allowances; Seafood; Vegetables; Vitamin A; Vitamin A Deficiency; Whole Grains

Inadequate dietary intake of vitamin C results in hypovitaminosis C, defined as a plasma ascorbate concentration ≤23 μmol/L. Our objective was to carry out a retrospective analysis of two vitamin C supplementation studies to determine whether supplementation with 50 mg/day vitamin C is sufficient to restore adequate ascorbate status (≥50 μmol/L) in individuals with hypovitaminosis C. Plasma ascorbate data from 70 young adult males, supplemented with 50 or 200 mg/day vitamin C for up to six weeks, was analyzed. Hypovitaminosis C status was identified based on plasma ascorbate being ≤23 μmol/L and the response of these individuals to vitamin C supplementation was examined. Of the participants consuming 50 mg/day vitamin C for up to six weeks, those with hypovitaminosis C at baseline achieved plasma concentrations of only ~30 μmol/L, whereas the remainder reached ~50 μmol/L. Participants who consumed 200 mg/day vitamin C typically reached saturating concentrations (>65 μmol/L) within one week, while those with hypovitaminosis C required two weeks to reach saturation. Regression modelling indicated that the participants' initial ascorbate status and body weight explained ~30% of the variability in the final ascorbate concentration. Overall, our analysis revealed that supplementation with 50 mg/day vitamin C, which resulted in a total dietary vitamin C intake of 75 mg/day, was insufficient to achieve adequate plasma ascorbate concentrations in individuals with hypovitaminosis C. Furthermore, increased body weight had a negative impact on ascorbate status.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Dose-Response Relationship, Drug; Humans; Male

Marginal vitamin C (vitC) deficiency affects 5% to 10% of adults including subpopulations such as pregnant women and newborns. Animal studies link vitC deficiency to deleterious effects on the developing brain, but exactly how the brain adapts to vitC deficiency and the mechanisms behind the observed deficits remain largely unknown. We hypothesized that vitC deficiency in utero may lead to a decreased neuronal maturation and increased cellular death giving rise to alterations of the hippocampal morphology in a guinea pig model. Brains from prenatal guinea pig pups (n=9-10 in each group) subjected to either a sufficient (918mg vitC/kg feed) or deficient (100mg vitC/kg feed) maternal dietary regimen were assessed with regards to hippocampal volume and β-tubulin isotype III staining intensity at 2 gestational time points (45 and 56). We found a distinct differential regional growth pattern of the hippocampus with a clear effect of gestational age, whereas vitC status did not affect either investigated parameters. Within hippocampal subdivisions, the overall expansion of the hippocampus from gestational day 45 to 56 was found to reside in the dentate gyrus. In conclusion, the present study found that hippocampal volume and β-tubulin isotype III intensity in the prenatal guinea pig were influenced by gestational day but not by maternal vitC intake.

Topics: Animals; Animals, Newborn; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Female; Guinea Pigs; Hippocampus; Maternal Nutritional Physiological Phenomena; Pregnancy; Prenatal Care; Tubulin

Globally, β-thalassemia major (β-TM) is one of the most common hereditary disorders. Multiple blood transfusions, that are a life-saving therapy in patients with β-TM, is a major source of iron overload. Iron overload can lead to significant morbidity and mortality. Research evidence indicates that oxidative stress induced by iron overload, is one of the major precipitating causes of vitamin C deficiency in β-TM patients. It has previously been shown that patients with β-TM have significantly lower levels of vitamin C as compared to healthy individuals. It is believed that vitamin C can reduce both ferric (Fe(3+)) and ferrous (Fe(2+)) ions, and also facilitate the accessibility of iron to chelators through increase of iron release from the reticuloendothelial system. Despite the potential benefits of vitamin C in patients with β-TM, several areas of concern exist that should be addressed by high quality research designs. Some recommendations have been provided through this study.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; beta-Thalassemia; Contraindications; Dietary Supplements; Humans; Iron Overload; Nutrition Policy; Oxidative Stress; Transfusion Reaction

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Exanthema; Humans; Male; Middle Aged; Muscle Weakness

Vitamin C deficiency is found in patients with cancer and might complicate various therapy paradigms. Here we show how this deficiency may influence the use of DNA methyltransferase inhibitors (DNMTis) for treatment of hematological neoplasias. In vitro, when vitamin C is added at physiological levels to low doses of the DNMTi 5-aza-2'-deoxycytidine (5-aza-CdR), there is a synergistic inhibition of cancer-cell proliferation and increased apoptosis. These effects are associated with enhanced immune signals including increased expression of bidirectionally transcribed endogenous retrovirus (ERV) transcripts, increased cytosolic dsRNA, and activation of an IFN-inducing cellular response. This synergistic effect is likely the result of both passive DNA demethylation by DNMTi and active conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) enzymes at LTR regions of ERVs, because vitamin C acts as a cofactor for TET proteins. In addition, TET2 knockout reduces the synergy between the two compounds. Furthermore, we show that many patients with hematological neoplasia are markedly vitamin C deficient. Thus, our data suggest that correction of vitamin C deficiency in patients with hematological and other cancers may improve responses to epigenetic therapy with DNMTis.

Topics: Apoptosis; Ascorbic Acid; Ascorbic Acid Deficiency; Azacitidine; Cell Proliferation; Decitabine; Dioxygenases; DNA Methylation; DNA-Binding Proteins; Drug Synergism; Endogenous Retroviruses; Enzyme Inhibitors; Female; Hematologic Neoplasms; Humans; Interferons; Male; Methyltransferases; Proto-Oncogene Proteins; RNA, Double-Stranded

This study explored the effects of vitamin C on the physical barriers and immune barriers, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) (1) increased reactive oxygen species, malondialdehyde and protein carbonyl (PC) contents (P < 0.05), decreased the copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and mRNA levels (P < 0.05), and glutathione and vitamin C contents (P < 0.05), down-regulated NF-E2-related factor 2 mRNA level (P < 0.05), and up-regulated Kelch-like ECH-associating protein (Keap) 1a (rather than Keap1b) mRNA level (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency induced oxidative injury in fish gill; (2) up-regulated caspase-3, -7, -8, -9, Fas ligand, B-cell lymphoma protein 2 associated X protein, apoptotic protease activating factor-1 mRNA levels (P < 0.05), and down-regulated inhibitor of apoptosis protein and B-cell lymphoma-2 (rather than myeloid cell leukemia-1) mRNA level (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency aggravated cell apoptosis in fish gill; (3) up-regulated pore-forming TJs Claudin-12, 15a, -15b, and related signaling molecules myosin light chain kinase, p38 mitogen-activated protein kinase (rather than c-Jun N-terminal kinases) mRNA levels (P < 0.05), and down-regulated barrier-forming TJs Occludin, zonula occludens (ZO) 1, ZO-2, Claudin-c, -3c, -7a, -7b mRNA levels (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency disrupted tight junctional complexes in fish gill; (4) decreased lysozyme and acid phosphatase (ACP) activities, and complement 3 (C3), C4 and IgM contents (P < 0.05), down-regulated the mRNA levels of antimicrobial peptides liver expressed antimicrobial peptide (LEAP) 2A, LEAP-2B, Hepcidin, β-defensin mRNA levels (P < 0.05) in the gill of grass carp under infection of F. columnare, suggesting that vitamin C deficiency decrease fish gill immune function; (5) down-regulated the mRNA levels of anti-inflammatory cytokines-related factors interleukin 10 (IL-10), IL-11, transforming growth factor (TGF) β1, TGF-β2, inhibitor of κBa and eIF4E-bi

Topics: Animal Feed; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carps; Diet; Dietary Supplements; Fish Diseases; Fish Proteins; Flavobacteriaceae Infections; Flavobacterium; Gills; Immunity, Innate; Random Allocation; Signal Transduction

Most patients attending cancer clinics have hypovitaminosis D. Correcting or preventing this abnormal condition could mitigate the emotional and physical complications of their disease, but clinical trials of vitamin D therapy in this setting are hindered by the unavailability of safe, effective and practical loading dose regimens.. In this single arm open-label pharmacokinetic trial, outpatients with advanced lung cancer consumed 20,000 IU vitamin D daily with the largest meal of the day for 14 days followed by 10,000 IU per day for a further 7 days. Plasma concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone, calcium, vitamin C and C-reactive protein were measured on protocol days 0, 14 and 21, and serum vitamin D binding protein (VDBP) concentrations on days 0 and 21. As a secondary objective, preliminary information was obtained regarding clinical effects of rapid vitamin D loading on mood and symptoms by administering appropriate questionnaires two times at baseline and after 14 and 21 days of vitamin D therapy.. Of the 91 patients enrolled in the study, 85 % had hypovitaminosis D and 41 % had hypovitaminosis C. Plasma VDBP concentrations were in the normal range. The vitamin D load increased the average plasma 25(OH)D concentration to 116 ± 34 nmol/L (mean ± SD); the median concentration was 122 nmol/L (interquartile range 103-134); VDBP concentrations did not change. Final plasma 25(OH)D concentrations were subnormal (<75 nmol/L) for 13 % of the patients and sub-target (<120 nmol/L) for 44 % of them. In most cases, subnormal and sub-target 25(OH)D concentrations were attributable to obesity and/or a low baseline 25(OH)D concentration. Mood and symptom scores did not change significantly throughout the 3-week protocol.. Hypovitaminosis D and C are very common in outpatients with advanced lung cancer. A vitamin D load of 20,000 IU per day for 14 days failed to achieve the target concentration in 44 % of the participants in this trial. These results suggest that a loading dose of 30,000 IU per day for 14 days would be safe and effective for patients who are obese or at risk of severe hypovitaminosis D. The preliminary nature of the study design, and the failure to achieve target 25(OH)D concentrations for a large proportion of the patients, do not allow any firm conclusion about the clinical effects of correcting hypovitaminosis D in this patient population. Nevertheless, no evidence was obtained that partial correction of hypovitaminosis D greatly improved mood, reduced distress or relieved cancer-related symptoms. This trial was registered at clinicaltrials.gov as NCT01631526.

Topics: Affect; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Availability; C-Reactive Protein; Calcium; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Middle Aged; Parathyroid Hormone; Prevalence; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

The role of endogenous vitamin C (VC) in emotion and psychiatric measures has long been uncertain. We aimed to investigate how an individual's VC status impacts his or her mental health. Our hypothesis is that body VC levels modulate anxiety, anorexia, and depressive phenotypes under the influence of psychosocial rearing environments and sex. The VC status of senescence marker protein-30/gluconolactonase knockout mice, which lack the ability to synthesize VC, were continuously shifted from adequate (VC+) to depleted (VC-) by providing a water with or without VC. Despite weight loss in both sexes, suppressed feeding was specifically seen in males only during the VC- phase. Anxiety responses in the novelty-suppressed feeding paradigm were worse during the VC-, especially in females. Sensitivity to the forced swim test as determined by the initial latency was significantly shorter in the socially stable animals compared with socially unstable animals during the VC+ condition. The stress coping underlying depressive phenotypes was assessed by immobility duration in a series of forced swim tests. No significant differences were apparent between contrasting VC status. Homeostatic symptoms following stressful behavioral tests consisted of a great loss of appetite during the VC-. It should be noted that anorexia is extremely serious for the females. We conclude that endogenous VC status is critical for determining vulnerability to anxiety and anorexia in a sex-specific manner.

Topics: Adaptation, Psychological; Animals; Anorexia; Anxiety; Ascorbic Acid; Ascorbic Acid Deficiency; Behavior, Animal; Body Weight; Calcium-Binding Proteins; Carboxylic Ester Hydrolases; Depression; Eating; Feeding Behavior; Female; Homeostasis; Intracellular Signaling Peptides and Proteins; Male; Mice, Knockout; Nutritional Status; Risk Factors; Sex Factors; Social Environment; Stress, Psychological; Swimming; Vitamins

This patient was a liver transplant recipient and had a history of malnutrition. One tell-tale sign on the physical exam, however, left no doubt as to the diagnosis.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Contusions; Female; Humans; Middle Aged; Purpura; Treatment Outcome

To determine the prevalence of vitamin C (ascorbic acid [AA]) deficiency in patients with end-stage renal disease, the effect of supplemental AA on plasma AA concentrations, and the extrinsic and intrinsic factors that affect plasma AA concentrations in this patient population.. In study 1, we compared the effect of hemodialysis (HD) on plasma AA concentrations between patients with low and high pre-HD AA concentrations. In study 2, we analyzed kinetic and nonkinetic factors for their association with increased plasma AA concentrations in patients on maintenance HD. Study 1 was performed in a single outpatient HD clinic in Cherry Hill, New Jersey. Study 2 was performed in 4 outpatient HD clinics in Southern New Jersey.. In study 1, we collected plasma samples from 8 adult patients on maintenance HD at various time points around their HD treatment and assayed them for AA concentration. In study 2, we enrolled 203 adult patients and measured pre-HD plasma AA concentrations. We ascertained supplemental AA use and assessed dietary AA intake.. In study 1, plasma AA concentrations were compared during the intradialytic and interdialytic period. In study 2, pre-HD plasma AA concentrations were correlated with supplement use and demographic factors.. Study 1 showed that over the course of a single HD treatment, the plasma AA concentration decreased by a mean (±standard deviation) of 60% (±6.6). In study 2, the median pre-HD plasma AA concentration was 15.7 μM (interquartile range, 8.7-66.8) in patients who did not take a supplement and 50.6 μM (interquartile range, 25.1-88.8) in patients who did take a supplement (P < .001). Supplement use, increasing age, and diabetes mellitus were associated with a pre-HD plasma AA concentration ≥30 μM.. HD depletes plasma AA concentrations, and AA supplementation allows patients to achieve higher plasma AA concentrations.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Diabetes Complications; Diet; Dietary Supplements; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Recently, we reported that preferential maternal-fetal vitamin C (vitC) transport across the placenta is likely to be impaired by prolonged maternal vitC deficiency. Maintenance of a basal maternal vitC supply at the expense of the fetus may impair fetal development; however, the knowledge of vitC's impact on intrauterine development is sparse. The aim of this study was to explore the effect of maternal vitC status on fetal and placental development in guinea pigs.. Twenty pregnant Dunkin Hartley guinea pigs were randomized into four groups to receive diets either sufficient (918 mg/kg CTRL) or deficient (100 mg/kg DEF) in vitC. Cesarean sections at gestational day (GD) 45 or 56 allowed for fetal and placental measurements.. At GD45, body, brain and placental weights were significantly reduced in DEF pups compared with CTRL (p < 0.05, p < 0.001 and p < 0.05, respectively). DEF plasma vitC levels were ~6% of those of CTRL (p < 0.0001), and the fetal/maternal plasma vitC ratio was significantly reduced at GD56 in the DEF animals compared with controls (p = 0.035). Placental vitC levels were reduced in DEF animals (p < 0.0001) and the ascorbate oxidation ratio and glutathione elevated compared with controls (p < 0.0001).. Although no clinical differences between CTRL and DEF pups were observed at GD56, the present data suggest that vitC plays a role in early fetal development. Although no clinical differences between CTRL and DEF pups were observed at GD56, the present data suggest that vitC plays a role in early fetal development. Low maternal vitC intake during pregnancy may compromise maternal weight gain, placental function and intrauterine development.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Disease Models, Animal; Euthanasia; Female; Fetal Development; Fetal Growth Retardation; Fetus; Guinea Pigs; Linear Models; Maternal Nutritional Physiological Phenomena; Maternal-Fetal Exchange; Placenta; Pregnancy; Sodium-Coupled Vitamin C Transporters

Vitamin C (VC) is an essential nutrient for humans and certain other animals. It has antioxidant properties and has been reported to ameliorate oxidative damage to lipids, DNA and proteins. However, the effects of VC on immune function are poorly understood, especially the influence of long-term high-dose VC intake on the number and function of immune cells. In the present study, to evaluate the immune effects of VC, VC-deficient senescence marker protein-30 knockout (SMP30KO) mice were fed a diet containing the recommended level of VC (20 mg/kg per d; 0·02 % VC) or a high level of VC (200 mg/kg per d; 0·2 % VC) for 1 year. The plasma VC concentration of the 0·02 % group was the same as that of age-matched C57BL/6 mice after 1 year of feeding; however, plasma VC concentration and thymus weight were significantly higher in the 0·2 % VC group than in the 0·02 % VC group. The total counts of leucocytes, lymphocytes, granulocytes and monocytes in the peripheral blood, as well as the number of splenocytes and thymocytes, were all significantly higher in the 0·2 % VC group than in the 0·02 % VC group. In addition, the number of naive T cells in peripheral blood lymphocytes, the number of memory T-cell populations in splenocytes, and the number of cluster of differentiation (CD)4⁺CD8⁺ or CD4⁺CD8⁻ or CD4⁻CD8⁺ T cells in thymocytes were all markedly higher in the 0·2 % VC group than in the 0·02 % VC group after 1 year of dietary treatment. These results suggest that a long-term high-dose intake of VC is effective in the maintenance of immune cells, partly through the suppression of age-related thymic involution in VC-deficient SMP30KO mice.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Atrophy; Calcium-Binding Proteins; Dietary Supplements; Immunologic Factors; Intracellular Signaling Peptides and Proteins; Leukocyte Count; Lymphatic Diseases; Macrophages; Male; Mice, Inbred C57BL; Mice, Knockout; Organ Size; Random Allocation; Specific Pathogen-Free Organisms; Spleen; T-Lymphocyte Subsets; Thymus Gland

Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Disease Models, Animal; Electrodes, Implanted; Electroencephalography; Female; Humans; Kainic Acid; Male; Malondialdehyde; Mice, Knockout; Mice, Transgenic; Oxidative Stress; Pentylenetetrazole; Presenilin-1; Seizures; Sodium-Coupled Vitamin C Transporters

Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways.

Topics: Aging; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Anxiety; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Cognition Disorders; Disease Models, Animal; Female; Learning; Male; Memory; Mice, Transgenic; Motor Activity; Oxidative Stress; Peptide Fragments; Presenilin-1; Sodium-Coupled Vitamin C Transporters

To assess in a population deprived from regular dental care the relationship between alveolar bone loss (ABL) and environmental/systemic conditions.. The study population consisted of subjects from the Purbasari tea estate on West Java, Indonesia. A full set of dental radiographs was obtained of each subject and amount of ABL was assessed. In addition, the following parameters were evaluated: plasma vitamin C, vitamin D3 , HbA1c and CRP, the haptoglobin phenotype, presence of putative periodontopathic bacteria and viruses, dietary habits, smoking and anthropometrics.. In this population 45% showed vitamin C depletion/deficiency, 82% had vitamin D3 insufficiency/deficiency, 70% were in a pre-diabetic state, 6% had untreated diabetes, 21% had elevated CRP values ranging from 3.1 to 16.1 mg/l. Results of the regression analysis, including all above mentioned parameters, showed four significant predictors, explaining 19.8% of the variance of ABL. Number of Porphyromonas gingivalis cells and CRP values showed a positive relationship with ABL, whereas BMI and number of guava fruit servings were negatively related.. Results confirm previous findings that elevated levels of P. gingivalis may be indicative for periodontitis progression. A new finding is that guava fruit consumption may play a protective role in periodontitis in a malnourished population.

Topics: Adult; Alveolar Bone Loss; Ascorbic Acid; Ascorbic Acid Deficiency; Body Mass Index; C-Reactive Protein; Cholecalciferol; Diabetes Mellitus; Environment; Feeding Behavior; Female; Glycated Hemoglobin; Haptoglobins; Herpesvirus 4, Human; Humans; Indonesia; Male; Middle Aged; Periodontitis; Phenotype; Pilot Projects; Porphyromonas gingivalis; Prediabetic State; Psidium; Smoking; Vitamin D Deficiency; Vitamins

Women show higher vitamin C plasma concentrations than men, but the reasons for this observation still require elucidation. The objective of the present study was to investigate whether sex differences in vitamin C plasma concentrations are present in elderly subjects and whether these differences are due to sex-specific lifestyles, total antioxidant status (TAOS) and/or body composition. Fasting plasma concentrations of vitamin C were assessed by photometric detection in a cross-sectional study of 181 women and eighty-nine men aged 62-92 years. Body composition was determined by bioelectrical impedance analysis. Vitamin C intake was assessed with a 3 d estimated dietary record. Stepwise multiple regression analyses were performed to investigate whether sex is an independent predictor of vitamin C plasma concentrations by controlling for age, vitamin C intake, lifestyle factors, TAOS and body composition. Women showed higher vitamin C plasma concentrations than men (76 v. 62 μmol/l, P< 0·0001). In the multiple regression analysis, male sex was a negative predictor of vitamin C plasma concentrations (β = -0·214), as long as absolute fat-free mass (FFM) was not considered as a confounder. When absolute FFM was included, sex was no longer a predictor of vitamin C plasma concentrations, whereas absolute FFM (β = -0·216), physical activity level (β = 0·165), intake of vitamin C supplements (β = 0·164), age (β = 0·147) and smoking (β = -0·125) affected vitamin C plasma concentrations. The results indicate that a higher absolute FFM, and thus a higher distribution volume of vitamin C, contributes to lower vitamin C plasma concentrations in men than women.

Topics: Aged; Aged, 80 and over; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Body Constitution; Cohort Studies; Cross-Sectional Studies; Dietary Supplements; Down-Regulation; Female; Germany; Humans; Longitudinal Studies; Male; Middle Aged; Motor Activity; Prevalence; Reproducibility of Results; Sex Factors; Smoking

Vitamin C (VitC) deficiency is surprisingly common in humans even in developed parts of the world. The micronutrient has several established functions in the brain; however, the consequences of its deficiency are not well characterised. To elucidate the effects of VitC deficiency on the brain, increased knowledge about the distribution of VitC to the brain and within different brain regions after varying dietary concentrations is needed. In the present study, guinea pigs (like humans lacking the ability to synthesise VitC) were randomly divided into six groups (n 10) that received different concentrations of VitC ranging from 100 to 1500 mg/kg feed for 8 weeks, after which VitC concentrations in biological fluids and tissues were measured using HPLC. The distribution of VitC was found to be dynamic and dependent on dietary availability. Brain saturation was region specific, occurred at low dietary doses, and the dose-concentration relationship could be approximated with a three-parameter Hill equation. The correlation between plasma and brain concentrations of VitC was moderate compared with other organs, and during non-scorbutic VitC deficiency, the brain was able to maintain concentrations from about one-quarter to half of sufficient levels depending on the region, whereas concentrations in other tissues decreased to one-sixth or less. The adrenal glands have similar characteristics to the brain. The observed distribution kinetics with a low dietary dose needed for saturation and exceptional retention ability suggest that the brain and adrenal glands are high priority tissues with regard to the distribution of VitC.

Topics: Adrenal Glands; Animals; Animals, Outbred Strains; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Cerebellum; Dietary Supplements; Female; Frontal Lobe; Guinea Pigs; Hippocampus; Kidney; Kinetics; Liver; Neurons; Organ Specificity; Phosphorylation; Random Allocation; Tissue Distribution

The developing brain of a neonate is particularly susceptible to damage by vitamin C deficiency because of its rapid growth and immature antioxidant system. Cognitive impairment and sensory motor deficits are found in the adult brain upon vitamin C deficiency. Therefore, the aim of this study was to clarify the role of vitamin C in its own right and its related mechanisms in Gulo(-/-) mice incapable of synthesizing vitamin C.. When vitamin C supplementation was ceased for 2 weeks until delivery, stillbirths and a significant reduction in neonatal mice were observed and the growth of neonates was remarkably decreased. In addition, intraparenchymal hemorrhages were found in most of the brains, especially in the stillborn neonates. In addition, the levels of malondialdehyde (MDA) and 8-isoprostanes were increased and structural abnormalities were found in the cortex, hippocampus, and cerebellum. Especially, vitamin C deficiency caused the failure of or a delay in the formation of cerebellar fissures accompanied by abnormal foliation and altered Purkinje cell alignment. In the developed adult brains from vitamin C-deficient Gulo(-/-) mice, the levels of glutathione, MDA, nitrate, IL-6, TNF-α, and Bax were increased and the expression of the GABRA6 and calbindin-28k was decreased. Due to atrophy of the granule and Purkinje cells, the motor behavior of vitamin C-deficient Gulo(-/-) mice declined.. Vitamin C deficiency during gestation induces intraparenchymal hemorrhages and severe defects in the development of the cerebellum. In fully developed brains, it induces the functional impairment by altering the cellular composition in the cerebellum.

Topics: Animals; Animals, Newborn; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Brain-Derived Neurotrophic Factor; Cerebellum; Disease Models, Animal; Interleukin-6; Intracranial Hemorrhages; L-Gulonolactone Oxidase; Mice; Mice, Knockout; Motor Activity; Neurodevelopmental Disorders; Oxidative Stress; Stillbirth; Tumor Necrosis Factor-alpha

Scurvy, or vitamin C deficiency, is rarely presented to a rheumatology clinic. It can mimic several rheumatologic disorders. Although uncommon, it may present as pseudovasculitis or chronic arthritis. Scurvy still exists today within certain populations, particularly in patients with neurodevelopmental disabilities, psychiatric illness or unusual dietary habits.Scurvy presentation to the rheumatologist varies from aches and mild pains to excruciating bone pain or arthritis. Musculoskeletal and mucocutaneous features of scurvy are often what prompts referrals to pediatric rheumatology clinics. Unless health care providers inquire about nutritional habits and keep in mind the risk of nutritional deficiency, it will be easy to miss the diagnosis of scurvy. Rarity of occurrence as compared to other nutritional deficiencies, combined with a lack of understanding about modern-day risk factors for nutritional deficiency, frequently leads to delayed recognition of vitamin C deficiency. We report a case of scurvy in a mentally handicapped Saudi child, who presented with new onset inability to walk with diffuse swelling and pain in the left leg. Skin examination revealed extensive ecchymoses, hyperkeratosis and follicular purpura with corkscrew hairs, in addition to gingival swelling with bleeding. Clinical diagnosis of scurvy was rendered and confirmed by low serum vitamin C level. The patient did extremely well with proper nutritional support and vitamin C supplementation. It has been noticed lately that there is increased awareness about scurvy in rheumatology literature. A high index of suspicion, together with taking a thorough history and physical examination, is required for diagnosis of scurvy in patient who presents with musculoskeletal symptoms. Nutritional deficiency should also be considered by the rheumatologist formulating differential diagnosis for musculoskeletal or mucocutaneous complaints in children, particularly those at risk.

Topics: Arthritis; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Chronic Disease; Dietary Supplements; Humans; Male; Pain; Refusal to Participate; Scurvy; Treatment Outcome; Walking

Vitamin C sufficiency may help prevent osteoporosis and fractures by mediating osteoclastogenesis, osteoblastogenesis, and bone collagen synthesis.. We determined whether dietary intakes and plasma concentrations of vitamin C were associated with a heel ultrasound and hip and spine fracture risks in older men and women.. Participants were recruited from the European Prospective Investigation into Cancer in Norfolk study with 7-d diet diary estimates of vitamin C intake and plasma concentrations. A random subset (4000 of 25,639 subjects) was available for the cross-sectional (ultrasound) study of broadband ultrasound attenuation (BUA) and velocity of sound (VOS), which were determined during the second health examination. The prospective (fracture) study was a case-cohort sample of all participants with a fracture up to March 2009 and the random subset (n = 5319). ANCOVA-determined associations between quintiles of vitamin C intake and plasma status with adjusted BUA and VOS and adjusted Prentice-weighted Cox proportional HRs were calculated for fracture risk.. Women were 58% of the population (39-79 y old), and the median follow-up was 12.6 y (range: 0-16 y). Positive associations across all quintiles of vitamin C intake but not plasma status were significant for VOS in men (β = 2.47 m/s, P = 0.008) and BUA in women (β = 0.82 dB/MHz, P = 0.004). Vitamin C intake was not associated with fracture risk, but there was an inverse association with plasma concentrations in men, with quintile 4 having significantly lower risks of hip fractures (HR: 0.35; 95% CI: 0.16, 0.80) and spine fractures (HR: 0.26; 95% CI: 0.10, 0.69) than quintile 1.. Higher vitamin C intake was significantly associated with higher heel ultrasound measures in men and women, and higher plasma vitamin C concentrations were significantly associated with reduced fracture risk in men only. Our findings that vitamin C intake and status were inconsistently associated with bone health variables suggest that additional research is warranted.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Density; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Diet; Diet Records; England; Female; Hip Fractures; Humans; Longitudinal Studies; Male; Middle Aged; Nutritional Status; Osteoporosis; Osteoporotic Fractures; Proportional Hazards Models; Prospective Studies; Risk Factors; Spinal Fractures

Public health advocates, government agencies, and commercial organizations increasingly use nutritional science to guide food choice and diet as a way of promoting health, preventing disease, or marketing products. We argue that in many instances such references to nutritional science can be characterized as nutritional scientism. We examine three manifestations of nutritional scientism: (1) the simplification of complex science to increase the persuasiveness of dietary guidance, (2) superficial and honorific references to science in order to justify cultural or ideological views about food and health, and (3) the presumption that nutrition is the primary value of food. This paper examines these forms of nutritional scientism in the context of biopolitics to address bioethical concerns related to the misuse of scientific evidence to make claims regarding the effect of diet on health. We argue that nutritional scientism has ethical implications (i) for individual responsibility and freedom, (ii) concerning iatrogenic harm, and (iii) for well-being.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Biological Science Disciplines; Deficiency Diseases; Diet; Food; Freedom; Health; Health Behavior; Health Promotion; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Iatrogenic Disease; Nutrition Policy; Policy Making; Public Health; Recommended Dietary Allowances; Social Responsibility; United States

Vitamins are essential micronutrients for maintenance of tissue functions. Vitamin deficiency is one of the most serious and common health problems among both chronic alcoholics and the homeless. However, the vitamin-level statuses of such people have been little studied. We evaluated the actual vitamin statuses of alcoholic homeless patients who visited an emergency department (ED). In this study the blood levels of vitamins B1, B12, B6, and C of 217 alcoholic homeless patients were evaluated retrospectively in a single urban teaching hospital ED. Vitamin C deficiency was observed in 84.3% of the patients. The vitamin B1, B12, and B6 deficiency rates, meanwhile, were 2.3%, 2.3%, and 23.5%, respectively. Comparing the admitted patients with those who were discharged, only the vitamin C level was lower. (P=0.003) In fact, the patients' vitamin C levels were markedly diminished, vitamin C replacement therapy for homeless patients should be considered in EDs.

Topics: Adult; Alcoholic Intoxication; Ascorbic Acid; Ascorbic Acid Deficiency; Emergency Service, Hospital; Female; Humans; Ill-Housed Persons; Male; Middle Aged; Republic of Korea; Retrospective Studies; Vitamin B Complex

Multiple organ dysfunction syndrome (MODS) is the principal cause of death in patients with sepsis. Recent work supports the notion that parenteral vitamin C (VitC) is protective in sepsis through pleiotropic mechanisms. Whether suboptimal levels of circulating VitC increase susceptibility to sepsis-induced MODS is unknown.. Unlike mice, humans lack the ability to synthesize VitC because of loss of L-gulono-γ-lactone oxidase (Gulo), the final enzyme in the biosynthesis of VitC. To examine whether physiological levels of VitC are required for defense against a catastrophic infection, we induced sepsis in VitC sufficient and VitC deficient Gulo(-/-) mice by intraperitoneal infusion of a fecal stem solution (FIP). Some VitC deficient Gulo(-/-) mice received a parenteral infusion of ascorbic acid (AscA, 200 mg/kg) 30 minutes after induction of FIP. We used molecular, histological, and biochemical analyses to assess for MODS as well as abnormalities in the coagulation system and circulating blood cells.. FIP produced injury to lungs, kidneys and liver (MODS) in VitC deficient Gulo(-/-) mice. MODS was not evident in FIP-exposed VitC sufficient Gulo(-/-) mice and attenuated in VitC deficient Gulo(-/-) mice infused with AscA. Septic VitC deficient Gulo(-/-) mice developed significant abnormalities in the coagulation system and circulating blood cells. These were attenuated by VitC sufficiency/infusion in septic Gulo(-/-) mice.. VitC deficient Gulo(-/-) mice were more susceptible to sepsis-induced MODS. VitC sufficiency or parenteral infusion of VitC, following induction of sepsis, normalized physiological functions that attenuated the development of MODS in sepsis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Cells; Blood Coagulation; Infusions, Parenteral; Kidney; L-Gulonolactone Oxidase; Liver; Lung; Mice, Knockout; Multiple Organ Failure; Sepsis; Vitamins

To examine (i) whether the consumption of fresh vegetables, fruit and berries is associated with plasma vitamin C concentration and (ii) educational differences in plasma vitamin C concentration in two neighbouring areas in Russia and Finland.. Cross-sectional risk factor surveys in 1992, 1997 and 2002. Logistic regression analysis was applied to examine the associations of consumption of selected foods and education with plasma vitamin C concentration.. District of Pitkäranta in the Republic of Karelia, Russia and North Karelia, Finland.. Adults aged 25-64 years: 579 men and 612 women in Pitkäranta; 974 men and 642 women in North Karelia.. The plasma vitamin C concentration was strikingly low in Pitkäranta, Russia across the study years. During the 10 years of monitoring, the mean plasma vitamin C concentration among men ranged from 2·5 to 8·0 μmol/l in Pitkäranta, Russia and from 27·1 to 53·9 μmol/l in North Karelia, Finland. In both areas, daily consumption of fruit was most strongly associated with plasma vitamin C, while the association of fresh vegetable consumption with plasma vitamin C was less consistent. Consumption of berries was less important in explaining plasma vitamin C. In Pitkäranta, the plasma vitamin C concentration was lower among respondents in the lowest education group.. Differences in the consumption of fresh vegetables and fruit resulted in notable differences in vitamin C status between Pitkäranta and North Karelia in spring. In comparative settings, knowledge of local food culture and validation pilots are important before conducting large population surveys.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Cohort Studies; Cross-Sectional Studies; Diet; Educational Status; Epidemiological Monitoring; Female; Finland; Fruit; Humans; Male; Middle Aged; Nutrition Policy; Nutrition Surveys; Patient Compliance; Risk Factors; Russia; Spatio-Temporal Analysis; Vegetables; White People

Given the involvement of oxidative stress in liver-disease- or hepato-toxicant-induced hepatic damage and fibrosis, antioxidants are an effective preventive and therapeutic tool. The beneficial results of vitamin C, one of the physiological antioxidants, have been observed both in experimental animals and in humans. However, most of these studies have been concerned with supplementary vitamin C; the effects of under vitamin C insufficiency, which humans sometimes confront, have not been substantially investigated. In the present study, we established a vitamin C-insufficient animal model (half-to-normal serum vitamin C concentration) with gulo(-/-) mice that cannot synthesize vitamin C, and induced hepatotoxicity by means of thioacetamide (TAA) injections twice a week for 18 weeks. Additionally, we explored the direct effects of vitamin C both on immortalized human hepatic stellate LX-2 cells and on rat primary hepatic stellate cells. Vitamin C insufficiency resulted in a decreased survival rate and increased serum markers for hepatocyte damage, such as alanine aminotransferase and aspartate aminotransferase. Concomitantly, the levels of reactive oxygen species (ROS) and lipid peroxides in the liver were increased. Histological examinations of the vitamin C-insufficient liver revealed increases in collagen fiber deposition and activated-hepatic-stellate-cell number. Vitamin C, when directly applied to the LX-2 cells as well as the rat primary hepatic stellate cells, suppressed not only proliferation but hydrogen peroxide-induced collagen expression as well. In conclusion, vitamin C insufficiency exacerbated TAA-induced hepatotoxicity. These effects seem to be mainly from insufficient scavenging of ROS in the liver, and possibly in part, by directly affecting hepatic stellate cells.

Topics: Alanine Transaminase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Aspartate Aminotransferases; Collagen; Gene Expression; Hepatic Stellate Cells; Humans; L-Gulonolactone Oxidase; Lipid Peroxidation; Liver Cirrhosis; Male; Mice; Mice, Knockout; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Thioacetamide

Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, is highly expressed in the liver and is involved in both the detoxification of carbonyl compounds and ascorbic acid biosynthesis. By comparison with wild-type mice, Akr1a-knockout (Akr1a(-/-)) mice and human Akrla-transgenic (Akr1a(tg/+)) mice experience different anesthetic actions from pentobarbital-prolonged in Akr1a-knockout (Akr1a(-/-)) mice and shortened in human Akrla-transgenic (Akr1a(tg/+)) mice.. We investigated this alteration in the anesthetic efficacy of pentobarbital in Akr1a genetically modified mice.. Neither the cytosolic protein of wild-type mouse liver nor purified rat AKR1A directly reduced pentobarbital. Ascorbic acid administration neutralized the prolonged duration of the loss of the righting reflex (LORR) in Akr1a(-/-) mice, but preincubation of pentobarbital with ascorbic acid prior to administration did not change the anesthetic effect. Those results indicated that ascorbic acid does not directly reduce pentobarbital. Enzymatic activities and levels of the proteins of some cytochrome P450s that make up a potent detoxification system for pentobarbital showed no changes in the genetically modified mice examined. Thus, ascorbic acid also had no effect on the detoxification system in the liver. The prolonged duration of LORR in the Akr1a(-/-) mice caused by pentobarbital and the neutralization of the anesthetic effect by ascorbic acid together with other results imply that ascorbic acid alters the responses of the neuronal system to anesthetics.. Pentobarbital action is increased under conditions of ascorbic acid deficiency, and this may have to be taken into account when anesthetizing malnourished patients.

Topics: Adjuvants, Anesthesia; Aldehyde Reductase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Pentobarbital; Rats; Reflex, Righting; Time Factors

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Evidence-Based Practice; Health Promotion; Humans; Recommended Dietary Allowances

The purpose of this study was to determine the system-wide consequences of deficiencies in two essential micronutrients, vitamins E and C, on the proteome using zebrafish (Danio rerio) as one of the few vertebrate models that similar to humans cannot synthesize vitamin C. We describe a label-free proteomics workflow to detect changes in protein abundance estimates dependent on vitamin regimes. We used ion-mobility-enhanced data-independent tandem mass spectrometry to determine differential regulation of proteins in response to low dietary levels of vitamin C with or without vitamin E. The detection limit of the method was as low as 20 amol, and the dynamic range was five orders of magnitude for the protein-level estimates. On the basis of the quantitative changes obtained, we built a network of protein interactions that reflect the whole organism's response to vitamin C deficiency. The proteomics-driven study revealed that in vitamin-E-deficient fish, vitamin C deficiency is associated with induction of stress response, astrogliosis, and a shift from glycolysis to glutaminolysis as an alternative mechanism to satisfy cellular energy requirements.

Topics: Adaptation, Physiological; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Chromatography, Liquid; Humans; Mass Spectrometry; Metabolic Networks and Pathways; Protein Interaction Mapping; Proteome; Tissue Extracts; Vitamin E; Vitamin E Deficiency; Zebrafish

ENA-actimineral resource A (ENA-A) is an alkaline mineral water and has a few biological activities such as antioxidant activity. The aim of this study was to examine the effects of ENA-A on lifespan in mice using senescence marker protein-30 knockout mice. The present study had groups of 18-week-old mice (n = 24), 26-week-old mice (n = 12), and 46-week-old mice (n = 20). Each differently aged mice group was divided into three subgroups: a control group, a 5 % ENA-A-treated group, and a 10 % ENA-A-treated group. Mice in the 18-week-old group were treated with vitamin C drinking water 1.5 g/L. However, the mice in the 26-week-old and 46-week-old groups were not treated with vitamin C. The experiments were done for 18 weeks. All vitamin C-treated mice were alive at week 18 (100% survival rate). In the non-vitamin C group, the 10% ENA-A-treated mice were alive at week 18. The control and 5% ENA-A-treated mice died by week 15. As expected, vitamin C was not detected in the non-vitamin C-treated group. However, vitamin C levels were increased in an ENA-A dose-dependent manner in the vitamin C-treated group. In the TUNEL assay, a number of positive hepatocytes significantly decreased in an ENA-A dose-dependent manner. Periodic acid Schiff positive hepatocytes were significantly increased in an ENA-A dose-dependent manner. In addition, the expression level of CuZnSOD was increased by the ENA-A treatment. These data suggest that the intake of ENA-A has a critical role in the anti-aging mechanism and could be applied toward the lifespans of humans.

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Bone and Bones; Calcium-Binding Proteins; Glycogen; Hepatocytes; Immunoblotting; Intracellular Signaling Peptides and Proteins; Liver; Longevity; Mice, Knockout; Minerals; Plant Preparations; Staining and Labeling; Superoxide Dismutase; Survival Analysis

We sought to elucidate the effect of an ascorbic acid (AA) deficiency on gene expression, because the water soluble antioxidant AA is an important bioactive substance in vivo.. We performed microarray analyses of the transcriptome in the liver from senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which are unable to synthesize AA in vivo.. Our microarray analysis revealed that the AA deficiency increased gene expression related to the oxidation-reduction process, i.e., the nuclear factor, erythroid derived 2, like 2 (Nrf2) gene, which is a reactive oxygen species-sensitive transcriptional factor. Moreover, this AA deficiency increased the expression of genes for lipid metabolism including the cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1), which is a late-limiting enzyme of the primary bile acid biosynthesis pathway. Although an AA deficiency increased the Cyp7a1 protein level, bile acid levels in the liver and gallbladder decreased. Since Cyp7a1 has a heme iron at the active site, AA must function as a reductant of the iron required for the continuous activation of Cyp7a1.. This experimental evidence strongly supports a role for AA in the physiologic oxidation-reduction process and lipid metabolism including bile acid biosynthesis.. Although many effects of AA supplementation have been reported, no microarray analysis of AA deficiency in vivo is available. Results from using this unique model of AA deficiency, the SMP30/GNL-KO mouse, now provide new information about formerly unknown AA functions that will implement further study of AA in vivo.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Intracellular Signaling Peptides and Proteins; Lipid Metabolism; Liver; Mice; Mice, Knockout; Microarray Analysis; Oxidation-Reduction; Transcriptome

Vitamin C (VitC) has several roles in the brain acting both as a specific and non-specific antioxidant. The brain upholds a very high VitC concentration and is able to preferentially retain VitC even during deficiency. The accumulation of brain VitC levels much higher than in blood is primarily achieved by the sodium dependent VitC transporter (SVCT2). This study investigated the effects of chronic pre-and postnatal VitC deficiency as well as the effects of postnatal VitC repletion, on brain SVCT2 expression and markers of oxidative stress in young guinea pigs. Biochemical analyses demonstrated significantly decreased total VitC and an increased percentage of dehydroascorbic acid, as well as increased lipid oxidation (malondialdehyde), in the brains of VitC deficient animals (p < 0.0001) compared to controls. VitC repleted animals were not significantly different from controls. No significant changes were detected in either gene or protein expression of SVCT2 between groups or brain regions. In conclusion, chronic pre-and postnatal VitC deficiency increased brain redox imbalance but did not increase SVCT2 expression. Our findings show potential implications for VitC deficiency induced negative effects of redox imbalance in the brain and provide novel insight to the regulation of VitC in the brain during deficiency.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Chronic Disease; Female; Gene Expression Regulation; Guinea Pigs; Lipid Metabolism; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Sodium-Coupled Vitamin C Transporters

Vitamin C deficiency in developed countries is typically observed in patients with unique clinical conditions such as cystic fibrosis or anorexia nervosa, or in patients on long-term tube feeds. We report here a clinical observation in six pediatric and adolescent patients (median age 17.5 yr, range 9.8-23.5 yr) with chronic GVHD with mucous membrane involvement found to be vitamin C deficient. These patients' baseline serum vitamin C levels ranged from <0.12 to 0.94 mg/dL (normal value 0.20-1.90 mg/dL), with a mean level 0.56 ± 0.36 mg/dL and a median level 0.6 mg/dL. Among these patients, signs and symptoms of mucositis failed to respond to standard chronic GVHD therapy. After receiving treatment with 2000 mg of ascorbic acid by mouth, daily patients displayed increased serum vitamin C levels. Clinically, this correlated with a remarkable improvement in patients' mucositis and ability to eat.

Topics: Administration, Oral; Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Chronic Disease; Graft vs Host Disease; Humans; Leukemia, Myeloid, Acute; Mucositis; Mucous Membrane; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Scurvy; Stem Cell Transplantation; Young Adult

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Autistic Disorder; Child; Down Syndrome; Humans; Male; Purpura; Scurvy

Moderate vitamin C (vitC) deficiency (plasma concentrations less than 23 μmol/L) affects as much as 10% of adults in the Western World and has been associated with an increased mortality in disease complexes such as cardiovascular disease and the metabolic syndrome. The distribution of vitC within the body is subjected to complex and nonlinear pharmacokinetics and largely depends on the sodium-dependent vitC-specific transporters, sodium-dependent vitamin C transporter 1 (SVCT1) and sodium-dependent vitamin C transporter 2 (SVCT2). Although currently not established, it is likely to expect that a state of deficiency may affect the expression of these transporters to preserve vitC concentrations in specific target tissues. We hypothesized that diet-induced states of vitC deficiency lead to alterations in the messenger RNA (mRNA) and/or protein expression of vitC transporters, thereby regulating vitC tissue distribution. Using guinea pigs as a validated model, this study investigated the effects of a diet-induced vitC deficiency (100 mg vitC/kg feed) or depletion (0 mg vitC/kg feed) on the expression of transporters SVCT1 and SVCT2 in selected tissues and the transport from plasma to cerebrospinal fluid (CSF). In deficient animals, SVCT1 was increased in the liver, whereas a decreased SVCT1 expression but increased SVCT2 mRNA in livers of depleted animals suggests a shift in transporter expression as response to the diet. In CSF, a constant plasma:CSF ratio shows unaltered vitC transport irrespective of dietary regime. The study adds novel information to the complex regulation maintaining vitC homeostasis in vivo during states of deficiency.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Diet; Female; Guinea Pigs; Homeostasis; Kidney; Liver; RNA, Messenger; Sodium-Coupled Vitamin C Transporters; Tissue Distribution; Vitamins

Researchers suspect that the accepted adequate ascorbic acid plasma concentration is not being met even after dietary intake of the recommended amount of vitamin C. Current dietary intake recommendation in Poland is 60 mg per day for women and 75 mg per day for man (EAR), while in Western Europe and North America is higher and amounts to 75-90 mg per day.. The paper aimed at studying a correlation between composition of nutrients in daily diet and plasma vitamin C levels in university students. Materials and methods. This study examined diet composition and the nutritional status of ascorbic acid in plasma of 120 university students in Szczecin, Poland. Ascorbic acid was determined in blood plasma using HPLC method. The information concerning diet composition was collected using the method of "7-days food record" prior to blood collection.. Plasma ascorbic acid deficiency (<40 μmol/L) was observed in 23% of women and 28% of men. The average plasma ascorbic acid concentration was 48.65 μmol/L in women and 45.61 μmol/L in men. The average intake of vitamin C in women with observed deficiency was average 46.55 mg/day, whereas in men it was 48.56 mg/day.. The recommendation of dietary intake of vitamin C in Poland is low in comparison to other countries. Population- based studies are necessary to determine the actual demand for vitamin C in various population groups in Poland. Key words: nutrition, vitamins, dietary intake, diet, ascorbic acid, plasma.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Chromatography, High Pressure Liquid; Feeding Behavior; Female; Food Preferences; Humans; Male; Nutritional Status; Poland; Students; Young Adult

A cross-sectional study was conducted among 775 adolescent girls (11-18 years) residing in a slum of Delhi to assess plasma vitamin C levels. The mean (SD) plasma levels of vitamin C were 0.76 (0.45) mg/dL. Overall, 6.3% and 27.6% girls had deficient (<0.2 mg/dL) and suboptimal levels (0.2-0.49 mg/dL) of plasma vitamin C, respectively.

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Cross-Sectional Studies; Female; Humans; India; Nutritional Status; Poverty Areas; Prevalence

Vitamin C is essential for fish diets because many species cannot syntethize it. This vitamin is needed for bone and cartilage formation. Moreover, it acts as antioxidant and improve the immunological system. The present work investigated the effects of vitamin C diet supplementation to spotted sorubim (Pseudoplatystoma coruscans) fingerlings by frequency of bone and cartilage deformation. Ascorbyl poliphosphate (AP) was used as source of vitamin C in the diets for spotted sorubim fingerlings during three months. Six diets were formulated: one diet control (0 mg/kg of vitamin C) and 500, 1,000, 1,500, 2,000 and 2,500 mg AP/kg diets. Fishes fed without vitamin C supplementation presented bone deformation in head and jaws, and fin fragilities. Thus, 500 mg AP/kg diet was enough to prevent deformation and the lack of vitamin C supplementation worsening the development of fingerlings.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cartilage; Dietary Supplements; Fish Diseases; Perciformes

l-ascorbic acid (vitamin C) insufficiency is considered one of the major risk factors for the development of liver disease. However, its specific effects and related mechanisms in vivo are largely unknown. The objective of this study was to investigate the in vivo protective role of vitamin C and its related mechanisms in liver injury with Gulo(-/-) mice that cannot synthesize vitamin C like humans due to the lack of l-gulonolactone-γ-oxidase (Gulo), an essential enzyme for vitamin C synthesis.. When liver injury was induced in Gulo(-/-) mice by injection of concanavalin A (Con A), there was greater extensive liver damage accompanied by an increased number of apoptotic hepatocytes in vitamin C-insufficient Gulo(-/-) mice. Additionally, the plasma and hepatic levels of the proinflammatory cytokines, such as TNF-α and IFN-γ, were much higher in the vitamin C-insufficient Gulo(-/-) mice than in the control mice. Moreover, increased numbers of liver-infiltrating T-cells in the vitamin C-insufficient Gulo(-/-) mice were related to the increased hepatic levels of IFN-inducible factor (IP-10). Although the vitamin C-insufficient Gulo(-/-) mice had higher amounts of interleukin-22 (IL-22), a hepatoprotective cytokine, a defect in IL-22Rα expression and its downstream STAT3 activation in hepatocytes were found.. We first demonstrate the novel in vivo action mechanisms of vitamin C on the prevention of disease development in the liver, through the regulation of excessive immune activation and maintenance of the IL-22Rα signaling pathways.. These results suggest that severe liver damage induced by inflammation could be prevented by sufficient supplementation with vitamin C.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Chemical and Drug Induced Liver Injury; Cytokines; Enzyme Activation; Hepatitis; Inflammation Mediators; L-Gulonolactone Oxidase; Male; Mice; Mice, Knockout; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; STAT3 Transcription Factor; T-Lymphocytes

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Melanoma, Experimental

Scurvy, a severe form of vitamin C deficiency, killed scores of people until its cause and treatment were firmly established at the end of the eighteenth century. Since then, cases have surged periodically around the world, mostly in developing countries and during times of war and famine. In developed countries, scurvy is still endemic and evidence is growing that vitamin C deficiency might affect up to 30 percent of the population. Low socio-economic status, alcoholism, severe psychiatric illness leading to poor nutrition and critical illness are significant risk factors. We hereby report the case of a patient admitted in a Swiss intensive care unit of a tertiary teaching hospital and presenting with clinical signs and symptoms of severe vitamin C deficiency.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Critical Illness; Endemic Diseases; Humans; Intensive Care Units; Male; Risk Factors; Scurvy; Severity of Illness Index; Switzerland

We hypothesized that zebrafish (Danio rerio) undergoing long-term vitamin E deficiency with marginal vitamin C status would develop myopathy resulting in impaired swimming. Zebrafish were fed for 1 y a defined diet without (E-) and with (E+) vitamin E (500 mg α-tocopherol/kg diet). For the last 150 days, dietary ascorbic acid concentrations were decreased from 3500 to 50 mg/kg diet and the fish sampled periodically to assess ascorbic acid concentrations. The ascorbic acid depletion curves were faster in the E- compared with E+ fish (P < 0.0001); the estimated half-life of depletion in the E- fish was 34 days, while in it was 55 days in the E+ fish. To assess swimming behavior, zebrafish were monitored individually following a "startle-response" stimulus, using computer and video technology. Muscle histopathology was assessed using hematoxylin and eosin staining on paramedian sections of fixed zebrafish. At study end, E- fish contained 300-fold less α-tocopherol (p < 0.0001), half the ascorbic acid (p = 0.0001) and 3-fold more malondialdehyde (p = 0.0005) than did E+ fish. During the first minute following a tap stimulus (p < 0.05), E+ fish swam twice as far as did E- fish. In the E- fish, the sluggish behavior was associated with a multifocal, polyphasic, degenerative myopathy of the skeletal muscle. The myopathy severity ranged from scattered acute necrosis to widespread fibrosis and was accompanied by increased anti-hydroxynonenal staining. Thus, vitamin E deficiency in zebrafish causes increased oxidative stress and a secondary depletion of ascorbic acid, resulting in severe damage to muscle tissue and impaired muscle function.

Topics: alpha-Tocopherol; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Behavior, Animal; Fibrosis; Half-Life; Malondialdehyde; Muscle, Skeletal; Muscular Diseases; Necrosis; Oxidative Stress; Severity of Illness Index; Swimming; Vitamin E Deficiency; Zebrafish

Human and guinea pig fetuses are completely dependent on an adequate maternal vitamin C (vitC) intake. Shortage of micronutrients can have negative implications for fetal health and pregnancy outcome; however, knowledge of maternal vitC deficiency's impact on fetal development is sparse and reports of pregnancy outcome have been divergent. The present study investigated whether maternal vitC deficiency affects pregnancy outcome and plasma vitC distribution between the mother and the offspring in a guinea pig model. A total of eighty pregnant Dunkin Hartley guinea pigs were randomised into two weight-stratified groups receiving either a deficient (100 mg/kg DEF) or a control (923 mg/kg CTRL) diet. VitC levels were measured in plasma during pregnancy and postpartum, and in the plasma and brain of newborns. Pregnancy outcome was recorded with respect to birth weight and perinatal survival and were similar between groups. Plasma vitC in dams declined throughout gestation in both groups (P< 0·01). Compared with maternal plasma vitC, plasma vitC of newborn pups was found to be significantly lower in the DEF group (P< 0·001) and higher in the CTRL group (P< 0·001), respectively. Brain vitC levels were significantly reduced in DEF newborn pups (P< 0·001). The present results indicate that preferential transport of vitC from the mother to the fetus is overridden during sustained maternal vitC deficiency, maintaining maternal vitC concentration at the expense of the offspring. This contradicts the notion that a fetus is protected from vitC deficiency by the placental Na-dependent vitC co-transporter, SVCT2, thus fetal development may be susceptible to the negative effects of maternal vitC deficiency.

Topics: Animals; Animals, Newborn; Ascorbic Acid; Ascorbic Acid Deficiency; Birth Weight; Brain; Diet; Female; Fetal Development; Fetus; Guinea Pigs; Male; Maternal-Fetal Exchange; Placenta; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Sodium-Coupled Vitamin C Transporters

To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we examined the associations between WMLs with vitamin and carotenoid levels in Japanese middle-aged and elderly subjects.. Four-hundred and sixty-nine healthy participants (male = 317; female = 152) that underwent medical examinations were examined. Deep white matter lesions (DWLs) were detected via magnetic resonance imaging (MRI) in 39 subjects. We evaluated the effects of vitamin and carotenoid levels on DWLs via logistic regression analysis.. Lower gamma-tocopherol levels were significantly associated with DWLs in all subjects. While lower gamma-tocopherol and vitamin C levels were significantly associated with DWLs in males, lower delta-tocopherol levels were associated with DWLs in females. The associations between DWLs and lower gamma- and delta-tocopherol and vitamin C levels were independent of age, hypertension, or smoking. However, the associations between DWLs and lower alfa-tocopherol were not significant following adjustments for smoking.. Lower carotenoid and vitamin levels were independently associated with cerebral DWLs in Japanese subjects.

Topics: Aged; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Brain Diseases; Carotenoids; Deficiency Diseases; Female; Geriatric Assessment; Humans; Japan; Male; Middle Aged; Nutrition Assessment; Nutritional Status; Sex Factors; Tocopherols; Vitamin E Deficiency; Vitamins

Scurvy, caused by lack of vitamin C, was a major problem for polar explorers. It may have contributed to the general ill-health of the members of Scott's polar party in 1912 but their deaths are more likely to have been caused by a combination of frostbite, malnutrition and hypothermia. Some have argued that Oates's war wound in particular suffered dehiscence caused by a lack of vitamin C, but there is little evidence to support this. At the time, many doctors in Britain overlooked the results of the experiments by Axel Holst and Theodor Frølich which showed the effects of nutritional deficiencies and continued to accept the view, championed by Sir Almroth Wright, that polar scurvy was due to ptomaine poisoning from tainted pemmican. Because of this, any advice given to Scott during his preparations would probably not have helped him minimise the effect of scurvy on the members of his party.

Topics: Antarctic Regions; Ascorbic Acid; Ascorbic Acid Deficiency; Expeditions; Famous Persons; History, 20th Century; Humans; Scurvy; United Kingdom

Tetrahydrobiopterin (BH₄) is an essential co-factor of nitric oxide synthases and is easily oxidized to dihydrobiopterin (BH₂) which promotes endothelial nitric oxide synthase uncoupling and deleterious superoxide production. Vitamin C has been shown to improve endothelial function by different mechanisms, some involving BH₄. The hypothesis of the present study was that vitamin C status, in particular low levels, influences biopterin redox status in vivo. Like humans, the guinea pig lacks the ability to synthesize vitamin C and was therefore used as model. Seven day old animals (n = 10/group) were given a diet containing 100, 250, 500, 750, 1000, or 1500 ppm vitamin C until euthanasia at age 60-64 days. Blood samples were drawn from the heart and analyzed for ascorbate, dehydroascorbic acid (DHA), BH₄ and BH₂ by high-performance liquid chromatography. Plasma BH₄ levels were found to be significantly lower in animals fed 100 ppm vitamin C compared to all other groups (P < .05 or less). BH₂ levels were not significantly different between groups but the BH₂-to-BH₄ ratio was higher in the group fed 100 ppm vitamin C (P < .001 all cases). Significant positive correlations between BH4 and ascorbate and between BH₂-to-BH₄ ratio and DHA were observed (P < .0001 both cases). Likewise, BH₂-to-BH₄ ratio was negatively correlated with ascorbate (P < .0001) as was BH₄ and DHA (P < .005). In conclusion, the redox status of plasma biopterins, essentially involved in vasodilation, depends on the vitamin C status in vivo. Thus, ingestion of insufficient quantities of vitamin C not only leads to vitamin C deficiency but also to increased BH₄ oxidation which may promote endothelial dysfunction.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Biopterins; Dehydroascorbic Acid; Endothelium, Vascular; Guinea Pigs; Oxidation-Reduction; Oxidative Stress

Tuberculosis (TB) is associated with oxidative stress and is traditionally linked to vitamin C deficiency.. To evaluate the time course of the oxidative stress marker, malondialdehyde (MDA), and vitamin C status during the clinical treatment of tuberculous meningitis (TBM).. MDA and vitamin C reduction/oxidation (redox) status were spectrophotometrically measured at admission and during hospital treatment in cerebrospinal fluid (CSF) and serum from 27 TBM patients and 20 controls.. Baseline CSF and serum MDA levels in TBM patients were higher than in controls (both P < 0.05), and remained elevated throughout the study. CSF MDA steadily increased from baseline 0.66 ± 0.24 mol/l to 1.02 ± 0.33 μmol/l at the end of the sixth week of treatment (P < 0.05), and then returned to baseline levels. Baseline CSF and serum total vitamin C were lower in TBM patients than in controls, but were soon normalised. CSF and serum ascorbate, reduced/oxidised vitamin C ratios and ascorbate CSF/serum ratio were markedly decreased in TBM patients (P < 0.05), and showed no improvement during treatment.. These results indicate increased local and systemic oxidative stress, accompanied by impaired redox status, but not total vitamin C deficiency, which persisted during conventional clinical treatment of TBM.

Topics: Antitubercular Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Case-Control Studies; Child; Child, Preschool; Female; Humans; Infant; Male; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Spectrophotometry; Time Factors; Treatment Outcome; Tuberculosis, Meningeal

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Expeditions; Humans; Scurvy

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Expeditions; Humans; Scurvy

Ascorbic acid (AA) functions as an electron donor and scavenges reactive oxygen species such as superoxide, singlet oxygen, and hydroxyl radicals in vitro. However, little is known about the effect of an AA deficiency on protein and lipid oxidation levels in the liver. Therefore, we measured the levels of protein carbonyl and thiobarbituric acid reactive substances (TBARS) in livers from senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice. These mice are deficient in AA, because they lack the SMP30/GNL gene, which is essential for the biosynthesis of AA in vivo. To track the effect of an AA deficiency, at 30 d of age, mice were divided into the following four groups: AA (-) SMP30/GNL KO, AA (+) SMP30/GNL KO, AA (-) wild type (WT), and AA (+) WT. The AA (+) groups were given water containing 1.5 g/L AA, whereas the AA (-) groups received water without AA for 57 d. All mice were fed an AA-free diet. Subsequently, protein carbonyl levels in livers from AA (-) SMP30/GNL KO mice were significantly higher than those from the other three groups; however, TBARS levels were not significantly different among the four groups. Therefore, AA must act as an anti-oxidant for proteins but might not directly protect lipid oxidation in the liver.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Lipid Metabolism; Liver; Mice; Mice, Knockout; Oxidation-Reduction; Protein Carbonylation; Proteins; Thiobarbituric Acid Reactive Substances

Severe vitamin C deficiency (ascorbic acid; AA) was induced in gulo-/- mice incapable of synthesizing their own AA. A number of behavioral measures were studied before and during the deprivation period, including a scorbutic period, during which weight loss was observed in the mice. Mice were then resuscitated with AA supplements. During the scorbutic period, gulo-/- mice showed decreased voluntary locomotor activity, diminished physical strength, and increased preference for a highly palatable sucrose reward. These behaviors all returned to control levels following resuscitation. Altered trial times in subordinate mice in the tube test for social dominance in the AA-deprived mice persisted following resuscitation and may signify a depressive-like behavior in these mice. Biochemical analyses were undertaken following a second deprivation period. AA deficiency was accompanied by decreased blood glucose levels, oxidative damage to lipids and proteins in the cortex, and decreases in dopamine and serotonin metabolites in both the cortex and striatum. Given the reasonably high proportions of the population that do not consume sufficient AA in the diet, these data have important implications for physical and psychological function in the general population.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Behavior, Animal; Biogenic Monoamines; Disease Models, Animal; Female; L-Gulonolactone Oxidase; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Severity of Illness Index

Degradation of the extracellular matrix (ECM) plays a critical role in the formation of tumors and metastasis and has been found to correlate with the aggressiveness of tumor growth and invasiveness of cancer. Ascorbic acid, which is known to be essential for the structural integrity of the intercellular matrix, is not produced by humans and must be obtained from the diet. Cancer patients have been shown to have very low reserves of ascorbic acid. Our main objective was to determine the effect of ascorbate supplementation on metastasis, tumor growth and tumor immunohistochemistry in mice unable to synthesize ascorbic acid [gulonolactone oxidase (gulo) knockout (KO)] when challenged with B16FO melanoma or 4T1 breast cancer cells. Gulo KO female mice 36-38 weeks of age were deprived of or maintained on ascorbate in food and water for 4 weeks prior to and 2 weeks post intraperitoneal (IP) injection of 5x105 B16FO murine melanoma cells or to injection of 5x105 4T1 breast cancer cells into the mammary pad of mice. Ascorbate-supplemented gulo KO mice injected with B16FO melanoma cells demonstrated significant reduction (by 71%, p=0.005) in tumor metastasis compared to gulo KO mice on the control diet. The mean tumor weight in ascorbate supplemented mice injected with 4T1 cells was reduced by 28% compared to tumor weight in scorbutic mice. Scorbutic tumors demonstrated large dark cores, associated with increased necrotic areas and breaches to the tumor surface, apoptosis and matrix metalloproteinase-9 (MMP-9), and weak, disorganized or missing collagen I tumor capsule. In contrast, the ascorbate-supplemented group tumors had smaller fainter colored cores and confined areas of necrosis/apoptosis with no breaches from the core to the outside of the tumor and a robust collagen I tumor capsule. In both studies, ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum inflammatory cytokine interleukin (IL)-6 (99% decrease, p=0.01 in the B16F0 study and 85% decrease, p=0.08 in the 4T1 study) compared to the levels in gulo KO mice deprived of ascorbate. In the B16FO study, ascorbate supplementation of gulo KO mice resulted in profoundly de

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Ascorbic Acid Deficiency; Breast Neoplasms; Cell Proliferation; Dietary Supplements; Female; Humans; Immunoenzyme Techniques; L-Gulonolactone Oxidase; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Metastasis; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Female; Food Preservation; Food Supply; Humans; Male; Middle Aged; Russia; Seasons

A 64-year-old woman presented with a hemorrhagic perifollicular rash on her legs while taking warfarin. After biopsy, vitamin C deficiency was suggested as the diagnosis, which ascorbic acid assays later confirmed. Clinical resolution of the rash followed supplementation with vitamin C. Patients on a vitamin K limited diet may also be limiting their intake of vitamin C. Physicians should be aware of this possible correlation, and consider checking vitamin C levels in patients with a perifollicular hemorrhagic rash or other signs of vitamin C deficiency while on warfarin.

Topics: Anticoagulants; Ascorbic Acid; Ascorbic Acid Deficiency; Drug Eruptions; Female; Humans; Leg Dermatoses; Middle Aged; Skin Diseases, Vascular; Warfarin

Considerable evidence supports the presence of oxidative stress in cystic fibrosis (CF). The disease has long been associated with both increased production of reactive oxygen species and impaired antioxidant status, in particular during the chronic pulmonary infection with Pseudomonas aeruginosa, which is the main cause of morbidity and mortality in CF. Guinea pigs are unable to synthesize ascorbate (ASC) or vitamin C, a major antioxidant of the lung, and thus like human beings rely on its presence in the diet. On this basis, guinea pigs receiving ASC-deficient diet have been used as a model of oxidative stress. The aim of our study was to investigate the consequences of a 7-day biofilm-grown P. aeruginosa lung infection in 3-month-old guinea pigs receiving either ASC-sufficient or ASC-deficient diet for at least 2 months. The animals receiving ASC-deficient diet showed significantly higher mortality during infection and increased respiratory burst of peripheral polymorphonuclear neutrophils (PMNs) compared with the animals receiving ASC sufficient diet. The inflammatory response at the site of lung infection consisted of PMNs and mononuclear leucocytes (MN), and higher PMN/MN ratios were present in animals on ASC-deficient diet compared with animals on ASC sufficient diet. Measurements of the ASC levels in the lung were significantly decreased in infected compared with non-infected animals. Interestingly, the infection by itself decreased the antioxidant capacity of the plasma (measured as plasma oxidizability) more than the ASC-deficient diet, suggesting a high consumption of the antioxidants during infection. Our data show that poor antioxidant status exacerbates the outcome of biofilm-related infections.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Biofilms; Disease Models, Animal; Female; Guinea Pigs; Inflammation; Leukocytes, Mononuclear; Lung Diseases; Neutrophils; Oxidative Stress; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Animal Feed; Animal Husbandry; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Chiroptera; Growth Disorders; Male; Nutritional Requirements; Weight Gain

Vitamin C alone or in combination with vitamin E has been proposed to prevent pre-eclampsia. In this study, we assayed the plasma vitamin C in women of reproductive age in Kampala and assessed its association with pre-eclampsia.. Participants in this study were 215 women with pre-eclampsia, 400 women with normal pregnancy attending antenatal clinic and 200 non-pregnant women attending family planning clinic at Mulago Hospital's Department of Obstetrics and Gynaecology from 1st May 2008 to 1st May 2009. Plasma vitamin C was assayed using the acid phosphotungstate method; differences in the means of plasma vitamin C were determined by ANOVA.. Mean plasma vitamin C levels were 1.72 (SD 0.68)×10(3)μg/l in women with pre-eclampsia, 1.89 (SD 0.73)×10(3)μg/l in women with normal pregnancy and 2.64 (SD 0.97)×10(3)μg/l in non-pregnant women. Plasma vitamin C was lower in women with pre-eclampsia than in women with normal pregnancy (P=0.005) and non-pregnant women (P<0.001).. Health workers need to advise women of reproductive age on foods that are rich in vitamin C, as this may improve the vitamin status and possibly reduce the occurrence of pre-eclampsia.

Topics: Adult; Analysis of Variance; Ascorbic Acid; Ascorbic Acid Deficiency; Case-Control Studies; Colorimetry; Family Planning Services; Female; Humans; Maternal Health Services; Pre-Eclampsia; Pregnancy; Uganda; Young Adult

We investigated whether decreased vitamin C (VC) in a mouse model increases lens opacity (cataract) induced by in vivo exposure to ultraviolet radiation type B (UVR-B). Senescence marker protein-30 (SMP30) knockout (KO) mice, which cannot synthesize VC due to genetic disruption of the gluconolactonase (GNL) gene, were divided into 2 groups: VC sufficient (VC (+)) and VC deficient (VC (-)). Starting at 1 month of age, these groups had free access to water containing 0.0375 and 1.5 g/L of VC, respectively. SMP30 KO VC (-), SMP30 KO VC (+), and wild-type (WT) mice, all 14 weeks of age, were unilaterally exposed in vivo to UVR-B (200 mW/cm(2)) for 100 s twice a week for 3 weeks (total: 1200 mJ/cm(2)). At 48 h after the last UVR-B exposure, cataract morphology was documented, and the ratio of cataract induction was quantified as the cataract area ratio (opacity area/anterior capsule). UVR-B exposure induced cataract mainly at anterior sub-capsular in SMP30 KO VC (-), SMP30 KO VC (+), and WT mice. In SMP30 KO VC (-) lenses the opacities were more extensive than in SMP30 KO VC (+) or WT lenses (cataract area ratios: 59.3% ± 10% vs. 32.2% ± 11.7% or 29.0% ± 9.0%; P < 0.01). In conclusion, VC depletion may increase the susceptibility to develop UVR-B induced cataracts in mice unable to endogenously produce VC.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Carboxylic Ester Hydrolases; Cataract; Disease Models, Animal; Intracellular Signaling Peptides and Proteins; Lens, Crystalline; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Radiation Injuries, Experimental; Ultraviolet Rays

Vitamin C (ascorbic acid, AA) is a cofactor for many important enzymatic reactions and a powerful antioxidant. AA provides protection against oxidative stress by acting as a scavenger of reactive oxygen species, either directly or indirectly by recycling of the lipid-soluble antioxidant, α-tocopherol (vitamin E). Only a few species, including humans, guinea pigs, and zebrafish, cannot synthesize AA. Using an untargeted metabolomics approach, we examined the effects of α-tocopherol and AA deficiency on the metabolic profiles of adult zebrafish. We found that AA deficiency, compared with subsequent AA repletion, led to oxidative stress (using malondialdehyde production as an index) and to major increases in the metabolites of the purine nucleotide cycle (PNC): IMP, adenylosuccinate, and AMP. The PNC acts as a temporary purine nucleotide reservoir to keep AMP levels low during times of high ATP utilization or impaired oxidative phosphorylation. The PNC promotes ATP regeneration by converting excess AMP into IMP, thereby driving forward the myokinase reaction (2ADP → AMP + ATP). On the basis of this finding, we investigated the activity of AMP deaminase, the enzyme that irreversibly deaminates AMP to form IMP. We found a 47% increase in AMP deaminase activity in the AA-deficient zebrafish, complementary to the 44-fold increase in IMP concentration. These results suggest that vitamin C is crucial for the maintenance of cellular energy metabolism.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Energy Metabolism; Guinea Pigs; Humans; Purine Nucleotides; Zebrafish

Organisms using oxygen for aerobic respiration require antioxidants to balance the production of reactive oxygen species during metabolic processes. Various species--including humans and other primates--suffer mutations in the GULO gene encoding L-gulono-γ-lactone oxidase; GULO is the rate-limiting enzyme in the biosynthesis of ascorbate, an important cellular antioxidant. Animals lacking the ability to synthesize vitamin C develop scurvy without dietary supplementation. The Gulo-/- knockout (KO) mouse requires oral supplemental vitamin C; without this supplementation the animal dies with a scorbutic condition within several weeks. Vitamin C is known to be most abundant in the brain, where it is believed to play important roles in neuroprotection, neurotransmission and neuromodulation. We therefore hypothesized that ascorbate deficiency in Gulo-/- KO mice might lead to an abnormal behavioral phenotype. We established the amount of ascorbate in the drinking water (220 ppm) necessary for generating a chronic low-ascorbate status in the brain, yet clinically the mice appeared healthy throughout 100 days postpartum at which time all behavioral-phenotyping tests were completed. Compared with Gulo+/+ wild-type littermates, ascorbate-deficient Gulo-/- mice were found to be less active in moving in their environment; when in water, these mice swam more slowly in some tests, consistent with a mild motor deficit. We found no evidence of cognitive, anxiety or sensorimotor-gating problems. Despite being less active, Gulo-/- mice exhibited exaggerated hyperactivity to the dopaminergic agonist methamphetamine. The subnormal movement, combined with hypersensitivity to a dopamine agonist, point to developmental ascorbate deficiency causing long-term striatal dysfunction.

Topics: Animals; Animals, Newborn; Ascorbic Acid; Ascorbic Acid Deficiency; Behavior, Animal; Disease Models, Animal; Female; L-Gulonolactone Oxidase; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Pregnancy

A corticostriatal-dependent deficit in the release of ascorbate (AA), an antioxidant vitamin and neuromodulator, occurs concurrently in striatum with dysfunctional GLT1-dependent uptake of glutamate in the R6/2 mouse model of Huntington's disease (HD), an autosomal dominant condition characterized by overt corticostriatal dysfunction. To determine if deficient striatal AA release into extracellular fluid is related to altered GLT1 activity in HD, symptomatic R6/2 mice between 6 and 9 weeks of age and age-matched wild-type (WT) mice received single daily injections of 200 mg/kg ceftriaxone, a β-lactam antibiotic that elevates the functional expression of GLT1, or saline vehicle for five consecutive days. On the following day, in vivo voltammetry was coupled with corticostriatal afferent stimulation to monitor evoked release of AA into striatum. In saline-treated mice, we found a marked decrease in evoked extracellular AA in striatum of R6/2 relative to WT. Ceftriaxone, in contrast, restored striatal AA in R6/2 mice to WT levels. In addition, intra-striatal infusion of either the GLT1 inhibitor dihydrokainic acid or dl-threo-beta-benzyloxyaspartate blocked evoked striatal AA release. Collectively, our results provide compelling evidence for a link between GLT1 activation and release of AA into the striatal extracellular fluid, and suggest that dysfunction of this system is a key component of HD pathophysiology.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Aspartic Acid; Ceftriaxone; Cerebral Cortex; Corpus Striatum; Electric Stimulation; Excitatory Amino Acid Transporter 2; Extracellular Fluid; Genotype; Huntington Disease; Kainic Acid; Male; Mice; Mice, Transgenic; Microinjections; Transcription, Genetic; Up-Regulation

  We designed a cross-sectional study to investigate plasma vitamin C level in patients who underwent maintenance haemodialysis (MHD) and continuous ambulatory peritoneal dialysis (CAPD) to explore whether there is a difference in vitamin C deficiency between MHD patients and CAPD patients..   This investigation included 382 dialysis patients without vitamin C supplement before the study. Demographic characteristics, laboratory tests, ascorbic acid and total plasma vitamin C level were measured. A linear regression model was built to explore the association between vitamin C deficiency and dialysis modalities after adjusting for age, dialysis vintage, gender, Charlson index, modality of dialysis and hsCRP..   The range of plasma vitamin C level was from 0.48 µg/mL to 31.16 µg/mL. 35.9% (n = 137) patients had severe vitamin C deficiency (<2 µg/mL). Plasma vitamin C level was inversely associated with age and dialysis vintage. After age and dialysis vintage were adjusted, vitamin C deficiency was associated with MHD. R square for model fitting was relatively low, which implied that there were other vitamin C influencing factors not included in the model..   Vitamin C deficiency is common in dialysis patients, especially in patients treated with MHD.

Topics: Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; C-Reactive Protein; Chi-Square Distribution; China; Cross-Sectional Studies; Female; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Peritoneal Dialysis, Continuous Ambulatory; Prealbumin; Prevalence; Renal Dialysis; Risk Assessment; Risk Factors; Sex Factors; Time Factors

Topics: Aged; Anemia, Megaloblastic; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Humans; Male; Pancytopenia; Treatment Outcome; Vitamin B 12; Vitamins

To determine the antioxidant levels of subrural Nigerian population where pre-eclampsia and eclampsia is the leading cause of maternal mortality.. Prospective case control study done at Department of Obstetrics and Gynaecology, Irrua Specialist Teaching Hospital Irrua, Edo State, Nigeria. Plasma level of vitamin C and E were evaluated in 80 pre-eclamptic patientswhich were compared with normotensive 80 pregnant women matched as controls.. Pre-eclampsia was associated with significant reduction in levels of vitamin C and E (p < 0.05). However, the correlation between the blood pressure (severity) and reduction in antioxidants level was not statistically significant.. Pre-eclampsia at Irrua in Nigeria is associated with significant reduction in plasma antioxidants level similar to some reports from the other parts of the world.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Case-Control Studies; Female; Hospitals, Teaching; Humans; Nigeria; Pre-Eclampsia; Pregnancy; Prospective Studies; Vitamin E; Vitamin E Deficiency; Young Adult

Iron chelation is essential to patients on chronic blood transfusions to prevent toxicity from iron overload and remove excess iron. Deferasirox (DFX) is the most commonly used iron chelator in the United States; however, some patients are relatively refractory to DFX therapy. We postulated that vitamin C supplementation would improve the availability of transfusional iron to DFX treatment by promoting iron's redox cycling, increasing its soluble ferrous form and promoting its release from reticuloendothelial cells. Osteogenic dystrophy rats (n = 54) were given iron dextran injections for 10 weeks. Cardiac and liver iron levels were measured after iron loading (n = 18), 12 weeks of sham chelation (n = 18), and 12 weeks of DFX chelation (n = 18) at 75 mg/kg/day. Ascorbate supplementation of 150 ppm, 900 ppm, and 2250 ppm was used in the chow to mimic a broad range of ascorbate status; plasma ascorbate levels were 5.4 ± 1.9, 8.2 ± 1.4, 23.6 ± 9.8 μM, respectively (p < 0.0001). The most severe ascorbate deficiency produced reticuloenthelial retention, lowering total hepatic iron by 29% at the end of iron loading (p < 0.05) and limiting iron redistribution from cardiac and hepatic macrophages during 12 weeks of sham chelation. Most importantly, ascorbate supplementation at 2250 ppm improved DFX efficiency, allowing DFX to remove 21% more hepatic iron than ascorbate supplementation with 900 ppm or 150 ppm (p < 0.05). We conclude that vitamin C status modulates the release of iron from the reticuloendothelial system and correlates positively with DFX chelation efficiency. Our findings suggest that ascorbate status should be probed in patients with unsatisfactory response to DFX.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Benzoates; Deferasirox; Guinea Pigs; Humans; Iron; Iron Chelating Agents; Iron Overload; Liver; Mononuclear Phagocyte System; Myocardium; Rats; Rats, Mutant Strains; Triazoles

We describe the case of a 40-year-old female patient who developed severe pulmonary hypertension and life-threatening right-sided heart failure in association with dietary scurvy and iron deficiency. Supplementation with oral vitamin C and iron very likely contributed to her complete cure. Scurvy-associated pulmonary arterial hypertension could result from impaired availability of endothelial nitric oxide, but inappropriate activation of the hypoxia-inducible family (HIF) of transcription factors could play an even more important role. HIF coordinates the body's responses to hypoxia, and its activity is regulated by oxygen-dependent prolyl hydroxylases, which need vitamin C and iron as cofactors. Deficiency of these cofactors could lead to uncontrolled HIF activity and pulmonary vasoconstriction responsive to vitamin C and iron administration.

Topics: Adult; Anemia, Iron-Deficiency; Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Echocardiography; Female; Heart Failure; Humans; Hypertension, Pulmonary; Iron; Scurvy; Treatment Outcome; Vasoconstriction

During investigations of the phenotypic diversity of hemoglobin (Hb) E β thalassemia, a patient was encountered with persistently high levels of methemoglobin associated with a left-shift in the oxygen dissociation curve, profound ascorbate deficiency, and clinical features of scurvy; these abnormalities were corrected by treatment with vitamin C. Studies of erythropoietin production before and after treatment suggested that, as in an ascorbate-deficient murine model, the human hypoxia induction factor pathway is not totally dependent on ascorbate levels. A follow-up study of 45 patients with HbE β thalassemia showed that methemoglobin levels were significantly increased and that there was also a significant reduction in plasma ascorbate levels. Haptoglobin levels were significantly reduced, and the high frequency of the 2.2 haptoglobin genotype may place an additional pressure on ascorbate as a free-radical scavenger in this population. There was, in addition, a highly significant correlation between methemoglobin levels, splenectomy, and factors that modify the degree of globin-chain imbalance. Because methemoglobin levels are modified by several mechanisms and may play a role in both adaptation to anemia and vascular damage, there is a strong case for its further study in other forms of thalassemia and sickle-cell anemia, particularly when splenic function is defective.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; beta-Thalassemia; Family; Female; Hemoglobin E; Humans; Male; Methemoglobin; Methemoglobinemia; Young Adult

To determine whether or not dogs develop a deficiency of ascorbic acid during hospitalisation in an intensive care unit.. Blood samples were collected daily for up to three days from dogs hospitalised in an intensive care unit for 36 to 72 hours (n = 16) or ê72 hours (n = 20) and from healthy dogs (n = 13). Plasma total ascorbic acid concentrations were measured using a colorimetric method involving a reaction between ascorbic acid, 2,6 dichlorophenol-indophenol, thiourea and dinitrophenyl hydrazine. Additionally, clinical data were recorded for each patient.. Dogs hospitalised for ê72 hours had significantly greater plasma ascorbic acid concentrations on day 3 compared to days 1 and 2. There was no difference in plasma ascorbic acid concentrations between days 1 and 2 for dogs hospitalised for 36 to 72 hours. Plasma ascorbic acid concentrations were significantly greater for each day of sampling for the hospitalised dogs compared to the control dogs.. Plasma ascorbic acid concentrations appear to increase during hospitalisation, and supplementation may not be indicated in dogs hospitalised in an intensive care unit.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Colorimetry; Dog Diseases; Dogs; Female; Hospitals, Animal; Male; Severity of Illness Index

The term 'scurvy' for the disease resulting from prolonged vitamin C deficiency had origins in 'scorbutus' (Latin), 'scorbut' (French), and 'Skorbut' (German). Scurvy was a common problem in the world's navies and is estimated to have affected 2 million sailors. In 1747, James Lind conducted a trial of six different treatments for 12 sailors with scurvy: only oranges and lemons were effective in treating scurvy. Scurvy also occurred on land, as many cases occurred with the 'great potato famine' in Ireland in 1845. Many animals, unlike humans, can synthesize their own vitamin C. Axel Holst and Theodor Frölich fortuitously produced scurvy in the guinea pig, which like humans requires vitamin C in the diet. In 1928, Albert Szent-Györgyi isolated a substance from adrenal glands that he called 'hexuronic acid'. Four years later, Charles Glen King isolated vitamin C in his laboratory and concluded that it was the same as 'hexuronic acid'. Norman Haworth deduced the chemical structure of vitamin C in 1933.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Citrus; Guinea Pigs; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Scurvy

Ascorbic acid, the active form of vitamin C, is a vital antioxidant in the human liver, yet the molecular mechanisms involved in the regulation of ascorbic acid transporters [human sodium-dependent vitamin C transporters (hSVCT) 1 and 2] in liver cells are poorly understood. Therefore, we characterized the minimal promoter regions of hSVCT1 and 2 in cultured human liver epithelial cells (HepG2) and examined the effects of ascorbic acid deprivation and supplementation on activity and regulation of the transport systems. Identified minimal promoters required for basal activity were found to include multiple cis regulatory elements, whereas mutational analysis demonstrated that HNF-1 sites in the hSVCT1 promoter and KLF/Sp1 sites in the hSVCT2 promoter were essential for activities. When cultured in ascorbic acid deficient or supplemented media, HepG2 cells demonstrated significant (P<.01) and specific reciprocal changes in [(14)C]-Ascorbic acid uptake, and in hSVCT1 mRNA and protein levels as well as hSVCT1 promoter activity. However, no significant changes in hSVCT2 expression or promoter activity were observed during ascorbic acid deficient or supplemented conditions. We mapped the ascorbic acid responsive region in the hSVCT1 promoter and determined that HNF-1 sites are important for the adaptive regulation response. The results of these studies further characterize the hSVCT1 and 2 promoters establish that ascorbic acid uptake by human liver epithelial cells is adaptively regulated and show that transcriptional mechanisms via HNF-1 in the hSVCT1 promoter may, in part, be involved in this regulation.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Gene Expression Regulation; Hep G2 Cells; Hepatocyte Nuclear Factor 1; Humans; Organic Anion Transporters, Sodium-Dependent; Promoter Regions, Genetic; Sodium-Coupled Vitamin C Transporters; Symporters

Because vitamin C (VC) has multiple metabolic and antioxidant functions, we investigated the movement of VC throughout the tissues of senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice.. SMP30/GNL KO mice, which cannot synthesize VC in vivo, were divided into two groups: VC sufficient and VC deficient. Starting at 2 mo of age, both groups had free access to water containing 1.5 and 0.0375 g/L of VC for 1 mo.. The average rate of VC retention in 20 tissues of VC-deficient SMP30/GNL KO mice was only 13.7% of that in VC-sufficient mice. Tissues that retained over 20% of VC were the cerebellum, white fat, testes, eyeballs, and pancreas, and those with less than 5% VC were the kidneys and heart. These results clearly indicate the different VC retention capacities among tissues. Next, we examined the time course of VC distribution and absorption in VC-deficient SMP30/GNL KO mice. After oral VC administration, VC content in the liver and kidney peaked at 3 h and then decreased. VC content in the lungs, adrenal glands, skin, white fat, and pancreas peaked at 6 h and in the cerebellum, cerebrum, skeletal muscles, eyeballs, thyroid gland, and testes at 12 h.. In this study, we found that exogenous VC administered orally in VC-deficient SMP30/GNL KO mice was distributed at distinctly different rates within individual tissues. The SMP30/GNL KO mice used in this study are a useful animal model that provides unique opportunities for investigating VC movement and metabolism in the entire body.

Topics: Administration, Oral; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Carboxylic Ester Hydrolases; Intestinal Absorption; Intracellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Tissue Distribution

A decreased plasma level of vitamin C has been reported to be associated with an increased risk of cardiovascular morbidity and mortality. Here, we sought to determine the vitamin C status of patients with chronic kidney disease and the pathophysiological role of vitamin C in these patients.. We studied 58 patients and evaluated the relationship between renal function and plasma vitamin C concentration, as well as the effect of diabetes on this relationship. Endothelium-dependent flow-mediated dilation of brachial artery was measured to assess the endothelial function. Serum malondialdehyde low-density lipoprotein was measured as a marker for oxidative stress.. Plasma vitamin C concentration had a positive linear relationship with eGFR in both diabetic and non-diabetic patients (P = 0.006 and P = 0.004, respectively). When vitamin C concentration and eGFR relationships were compared in the two groups, vitamin C concentration was significantly lower in diabetic patients at every eGFR (P = 0.006). Flow-mediated vasodilatation of the brachial artery was positively correlated with vitamin C concentration in non-diabetic patients (P = 0.047) but not in diabetic patients. There was a negative correlation between serum malondialdehyde low-density lipoprotein and vitamin C concentration in non-diabetic patients (P = 0.044) but not in diabetic patients.. Renal dysfunction was associated with a decrease in plasma vitamin C level. Moreover, decreased vitamin C may cause endothelial dysfunction via an increase in oxidative stress in non-diabetic chronic kidney disease patients.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Diabetes Mellitus, Type 2; Female; Humans; Kidney Function Tests; Male; Middle Aged; Prognosis; Renal Insufficiency, Chronic

Vitamin C deficiency - or hypovitaminosis C defined as a plasma concentration below 23 μm - is estimated to affect hundreds of millions of people in the Western world, in particular subpopulations of low socio-economic status that tend to eat diets of poor nutritional value. Recent studies by us have shown that vitamin C deficiency may result in impaired brain development. Thus, the aim of the present study was to investigate if a poor diet high in fat and cholesterol affects the vitamin C status of guinea pigs kept on either sufficient or deficient levels of dietary ascorbate (Asc) for up to 6 months with particular emphasis on the brain. The present results show that a high-fat and cholesterol diet significantly decreased the vitamin C concentrations in the brain, irrespective of the vitamin C status of the animal (P < 0·001). The brain Asc oxidation ratio only depended on vitamin C status (P < 0·0001) and not on the dietary lipid content. In plasma, the levels of Asc significantly decreased when vitamin C in the diet was low or when the fat/cholesterol content was high (P < 0·0001 for both). The Asc oxidation ratio increased both with low vitamin C and with high fat and cholesterol content (P < 0·0001 for both). We show here for the first time that vitamin C homoeostasis of brain is affected by a diet rich in fat and cholesterol. The present findings suggest that this type of diet increases the turnover of Asc; hence, individuals consuming high-lipid diets may be at increased risk of vitamin C deficiency.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Cholesterol, Dietary; Chronic Disease; Dietary Fats; Disease Models, Animal; Guinea Pigs; Homeostasis; Oxidation-Reduction; Oxidative Stress

To test whether severe ascorbic acid deficiency in macrophages affects progression of early atherosclerosis, we used fetal liver cell transplantation to generate atherosclerosis-prone apolipoprotein E-deficient (apoE(-/-)) mice that selectively lacked the ascorbate transporter (SVCT2) in hematopoietic cells, including macrophages. After 13 weeks of chow diet, apoE(-/-) mice lacking the SVCT2 in macrophages had surprisingly less aortic atherosclerosis, decreased lesion macrophage numbers, and increased macrophage apoptosis compared to control-transplanted mice. Serum lipid levels were similar in both groups. Peritoneal macrophages lacking the SVCT2 had undetectable ascorbate; increased susceptibility to H(2)O(2)-induced mitochondrial dysfunction and apoptosis; decreased expression of genes for COX-2, IL1β, and IL6; and decreased lipopolysaccharide-stimulated NF-κB and antiapoptotic gene expression. These changes were associated with decreased expression of both the receptor for advanced glycation end products and HIF-1α, either or both of which could have been the proximal cause of decreased macrophage activation and apoptosis in ascorbate-deficient macrophages.

Topics: Animals; Apolipoproteins E; Ascorbic Acid; Ascorbic Acid Deficiency; Atherosclerosis; Cells, Cultured; Disease Progression; Female; Genetic Predisposition to Disease; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Organ Specificity; Organic Anion Transporters, Sodium-Dependent; Sodium-Coupled Vitamin C Transporters; Symporters; Time Factors

Humans acquire vitamin C (ascorbate) from their diet, and optimal tissue concentrations are required to maintain its enzyme cofactor and antioxidant activities. How dietary intake affects tissue concentrations is difficult to monitor and has generally been based on the measurement of plasma concentrations.. We aimed to determine the effect of various ascorbate intakes on tissue concentrations in the Gulo mouse model of vitamin C deficiency and to compare the effectiveness of delivery when ascorbate was added to the drinking water or obtained through a fruit source (kiwifruit).. Gulo(-/-) mice were fed various amounts of ascorbate for 1 mo, either in their drinking water or as a kiwifruit gel. Tissue vitamin C content was measured and compared with concentrations in wild-type mice.. Ascorbate concentrations in serum, liver, kidney, heart, and white blood cells were extremely labile and were well below concentrations observed in the wild-type mice when serum concentrations were below saturation. All tissues except for brain were rapidly depleted when intake was stopped. Consumption of a preparation of fresh kiwifruit (either green or gold varieties) resulted in up to 5 times more effective delivery to tissues than when ascorbate was administered via the drinking water.. Subsaturation concentrations of plasma ascorbate resulted in severe deficiency in many tissues, and saturating amounts were required to achieve tissue concentrations similar to those found in wild-type animals. It is possible that the bioavailability of ascorbate is superior from some foods, such as kiwifruit. These results have important implications for human nutrition.

Topics: Actinidia; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Availability; Diet; Disease Models, Animal; Drinking; Fruit; Mice; Mice, Inbred C57BL; Mice, Knockout; Plant Extracts; Tissue Distribution; Water

Prolyl-4-hydroxylation is necessary for proper structural assembly of collagens and oxygen-dependent protein stability of hypoxia-inducible transcription factors (HIFs). In vitro function of HIF prolyl-4-hydroxylase domain (PHD) enzymes requires oxygen and 2-oxoglutarate as cosubstrates with iron(II) and vitamin C serving as cofactors. Although vitamin C deficiency is known to cause the collagen-disassembly disease scurvy, it is unclear whether cellular oxygen sensing is similarly affected. Here, we report that vitamin C-deprived Gulo(-/-) knockout mice show normal HIF-dependent gene expression. The systemic response of Gulo(-/-) animals to inspiratory hypoxia, as measured by plasma erythropoietin levels, was similar to that of animals supplemented with vitamin C. Hypoxic HIF induction was also essentially normal under serum- and vitamin C-free cell-culture conditions, suggesting that vitamin C is not required for oxygen sensing in vivo. Glutathione was found to fully substitute for vitamin C requirement of all 3 PHD isoforms in vitro. Consistently, glutathione also reduced HIF-1α protein levels, transactivation activity, and endogenous target gene expression in cells exposed to CoCl(2). A Cys201Ser mutation in PHD2 increased basal hydroxylation rates and conferred resistance to oxidative damage in vitro, suggesting that this surface-accessible PHD2 cysteine residue is a target of antioxidative protection by vitamin C and glutathione.

Topics: Amino Acid Substitution; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Hypoxia; Cell Line; Cobalt; Glutathione; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; L-Gulonolactone Oxidase; Mice; Mice, Knockout; Mutagenesis, Site-Directed; Mutant Proteins; Oxygen; Procollagen-Proline Dioxygenase

Nutrient deficiencies are an ongoing problem in many populations and ascorbic acid is a key vitamin whose mild or acute absence leads to a number of conditions including the famously debilitating scurvy. As such, the biochemical effects of ascorbate deficiency merit ongoing scrutiny, and the Gulo knockout mouse provides a useful model for the metabolomic examination of vitamin C deficiency. Like humans, these animals are incapable of synthesizing ascorbic acid but with dietary supplements are otherwise healthy and grow normally. In this study, all vitamin C sources were removed after weaning from the diet of Gulo-/- mice (n = 7) and wild type controls (n = 7) for 12 weeks before collection of serum. A replicate study was performed with similar parameters but animals were harvested pre-symptomatically after 2-3 weeks. The serum concentration of 50 metabolites was determined by quantitative profiling of 1D proton NMR spectra. Multivariate statistical models were used to describe metabolic changes as compared to control animals; replicate study animals were used for external validation of the resulting models. The results of the study highlight the metabolites and pathways known to require ascorbate for proper flux.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; L-Gulonolactone Oxidase; Magnetic Resonance Spectroscopy; Metabolic Networks and Pathways; Metabolome; Mice; Mice, Knockout

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Endothelium; Humans; Immunity; Injections, Intravenous; Neoplasms; Sepsis

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Dehydroascorbic Acid; Disease Models, Animal; Glucose Transporter Type 1; Humans; Intracellular Signaling Peptides and Proteins; Liver Cirrhosis; Mice; Mice, Knockout; PPAR gamma

We report the case of the case of a 56 year old female with sepsis on a background of rheumatoid arthritis and steroid use manifesting with overt clinical features of scurvy. Ascorbic acid assays were able to demonstrate severe deficiency and confirm a diagnosis of scurvy. Clinical resolution of signs and symptoms following commencement of vitamin C replacement was rapid. The intensivist and dietitian need to consider this diagnosis even in the first world setting, particularly in the presence of sepsis, inflammatory conditions, steroid use and importantly malnutrition.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Intensive Care Units; Middle Aged; Military Personnel; Plague; Scurvy; Sepsis

Subclinical inflammation is a common phenomenon in patients on either continuous ambulatory peritoneal dialysis (CAPD) or maintenance hemodialysis (MHD). We hypothesized that vitamin C had anti-inflammation effect because of its electron offering ability. The current study was designed to test the relationship of plasma vitamin C level and some inflammatory markers.. In this cross-sectional study, 284 dialysis patients were recruited, including 117 MHD and 167 CAPD patients. The demographics were recorded. Plasma vitamin C was measured by high-performance liquid chromatography. And we also measured body mass index (BMI, calculated as weight/height(2)), Kt/V, serum albumin, serum prealbumin, high-sensitivity C-reactive protein (hsCRP), ferritin, hemoglobin. The relationships between vitamin C and albumin, pre-albumin and hsCRP levels were tested by Spearman correlation analysis and multiple regression analysis. Patients were classified into three subgroups by vitamin C level according to previous recommendation 12 in MHD and CAPD patients respectively: group A: < 2 ug/ml (< 11.4 umol/l, deficiency), group B: 2-4 ug/ml (11.4-22.8 umol/l, insufficiency) and group C: > 4 ug/ml (> 22.8 umol/l, normal and above).. Patients showed a widely distribution of plasma vitamin C levels in the total 284 dialysis patients. Vitamin C deficiency (< 2 ug/ml) was present in 95(33.45%) and insufficiency (2-4 ug/ml) in 88(30.99%). 73(25.70%) patients had plasma vitamin C levels within normal range (4-14 ug/ml) and 28(9.86%) at higher than normal levels (> 14 ug/ml). The similar proportion of different vitamin C levels was found in both MHD and CAPD groups. Plasma vitamin C level was inversely associated with hsCRP concentration (Spearman r = -0.201, P = 0.001) and positively associated with prealbumin (Spearman r = 0.268, P < 0.001), albumin levels (Spearman r = 0.161, P = 0.007). In multiple linear regression analysis, plasma vitamin C level was inversely associated with log(10)hsCRP (P = 0.048) and positively with prealbumin levels (P = 0.002) adjusted for gender, age, diabetes, modality of dialysis and some other confounding effects.. The investigation indicates that vitamin C deficiency is common in both MHD patients and CAPD patients. Plasma vitamin C level is positively associated with serum prealbumin level and negatively associated with hsCRP level in both groups. Vitamin C deficiency may play an important role in the increased inflammatory status in dialysis patients. Further studies are needed to determine whether inflammatory status in dialysis patients can be improved by using vitamin C supplements.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; C-Reactive Protein; Comorbidity; Cross-Sectional Studies; Female; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Peritoneal Dialysis; Prealbumin; Prevalence; Renal Dialysis; Severity of Illness Index

The etiology of myelodysplastic syndromes (MDS) is largely unknown. Exposure to cigarette smoke (CS) is reported to be associated with MDS risk. There is inconsistent evidence that deficiency of NAD(P)H-quinone: oxidoreductase 1 (NQO1) increases the risk of MDS. Earlier we had shown that CS induces toxicity only in marginal vitamin C-deficient guinea pigs but not in vitamin C-sufficient ones. We therefore considered that NQO1 deficiency along with marginal vitamin C deficiency might produce MDS in CS-exposed guinea pigs.. Here we show that CS exposure for 21 days produces MDS in guinea pigs having deficiency of NQO1 (fed 3 mg dicoumarol/day) conjoint with marginal vitamin C deficiency (fed 0.5 mg vitamin C/day). As evidenced by morphology, histology and cytogenetics, MDS produced in the guinea pigs falls in the category of refractory cytopenia with unilineage dysplasia (RCUD): refractory anemia; refractory thrombocytopenia that is associated with ring sideroblasts, micromegakaryocytes, myeloid hyperplasia and aneuploidy. MDS is accompanied by increased CD34(+) cells and oxidative stress as shown by the formation of protein carbonyls and 8-oxodeoxyguanosine. Apoptosis precedes MDS but disappears later with marked decrease in the p53 protein. MDS produced in the guinea pigs are irreversible. MDS and all the aforesaid pathophysiological events do not occur in vitamin C-sufficient guinea pigs. However, after the onset of MDS vitamin C becomes ineffective.. CS exposure causes MDS in guinea pigs having deficiency of NQO1 conjoint with marginal vitamin C deficiency. The syndromes are not produced in singular deficiency of NQO1 or marginal vitamin C deficiency. Our results suggest that human smokers having NQO1 deficiency combined with marginal vitamin C deficiency are likely to be at high risk for developing MDS and that intake of a moderately large dose of vitamin C would prevent MDS.

Topics: Animals; Apoptosis; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Marrow; Flow Cytometry; Guinea Pigs; Humans; In Situ Nick-End Labeling; Male; Myelodysplastic Syndromes; NAD(P)H Dehydrogenase (Quinone); Reactive Oxygen Species; Tobacco Smoke Pollution

To examine the association between vitamin C and cataract in the Indian setting.. Population-based cross-sectional analytic study.. A total of 5638 people aged ≥60 years.. Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography.. Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract.. Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51-0.74; P=1.1×10(-6)). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, β-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57-0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54-0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54-0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45-0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract.. We found a strong association with vitamin C and cataract in a vitamin C-depleted population.. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; beta Carotene; Cataract; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; India; Lutein; Male; Middle Aged; Prevalence; Risk Factors; Xanthophylls; Zeaxanthins

Osteogenic disorder shionogi (ODS) rats carry a hereditary defect in ascorbic acid synthesis, mimicking human scurvy when fed with an ascorbic acid-deficient (aa-def) diet. As aa-def ODS rats were shown to feature disordered bone formation, we have examined the bone mineralization in this rat model. A fibrous tissue layer surrounding the trabeculae of tibial metaphyses was found in aa-def ODS rats, and this layer showed intense alkaline phosphatase activity and proliferating cell nuclear antigen-immunopositivity. Many osteoblasts detached from the bone surfaces and were characterized by round-shaped rough endoplasmic reticulum (rER), suggesting accumulation of malformed collagen inside the rER. Accordingly, fine, fragile fibrillar collagenous structures without evident striation were found in aa-def bones, which may result from misassembling of the triple helices of collagenous α-chains. Despite a marked reduction in bone formation, ascorbic acid deprivation seemed to have no effect on mineralization: while reduced in number, normal matrix vesicles and mineralized nodules could be seen in aa-def bones. Fine needle-like mineral crystals extended from these mineralized nodules, and were apparently bound to collagenous fibrillar structures. In summary, collagen mineralization seems unaffected by ascorbic acid deficiency in spite of the fine, fragile collagenous fibrils identified in the bones of our animal model.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Diseases; Calcification, Physiologic; Collagen; Disease Models, Animal; Humans; Male; Osteoblasts; Rats; Rats, Mutant Strains; Tibia

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Fractures, Bone; Humans; Scurvy

Striae gravidarum, a clinical condition commonly seen in pregnant women, produces serious cosmetic problems and may lead to psychological problems.. The present study investigated whether there was any relation between the presence of striae in primigravid pregnant women and blood vitamin C levels, and factors thought to contribute to the formation of striae such as family history, weight gained during pregnancy, smoking status, abdominal and thigh circumference, and age.. Overall, 69 primigravid women attending routine antenatal follow-up and, using prophylactic iron and vitamin preparations, underwent investigation. All were pregnant 36 or more weeks. Scoring was based on striae examination and whether striae were present. The relation between the presence of striae, vitamin C blood levels, and other factors was investigated.. Multiple logistic regression analysis showed a significant relation between the presence of striae and blood vitamin C levels (p = 0.046) and between the presence of striae and family history (p = 0.023). No significant relation was found between the presence of striae and age, weight gained during pregnancy, abdominal and thigh circumference, or smoking status. It was concluded that further, more comprehensive studies on the issue are required.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Erythema; Family Health; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Reproducibility of Results; Risk Factors; Severity of Illness Index; Striae Distensae; Turkey

Scurvy is well known since ancient times, but it is rarely seen in the developed world today owing to the discovery of its link to the dietary deficiency of ascorbic acid. It is very uncommon in the pediatric population, and is usually seen in children with severely restricted diet attributable to psychiatric or developmental disturbances. The condition presents itself by the formation of perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We report a case of scurvy in a 10-year-old developmentally delayed boy who had a diet markedly deficient in vitamin C resulting from extremely limited food choices. He presented with debilitating bone pain, inflammatory gingival disease, and perifollicular hyperkeratosis. The diagnosis was made based on clinical and radiographic findings. The importance of diet history is emphasized. We present this case with the aim to help the clinician identify scurvy and implement treatment for a potentially fatal but easily curable disease.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Developmental Disabilities; Diagnosis, Differential; Diet; Humans; India; Male; Scurvy

The traditional assumption that bats cannot synthesize vitamin C (Vc) has been challenged recently. We have previously shown that two Old World bat species (Rousettus leschenaultii and Hipposideros armiger) have functional L-gulonolactone oxidase (GULO), an enzyme that catalyzes the last step of Vc biosynthesis de novo. Given the uncertainties surrounding when and how bats lost GULO function, exploration of gene evolutionary patterns is needed. We therefore sequenced GULO genes from 16 bat species in 5 families, aiming to establish their evolutionary histories. In five cases we identified pseudogenes for the first time, including two cases in the genus Pteropus (P. pumilus and P. conspicillatus) and three in family Hipposideridae (Coelops frithi, Hipposideros speoris, and H. bicolor). Evolutionary analysis shows that the Pteropus clade has the highest ω ratio and has been subjected to relaxed selection for less than 3 million years. Purifying selection acting on the pseudogenized GULO genes of roundleaf bats (family Hipposideridae) suggests they have lost the ability to synthesize Vc recently. Limited mutations in the reconstructed GULO sequence of the ancestor of all bats contrasts with the many mutations in the ancestral sequence of recently emerged Pteropus bats. We identified at least five mutational steps that were then related to clade origination times. Together, our results suggest that bats lost the ability to biosynthesize vitamin C recently by exhibiting stepwise mutation patterns during GULO evolution that can ultimately lead to pseudogenization.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Base Sequence; Biological Evolution; Chiroptera; L-Gulonolactone Oxidase; Molecular Sequence Data; Mutation; Phylogeny; Pseudogenes; Sequence Homology, Nucleic Acid

Studies from the UK and North America have reported vitamin C deficiency in around 1 in 5 men and 1 in 9 women in low income groups. There are few data on vitamin C deficiency in resource poor countries.. To investigate the prevalence of vitamin C deficiency in India.. We carried out a population-based cross-sectional survey in two areas of north and south India. Randomly sampled clusters were enumerated to identify people aged 60 and over. Participants (75% response rate) were interviewed for tobacco, alcohol, cooking fuel use, 24 hour diet recall and underwent anthropometry and blood collection. Vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid. We categorised vitamin C status as deficient (<11 µmol/L), sub-optimal (11-28 µmol/L) and adequate (>28 µmol/L). We investigated factors associated with vitamin C deficiency using multivariable Poisson regression.. The age, sex and season standardized prevalence of vitamin C deficiency was 73.9% (95% confidence Interval, CI 70.4,77.5) in 2668 people in north India and 45.7% (95% CI 42.5,48.9) in 2970 from south India. Only 10.8% in the north and 25.9% in the south met the criteria for adequate levels. Vitamin C deficiency varied by season, and was more prevalent in men, with increasing age, users of tobacco and biomass fuels, in those with anthropometric indicators of poor nutrition and with lower intakes of dietary vitamin C.. In poor communities, such as in our study, consideration needs to be given to measures to improve the consumption of vitamin C rich foods and to discourage the use of tobacco.

Topics: Aged; Anthropometry; Ascorbic Acid; Ascorbic Acid Deficiency; Cross-Sectional Studies; Female; Humans; India; Male; Middle Aged; Multivariate Analysis; Poisson Distribution; Prevalence; Risk Factors; Seasons

Our main objective was to determine the effect of ascorbate supplementation in mice unable to synthesize ascorbic acid (gulo KO) when challenged with murine B16FO cancer cells.. Gulo KO female mice 36-40 weeks of age were deprived of or maintained on ascorbate in food and water for 4 weeks prior to subcutaneous injection of 2.5×10(6) B16FO murine melanoma cells in the right flank of mice. A control group of wild type mice were also injected with the melanoma cells and maintained on a regular murine diet. Mice were continued on their respective diets for another 2 weeks after injection. The mice were then sacrificed, blood was drawn and their tumors were measured, excised and processed for histology.. Mean weight of animals decreased significantly (30%, p < 0.0001) in the ascorbate-restricted group but increased slightly, but insignificantly, in the ascorbate-supplemented group. The mean tumor weight in ascorbate supplemented mice was significantly reduced (by 64%, p = 0.004) compared to tumor weight in ascorbate-deprived gulo mice. The mean tumor weight of wild type mice did not differ significantly from the ascorbate-supplemented mice. Gulo KO mice supplemented with ascorbate developed smaller tumors with more collagen encapsulation and fibrous capsule interdigitation, while gulo KO mice deprived of ascorbate hosted large tumors with poorly defined borders, showing more necrosis and mitosis. Ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum inflammatory cytokine IL-6 (90% decrease, p = 0.04) and IL-1β (62% decrease) compared to the levels in gulo KO mice deprived of ascorbate.. Ascorbate supplementation modulated tumor growth and inflammatory cytokine secretion as well as enhanced encapsulation of tumors in scorbutic mice.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cell Proliferation; Diet, Carbohydrate-Restricted; Female; Inflammation Mediators; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Metastasis; Tumor Burden

Some studies have hypothesized the protective role of vitamin C against cardiovascular disorders (CVD) in patients with end-stage renal disease (ESRD). This study was designed to assess plasma vitamin C concentration and its relationship to hemodialysis (HD) patients' morbidity and mortality.. Plasma vitamin C concentrations were assessed in HD patients using spectrophotometry and subjects were prospectively followed for up eighteen months for all-cause mortality. Any association between vitamin C concentration and patients' demographic data, co-morbidities, or the cause of ESRD were investigated using the Chi-square test.. Ninety-one patients with a mean age of 56.7 ± 15.7 years were included in this study. The most frequent cause of ESRD was simultaneous hypertension and diabetes in 30 % of patients, followed by hypertension in 25.6 %, and diabetes in 11.1 %, respectively. About 34 % of patients had CVD as the most prevalent co-morbidity. Forty-nine patients (53.8 %) had low levels of vitamin C concentration. There was a significant relationship between vitamin C insufficiency and presence of any co-morbidity in HD patients (p < 0.05). There was a significant difference in vitamin C concentrations between patients without co-morbidities and those with cardiovascular ones (F[2,88]=3.447, p = 0.036). Twenty-two (24.2 %) patients died over a median duration of 227 days. There was a significant difference in time to death of patients with and without low levels of vitamin C concentration (p = 0.04).. The results showed lower plasma vitamin C levels in HD patients who suffered any co-morbidity and sooner time to death in these patients.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Diabetic Nephropathies; Female; Follow-Up Studies; Hospitals, University; Humans; Hypertension; Iran; Kidney Failure, Chronic; Male; Middle Aged; Morbidity; Mortality; Prospective Studies; Renal Dialysis; Survival Analysis; Young Adult

Vitamin A, B(9), C, E, and uric acid are well-known antioxidants and may prevent age-related eye disorders. The aim of the present study was to investigate the levels of antioxidant vitamins, A, B(9), C, E, and antioxidative substance, uric acid in the serum of Japanese patients with normal-tension glaucoma and compare the results with normal controls.. All subjects with suspicion of primary open-angle glaucoma who came to the glaucoma subspeciality clinic of Keio University Hospital were enrolled in this study. Sixty patients (28 males, 32 females; mean age +/- standard deviation: 59.9 +/- 9.8 years) with newly diagnosed primary open-angle glaucoma patients were consecutively enrolled in this study. After the diagnosis of primary open-angle glaucoma, the patients underwent 24-h IOP measurements. Forty-seven newly diagnosed consecutive normal-tension glaucoma patients (18 males, 29 females; mean age +/- standard deviation: 59.5 +/- 10.2 years) were enrolled in this study. The control subjects were recruited from subjects who came to the clinic for annual refractive check-up. The 44 consecutive control subjects of the current study, (16 males, 28 females; 62.7 +/- 14.8 years) did not have any ocular diseases. The serum levels of vitamins A, B(9), C, E, and uric acid were measured. The values were compared between the normal-tension glaucoma and control groups by the Mann-Whitney U test.. Serum levels of vitamin C were significantly lower in normal-tension glaucoma patients than in normal healthy controls (P = 0.04; normal-tension glaucoma; 4.6 +/- 4.0 microg/ml control; 6.3 +/- 3.9 microg/ml). Uric acid level was significantly higher in normal-tension glaucoma patients than in controls (P = 0.01; normal-tension glaucoma; 5.8 +/- 1.5 mg/dl control; 4.9 +/- 1.4 mg/dl). No statistically significant difference was seen in vitamin A (P = 0.41; normal-tension glaucoma; 82.1 +/- 26.7 microg/dl control; 77.1 +/- 30.1 microg/dl), B(9) (P = 0.37; normal-tension glaucoma; 8.7 +/- 4.3 ng/ml control; 8.0 +/- 3.1 ng/ml)and E (P = 0.83; normal-tension glaucoma; 1.5 +/- 0.6 control; 1.5 +/- 0.6) levels between normal-tension glaucoma and control groups.. Normal-tension glaucoma patients had lower serum levels of vitamin C and increased levels of uric acid. These observations may pave the way for possible alternative treatment for normal-tension glaucoma.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Asian People; Female; Glaucoma, Open-Angle; Humans; Low Tension Glaucoma; Male; Middle Aged; Oxidative Stress; Uric Acid; Vitamin B Complex; Vitamin E

The human aging process is often accompanied by significant increases in degenerative spine disease. The pathophysiology of intervertebral disc degeneration has been extensively studied, but the etiology of this aging-related problem remains poorly understood. The elderly often have lower daily vitamin C intakes and circulating ascorbic acid values than younger people because of problems with poor dentition or mobility, and also are more likely to have underlying sub-clinical diseases that can reduce plasma ascorbate concentrations. Ascorbate is essential for collagen production, and vitamin C deficiency will result in defective connective tissue, including reductions in collagen synthesis and structural stability. It is hypothesised that vitamin C deficiencies may be a key contributing factor in the development of degenerative disk disease (DDD) in the elderly. Once degenerative disc disease has begun, the tissue inflammation that accompanies DDD may further increase vitamin C requirements in the affected patient, thereby creating a cascade of positive feedbacks that potentially accelerates and contributes to further disc degeneration and low-back pain. Aggressive monitoring of patient ascorbate status, as well as more finely-calibrated RDAs for vitamin C that explicitly take into account the patient's age, may be required if aging-related degenerative disk disease is to be minimised.

Topics: Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Extracellular Matrix; Humans; Intervertebral Disc Degeneration; Low Back Pain

Vitamin C is a powerful antioxidant and its levels are decreased in Alzheimer's patients. Even sub-clinical vitamin C deficiency could impact disease development. To investigate this principle we crossed APP/PSEN1 transgenic mice with Gulo knockout mice unable to synthesize their own vitamin C. Experimental mice were maintained from 6 weeks of age on standard (0.33 g/L) or reduced (0.099 g/L) levels of vitamin C and then assessed for changes in behavior and neuropathology. APP/PSEN1 mice showed impaired spatial learning in the Barnes maze and water maze that was not further impacted by vitamin C level. However, long-term decreased vitamin C levels led to hyperactivity in transgenic mice, with altered locomotor habituation and increased omission errors in the Barnes maze. Decreased vitamin C also led to increased oxidative stress. Transgenic mice were more susceptible to the activity-enhancing effects of scopolamine and low vitamin C attenuated these effects in both genotypes. These data indicate an interaction between the cholinergic system and vitamin C that could be important given the cholinergic degeneration associated with Alzheimer's disease.

Topics: Amyloid; Amyloid beta-Protein Precursor; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Exploratory Behavior; Female; L-Gulonolactone Oxidase; Lipid Peroxidation; Male; Maze Learning; Mice; Mice, Transgenic; Oxidative Stress; Presenilin-1; Survival Rate

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Blood Preservation; Canada; Humans

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Genetic Variation; Genotype; Humans; Nutrigenomics; Odds Ratio; Reproducibility of Results; Surveys and Questionnaires

Vitamin C (VC) is a potent antioxidant and plays an essential role in collagen synthesis. As we previously reported, senescence marker protein-30 (SMP30) knockout (KO) mice cannot synthesize VC due to the genetic disruption of gluconolactonase (i.e., SMP30). Here, we utilized SMP30 KO mice deprived of VC and found that VC depletion caused pulmonary emphysema due to oxidative stress and a decrease of collagen synthesis by the third month of age. We grew SMP30 KO mice and wild-type (WT) mice on VC-free chow and either VC water [VC(+)] or plain water [VC(-)] after weaning at 4 wk of age. Morphometric findings and reactive oxygen species (ROS) in the lungs were evaluated at 3 mo of age. No VC was detected in the lungs of SMP30 KO VC(-) mice, but their ROS increased 50.9% over that of the VC(+) group. Moreover, their collagen content in the lungs markedly decreased, and their collagen I mRNA decreased 82.2% compared with that of the WT VC(-) group. In the SMP30 KO VC(-) mice, emphysema developed [21.6% increase of mean linear intercepts (MLI) and 42.7% increase of destructive index compared with VC(+) groups], and the levels of sirtuin 1 (Sirt1) decreased 16.8%. However, VC intake increased the MLI 16.2% and thiobarbituric acid reactive substances 22.2% in WT mice, suggesting that an excess of VC can generate oxidative stress and may be harmful during this period of lung development. These results suggest that VC plays an important role in lung development through affecting oxidant-antioxidant balance and collagen synthesis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Collagen Type I; Intracellular Signaling Peptides and Proteins; Lung; Mice; Mice, Knockout; Oxidative Stress; Pulmonary Emphysema; Reactive Oxygen Species; Sirtuin 1

Sulfonamide antimicrobials such as sulfamethoxazole (SMX) have been associated with drug hypersensitivity reactions, particularly in patients with AIDS. A reactive oxidative metabolite, sulfamethoxazole-nitroso (SMX-NO), forms drug-tissue adducts that elicit a T-cell response. Antioxidants such as ascorbic acid (AA) and glutathione (GSH) reduce SMX-NO to the less reactive hydroxylamine metabolite (SMX-HA), which is further reduced to the non-immunogenic parent compound by cytochrome b (5) (b5) and its reductase (b5R). We hypothesized that deficiencies in AA and GSH would enhance drug-tissue adduct formation and immunogenicity toward SMX-NO and that these antioxidant deficiencies might also impair the activity of the b5/b5R pathway. We tested these hypotheses in guinea pigs fed either a normal or AA-restricted diet, followed by buthionine sulfoximine treatment (250 mg/kg SC daily, or vehicle); and SMX-NO (1 mg/kg IP 4 days per week, or vehicle), for 2 weeks. Guinea pigs did not show any biochemical or histopathologic evidence of SMX-NO-related toxicity. Combined AA and GSH deficiency in this model did not significantly increase tissue-drug adduct formation, or splenocyte proliferation in response to SMX-NO. However, combined antioxidant deficiency was associated with decreased mRNA and protein expression of cytochrome b (5), as well as significant decreases in SMX-HA reduction in SMX-NO-treated pigs. These results suggest that SMX-HA detoxification may be down-regulated in combined AA and GSH deficiency. This mechanism could contribute to the higher risk of SMX hypersensitivity in patients with AIDS with antioxidant depletion.

Topics: Animals; Anti-Infective Agents; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Proliferation; Cytochrome-B(5) Reductase; Cytochromes b5; Drug Hypersensitivity; Glutathione; Guinea Pigs; Inactivation, Metabolic; Liver; Male; Sulfamethoxazole; T-Lymphocytes

To assess the role of combined deficiencies of vitamins C and E on the earliest stages of atherosclerosis (an inflammatory condition associated with oxidative stress), 4 combinations of vitamin supplementation (low C/low E, low C/high E, high C/low E, and high C/high E) were studied in atherosclerosis-prone apolipoprotein E-deficient mice also unable to synthesize their own vitamin C (gulonolactone oxidase(-/-)); and to evaluate the effect of a more severe depletion of vitamin C alone in a second experiment using gulonolactone oxidase(-/-) mice carrying the hemizygous deletion of SVCT2 (the vitamin C transporter).. After 8 weeks of a high-fat diet (16% lard and 0.2% cholesterol), atherosclerosis developed in the aortic sinus areas of mice in all diet groups. Each vitamin-deficient diet significantly decreased liver and brain contents of the corresponding vitamin. Combined deficiency of both vitamins increased lipid peroxidation, doubled plaque size, and increased plaque macrophage content by 2- to 3-fold in male mice, although only plaque macrophage content was increased in female mice. A more severe deficiency of vitamin C in gulonolactone oxidase(-/-) mice with defective cellular uptake of vitamin C increased both oxidative stress and atherosclerosis in apolipoprotein E(-/-) mice compared with littermates receiving a diet replete in vitamin C, again most clearly in males.. Combined deficiencies of vitamins E and C are required to worsen early atherosclerosis in an apolipoprotein E-deficient mouse model. However, a more severe cellular deficiency of vitamin C alone promotes atherosclerosis when vitamin E is replete.

Topics: Animals; Aortic Diseases; Apolipoproteins E; Ascorbic Acid; Ascorbic Acid Deficiency; Atherosclerosis; Brain; Dietary Supplements; Disease Models, Animal; Disease Progression; Female; L-Gulonolactone Oxidase; Lipid Peroxidation; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Organic Anion Transporters, Sodium-Dependent; Oxidative Stress; Severity of Illness Index; Sex Factors; Sodium-Coupled Vitamin C Transporters; Symporters; Time Factors; Vitamin E; Vitamin E Deficiency; Vitamins

Vitamin C (VC) is a crucial antioxidant in the brain. To assess whether different brain regions vary in their sensitivity to oxidative stress induced by VC depletion, we used the gulonolactone oxidase (gulo) knockout mouse. This mouse, like humans, cannot synthesize VC and thus its tissue VC levels can be varied by dietary VC intake. Gulo knockout mice were fed drinking water containing standard (0.33g/L), low (0.033g/L) or zero (0g/L) VC supplementation levels. After 4weeks, mice were sacrificed and different brain regions removed for assay of VC and malondialdehyde, a marker of lipid peroxidation. Compared to age-matched wild-type controls, the cerebellum, olfactory bulbs and frontal cortex had the highest VC content, whereas the pons and spinal chord had the lowest. However, in mice that did not receive VC, area differences were no longer significant as all values trended towards zero. Malondialdehyde increased in the cortex as VC supplementation was decreased. The same changes were not observed in the cerebellum or pons, suggesting that cortex is more susceptible to oxidative damage from low VC. These results suggest enhanced susceptibility of the cortex to oxidative stress induced by low VC compared to other brain regions.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Disease Models, Animal; L-Gulonolactone Oxidase; Malondialdehyde; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Statistics, Nonparametric; Tissue Distribution

Haptoglobin (which is encoded by the Hp gene) is a hemoglobin-binding protein that has antioxidant properties and a common polymorphism that consists of 2 structurally different alleles: Hp1 and Hp2. The capacity of Hp2 to inhibit oxidation and vitamin C depletion is less than that of Hp1, but the influence on vitamin C requirements remains unknown.. This study aimed to determine whether the Hp polymorphism modifies the association between dietary vitamin C and serum ascorbic acid deficiency (<11 μmol/L).. Nonsmoking men and women (n = 1046) between 20 and 29 y of age participated in the Toronto Nutrigenomics and Health Study. Blood samples were collected after the subjects had fasted overnight to determine serum ascorbic acid concentrations by HPLC and for genotyping. A 196-item food-frequency questionnaire was used to estimate vitamin C intake.. A gene-diet interaction on serum ascorbic acid was observed (P = 0.02). The overall odds ratio (95% CI) for serum ascorbic acid deficiency was 2.84 (1.73, 4.65) for subjects who did not meet the Recommended Dietary Allowance for vitamin C compared with those who did. The corresponding odds ratios were 4.77 (2.36, 9.65) for the Hp2-2 genotype and 1.69 (0.80, 3.63) for carriers of the Hp1 allele.. Individuals with the Hp2-2 genotype had an increased risk of deficiency if they did not meet the Recommended Dietary Allowance for vitamin C, whereas carriers of the Hp1 allele did not. The findings suggest that the greater antioxidant capacity of Hp1 might spare serum ascorbic acid.

Topics: Adult; Alleles; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Female; Genotype; Haptoglobins; Humans; Male; Odds Ratio; Polymorphism, Genetic; Surveys and Questionnaires; Young Adult

Frequent or rare, minor or serious, numerous skin conditions exist. Allergic, inflammatory, infectious or bullous, dermatoses may also reveal underlying pathologies.

Topics: Acne Vulgaris; Adrenal Cortex Hormones; Ascorbic Acid; Ascorbic Acid Deficiency; Dermatomyositis; Erythema; Humans; Lupus Erythematosus, Cutaneous; Psoriasis; Skin Diseases; Skin Diseases, Vesiculobullous; Vitamin A; Vitamin A Deficiency

Ascorbic acid (AA) protects plants against abiotic stress. Previous studies suggested that this antioxidant is also involved in the control of flowering. To decipher how AA influences flowering time, we studied the four AA-deficient Arabidopsis (Arabidopsis thaliana) mutants vtc1-1, vtc2-1, vtc3-1, and vtc4-1 when grown under short and long days. These mutants flowered and senesced before the wild type irrespective of the photoperiod, a response that cannot simply be attributed to slightly elevated oxidative stress in the mutants. Transcript profiling of various flowering pathway genes revealed a correlation of altered mRNA levels and flowering time. For example, circadian clock and photoperiodic pathway genes were significantly higher in the vtc mutants than in the wild type under both short and long days, a result that is consistent with the early-flowering phenotype of the mutants. In contrast, when the AA content was artificially increased, flowering was delayed, which correlated with lower mRNA levels of circadian clock and photoperiodic pathway genes compared with plants treated with water. Similar observations were made for the autonomous pathway. Genetic analyses demonstrated that various photoperiodic and autonomous pathway mutants are epistatic to the vtc1-1 mutant. In conclusion, our transcript and genetic analyses suggest that AA acts upstream of the photoperiodic and autonomous pathways.

Topics: Antioxidants; Arabidopsis; Arabidopsis Proteins; Ascorbic Acid; Ascorbic Acid Deficiency; Cellular Senescence; Flowers; Phenotype; Phosphoric Monoester Hydrolases; Plant Leaves

Scurvy, the rare but potentially mortal manifestation of severe and prolonged lack of vitamin C, is often confused with hypovitaminosis C, i.e. the mere definition of vitamin C deficiency. While the latter condition can be diagnosed in millions, the clinical consequences (if they exist) remain largely unknown, since only a tiny fraction of those deficient in vitamin C actually develop clinical scurvy. Is hypovitaminosis C itself a problem at all then? Yes, it may well be in some cases. Recent data from our laboratory suggest that the neonatal brain is particularly susceptible to vitamin C deficiency and that this condition may adversely affect early brain development.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Humans; Infant; Infant, Newborn; Models, Biological; Scurvy

Vascular tolerance to nitroglycerin (GTN) may be caused by impaired GTN bioactivation due to inactivation of mitochondrial aldehyde dehydrogenase (ALDH2). As relaxation to GTN is reduced but still sensitive to ALDH2 inhibitors in ascorbate deficiency, we compared the contribution of ALDH2 inactivation to GTN hyposensitivity in ascorbate deficiency and classical in vivo nitrate tolerance.. Guinea pigs were fed standard or ascorbate-free diet for 2 weeks. Reversibility was tested by feeding ascorbate-deficient animals standard diet for 1 week. Nitrate tolerance was induced by subcutaneous injection of 50 mg x kg(-1) GTN 4 times daily for 3 days. Ascorbate levels were determined in plasma, blood vessels, heart and liver. GTN-induced relaxation was measured as isometric tension of aortic rings; vascular GTN biotransformation was assayed as formation of 1,2- and 1,3-glyceryl dinitrate (GDN).. Two weeks of ascorbate deprivation had no effect on relaxation to nitric oxide but reduced the potency of GTN approximately 10-fold in a fully reversible manner. GTN-induced relaxation was similarly reduced in nitrate tolerance but not further attenuated by ALDH inhibitors. Nitrate tolerance reduced ascorbate plasma levels without affecting ascorbate in blood vessels, liver and heart. GTN denitration was significantly diminished in nitrate-tolerant and ascorbate-deficient rings. However, while the approximately 10-fold preferential 1,2-GDN formation, indicative for active ALDH2, had been retained in ascorbate deficiency, selectivity was largely lost in nitrate tolerance.. These results indicate that nitrate tolerance is associated with ALDH2 inactivation, whereas ascorbate deficiency possibly results in down-regulation of ALDH2 expression.

Topics: Aldehyde Dehydrogenase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biotransformation; Chloral Hydrate; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Drug Tolerance; Enzyme Activation; Enzyme Inhibitors; Female; Guinea Pigs; Hydrazines; Injections, Subcutaneous; Isoflavones; Male; Nitric Oxide; Nitric Oxide Donors; Nitroglycerin; Time Factors; Vasodilation; Vasodilator Agents

Combined antioxidant deficiencies of selenium and vitamin E or vitamin E and vitamin C in guinea pigs result in clinical illness. We hypothesized that combined selenium and vitamin C deficiency would have clinical consequences because in vitro interactions of these antioxidant nutrients have been reported. Because guinea pigs are dependent on dietary vitamin C, weanling male guinea pigs were fed selenium-deficient or control diet for 15 weeks before imposing vitamin C deficiency. Four dietary groups were formed and studied 3 weeks later: controls, vitamin C deficient, selenium deficient, and doubly deficient. Deficiencies were confirmed by determinations of glutathione peroxidase activity and vitamin C concentration in liver and skeletal muscle. Plasma creatine phosphokinase activity and liver, kidney, heart, and quadriceps histopathology were determined. Doubly deficient animals had moderately severe skeletal muscle cell death as judged by histopathology and plasma creatine phosphokinase activity of 6630 +/- 4400 IU/L (control, 70 + or - 5; vitamin C deficient, 95 + or - 110; selenium deficient, 280 + or - 250). Liver, kidney, and heart histology was normal in all groups. Muscle alpha-tocopherol levels were not depressed in the doubly deficient group, but muscle F2 isoprostane concentrations were elevated in them and correlated with markers of cell death. We conclude that combining selenium and vitamin C deficiencies in the guinea pig causes cell death in skeletal muscle that is more severe than the injury caused by selenium deficiency. The elevation of muscle F2 isoprostanes is compatible with the cell death being caused by oxidative stress.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Death; Creatine Kinase; Diet; F2-Isoprostanes; Glutathione Peroxidase; Guinea Pigs; Lipid Peroxidation; Male; Muscle, Skeletal; Necrosis; Scurvy; Selenium

Senescence marker protein-30 (SMP30) is a gluconolactonase required for vitamin C (VC) synthesis. We examined effects of VC deficiency on the mouse skin using SMP30 knockout (KO) mice. SMP30 KO or wild type male mice were weaned around day 30 of age, and fed VC-deficient diet. They were given either VC water or control water. VC deficiency for 36 days did not affect skin hydroxyproline contents, while VC deficiency for 60 days decreased the hydroxyproline levels. Levels of some collagen mRNAs were different among the groups, but did not correlate with skin VC levels. The epidermis was morphologically abnormal in VC-deficient SMP30 KO mouse at 60 days after the weaning. Interestingly, the hair cycle was not synchronized among the groups. These data suggest low susceptibility of the mouse skin to VC deficiency and involvement of VC in the regulation of keratinocyte function and hair cycle in vivo.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium-Binding Proteins; Collagen; Hair; Intracellular Signaling Peptides and Proteins; Keratinocytes; Male; Mice; Mice, Knockout; Skin

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biology; Emphysema; Genetic Predisposition to Disease; History, 20th Century; History, 21st Century; Humans; India; Models, Biological; Models, Chemical

A cross-sectional study of the 979 nonsmoking women and men aged 20-29 years who participated in the Toronto Nutrigenomics and Health Study from 2004 to 2008 was conducted to determine the prevalence of serum ascorbic acid (vitamin C) deficiency and its association with markers of chronic disease in a population of young Canadian adults. High performance liquid chromatography was used to determine serum ascorbic acid concentrations from overnight fasting blood samples. A 1-month, 196-item food frequency questionnaire was used to assess dietary intakes. Results showed that 53% of subjects had adequate, 33% had suboptimal, and 14% had deficient levels of serum ascorbic acid. Subjects with deficiency had significantly higher measurements of mean C-reactive protein, waist circumference, body mass index, and blood pressure than did subjects with adequate levels of serum ascorbic acid. The odds ratio for serum ascorbic acid deficiency was 3.43 (95% confidence interval: 2.14, 5.50) for subjects who reported not meeting the recommended daily intake of vitamin C compared with those who did. Results suggest that 1 of 7 young adults has serum ascorbic acid deficiency, in part, because of unmet recommended dietary intakes. Furthermore, serum ascorbic acid deficiency is associated with elevated markers of chronic disease in this population of young adults, which may have long-term adverse health consequences.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; C-Reactive Protein; Canada; Chronic Disease; Cross-Sectional Studies; Feeding Behavior; Female; Humans; Logistic Models; Male; Multivariate Analysis; Prevalence; Risk Factors; Sex Distribution

The neonatal brain is particularly vulnerable to imbalances in redox homeostasis because of rapid growth and immature antioxidant systems. Vitamin C has been shown to have a key function in the brain, and during states of deficiency it is able to retain higher concentrations of vitamin C than other organs. However, because neurons maintain one of the highest intracellular concentrations of vitamin C in the organism, the brain may still be more sensitive to deficiency despite these preventive measures.. The objective was to study the potential link between chronic vitamin C deficiency and neuronal damage in newborn guinea pigs.. Thirty 6- to 7-d-old guinea pigs were randomly assigned to 2 groups to receive either a vitamin C-sufficient diet or the same diet containing a low concentration of vitamin C (but adequate to prevent scurvy) for 2 mo. Spatial memory was assessed by the Morris Water Maze, and hippocampal neuron numbers were quantified by stereologic techniques.. The results showed a reduction in spatial memory (P < 0.05) and an increased time to first platform hit (P < 0.05) in deficient animals compared with controls. The deficient animals had a lower total number of neurons in hippocampal subdivisions (dentate gyrus, cornu ammonis 1, and cornu ammonis 2-3) than did the normal controls (P < 0.05).. Our data show that vitamin C deficiency in early postnatal life results in impaired neuronal development and a functional decrease in spatial memory in guinea pigs. We speculate that this unrecognized effect of vitamin C deficiency may have clinical implications for high-risk individuals, such as in children born from vitamin C-deficient mothers.

Topics: Animals; Animals, Newborn; Ascorbic Acid; Ascorbic Acid Deficiency; Behavior, Animal; Biomarkers; Guinea Pigs; Hippocampus; Maze Learning; Memory; Memory Disorders; Neurogenesis; Random Allocation

Vitamin C (ascorbic acid) may be the most important water-soluble antioxidant in human plasma. In the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), approximately 13% of the US population was vitamin C deficient (serum concentrations <11.4 micromol/L).. The aim was to determine the most current distribution of serum vitamin C concentrations in the United States and the prevalence of deficiency in selected subgroups.. Serum concentrations of total vitamin C were measured in 7277 noninstitutionalized civilians aged > or =6 y during the cross-sectional, nationally representative NHANES 2003-2004. The prevalence of deficiency was compared with results from NHANES III.. The overall age-adjusted mean from the square-root transformed (SM) concentration was 51.4 micromol/L (95% CI: 48.4, 54.6). The highest concentrations were found in children and older persons. Within each race-ethnic group, women had higher concentrations than did men (P < 0.05). Mean concentrations of adult smokers were one-third lower than those of nonsmokers (SM: 35.2 compared with 50.7 micromol/L and 38.6 compared with 58.0 micromol/L in men and women, respectively). The overall prevalence (+/-SE) of age-adjusted vitamin C deficiency was 7.1 +/- 0.9%. Mean vitamin C concentrations increased (P < 0.05) and the prevalence of vitamin C deficiency decreased (P < 0.01) with increasing socioeconomic status. Recent vitamin C supplement use or adequate dietary intake decreased the risk of vitamin C deficiency (P < 0.05).. In NHANES 2003-2004, vitamin C status improved, and the prevalence of vitamin C deficiency was significantly lower than that during NHANES III, but smokers and low-income persons were among those at increased risk of deficiency.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Body Mass Index; Child; Cross-Sectional Studies; Diet; Dietary Supplements; Ethnicity; Female; Humans; Interviews as Topic; Male; Nutrition Surveys; Poverty; Probability; Smoking; Socioeconomic Factors; United States; Young Adult

Glutathione S-transferases (GSTs) are detoxifying enzymes that contribute to the glutathione-ascorbic acid (vitamin C) antioxidant cycle.. The objective was to determine whether GST genotypes modify the association between dietary vitamin C and serum ascorbic acid.. Nonsmoking men and women (n = 905) between 20 and 29 y of age were participants in the Toronto Nutrigenomics and Health Study. Overnight fasting blood samples were collected to determine serum ascorbic acid concentrations by HPLC and to genotype for deletion polymorphisms in GSTM1 and GSTT1 and an Ile105Val substitution in GSTP1. A 196-item food-frequency questionnaire was used to estimate vitamin C intake.. A gene-diet interaction on serum ascorbic acid was observed for GSTM1 (P = 0.04) and GSTT1 (P = 0.01) but not for GSTP1 (P = 0.83). The odds ratio (95% CI) for serum ascorbic acid deficiency (<11 micromol/L) was 3.20 (1.88, 5.44) for subjects who did not meet the Recommended Dietary Allowance of vitamin C compared with those who did. The corresponding odds ratios (95% CIs) were 2.17 (1.10, 4.28) and 12.28 (4.26, 33.42), respectively, for individuals with the GSTT1*1/*1 +*1/*0 (functional) and GSTT1*0/*0 (null) genotypes and 2.29 (0.96, 5.45) and 4.03 (2.01, 8.09), respectively, for the GSTM1*1/*1+GSTM1*1/*0 and GSTM1*0/*0 genotypes.. The recommended intake of vitamin C protects against serum ascorbic acid deficiency, regardless of genotype. Individuals with GST null genotypes had an increased risk of deficiency if they did not meet the Recommended Dietary Allowance for vitamin C, which suggests that the GST enzymes protect against serum ascorbic acid deficiency when dietary vitamin C is insufficient.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Cross-Sectional Studies; Exercise; Female; Genetic Variation; Genotype; Glutathione Transferase; Humans; Male; Ontario; Young Adult

Using senescence marker protein 30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which cannot synthesize vitamin C (VC), we examined whether modulating VC level affects age-related hearing loss (AHL). KO and wild-type (WT) C57BL/6 mice were given water containing 1.5 g/L VC [VC(+)] or 37.5mg/L VC [VC(-)]. At 10 months of age, KO VC(-) mice showed significant reduction in VC level in the inner ear, plasma, and liver, increase in auditory brainstem response (ABR) thresholds, and decrease in the number of spiral ganglion cells compared to WT VC(-), WT VC(+), and KO VC(+) mice. There were no differences in VC level in the inner ear, ABR thresholds, or the number of spiral ganglion cells among WT VC(-), WT VC(+), and KO VC(+) mice. These findings suggest that VC depletion can accelerate AHL but that supplementing VC may not increase VC level in the inner ear or slow AHL in mice.

Topics: Aging; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Auditory Threshold; Calcium-Binding Proteins; Carboxylic Ester Hydrolases; Intracellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Presbycusis; Spiral Ganglion

Studies that have investigated ascorbic acid (AA) concentrations in cord blood have pointed to significant associations with maternal blood AA concentrations, smoking, age, diet, type of delivery, duration of gestation, fetal distress and birth weight. The aim of the present study was to determine the relationship between cord blood AA concentrations in newborns and maternal characteristics. A total of 117 Brazilian healthy parturients were included in this cross-sectional study. The concentrations of AA in blood were determined by the HPLC method. Data concerning socio-economic, demographic, obstetric, nutritional and health characteristics of the parturients, including alcohol consumption and smoking habit, were assessed by a standardised questionnaire. A FFQ was used to investigate the intake of foods rich in vitamin C. Cord blood AA concentration was significantly correlated with per capita income (r 0.26; P = 0.005), maternal blood AA concentration (r 0.48; P < 0.001) and maternal vitamin C-rich food intake score (r 0.36; P < 0.001). The linear regression model including maternal AA concentration, alcohol consumption, smoking, parity, vitamin C-rich food intake score and per capita income explained 31.13 % of the variation in cord blood AA concentrations in newborns. We recommend further experimental studies to assess the effects of ethanol on placental AA uptake, and epidemiological cohort studies to evaluate in detail the influence of maternal alcohol consumption on cord blood AA concentrations.

Topics: Alcohol Drinking; Ascorbic Acid; Ascorbic Acid Deficiency; Cross-Sectional Studies; Dietary Supplements; Female; Fetal Blood; Humans; Income; Infant, Newborn; Maternal Nutritional Physiological Phenomena; Parity; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects

Topics: Adult; Arthralgia; Ascorbic Acid; Ascorbic Acid Deficiency; Edema; Epistaxis; Gastrointestinal Hemorrhage; Humans; Knee Joint; Male; Pigmentation Disorders; Scurvy

We report three cases of scurvy, with differing musculoskeletal presentations, from a tertiary teaching hospital in Sydney, Australia. Case 1 was a man with cerebral palsy who presented with knee swelling following a minor injury. In Case 2, a patient with thalassaemia major presented with purpuric rash, difficulty walking and distal thigh swelling and ecchymosis. Case 3 was a man with Down's syndrome who presented with acute ankle arthritis. Scurvy in Cases 1 and 3 were related to abnormal dietary preferences, whereas in Case 2, scurvy was thought to be related to thalassaemia. All three cases responded rapidly to vitamin C replacement. The subjects did not appear malnourished as they had adequate carbohydrate and protein intake.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; beta-Thalassemia; Cerebral Palsy; Down Syndrome; Feeding Behavior; Hospitals, Teaching; Humans; Male; Scurvy; Treatment Outcome

Topics: Aldehyde Dehydrogenase; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Drug Tolerance; Humans; Nitroglycerin; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Research Design; Vasodilation; Vasodilator Agents

Previous studies from this lab have demonstrated that in vitro ascorbate augments neutrophil nitric oxide (NO) generation and oxidative burst. The present study was therefore undertaken in guinea pigs to further assess the implication of ascorbate deficiency in vivo on neutrophil ascorbate and tetrahydrobiopterin content, NOS expression/activity, phagocytosis, and respiratory burst. Ascorbate deficiency significantly reduced ascorbate and tetrahydrobiopterin amounts, NOS expression/activity, and NO as well as free radical generation in neutrophils from scorbutics. Ascorbate and tetrahydrobiopterin supplementation in vitro, though, significantly enhanced NOS catalysis in neutrophil lysates and NO generation in live cells, but could not restore them to control levels. Although phagocytic activity remained unaffected, scorbutic neutrophils were compromised in free radical generation. Ascorbate-induced free radical generation was NO dependent and prevented by NOS and NADPH oxidase inhibitors. Augmentation of oxidative burst with dehydroascorbate (DHA) was counteracted in the presence of glucose (DHA uptake inhibitor) and iodoacetamide (glutaredoxin inhibitor), suggesting the importance of ascorbate recycling in neutrophils. Ascorbate uptake was, however, unaffected among scorbutic neutrophils. These observations thus convincingly demonstrate a novel role for ascorbate in augmenting both NOS expression and activity in vivo, thereby reinforcing oxidative microbicidal actions of neutrophils.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biopterins; Flow Cytometry; Free Radicals; Guinea Pigs; Male; NADPH Oxidases; Neutrophils; Nitric Oxide Synthase; Phagocytosis; Respiratory Burst; Reverse Transcriptase Polymerase Chain Reaction; Vitamins

Carnitine is an essential cofactor in the transport of long-chain fatty acids into the mitochondrial matrix and plays an important role in energy production via beta-oxidation. Vitamin C (VC) has long been considered a requirement for the activities of two enzymes in the carnitine biosynthetic pathway, i.e., 6-N-trimethyllysine dioxygenase and gamma-butyrobetaine dioxygenase. Our present study using senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which cannot synthesize VC in vivo, led to the conclusion that this notion is not true. After weaning at 40 d of age, SMP30/GNL KO mice were fed a diet lacking VC and carnitine, then given water containing 1.5 g/l VC (VC(+) mice) or no VC (VC(-) mice) for 75 d. Subsequently, total VC and carnitine levels were measured in the cerebrum, cerebellum, liver, kidney, soleus muscle, extensor digitorum longus muscle, heart, plasma and serum. The total VC levels in all tissues and plasma from VC(-) SMP30/GNL KO mice were negligible, i.e., <2% of the levels in SMP30/GNL KO VC(+) mice; however, the total carnitine levels of both groups were similar in all tissues and serum. In addition, carnitine was produced by incubated liver homogenates from the VC-depleted SMP30/GNL KO mice irrespective of the presence or absence of 1 mM VC. Collectively, these results indicate that VC is not essential for carnitine biosynthesis in vivo.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Calcium-Binding Proteins; Carboxylic Ester Hydrolases; Carnitine; Glutathione; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Knockout; Tissue Distribution

There is almost no information regarding the vitamin C status of patients treated in Canadian and American hospitals. We determined the prevalence and predictors of vitamin C deficiency in patients hospitalized on the acute-care wards of a Canadian teaching hospital, and tracked their plasma vitamin C concentrations while they were there.. This was a population-based cross-sectional and time course survey of 149 medical patients shortly after admission to a university teaching hospital. The procedure for sample handling, storage and analysis was validated by measuring the vitamin C concentrations of a reference sample of 141 presumably well nourished people and comparing the results with published norms.. In keeping with published norms, 13% of people in the reference group had a subnormal vitamin C concentration (<28.4 micromol/L) and 3% were vitamin C deficient (<11.4 micromol/L). By contrast, 60% of hospitalized patients had a subnormal vitamin C concentration and 19% were deficient. A history of inadequate nutrition or failure to use a vitamin supplement prior to admission, low serum albumin, and male sex predicted plasma vitamin C deficiency, whereas use of a vitamin supplement prior to admission was associated with adequate vitamin C status in hospital. In a second measurement, obtained in 52 patients after an average of 17 days in hospital, vitamin C status had not improved.. Vitamin C deficiency is prevalent and sustained in patients in a Canadian teaching hospital. The abnormality can be prevented by providing a diet sufficient in vitamin C or by prescribing a multiple vitamin tablet.

Topics: Aged; Analysis of Variance; Ascorbic Acid; Ascorbic Acid Deficiency; Canada; Cross-Sectional Studies; Female; Hospitalization; Hospitals, University; Humans; Male; Prevalence; Vitamins

Topics: Adrenal Glands; Aldosterone; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Guinea Pigs; Humans

An adequate total body pool of ascorbate is essential for optimum health in humans. Requirements for ascorbate are increased in peritoneal dialysis (PD) patients most likely due to a combination of poor nutrition and increased dialysate losses.. We measured serum ascorbate levels in 45 clinically stable PD patients to assess the prevalence of ascorbate insufficiency (level between 2 and 4 mg/L) and deficiency (level <2 mg/L). We also assessed the efficacy of subsequent supplementation and patients' adherence to the prescribed supplementation. All patients were advised on commencement of dialysis to take a multivitamin tablet containing 100-120 mg ascorbate.. Eighteen (41%) PD patients were regularly taking ascorbate-containing multivitamins, while 27 (59%) patients did not take ascorbate supplements. Serum ascorbate levels ranged from <0.2 to 41 mg/L, with wide variations in serum ascorbate at any given intake level. Ascorbate deficiency was present in 1/3 of the current PD population (44% of patients not taking supplements and in 16% of those on supplements), although none of the patients demonstrated clinical manifestations of scurvy. Targeted supplementation of ascorbate insufficient patients increased the median serum ascorbate level from 1.7 mg/L (IQR 1.2-2.2) to 22.5 mg/L (IQR 16.7-32.9).. Our results show that, in PD patients, ascorbate deficiency is common and can readily be identified with serum ascorbate measurements. Oral supplements in the form of inexpensive multivitamin preparations restore adequate serum ascorbate levels in the majority of these patients. We therefore suggest measurement of ascorbate levels in all PD patients at the commencement of dialysis with a target level in the normal range (4-14 mg/L).

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Prevalence

Pregnancy is a period characterized by high metabolic requirements and physiological changes in the female organism. During this period, low body stores of vitamins and minerals including antioxidants can have adverse effects on the mother and foetus. This cross-sectional study assessed plasma concentrations of ascorbic acid (AA) in 117 parturients admitted into a university hospital in São Paulo city, Brazil.. The concentrations of AA were determined by the high performance liquid chromatographic method. Data concerning socioeconomic, demographic, obstetric and nutritional characteristics of the parturients were collected by a standardized questionnaire.. The prevalence of AA deficiency (<22.7 micromol/L) among the parturients was 30.8%. Mean plasma AA concentrations were lower in single/divorced women (27.84+/-3.48 micromol/L) compared with married/single with partner women (34.78+/-1.85 micromol/L) (p=0.047). Blood AA concentrations were significantly correlated with per capita income (r=0.36, p<0.001) and vitamin C-rich food intake score (r=0.42, p<0.001).. The high prevalence of hypovitaminosis C detected in this study is probably due to an inadequate intake of foods rich in vitamin C and low income. We alert to the need for increasing the intake of vitamin C-rich foods through educational programs, especially for low income populations.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Brazil; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Diet; Female; Humans; Income; Marital Status; Nutritional Requirements; Nutritional Status; Parturition; Pregnancy; Prenatal Nutritional Physiological Phenomena; Prevalence; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires; Vitamins

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Female; Humans; Kidney Transplantation; Liver Failure; Liver Transplantation; Membrane Lipids; Oxidative Stress; Renal Insufficiency; Scurvy; Tissue and Organ Procurement; Tocopherols

First described in the 1500 s, scurvy is infrequently seen in industrialized countries today, although vulnerable patient groups remain. A 15-yr-old girl underwent liver transplantation at age 26 months for a primary diagnosis of biliary hypoplasia, and subsequently developed late allograft failure and progressive renal insufficiency culminating in listing for combined liver retransplantation and kidney transplantation at age 13 yr. She required regular hemodialysis treatment for 12 months prior to deceased donor organ availability, with a complicated clinical course including recurrent septic episodes and severe cachexia. Ten months after initiation of hemodialysis, she presented with severe bone pain, purpura, ecchymoses, gingival hyperplasia, mucosal bleeding, and subconjunctival hemorrhages. Serial serum ascorbic acid levels were found to be extremely low (<10 micromol/L) despite routine supplementation both in her dialysate and via regular oral supplementation. Histopathology from skin biopsy revealed purpura, hyper- and parakeratosis, and follicular plugging. She had ECG and 2D echocardiogram disturbances, as well as osteopenia and sclerosis of the extremities on radiological evaluations. Therapy with high-dose ascorbic acid (1 g/day orally) led to complete resolution of skin lesions. This case highlights the importance of awareness and recognition of this historic diagnosis, and particularly in children with end-stage organ disease with severely compromised nutrition.

Topics: Adolescent; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Biopsy; Female; Humans; Kidney Transplantation; Liver Failure; Liver Transplantation; Renal Dialysis; Renal Insufficiency; Reoperation; Scurvy; Tissue and Organ Procurement

The use of clozapine is limited by a relatively high incidence of drug-induced agranulocytosis. Clozapine is oxidized by bone marrow cells to a reactive nitrenium ion. Although many idiosyncratic drug reactions are immune-mediated, the fact that patients with a history of clozapine-induced agranulocytosis do not immediately develop agranulocytosis on rechallenge suggests that some other factor may be responsible for the idiosyncratic nature of this reaction. The reactive nitrenium ion is very rapidly reduced back to clozapine by vitamin C, and many schizophrenic patients are vitamin C deficient. We set out to test the hypothesis that vitamin C deficiency is a major risk factor for clozapine-induced agranulocytosis using a vitamin C deficient guinea pig model. Although the vitamin C deficient guinea pigs did not develop agranulocytosis, the amount of clozapine covalent binding in these animals was less than we had previously observed in samples from rats and humans. Therefore, we studied ODS rats that also cannot synthesize vitamin C. Vitamin C deficient ODS rats also did not develop agranulocytosis, and furthermore, although covalent binding in the bone marrow was greater than that in the guinea pig, it was not increased in the vitamin C deficient ODS rats relative to ODS rats that had adequate vitamin C in their diet. Therefore, it is very unlikely that vitamin C deficiency is a major risk factor for clozapine-induced agranulocytosis.

Topics: Agranulocytosis; Animals; Antipsychotic Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Clozapine; Female; Guinea Pigs; Leukocyte Count; Rats; Risk Factors

Nitroglycerin (GTN) acts through release of a nitric oxide (NO)-related activator of soluble guanylate cyclase in vascular smooth muscle. Besides enzymatic GTN bioactivation catalysed by aldehyde dehydrogenase, non-enzymatic reaction of GTN with ascorbate also results in the formation of a bioactive product. Using an established guinea pig model of ascorbate deficiency, we investigated whether endogenous ascorbate contributes to GTN-induced vasodilation.. Guinea pigs were fed either standard or ascorbate-free diet for 2 or 4 weeks prior to measuring the GTN response of aortic rings and isolated hearts. The effects of ascorbate on GTN metabolism were studied with purified mitochondrial aldehyde dehydrogenase (ALDH2) and isolated mitochondria. Ascorbate deprivation led to severe scorbutic symptoms and loss of body weight, but had no (2 weeks) or only slight (4 weeks) effects on aortic relaxations to a direct NO donor. The EC(50) of GTN was increased from 0.058 +/- 0.018 to 0.46 +/- 0.066 and 5.5 +/- 0.9 microM after 2 and 4 weeks of ascorbate-free diet, respectively. Similarly, coronary vasodilation to GTN was severely impaired in ascorbate deficiency. The potency of GTN was reduced to a similar extent by ALDH inhibitors in control and ascorbate-deficient blood vessels. Up to 10 mM ascorbate had no effect on GTN metabolism catalysed by purified ALDH2 or liver mitochondria isolated from ascorbate-deficient guinea pigs.. Our results indicate that prolonged ascorbate deficiency causes tolerance to GTN without affecting NO/cyclic GMP-mediated vasorelaxation.

Topics: Aldehyde Dehydrogenase; Animals; Aorta; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Female; Guinea Pigs; Heart; Heart Rate; Male; Mitochondria, Liver; Nitroglycerin; Regional Blood Flow; Scurvy; Vasodilation; Vasodilator Agents

Topics: Aged; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Atrial Fibrillation; Coronary Artery Disease; Humans; Male; Myocardial Revascularization; Postoperative Complications; Risk Factors

Oxidative stress is implicated in the cognitive deterioration associated with normal aging as well as neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. We investigated the effect of ascorbic acid (vitamin C) on oxidative stress, cognition, and motor abilities in mice null for gulono-gamma-lactone oxidase (Gulo). Gulo-/- mice are unable to synthesize ascorbic acid and depend on dietary ascorbic acid for survival. Gulo-/- mice were given supplements that provided them either with ascorbic acid levels equal to- or slightly higher than wild-type mice (Gulo-sufficient), or lower than physiological levels (Gulo-low) that were just enough to prevent scurvy. Ascorbic acid is a major anti-oxidant in mice and any reduction in ascorbic acid level is therefore likely to result in increased oxidative stress. Ascorbic acid levels in the brain and liver were higher in Gulo-sufficient mice than in Gulo-low mice. F(4)-neuroprostanes were elevated in cortex and cerebellum in Gulo-low mice and in the cortex of Gulo-sufficient mice. All Gulo-/- mice were cognitively normal but had a strength and agility deficit that was worse in Gulo-low mice. This suggests that low levels of ascorbic acid and elevated oxidative stress as measured by F(4)-neuroprostanes alone are insufficient to impair memory in the knockouts but may be responsible for the exacerbated motor deficits in Gulo-low mice, and ascorbic acid may have a vital role in maintaining motor abilities.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cognition; Female; L-Gulonolactone Oxidase; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Motor Skills Disorders; Oxidative Stress; Psychomotor Performance

We describe the clinical presentation and diagnostic tests of a patient with regional transient osteoporosis (RTO) of the foot. This patient presented with a 4-month history of left-foot pain, nonpitting edema, and brownish discolorations of both feet. He had a history of tobacco abuse, alcohol abuse, and malnutrition. Radiological studies revealed severe osteopenia in the feet, and a MRI revealed bone marrow edema. The bone biopsy was consistent with RTO. This patient also had vitamin C deficiency. This case suggests a link between vitamin C deficiency and RTO, a hypothesis supported by our review of relevant literature on osteoporosis and vitamin C.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Bone Diseases, Metabolic; Dietary Supplements; Foot Bones; Humans; Male; Middle Aged; Osteoporosis; Radiography

In our efforts to meet the vitamin C requirements of dialysis patients we confront a medical dilemma--do we allow the patient to become depleted of vitamin C, with the accompanying hematological and other consequences (Scylla), or do we provide for adequate tissue levels of vitamin C, which has been thought to carry the risk of oxalosis (Charybdis). Many practitioners are certain that either one outcome (deficiency) or the other (oxalic acid toxicity) is inevitable, and much like Odysseus, no safe course is to be found. The recent accumulating evidence that vitamin C improves the management of anemia in dialysis patients compels us to find a safe passage through this dilemma. The serious vitamin C deficiency seen in many patients may also contribute to poor oral health and chronic fatigue. The evidence for oxalosis from vitamin C supplements stems from hemodialysis as practiced 20 years ago. Investigators using this therapy are not observing systemic oxalosis, and the most current data support the conclusion that vitamin C therapy is safe for dialysis patients. The question will be resolved by controlled trials that address both vitamin C effectiveness and safety.

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Erythropoiesis; Fatigue; Humans; Hyperoxaluria; Oral Health; Oxalates; Renal Dialysis

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Susceptibility; Down-Regulation; Humans; Mice; Mice, Knockout; Mutation; Porphyria Cutanea Tarda; Uroporphyrinogen Decarboxylase

Excess hepatic iron is known to enhance both porphyria cutanea tarda (PCT) and experimental uroporphyria. Since previous studies have suggested a role for ascorbate (AA) in suppressing uroporphyria in AA-requiring rats (in the absence of excess iron), the present study investigated whether AA could suppress uroporphyria produced by excess hepatic iron. Hepatic URO accumulation was produced in AA-requiring Gulo(-/-) mice by treatment with 3,3',4,4',5-pentachlorbiphenyl, an inducer of CYP1A2, and 5-aminolevulinic acid. Mice were administered either sufficient AA (1000 ppm) in the drinking water to maintain near normal hepatic AA levels or a lower intake (75 ppm) that resulted in 70 % lower hepatic AA levels. The higher AA intake suppressed hepatic URO accumulation in the absence of administered iron, but not when iron dextran (300-500 mg Fe/kg) was administered. This effect of iron was not due to hepatic AA depletion since hepatic AA content was not decreased. The effect of iron to prevent AA suppression of hepatic URO accumulation was not observed until a high hepatic iron threshold was exceeded. At both low and high AA intakes, hepatic malondialdehyde (MDA), an indicator of oxidative stress, was increased three-fold by high doses of iron dextran. MDA was considerably increased even at low iron dextran doses, but without any increase in URO accumulation. The level of hepatic CYP1A2 was unaffected by either AA intake.. In this mouse model of PCT, AA suppresses hepatic URO accumulation at low, but not high hepatic iron levels. These results may have implications for the management of PCT.

Topics: Aminolevulinic Acid; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 CYP1A2; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Iron; Iron-Dextran Complex; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Polychlorinated Biphenyls; Porphyria Cutanea Tarda; Uroporphyrins

We studied the effect of vitamin C on fracture healing in the elderly. A total of 80 elderly Osteogenic Disorder Shionogi rats were divided into four groups with different rates of vitamin C intake. A closed bilateral fracture was made in the middle third of the femur of each rat. Five weeks after fracture the femora were analysed by mechanical and histological testing. The groups with the lower vitamin C intake demonstrated a lower mechanical resistance of the healing callus and a lower histological grade. The vitamin C levels in blood during healing correlated with the torque resistance of the callus formed (r = 0.525). Therefore, the supplementary vitamin C improved the mechanical resistance of the fracture callus in elderly rats. If these results are similar in humans, vitamin C supplementation should be recommended during fracture healing in the elderly.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biomechanical Phenomena; Dietary Supplements; Disease Models, Animal; Female; Femoral Fractures; Femur; Fracture Healing; Rats; Rats, Mutant Strains; Stress, Mechanical; Vitamins

To study the relationship between vitamin C and the severity of periodontitis.. The study population consisted of subjects from the Malabar/Purbasari tea estate on West Java, Indonesia. In 2002, clinical measurements were performed in 128 subjects, including evaluation of plaque, bleeding on probing, pocket depth and attachment loss. In 2005, 123 out of 128 subjects could be retrieved who were present at the examination of 2002. Blood samples were taken to measure plasma vitamin C levels. Information about the subject's dietary habit was obtained by means of a personal interview guided by a questionnaire.. Plasma levels of vitamin C ranged from 0.02 to 34.45 mg/l with a mean of 7.90 mg/l (+/-5.35). The correlation coefficient between plasma vitamin C level and periodontal attachment loss was -0.199 (p<0.05); stepwise linear regression revealed that vitamin C levels explained 3.9% of the variance in periodontal attachment loss. Subjects with vitamin C deficiency (14.7% of the study population) had more attachment loss compared with those with depletion or normal plasma vitamin C values.. The negative association between plasma vitamin C levels and periodontal attachment loss suggests that vitamin C deficiency may contribute to the severity of periodontal breakdown.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Diet Surveys; Female; Humans; Indonesia; Linear Models; Male; Periodontal Attachment Loss; Periodontal Index; Periodontitis

Vitamin C is a necessary cofactor for collagen synthesis. A deficiency of vitamin C results in the breakdown of connective tissue in and around the walls of blood vessels. The disease is thus characterized by poor healing of wounds. Chronic leg ulcers are defined as wounds that do not heal.. To investigate whether patients with chronic leg ulcers have vitamin C deficiency.. Case control study; vitamin C was assayed in peripheral blood samples of 42 consecutive patients with chronic leg ulcers and in 37 consecutive patients without chronic leg ulcers. Patients without leg ulcers had peripheral vascular disease, or hypertension, or connective disorders. Patients with diabetes, immunodepression (cancer, HIV infection, corticosteroid therapy) and aged under 65 years were excluded. Reference range for plasma vitamin C was above 26 micromol/l (normal levels, group I), hypovitaminosis C as 6-26 micromol/l (group II) and concentrations<6 micromol/l as scurvy (group III).. Mean age was 77.2 years in the ulcers group and 73.8 in the control group (NS), mean weight 73.1 kg in the ulcers group and 67.5 kg in the control group (NS). Smoking was more frequent in the control group (P<0.001). Mean vitamin C levels were lower in the leg ulcers group: 23.9 vs 33.8 micromol/l (P<0.003). Normal levels of vitamin C (group I) were more frequent in the control group: 78.4 vs 50% (P<0.01). Hypovitaminosis C (group II) was more frequent in the leg ulcers group: 23.8 vs 16.2% (P<0.01). Scurvy was more frequent in the leg ulcers group: 26.2 vs 5.4% (P<0.01). C reactive protein levels were higher in the leg ulcers group: 31.8 vs 9.3 mg (P=0.002) and albumin levels were lower in the leg ulcers group: 25 vs 38 g/l (P=0.01) [retrospective data].. Patients with chronic leg ulcers have lower levels of vitamin C than patients without leg ulcers, although smoking was more frequent in patients without leg ulcers. The question is whether vitamin C deficiency is a cofactor of impaired healing or is a simple marker of poor healing? It would be interesting to conduct a randomized controlled study about treatment of chronic leg ulcers with vitamin C.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Case-Control Studies; Female; Humans; Leg Ulcer; Male; Patient Selection; Reference Values

Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype-related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis between Hp phenotypes is attributable to variation in LDL oxidation. The classical view of vitamin C and scurvy being a pure nutritional condition needs to be updated. These findings should foster research investigating the role of Hp polymorphism in human disease, and in vitamin C deficiency and atherosclerosis in particular.

Topics: American Indian or Alaska Native; Ascorbic Acid; Ascorbic Acid Deficiency; Asian People; Diet; Gene Frequency; Genetic Predisposition to Disease; Haptoglobins; History, 16th Century; History, 17th Century; History, 19th Century; History, Medieval; Humans; Polymorphism, Genetic; Scurvy; White People

Scurvy is an ancient disease. Over the years, with advances in the understanding of the disease, general improvement in health standards and nutrition, scurvy is now rarely encountered. The few cases of scurvy reported in the 21st century mainly occurred in the neglected elderly, alcoholics and food faddist. We describe scurvy due to food selection in a 37-year-old woman with underlying eating and obsessive-compulsive disorders. With vitamin C replacement, psychiatric medication and cognitive behavioural therapy, there was a dramatic improvement in her condition. This case serves as a reminder to the clinician that, even though rare in today's practice, ascorbic acid deficiency is still encountered, and when recognised, is an easily treatable disease.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Follow-Up Studies; Humans; Risk Assessment; Scurvy; Singapore; Treatment Outcome

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency caused rapid and significant depletion of ascorbate (P < 0.001), tocopherols (P < 0.001) and glutathione (P < 0.001), and a decrease in superoxide dismutase activity (P = 0.005) in the liver, while protein oxidation was significantly increased (P = 0.011). No changes in lipid oxidation or oxidatively damaged DNA were observed in this tissue. In the brain, the pattern was markedly different. Of the measured antioxidants, only ascorbate was significantly depleted (P < 0.001), but in contrast to the liver, ascorbate oxidation (P = 0.034), lipid oxidation (P < 0.001), DNA oxidation (P = 0.13) and DNA incision repair (P = 0.014) were all increased, while protein oxidation decreased (P = 0.003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during the neonatal period.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Brain; Brain Chemistry; Chromatography, High Pressure Liquid; DNA Repair; Guinea Pigs; Lipid Peroxidation; Liver; Malondialdehyde; Oxidative Stress; Weaning

Plasma ascorbic acid is decreased in women with the pregnancy disorder preeclampsia. We used a mutant strain of rats (Osteogenic Disorder Shionogi), dependent on dietary sources of vitamin C, to investigate whether reduced intake of the vitamin would differentially affect vascular function in late-pregnant (day 19) and age-matched virgin rats. The animals were given either 1 mg/mL of ascorbic acid ad libitum in drinking water [fully supplemented (FS)] or 0.25 mg/mL [marginally supplemented (MS)]. Fetal weights were 21% lower in MS than FS rats, whereas mean maternal weights and pup numbers did not differ. Small mesenteric arteries (diameter, 268+/-7 microm) were mounted in a pressurized arteriograph. Myogenic reactivity (contractile response to step increases in intraluminal pressure) was increased in arteries from MS pregnant compared with FS pregnant rats to levels observed in virgin rats. Ascorbic acid intake did not affect myogenic responses of arteries from virgin rats. Hence, the normal pregnancy-induced reduction in myogenic reactivity was abrogated in MS pregnant animals. Inhibition of nitric oxide synthase had no effect on the myogenicity of arteries from virgin or MS pregnant rats but increased myogenicity of FS pregnant rats to the level of MS pregnant rats. Free radical scavengers reversed the accentuated myogenicity of MS pregnant rats without affecting FS pregnant or virgin rat arteries. These data indicate that moderate ascorbate deprivation increases mesenteric artery myogenic responsiveness during pregnancy. This increase may result from a decrease in nitric oxide-mediated modulation of the myogenic contractile response.

Topics: Administration, Oral; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Dose-Response Relationship, Drug; Female; Fetal Weight; Gestational Age; Mesenteric Arteries; Methacholine Chloride; Phenylephrine; Pregnancy; Pregnancy Complications; Rats; Rats, Mutant Strains; Vasoconstrictor Agents; Vasodilator Agents; Vasomotor System

ODS rat has a hereditary defect in ascorbic acid biosynthesis and is a useful animal model for elucidating the physiological role of ascorbic acid. We previously demonstrated by using ODS rats that ascorbic acid deficiency changes the hepatic gene expression of acute phase proteins, as seen in acute inflammation. In this study, we investigated the effects of ascorbic acid deficiency on the production of inflammatory chemokine, cytokine-induced neutrophil chemoattractant-1 (CINC-1), in ODS rats. Male ODS rats (6 wk of age) were fed a basal diet containing ascorbic acid (300 mg/kg diet) or a diet without ascorbic acid for 14 d. Obvious symptoms of scurvy were not observed in the ascorbic acid-deficient rats. Ascorbic acid deficiency significantly elevated the serum concentration of CINC-1 on d 14. The liver and spleen CINC-1 concentrations in the ascorbic acid-deficient rats were significantly elevated to 600% and 180% of the respective values in the control rats. However, the lung concentration of CINC-1 was not affected by ascorbic acid deficiency. Ascorbic acid deficiency significantly elevated the hepatic mRNA level of CINC-1 (to 480% of the value in the control rats), but not the lung mRNA level. These results demonstrate that ascorbic acid deficiency elevates the serum, liver and spleen concentrations of CINC-1 as seen in acute inflammation, and suggest that ascorbic acid deficiency stimulate the hepatic CINC-1 gene expression.

Topics: Animals; Apolipoprotein A-I; Apolipoproteins E; Ascorbic Acid; Ascorbic Acid Deficiency; Blotting, Northern; Body Weight; Chemokine CXCL1; Chemokines, CXC; Gene Expression; Genetic Predisposition to Disease; Haptoglobins; Liver; Lung; Male; Organ Size; Rats; Rats, Mutant Strains; RNA, Messenger; Scurvy; Spleen

A 12-week growth experiment was conducted to establish the necessity of vitamin C in the nutrition of Heterobranchus longifilis fingerlings. Vitamin C was supplemented at levels of 0 and 50 mg x kg(-1) to a basal diet (42.5% CP), which was fed to triplicate groups of H. longifilis fingerlings. Fish receiving the vitamin C-supplemented diet had significantly improved weight gain (20.7 vs. 16.7 g per fish), feed efficiency ratio (1.03 vs. 1.42), specific growth rate (3.00 vs. 2.74%), protein efficiency ratio (2.26 vs. 1.64), and survival rate (90% vs. 50%). There was a significant decrease in haematocrit and haemoglobin levels in the blood of fish fed no supplemental vitamin C. Furthermore, this group exhibited retarded growth and pathological changes such as vertebral curvature, condensation associated with fragility of the spinal bones. Supplementation of 50 mg vitamin C per kg diet was adequate to prevent the occurrence of vitamin C deficiency in H. longifilis and it was concluded that vitamin C is essential in the nutrition of these fishes.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Aquaculture; Ascorbic Acid; Ascorbic Acid Deficiency; Catfishes; Dietary Supplements; Dose-Response Relationship, Drug; Fish Diseases; Nutritional Requirements; Random Allocation; Weight Gain

This study was designed to determine the effects of vitamin C deficiency on the immune response to infection with influenza virus. l-Gulono-gamma-lactone oxidase gene-inactivated mice (gulo-/- mice) require vitamin C supplementation for survival. Five-wk-old male and female gulo-/- mice were provided water or water containing 1.67 mmol/L vitamin C for 3 wk before inoculation with influenza A/Bangkok/1/79. There were no differences in lung influenza virus titers between vitamin C-adequate and -deficient mice; however, lung pathology in the vitamin C-deficient mice was greater at 1 and 3 d after infection but less at d 7 compared with vitamin C-adequate mice. Male vitamin C-deficient mice had higher expression of mRNA for regulated upon activation normal T expressed and secreted (RANTES), IL-1beta, and TNF-alpha in the lungs at d 1 after infection compared with male controls. However, at d 3 after infection, male vitamin C-deficient mice had less expression of mRNA for RANTES, monocyte chemotactic protein-1 (MCP-1), and IL-12 compared with male controls. None of these differences were observed in female mice. Vitamin C-deficient male mice also had greater nuclear factor-kappaB activation as early as 1 d after infection compared with male controls. These data suggest that vitamin C is required for an adequate immune response in limiting lung pathology after influenza virus infection.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Chemokine CCL2; Chemokine CCL5; Gene Expression; Glutathione; Influenza A virus; Interleukin-1; L-Gulonolactone Oxidase; Lung; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B; Orthomyxoviridae Infections; Oxidation-Reduction; RNA, Messenger; Tumor Necrosis Factor-alpha

We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Gastric Mucosa; Lipid Peroxides; Male; Oxidative Stress; Rats; Rats, Inbred Strains; Restraint, Physical; Stress, Psychological; Sulfhydryl Compounds; Vitamin E

This investigation aims to explore the association among anemia and vitamins A, C, and folate deficiencies in a probabilistic sample of Mexican children.. Data on hemoglobin, serum vitamins A and C and folate concentrations and percent transferrin saturation (PTS) in children 0.5-11 years (n = 1,770) were extracted from the database of the probabilistic Mexican National Nutrition Survey 1999 (NNS-99).. Overall, 16.6% of children were anemic. Iron deficiency children with or without anemia had more frequent low serum retinol (40.6 vs. 16% and 27.7 vs. 11.9%, p < 0.05, respectively) and lower hemoglobin folate (11.5 vs. 22%, p < 0.05) than their non-iron deficiency counterparts. Mean concentrations of serum iron (p < 0.01), folate (p < 0.001) and retinol (p < 0.0001), but not ascorbic acid (p < 0.6), were significantly lower in anemic than in nonanemic children. In a linear regression model, 15% of hemoglobin variation in children was explained by retinol, folate and PTS, but not vitamin C (p <0.0001).. Anemia was mostly associated with iron deficiency and with a lesser proportion of folate and vitamin A deficiencies. Vitamin A deficiency might be overestimated since iron deficiency may lower serum retinol concentrations. Interventions aimed to reduce anemia in this population must consider interactions between those micronutrients in designing strategies.

Topics: Adolescent; Adult; Anemia; Ascorbic Acid; Ascorbic Acid Deficiency; C-Reactive Protein; Child; Child, Preschool; Comorbidity; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Hemoglobins; Humans; Infant; Iron; Iron Deficiencies; Male; Mexico; Micronutrients; Middle Aged; Prevalence; Sampling Studies; Transferrin; Vitamin A; Vitamin A Deficiency

Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.

Topics: Adult; Aged; Aged, 80 and over; Alcoholism; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Black People; Bone Marrow; Female; Femoral Neck Fractures; Humans; Ilium; Iron Overload; Leukocytes; Male; Middle Aged; Osteoporosis; Siderosis

To assess the prevalence of vitamin C deficiency within a group of hospice patients. To assess the relationship between plasma vitamin C, dietary intake and subsequent survival.. Patients with advanced cancer were recruited from a large hospice. Data were collected on demographic details, physical functioning and smoking history. An estimate was obtained of the number of weekly dietary portions consumed equivalent to 40 mg of vitamin C, the recommended daily intake. Plasma vitamin C was measured by a single blood sample. The study had local ethical approval.. Fifty patients were recruited (mean age 65.2 years, 28 female). Plasma vitamin C deficiency was found in 15 (30%). Dietary intake of vitamin C was correlated to plasma vitamin C (r=0.518, P<0.0001). Low dietary intake, low albumin, high platelet count, high CRP level and shorter survival were all significantly associated with low plasma vitamin C concentrations (<11 micromol/L). There was no correlation between plasma vitamin C, smoking history or physical functioning.. Vitamin C deficiency is common in patients with advanced cancer and the most important factors determining plasma levels are dietary intake and markers of the inflammatory response. Patients with low plasma concentrations of vitamin C have a shorter survival.

Topics: Acute Disease; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; England; Female; Hospice Care; Humans; Male; Middle Aged; Neoplasms; Nutritional Status; Prevalence; Serum Albumin

Hemodialysis patients are prone to deficiency of vitamin C, which constitutes the most abundant nonenzymatic antioxidant in blood. Because antioxidants are involved in the pathogenesis of atherosclerosis, the authors examined the association of total vitamin C plasma level with cardiovascular outcomes in such patients. One hundred thirty-eight consecutive maintenance hemodialysis patients (median age 61 yr, 90 males) were enrolled in a single-center study. At baseline, routine laboratory parameters were recorded, and predialysis total vitamin C plasma levels were measured by high-pressure liquid chromatography. Patients were prospectively followed-up for the occurrence of a primary composite endpoint consisting of fatal and nonfatal major adverse cardiovascular events (MACE) and for all-cause and cardiovascular mortality. MACE occurred in 35 patients (25%) over a period of median 30 mo, and 42 patients (30%) died [29 cardiovascular deaths (21% of total)]. Using Cox proportional hazards modeling, adjusted hazard ratios for the occurrence of MACE were 3.90 (95% confidence interval [CI]: 1.42 to 10.67; P = 0.008) and 3.03 (95% CI: 1.03 to 8.92; P = 0.044) for patients in the lower (<32 micromol/L) and middle (32 to 60 micromol/L) tertile of total vitamin C levels, compared with patients in the upper tertile (>60 micromol/L). Hazard ratios for cardiovascular death were 3.79 (95% CI: 1.23 to 11.66; P = 0.020) and 2.89 (95% CI: 0.89 to 9.37; P = 0.076). Total vitamin C levels were not independently associated with all-cause mortality. This study concludes that low total vitamin C plasma levels predict adverse cardiovascular outcomes among maintenance hemodialysis patients. Future studies should address the potential protective effect of an adequate vitamin C supplementation.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Risk Factors

Vitamin C (ascorbate) is essential for hydroxylation of prolyl and lysyl residues in nascent collagen, the failure of which leads to connective tissue lesions of scurvy. Of the pyridinium-type cross-links in mature collagen, pyridinoline requires more hydroxylysyl residues than does deoxypyridinoline. Our study tested the hypothesis that pyridinoline:deoxypyridinoline ratios in urinary degradation products may vary with ascorbate status in man. These ratios were compared between British and Gambian prepubertal boys, mean age 8.3 years, and in Gambian boys between two seasons with contrasting ascorbate availability. The mean cross-links ratio in 216 British boys was 4.36 (SD 0.71), significantly greater (P<0.0001) than in sixty-two Gambian boys: 3.83 (SD 0.52). In the Gambians the cross-links ratio was significantly higher in the dry season (with high ascorbate intake and status) than in the rains (with low intake and status). A 7-week controlled intervention was carried out in Gambian boys during the rainy season (the 'hungry' season, when vitamin C-containing foods are virtually unavailable): 100 mg ascorbate/d was given to one group of thirty-two Gambian boys and placebo to another group. The intervention did not, however, significantly alter the cross-link ratio, possibly because the response time and/or intervention-response delay is >7 weeks. If confirmed, the putative association between ascorbate and collagen cross-link ratios in man could become the basis for a functional test for adequacy of ascorbate status.

Topics: Amino Acids; Anthropometry; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Body Mass Index; Bone and Bones; Child; Child, Preschool; Collagen; Creatinine; Gambia; Humans; Male; Rain; Seasons; United Kingdom

Several reports have shown that Vitamin C is depleted in animals with age. Based mainly on comparisons between young animals that have not yet reached maturity and old animals, it appears to be the general assumption that the change in Vitamin C status occurs at a late stage in life and that this phenomenon may either contribute to or result from the ageing process. In the present study, young (3 months old, n = 8) and old (36 months old, n = 8) female guinea pigs were followed for 6 months with monthly blood samplings and monitored for Vitamin C status as measured by plasma ascorbate and erythrocyte ascorbate recycling capacity after which the animals were euthanized. While remaining unchanged in the old animals, plasma Vitamin C status of the young animals significantly declined to that of the old animals within 3 months. During the following 3 months, the Vitamin C status of the young animals remained unchanged. Furthermore, post mortem Vitamin C analyses of the animals now aged 9 and 42 months, respectively, showed no effect of age on Vitamin C in plasma, liver, kidney, heart and brain between the groups while concentrations were significantly increased in cerebrospinal fluid and lung with age (p < 0.05). Moreover, a significantly elevated ascorbic acid oxidation ratio was observed in young compared to old animals (p < 0.05). The present data suggest that the decline in Vitamin C status with age occur early in life and is a phenomenon of maturation rather than of ageing. Data from other species and humans are discussed.

Topics: Age Factors; Aging; Analysis of Variance; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cerebrospinal Fluid; Erythrocytes; Female; Glutathione; Guinea Pigs; Oxidative Stress; Oxygen; Temperature; Time Factors

Using a mouse mutant that fractures spontaneously and dies at a very young age, we identified that a deletion of the GULO gene, which is involved in the synthesis of vitamin C, is the cause of impaired osteoblast differentiation, reduced bone formation, and development of spontaneous fractures.. A major public health problem worldwide, osteoporosis is a disease characterized by inadequate bone mass necessary for mechanical support, resulting in bone fracture. To identify the genetic basis for osteoporotic fractures, we used a mouse model that develops spontaneous fractures (sfx) at a very early age.. Skeletal phenotype of the sfx phenotype was evaluated by DXA using PIXImus instrumentation and by dynamic histomorphometry. The sfx gene was identified using various molecular genetic approaches, including fine mapping and sequencing of candidate genes, whole genome microarray, and PCR amplification of candidate genes using cDNA and genomic DNA as templates. Gene expression of selected candidate genes was performed using real-time PCR analysis. Osteoblast differentiation was measured by bone marrow stromal cell nodule assay.. Femur and tibial BMD were reduced by 27% and 36%, respectively, in sfx mice at 5 weeks of age. Histomorphometric analyses of bones from sfx mice revealed that bone formation rate is reduced by >90% and is caused by impairment of differentiated functions of osteoblasts. The sfx gene was fine mapped to a 2 MB region containing approximately 30 genes in chromosome 14. By using various molecular genetic approaches, we identified that deletion of the gulonolactone oxidase (GULO) gene, which is involved in the synthesis of ascorbic acid, is responsible for the sfx phenotype. We established that ascorbic acid deficiency caused by deletion of the GULO gene (38,146-bp region) contributes to fractures and premature death because the sfx phenotype can be corrected in vivo by treating sfx mice with ascorbic acid and because osteoblasts derived from sfx mice are only able to form mineralized nodules when treated with ascorbic acid. Treatment of bone marrow stromal cells derived from sfx/sfx mice in vitro with ascorbic acid increased expression levels of type I collagen, alkaline phosphatase, and osteocalcin several-fold.. The sfx is a mutation of the GULO gene, which leads to ascorbic acid deficiency, impaired osteoblast cell function, and fractures in affected mice. Based on these and other findings, we propose that ascorbic acid is essential for the maintenance of differentiated functions of osteoblasts and other cell types.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone and Bones; Bone Marrow Cells; Cell Differentiation; Chromosome Mapping; Densitometry; DNA Primers; DNA, Complementary; Femur; Fracture Healing; Fractures, Bone; Gene Deletion; Genome; Genotype; L-Gulonolactone Oxidase; Mice; Mice, Inbred BALB C; Models, Genetic; Mutation; Oligonucleotide Array Sequence Analysis; Osteoblasts; Osteoporosis; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA; Stromal Cells; Tibia; X-Rays

A 53-year-old woman was referred because of progressive haematomas of the lower extremities and fatigue. Her medical history included hyperplastic gums and tooth loss. Scurvy was diagnosed; this was the result of an insufficient diet due to a paranoid psychosis. There was a dramatic improvement within a few days after addition of vitamin C and starting highly nutritious food. Scurvy is easily treated, but is not a disease of the past.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Contusions; Diet; Fatigue; Female; Humans; Middle Aged; Schizophrenia; Schizophrenic Psychology; Tooth Loss; Treatment Outcome

Infantile Tremor Syndrome is a distinct clinical entity most commonly seen in Indian Subcontinent. Syndrome consists of tremors, mental and developmental retardation, abnormal skin pigmentation and anemia in children between 6 months to 2 years. The etiology is still elusive. Amongst various theories, nutritional theory is the most accepted. So far there are no cases reported of vitamin C deficiency in ITS. In this article, three cases of ITS associated with vitamin C deficiency are reported.

Topics: Age Factors; Ascorbic Acid; Ascorbic Acid Deficiency; Folic Acid; Humans; Infant; Iron; Male; Malnutrition; Propranolol; Scurvy; Socioeconomic Factors; Syndrome; Treatment Outcome; Tremor

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Contusions; Fatigue; Humans; Schizophrenia; Tooth Loss

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Schizophrenia; Tooth Loss; Vitamins

Topics: Age Factors; Aged; Aged, 80 and over; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Geriatric Assessment; Humans; Nutritional Requirements; Risk Factors

l-Gulono-gamma-lactone oxidase (GULO) is a critical enzyme present in most mammalian species that is required for the terminal step in vitamin C biosynthesis. Primates are absolutely dependent on exogenously supplied dietary vitamin C due to inactivation of the Gulo gene by mutation over 40 million years ago. In this study, we report the cloning and expression of the murine l-gulono-gamma-lactone oxidase cDNA and gene. The cDNA (2.3 kb) encodes an open reading frame of 440 amino acids that shows high homology to the rat l-gulono-gamma-lactone oxidase (>94%). The Gulo gene is 22 kb long and contains 12 exons. The 11 introns range in size from 479 to 5641 bp. Northern blot analysis revealed high expression of Gulo transcript in the liver. To investigate whether metabolic loss of vitamin C biosynthesis in human cells can be corrected by heterologous expression of GULO, we constructed a first-generation adenoviral vector expressing the murine GULO cDNA under the transcriptional control of the murine cytomegalovirus (MCMV) early promoter. Low rescue efficiency of Gulo-expressing adenoviral constructs and reduced viral growth in HEK293 cells were observed, suggesting that overexpression of Gulo may be inhibitory to cell growth. Placement of a removable stuffer fragment flanked by lox sites between the MCMV promoter and the Gulo gene resulted in efficient vector rescue and normal viral replication in parental HEK293 cells and high-level expression of Gulo in HEK293 cells expressing Cre recombinase. Cells infected with Gulo-expressing vectors overexpressed an FAD-containing protein that corresponded in size to that predicted for recombinant GULO protein and expressed a functional enzyme as measured by the conversion of l-gulono-gamma-lactone to ascorbic acid in cell-free extracts. The cloning of the murine Gulo cDNA and the construction of Gulo-expressing adenoviral vectors are vital steps toward determining the role of vitamin C in basic metabolism and in disease.

Topics: Adenoviridae; Amino Acid Sequence; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Line; Cloning, Molecular; Female; Gene Library; Genetic Vectors; Humans; L-Gulonolactone Oxidase; Male; Mice; Models, Genetic; Molecular Sequence Data; Plasmids; Recombinant Proteins; Sugar Alcohol Dehydrogenases; Transfection

Alzheimer s disease (AD), according to the free radical hypothesis, affects brain regions where free radical damage occurs. Antioxidant nutrients may help to protect these brain regions.. To investigate whether plasma vitamin C and E status is lowered in subjects with AD and dementia.. A case control study was conducted in 93 institutionalized subjects aged 65 + yrs. The dementia group (N = 43) included 15 subjects with Alzheimer s Disease (AD) and 28 subjects with senile dementia, while the control group included 50 subjects with no cognitive impairment. Subjects with uncontrolled hypertension and/or diabetes were excluded from the study. Plasma vitamin C and E was determined using the 2,6- dichlorophenolindophenol and the HPLC methods, respectively. Dietary intake, including dietary supplements, was assessed using a 2-day plate-waste method. Cognitive function was measured using the MMSE and nutritional status assessed using the Mini Nutritional Assessment (MNA) tool.. The control group had significantly higher scores for the MNA, MMSE and Activities of Daily Living, compared with the dementia group. Controls had a significantly higher plasma vitamin C concentration than dementia patients (median = 0.84 (IQR = 0.54) mg/dl and 0.56 (0.80) mg/dl, respectively; P<0.05). The dementia group were more likely to have sub-optimal plasma vitamin C levels (< 0.6 mg/dl) than control subjects (OR = 2.99; 95 % CI = 0.95 9.79; P<0.05), despite having similar dietary vitamin C intakes. Plasma vitamin C was positively associated with MMSE score (r = 0.21; P<0.05). No difference was found between the groups for either plasma or dietary vitamin E.. Plasma vitamin C levels were lower in subjects with dementia compared to controls, which was not explained by their dietary vitamin C intakes. This data supports the free radical theory of oxidative neuronal damage. Further investigations of whether supplementation with this vitamin may prevent or delay the progression of cognitive decline in patients with AD and senile dementia appear warranted.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Case-Control Studies; Dementia; Female; Geriatric Assessment; Humans; Male; Nutritional Status; Psychiatric Status Rating Scales; Vitamin E

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Histamine; Humans; Military Medicine; Vaccines

The findings of subdural hematoma and retinal hemorrhages in infants, without any documented history of major trauma, do not always indicate child abuse. A combination of ascorbate depletion and the injection of foreign proteins can cause a very high blood histamine level, leading to capillary fragility and venular bleeding. This can be prevented by the administration of vitamin C.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Capillary Fragility; Hematoma, Subdural; Histamine; Humans; Infant, Newborn; Retinal Hemorrhage; Shaken Baby Syndrome; Vaccination

Vitamin C is considered to be a very efficient water-soluble antioxidant, for which several new cardiovascular properties were recently described. The aim of this study was to determine in vivo the effects of a severe depletion of vitamin C on cardiac and vascular variables and reperfusion arrhythmias. For this purpose, we used a mutant strain of Wistar rats, osteogenic disorder Shionogi (ODS). After 15 d of consuming a vitamin C-deficient diet, ODS rats had a 90% decrease in plasma and tissue levels of ascorbate compared with ODS vitamin C-supplemented rats and normal Wistar rats. However, plasma antioxidant capacity, proteins, alpha-tocopherol, urate, catecholamines, lipids, and nitrate were not influenced by the vitamin C deficiency in ODS rats. Moreover, there was no difference between ODS vitamin C-deficient and -supplemented rats in heart rate and arterial pressure. After 5 min of an in vivo regional myocardial ischemia, various severe arrhythmias were observed, but their intensities were not modified by vitamin C in vitamin C-deficient ODS rats. The vascular reactivity, measured in vitro on thoracic arteries, was not altered by ascorbate deficiency in ODS rats. These unexpected results suggest that unidentified compensatory mechanisms play a role in maintaining normal cardiac function and vascular reactivity in vitamin C-deficient rats.

Topics: Acetylcholine; alpha-Tocopherol; Animals; Aorta; Arrhythmias, Cardiac; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Bone Diseases; Cardiovascular Diseases; Diet; Epinephrine; Heart Rate; Male; Muscle Contraction; Myocardial Ischemia; Myocardial Reperfusion; Norepinephrine; Osteogenesis; Phenylephrine; Rats; Rats, Mutant Strains; Rats, Wistar

The ozone-sensitive Arabidopsis mutant vitamin c-1 (vtc1) is deficient in l-ascorbic acid (AsA) due to a mutation in GDP-Man pyrophosphorylase (Conklin et al., 1999), an enzyme involved in the AsA biosynthetic pathway (Smirnoff et al., 2001). In this study, the physiology of this AsA deficiency was initially investigated in response to biotic (virulent pathogens) stress and subsequently with regards to the onset of senescence. Infection with either virulent Pseudomonas syringae or Peronospora parasitica resulted in largely reduced bacterial and hyphal growth in the vtc1 mutant in comparison to the wild type. When vitamin c-2 (vtc2), another AsA-deficient mutant, was challenged with P. parasitica, growth of the fungus was also reduced, indicating that the two AsA-deficient mutants are more resistant to these pathogens. Induction of pathogenesis-related proteins PR-1 and PR-5 is significantly higher in vtc1 than in the wild type when challenged with virulent P. syringae. In addition, the vtc1 mutant exhibits elevated levels of some senescence-associated gene (SAG) transcripts as well as heightened salicylic acid levels. Presumably, therefore, low AsA is causing vtc1 to enter at least some stage(s) of senescence prematurely with an accompanying increase in salicylic acid levels that results in a faster induction of defense responses.

Topics: Arabidopsis; Ascorbic Acid; Ascorbic Acid Deficiency; Gene Expression Regulation, Plant; Immunity, Innate; Mutation; Plant Diseases; Pseudomonas; Time Factors; Transcription, Genetic

The absence of L-ascorbic acid (L-AA, or AA) synthesis in scurvy-prone organisms, including humans, other primates, guinea pigs, and flying mammals, was traced to the lack of L-gulonolactone oxidase (GULO) activity. GULO is a microsomal enzyme that catalyzes the terminal step in the biosynthesis of L-AA. Clinical cases of scurvy were described in a family of Danish pigs. This trait is controlled by a single autosomal recessive allele designated od (osteogenic disorder). Here we demonstrate that the absence of GULO activity and the associated vitamin C deficiency in od/od pigs is due to the occurrence of a 4.2-kbp deletion in the GULO gene. This deletion includes 77 bp of exon VIII, 398 bp of intron 7 and 3.7 kbp of intron 8, which leads to a frame shift. The mutant protein is truncated to 356 amino acids, but only the first 236 amino acids are identical to the wild-type GULO protein. In addition, the od allele seems to be less expressed in deficient and heterozygous pigs compared with the normal allele in heterozygous and wild-type animals as determined by ribonuclease protection assay. We also developed a DNA-based test for the diagnosis of the deficient allele. However, we failed to identify the mutated allele in other pig populations.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Base Sequence; Blotting, Northern; Crosses, Genetic; DNA; Female; Gene Deletion; L-Gulonolactone Oxidase; Liver; Male; Microsomes, Liver; Molecular Sequence Data; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sugar Alcohol Dehydrogenases; Swine

To examine whether low maternal dietary intake of vitamin C and low maternal plasma ascorbic acid (AA) concentrations are associated with an increased risk of gestational diabetes mellitus (GDM).. Cases were 67 women with GDM meeting National Diabetes Data Group criteria. Controls were 260 women without such a diagnosis. Maternal dietary vitamin C consumption during the periconceptional period and during pregnancy was assessed using a 121-item, semiquantitative food frequency questionnaire. Maternal plasma AA concentrations were determined using automated enzymatic procedures on specimens collected during the intrapartum period.. Mean maternal daily consumption of vitamin C and plasma AA concentrations were 10% and 31% lower, respectively, among GDM cases as compared with controls (130.7 +/- 10.2 vs. 145 +/- 4.9 mg/d, P = .190; 36 +/- 2.0 vs. 53 +/- 1.0 micromol/L, P <.001). After controlling for maternal age, race, prepregnancy adiposity, family history of type 2 diabetes, energy intake and income, women reporting low daily vitamin C intake (< 70 mg/d), as compared with the other women, experienced a 3.7-fold increased risk of GDM (odds ratio [OR] = 3.7, 95% confidence interval [CI] 1.7-8.2). There was a linear relation in risk of GDM with decreasing concentrations of plasma AA (P for linear trend <.001). After adjusting for confounders, women in the lowest quartile (< 42.6 micromol/L), as compared with women in the highest quartile (> 63.3 micromol/L), experienced > 12-fold increased risk of GDM (OR = 12.8, 95% CI 3.5-46.2).. Low maternal dietary vitamin C intake and low plasma AA concentrations are associated with an increased risk of GDM. Large, prospective, cohort studies are needed to further evaluate the potential beneficial role of vitamin C and other antioxidants in the prevention of impaired glucose tolerance in pregnancy.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Case-Control Studies; Diabetes, Gestational; Female; Humans; Pregnancy; Risk Factors

We examined whether short-term ascorbic acid deficiency impairs antioxidant status in the lens of guinea pigs. Male guinea pigs aged 4 wk were given a scorbutic diet (20 g/animal per day) with and without ascorbic acid (400 mg/animal per day) in drinking water for 3 wk. The ascorbic acid-deficient group showed no lens opacity. The ascorbic acid-deficient group had 14% of serum ascorbic acid concentration, 6% of aqueous humor ascorbic acid concentration, and 18% of lens ascorbic acid content in the ascorbic acid-adequate group. There were no differences in the contents of lens reduced glutathione and thiobarbituric acid reactive substances, an index of lipid peroxidation, between the ascorbic acid-deficient and adequate groups, while the deficient group had higher lens vitamin E content than the adequate group. The ascorbic acid-deficient group had higher serum vitamin E concentration than the ascorbic acid adequate group, while there were no differences in the concentrations of serum reduced glutathione and tiobarbituric acid reactive substances between the deficient and adequate groups. These results indicate that short-term ascorbic acid deficiency does not impair antioxidant status in the lens of guinea pigs despite induction of severe ascorbic acid depletion in the tissue, which may result in no cataract formation.

Topics: Animals; Antioxidants; Aqueous Humor; Ascorbic Acid; Ascorbic Acid Deficiency; Cataract; Diet; Glutathione; Guinea Pigs; Lens, Crystalline; Lipid Peroxidation; Male; Oxidation-Reduction; Thiobarbituric Acid Reactive Substances; Vitamin E

The objective of these studies was to determine the role of ascorbate deficiency in HIV infection in the defective detoxification of sulfamethoxazole-nitroso, the metabolite thought to mediate sulfonamide hypersensitivity reactions.. Fifty-one HIV-infected patients and 26 healthy volunteers were evaluated. Vitamin supplementation histories were obtained, and blood samples were collected for determination of plasma ascorbate, dehydroascorbate, and cysteine concentrations, erythrocyte glutathione concentrations, and plasma reduction of sulfamethoxazole-nitroso in vitro.. Plasma ascorbate concentrations were significantly lower in HIV-positive patients not taking vitamin supplements (29.5 +/- 22.3 microM) than in healthy subjects (54.8 +/- 22.3 microM; P = 0.0005) and patients taking 500-1000 mg of ascorbate daily (82.5 +/- 26.3 microM; P < 0.0001). Plasma ascorbate deficiency was strongly correlated with impaired reduction of sulfamethoxazole-nitroso to its hydroxylamine (r = 0.60, P < 0.0001), and during in vitro reduction, the loss of plasma ascorbate was strongly associated with the amount of nitroso reduced (r = 0.70, P < 0.0001). Ascorbate added ex vivo normalized this reduction pathway. Erythrocyte glutathione concentrations were significantly lower in HIV-positive patients (0.98+/-0.32 mM) than in healthy subjects (1.45+/-0.49 mM; P = 0.001), but this finding was unrelated to ascorbate supplementation. There was trend toward lower plasma cysteine concentrations in patients (8.4+/-3.9 microM) than in controls (10.3+/-4.3 microM), but this trend was similarly unrelated to ascorbate supplementation. Dehydroascorbate concentrations were not significantly higher in HIV-positive patients (7.4+/-10.5%) than in healthy controls (4.0+/-6.2%), even in the subset of patients taking ascorbate (8.4+/-9.4%).. Ascorbate deficiency is common in HIV-positive patients and is associated with impaired detoxification of sulfamethoxazole-nitroso, the suspected proximate toxin in sulfonamide hypersensitivity. Patients taking daily ascorbate supplements (500-1000 mg) achieved high plasma ascorbate concentrations and did not show this detoxification defect. Ascorbate deficiency (or supplementation) was not associated with changes in glutathione or cysteine concentrations. These data suggest that ascorbate deficiency, independent of thiol status, may be an important determinant of impaired drug detoxification in HIV infection.

Topics: Adult; Anti-Infective Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Case-Control Studies; CD4-CD8 Ratio; Cysteine; Dehydroascorbic Acid; Female; Glutathione; HIV Infections; Humans; In Vitro Techniques; Male; Middle Aged; Oxidation-Reduction; Sulfamethoxazole

A cross-sectional study was carried out to determine the differences in vitamin C status of Brazilian pregnant women smokers and nonsmokers and their respective newborn babies, and to assess the prevalence of hypovitaminosis C among these two groups of women. The study involved 127 pregnant women, 40 pregnant smokers and 87 pregnant nonsmokers, admitted to a maternity hospital in São Paulo, Brazil. Data concerning the pregnant women's socioeconomic, demographic, obstetric, and nutritional characteristics were collected, as well as data concerning the newborns' anthropometry and Apgar scores. A strongly significant correlation (p < 0.001) was found between the concentrations of ascorbic acid (AA) in both pregnant smokers (r = 0.77) and pregnant nonsmokers (r = 0.61) and their respective umbilical cords. The mean umbilical AA concentration was significantly higher than the meanAA concentration in pregnant women (92.05 +/- 41.13 vs. 33.39 +/- 18.25 micromol/L, p < 0.001). It was observed that the mean AA was significantly lower for the newborns (p = 0.03) and pregnant women (p = 0.02) from the smoking group. Forty percent (40%) of the smokers and 27% of the nonsmokers presented hypovitaminosis C. We suggest an increase in the consumption of fruits and vegetables by pregnant women, especially the smokers.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Brazil; Diet; Female; Fetal Blood; Fruit; Humans; Infant, Newborn; Maternal Nutritional Physiological Phenomena; Nutritional Status; Pregnancy; Smoking; Socioeconomic Factors; Vegetables

The status of ascorbic acid (AA) in dialysis patients is the subject of debate. Some reports have found AA to be deficient in dialysis patients, while others have found that AA is not deficient. In an attempt to confirm AA serum concentrations in dialysis patients, we analyzed the concentrations of AA as well as its metabolites using the specific determination of AA with chemical derivatization and the HPLC method. We studied 131 patients under maintenance hemodialysis therapy (HD), 23 patients with chronic renal failure (CRF) and 48 healthy controls (C). Serum concentrations of AA and the AA metabolites dehydroascorbic acid (DHA) and 2, 3-diketogulonate (DKG) were measured by HPLC. Nine HD patients were taking AA supplements. Seventy-six (62.3%) of the 122 HD patients not taking AA supplements exhibited deficient levels of AA (< 20 microM), while 13 (56.5%) of the 23 CRF patients and 9 (18.8%) of the 48 C showed deficient levels of AA. Analysis of AA metabolites in the normal-range AA (20-80 microM) group revealed that the DHA/AA ratio in HD patients was significantly higher than in C (3.3 +/- 2.6% and 1.2 +/- 2.2%, respectively). The DKG/AA ratio in HD patients was higher than in CRF patients (3.6 +/- 5.2% vs. 0.9 +/- 1.9%), whereas DKG was not detected in C. When compared to serum levels before the start of dialysis, serum AA, DHA and DKG concentrations at the end of the dialysis session decreased by an average of 74.2, 84.0 and 78.8% respectively. In HD patients, serum levels of thiobarbituric reactive substances (TBARS) were significantly lower in the higher AA (> 80 microM) group than in the deficient and normal-range AA groups. In 12 AA-deficient patients, after 1 month of taking AA supplements (200 mg/day), serum AA levels rose to 79.9 microM, while serum TBARS level declined when compared with levels before supplementation. In conclusion, the frequency of AA deficiency in dialysis patients is extremely high. AA deficiency in HD patients may result in high TBARS levels, which reflect increased oxidative stress. Adequate AA supplementation should therefore be considered in such patients.

Topics: 2,3-Diketogulonic Acid; Administration, Oral; Aged; Aorta; Ascorbic Acid; Ascorbic Acid Deficiency; Calcinosis; Calcium Oxalate; Chromatography, High Pressure Liquid; Dehydroascorbic Acid; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Thiobarbituric Acid Reactive Substances

Physiconutritional qualities of fruits viz. apple, lime, pomegranate, Perlette grape, and Pusa Navrang grape were analyzed and compared with those of Indian gooseberry (Emblica officinalis Gaertn.). Indian gooseberry juice contained the highest vitamin C (478.56 mg/100 ml). Hence, when gooseberry juice was blended with other fruits' juice for the preparation of ready-to-serve (RTS) beverages, it boosted their nutritional quality in terms of vitamin C content. On the basis of overall sensory quality and vitamin C content, RTS beverage prepared by blending gooseberry and Pusa Navrang grape juice in 20:80 ratio was found to be the best.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Beverages; Food, Fortified; Humans; Nutritional Requirements; Nutritive Value; Ribes; Taste

We have previously reported the establishment of a novel rat strain, SHR-od, with both spontaneous hypertension and a defect of ascorbic acid biosynthesis. Blood pressure in mature SHR-od fed an ascorbic acid-supplemented diet is over 190-200 mmHg, while it decreased to around 120 mmHg at 4-5 weeks after the cessation of ascorbic acid supplementation. With regard to possible mechanisms of blood pressure lowering, we focused on catecholamine synthesis in adrenal glands, since catecholamine is a major factor for blood pressure regulation and ascorbic acid is a co-factor of dopamine beta-hydroxylase (DBH) in catecholamine biosynthesis. Male SHR-od (25-week-old) and normotensive ODS rats with a defect in ascorbic acid biosynthesis (25-week-old) were fed a Funabashi-SP diet with or without ascorbic acid (300 mg/kg diet) for 28 days or 35 days. In SHR-od, systolic blood pressure (191 +/- 6 mmHg) began to decrease from day 21 in the ascorbic acid-deficient group, whereas no significant difference was found in ODS rats. In spite of significant lowering of blood pressure, no significant differences were found in catecholamine levels in serum, adrenal glands and brain on day 28. On day 35, however, urinary excretion of norepinephrine and epinephrine in the ascorbic acid-deficient SHR-od were higher at 490% (P < 0.05) and 460% (P < 0.05) of the respective control. Serum catecholamine concentrations and the adrenal catecholamine content tended to be higher in the ascorbic acid-deficient SHR-od than the control of SHR-od and reached to similar level in ODS rats. The administration of ascorbic acid (intraperitoneal injection, 60 mg ascorbic acid/kg body weight, once a day) to the ascorbic acid-deficient SHR-od restored blood pressure to the range 180-190 mmHg within two days. These findings indicate that ascorbic acid deficiency affects catecholamine metabolism in the adrenal glands of SHR-od in response to blood pressure lowering, suggesting catecholamines are not involved in the mechanism for the remarkable reduction in blood pressure in response to ascorbic acid deficiency.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Blotting, Northern; Body Weight; Catecholamines; Diet; Dopamine; Epinephrine; Male; Norepinephrine; Organ Size; Rats; Rats, Inbred SHR; Tissue Distribution

Mild-to-moderate vitamin C depletion in weanling guinea-pigs affects pyridinoline:deoxypyridinoline (collagen cross-link) ratios in femur shaft and urine, attributed to impairment of hydroxylation of collagen lysine. We investigated: (1). whether the picture at two time points is compatible with progressive accumulation of abnormal collagen; (2). whether any changes are seen in skin, where little deoxypyridinoline occurs; (3). whether total food restriction has similar effects. Male weanling Dunkin-Hartley guinea-pigs were fed diets containing either 0.5 (vitamin C-restricted) or 160.0-320.0 (vitamin C-adequate) mg vitamin C/d. Two groups receiving the vitamin C-adequate diet received it ad libitum. Two other groups received the vitamin C-adequate diet in a restricted amount, limited to that which permitted nearly the same growth rate as in the vitamin C-restricted groups. Animals were fed for 4 or 8 weeks; urine was collected, and vitamin C and collagen indices were measured. In the femur shaft, the hydroxyproline content per unit weight was unaffected by vitamin C restriction or by total food restriction. Deoxypyridinoline was increased and the pyridinoline:deoxypyridinoline ratio was decreased in vitamin C-restricted groups, but not in food-restricted groups. Changes in the value of the ratio were greater after 8 than after 4 weeks. Urine indices mirrored bone indices. In skin, the main effect of vitamin C restriction was to reduce hydroxyproline. Here, the cross-link ratios changed less markedly than in bone, and there was less deoxypyridinoline. We conclude that the picture at two time points is compatible with a progressive accumulation of pyridinoline-enriched collagen in vitamin C-deprived animals, that the picture in skin differs from that of bone and urine, and that cross-link changes are not produced by total food restriction.

Topics: Amino Acids; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Bone and Bones; Collagen; Eating; Food Deprivation; Guinea Pigs; Male; Skin

After supplementation trials, vitamin C, iron and zinc levels were increased by 1789%, 59% and 30%, respectively. Partially supplemented pasteurized milk could be a new alternative with its high nutritive value, good sensory properties and low cost.

Topics: Anemia, Iron-Deficiency; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Availability; Child; Child Nutritional Physiological Phenomena; Child, Preschool; Female; Food, Fortified; Humans; Infant; Iron; Male; Milk; Nutritional Status; Turkey; Zinc

The scurvy shows an inflammatory disease and gingival bleeding. Nevertheless, in an animal model for guinea pigs, described by Den Hartog Jager in 1985, scurvy was associated with a motor neuron disease with demyelinization of the pyramidal tract, provoking neurogenic atrophy of muscles. Aiming at searching the protective role of vitamin C in nervous system, a pharmacological, morphological and behavioral study was conducted. Three experimental groups were used: A100, animals receiving 100 mg/ vitamin C/ day; A5.0, animals receiving 5.0 mg/vitamin C/ day; and A0, animals without vitamin C. We analyzed the weight gain, muscular diameter and behavioral tests. In all tests examined, we found significant differences between the supplemented groups in comparison with scorbutic group (p<0.05). Thereafter, the animals were killed for histopathology of gastrocnemius muscle, spinal cord and tooth tissues. In addition, a morphometric study of periodontal thickness and alpha-motor neuron cell body diameter were done. The vitamin C-diet free regimen seemed to induce a disruption in spinal cord morphology, involving the lower motor neuron, as confirmed by a significant reduction in neuron perycaria diameter and muscular atrophy, complicated by increased nutritional deficit.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Guinea Pigs; Motor Neuron Disease; Motor Neurons; Muscle, Skeletal; Spinal Cord; Weight Gain

Gulonolactone oxidase (GLO) is the enzyme responsible for the last step of ascorbic acid biosynthesis. The aim of this study was to investigate the effect of dietary alpha-tocopherol and ascorbic acid on GLO activity in a lower vertebrate, the white sturgeon (Acipenser transmontanus). Both alpha-tocopherol and ascorbic acid modulated renal GLO activity. The increase of dietary levels of alpha-tocopherol and/or ascorbic acid significantly raised the liver concentrations of these two antioxidants and concomitantly lowered kidney's GLO activity. The results suggest that the enzyme of ascorbic acid synthetic pathway responded to the animal's antioxidant status and that its activity was downregulated by alpha-tocopherol. This is the first record of alpha-tocopherol being involved in the regulation of ascorbic acid synthesis. This new observation may provide a hypothesis for the evolutionary loss of GLO expression in teleost fishes.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Down-Regulation; Fishes; Kidney; L-Gulonolactone Oxidase; Liver; Sugar Alcohol Dehydrogenases; Survival Rate

The study was undertaken to determine the intake of vitamin A and C and plasma concentrations of these vitamins among in-school adolescents. The factors affecting the vitamin status of these adolescents were also determined. Data for this report were obtained from a cross-sectional survey of 600 in-school adolescents in Nsukka local government area (LGA) of Enugu State, Nigeria. Ninety and 45 of the adolescents were randomly selected for determining plasma concentrations of vitamin A and C and intake of these vitamins respectively. Dietary assessment was done using a three-day weighed food intake method. Venous blood samples were collected and used for determining plasma vitamin A using the trifluoroacetic acid (TFA) method, while plasma vitamin C was determined by the thiourea method. Values obtained were matched against standards. The intake of vitamin A by all the adolescents was adequate (126-137% of recommended intake), while the intake of vitamin C was inadequate (51-91% of recommended intake). The mean intake of vitamin C was higher among males (23.7 +/- 0.71-27.3 +/- 8.0) than among females (15.3 +/- 2.8-19.5 +/- 5.1). Despite the adequate intake of vitamin A, 40% of the male and 32% of the female adolescents had low plasma concentrations of the vitamin (< 20 microg/dL). On the other hand, concentrations of plasma vitamin C were low among about 47% of these adolescents. Using multiple regression analysis, the two most important variables influencing vitamin A status were household size (b = -0.629; p < 0.0 1) and nutrition knowledge (b = -1.372; p < 0.01), while for vitamin C status, these were household size (b = -0.110; p = 0.05) and age (b = 0.226; p < 0.05). The daytime students had a significantly (p < 0.05) better vitamin A and C status than the boarders. The prevalence of vitamin A and C deficiencies among the adolescents may be more than estimated due to inadequate intake and/or poor bioavailability. This may pose a serious health risk for adolescents. There is, therefore, a need for adequate nutrition education and awareness about healthy lifestyles among Nigerian adolescents.

Topics: Adolescent; Adolescent Nutritional Physiological Phenomena; Adult; Age Distribution; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Cross-Sectional Studies; Female; Humans; Male; Nigeria; Nutritional Status; Regression Analysis; Risk Factors; Sex Distribution; Vitamin A; Vitamin A Deficiency

On the basis of in vitro studies, the antioxidant nutrients vitamins E and C are postulated to interact in vivo.. We developed a guinea pig model to evaluate the combined deficiency of vitamins E and C in vivo.. Weanling guinea pigs were fed a control diet or a vitamin E-deficient diet for 14 d, after which one-half of each group had vitamin C removed from their diet, thus creating 4 diet groups. Some animals were observed for clinical signs. Others were killed for evaluation.. Of 21 guinea pigs that were observed after being fed the diet deficient in both vitamins, 8 died 9 +/- 2 d (x +/- SD) after starting the diet. Eight additional guinea pigs developed a characteristic syndrome at 11 +/- 3 d. First, they became paralyzed in the hind limbs. Within a few hours, the paralysis progressed to include all 4 limbs and caused difficulty in breathing, which would have caused death had the animals not been euthanized. Histopathologic evaluation did not identify a lesion in the muscles or nervous system that could account for the paralysis. Biochemical measurements confirmed the deficiencies and indicated that the double deficiency caused lipid peroxidation in the central nervous system.. A distinct clinical syndrome of combined vitamin E and vitamin C deficiency occurs in guinea pigs. This syndrome indicates that these antioxidant vitamins are related in vivo. We speculate that acute oxidative injury in the central nervous system underlies the clinical syndrome.

Topics: alpha-Tocopherol; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Disease Models, Animal; Guinea Pigs; Male; Osmolar Concentration; Paralysis; Sciatic Nerve; Spinal Cord; Vitamin E Deficiency

The custom of allowing British seamen the regular use of fermented liquor is an old one. Ale was a standard article of the sea ration as early as the fourteenth century. By the late eighteenth century, beer was considered to be at once a food (a staple beverage and essential part of the sea diet), a luxury (helping to ameliorate the hardship and irregularity of sea life) and a medicine (conducive to health at sea). In particular, beer and its precursors, wort and malt, were administered with the aim of preventing and curing scurvy. This paper examines the use of malt and beer during late eighteenth century British sea voyages, particularly their use as antiscorbutic agents, focusing on James Cook's three voyages during the period 1768-1780. Cook administered sweet wort (an infusion of malt), beer (prepared from an experimental, concentrated malt extract), and spruce beer (prepared mainly from molasses), among many other items, in his attempts to prevent and to cure scurvy. Despite the inconclusive nature of his own experiments, he reported favourably after his second voyage (1772-1775) on the use of wort as an antiscorbutic sea medicine (for which purpose it is now known to be useless). Cook thereby lent credibility to erroneous medical theories about scurvy, helping to perpetuate the use of ineffective treatments and to delay the discovery of a cure for the disorder.

Topics: Alcoholic Beverages; Ascorbic Acid; Ascorbic Acid Deficiency; Beer; Edible Grain; England; Famous Persons; Fermentation; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; Humans; Naval Medicine; Scurvy

Golden shiners (Notemigonus crysoleucas) require a dietary source of ascorbic acid (AA) for growth or survival, depending on diet composition. However, no quantitative requirements of golden shiners for AA for growth, health or survival have been determined, and specific deficiency signs have not been observed. The purpose of this study was to determine the effects of different dietary levels of AA on the growth and health of golden shiners fed diets containing 0-218.5 mg AA/kg diet for 10-16 wk. Weight gain, survival and gross deformities were assessed at 10 wk. The remaining fish were fed the same diets from wk 11-16; hematology and alternative complement activity were then assessed and a subset of live fish from each tank was exposed to elevated temperature. Gross deformities appeared in fish fed 0 mg AA/kg diet at 9 wk. The 19.5 mg AA/kg diet was sufficient to prevent the deformities and optimize survival, whereas growth did not differ among treatments. Fish fed 40.3 mg of AA/kg diet had a higher survival rate than fish fed 0 or 19.5 mg AA/kg diet after exposure to elevated temperatures (34-35.5 degrees C). Alternative complement activity and visceral AA concentrations were greater in fish fed diets with 218.5 mg AA/kg than in all other groups. The results indicate that the dietary requirement of AA for golden shiners increases in response to heat stress, and that the alternative complement activity (one index of immune competence) was strongly enhanced in fish fed a diet with approximately 10 times the amount of AA required to prevent deficiency signs.

Topics: Adaptation, Physiological; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Complement System Proteins; Cyprinidae; Heat Stress Disorders

A series of novel acylated ascorbic acid derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids with a branched-acyl chain (6-bAcyl-AA-2G) were recently developed in our laboratory as stable and lipophilic ascorbate derivatives. In this study, the bioavailability of 6-bAcyl-AA-2G was investigated in guinea pigs. Various tissue homogenates from guinea pigs hydrolyzed 6-bAcyl-AA-2G to give ascorbic acid (AA), 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), and 6-O-acyl AA. The releasing pattern of the three hydrolysates suggested that 6-bAcyl-AA-2G was hydrolyzed via 6-O-acyl AA to AA as a main pathway and via AA-2G to AA as a minor pathway. The former pathway seems to be of advantage, because 6-O-acyl AA, as well as AA, can have vitamin C activity. In addition, we found that a derivative with an acyl chain of C(12), 6-bDode-AA-2G, had a pronounced therapeutic effect in scorbutic guinea pigs by its repeated oral administrations. These results indicate that 6-bAcyl-AA-2G is a readily available source of AA in vivo, and may be a promising antioxidant for skin care and treatment of diseases associated with oxidative stress.

Topics: Acylation; Alkaline Phosphatase; alpha-Glucosidases; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Availability; Brain; Esterases; Guinea Pigs; Hydrolysis; Intestine, Small; Kidney; Liver; Scurvy; Weight Loss

The ingestion of dietary antioxidants, including vitamin C (VC), is suggested to play an important role in the prevention of gastric cancer associated with Helicobacter pylori (HP) infection. Recently, water extracts of Tochu (Du-zhong, Eucommia ulmoidea OLIVER) leaves (WETL) have been reported to have potent antioxidant and antimutagenic effects. The present study investigated the effect(s) of VC and WETL on gastric mucosal injury induced by ammonia and a VC deficient diet. Guinea pigs fed the water containing ammonia and/or a VC-deficient diet were simultaneously treated with WETL or VC. Intramucosal levels of thiobarubiturate reactive substances (TBARS), an index of lipid peroxidation, increased significantly in animals fed ammoniated water and VC-deficient diets. This was accompanied by accelerated cell proliferation and increases in immunohistochemical staining indices for oxidative stress-induced DNA adducts and strand breaks (e.g., BrdU-uptake, 8-OhdG, ssDNA and the TUNEL reaction). The administration of either WETL or VC to the ammoniated water and VC-deficient diets ameliorated the increases in intramucosal TBARS levels and labeling indices of BrdU, 8-OHdG, ssDNA and TUNEL, i.e., the levels were similar to those measured in the normal-fed control animals. These data suggest that insufficient VC ingestion may be an important risk factor for gastric cancer development in patients with HP infections. Furthermore, our results suggest that WETL or some constituent may contribute to the prevention of oxidative gastric injury that precedes carcinogenesis.

Topics: Ammonia; Animals; Anti-Ulcer Agents; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Division; Disease Models, Animal; DNA Damage; Drugs, Chinese Herbal; Eucommiaceae; Gastric Mucosa; Guinea Pigs; In Situ Nick-End Labeling; Male; Plant Leaves; Plants, Medicinal; Thiobarbituric Acid Reactive Substances

In March 2002, there were reports of a hemorrhagic fever outbreak in western Afghanistan. It was later confirmed that the hemorrhagic symptoms and increased mortality were actually due to scurvy. Most aid workers did not include scurvy in the initial differential diagnosis because it is uncommon throughout the world and has mainly been reported in refugee populations in recent times. A rapid assessment confirmed the cases clinically, estimated a prevalence rate of 6.3% (a severe public health problem), and determined that the attack rates peaked each year in January and February (the end of the winter). Many Afghans have limited dietary diversity due to isolated locations, lengthy winters, the continuing drought of the last four years, asset depletion, and loss of livelihood. After numerous food and fortification options to prevent future outbreaks had been considered, vitamin C tablet supplementation was selected because of the relatively rapid response time as compared with other prevention methods. A three-month course of vitamin C tablets was distributed to 827 villages in at-risk areas. The tablets were acceptable and compliance was good. No cases of scurvy were reported for the winter of 2002-03. The case study from Afghanistan demonstrates that scurvy can occur in nonrefugee or nondisplaced populations; vitamin C supplementation can be an effective prevention strategy; there is an urgent need to develop field-friendly techniques to diagnose micronutrient-deficiency diseases; food-security tools should be used to assess and predict risks of nutritional deficiencies; and the humanitarian community should address prevention of scurvy in outbreak-prone areas.

Topics: Adolescent; Adult; Afghanistan; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Dietary Supplements; Disease Outbreaks; Humans; Infant; Infant, Newborn; Middle Aged; Oral Hemorrhage; Patient Compliance; Scurvy; Seasons

Transferrin and hemoglobin have been reported to oxidize L-ascorbic acid (AA) in vitro. The aim of this study was to determine whether or not physiological concentrations of serum transferrin (reference range 22-45 micromol/L) and hemoglobin (reference range 0-3.0 micromol/L) interfer with the measurement of AA in the serum. Transferrin (33 to 41 micromol/L) and hemoglobin (1.9 micromol/L) added to freshly pooled serum significantly decreased measured AA in the serum (p < 0.05). However, we found that the magnitude of the decrease in AA due to transferrin at concentrations within the reference range or up to 80 micromol/L was inconsequential, and had no clinical importance in diagnosing a low AA concentration. Hemoglobin at concentrations within the reference range had little affect on the serum AA measurement. However, when serum specimens were stored at 4 degrees C for more than 1.5 h, the magnitude of the decrease in AA due to hemoglobin at physiological concentrations may cause a misleading clinical diagnostic evaluation of low AA concentration.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Blood Specimen Collection; Hemoglobins; Humans; Oxidation-Reduction; Reference Values; Time Factors; Transferrin

Ascorbic acid (AA) recycling, i.e. the intracellular regeneration of AA from its oxidized forms semidehydroascorbyl radical and dehydroascorbic acid (DHA), presumably has a key function in maintaining redox homeostasis. Like humans, guinea pigs cannot synthesize AA. In the present paper, the effects of severe AA deficiency on the AA recycling capacity in erythrocytes (RBCs) and liver homogenates were studied in young and mature guinea pigs. Twelve animals of each age category were divided into weight-matched groups of six animals and fed either an AA deficient or sufficient diet. After 5 weeks, they were sacrificed and RBC and liver ascorbate recycling was estimated along with glutathione, tocopherols, AA, SOD, and malondialdehyde (MDA). For young animals, AA recycling capacity was significantly increased in RBCs from the deficient group as compared to the controls (p < 0.001). RBC MDA was not increased by incubation with t-butylhydroperoxide (TBH) while the initial MDA level was significantly elevated (p < 0.001). In mature animals, neither RBC recycling nor MDA levels depended on AA status. Liver recycling capacity was not affected by age or diet, while liver MDA was significantly higher in young but not in mature deficient animals compared to respective controls (p < 0.01). In young animals, incubation with TBH resulted in significant MDA formation in the deficient compared to sufficient animals in both liver and RBCs (p < 0.05). RBC glutathione was not significantly changed by age or diet indicating that the observed changes in recycling capacity are enzyme dependent. The results suggest that young guinea pigs may have a more adaptable antioxidant defense system compared to mature animals while also being more susceptible to oxidative stress.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Catalase; Dose-Response Relationship, Drug; Erythrocytes; Glutathione; Guinea Pigs; Lipid Peroxidation; Liver; Male; Malondialdehyde; Oxidative Stress; Superoxide Dismutase; Vitamin E

The effects of vitamin C and/or E deficiency on lipoprotein metabolism were investigated in the inherently scorbutic Osteogenic Disorder Shionogi (ODS) rat. In the vitamin C-deficient (C-def) group, marked increases in plasma VLDL and LDL cholesterol were observed (by comparison with the vitamins C- and E-sufficient control group). In rats kept deficient in both vitamin C and vitamin E (C,E-def), LDL cholesterol was significantly higher than in the C-def group even though the levels of VLDL and HDL cholesterol were similar between the two groups. TBARS values for the LDL fraction in the C-def group were of the same magnitude as in the E-def group, and these values were significantly higher than those obtained for the control group. In the C,E-def group, the values were even higher than in the E-def and C-def groups. The nondenatured PAGE of the LDL fraction indicated the appearance of HDLc in the C-def and C,E-def groups. The SDS-PAGE of the LDL fraction showed increased apo B-48 in the C-def and C,E-def groups and increased apo E in the C,E-def group. Decreased plasma LCAT activity in the E-def, C-def, and C,E-def groups indicated an alteration in HDL metabolism as a result of oxidation. These results suggest that lipid peroxidation and some distinct features of lipoprotein metabolism resulting from vitamin C deficiency become more significant when vitamin E is also deficient along with vitamin C deficiency.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cholesterol, LDL; Cholesterol, VLDL; Lipids; Lipoproteins; Male; Random Allocation; Rats; Rats, Inbred Strains; Rats, Mutant Strains; Thiobarbituric Acid Reactive Substances; Vitamin E; Vitamin E Deficiency

The bioavailability of a series of novel acylated ascorbic acid derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids (6-Acyl-AA-2G), as an ascorbic acid (AA) supplement was investigated in rats and guinea pigs. Oral administration of 6-Acyl-AA-2G to rats resulted in an increase in the plasma AA level. However, the intact form was not detectable in the plasma by high-performance liquid chromatography, indicating its hydrolysis through the process of absorption. After an intravenous injection to rats of 6-Octa-AA-2G as a representative derivative, the intact form rapidly disappeared from the plasma, being followed by a prolonged and marked elevation of the plasma AA level. Various tissue homogenates from guinea pigs were examined for their releasing activity of AA, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) and 6-O-acyl-AA from 6-Acyl-AA-2G. High activity was observed in the small intestine. These hydrolytic activities to AA and 6-O-acyl-AA were completely inhibited by castanospermine, an alpha-glucosidase inhibitor, and AA-2G was observed as the only resulting hydrolysate, suggesting the participation of alpha-glucosidase and esterase in the in vivo hydrolysis of 6-Acyl-AA-2G. 6-Octa-AA-2G was found to exhibit an obvious therapeutic effect in scorbutic guinea pigs from its repeated oral administration. These results indicate that 6-Acyl-AA-2G is a readily available source of AA activity in vivo, and may be useful as an effective pharmacological agent and as a promising food additive.

Topics: alpha-Glucosidases; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Availability; Brain; Dietary Supplements; Esterases; Guinea Pigs; Hydrolysis; Intestine, Small; Liver; Male; Rats; Rats, Wistar; Scurvy; Skin

Topics: Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Beverages; Biological Availability; Citrus; Dehydroascorbic Acid; Evidence-Based Medicine; Food Handling; Food, Fortified; Humans; Intestinal Absorption; Nutrition Policy; Oxidation-Reduction; United States

To examine interrelationships between (1) dietary habits, (2) socioeconomic and (3) environmental factors, and their impact on plasma retinol and plasma ascorbic acid.. Cross-sectional study on adults from Western India.. Rural, semi urban, urban higher/middle/lower socioeconomic regions (HSE/MSE/LSE) having diverse dietary habits and environmental conditions.. A total of 214 men and 108 women (20-50 y), apparently healthy and non-anemic.. Food intake by food frequency questionnaire, weight, height, age, smoking, environmental score, education, income, plasma retinol and plasma ascorbic acid.. Mean plasma retinol in women (24.84+/-5.1 microg/dl) and men (24.75+/-4.53 microg/dl) were not significantly different and 21% had plasma retinol below 20 microg/dl. Mean plasma ascorbic acid in women (0.35+/-0.12 mg/dl) and men (0.30+/-0.12 mg/dl) was similar with 75% having plasma ascorbic acid below 0.4 mg/dl. Vitamin A intake (as retinol equivalent) and plasma retinol showed a significant dose response (P<0.05) but not vitamin C intake and plasma ascorbic acid. Plasma retinol showed significant correlation with income (rho=0.24), education (rho=0.27), and environment (rho=0.21; rho=0.0001). Similar correlations with plasma ascorbic acid were 0.29, 031, -0.23 respectively (P=0.0001). Logistic regression showed education, environment, green leafy vegetables (GLV) and milk intake as predictors of plasma retinol deficiency, while non-sweet fruit intake, education and passive smoking for plasma ascorbic acid deficiency (P<0.05).. Subnormal status of retinol and vitamin C emphasizes the need to increase consumption of fruit, GLV and milk products, and also better education and environment. Avoiding passive smoking demands attention in order to improve levels of these vitamins.. Department of Science and Technology, India (project no. SP/SO/B39/94).

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Cross-Sectional Studies; Dairy Products; Diet Surveys; Dose-Response Relationship, Drug; Educational Status; Female; Humans; India; Life Style; Male; Middle Aged; Nutritional Status; Smoking; Surveys and Questionnaires; Vegetables; Vitamin A; Vitamin A Deficiency

Oxidative stress is thought to play an important role in atherogenesis, suggesting that antioxidants could prevent coronary artery disease. However, the efficacy of vitamin C in reducing atherosclerosis is debatable in humans and has not been tested rigorously in animals.. Gulo(-/-)Apoe(-/-) mice were used to test a hypothesis that chronic vitamin C deficiency enhances the initiation and development of atherosclerosis. These mice are dependent on dietary vitamin C because of the lack of L-gulonolactone-gamma-oxidase and are prone to develop atherosclerosis because of lacking apolipoprotein E. Beginning at 6 weeks of age, the Gulo(-/-)Apoe(-/-) mice were fed regular chow or Western-type diets containing high fat and supplemented with either 0.033 g or 3.3 g/L of vitamin C in their drinking water. This regimen produced mice with chronically low vitamin C (average 1.5 microg/mL in plasma) or high vitamin C (average 10 to 30 microg/mL in plasma). Morphometric analysis showed that within each sex, age, and diet group, the sizes of the atherosclerotic plaques were not different between low vitamin C mice and high vitamin C mice. However, advanced plaques in the low vitamin C mice had significantly reduced amounts of Sirius red-staining collagen (36.4+/-2.2% versus 54.8+/-2.3%, P<0.0001), larger necrotic cores within the plaques, and reduced fibroproliferation and neovascularization in the aortic adventitia.. Chronic vitamin C deficiency does not influence the initiation or progression of atherosclerotic plaques but severely compromises collagen deposition and induces a type of plaque morphology that is potentially vulnerable to rupture.

Topics: Animals; Aorta; Apolipoproteins E; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Glucose; Cholesterol; Cholesterol, HDL; Collagen; Crosses, Genetic; Dietary Fats; Dietary Supplements; Disease Models, Animal; Disease Progression; Female; L-Gulonolactone Oxidase; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Sex Factors; Sugar Alcohol Dehydrogenases; Triglycerides

Diffuse hemorrhage in surgical patients with normal coagulation parameters may be caused by vitamin C deficiency and is rapidly reversed by vitamin C replacement.. Patients treated on a surgical service were entered into a clinical registry over a 12-month period if they experienced diffuse hemorrhage in the face of normal coagulation parameters and a plasma ascorbic acid level < 0.6 mg/dL (normal 0.6-2.0 mg/dL). Oral vitamin C replacement was administered after determination of plasma ascorbic acid level. Response to therapy, including subsequent bleeding events, need for blood transfusions, and demographic data including social and dietary history were retrospectively reviewed from hospital and outpatient clinic records.. Twelve patients with bleeding diatheses and low plasma ascorbic acid levels were identified. Plasma ascorbic acid levels were 0.1 to 0.5 mg/dL (mean, 0.3 mg/dL). There were 6 men and 6 women; age ranged from 46 to 90 years (mean, 78 years). Coagulation parameters were normal in all patients. Diffuse postoperative bleeding from nonsurgical causes was evident in 10 of 12 patients. Four patients, 2 of whom had operations, presented with chronic recurrent blood loss from the gastrointestinal tract. Each patient received 250 to 1000 mg of vitamin C replacement daily. Within 24 hours of vitamin C administration, there was no further evidence of clinical bleeding nor need for subsequent blood transfusions in any patient.. Vitamin C deficiency should be included in the differential diagnosis of nonspecific bleeding in surgical patients. Prolonged hospitalization, severe illness, and poor diet create vitamin C deficiency with significant clinical consequences. Oral vitamin C replacement rapidly reverses the effects of this disorder.

Topics: Abdomen; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Surgical Procedures; Diagnosis, Differential; Female; Hemorrhage; Humans; Male; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Retrospective Studies

We examined whether prolonged marginal ascorbic acid deficiency induces oxidative stress in the retina of guinea pigs. Male guinea pigs aged four weeks were given a scorbutic diet (20 g/animal per day) with either marginally deficient ascorbic acid (0.5 mg/animal per day) or adequate ascorbic acid (1 g/animal per day) in drinking water for three and six months. The retinal contents of the reduced form of ascorbic acid in the deficient group at three and six months were 68.1 and 43.5%, respectively, of that in the corresponding adequate group. The retinal contents of the oxidized form of ascorbic acid in the deficient group at three and six months were 1.9- and 2.7-fold, respectively, higher than that in the corresponding adequate group. The content of retinal thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, in the deficient group was 2.5-fold higher than that in the adequate group at six months. The retinal contents of reduced glutathione (GSH) in the deficient group at three and six months were 84.8 and 66.7%, respectively, of that in the corresponding adequate group. The deficient group had 37.5% of retinal vitamin E content of the adequate group at six months. The deficient group had higher serum vitamin E concentration than the adequate group in both experimental periods. There were no differences in serum TBARS and GSH concentrations between the groups at both periods. These results indicate that prolonged marginal ascorbic acid deficiency induces oxidative stress in the retina of guinea pigs without systemic oxidative stress.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Glutathione; Guinea Pigs; Lipid Peroxidation; Male; Nutritional Status; Oxidation-Reduction; Oxidative Stress; Retina; Thiobarbituric Acid Reactive Substances; Time Factors; Vitamin E

To compare the vitamin C content of reconstituted frozen orange juice concentrates at preparation to that of ready-to-drink orange juices purchased 4 to 5 weeks from expiration.. Juices were unsealed and analyzed for reduced and oxidized vitamin C content at the time of purchase and reanalyzed 3 times weekly for 4 to 5 weeks. Same-lot samples of the ready-to-drink juices remained sealed after purchase and were opened for analyses at 3, 2, 1, or 0 weeks before expiration. SAMPLES/SETTING: Orange juices were reconstituted frozen concentrates, ready-to-drink juice packaged in resealable, screw-top containers, or ready-to-drink juice packaged in nonresealable containers. Juices were obtained from local retailers and stored at 4 degrees C in their original containers when appropriate.. The reduced vitamin C content of juices analyzed repeatedly, 3 times weekly for 4 weeks, were compared using repeated measures analysis of variance. Linear regression lines were computed for reduced vitamin C in each juice over time, and differences between slopes were analyzed by oneway analysis of variance.. The orange juices from frozen concentrates contained 86 mg reduced vitamin C per fluid cup at initial preparation and 39 to 46 mg/c after 4 weeks of storage. Ready-to-drink juices averaged significantly lower reduced vitamin C: 27 to 65 mg/c at opening and 0 to 25 mg/c at expiration 4 weeks later. Ready-to-drink orange juices had twofold to threefold higher concentrations of oxidized vitamin C vs the orange juices reconstituted from frozen, and the decomposition rate of reduced vitamin C was similar for all juices, about 2% per day once opened.. Ready-to-drink orange juices should be purchased 3 to 4 weeks before expiration date and consumed within 1 week of opening.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Beverages; Citrus; Food Packaging; Frozen Foods; Humans; Linear Models; Nutritional Requirements; Nutritional Status; Oxidation-Reduction; Time Factors

Vitamin C, E and A levels in maternal and cord blood sera were examined at delivery in two districts of the Czech Republic. Information on personal and social characteristics, health, ethnicity, and lifestyle was also collected. A highly significant correlation between ascorbate levels in maternal and cord blood was found. Vitamin C levels in cord blood were about 1.7 times those in maternal blood. This ratio was much higher for mothers deficient in vitamin C: it was about 3 for deficient nonsmokers and as high as 5 for deficient mothers who smoked cigarettes (p < 0.01). This finding may suggest a compensatory mechanism in fetuses that are endangered by oxidative stress. The mean maternal blood levels of vitamin A and E were higher than in fetal blood (both p < 0.001). The mean fetal/maternal ratios were 0.7 for vitamin A and 0.2 for vitamin E levels; these ratios were considerably higher for mothers deficient in a particular vitamin as compared with those for well-nourished mothers. Ascorbate levels were associated with maternal education and smoking. Significantly decreased vitamin C levels were observed in Gypsy mothers and their babies; this may be attributed to unfavorable diet and smoking habits: about 78% of Gypsy mothers admitted smoking as compared with 31% of Czech mothers.

Topics: Alcohol Drinking; Ascorbic Acid; Ascorbic Acid Deficiency; Czech Republic; Diet; Dietary Supplements; Educational Status; Ethnicity; Female; Fetal Blood; Humans; Infant, Newborn; Pregnancy; Roma; Smoking; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamin E Deficiency

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Chronic Disease; Colitis, Ulcerative; Diagnosis, Differential; Dietary Proteins; Ecchymosis; Fruit; Gastritis; Humans; Male; Middle Aged; Purpura

Inhaled urban particulate matter (PM) often contains metals that appear to contribute to its toxicity. These particles first make contact with a thin layer of epithelial lining fluid in the respiratory tract. Antioxidants present in this fluid and in cells might be important susceptibility factors in PM toxicity. We investigated the role of ascorbic acid (C) and glutathione (GSH) as determinants of susceptibility to inhaled residual oil fly ash (ROFA) in guinea pigs (male, Hartley). Guinea pigs were divided into four groups, +C+GSH, +C-GSH, -C+GSH, and -C-GSH, and exposed to clean air or ROFA (< 2.5 micron diameter, 19--25 mg/m(3) nose-only for 2.0 h). C and/or GSH were lowered by either feeding C-depleted diet (1 microg C/kg diet, 2 weeks) and/or by ip injection of a mixture of buthionine-S,R-sulfoximine (2.7 mmol/kg body weight) and diethylmaleate (1.2 mmol/kg, 2 h prior). Nasal lavage (NL) and bronchoalveolar lavage (BAL) fluid and cells were examined at 0 h and 24 h postexposure to ROFA. The C-deficient diet lowered C concentrations in BAL fluid and cells and in NL fluid by 90%, and the GSH-depletion regimen lowered both GSH and C in the BAL fluid and cells by 50%. ROFA deposition was calculated at time 0 from lung Ni levels to be 46 microg/g wet lung. In unexposed animals, the combined deficiency of C and GSH modified the cellular composition of cells recovered in lavage fluid, i.e., the increased number of eosinophils and macrophages in BAL fluid. ROFA inhalation increased lung injury in the -C-GSH group only (evidenced by increased BAL protein, LDH and neutrophils, and decreased BAL macrophages). ROFA exposure decreased C in BAL and NL at 0 h, and increased BAL C and GSH (2- to 4-fold above normal) at 24 h in nondepleted guinea pigs, but had no effect on C and GSH in depleted guinea pigs. Combined deficiency of C and GSH resulted in the highest macrophage and eosinophil counts of any group. GSH depletion was associated with increased BAL protein and LDH, increased numbers of BAL macrophages and eosinophils, and decreased rectal body temperatures. We conclude that combined deficiency of C and GSH increased susceptibility to inhaled ROFA; caused unusual BAL cellular changes; resulted in lower antioxidant concentrations in BAL than were observed with single deficiencies. Antioxidant deficiency may explain increased susceptibility to PM in elderly or diseased populations and may have important implications for extrapolating animal toxicity data to huma

Topics: Administration, Inhalation; Air Pollutants; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Body Temperature; Bronchoalveolar Lavage Fluid; Carbon; Cell Count; Coal Ash; Disease Models, Animal; Eosinophils; Glutathione; Guinea Pigs; L-Lactate Dehydrogenase; Lung; Lung Diseases; Macrophages, Alveolar; Male; Nasal Lavage Fluid; Neutrophils; Particle Size; Particulate Matter; Survival Rate; Time Factors; Uric Acid

The carried out research of vitamin C status of 250 young people 17-20 years old constantly living in region of the periodic radioactive control of the Gomel region of Republic Byelorussia have shown, that in the spring the vitamin C deficiency is observed at more than 55% examined, and autumn this parameter is reduced approximately on 20%. The vitamin C provision of the women is slightly higher, than one of men. The vitaminization of the population within 1 month by polyvitaminic complexes results in twofold reduction of number examined with vitamin deficiency.

Topics: Adolescent; Adult; Age Factors; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Male; Republic of Belarus; Seasons; Sex Factors

We examined the effect of prolonged marginal ascorbic acid deficiency of the levels of antioxidants and lipid peroxide in lenses of guinea pigs in order to clarify lenticular antioxidant status under ascorbic acid deficiency. Male guinea pigs aged 4 weeks were given a scorbutic diet (20 g/animal per day) with either marginally deficient ascorbic acid (0.5 mg/animal per day) or sufficient ascorbic acid (1 g/animal per day) in drinking water for 3 and 6 months. The deficient group showed no lens opacity during the administration period. The deficient group had 62.3 and 53.9% of lenticular ascorbic acid content in the sufficient group at 3 and 6 months of ascorbic acid deficiency, respectively. There were no differences in lenticular contents of reduced glutathione and thiobarbituric acid reactive substances, an index of lipid peroxidation, between both groups at 3 and 6 months of ascorbic acid deficiency, while the deficient group tended to have higher lenticular vitamin E content than the sufficient group. The deficient group had higher serum vitamin E concentration than the sufficient group at 3 and 6 months of ascorbic acid deficiency. These results indicate that lenticular antioxidant status is maintained well in guinea pigs with prolonged marginal ascorbic acid deficiency, which may result in no cataract formation.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cataract; Glutathione; Guinea Pigs; Lens, Crystalline; Lipid Peroxidation; Male; Nutritional Status; Thiobarbituric Acid Reactive Substances; Vitamin E

Four litters (41 pigs) of cross-bred pigs were studied from 6 to 26 weeks of age. Blood samples were collected at 6, 13, 21 and 26 weeks of age and analysed for contents of vitamin C, calcium (Ca), inorganic phosphorus (P) and alkaline phosphatase (ALP). The pigs were examined clinically for foreleg weakness at the ages of 21 and 26 weeks. At the age of 26 weeks the pigs were slaughtered and the right forelegs were examined macroscopically and selected samples were collected for radiological, histological and ultrastructural examination. The prevalence of foreleg lesions was high, with lesions of dyschondroplasia of the distal growth plate of the ulna in 30 pigs, synovitis of the elbow joint in 24 pigs and osteochondritis dissecans of the elbow joint in 25 pigs. At the ages of 21 and 26 weeks, five pigs had evidently crooked forelegs and 14 pigs (age 21 weeks) and 25 pigs (age 26 weeks) had mildly deformed forelegs. The serum levels of Ca, P and ALP were within normal values for growing-finishing pigs. The range of vitamin C concentrations in plasma showed a wide difference (7.1-49.8 mumol/l) but was not associated with deformed forelegs. The serum concentrations of Ca, P and ALP and the plasma concentration of vitamin C differed significantly (P = 0.05) between age groups and there was a significant (P = 0.001) positive correlation between the levels of vitamin C in plasma and the serum levels of ALP at 6 weeks of age. The aim of the present study was to determine if there was any association between the plasma levels of vitamin C and the extent of crooked or deviated forelegs in growing-finishing pigs. We could not find a vitamin C deficiency during the study and no association between low levels of vitamin C in plasma and the presence of deformed forelegs of these 40 pigs.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Forelimb; Growth Plate; Joints; Male; Swine; Swine Diseases

To investigate the role of vitamin C tissue content as a protective agent during myocardial ischemia-reperfusion injury, we have evaluated the postischemic functional recovery and free radical release of osteogenic disorder Shionogi (ODS) inherently scorbutic rat hearts and compared them to healthy Wistar rat hearts.. Isolated perfused hearts of ODS or Wistar rats underwent 30 min of a global total normothermic ischemia followed by 30 min of reperfusion. The lipid-soluble spin trap alpha-phenyl N-tert-butylnitrone (3 mM) was perfused upstream of the coronary bed. Functional parameters were recorded and samples of coronary effluents were analysed using electron spin resonance spectroscopy to characterise and quantify the amount of radical species released.. From the onset of reperfusion, a large and long-lasting release of alkyl/alkoxyl radicals was detected, with a peak value of 29.0+/-3.2 nM obtained after 13 min, which was associated with a persistent contractile dysfunction. However, ODS rat hearts showed a higher myocardial recovery with lower left ventricular end diastolic pressure (44.34+/-1.74 vs. 55.03+/-1.57 mmHg for Wistar), higher recovery of rate pressure product (12.3+/-1.4 vs. 1.9+/-1.7x10(3) mmHg beats/min for Wistar) and shorter duration of contractile abnormalities during reperfusion (3.7+/-1.0 vs. 20.8+/-5.3 min for Wistar). Moreover, free radical release was identical in ODS rat hearts as compared to control Wistar rats. Ascorbic acid tissue content was significantly altered in ODS rats (31.9+/-3.3 vs. 591.0+/-54.9 mmol/g of tissue for Wistar) but superoxide dismutases, glutathion peroxidases and inducible heat shock protein 70 genes were up-regulated.. This study shows that ascorbic-acid-deficient ODS rat hearts are more resistant to an ischemic insult than control Wistar rats, probably through the development of alternative protective defences, like the induction of heat shock proteins. These paradoxical results raise the question of the relative importance of each endogenous antioxidant in the cardiac resistance to ischemia-reperfusion injury.

Topics: Analysis of Variance; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Electron Spin Resonance Spectroscopy; Free Radicals; Gene Expression Regulation; Glutathione Peroxidase; HSP70 Heat-Shock Proteins; Male; Myocardial Contraction; Myocardial Reperfusion Injury; Myocardium; Oxidative Stress; Perfusion; Rats; Rats, Mutant Strains; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Superoxide Dismutase; Uric Acid; Vitamin E

Previous studies indicate that benzanthrone, an anthraquinone dye intermediate, caused significant depletion of ascorbic acid (AsA). In this investigation the effect of benzanthrone on the status of different forms of AsA and other bio-antioxidants such as glutathione (GSH) was studied. Oral administration of benzanthrone (50, 125 or 250 mg/kg body weight) resulted in a significant increase of urinary AsA levels with a concomitant decrease in the urinary dehydroascorbic acid (DHA) content in both rats and guinea-pigs. Benzanthrone caused a dose-dependent decrease in hepatic, adrenal and serum AsA levels with a subsequent increase in DHA and diketogulonic acid (DKA) levels in both rats and guinea-pigs. Following benzanthrone treatment, rats showed an increase in the scorbutic index (to 1.01-1.21) of the liver, adrenal glands and serum compared to controls (0.12-0.24). The scorbutic indices of liver, adrenal glands and serum were also substantially increased (to 3.61-11.20) in benzanthrone-treated guinea-pigs compared to controls (0.16-0.38). Single oral administration of benzanthrone to guinea-pigs caused a dose-dependent depletion of GSH in liver (15-51%), adrenal glands (27-64%) and serum (32-86%). Furthermore, the depletion of GSH by benzanthrone in rats was of a lesser degree. This suggests that continued exposure of guinea-pigs to benzanthrone may lead to scurvy-type changes in this animal species but not to the same extent in rats, since the latter has the enzymatic capacity to synthesise AsA. Therefore, it can be hypothesised that benzanthrone per se, or its metabolites, interact with reduced GSH thereby causing its depletion. Furthermore, in order to replenish the depleted GSH levels, AsA might be oxidized to DHA and hence the decrease in AsA with the simultaneous increase in DHA was observed.

Topics: 2,3-Diketogulonic Acid; Adrenal Glands; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Benz(a)Anthracenes; Dehydroascorbic Acid; Dose-Response Relationship, Drug; Glutathione; Guinea Pigs; Liver; Male; Rats; Scurvy

Oral intake of ascorbic acid is essential for optimum health in human beings. Continuous ambulatory peritoneal dialysis (CAPD) patients have an increased need for ascorbic acid, because of increased loss through dialysate, reduced intake owing to nausea and loss of appetite, and increased oxidative stress. However, optimum intake is still controversial. We studied 50 clinically stable patients to determine the relationship between oral ascorbic acid intake and serum ascorbic acid (SAA) level. Total oral intake ranged from 28 mg daily to 412 mg daily. Only one patient had an oral intake of ascorbic acid below 60 mg per day. The SAA levels ranged from 1 mg/L to 36.17 mg/L. Although a strong correlation existed between intake and SAA (p < 0.001, R2 = 0.47), the variation in SAA at any given intake level was wide. Of the studied patients, 62% had an SAA < 8.7 mg/L, 40% had an SAA < 5.1 mg/L (below the level in a healthy population), and 12% had a level below 2 mg/L (scorbutic). None of the patients demonstrated clinical manifestations of scurvy. Our results show that, in CAPD patients, ascorbic acid deficiency can be reliably detected only with SAA measurements, and oral intake may influence SAA level. To maintain ascorbic acid in the normal range for healthy adults, daily oral intake needs to be increased above the U.S. recommended dietary allowance to 80-140 mg.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Dietary Supplements; Female; Humans; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

Scurvy has been known since ancient times, but the discovery of the link between the dietary deficiency of ascorbic acid and scurvy has dramatically reduced its incidence over the past half-century. Sporadic reports of scurvy still occur, primarily in elderly, isolated individuals with alcoholism. The incidence of scurvy in the pediatric population is very uncommon, and it is usually seen in children with severely restricted diets attributable to psychiatric or developmental problems. The condition is characterized by perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We describe a case of scurvy in a 9-year-old developmentally delayed girl who had a diet markedly deficient in vitamin C resulting from extremely limited food preferences. She presented with debilitating bone pain, inflammatory gingival disease, perifollicular hyperkeratosis, and purpura. Severe hypertension without another apparent secondary cause was also present, which has been previously undescribed. The signs of scurvy and hypertension resolved after treatment with vitamin C. The diagnosis of scurvy is made on clinical and radiographic grounds, and may be supported by finding reduced levels of vitamin C in serum or buffy-coat leukocytes. The response to vitamin C is dramatic. Clinicians should be aware of this potentially fatal but easily curable condition that is still occasionally encountered among children.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Developmental Disabilities; Diet; Epilepsy; Female; Fruit; Humans; Knee Joint; Magnetic Resonance Imaging; Radiography; Scurvy

Few studies have evaluated the relationship between drugs of abuse consumption and plasma levels of vitamin C. Because of the importance of vitamin C due to its role in prevention of acute and chronic diseases, this study was carried out with the purpose of testing the influence of consumption of drugs of abuse on the plasmatic levels of vitamin C (ascorbic acid) of 56 male chronic users of drugs of abuse with an age range of 16 to 40 years. The following was performed: 1) A survey of consumption to determine the kind, frequency and quantity of drug(s) used and 2) The plasmatic levels of vitamin C in fasting condition, using the Rue and Kuether method. The results obtained showed that 89% of the population under study used drugs for the first time before the age of 18, and 78.4% started with marijuana; 60.7% of them were mixed drug users. The average level of plasmatic ascorbic acid was 0.89 +/- 0.06 mg/dL, nevertheless, according to nutritional category, 76% have values greater than 0.4 mg/dL and 23.2% were at moderated risk (0.35 +/- 0.01 mg/dL) of vitamin C deficiency. Likewise, classifying them in the antioxidant category (according to the suggested values of Gey, 1993) it was obtained that 55.4% had suboptimal or inadequate concentrations to carry out its antioxidant protective function. The length of time of drug's consumption influenced on the ascorbic acid level too. It can be concluded that chronic consumption of drugs of abuse can negatively influence the plasmatic levels of ascorbic acid, leading these patients to a latent condition of vitamin C deficiency. Finally it is necessary to deepen the study of vitamin C levels of users of drugs of abuse.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Chronic Disease; Cross-Sectional Studies; Humans; Male; Substance-Related Disorders; Venezuela

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Hospitalization; Humans; Male; Prevalence

To investigate the effects of ascorbic acid deficiency on the pathogenesis of hypertension and/or its complications, we established a rat strain with both genetic hypertension and a defect of ascorbic acid biosynthesis. The od gene (L-gulono-gamma-lactone oxidase gene) of the ODS (Osteogenic Disorder Shionogi) rat, which is a rat mutant unable to synthesize ascorbic acid, was introduced into spontaneously hypertensive rats (SHR), and a novel congenic strain, SHR-od, was established. SHR-od showed scurvy when fed an ascorbic acid-free diet. Systolic blood pressure of male SHR-od began to increase at 9 weeks of age and reached 190-200 mmHg at 20 weeks of age. In 25-week-old SHR-od, ascorbic acid deficiency when fed an ascorbic acid-free diet for 6 weeks caused a remarkable reduction of blood pressure to lower than 110 mmHg. The wall to lumen ratio of the testicular artery in ascorbic acid-deficient SHR-od was lower than that of the control rats. When rats were fed a diet supplemented with ascorbic acid (300 mg/kg), ascorbic acid concentration in SHR-od was lower in the serum and liver than that in ODS rats. These results indicate that ascorbic acid could be closely related to the development of hypertension in SHR-od. We believe that SHR-od will be a useful model for experimental studies on hypertension and its complications, since all of them suffer from hypertension spontaneously and the level of ascorbic acid deficiency in these rats could be controlled at will both in concentration and duration.

Topics: Aging; Alkaline Phosphatase; Animals; Animals, Congenic; Arteries; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Disease Models, Animal; Epinephrine; Heterozygote; Hypertension; L-Gulonolactone Oxidase; Liver; Male; Norepinephrine; Rats; Rats, Inbred SHR; Rats, Mutant Strains; Sugar Alcohol Dehydrogenases; Testis

Although the coordination of various antioxidants is important for the protection of organisms from oxidative stress, dynamic aspects of the interaction of endogenous antioxidants in vivo remain to be elucidated. We studied the metabolic coordination of two naturally occurring water-soluble antioxidants, ascorbic acid (AA) and reduced glutathione (GSH), in liver, kidney and plasma of control and scurvy-prone osteogenic disorder Shionogi (ODS) rats that hereditarily lack the ability to synthesize AA. When supplemented with AA, its levels in liver and kidney of ODS rats increased to similar levels of those in control rats. Hepato-renal levels of glutathione were similar with the two animal groups except for the slight increase in its hepatic levels in AA-supplemented ODS rats. Administration of L-buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, rapidly decreased the hepato-renal levels of glutathione in a biphasic manner, a rapid phase followed by a slower phase. Kinetic analysis revealed that glutathione turnover was enhanced significantly in liver mitochondria and renal cytosol of ODS rats. Administration of BSO significantly increased AA levels in the liver and kidney of control rats but decreased them in AA-supplemented ODS rats. Kinetic analysis revealed that AA is synthesized by control rat liver by some BSO-enhanced mechanism and the de novo synthesized AA is transferred to the kidney. Such a coordination of the metabolism of GSH and AA in liver and kidney is suppressed in AA-deficient ODS rats. These and other results suggest that the metabolism of AA and GSH forms a compensatory network by which oxidative stress can be decreased.

Topics: Animals; Antimetabolites; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Diseases; Buthionine Sulfoximine; Chelating Agents; Edetic Acid; Glutathione; Indicators and Reagents; Kidney; Liver; Male; Oxidoreductases; Rats; Rats, Inbred Strains; Rats, Wistar

A reduction of dehydroerythorbic acid (DERA) to erythorbic acid (ERA) in vitamin C-deficient guinea pigs was evaluated and compared with that of dehydroascorbic acid (DASA). Thirty-six guinea pigs were fed with vitamin C-deficient diets for 18 days. On day 19, the guinea pigs were divided into four groups for the administration of 100 mg of DERA, ERA, ascorbic acid (ASA), or DASA every day. After 12 days of oral administration, the concentration of DERA, ERA, ASA, and DASA in the liver, adrenal, spleen, kidney, and plasma of guinea pigs was determined by HPLC. A recovery from scurvy was measured in terms of weight gain and serum alkaline phosphatase activity. All four groups showed similar recovery, indicating that the oral administration of relatively high concentrations of DERA reversed the effects of scurvy in vitamin C-deficient guinea pigs. In spite of DERA or DASA administration, ERA or ASA was mainly detected in the tissues. The reduction ratios of DEAR and DASA were similar (approximately 80%) in all tissues except spleen. These results suggest that both DASA and DERA are taken up and reduced to ASA or ERA in vivo.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Dehydroascorbic Acid; Guinea Pigs; Male; Scurvy

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Cause of Death; Female; France; Humans; Male; Nutrition Surveys; Risk Factors

By inactivating the gene for L-gulono-gamma-lactone oxidase, a key enzyme in ascorbic acid synthesis, we have generated mice that, like humans, depend on dietary vitamin C. Regular chow, containing about 110 mg/kg of vitamin C, is unable to support the growth of the mutant mice, which require L-ascorbic acid supplemented in their drinking water (330 mg/liter). Upon withdrawal of supplementation, plasma and tissue ascorbic acid levels decreased to 10-15% of normal within 2 weeks, and after 5 weeks the mutants became anemic, began to lose weight, and die. Plasma total antioxidative capacities were approximately 37% normal in homozygotes after feeding the unsupplemented diet for 3-5 weeks. As plasma ascorbic acid decreased, small, but significant, increases in total cholesterol and decreases in high density lipoprotein cholesterol were observed. The most striking effects of the marginal dietary vitamin C were alterations in the wall of aorta, evidenced by the disruption of elastic laminae, smooth muscle cell proliferation, and focal endothelial desquamation of the luminal surface. Thus, marginal vitamin C deficiency affects the vascular integrity of mice unable to synthesize ascorbic acid, with potentially profound effects on the pathogenesis of vascular diseases. Breeding the vitamin C-dependent mice with mice carrying defined genetic mutations will provide numerous opportunities for systematic studies of the role of antioxidants in health and disease.

Topics: Animals; Antioxidants; Aorta, Thoracic; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Division; Cholesterol; Cholesterol, HDL; Diet; Elastic Tissue; Female; Genotype; Homozygote; L-Gulonolactone Oxidase; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Microscopy, Electron; Muscle, Smooth, Vascular; Mutagenesis, Site-Directed; Rats; Sugar Alcohol Dehydrogenases

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Myocardial Infarction

To determine the contribution of different foods to the estimated intakes of vitamin C among those differing in plasma vitamin C levels, and thereby inform dietary strategies for correcting possible deficiency.. Cross sectional random population survey.. North Glasgow, Scotland, 1992.. 632 men and 635 women, aged 25 to 74 years, not taking vitamin supplements, who participated in the third MONICA study (population survey monitoring trends and determinants of cardiovascular disease).. Dietary and sociodemographic information was collected using a food frequency and lifestyle questionnaire. Plasma vitamin C was measured in non-fasted venous blood samples and subjects categorised by cut points of 11.4 and 22.7 micromol/l as being of low, marginal or optimal vitamin C status. Food sources of dietary vitamin C were identified for subjects in these categories. Plasma vitamin C concentrations were compared among groups classified according to intake of key foods. More men (26%) than women (14%) were in the low category for vitamin C status; as were a higher percentage of smokers and of those in the older age groups. Intake of vitamin C from potatoes and chips (fried potatoes) was uniform across categories; while the determinants of optimal versus low status were the intakes of citrus fruit, non-citrus fruit and fruit juice. Optimal status was achieved by a combined frequency of fruit, vegetables and/or fruit juice of three times a day or more except in older male smokers where a frequency greater than this was required even to reach a marginal plasma vitamin C level.. Fruit, vegetables and/or fruit juice three or more times a day increases plasma vitamin C concentrations above the threshold for risk of deficiency.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Cross-Sectional Studies; Diet; Female; Humans; Life Style; Male; Middle Aged; Scotland; Smoking; Social Class

The risk of vitamin C deficiency is underestimated in industrialized countries and is only disclosed in rare cases of severe scurvy.. We report three cases of scurvy presenting with ecchymotic purpura and hemorrhagic ulcerations of the lower limbs. Vitamin C supplementation led to rapid improvement of the skin lesions.. Clinical diagnosis of low-grade deficiency can be difficult. Biological diagnosis requires special care in sample taking and transport.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Diagnosis, Differential; Ecchymosis; Female; Hemorrhage; Humans; Leg Dermatoses; Leg Ulcer; Purpura; Risk Factors; Scurvy

Low vitamin C status may increase the risk of mortality from cancer and cardiovascular disease.. The objective was to test whether an association existed between serum ascorbate concentrations and mortality and whether the association was modified by cigarette smoking status or sex.. Serum ascorbate concentrations were measured in adults as part of the second National Health and Nutrition Examination Survey (1976-1980). Vital status was ascertained 12-16 y later.. The relative risk (RR) of death, adjusted for potential confounders, was estimated by using Cox proportional hazards models. Men in the lowest (<28.4 micromol/L) compared with the highest (>/=73.8 micromol/L) serum ascorbate quartile had a 57% higher risk of dying from any cause (RR: 1.57; 95% CI: 1.21, 2.03) and a 62% higher risk of dying from cancer (RR: 1.62; 95% CI: 1.01, 2.59). In contrast, there was no increased risk among men in the middle 2 quartiles for these outcomes and no increased risk of cardiovascular disease mortality in any quartile. There was no association between serum ascorbate quartile and mortality among women. These findings were consistent when analyses were limited to nonsmokers or further to adults who never smoked, suggesting that the observed relations were not due to cigarette smoking.. These data suggest that men with low serum ascorbate concentrations may have an increased risk of mortality, probably because of an increased risk of dying from cancer. In contrast, serum ascorbate concentrations were not related to mortality among women.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Neoplasms; Nutrition Surveys; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors; Smoking; United States

To determine vitamin C intakes among adults and to identify differences in dietary intake associated with vitamin C consumption.. This cross-sectional study compared vitamin C intake, nutrient intake, and food group choices of adults with low (<30 mg/d), marginal (30-60 mg/d), and desirable (>60 mg/d) vitamin C intakes.. Data from 2472 men and 2334 women aged 25-75 y were obtained from the 1994-1996 Continuing Survey of Food Intakes by Individuals (CSFII).. Overall, 18% of the sample had low vitamin C intakes, 24% had marginal intakes, and 58% had desirable intakes. In addition to consuming less vitamin C, adults with low vitamin C intakes consumed significantly less (P

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Citrus; Cross-Sectional Studies; Diet; Diet Surveys; Feeding Behavior; Female; Fruit; Humans; Male; Middle Aged; Vegetables

The comparative study of influence of two biologically active food additives with the different contents of vitamins is carried out: a drink "Zolotoi Shar", the dose of vitamins in which makes 50-90% from recommended daily consumption, and "Vitabalance 2000", the contents of vitamins in which at 2-17 of time exceeds need of organism. The use of both additives within 3 weeks resulted in increase of levels of vitamins C, A, E, B2, B6 and carotenoids in blood serum. However if in case of consumption of a drink an authentic level was reached only for vitamin C and beta-carotene, in a case "Vitabalance 2000" for all investigated vitamins except vitamin A. Thus, if the consumption of a drink has lowered frequency of deficiency of 3-4 vitamins, but has not allowed to liquidate it completely, in case of "Vitabalance 2000" consumption the simultaneous deficiency 3-4 vitamins. The received data allow to believe the biologically active food additives containing vitamins in amounts exceeding recommended consumption, are convenient for fast liquidation of hypovitaminoses, and the preparations containing vitamins in doses making 30-50% from need of organism, are acceptable for daily filling of insufficient consumption of vitamins with a usual diet for a long time.

Topics: Adenine; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; beta Carotene; Beverages; Female; Food, Fortified; Humans; Male; Middle Aged; Riboflavin; Time Factors; Vitamin A; Vitamin A Deficiency; Vitamin B Deficiency; Vitamins

Vitamin C has long been a candidate for modulating periodontal disease. Studies of scorbutic gingivitis and the effects of vitamin C on extracellular matrix and immunologic and inflammatory responses provide a rationale for hypothesizing that vitamin C is a risk factor for periodontal disease.. We evaluated the role of dietary vitamin C as a contributing risk factor for periodontal disease utilizing the Third National Health and Nutrition Examination Survey (NHANES III) which is representative of the U.S. civilian, non-institutionalized population.. A sample of 12,419 adults (20 to 90+ years of age), with dental measurements and assessment of dietary information as well as demographic and medical histories were included in the studies. Dietary vitamin C was estimated by a 24-hour dietary record. Individuals with periodontal disease were arbitrarily defined as those who had mean clinical attachment levels of > or =1.5 mm. Using multiple logistic regression analysis, we found a relationship between reduced dietary vitamin C and increased risk for periodontal disease for the overall population (odds ratio [OR] = 1.19; 95% CI: 1.05 to 1.33). Current and former tobacco users who were taking less dietary vitamin C showed an increased risk of periodontal disease with OR of 1.28, 95% CI: 1.04 to 1.59 for former smokers, and an OR of 1.21, 95% CI: 1.02 to 1.43 for current tobacco users. There was a dose-response relationship between the levels of dietary vitamin C and periodontal disease with an OR of 1.30 for those taking 0 to 29 mg of vitamin C per day, to 1.16 for those taking 100 to 179 mg of vitamin C per day as compared to those taking 180 mg or more of vitamin C per day.. Dietary intake of vitamin C showed a weak, but statistically significant, relationship to periodontal disease in current and former smokers as measured by clinical attachment. Those taking the lowest levels of vitamin C, and who also smoke, are likely to show the greatest clinical effect on the periodontal tissues.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Confidence Intervals; Dose-Response Relationship, Drug; Feeding Behavior; Female; Health Surveys; Humans; Logistic Models; Male; Medical Records; Middle Aged; Odds Ratio; Periodontal Attachment Loss; Periodontal Diseases; Population Surveillance; Risk Factors; Smoking

Our recent in vitro results [4] indicate that cigarette smoke induces oxidation of human plasma proteins and extensive oxidative degradation of the guinea pig lung, heart, and liver microsomal proteins, which is almost completely prevented by ascorbic acid. In this paper, we substantiate the in vitro results with in vivo observations. We demonstrate that exposure of subclinical or marginal vitamin C-deficient guinea pigs to cigarette smoke causes oxidation of plasma proteins as well as extensive oxidative degradation of the lung microsomal proteins. Cigarette smoke exposure also results in some discernible damage of the heart microsomal proteins. The oxidative damage has been manifested by SDS-PAGE, accumulation of carbonyl and bityrosine, as well as loss of tryptophan and protein thiols. Cigarette smoke exposure also induces peroxidation of microsomal lipids as evidenced by the formation of conjugated dienes, malondialdehyde, and fluorescent pigment. Cigarette smoke-induced oxidative damage of proteins and peroxidation of lipids are accompanied by marked drop in the tissue ascorbate levels. Protein damage and lipid peroxidation are also observed in cigarette smoke-exposed pair-fed guinea pigs receiving 5 mg vitamin C/animal/day. However, complete protection against protein damage and lipid peroxidation occurs when the guinea pigs are fed 15 mg vitamin C/animal/day. Also, the cigarette smoke-induced oxidative damage of proteins and lipid is reversed after discontinuation of cigarette smoke exposure accompanied by ascorbate therapy. The results, if extrapolated to humans, indicate that comparatively large doses of vitamin C may protect the smokers from cigarette smoke-induced oxidative damage and associated degenerative diseases.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Supplements; Guinea Pigs; Humans; Lung; Male; Microsomes; Myocardium; Oxidative Stress; Proteins; Smoking; Tobacco Smoke Pollution

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; California; Disabled Persons; Female; Humans; Male

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Critical Illness; Hemofiltration; Humans; Trace Elements

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Diet Records; Fruit; Humans; Risk Factors; Vegetables

Maori and Pacific Island ethnic groups in New Zealand have a high risk for gastric cancer. Low levels of gastric juice ascorbic acid (vitamin C) have been suggested to be a risk factor for gastric cancer. Previous studies have shown that gastric juice ascorbic acid may be independently associated with both ethnicity and Helicobacter pylori infection. This study aimed to examine the interrelationship between H. pylori and ethnicity in New Zealand.. Gastric juice was collected into 70% perchloric acid preservative and stored at -80 degrees C. Ascorbic acid was analysed by high-performance liquid chromatography using ion-pair chromatography and electrochemical detection. Inflammation and atrophy was graded from biopsies from multiple sites in the antrum and body. Gastric juice was collected from 89 patients during routine endoscopy.. There was a wide range of measured gastric juice ascorbic acid from 0.001 to 410 microg/mL. The median concentration of ascorbic acid for H. pylori-negative patients was 1.78 microg/mL (n = 57) and 0.12 microg/mL (n = 32) for H. pylori-positive patients (P = 0.001). Gastric juice ascorbic acid concentration was not associated with age, endoscopic diagnosis or intestinal metaplasia, but was significantly associated with the degree of acute inflammation (P = 0.01) and the presence of atrophy (P = 0.04). The median ascorbic acid concentration for European patients was 0.92 microg/mL (n = 44) and 0.09 microg/mL (n = 38) for Maori and Pacific Island ethnic groups combined (P = 0.1). Multiple step-wise regression analysis showed that only H. pylori infection was a significant factor for predicting ascorbic acid concentrations (r2 = 0.12).. This study has confirmed that gastric juice ascorbic acid concentration is lower in the presence of H. pylori infection.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Biopsy; Cross-Cultural Comparison; Female; Gastric Juice; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Native Hawaiian or Other Pacific Islander; New Zealand; Risk Factors; Stomach Neoplasms

High levels of ascorbic acid are known to be present in the aqueous humor of many diurnal species, whereas nocturnal animals have low concentrations of the compound. The purpose of this study was to test the hypothesis that the high concentration of aqueous ascorbate in diurnal animals protects the lens against ultraviolet (UV)-induced damage to the eye. This study compares the effect of UV-B-induced DNA strand breaks on the lens epithelia of guinea pigs and rats after depletion or elevation of aqueous humor ascorbate, respectively.. Eyes of guinea pigs and rats were exposed to UV-B radiation (0.25-0.75 J/cm2 on the cornea) for 10 minutes, and DNA strand breaks in lens epithelium were measured by single-cell gel electrophoresis. Ascorbic acid concentration in the aqueous humor, lens, and lens-capsule epithelium were assayed by spectrophotometric and electrochemical methods. For depletion of aqueous humor and lens ascorbate in guinea pigs, the animals were maintained on an ascorbate-deficient diet. Aqueous ascorbic acid was elevated in the rat by intraperitoneal injections of sodium ascorbate (1 g/kg).. The ascorbate concentration in the aqueous humor of the normal rat was approximately 3% that of the guinea pig, whereas the concentration of the compound in the lens of the normal rat was 10% that of the guinea pig. Guinea pigs fed an ascorbate-deficient diet showed a dramatic drop of more than 80% in aqueous humor ascorbate in the first week, whereas lens ascorbate decreased by approximately 25% during this time period. After a single intraperitoneal injection of sodium ascorbate in the rat, aqueous humor ascorbic acid increased nearly 30 times that in the control, whereas lens ascorbate increased by approximately 30%. The extent of DNA damage in the lens epithelium of a normal rat exposed to UV-B was significantly greater than that occurring in lenses of normal guinea pigs after exposure to the same dose of radiation. Lenses from ascorbate-deficient guinea pigs showed 50% more DNA damage than those from normal guinea pigs after UV exposure, whereas the lenses in ascorbate-injected rats exhibited significant protection against UV-induced DNA strand breaks.. High levels of ascorbic acid in the aqueous humor had a protective effect against UV-induced DNA damage to lens epithelium. The results were consistent with the hypothesis that high ascorbic acid in diurnal animals protects the lens against the cataractogenic effect of UV radiation in sunlight.

Topics: Animals; Aqueous Humor; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; DNA Damage; Epithelium; Guinea Pigs; Lens, Crystalline; Male; Radiation Injuries, Experimental; Rats; Rats, Sprague-Dawley; Ultraviolet Rays

Pigs with hereditary ascorbate deficiency (OD pigs) were depleted of, or supplemented with, ascorbic acid by respective diets. Depletion of young (i.e. 5-7 weeks old) animals for at least three weeks had a negative effect on growth, body temperature and levels of bone alkaline phosphatase and induced symptoms of scurvy. Doses of 5 mg ascorbic acid kg-1 body weight day-1 were sufficient to reverse these effects. The level of ascorbic acid sharply decreased in plasma within one week of depletion, whereas in leukocytes it declined more slowly and to a lower extent. Bone alkaline phosphatase levels substantially declined in ascorbic acid depleted animals. Supplementation with > 100 mg ascorbic acid kg-1 body weight day-1 did not improve growth. Dietary ascorbic acid was absorbed from the intestinal lumen into the blood within less than 1 hour and reached a peak 5-6 hours after the meal. The extent of this absorption depended on the systemic ascorbic acid level. Ascorbic acid influenced leukocyte function, since the production of reactive oxygen intermediates by polymorphonuclear leukocytes decreased in supplemented animals. Thus, this animal model permits to establish the level of dietary ascorbic acid that is critical for growth of pigs as well as to study its absorption into the blood and the associated alterations in polymorphonuclear leukocytes and bone metabolism.

Topics: Alkaline Phosphatase; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Temperature; Bone and Bones; Dietary Supplements; Dose-Response Relationship, Drug; Female; Intestinal Absorption; Male; Neutrophils; Respiratory Burst; Swine; Time Factors; Weight Gain

Diet and the vitamin C status of two samples of college students were examined. Nonsmoking participants were recruited from a campus population during the fall and winter months. The prevalence of vitamin C deficiency (plasma vitamin C concentrations less than 11 mumol/L) ranged from 1% to 2% in the sampled campus populations. Marginal vitamin C status (plasma vitamin C concentrations from 11 to less than 28 mumol/L) was observed in 12% of the fall sample and 16% in the winter sample. Participants with marginal vitamin C status consumed significantly fewer servings of fruits and vegetables daily than participants with adequate vitamin C status. Marginal vitamin C status, which is even more pronounced in smokers, has been associated with fatigue and increased severity of respiratory tract infections. Because the vitamin C status of many college students, both smokers and nonsmokers, may be inadequate, health promotion or wellness programs for all students should emphasize the importance of adequate fruit and vegetable consumption.

Topics: Adult; Arizona; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Feeding Behavior; Female; Fruit; Humans; Male; Nutrition Surveys; Population Surveillance; Prevalence; Risk Factors; Seasons; Sex Distribution; Students; Surveys and Questionnaires; Universities; Vegetables

Topics: Adenocarcinoma; Ascorbic Acid; Ascorbic Acid Deficiency; Gingivitis; Humans; Lung Neoplasms; Male; Middle Aged; Polycythemia Vera; Scurvy

The relations of nutritional factors to lead accumulation in the body were examined cross-sectionally among 747 men aged 49-93 years (mean 67 years) in the Normative Aging Study in 1991-1995. Means (standard deviations) for blood lead, tibia lead, and patella lead were 6.2 (4.1) microg/dl, 21.9 (13.3) microg/g, and 32.0 (19.5) microg/g, respectively. In multiple regression models adjusting for age, education level, smoking, and alcohol consumption, men in the lowest quintile of total dietary intake levels of vitamin D (including vitamin supplements) (<179 i.u./day) had mean tibia and patella lead levels 5.6 microg/g and 6.0 microg/g higher than men with intake in the highest quintile (> or =589 i.u./day). Higher calcium intake was associated with lower bone lead levels, but this relation became insignificant when adjustment was made for vitamin D. The authors also observed inverse associations of blood lead levels with total dietary intake of vitamin C and iron. When analyses were controlled for patella lead, age, smoking, and alcohol consumption, men in the lowest vitamin C intake quintile (<109 mg/day) had a mean blood lead level 1.7 microg/dl higher than men in the highest quintile (> or =339 mg/day), while men in the lowest iron intake quintile (<10.9 mg/day) had a mean blood lead level 1.1 microg/dl higher than men in the highest quintile (> or =23.5 mg/day). This study suggests that low dietary intake of vitamin D may increase lead accumulation in bones, while lower dietary intake of vitamin C and iron may increase lead levels in the blood.

Topics: Aged; Aged, 80 and over; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Bone and Bones; Diet; Disease Susceptibility; Humans; Lead; Male; Middle Aged; Nutritional Status; Reference Values; Vitamin D; Vitamin D Deficiency

We studied the influence of ascorbate (vitamin C) on peripheral blood mononuclear cells (PBMC) of pigs with hereditary deficiency in ascorbate synthesis. Groups of animals were depleted of, or supplemented with dietary ascorbate for up to 5 weeks. B lymphocytes and T lymphocyte subsets differed in the two experimental groups only marginally and transiently as determined by analysis of cell surface markers. The proliferative response of PBMC to B and T lymphocyte mitogens was lower in depleted as compared to supplemented animals. Interleukin (IL)-2 and IL-6 were determined by bioassays and were secreted within few hours after mitogenic activation of PBMC which contained normal physiological concentrations of ascorbate. IL-2 production peaked at about 24 h of in vitro culture after Con A activation, but it lasted for 2-3 days after PWM activation. The production of IL-2 and IL-6 were compared during systemic depletion and supplementation with ascorbate. Depleted PBMC produced IL-2 which accumulated in cultures instead of being rapidly consumed by IL-2 dependent cell growth. This suggests that cellular ascorbate influences the production of IL-2. Secretion of IL-6 by mitogen activated PBMC was also affected by prolonged dietary ascorbate depletion. The results suggest that ascorbate levels exert an early effect on immune homeostasis via reactive oxygen intermediates (ROI)-dependent expression of interleukin genes, since the transcription factor NF-kappa B is sensitive to ROI and regulates the expression of interleukin genes.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; B-Lymphocytes; In Vitro Techniques; Interleukin-2; Interleukin-6; Interleukins; Kinetics; Leukocytes, Mononuclear; Lymphocyte Activation; Mitogens; Phenotype; Reactive Oxygen Species; Swine; Swine Diseases; T-Lymphocytes

The National University of Singapore Heart Study measured cardiovascular risk factors, including selected plasma vitamins, on a random sample of the general population aged 30 to 69 years. Plasma vitamins A and E were normal and similar by ethnic group. Mean plasma vitamin A levels were: Chinese (males 0.68 and females 0.52 mg/L), Malays (males 0.67 and females 0.54 mg/L), and Indians (males 0.66 and females 0.51 mg/L). Mean plasma vitamin E levels were: Chinese (males 12.6 and females 12.6 mg/L), Malays (males 13.6 and females 13.3 mg/L), and Indians (males 12.9 and females 12.8 mg/L). No person had plasma vitamin A deficiency (< 0.01 mg/L) and only 0.1% had vitamin E deficiency (< 5.0 mg/L). In contrast, plasma vitamin C was on the low side and higher in Chinese than Malays and Indians. Mean plasma vitamin C levels were: Chinese (males 6.3 and females 8.4 mg/L), Malays (males 5.1 and females 6.4 mg/L), and Indians (males 5.7 and females 6.9 mg/L). Likewise, the proportions with plasma vitamin C deficiency (< 2.0 mg/L) were lower in Chinese (males 14.4 and females 0.7%), than Malays (males 19.7 and females 7.2%), and Indians (males 17.8 and females 11.0%). Relatively low levels of plasma vitamin C may contribute to the high rates of coronary heart disease and cancer in Singapore. In particular, lower plasma vitamin C in Malays and Indians than Chinese may contribute to their higher rates of coronary heart disease. However, plasma vitamin C does not seem to be involved in the higher rates of cancer in Chinese than Malays and Indians. The findings suggest a relatively low intake of fresh fruits and a higher intake is recommended. Also, food sources of vitamin C may be destroyed by the high cooking temperatures of local cuisines, especially the Malay and Indian ones.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; China; Cooking; Coronary Disease; Ethnicity; Feeding Behavior; Female; Fruit; Heart Diseases; Humans; India; Malaysia; Male; Middle Aged; Neoplasms; Risk Factors; Singapore; Smoking; Vitamin A; Vitamin E; Vitamin E Deficiency

In order to elucidate the effect of L-ascorbic acid (AsA) on the formation of pyridinoline, a mature crosslink of collagen, its content in cartilage collagen of guinea pigs supplemented with and without AsA in the growing process (4-8 weeks of age) and in the period of maturity (10-14 weeks of age) was examined. The AsA-deficient animals, for four weeks during the growing process, had a significantly higher content of pyridinoline in their collagen than the AsA-supplemented group, indicating that the depletion of AsA induced increasing contents of pyridinoline. On the other hand, in the period of maturity, the pyridinoline content in the collagen decreased with age, whereas no difference between AsA-deficient and -supplemented groups was observed. Based on these results, it is assumed that AsA affects the formation of pyridinoline, especially in the growing period.

Topics: Adrenal Glands; Aging; Amino Acids; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cartilage; Collagen; Guinea Pigs; Liver; Male; Weight Gain

The ability of rainbow trout liver and kidney preparations to produce L-ascorbic acid with an added source of L-gulono-gamma-lactone oxidase (GLO) and the absence of their own GLO activity suggested that the reason for the absence of L-ascorbic acid biosynthesis in fish and in guinea pig, a scurvy-prone mammal, can be similar. Nevertheless, results of rat GLO cDNA expression in guinea pig cells and in rainbow trout proved different. In guinea pig cells, rat GLO was expressed in a functional form. Regardless of recombinant GLO transcripts detected in rainbow trout embryos, alevins and in juvenile fish, neither GLO protein nor GLO activity were found. Furthermore, production of L-ascorbic acid in transgenic rainbow trout was not revealed in feeding tests with vitamin C-free diets or after direct administration of L-gulono-gamma-lactone. These results indicate that conditions required for translation or stability of rat GLO are absent in rainbow trout tissues.

Topics: Animals; Animals, Genetically Modified; Ascorbic Acid; Ascorbic Acid Deficiency; Base Sequence; Diet; DNA Primers; DNA, Complementary; Gene Expression; Gene Transfer Techniques; Guinea Pigs; L-Gulonolactone Oxidase; Oncorhynchus mykiss; Polymerase Chain Reaction; Rats; Scurvy; Species Specificity; Sugar Alcohol Dehydrogenases

To determined the prevalence of vitamin C deficiency (plasma vitamin C concentrations less than 11.4 mumol/L) and vitamin C depletion (plasma vitamin C concentrations from 11.4 to less than 28.4 mumol/L) in an outpatient population.. A consecutive sample of patients presenting at a health maintenance organization laboratory for outpatient procedures was utilized. Plasma vitamin C concentrations were determined in 350 females and 144 males, aged 6 to 92 years (mean +/- SD: 46.7 +/- 18.7 years).. The mean plasma vitamin C concentration for all subjects was 32.4 +/- 13.6 mumol/L. Mean plasma vitamin C did not vary by sex, race, or fasted state. Diabetics had a significantly lower mean plasma vitamin C concentration (25.6 +/- 10.8 mumol/L) compared to patients presenting for general check-up/gynecological exams (33.5 +/- 14.8 mumol/L) or pregnancy exams (32.4 +/- 9.7 mumol/L). Six percent of subjects had plasma vitamin C concentrations indicative of vitamin C deficiency (n = 31), and 30.4% of the sample were vitamin C depleted (n = 150). The prevalence of vitamin C deficiency or vitamin C depletion did not differ by race or visit category.. Surprisingly high rates of vitamin C deficiency and vitamin C depletion were evident among generally healthy, middle class patients visiting a health care facility for routine health exams, gynecological exams, and pregnancy exams.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Female; Humans; Male; Middle Aged; Outpatients; Pregnancy

We found that vitamin C is an essential nutrient for an Amazonian ornamental fish, the oscar (Astronotus ocellatus). This was demonstrated by the absence of L-gulonolactone oxidase activity, the enzyme responsible for the biosynthesis of vitamin C, in liver or kidney of oscars and by a feeding trial in which oscars without vitamin C dietary supplementation developed clinical deficiency signs. Fish weighing 29.2 +/- 1.9 g were divided into four groups, and each group was fed a casein-based semipurified diet containing 0, 25, 75 or 200 mg ascorbic acid equivalent (AA)/kg diet for 26 wk. Vitamin C was supplemented in the diets as L-ascorbyl-2-polyphosphate, a mixture of phosphate esters of ascorbate, which is more stable to oxidation than AA. At the end of 26 wk, fish fed no AA had significantly lower weight gain than fish fed the AA-supplemented diets (P < 0.05). Oscars without dietary AA supplementation gained only 37% of their initial weight, compared with 112, 102 and 91% gained by fish fed 25, 75 and 200 mg AA/kg diet, respectively. After 25 wk without dietary supplementation of AA, fish began to develop clinical deficiency signs, including deformed opercula and jaws, hemorrhage in the eyes and fins, and lordosis. Histology indicated that fish without AA supplementation had deformed gill filament support cartilage and atrophied muscle fibers. Collagen content of the vertebral column was significantly lower in fish devoid of dietary AA (P < 0.05). Liver AA concentration varied in proportion to dietary concentration of AA. The minimum dietary AA concentration tested in this study, 25 mg AA/kg diet, was sufficient to prevent growth reduction and AA deficiency signs in oscars.

Topics: Analysis of Variance; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Fishes; Hematocrit; Kidney; L-Gulonolactone Oxidase; Liver; Muscles; Nutritional Requirements; Sugar Alcohol Dehydrogenases

To compare the vitamin C and E plasma levels in patients with Alzheimer's disease (AD) and to assess the vitamin C intake and nutritional status.. Case-control study. Four groups of sex- and age-matched subjects were compared: severe AD and moderate AD, in patients with moderate AD and controls.. Community and hospitalized patients in the region of Toulouse, France.. Patients with dementia who fulfilled criteria for Alzheimer's disease: severe Alzheimer group (N = 20), Mini-Mental State Examination (MMSE) score range 0-9; moderate Alzheimer group (N = 24), MMSE 10-23; hospitalized Alzheimer group (N = 9), MMSE 10-23. Control group (N = 19), MMSE 24-30.. Plasma vitamin E and C were quantified by HPLC-fluorescence. Consumption of raw and cooked fruit and vegetables was evaluated in order to determine the mean vitamin C intakes. Mini Nutritional Assessment (MNA) and plasma albumin were used to measure nutritional status.. Institutionalized and community subjects were analysed separately. MNA scores were normal in home-living Alzheimer subjects with moderate dementia and significantly lower in those with severe disease, despite normal plasma albumin levels. In the home-living Alzheimer subjects, vitamin C plasma levels decreased in proportion to the severity of the cognitive impairment despite similar vitamin C intakes, whereas vitamin E remained stable. The hospitalized Alzheimer subjects had lower MNA scores and albumin levels but normal vitamin C intakes, but their plasma vitamin C was lower than that of community-living subjects. Institutionalized Alzheimer subjects had significantly lower MNA scores but normal vitamin C and albumin levels and vitamin C intakes compared with community-dwelling subjects of similar degree of cognitive impairment.. Plasma vitamin C is lower in AD in proportion to the degree of cognitive impairment and is not explained by lower vitamin C intake. These results support the hypothesis that oxygen-free radicals may cause damage.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Ascorbic Acid; Ascorbic Acid Deficiency; Female; France; Geriatric Assessment; Humans; Male; Mental Status Schedule; Middle Aged; Nutrition Assessment; Reference Values; Social Environment; Vitamin E

The contents of ascorbic acid (AsA) and erythrobic acid (ErA) in the tissues of guinea pigs intraperitoneally injected with AsA and/or ErA were determined to learn the difference in their retention in the tissues. After 10 d of AsA depletion, the guinea pigs were intraperitoneally injected with 5 mg of AsA, or 5 mg of ErA, or 5 mg of each. At day 5 of repletion, the guinea pigs were killed and liver, adrenal glands, spleen, and kidneys were removed. AsA and ErA in these tissues were measured by using HPLC. The contents of AsA in the tissues of only the AsA-injected guinea pigs were similar to those of the AsA- + ErA-injected guinea pigs. The contents of ErA in the tissues of the ErA-injected guinea pigs were higher than those of the AsA- + ErA-injected guinea pigs, but apparently lower than the contents of AsA in the AsA-injected guinea pigs. ErA was scarcely retained in the tissues of guinea pigs.

Topics: Adrenal Glands; Alkaline Phosphatase; Aniline Hydroxylase; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Guinea Pigs; Injections, Intraperitoneal; Kidney; Liver; Male; Spleen; Stereoisomerism

The cytochrome P-450 monooxygenase system plays a central role in the oxidation of a wide variety of structurally unrelated compounds. Its contribution is affected by nutritional and several other factors. Ascorbic acid (AA) deficiency decreases the content of cytochrome P-450 in liver microsomes of guinea pigs (GPs). Included in the group of cytochromes P-450 are the phenobarbital and 3-methylcholanthrene inducible moieties. In the present study the effect of AA status on another specific cytochrome P-450, CYP4A1, laurate omega-hydroxylase was investigated. Ascorbic acid may selectively increase or decrease certain forms of cytochromes. For four weeks adult male Hartley GPs were fed a diet containing 2.5 (Group I), 0.1 (Group II) and 0% (Group III) AA. The liver microsomes were isolated at this stage and cytochrome P-450 content was determined. Group III showed a significant decrease in cytochrome P-450 compared to groups I and II. They also showed a marked decrease in aminopyrine N-demethylase activity. The expression of CYP4A1 was evaluated using Western blot and anti-CYP4A1 antibody. Group III GPs showed a marked decrease in CYP4A1 expression. Groups I and II showed similar expression. This study demonstrates that CYP4A1, a specific cytochrome induced by hypolipidemic agents, is decreased by AA deficiency.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 CYP4A; Cytochrome P-450 Enzyme System; Guinea Pigs; Male; Microsomes, Liver; Mixed Function Oxygenases

The influence of ascorbic acid (AA) on lymphocyte functions was examined in vitro and ex vivo in peripheral blood mononuclear cells (PBMC) of vitamin C-deficient pigs, which are unable to synthesise ascorbic acid. AA is accumulated to physiological levels in PBMC in vitro. The cell proliferation induced by T lymphocyte mitogens was unaltered at all AA concentrations tested (0-400 micrograms/ml, i.e., 0-2.3 mM). Conversely, the response to pokeweed mitogen (PWM) which activates T and B lymphocytes was significantly reduced with increasing intracellular and extracellular AA concentrations. The response to lipopolysaccharide (LPS) showed a tendency to increase at low (9 microM) and was significantly reduced at high AA concentrations (> 36 microM). The IL2 production induced by PWM (but not by concanavalin A (Con A) or phytohemagglutinin (PHA)) decreased at high AA (> 142 microM). In contrast, IL6 production induced by mitogens was not dependent on AA concentrations. In concordance with these results, AA-depleted PBMC which were obtained from pigs that were fed an AA-free diet, displayed an increasing response to LPS and PWM. Collectively, the data indicate that ascorbic acid selectively influences the proliferation of B lymphocytes and negatively acts on IL2 production by T lymphocytes when a threshold of saturation is exceeded.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; B-Lymphocytes; Cells, Cultured; Concanavalin A; Interleukin-2; Interleukin-6; Lipopolysaccharides; Lymphocyte Activation; Lymphocytes; Mitogens; Phytohemagglutinins; Pokeweed Mitogens; Swine; T-Lymphocytes

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Chromatography, High Pressure Liquid; Cystic Fibrosis; Humans; Scurvy; Thiobarbituric Acid Reactive Substances

It has been previously theorized that free-radical reactions led to the first life on Earth, and their ability to randomly cause mutations may have subsequently led to the evolution of life. One of the most efficient free-radical quenchers is ascorbate, which most animals manufacture endogenously. It is generally believed that, approximately 25 million years ago, an ancestor of the Anthropoidea primate suborder, which includes Homo sapiens, lost the ability to produce its own ascorbate, and all descending species inherited this genetic defect. The first of three hypotheses presented here proposes that a genetic defect, caused by either free radicals or a virus, deleted the gene needed by Anthropoidea to manufacture endogenous ascorbate. The second hypothesis proposes that this evolutionary accident permitted large numbers of free radicals to remain metabolically unquenched. The third hypothesis proposes that the presence of these excessive free radicals increased the likelihood of free-radical-induced genetic mutations, and these mutations propelled the evolution of Anthropoidea, leading to Homo sapiens.

Topics: Aging; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Evolution; Free Radicals; Gene Deletion; Haplorhini; Hominidae; Humans; Models, Biological; Mutation

The functional ability of hepatic stimulatory substance (HSS)-stimulated proliferating hepatocytes was investigated by intrasplenic and/or intraportal transplantation in ascorbic acid (AsA) biosynthetic enzyme-deficient (ODS-od/od) rats that die of osteogenic disorders unless there is AsA supplementation. HSS was extracted from regenerating porcine livers. Hepatocytes isolated from the livers of congeneic ODS-+/+ rats that are capable of synthesizing AsA were transplanted into the spleen (Sp-HTx) and/or the portal vein (Pv-HTx) of ODS-od/od rats. The recipients were divided into eight groups as follows: HSS-untreated groups [group Ia, sham-operated, HTx(-); group IIa, Sp-HTx; group IIIa, Pv-HTx; and group IVa, Sp- and Pv-HTx], HSS-treated groups [group Ib, HSS only; group IIb, Sp-HTx + HSS; group IIIb, Pv-HTx + HSS; and group IVb, Sp- and Pv-HTx + HSS]. The recipients were given a diet and water containing AsA for 6 weeks after HTx, and AsA supplementation was then halted. The average bromodeoxyuridine (BrdU) labeling index (LI) and hepatocyte-occupied ratio in the spleen (H/S ratio) of HSS-treated rats were significantly higher than those of HSS-untreated rats. All the rats in HSS-untreated groups and group Ib died by 8 weeks after the cessation of AsA. In HSS-treated groups IIb, IIIb, and IVb, the survival rates were 60%, 50%, and 80%, respectively, at 16 weeks after HTx. The average serum AsA level of the surviving rats in groups IIb, IIIb, and IVb was significantly higher than that in HSS-untreated groups. These results indicate that HSS treatment induced rapid proliferation of transplanted hepatocytes in the spleen and the portal vein, and that these proliferating hepatocytes synthesized AsA and improved the survival rate of ODS-od/ od rats.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Division; Cell Transplantation; DNA; L-Gulonolactone Oxidase; Liver; Male; Rats; Sugar Alcohol Dehydrogenases; Swine

Topics: Animals; Apolipoprotein A-I; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol, HDL; Female; Heart Diseases; Humans; Male; Rats; Sex Characteristics

Porphyria cutanea tarda (PCT), the most common form of porphyria, is manifested as skin photosensitivity caused by excess hepatic production of uroporphyrin and heptacarboxylporphyrin. In experimental animal models, ascorbic acid modulates chemically induced uroporphyrin accumulation. The purpose of this study was to determine whether ascorbic acid is decreased in the plasma of patients with PCT. Plasma was obtained after an overnight fast from 21 PCT patients, 16 of whom were infected with hepatitis C virus (HCV), and from a separate group of 9 patients with HCV infection but not PCT. Thirteen PCT patients were studied when they had active disease and 8 after treatment-induced remission. Plasma ascorbic acid was low (<23 micromol/L) in 11 (85%) of the 13 untreated PCT patients and deficient (<11 micromol/L) in 8 (62%). Two patients with normal ascorbic acid levels (45 and 62 micrommol/L) had consumed multivitamins. In 2 patients with deficient ascorbic acid, plasma levels returned to normal after phlebotomy treatment. Of the 8 patients studied during remission, 4 had normal ascorbic acid values and 4 were deficient (5 to 8 micromol/L). Plasma ascorbic acid values were normal for all patients who had HCV but no PCT. These data suggest that plasma ascorbic acid concentrations are commonly low in PCT, but this decrease is unrelated to HCV infection. Ascorbic acid deficiency may be one of the factors that contributes to the pathogenesis of PCT.

Topics: Adult; Alanine Transaminase; Ascorbic Acid; Ascorbic Acid Deficiency; Aspartate Aminotransferases; Female; Ferritins; Hepatitis C; Humans; Male; Middle Aged; Pilot Projects; Porphyria Cutanea Tarda; Transferrin

To investigate in vivo interactions between antioxidant vitamins C and E, sparing effects of vitamin C on vitamin E as well as those of vitamin E on vitamin C were evaluated using inherently scorbutic [Osteogenic Disorder Shionogi (ODS)] rats. Rats were divided into four groups (control, vitamin E-deficient, vitamin C-deficient and simultaneously vitamins C and E-deficient). The levels of vitamins C and E in tissues were determined at 0, 14 and 21 d of deficiency. On d 14, the vitamin E concentration in plasma, liver, brain and lung of the vitamin C-deficient group was significantly lower than that of the control, in agreement with the literature concerning the sparing of vitamin E by ascorbate. The vitamin E concentration of the vitamin C-deficient group also was significantly lower in plasma, heart, liver, lung and kidney than that of the control group on d 21. On the basis of two-way ANOVA, significant interactions between vitamins C and E were observed on d 21 for vitamin E concentration in these tissues. The ascorbate level in plasma, heart, liver, muscle and kidney of the vitamin E-deficient group was significantly lower than that of the corresponding control group on d 21. Significant interactions between vitamins C and E were observed on d 21 for vitamin C concentration in these tissues. These results suggest a sparing effect of vitamin E on vitamin C, an effect that was observed for the first time in this study. These results suggest that the interaction between vitamins C and E exists in vivo and that the extent of the interaction depends on the tissue. Thiobarbituric acid reactive substances (TBARS) in plasma and liver of the vitamin C-deficient rats were significantly higher than those of the control and the vitamin E-deficient groups on d 21, suggesting that the deficiency of vitamin C caused a larger increase in oxidative stress than the deficiency of vitamin E. TBARS of the liver in rats deficient in both vitamins C and E were significantly higher than those in all other groups, suggesting an additive effect of the deficiencies of vitamins C and E on hepatic TBARS. These data suggest that in vivo, vitamins E and C interact, and each can exert sparing effects in the absence of the other.

Topics: Analysis of Variance; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Drug Interactions; Liver; Male; Rats; Rats, Inbred Strains; Thiobarbituric Acid Reactive Substances; Tissue Distribution; Vitamin E; Vitamin E Deficiency

The effects of ascorbic acid (AA) or vitamin C in atherosclerosis has attracted considerable attention; however results of clinical studies are conflicting. Several studies indicate an increase in plasma triglyceride (TG) and cholesterol (CH) levels in guinea pigs (GP) that have been fed a diet containing a minimal amount of AA. Previous studies carried out in GP fed a diet devoid of AA showed a significant decrease in cytochrome P-450 level compared to GP fed high and adequate amounts; however, the level of cytochrome P-450 in the two groups were not significantly different. The enzymes that synthesize TG and CH are located in endoplasmic reticulum which is also the site for cytochrome P-450 synthesis. It is of interest to determine whether there is an association between TG and CH synthesis and cytochrome P-450 induction. Adult male Hartley GP weighing 350-400 g were fed a diet containing 2.5% (Group I), 0.1% (Group II) and 0% (Group III) AA. The food consumption and weight gain were not significantly different in different groups. After feeding the diet for four weeks, half of the animals in each group were starved. Blood was withdrawn and TG and CH were determined in the serum. TG and CH were markedly elevated in both starved and nonstarved Group III GP; however, these levels were not altered in Group 1 and Group II GP. Plasma AA showed significant differences in all three nonstarved and starved groups. Plasma alpha-lipoprotein was decreased and beta-lipoprotein was increased in Group III GP. Hepatic CH and TG were also significantly elevated in Group III GP, and Groups I and II showed no changes. TG and CH showed a negative correlation with cytochrome P-450, whereas CH and TG showed a positive correlation. We conclude that AA deficiency causes extensive hyperlipidemia, feeding high level of AA does not alter the lipid metabolism and induction ofcytochrome P-450 is inversely related to TG and CH synthesis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Cytochrome P-450 Enzyme System; Enzyme Induction; Guinea Pigs; Hyperlipidemias; Lipoproteins, HDL; Lipoproteins, LDL; Liver; Male; Triglycerides

The evidence for the role of ascorbic acid in gene expression or protein synthesis in vivo is limited. To investigate this role of ascorbic acid, we surveyed proteins whose tissue levels are changed by ascorbic acid deficiency by using ODS rats with a hereditary defect in ascorbic acid biosynthesis. Male ODS rats (7 wk old, body weight approximately 130 g) were fed a basal diet containing ascorbic acid (300 mg/kg diet) or an ascorbic acid-free diet for 14 d. Ascorbic acid deficiency decreased a renal protein with an apparent molecular mass of 17 kDa. The amino-terminal amino acid sequence of 16 residues of this 17-kDa protein was identical to a kidney fatty acid-binding protein known to be generated by proteolytic degradation of alpha2u-globulin, a major urinary protein of adult male rats. alpha2u-Globulin is synthesized in liver, secreted into blood and excreted into urine, but partially reabsorbed by renal proximal tubules. It exists in kidney in a proteolytically modified form. Ascorbic acid deficiency lowered the renal level of kidney fatty acid-binding protein to 53% (P < 0.05) and lowered the serum level of alpha2u-globulin to 52% (P < 0.05) of the level of the control group, but did not affect the amount of alpha2u-globulin excreted into urine. The hepatic level of alpha2u-globulin mRNA of the ascorbic acid-deficient rats was significantly lower (30%) than that of the control rats. These results suggest that in male ODS rats, ascorbic acid deficiency decreases the renal level of kidney fatty acid-binding protein by lowering alpha2u-globulin gene expression in liver.

Topics: Alpha-Globulins; Amino Acid Sequence; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Base Sequence; Blotting, Northern; Carrier Proteins; Disease Susceptibility; DNA Primers; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Female; Gene Expression Regulation; Kidney; Liver; Male; Molecular Sequence Data; Myelin P2 Protein; Neoplasm Proteins; Nerve Tissue Proteins; Rats; Rats, Mutant Strains; Rats, Wistar; RNA, Messenger; Scurvy; Weight Gain

The objective of this study was to determine the impact of limited ascorbate (Asc) availability on type II cell sensitivity to oxidant stress. Guinea pigs were fed diets with or without Asc for 18 days, and type II cells were isolated. Although lung Asc was decreased by 90% in deficient animals (scorbutic), type II cell Asc was decreased by 50%. Upon treatment with 250 microM H2O2, the necrotic injury was twofold greater in scorbutic cells compared with control cells. With 100 microM H2O2 treatment, apoptotic injury was twofold greater in scorbutic cells compared with control cells. Although there was less necrotic injury in cells exposed to 95% O2, the scorbutic cells were more sensitive than control cells. Asc pretreatment protected against necrosis and apoptosis. The Asc analog isoascorbate provided partial protection and suggested that part of the protection was not chemical detoxification but was Asc specific. We conclude that limited Asc availability resulted in a functional type II cell but a cell more sensitive to oxidant-induced injury.

Topics: Animals; Apoptosis; Ascorbic Acid; Ascorbic Acid Deficiency; Epithelial Cells; Guinea Pigs; Hydrogen Peroxide; Kinetics; Lung; Necrosis; Oxidative Stress; Pulmonary Alveoli; Time Factors

In previous studies, we found that the ascorbic acid (AsA) deficiency caused changes in the amounts of the various forms of cytochrome P450 (P450) in liver microsomes from guinea pigs in a form-specific manner. Thus, the aim of this study was to clarify whether the changes seen in the protein contents of the various forms of P450 were associated with the levels of the expression of their mRNAs. Prior to determining the mRNA level, we isolated four cDNA clones, encoding CYP1A2, CYP3A14, CYP3A15, and CYP3A17, from guinea pig liver cDNA libraries to use them as probes in further experiments. The amino acid sequence of the guinea pig CYP1A2 showed identity ranging from 73 to 77% with those of other mammalian P450s. The amino acid sequences among guinea pig CYP3As had about 94% identities with each other. The AsA deficiency apparently decreased the expression of mRNA for CYP1A1 and CYP1A2. These results were in agreement with the decrease in the content of CYP1A1 and CYP1A2 proteins. The amount of P450 protein(s) immunochemically cross-reactive with antibodies to human CYP3A4 was likely unaffected while that of human CYP3A7 tended to be decreased by the AsA deficiency. It suggested that the expression of each CYP3A isozyme was regulated differently by AsA. In fact, the level of mRNA for CYP3A14 was unaffected by the AsA deficiency, while those for CYP3A15 and CYP3A17 were significantly decreased by the AsA deficiency, clearly indicating that the expression of each isozyme within the CYP3A subfamily is differently regulated by AsA. These results support the idea that the transcription of P450 is regulated by AsA in guinea pigs.

Topics: Amino Acid Sequence; Animals; Aryl Hydrocarbon Hydroxylases; Ascorbic Acid; Ascorbic Acid Deficiency; Base Sequence; Blotting, Western; Cloning, Molecular; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Gene Expression Regulation, Enzymologic; Guinea Pigs; Isoenzymes; Liver; Male; Microsomes, Liver; Molecular Sequence Data; Oxidoreductases, N-Demethylating; RNA, Messenger; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Transcription, Genetic

Graded amounts (0, 50, 500 and 5,000 mg/liter) of ascorbic acid (AsA) were given in drinking water to guinea pigs for 21 days to prepare AsA-deficient, low-AsA, moderate-AsA and excess-AsA animals, and the plasma phospholipid hydroperoxide level and lipid concentration were quantitatively determined to investigate the antioxidant effect of AsA in vivo. Phosphatidylcholine hydroperoxide (PCOOH) was a predominant phospholipid hydroperoxide present in the plasma, and the PCOOH concentration was significantly higher in AsA-deficient, low-AsA and excess-AsA animals (80.4 nM, 54.8 nM and 42.2 nM, respectively) as compared with that in moderate-AsA animals (27.2 nM). Hyperlipidemic plasma characterized as high cholesterol and high triacylglycerol concentrations was confirmed in AsA-deficient animals. Molar ratios of plasma AsA and alpha--tocopherol against 10(4) moles of phospholipids were significantly lower in AsA-deficient and low-AsA animals (0.6-2.1 and 5.5-8.5, respectively) than in moderate-AsA and excess-AsA animals (14.2-18.0 and 11.2-11.9, respectively). In plasma, a high correlation coefficient (r = 0.979) was observed between PCOOH and AsA for which there was optimum AsA level to keep the low PCOOH and such correlation was stronger than that (r = 0.558) observed with alpha-tocopherol. The results indicated that AsA has an important function to control the phospholipid hydroperoxide level in plasma and that moderate supplementation of AsA is required to reveal its optimal antioxidant effect in vivo. The present study also showed that AsA-deficiency especially invites an increase in plasma PCOOH together with a hyperlipidemic state which are risk factors in developing atherogenesis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Drinking; Guinea Pigs; Hyperlipidemias; Lipids; Male; Phosphatidylcholines; Triglycerides; Vitamin E; Weight Gain

Topics: Amino Acid Sequence; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Lactoylglutathione Lyase; Molecular Sequence Data

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; History, 20th Century; Scurvy

Ascorbate-deficiency leads to extensive oxidative damage of proteins and protein loss in the guinea pig tissue microsomes as evidenced by sodium dodecyl sulfate polyacrylamide gel electrophoresis, accumulation of carbonyl, bityrosine as well as by tryptophan loss. Oxidative damage is reversed by ascorbate therapy. Oxidative damage in ascorbate deficiency also leads to lipid peroxidation in guinea pig tissue microsomes as evidenced by accumulation of conjugated dienes, malondialdehyde and fluorescent pigment. Lipid peroxides, disappear after ascorbate therapy but not by vitamin E. The observations substantiate the previous in vitro findings that ascorbate specifically prevents oxidative degradation of microsomal membranes. The results indicate that vitamin C may exert a powerful protection against degenerative diseases associated with oxidative damage and play a critical role in wellness and health maintenance.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Guinea Pigs; Kidney; Lipid Peroxidation; Liver; Lung; Malondialdehyde; Microsomes; Oxidative Stress; Proteins; Vitamin E

Wistar Shionogi rats of the (od/od) substrain with the osteogenic disorder are unable to synthesize L-ascorbic acid (L-AA) and appear to be an appropriate animal model for studying the effect of L-AA in carcinogenesis. To determine the minimal L-AA requirements of these animals for prolonged survival in a satisfactory physical condition during experimentation, four concentrations of L-AA (0.33 g/l, 0.67 g/l, 1.67 g/l and 3.33 g/l) were administered via drinking water to four groups of animals (n = 2). Their water intake per cage was recorded three times weekly and the plasma L-AA levels were determined at the start, after 2, 4, 8 and 12 weeks and at the termination of the experiment. To simulate the procedures to be undertaken in oral mucosal carcinogenesis experiments, the animals were gently restrained and a designated amount of sterile NaCl was applied to the palatal mucosa three times a week for 26 weeks. The L-AA supplement group with the lowest concentration (0.33 g/l L-AA) achieved mean plasma levels of 7 +/- 1.38 microM, approximately one-eighth that of the normal level (mean plasma L-AA level in outbred Wistar rats was found to be 58 +/- 3 microM) whilst those in the higher supplement group (3.33 g/l L-AA) achieved a mean of 18 +/- 1.25 microM. All of the animals employed in the present study survived for 26 weeks and showed no clinical signs of L-AA deficiency during this period.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Male; Mouth Neoplasms; Nutritional Requirements; Osteogenesis; Point Mutation; Rats; Rats, Mutant Strains; Rats, Wistar

The purpose of this study was to determine whether carnitine metabolism or histamine degradation would be useful parameters for investigating the optimal requirement for vitamin C.. Twenty-two non-scorbutic subjects with subnormal vitamin C status (plasma vitamin C < 28 mumol/L) were placed on a metabolic diet low in vitamin C for 3 weeks and repleted with graded doses of vitamin C: 10, 30 and 60 mg vitamin C daily (group 1) or 10,125 and 250 mg vitamin C daily (group 2) for weeks 1, 2 and 3, respectively. Fasting blood samples were collected weekly and analyzed for plasma vitamin C, plasma free carnitine and blood histamine.. Group 1 subjects remained in a subnormal vitamin C state throughout the 3-week study, and blood histamine and plasma free carnitine were not impacted by the experimental treatment. Plasma vitamin C in group 2 subjects rose significantly during the study, and these subjects finished the study with an ample vitamin C status indicative of vitamin C intakes above the recommended dietary allowance. Both blood histamine and plasma free carnitine were inversely related to vitamin C status in group 2 subjects.. These data indicate that blood histamine and plasma free carnitine are altered in individuals with subnormal, non-scorbutic vitamin C status and provide evidence that metabolic changes independent of collagen metabolism occur prior to the manifestation of scurvy. Thus utilizing scurvy as an end-point to determine vitamin C requirements may not provide adequate vitamin C to promote optimal health and well-being.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Carnitine; Female; Histamine; Humans; Male; Scurvy

The roles of vitamin C on secondary pathological changes after spinal cord injury were investigated by evaluating the effects of dietary vitamin C on experimental spinal cord injury in a mutant strain of Wistar rats unable to synthesize ascorbic acid (ODS rats). Two groups of ODS rats were given vitamin C-deficient or vitamin C-supplemented diet for 1 week before injury. Motor disturbance induced by spinal cord injury was found to be greater in the vitamin C-deficient group. Histologically, the area of bleeding in the spinal cord was also greater in the vitamin C-deficient group. The levels of ascorbic acid and alpha-tocopherol in the spinal cord tissue and serum decreased during and after compression injury of the spinal cord. The decrease of alpha-tocopherol was similar in the two groups. However, the decrease of ascorbic acid was greater in the vitamin C-supplemented group. These results indicated that their protective effects against spinal cord injury are through scavenging water-soluble free radicals by vitamin C and lipid-soluble by vitamin E, and the effects of these vitamins were suggested to be independent.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Free Radical Scavengers; Hindlimb; Movement; Mutation; Rats; Rats, Wistar; Spinal Cord; Spinal Cord Compression; Thiobarbituric Acid Reactive Substances; Vitamin E

The investigations carried out in 1983-1993 showed increasing of insufficiency of vitamin C and carotene in population of almost all investigated areas of Russian Federation. Insufficiency of vitamin C was found in 70-95%, pronounced deficit in 45-70% of adults. Deficiency of carotene was was detected in 30-90% of adults. Insufficiency of these nutrients is unfavourable long condition detected not only during spring but also in summer in different occupational groups of population. Vitamins A and E nutritional status of different groups of population are good enough in all seasons.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Carotenoids; Female; Humans; Male; Middle Aged; Nutritional Status; Reference Values; Russia; Seasons; Sex Distribution; Time Factors; Vitamin A; Vitamin E

The concentration of ascorbic acid (vitamin C) in the adrenal cortex is higher than in any other organ. The role of vitamin C in the adrenal cortex is unknown, but data obtained with bovine adrenocortical cells in vitro favour its role as an antioxidant that especially protects aldosterone synthesis from damaging lipid peroxides. Alternatively, vitamin C could act as part of an auxiliary electron transport system for the last step of aldosterone synthesis. The effects of vitamin C depletion on adrenocortical function cannot be studied in the human for ethical reasons, so we subjected different groups of guinea pigs to vitamin C depletion, sodium depletion and combined vitamin C and sodium depletion. Other groups of animals on normal or vitamin C-deficient diets received high-dose adrenocorticotrophin (ACTH) injections for 3 days before sacrifice. Fifteen days of a vitamin C-free diet led to very low vitamin C levels in adrenals, liver and plasma without clear signs of scurvy. At this time, plasma aldosterone and aldosterone secretion by isolated adrenal cells were stimulated significantly by sodium deficiency. Simultaneous vitamin C depletion completely abolished the rise in aldosterone in vivo and in vitro, significantly reduced the conversion of [3H]deoxycorticosterone to [3H]aldosterone and impaired renal sodium conservation. Plasma renin activity (PRA), plasma ACTH and serum potassium were not different in the sodium-depleted and sodium plus vitamin C-depleted groups. Sodium depletion did not affect cortisol. Vitamin C depletion led to a significant increase in plasma cortisol without an increase in ACTH, while in vitro secretion of cortisol was slightly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Aldosterone; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Desoxycorticosterone; Diet; Guinea Pigs; Hydrocortisone; Liver; Sodium

Urinary excretions of nitrate and N-nitrosothiazolidine-4-carboxylic acid (N-nitrosothioproline; NTPRO) were determined in rats with osteogenic disordered syndrome (ODS, od/od), lacking L-ascorbic acid (ASC) biosynthesis, after i.p. administration of Escherichia coli lipopolysaccharide (LPS, 1 mg/kg) followed by thiazolidine-4-carboxylic acid (thioproline, 20 mg/rat). L-Ascorbic acid-sufficient ODS rats showed the excretion of nitrate and NTPRO at the levels of 20.3 +/- 7.9 mumol/24h and 369 +/- 111 pmol/24 h respectively, whereas the levels of nitrate and NTPRO in ASC-deficient (scorbutic) rats increased to 54.7 +/- 5.6 mumol/24 h (P < 0.01) and 796 +/- 367 pmol/24 h (P < 0.05) respectively. Administration of L-arginine further increased urinary excretion of nitrate and NTPRO while D-arginine showed no effect. NG-Monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase (NOS), strongly inhibited endogenous formation of both nitrate and NTPRO. These results indicate that increased excretion of NTPRO in ODS rats stimulated by LPS involves induction of NOS leading to an increase in endogenous formation of reactive nitrogen oxides such as N2O3, a potent nitrosating agent at physiological pH conditions. Increased NOS activities in the plasma and various tissues of ODS rats were observed 5 h after treatment with LPS. The possibility of extragastric N-nitroso compound formation in inflammation sites is discussed.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Diseases; Female; Lipopolysaccharides; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitroso Compounds; Rats; Thiazoles; Thiazolidines

The purpose of this study was to investigate suitable sites for hepatocyte transplantation in rats with congenital liver enzyme deficiency. Hepatocytes were isolated from ODS-(+)/+ rats, which are congenic to ODS-od/od rats and have hepatic L-gulonolactone oxidase. A total of 1 x 10(7), 1 x 10(7), and 2.5 x 10(6) hepatocytes were respectively transplanted into the peritoneal cavity, spleen, or portal vein of ODS-od/od rats, which are unable to synthesize ascorbic acid (AsA) due to lack of hepatic L-gulonolactone oxidase. After 4 days of oral pretreatment with 0.05% 2-acetylaminofluorene, recipients underwent 70% partial hepatectomy just before transplantation. AsA administration was discontinued at 6 weeks after transplantation. The symptom-free survival rate and the serum AsA level of recipient rats were determined at 6 weeks after discontinuing AsA administration. The symptom-free survival rate of untransplanted rats and recipient rats with intraperitoneal, intrasplenic and intraportal hepatocyte transplantation were 0%, 0%, 60%, and 100%, respectively. The serum AsA levels were 0.20 +/- 0.20 microgram/ml, 0.14 +/- 0.05 microgram/ml, 1.06 +/- 0.26 microgram/ml, and 1.58 +/- 0.61 microgram/ml, respectively. Intrasplenic or intraportal transplantation was able to cure ODS-od/od rats. A subsequent splenectomy study showed that hepatocytes reaching the liver via the splenic vein following intrasplenic hepatocyte transplantation played a major role in this experimental success.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cell Transplantation; L-Gulonolactone Oxidase; Liver; Male; Peritoneal Cavity; Portal Vein; Rats; Rats, Mutant Strains; Spleen; Sugar Alcohol Dehydrogenases

The vitamin C activity of erythorbic acid (ErA) in ascorbic acid (AsA)-deficient guinea pigs was evaluated. The guinea pigs depleted AsA for 16 days were divided into two groups: one group (control group) was supplemented with 1, 5, or 100 mg/day AsA and the other group (experimental group) was supplemented with 1, 5, 20, or 100 mg/day ErA for 4 days. The contents of AsA and ErA in the tissues of guinea pigs were determined by using HPLC, and the activities of liver aniline hydroxylase, of serum alkaline phosphatase and the content of liver cytochrome P-450 were measured. The AsA tissue content of AsA-supplemented guinea pigs was much higher than the ErA tissue content of ErA-supplemented ones, and also, the activities of liver aniline hydroxylase, of serum alkaline phosphatase and the content of liver cytochrome P-450 of AsA-supplemented animals were much higher than those of ErA-supplemented animals, even when the supplemented amount of ErA was equal to that of AsA. Based on these results, the vitamin C activity of ErA seems to be much lower than that of AsA in the AsA-deficient guinea pigs. This suggested that the apparent vitamin C activity of ErA was dependent on the AsA tissue levels of guinea pigs.

Topics: Adrenal Glands; Alkaline Phosphatase; Aniline Hydroxylase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Guinea Pigs; Liver; Male; Stereoisomerism

It has been reported previously that ozone (O3) toxicity from acute (4 hr) exposure is enhanced by ascorbate (AH2) deficiency in guinea pigs. We hypothesized that lung injury from continuous 1-week O3 exposure would also be increased under conditions of AH2 deficiency because of (1) a diminished antioxidant pool to counteract the oxidant challenge, (2) impaired reparation of tissue injury, and/or (3) altered antioxidant redox homeostasis. Female Hartley guinea pigs (260-330 g) were made AH2 deficient by providing a diet similar to guinea pig chow, but having no AH2. The dietary regimen was started 1 week prior to exposure and was continued during exposure to O3 (0, 0.2, 0.4, or 0.8 ppm, 23 hr/day, 7 days) as well as 1 week post-exposure. Bronchoalveolar lavage (BAL) and tissue AH2 were measured in subgroups at the beginning of exposure (1 week on the AH2-deficient diet), at its termination and 1 week post-exposure. AH2 measured in ear tissue punches proved to be an easy and effective monitor for AH2 deficiency. One week on the AH2-deficient diet caused a 70-80% drop in ear, lung and liver AH2, while AH2 in BAL was decreased by 90%. Immediately after the exposure, total BAL protein and albumin (markers of lung permeability) were increased (approximately 50%) at 0.8 ppm with no difference between the dietary groups. O3 caused an increase in total BAL cells and neutrophils in a concentration-dependent manner with only a slight augmentation due to diet. Exposure to O3 caused an increase in lung and BAL AH2 in normal guinea pigs. Glutathione and uric acid were also increased in the lung and BAL after O3 exposure (40-570%) in both dietary groups, and the levels remained elevated during the recovery period. Lung alpha-tocopherol was not changed due to O3. A significant overall diet-related decrease was seen in AH2-deficient guinea pigs, immediately after the exposure and recovery. In summary, lung injury/inflammation following 1 week O3 exposure and recovery were minimally affected by AH2 deficiency. Antioxidants also appeared to increase in response to O3 exposure despite the deficiency in AH2.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Bronchoalveolar Lavage Fluid; Cell Count; Female; Glutathione; Guinea Pigs; Homeostasis; Lung; Organ Size; Ozone; Uric Acid; Vitamin E

Estimation of cadmium and vitamin C was performed in the blood and lens of smokers in three age groups up to a maximum age of 58, habituated to smoking a minimum of 10 beedies a day for many years, as well as those of non-smokers in the same age groups. Only nuclear cataracts with or without posterior or anterior subcapsular cataract were chosen. It was found that there was a significant accumulation of cadmium in both the blood and the lens of the smokers. Such an accumulation of cadmium might have a role in cataractogenesis in chronic smokers. In a similar experiment, with smokers and non-smokers of two age groups up to a maximum age of 40, both without cataract, increased levels of cadmium were found in the blood of smokers only, though the extent of accumulation was not as high as in chronic smokers of higher age groups. Vitamin C content of lens was on the lower side of normal in both chronic smokers of beedies in the two age groups and non-smokers with nuclear cataract with or without posterior and anterior subcapsular cataract, and there was no significant change brought about by smoking. Vitamin C levels in blood were towards the lower side of the normal in smokers and non-smokers with and without cataract.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Cadmium; Cataract; Cataract Extraction; Double-Blind Method; Humans; Lens, Crystalline; Male; Middle Aged; Risk Factors; Smoking

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Hemophilia A; Hemorrhage; Humans

Since Vitamin C (ascorbate, AH2) is an important airway antioxidant and is an essential component of tissue repair, and since acute (4 hr) O3 toxicity is enhanced by AH2 deficiency, we hypothesized that longer-term O3 effects might also be increased. Female Hartley guinea pigs (260-330 g) were fed either an AH2-sufficient or an AH2-deficient diet 1 week prior to exposure, and were maintained on their respective diets during 1 week of continuous exposure to O3 (0, 0.2, 0.4, and 0.8 ppm, 23 hr/day), and during 1 week postexposure recovery in clean air. The AH2-deficient diet caused lung AH2 to drop to about 30% of control in 1 week, and to below 10% by the end of exposure and recovery. Body weight gains during exposure were decreased in the 0.8 ppm O3 group, while the AH2 deficiency began to affect body weights only during recovery. O3 caused a concentration-dependent decrease in total lung capacity, vital capacity, carbon monoxide diffusing capacity, nitrogen washout, and static compliance, while increasing forced expiratory flow rates and residual or end-expiratory volume (suggestive of pulmonary gas-trapping). The lung/body weight ratio and fixed lung displacement volume were also increased in O3-exposed animals. Lung pathology consisted of mononuclear cell and neutrophil infiltration, airway as well as alveolar epithelial cell hyperplasia, and general decrease in epithelial cell cytoplasm. Thickening of the interstitium and an apparent increase in collagen staining were seen at the terminal bronchiolar regions. Some of these effects were marginally exacerbated in AH2-deficient guinea pigs. One week postexposure to air reversed all O3-induced abnormalities, irrespective of AH2 deficiency. Whole lung hydroxyproline and desmosine were not changed at any time by either O3 or AH2 deficiency. Measurement of lung prolyl hydroxylase activity suggested that AH2 deficiency as well as O3 exposure may have increased the tissue levels of this enzyme. The lack of a significant increase in toxicity with the longer-term exposure scenario suggests that AH2 has minimal influence on other compensatory mechanisms developed over time.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Collagen; Desmosine; Elastin; Female; Guinea Pigs; Hydroxyproline; Lung Diseases; Lung Volume Measurements; Organ Size; Ozone; Procollagen-Proline Dioxygenase; Respiratory Function Tests; Tissue Fixation

Pancreatic islets from young normal and scorbutic male guinea pigs were examined for their ability to release insulin when stimulated with elevated D-glucose. Islets from normal guinea pigs released insulin in a D-glucose-dependent manner showing a rapid initial secretion phase and three secondary secretion waves during a 120-min period. Islets from scorbutic guinea pigs failed to release insulin during the immediate period, and only delayed and decreased responses were observed over the 40-60 min after D-glucose elevation. Insulin release from scorbutic islets was greatly elevated if 5 mM L-ascorbic acid 2-phosphate was supplemented in the perifusion medium during the last 60 min of perifusion. When 5 mM L-ascorbic acid 2-phosphate was added to the perifusion medium concurrently with elevation of medium D-glucose, islets from scorbutic guinea pigs released insulin as rapidly as control guinea pig islets and to a somewhat greater extent. L-Ascorbic acid 2-phosphate without elevated D-glucose had no effect on insulin release by islets from normal or scorbutic guinea pigs. The pancreas from scorbutic guinea pigs contained 2.4 times more insulin than that from control guinea pigs, suggesting that the decreased insulin release from the scorbutic islets was not due to decreased insulin synthesis but due to abnormal insulin secretion.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Transport; Glucose; Glutathione; Glutathione Disulfide; Guinea Pigs; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Male; Perfusion

Low ascorbate concentrations in diabetes may be secondary to inadequate dietary vitamin C intake or may relate to the varied metabolic roles of the vitamin. To determine whether inadequate dietary intake is a factor we calculated daily vitamin C intakes using both a vitamin C questionnaire and a 4-day food diary in a group of 30 patients with Type 2 diabetes (mean age 68.8 +/- 6.9 yr, 17M/13F) and in 30 community controls (mean age 68.0 +/- 5.5 yr, 12M/18F)). Measures of plasma glucose, serum fructosamine, and plasma ascorbic and dehydroascorbic acid were obtained from 20 subjects in each group. There was no significant difference in daily vitamin C intake between the two groups using both methods: food diary, 61.4 +/- 28.3 (patients) vs 69.5 +/- 33.4 (controls) mg; questionnaire, 54.0 +/- 28.9 (patients) vs 65.0 +/- 30.9 (controls) mg. Vitamin C intake derived from both methods was significantly correlated (p < 0.001). Plasma ascorbate (30.4 +/- 19.1 mumol l-1) and dehydroascorbate (27.6 +/- 6.4 mumol l-1) levels were significantly lower in patients vs in controls (68.8 +/- 36.0 and 31.8 +/- 4.8 mumol l-1, respectively), p < 0.0001 and p < 0.01. Plasma ascorbate levels were significantly correlated with vitamin C intake derived from the food diary (p < 0.01) and questionnaire (p < 0.01) methods in the diabetic group only. Low ascorbate levels in diabetes appears to be a consequence of the disease itself and not due to inadequate dietary intake of vitamin C. A short vitamin C questionnaire is a convenient and reliable estimate of vitamin C intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Dehydroascorbic Acid; Diabetes Mellitus, Type 2; Diet; Female; Humans; Male; Middle Aged

Acute zymosan-induced peritonitis in rats produces lung inflammation and lipid peroxidation. The effect of this process on plasma and lung tissue ascorbic acid was determined, as was the effect of infusing 150 mg/kg of ascorbic acid immediately after zymosan on the degree of lung insult. Ascorbic acid levels were significantly decreased in plasma and lung tissue at 24 h after zymosan, and lung tissue conjugated diene and neutrophil content was also significantly increased. Vitamin C infusion increased postzymosan plasma levels by 50% over normal control levels. However, lung tissue ascorbic acid was still decreased, and no decrease in the lung injury process was noted. Added ascorbic acid also did not prevent a decrease in plasma vitamin E with the peritonitis. We conclude that the amount of ascorbic acid given in this study did not diminish the lung oxidant inflammatory changes. An insufficient dose or inadequate time for plasma ascorbic acid to equilibrate with the lung cytosol are possible explanations for the lack of attenuation of lung oxidant stress.

Topics: Acute Disease; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Inflammation; Lipid Peroxidation; Lung; Male; Oxidation-Reduction; Peritonitis; Pulmonary Edema; Rats; Rats, Wistar; Vitamin E; Vitamin E Deficiency; Zymosan

Topics: Animal Husbandry; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Disease Models, Animal; Guinea Pigs; Paper; Wood

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Diet; Female; Fruit; Gingivitis; Grief; Humans; Scurvy; Spain; Vegetables

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cell Division; Graft Survival; L-Gulonolactone Oxidase; Liver; Liver Regeneration; Liver Transplantation; Male; Rats; Rats, Mutant Strains; Spleen; Sugar Alcohol Dehydrogenases; Time Factors; Transplantation, Heterologous

Prior studies have shown that the absorption of dietary nonheme iron in rats is much higher and less responsive to dietary variables than in human subjects. The aim of the present study was to determine whether this dissimilarity is explained by species differences in ascorbic acid status or metabolism. Iron absorption studies were performed with normal rats and with a genetic strain that lacks the ability to synthesize the vitamin. Ascorbic acid deficiency was produced in these animals by removing supplemental vitamin C from the diet for a brief period before the study. Iron absorption was measured from meals tagged extrinsically with 59Fe and measured by whole-body counting. We studied the effect on iron absorption of adding meat, ascorbic acid, soybean, tea, or bran to the test meal. A significant but modest effect of bran on iron absorption was observed in normal rats and of ascorbic acid and tea in ascorbate-depleted animals. However, the overall sensitivity of rats to dietary facilitators or inhibitors of nonheme iron absorption was not altered dramatically by ascorbic acid depletion. The relative insensitivity of rats to dietary factors affecting nonheme iron absorption in humans is not explained by differences in ascorbic acid metabolism between rats and humans.

Topics: Administration, Oral; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Diet; Female; Intestinal Absorption; Iron; Liver; Male; Rats; Rats, Mutant Strains; Rats, Wistar; Species Specificity

The influence of maternal vitamin C deficiency on fetal development was studied in swine with a hereditary lack of ability to synthesize ascorbic acid (OD pigs). Thirteen pregnant sows homozygous (od/od) for the defect were depleted of ascorbic acid for 24 to 38 d at various stages of gestation. Six normal (OD/OD) sows were used as controls. Only a few experimental sows showed clinical symptoms of vitamin C deficiency. Nevertheless, severe pathological changes were seen in the uterus and fetuses. Characteristic findings were hemorrhages and hematomas in both fetal and maternal placenta, and general edema and subcutaneous hemorrhages in the fetuses. Similarities were noted to the abruptio placentae syndrome in women. Depletion of vitamin C resulted in a pronounced decline in ascorbic acid concentration in most maternal and fetal organs as well as in plasma and embryonic fluids. No morphological malformations were found in the fetuses, but the ossification of the skeleton was severely deranged. Macroscopically the lesions comprised swelling of the costochondral junction and separation of the epiphysial cartilage from the spongiosa in ribs and limb bones. Another characteristic finding was loosening of the periost from the cortex, often resulting in subperiosteal bleedings. Microscopically normal osteoblasts were few and the formation of osteoid defective.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone and Bones; Edema; Embryonic and Fetal Development; Female; Fetal Diseases; Fetus; Hematoma; Hemorrhage; Male; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Swine; Swine Diseases; Uterine Diseases; Uterus

We report the case of a 82-year-old man, living in institution, hospitalized for a severe anaemia due to scurvy. Scurvy is rare in Occident. A multifactorial anaemia is usually associated with scurvy, but is rarely symptomatic. Alcoholism favours scurvy and anaemia. Treatment consisted of parenteral vitamin C supplementation associated with blood transfusion.

Topics: Aged; Aged, 80 and over; Alcoholism; Anemia; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Transfusion; Hematoma; Humans; Male

Ascorbic acid (AsA) deficiency causes a decrease in hepatic concentration of cytochrome P-450 and a decrease in hepatic activity of drug-metabolizing enzymes in rats unable to synthesize AsA (ODS rats). To study the mechanism of the decrease in hepatic concentration of cytochrome P-450 isozymes by AsA deficiency, we chose the xenobiotics-inducible cytochrome P-450 and performed the experiments indicated below. AsA-deficient rats were fed polychlorinated biphenyls (PCB) which markedly induce both CYP1A subfamily and several isozymes in CYP2B subfamily. First, we assayed the activities of two drug-metabolizing enzymes so that one could be functionally distinguished from another. AsA deficiency significantly reduced the hepatic activity of aminopyrine-N-demethylase in ODS rats with and without dietary PCB, but had no effect on benzo(a)pyrene hydroxylase activity. Secondly, quantitative immunoblot analyses demonstrated that the levels of CYP2B1/2B2 and CYP1A1 in the AsA-deficiency rats fed PCB were approximately 60 and 80% lower than those found in rats fed AsA-supplemented diet. The degree of reduction in CYP2B1/2B2 was greater than CYP1A1. Thirdly, AsA deficiency caused a decrease in hepatic abundance of CYP2B1/2B2 mRNA, whereas it had no effect on the levels of CYP1A1 and 1A2 mRNA. These results indicated that dietary AsA selectively affects the levels of CYP2B1/2B2 mRNA among cytochrome P-450 induced by PCB and plays important roles for optimum induction of drug-inducible cytochrome P-450. We concluded that AsA deficiency decreases specific froms of drug-inducible cytochrome P-450, especially CYP2B1/2B2 and that the reduction of CYP2B1/2B2 mRNA level in AsA-deficient rats caused a decrease in cytochrome P-450 concentration and hepatic activity of drug-metabolizing enzymes.

Topics: Aminopyrine N-Demethylase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blotting, Western; Cytochrome P-450 CYP2B1; Cytochrome P-450 Enzyme System; Enzyme Induction; Isoenzymes; Liver; Male; Microsomes, Liver; Oxidoreductases; Polychlorinated Biphenyls; Rats; Rats, Mutant Strains; RNA, Messenger

The exact relationship between plaque-induced periodontal diseases and vitamin C deficiency is not known. The aim of this study was to evaluate the possible effect of ascorbic acid (AA) on the severity of periodontal diseases. The periodontal condition of 75 dentulous subjects with a low level of AA in the plasma (< or = 25 mumol/l) was compared with that of 75 control subjects (plasma level > or = 50 mumol/l) matched for age, sex and number of teeth. The subjects were asked to list foods containing AA in their diet, and intake of AA in milligrams per day was calculated. The daily diet of the study subjects contained on average 52 mg +/- 24.9 (SD) of AA, and that of the controls 77 mg +/- 43.2 (SD). For each individual, site-specific recordings for the presence or absence of plaque and supra- and subgingival calculus, filling overhangs, gingival bleeding after probing, probing pocket depth, and gingival recession were made clinically in a double blind examination carried out by one dentist. Five per cent of the subjects in the study group (low plasma level of AA) and 18 per cent of the controls had healthy periodontal tissues. The proportion of sites in which bleeding after probing and a probing pocket depth of 4 mm or over were observed was significantly higher in the study group than in the controls. Sixty per cent of the subjects in the study group and 37 per cent of the controls had pathological pockets of 4 mm or over.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Case-Control Studies; Dental Calculus; Dental Plaque; Diet; Double-Blind Method; Female; Gingival Hemorrhage; Gingivitis; Humans; Male; Middle Aged; Periodontal Diseases; Periodontal Pocket

Trichlorobiphenyl induced only CYP1A2 mRNA, while pentachlorobiphenyl induced both CYP1A2 and CYP2B1 mRNAs in rat liver. The mRNA levels for these P450s were elevated when ascorbic acid-deficient ODS rats (mutant rats with a hereditary osteogenic disorder) were fed a diet supplemented with ascorbic acid. The amount of CYP2B1 mRNA increased rapidly and reached a maximum level of approximately double within 24 hr of injection of pentachlorobiphenyl. Thereafter, the amount of its mRNA decreased to a steady level. This pattern was roughly paralleled by changes in the amount of CYP1A2 mRNA.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Diseases, Developmental; Cytochrome P-450 Enzyme System; Enzyme Induction; Isoenzymes; Liver; Male; Polychlorinated Biphenyls; Rats; Rats, Mutant Strains; RNA, Messenger

The study investigated the possibility of influencing immunotoxic effects of Cd through ascorbic acid. Guinea pigs with high and low intake of ascorbic acid were perorally exposed to cadmium chloride (1 mg Cd/animal/day). The daily vitamin C intake was 2 and 100 mg per animal, respectively. Phagocytic activity of polymorphonuclear leucocytes and monocytes as well as the percentage of active and total T lymphocytes in peripheral blood of animals were evaluated. Five- and 12-week experiments showed a mutual potentiation of negative effects of Cd on the immune system by suboptimal intake of ascorbic acid. Toxic effects of Cd on the immune system can be reduced by a sufficient intake of vitamin C.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cadmium; Cadmium Poisoning; Drug Interactions; Environmental Exposure; Guinea Pigs; Immunity, Cellular; Liver; Lymphocyte Activation; Male; Monocytes; Neutrophils; Organ Size; Phagocytosis; Rosette Formation; Spleen; T-Lymphocytes

Previous studies showed that administration of ascorbate to glutathione (GSH)-deficient newborn rats and guinea pigs prevented toxicity and mortality and led to increased tissue and mitochondrial GSH levels; ascorbate thus spares GSH. In the present work, we tried to answer the converse question: Does administration of GSH spare ascorbate? Because administered GSH is not well transported into most cells, we gave GSH monoethyl ester (which is readily transported and converted into GSH intracellularly) to guinea pigs fed an ascorbate-deficient diet. We found that treatment with GSH ester significantly delays appearance of the signs of scurvy and that this treatment spares ascorbate; thus, the decrease of tissue levels of ascorbate was delayed. The findings support the conclusions that (i) GSH is essential for the physiological function of ascorbate because it is required in vivo for reduction of dehydroascorbate and (ii) there is metabolic redundancy and overlap of the functions of these antioxidants. The sparing effect of GSH in scurvy may be mediated through an increase in the reduction of dehydroascorbate (which would otherwise be degraded) and to antioxidant effects of GSH that are also produced by ascorbate. Other studies indicate that GSH deficiency in adult mice stimulates ascorbate synthesis in liver. During this work we found that administration of GSH itself is highly toxic to ascorbate-deficient guinea pigs when given in divided i.p. doses totaling 3.75 mmol/kg daily.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Glutathione; Guinea Pigs; Kidney; Liver; Lung; Male; Mitochondria; Mitochondria, Liver; Scurvy

We examined the secretion of prolactin (PRL) in the hereditary scurvy-prone Osteogenic Disorder Shionogi (ODS) rat to investigate the role of ascorbic acid (AsA) in pituitary lactotroph and hypothalamic function. Plasma PRL concentrations of conscious AsA-deficient or control ODS rats were measured before and after the administration of metoclopramide (MCP), 5-hydroxy-L-tryptophan (5-HTP) or saline. The basal plasma PRL levels did not differ between the two groups. However, the AsA-deficient rats exhibited significantly larger changes in plasma prolactin concentration in response to MCP or 5-HTP than the control ODS rats. Thus, AsA deficiency enhanced the stimulated, but not the basal, secretion of PRL in ODS rats. Our findings suggest that AsA may have an inhibitory effect on PRL secretion.

Topics: 5-Hydroxytryptophan; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Liver; Male; Metoclopramide; Pituitary Gland; Prolactin; Rats; Rats, Mutant Strains

Previous cross-cultural comparisons of the mortality from ischemic heart disease in European communities with associated plasma levels of essential antioxidants have revealed strong inverse correlations for vitamin E and relatively weak correlations for other antioxidants. Similarly, in a case-control study in Edinburgh low plasma levels of vitamin E were significantly associated with an increased risk of previously undiagnosed angina pectoris whereas low levels of other essential antioxidants lacked statistical significance. The current Basel Prospective Study is particularly well suited to elucidate the impact of antioxidants other than vitamin E. In this population (which was recently evaluated regarding cancer mortality) the plasma levels of vitamins E and A are exceptionally high and above the presumed threshold level of risk for ischemic heart disease. The present 12-year follow-up of cardiovascular mortality in this study reveals a significantly increased relative risk of ischemic heart disease and stroke at initially low plasma levels of carotene (< 0.23 mumol/l) and/or vitamin C (< 22.7 mumol/l), independently of vitamin E and of the classical cardiovascular risk factors. Low levels of both carotene and vitamin C increase the risk further, in the case of stroke even with significance for overmultiplicative interaction. In conclusion, in cardiovascular disease independent inverse correlations may exist for every major essential antioxidant although the latter can also interact synergistically. Therefore future intervention trials of antioxidants in the prevention of ischemic heart disease should primarily test the simultaneous optimization of the status of all principal essential antioxidants.

Topics: Adult; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Carotenoids; Cerebrovascular Disorders; Cohort Studies; Comorbidity; Humans; Male; Myocardial Ischemia; Proportional Hazards Models; Prospective Studies; Risk; Risk Factors; Switzerland; Vitamin A; Vitamin E

Decreased activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolism of cholesterol to bile acids, is known to result in increased biliary cholesterol concentration and supersaturation of bile. Supersaturation of bile by cholesterol is a necessary condition for cholesterol gallstone formation. In guinea pigs, the hepatic concentration of ascorbic acid affects the catabolism of cholesterol: hypovitaminosis C reduces cholesterol 7 alpha-hydroxylase activity. Cholesterol gallstones are frequently found in ascorbic acid-deficient guinea pigs. Risk factors for cholesterol gallstones in humans include obesity, aging, estrogen treatment, pregnancy and diabetes. Plasma ascorbic acid levels are reduced in these groups. Vegetarian diets, which typically have high ascorbic acid contents, protect against gallstones. Since ascorbic acid effects the rate-limiting step in the catabolism of cholesterol in the guinea pig and many human risk groups for cholesterol gallstones are associated with reduced ascorbic acid levels, ascorbic acid may play a contributory role in human gallbladder disease.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile; Cholelithiasis; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Diet, Vegetarian; Guinea Pigs; Humans

Neurolathyrism is a neurological condition seen among people who eat the seeds of Lathyrus sativus (LS) as a principal source of food energy for 2 months or more. It is characterized by severe muscular rigidity and paralysis of the lower limbs. beta-N-Oxalyl-L-alpha,beta-diaminopropionic acid is the principal toxin found in the seed. No experimental animal model for neurolathyrism could be produced by feeding either the seeds or the toxin, although the condition has been known for centuries. We discovered that experimental neurolathyrism could be produced in guinea pigs and primates that needed an external supply of ascorbic acid by making them subclinically deficient in ascorbic acid and feeding them the seeds of LS or extracts thereof. Autoclaving the seeds of LS with lime removes the toxin.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Fabaceae; Food Contamination; Guinea Pigs; Haplorhini; Lathyrism; Male; Muscular Diseases; Plants, Medicinal

This analysis of a large, population based, cross-sectional survey demonstrates that the association of smoking with decreased serum ascorbic acid (AA) levels is independent of the reduced AA intake found in smokers. Smokers have a threefold higher incidence of low serum AA levels (< or = 11 mumol/L) which could place them at increased risk for the clinical manifestations of AA deficiency. Smokers not taking vitamin supplements who consumed less than 15 servings weekly of fruits and vegetables were especially prone to have serum AA levels less than 11 mumol/L. An AA intake of > or = 200 mg was necessary to provide smokers with equivalent protection from hypovitaminosis AA as had nonsmokers whose AA intake exceeded the recommended dietary allowance (RDA [60 mg]). This level of dietary AA intake is considerably higher than the newly increased RDA for smokers of 100 mg. Although the simplest and most direct method to increase the low serum vitamin C levels found in many smokers would be to stop smoking, markedly increasing dietary AA consumption is appropriate when this is unsuccessful. However, if dietary modification fails to sufficiently increase AA intake, then vitamin supplementation may be necessary to significantly reduce the high prevalence of hypovitaminosis AA present in smokers.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Ascorbic Acid; Ascorbic Acid Deficiency; Cross-Sectional Studies; Diet; Female; Humans; Male; Middle Aged; Nutrition Surveys; Nutritional Requirements; Odds Ratio; Prevalence; Regression Analysis; Risk Factors; Scurvy; Smoking; United States

The role of vitamin C in maintaining mucosal health is poorly documented. The purpose of this study was to examine the presence of oral mucosal lesions in subjects with low ascorbic acid (AA) levels in plasma. AA plasma levels of 843 working elderly people in six rural villages in Eastern Finland were determined. All subjects with low plasma AA levels (< or = 25 mumol/l) (n = 106) formed the study group. Controls with normal AA levels (> or = 50 mumol/l) (n = 103) were drawn from the same population. They were matched for age, sex and number of teeth. Oral mucosal lesions in all subjects were recorded clinically using a double-blind method in all subjects. Petechias, leukoplakia and lichenoid lesions were the commonest lesions of the oral mucosa. Only in leukoplakia there was a statistically significant difference between the groups (p < 0.01). Smokers had more leukoplakia than non-smokers. The prevalence of leukoplakia was higher when smoking was combined with AA deficiency.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Double-Blind Method; Female; Humans; Leukoplakia, Oral; Lichenoid Eruptions; Male; Middle Aged; Mouth Diseases; Mouth Mucosa; Prevalence; Purpura; Smoking; Surveys and Questionnaires

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Brain Chemistry; Colorimetry; Guinea Pigs; Liver; Nasal Mucosa; Nose; Rabbits; Rats; Reference Values; Respiratory System

The endogenous formation of N-nitrosoproline (NPRO) and N-nitrosothioproline (NTPRO, N-nitrosothiazolidine-4-carboxylic acid) was studied by monitoring their excretion in the urine of guinea pigs given oral doses of 10 mg proline or thioproline after supplementation with 34 mg (0.4 mmol) sodium nitrate. In order to estimate the conversion of nitrate to nitrite, the animals were also supplemented with 3.5 mg (0.05 mmol) sodium nitrite instead of sodium nitrate. In animals fed commercial diets, the excretion of NPRO and NTPRO under supplementation with sodium nitrate was 2.0 micrograms and 28.7 micrograms/animal/day, respectively, whereas the excretion under supplementation with sodium nitrite was 0.7 micrograms and 13.3 micrograms/animal/day, respectively. The higher excretion of NTPRO than NPRO in each case shows that thioproline is more effective for nitrite trapping than proline. The animals supplemented with nitrate excreted more than twice the amounts of NPRO or NTPRO than those supplemented with nitrite. It is assumed, therefore, that more than 0.1 mmol nitrate is reduced to nitrite and takes part in the endogenous nitrosation of the guinea pig. When various concentrations of L-ascorbic acid (AsA), known to inhibit the formation of N-nitroso compounds, were also administered orally to animals immediately after supplementation with sodium nitrate, the NPRO excretion decreased with increasing AsA concentration. These data indicate that the guinea pig, which is unable to synthesize AsA as well as humans, may be an appropriate animal model for evaluation of the endogenous nitrosation ability of humans ingesting nitrate.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Gastric Acidity Determination; Guinea Pigs; Hydrogen-Ion Concentration; Male; Nitrates; Nitrosamines; Nitrosation; Nitroso Compounds; Proline; Thiazoles; Thiazolidines

Plasma levels of ascorbic acid (AA) and dehydroascorbic acid (DHA) were estimated in 27 patients of end stage renal failure (ESRF) on standard conservative therapy (group A) and 9 patients of ESRF on maintenance haemodialysis (MHD; group B). Fourteen healthy subjects matched for age and sex served as control (group C). The dietary intake of vitamin C was significantly decreased in group A than in group B compared to control. Similarly, plasma AA was significantly lowered to 0.801 +/- 0.283 mg per cent in group A compared to 1.421 +/- 0.47 mg per cent in control. While it was just lowered to 1.058 +/- 0.272 mg per cent in group B. Although plasma level of DHA was raised to 0.243 +/- 0.486 mg per cent and 0.166 +/- 0.54 mg per cent in groups A and B respectively, the increase was not statistically significant. In our present study, the DHA/AA ratio was found to be inversely proportional to the plasma AA. Further, this ratio has been claimed to be a better indicator of overall reducing atmosphere (i.e., profile of vitamin C) of the body.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Dehydroascorbic Acid; Eating; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Uremia

Xerostomia, the subjective feeling of dry mouth, affects millions of people particularly the elderly. It is invariably associated with hypofunction of the salivary glands. The amount, rate of secretion, and composition of saliva are regulated by both sympathetic and parasympathetic receptor systems whose stimulation transmits signals through intracellular messengers (cations, nucleotides, phospholipid derivatives) to structures and enzymes within the cell. Salivary glands express a variety of cell-surface receptors including adrenergic (alpha and beta), muscarinic-cholinergic, substance P, vasoactive intestinal peptide hormone, and ATP receptors. Ascorbate which is present in salivary acinar cells in relatively high concentrations, is closely involved in many cellular functions including the metabolism of pyrimidines, intracellular calcium, the catecholamines and other neurotransmitters which regulate salivary gland exocytosis. Ascorbate-dependent carboxyl-terminal peptide alpha-amidation enzyme similar to the pituitary peptidyl-glycine alpha-amidating monooxygase, is also present in salivary glands. It is therefore not fortuitous that the seemingly unrelated numerous factors like aging, drug ingestion, pregnancy, smoking, ionizing radiation, stress, and various pathological states such as cancer, autoimmune disorders, diabetes mellitus, and hypertension often implicated in the causation of xerostomia, all promote increased tissue requirement for and/or depletion of ascorbate.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Salivary Glands; Xerostomia

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Liver; Liver Transplantation; Rats; Rats, Inbred Strains; Spleen; Transplantation, Heterotopic

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cell Separation; Cells, Cultured; Graft Survival; Liver; Liver Transplantation; Male; Peritoneal Cavity; Portal Vein; Rats; Spleen; Transplantation, Heterotopic

Topics: Animals; Antioxidants; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Disease Models, Animal; Humans; Lipid Peroxidation; Lipoproteins, LDL; Rats; Vitamin E; Vitamin E Deficiency

The effects of dietary ascorbic acid on plasma lipoprotein and liver lipid peroxide concentrations were examined using ODS od/od rats with a genetic defect in the ability to synthesize ascorbic acid. ODS od/od rats were fed purified diets supplemented with 0 to 300 mg ascorbic acid/kg diet for 21 d. An ascorbic acid-free diet induced body weight loss, depleted ascorbic acid in the plasma and increased thiobarbituric acid-reactive substances in the plasma and liver as compared with rats fed ascorbic acid supplemented diets and with normal ODS +/+ rats fed the ascorbic acid-free diet. Increasing ascorbic acid concentration in the diet inhibited the development of these ascorbic acid deficiency symptoms in a dose-dependent manner. The dietary requirement of ascorbic acid to maintain normal body weight gain and plasma lipid peroxide concentrations was approximately 150 mg ascorbic acid/kg diet. On the other hand, even 300 mg ascorbic acid/kg diet was insufficient to maintain a hepatic concentration of ascorbic acid comparable to that in the liver of ODS +/+ rats. The lipid peroxide concentration in plasma LDL and liver was significantly elevated in ODS od/od rats fed the ascorbic acid-free diet. Supplementing the diet with 300 mg ascorbic acid/kg kept those concentrations within the normal ranges seen in the ODS +/+ rats.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Diet; Lipid Peroxidation; Lipid Peroxides; Lipoproteins, LDL; Liver; Male; Rats; Rats, Mutant Strains; Thiobarbiturates; Triglycerides; Weight Gain

Marginally vitamin C-deficient guinea-pigs treated with the diabetogenic agent streptozotocin were compared with those liberally supplied with vitamin C, for functional indices of vitamin C status, particularly in the eye lens. Weanling male Dunkin-Hartley guinea-pigs were fed on diets with 0.1 g vitamin C/kg (marginally deficient), or 5 g/kg (liberally supplied), and some received intraperitoneal streptozotocin (two doses of 150 mg/kg body-weight). About half the streptozotocin-treated animals had high urinary glucose following an oral glucose dose; these animals also grew more slowly than the others. At 4 months after streptozotocin the animals were killed for measurement of tissue vitamin C, glucose and sorbitol. Streptozotocin moderately increased the concentration of glucose in plasma, lens and aqueous humour. Lens sorbitol levels increased only in the group exposed to streptozotocin plus marginal vitamin C. There was a significant (P less than 0.02) positive correlation between urinary glucose and lens sorbitol levels overall. Liberal vitamin C intake may thus counteract the effect of streptozotocin diabetes on lens sorbitol, suggesting a new function of vitamin C, possibly related to cataractogenesis and to the biochemical lesions associated with diabetes.

Topics: Adenosine Triphosphate; Animals; Aqueous Humor; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diet; Glycosuria; Guinea Pigs; Lens, Crystalline; Liver; Male; Sorbitol; Streptozocin; Time Factors

To clarify the relationship of plasma ascorbic acid to cellular ascorbic acid levels, we determined plasma, lymphocyte, buccal cell and semen ascorbic acid in eight healthy men consuming controlled ascorbic acid intakes of 5, 10, 20, 60 or 250 mg/d over 13 wk while living in a metabolic unit. Levels of ascorbic acid in all four specimen types were significantly lower during the three lowest intakes (5, 10, or 20 mg/d) compared with the 60 or 250 mg/d intakes, but only plasma and lymphocyte ascorbic acid levels discriminated between these intakes unequivocally and with no overlap. Priority for maintenance of intracellular lymphocyte ascorbic acid was indicated by rapid repletion of lymphocytes compared with plasma and semen at 60 mg/d intake. Strong correlations of plasma with lymphocyte ascorbic acid within individuals indicated that plasma levels would reliably reflect low lymphocyte levels in nutrition monitoring surveys. Buccal cell ascorbic acid may be useful as a noninvasive screening test for ascorbic acid deficiency. Semen and sperm qualities were unchanged despite an average decline in semen ascorbic acid to 24% of baseline. Short-term ascorbic acid depletion in healthy men did not adversely affect sperm qualities related to fertility nor did moderate supplementation improve them.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Chromatography, High Pressure Liquid; Diet; Fertility; Humans; Leukocytes; Male; Nutritional Status; Semen; Sperm Motility

This study describes the relationship between varying ascorbate intake, periodontal status, and subgingival microflora as part of a multidisciplinary investigation of ascorbic acid (AA) metabolism in young men housed for 13 weeks in a nutrition suite that provided controlled periods of ascorbic acid depletion and repletion. Twelve medically healthy non-smoking men, aged 25 to 43 years, ate a rotating four-day diet adequate in all nutrients except ascorbic acid. Following an initial baseline period during which the subjects received 250 mg AA/day, the subjects received 5 mg AA/day for a 32-day depletion period. Eight of the 12 subjects participated in a subsequent 56-day repletion period designed to replace the reduced body AA pool slowly. Plasma and leukocyte ascorbate levels, Plaque Index, Gingival Index, probing depths, and attachment level were monitored at the beginning and end of the depletion and repletion periods. Subgingival plaque samples were obtained and examined for selected organisms by indirect immunofluorescence microscopy. A uniform oral hygiene program was reinforced after each examination. Ascorbate concentrations in plasma and leukocytes responded rapidly to changes in vitamin C intake. There were no significant changes in plaque accumulation, probing pocket depth, or attachment level during the study. In contrast, gingival bleeding increased significantly after the period of AA depletion and returned to baseline values after the period of AA repletion. However, no relationship could be demonstrated between either the presence or proportion of target periodontal micro-organisms and measures of bleeding or ascorbate levels.

Topics: Actinomyces viscosus; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Bacteria; Bacteroides; Dental Plaque; Gingival Hemorrhage; Gingival Pocket; Humans; Leukocytes; Male; Porphyromonas gingivalis; Stomatitis, Aphthous

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Combined Modality Therapy; Enzymes; Humans; In Vitro Techniques; Neoplasms

The effect of lipid peroxidation in vitro on the amounts of several forms of cytochrome P-450 in liver microsomes from guinea-pigs was investigated. Lipid peroxide formation in liver microsomes from ascorbic acid (VC)-deficient animals was much higher than that observed in control animals. The antibodies to rat P-450IA2 (P-448-H), P-450IIB1 (P-450b) and human P-450IIIA4 (P-450NF) recognized one or two forms of cytochrome P-450 in liver microsomes of guinea-pigs. Neither cytochrome P-450 cross-reactive with anti-P-450IIB1 antibodies nor cytochrome P-450 cross-reactive with antibodies to P-450IIIA4 was virtually affected by microsomal lipid peroxidation induced by NADPH in vitro. In contrast, the forms of cytochrome P-450 immunochemically related to P-450IA2 were decreased with the increased level of lipid peroxide formation. The form-specific degradation of cytochrome P-450 due to lipid peroxidation was in agreement with our previous observation that the amounts of cytochrome P-450 cross-reactive with antibodies to P-450IA2 but not with antibodies to P-450IIIA (P-450PB-1) were predominantly decreased in VC-deficient guinea-pigs compared to control animals in vitro.

Topics: Animals; Antibody Specificity; Ascorbic Acid; Ascorbic Acid Deficiency; Blotting, Western; Cross Reactions; Cytochrome P-450 Enzyme System; Guinea Pigs; Humans; In Vitro Techniques; Isoenzymes; Lipid Peroxidation; Male; Microsomes, Liver; Rats

The present study was undertaken to explore the association between vitamin C nutritional status in pregnant women with premature rupture of the chorioamniotic membranes (PRM). A case-control cross-sectional study was carried out in 10 women with PRM and 19 women without PRM. The women were evaluated in the first hours postpartum while hospitalized: 10 ml of blood were obtained from each woman to determine vitamin C expressed as micrograms/10(8) leucocytes or microgram/mg of leucocyte protein. Data on fruit and vegetable consumption was collected by a frequency dietary survey and the hospital clinical records were reviewed to obtain their obstetric history and data on the presence of infection during pregnancy, in placenta and/or in fetal membranes. Low vitamin C levels were considered at a cut-off point equal or less than 26.33 micrograms/10(8) leucocytic cells and 3.15 micrograms/mg leucocyte protein. An association was found between low vitamin C levels and cases with PRM. No difference was found in the frequency of consumption of fruit and vegetables between the two groups. Infections were more frequently found in the PRM group, when the women had low levels of vitamin C, and when both risk factors were present simultaneously the proportion of PRM cases identified was greater than 0.75.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Case-Control Studies; Cross-Sectional Studies; Female; Fetal Membranes, Premature Rupture; Humans; Incidence; Leukocytes; Pregnancy; Risk Factors

Damage to the DNA of germ cells can lead to mutation, which may result in birth defects, genetic diseases, and cancer. The very high endogenous rate of oxidative DNA damage and the importance of dietary ascorbic acid (AA) in preventing this damage has prompted an examination of these factors in human sperm DNA. The oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (8-oxo-7,8-dihydro-2'-deoxyguanosine; oxo8dG), 1 of approximately 20 major products of oxidative damage to DNA, was measured in DNA isolated from human sperm provided by healthy subjects and compared to the seminal fluid AA levels. This relationship was studied in two groups. In a group of 24 free-living individuals 20-50 years old high levels of oxo8dG were correlated with low seminal plasma AA. The endogenous level of oxo8dG in this group was 13 fmol per microgram of DNA or approximately 25,000 adducts per sperm cell. The second group of individuals was maintained on a controlled diet that varied only in AA content. When dietary AA was decreased from 250 to 5 mg/day, the seminal fluid AA decreased by half and the level of oxo8dG in sperm DNA increased 91%. Repletion of dietary AA for 28 days (from 5 mg/day to 250 or 60 mg/day) caused a doubling in seminal fluid AA and reduced oxo8dG by 36%. These results indicate that dietary AA protects human sperm from endogenous oxidative DNA damage that could affect sperm quality and increase risk of genetic defects, particularly in populations with low AA such as smokers.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Deoxyguanosine; DNA; DNA Damage; Humans; Male; Oxidation-Reduction; Reference Values; Semen; Smoking; Spermatozoa

Channel catfish (Ictalurus punctatus) fingerlings (13 g average initial weight) were fed semipurified diets supplemented with 0, 0.06, 0.12, 0.24 and 0.72 mmol/kg (0, 11, 22, 44 or 132 mg/kg) of ascorbic acid molar equivalent supplied by either L-ascorbic acid, L-ascorbyl-2-monophosphate (Mg salt) (AAP), or L-ascorbyl-2-sulfate (K salt) (AAS). After 14 wk, weight gains were equal for all fish fed diets containing L-ascorbic acid or AAP; however, growth rates were less for fish fed AAS at all dietary levels and for fish fed the ascorbic acid-free diet (control). There were no gross signs of vitamin C deficiency in any of the fish fed L-ascorbic acid or AAP, whereas spinal deformities were found in the controls and in fish fed all but the highest concentration of AAS. The percentage of spinal deformities decreased as dietary levels of AAS increased. Reduced bone collagen content and histopathology in liver and gill tissues also indicated ascorbic acid deficiency in the controls and in fish fed all but the highest concentration of AAS. Limited histopathology was found in fish fed the lowest level of L-ascorbic acid but not in those fed the lowest level of AAP. Regression analysis of weight gain data showed that the vitamin activity of ascorbic acid from AAS was only 5.2% of that from L-ascorbic acid for growth. This study indicates that AAP has equimolar activity to L-ascorbic acid as a vitamin C source for channel catfish and that AAS has vitamin activity for this species but at a much lower level than the other compounds.

Topics: Administration, Oral; Animals; Anticholesteremic Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Ictaluridae; Liver

Both the ascorbic acid (AsA) and erythorbic acid (ErA) absorption in the small intestine of guinea pigs were determined by the perfusion of the small intestine using isotonic phosphate buffer recycled in situ. The absorption rate of AsA in the small intestine of guinea pigs was higher than that of ErA; however, Km of AsA absorption was lower than that of ErA in normal guinea pigs. In AsA-deficient guinea pigs, the absorption rates of both AsA and ErA were higher than those in normal ones. The absorption of AsA and ErA in the small intestine of guinea pigs was inhibited by ouabain. Furthermore, AsA and ErA inhibited each other's absorption. Based on the results, the net amount of the absorbed ErA in the small intestine may be lower than that of AsA, and ErA absorption mechanism seemed to be similar to that of AsA. The absorption rate of both AsA and ErA in the small intestine of guinea pig might be dependent on the AsA level in the tissues.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; In Vitro Techniques; Intestinal Absorption; Intestine, Small; Male; Perfusion

Because ascorbic acid is an important contributor to the oxidant defense system in body tissues, we studied the effects of a low dietary intake of ascorbic acid on various indicators of oxidant defense and oxidant damage. During a 13-wk study eight healthy men (25-43 y), residing in a live-in metabolic unit, were fed controlled diets containing different amounts of ascorbic acid for four consecutive periods: period 1 = 250 mg/d for 4 d; period 2 = 5 mg/d for 32 d; period 3 = 10 or 20 mg/d for 28 d and period 4 = 60 or 250 mg/d for 28 d. Measurements were made at several time intervals of the activities of glutathione peroxidase and superoxide dismutase in RBC, DNA strand breaks in mononuclear leucocytes, glutathione concentrations in plasma and RBC and NAD and NADP in RBC. After 60 d of low ascorbic acid intakes and associated with plasma ascorbic acid levels less than 6 mumol/L, the total glutathione concentration and the reduced glutathione:oxidized glutathione ratio were decreased in plasma. At the same time NAD and NADP levels in RBC were elevated. It seems that chronic marginal vitamin C deficiency states may be associated with selected biochemical changes in oxidant defense indices.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Glutathione; Glutathione Peroxidase; Humans; Male; NAD; NADP; Superoxide Dismutase

Patients (n = 15) with metastatic malignant melanoma, hypernephroma, and colon carcinoma received a three-phase adoptive immunotherapy protocol: phase 1, 10(5) units (high-dose) interleukin-2 (IL-2) iv every 8 h or 1 mg/m2 continuous intravenous infusion; phase 2, 6.5 d rest + leukapheresis; phase 3, 4 d of high-dose IL-2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities of treatment included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Patients entering the trial were not malnourished, and mean plasma ascorbic acid concentrations before therapy were normal (36.3 +/- 14.2 mumol/L). Mean concentrations dropped by 80% after the first phase of treatment with high-dose IL-2 alone (to 7.4 +/- 4.5 mumol/L). Mean plasma ascorbic acid concentrations remained severely depleted (between 4.5 and 7.4 mumol/L) throughout the remainder of the 15-d treatment. Ascorbic acid concentrations became undetectable (less than 2.8 mumol/L) in 12/15 patients during this time. Blood pantothenate and plasma vitamin E concentrations remained within normal limits in all patients tested throughout the phases of therapy.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Catecholamines; Female; Humans; Immunotherapy, Adoptive; Interleukin-2; Killer Cells, Lymphokine-Activated; Male; Middle Aged; Pantothenic Acid; Vitamin E

To determine nonscorbutic effects of moderate vitamin C deficiency we measured immune function and oxidative damage in eight healthy men (25-43 y) who consumed 5-250 mg/d of ascorbic acid over 92 d on a metabolic unit. During ascorbic acid intakes of 5, 10, or 20 mg/d, subjects attained a state of moderate ascorbic acid deficiency as ascorbic acid concentrations in plasma, leucocytes, semen, and buccal cells dropped to less than 50% of baseline with no scorbutic symptoms observed. No changes in cell proliferation, erythrocyte antioxidant enzymes, and DNA strand breaks were observed; however, blood levels of glutathione and NAD(P) decreased during ascorbic acid deficiency, as did delayed hypersensitivity responsiveness. Concentrations of the oxidatively modified DNA base, 8-hydroxydeoxyguanosine in sperm DNA and fecapentaenes, ubiquitous fecal mutagens, were increased during ascorbic acid depletion. Moderate vitamin C deficiency, in the absence of scurvy, results in alteration of antioxidant chemistries and may permit increased oxidative damage.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Immunocompetence; Male; Oxidants; Polyenes

Being a catechol, dopamine (DA) is easily autoxidized in solution to a semiquinone and then further to a quinone. These quinones and by-products, as reduced forms of oxygen, are all cytotoxic. By quantifying quinone metabolites, such as 5-S-cysteinyl adducts of DA, 3,4-dihydroxyphenylalanine (DOPA), and 3,4-dihydroxyphenylacetic acid (DOPAC), an indirect measure of catechol autoxidation is available. Ascorbic acid (AA) has an important role as an antioxidant in the organism. A group of guinea pigs (Dunkin-Hartley) received an AA-free diet for 37 days, whereas a control group was fed an AA-containing diet (1,400 mg/kg of pellets). To one group of AA-deprived animals a single dose of AA (500 mg/kg, i.p.) was administered 2 h before death, whereas another group received two doses 9 and 24 h before death. The striatal levels of 5-S-cysteinyl adducts, DA, noradrenaline, and DOPAC and the cerebellar and the limbic levels of AA were determined. A significant increase in 5-S-cysteinyl-DA content was found in the striatum of AA-deficient animals (143 +/- 12% of control values). A further increase was found 2 h after an AA injection (177 +/- 16% of control values), which was significant compared with both controls and AA-deficient animals. An elevation in 5-S-cysteinyl-DA content was still observed following two AA injections during a 24-h period (153 +/- 7% of control values). The 5-S-cysteinyl-DOPAC content increased significantly (134 +/- 14% of control values) in the AA-deficient animals given AA acutely (2 h), both compared with controls and with the AA-deficient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cerebellum; Corpus Striatum; Dopamine; Female; Guinea Pigs; Limbic System; Norepinephrine

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bilirubin; Fetal Tissue Transplantation; Hyperbilirubinemia, Hereditary; Liver Transplantation; Metabolic Diseases; Rats; Rats, Inbred F344; Rats, Inbred Strains; Serum Albumin

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; India; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy

The recommended dietary allowance (RDA) of ascorbic acid for smokers was recently increased from 60 to 100 mg. To determine whether this new RDA for smokers is sufficient to reduce the risk of low serum ascorbic acid (AA) concentrations (LoC) to the same concentration as nonsmokers, we analyzed the dietary intakes and serum concentrations of AA in 11,582 adult respondents in the National Health and Nutrition Examination Survey (1976-1980). Serum AA concentrations and the risk of LoC (serum ascorbic acid levels less than 23 mumol/L) for smokers consuming different amounts of AA were compared with those for nonsmokers whose AA intake exceeded the RDA (60 mg). Serum AA concentrations were reduced, and risk of LoC increased, in smokers maintaining AA intakes greater than 60, 100, and 150 mg. Only smokers consuming greater than 200 mg AA/d had serum ascorbate concentrations and risk of LoC equivalent to nonsmokers meeting the RDA.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Female; Humans; Male; Middle Aged; Smoking

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Infant, Newborn; Radiography; Scurvy

Topics: Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Cerebrovascular Disorders; Diabetes Complications; Diet, Vegetarian; Humans; Hypertension; Prevalence; United States

A cross-sectional study on 64 institutionalized and 65 noninstitutionalized elderly women has been undertaken. The age range was 60 through 90 years. Vitamin C status was assessed by serum ascorbic acid measurement and the nutritional status was evaluated by a three-day dietary record and main anthropometric measurements. Mean concentration of ascorbic acid was 1.03 mg/dl in the noninstitutionalized and 0.67 mg/dl in the institutionalized group (p less than 0.001). A serum ascorbic acid level less than 0.2 mg/dl was found in one (1.5%) and seven (10.9%) subjects respectively (p less than 0.03). Mean intake of vitamin C was 104.1 mg/d in the former and 87.3 mg/d in the latter group (p = NS), being less than 45 mg/d in 16 living at home and 11 institutionalized women. Serum ascorbic acid level did not correlate significantly to dietary nutrient intake but correlated to activity of daily living level (r = 0.29), vitamin C intake (r = 0.23), ideal body weight (r = -0.15), relative body weight (r = 0.15) and body mass index (r = 0.14). Suggestions are made concerning a higher intake of vitamin C and a more careful catering to improve the health status of the elderly people living in large institutions. The authors also suggest to include the serum ascorbic level determination in the assessment of the general health status of the elderly.

Topics: Aged; Aged, 80 and over; Anthropometry; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cross-Sectional Studies; Depression; Eating; Energy Metabolism; Female; Humans; Institutionalization; Middle Aged; Nutritional Status; Risk Factors; Rome; Surveys and Questionnaires

The effect of dietary ascorbate on hepatic UDP glucuronyltransferase (UDPGT) appears to be selective in that only certain isozymes of UDPGT are jeopardized. In this study, ascorbic acid deficiency produced a 68% reduction in the specific activity of hepatic UDPGT towards p-nitrophenol. Earlier studies showed a reduction in UDPGT activity towards p-aminophenol in ascorbate-deficient guinea pigs, whereas bilirubin and acetaminophen glucuronidation were unaffected. Kinetic studies suggest that p-aminophenol and p-nitrophenol are metabolized by a single isozyme in that p-nitrophenol was found to be a competitive inhibitor of p-aminophenol glucuronidation. Both qualitative and quantitative studies on partially purified UDPGT from ascorbate-deficient and ascorbate-supplemented guinea pigs were carried out to investigate the biochemical role of the vitamin. Qualitative differences were observed in UDPGT from ascorbate-deficient animals and included an increased lability to: thermal inactivation; storage at 4 degrees; and purification with UDP-glucuronic acid agarose column chromatography. Furthermore, an analysis of the microsomal membrane showed a 14% increase in membrane fluidity in ascorbate deficiency. Ascorbic acid added in vitro could not reverse the increase in fluidity observed in ascorbate-deficient microsomal membranes; however, ascorbylpalmitate, a more lipophilic form of the vitamin, was effective. Palmitic acid had no effect on membrane fluidity in microsomes from either the ascorbate-supplemented or ascorbate-deficient animals. This increase in membrane fluidity could not be explained by differences in cholesterol, total phospholipid, or phosphatidylcholine content of hepatic microsomes. Furthermore, a quantitative reduction in UDPGT partially purified from ascorbate-deficient guinea pigs was indicated by a marked reduction in protein banding at 55,000 daltons when compared to UDPGT partially purified from ascorbate-supplemented animals.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Chromatography, Thin Layer; Electrophoresis, Polyacrylamide Gel; Enzyme Stability; Glucuronosyltransferase; Guinea Pigs; Hot Temperature; Intracellular Membranes; Liver; Membrane Fluidity; Microsomes, Liver

When guinea pigs were kept on a restricted vitamin C intake of only 0.5 mg daily, their serum ascorbic acid fell to 0.16 +/- 0.06 mg/d1 in 16 weeks as compared to 0.73 +/- 0.11 in control. This was associated with significant increase in liver cholesterol and triglycerides. When they were simultaneously challenged with a high cholesterol load, this fat accumulation was markedly exaggerated. The weight of the liver now increased by almost two-and-half times. Liver cholesterol rose to 12.90 +/- 2.63 mg/gm as compared to 3.23 +/- 0.56 mg/gm with low vitamin C alone. Histopathology showed marked distension and vacuolation of hepatocytes, focal necrosis and fibroplasia. Administration of excess vitamin C (100 mg daily) significantly countered these changes. The vitamin C-lipid relationship has important clinical bearings and liver could be an important site of vitamin C action.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Cholesterol, Dietary; Guinea Pigs; Liver; Male; Organ Size; Triglycerides

Scurvy was diagnosed in 19 rhesus monkeys (Macaca mulatta) and four squirrel monkeys (Saimiri sciureus) from a colony of nonhuman primates maintained on a commercial diet. Signs of weakness, reluctance to move, gingival hemorrhage, bruising, proximal and distal metaphyseal fractures, weight loss and anemia appeared in juvenile and young adult rhesus monkeys over a 2 week period. Clinical signs subsided after 5 days of vitamin C therapy. At the same time, cephalohematomas and weakness developed in squirrel monkeys, which failed to respond to treatment. These cases were associated with manufacturer's admitted error in preparation of the commercially prepared monkey diet.

Topics: Anemia; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Macaca mulatta; Male; Monkey Diseases; Radiography; Saimiri

Marked formation of N-nitrosothioproline (N-nitrosothiazolidine-4-carboxylic acid) by stimulation with Escherichia coli lipopolysaccharide (LPS) was demonstrated in ascorbic acid-deficient mutant rats (osteogenic disorder syndrome rats; ODS rats) unable to synthesize ascorbic acid. The amounts of urinary nitrate and N-nitrosothioproline excretion after thioproline administration was measured in ODS rats with and without ascorbic acid supplement before and after the injection of LPS. LPS caused marked increase of urinary nitrate excretion in both groups. Urinary N-nitrosothioproline excretion increased 6-fold after LPS injection in ODS rats not supplied with ascorbic acid, but supplement with ascorbic acid markedly decreased the excretion of N-nitrosothioproline.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Bone Diseases, Metabolic; Escherichia coli; Female; Kidney; Lipopolysaccharides; Liver; Nitrates; Nitroso Compounds; Rats; Rats, Mutant Strains; Spleen; Thiazoles; Thiazolidines

The effect of ascorbic acid deficiency on serum and liver cholesterol, phospholipid and triglyceride levels, serum lipoprotein levels and serum lipoprotein cholesterol levels were examined in male rats with a hereditary defect in ascorbic acid synthesis (ODS rats). Male homozygotes (od/od) and male rats of their parent strain (+/+) were each divided into four treatment groups and were fed vitamin C-deficient or vitamin C-replete diets containing either 0 or 0.5% cholesterol. During the 3-wk feeding-period the ODS (od/od) rats fed the vitamin C-deficient diet gradually decreased food intake, resulting in a lower body weight than that of od/od rats given ascorbic acid. The serum cholesterol level was significantly higher in the vitamin C-deficient od/od rats fed the cholesterol diet, and it tended to be higher in those fed the control (0% cholesterol) diet, whereas the liver lipid levels remained unchanged relative to those in od/od rats fed the vitamin C-replete diet. The serum very low density lipoprotein and high density lipoprotein (HDL) cholesterol levels were lower in od/od rats fed the vitamin C-deficient diet without cholesterol, but intermediate density lipoprotein and low density lipoprotein cholesterol levels were markedly higher in the vitamin C-deficient od/od rats than in od/od rats given ascorbic acid, regardless of dietary cholesterol level. The ratio of HDL2 cholesterol to HDL3 cholesterol was also higher in the vitamin C-deficient od/od rats. The parent strain of the od/od rats (+/+) showed no change due to vitamin C deficiency. These results suggest that vitamin C deficiency delays low density lipoprotein metabolism and produces hypercholesterolemia in male od/od rats.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cholesterol, Dietary; Lipoproteins; Liver; Male; Phospholipids; Rats; Rats, Mutant Strains; Triglycerides

Because peroxidative damage to red cell membranes may contribute to the pathophysiology of sickle cell disease, deficiency of fat- and water-soluble antioxidants could be a determinant in the pathogenesis of this disease. We have previously reported a deficiency of vitamin E in sickle cell disease. The present study was undertaken to see if a deficiency in vitamin C might also be detected. Leukocyte vitamin C, which reflects total body vitamin C reserve, was measured by a modified 2,4-dinitrophenylhydrazine method. Sickle cell patients (N = 18) had lower leukocyte vitamin C levels (18.3 +/- 9.4 micrograms/10(8) cells) than normal controls (N = 12; 30.3 +/- 7.5 micrograms/10(8) cells; p less than 0.01). Furthermore, 50% of the patients had vitamin C levels below 15 micrograms/10(8) cells, a value consistent with vitamin C deficiency. A statistically significant correlation (r = -0.62 with 0.01 less than p less than or equal to 0.025) was found between leukocyte vitamin C levels and serum ferritin concentration. Because dietary vitamin C intake appeared to be adequate, increased vitamin C utilization may account for this deficiency. However, the mechanisms for this deficiency as well as its pathophysiologic consequences remain to be established.

Topics: Anemia, Sickle Cell; Ascorbic Acid; Ascorbic Acid Deficiency; Ferritins; Humans; Leukocytes; Oxidation-Reduction

Schizophrenic patients on the same hospital diet as control group subjects had significantly lower levels of fasting plasma vitamin C (p less than 0.05) and 6-hr urinary vitamin C excretion after an ascorbic acid load test (p less than 0.01). After administration of 70 mg of ascorbic acid for 4 weeks there was no longer any difference in plasma vitamin C levels between schizophrenics and control group subjects, but the urinary vitamin C excretion after the vitamin C loading test remained significantly lower in schizophrenics (p less than 0.05). The administration of 1 g ascorbic acid for 4 weeks, in addition to eliminating differences in the plasma vitamin C level, also increased the urinary vitamin C excretion of schizophrenic patients to the level of the control group subjects. The results of this study are in agreement with the hypothesis that schizophrenic patients require higher levels of vitamin C than the suggested optimal ascorbic acid requirement for healthy humans.

Topics: Adult; Anxiety Disorders; Ascorbic Acid; Ascorbic Acid Deficiency; Dose-Response Relationship, Drug; Female; Humans; Male; Nutritional Requirements; Schizophrenia; Schizophrenic Psychology; Somatoform Disorders

Ascorbic acid (AsA) is known to be required for the synthesis of carnitine. The present study was designed to clarify the effect of AsA on the carnitine synthesis and lipid metabolism in guinea pigs. The animals were divided into four groups, and fed AsA-free diets for three weeks. Each group was supplemented with AsA in the following doses; high-AsA group, 100 mg AsA/day/animal; control group, 5 mg AsA/day/animal; AsA-deficient group, 0.1 mg AsA/day/animal; pair-fed group, 5 mg AsA/day/animal. The pair-fed group was restricted to the amount of diet consumed by the AsA-deficient group. Tissue carnitine levels of the AsA-deficient group were significantly lower than not only the control group but the pair-fed group. Total cholesterol and phospholipid levels in plasma of the AsA-deficient group were found to be similar to those of the pair-fed group; however, plasma triglyceride levels were significantly higher than that of the pair-fed group. Furthermore, there was an inverse relationship between tissue AsA and plasma triglyceride levels. We concluded that carnitine synthesis and triglyceride metabolism in guinea pigs may be impaired by the decrease of tissue AsA level rather than by the insufficient food intake. It is suggested that tissue carnitine level altered by tissue AsA content affects plasma triglyceride level.

Topics: Alkaline Phosphatase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Carnitine; Cholesterol; Guinea Pigs; Lipids; Male; Organ Specificity; Phospholipids; Triglycerides

Two physicochemically and metabolically separate pools of ferritin, namely cytosolic ferritin and lipid-associated ferritin, are present in the livers of guinea pigs. In this paper we establish that the iron content of cytosolic ferritin is dependent on and linearly related to ascorbic acid concentration, whereas changes in concentration of this vitamin do not affect the iron content of lipid-associated ferritin. In livers of ascorbic acid-deficient guinea pigs both synthesis and degradation of cytosolic ferritin are diminished equally. Consequently cytosolic ferritin is metabolized more slowly without changes in its pool size. In contrast with cytosolic ferritin, the metabolism of lipid-associated ferritin is unaffected by ascorbic acid deficiency. The differential effects of ascorbic acid deficiency on the physicochemical characteristics as well as on the metabolism of cytosolic ferritin and lipid-associated ferritin suggest that the two forms of ferritin have different functional roles.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytosol; Ferritins; Guinea Pigs; Kinetics; Lipid Metabolism; Liver

The effect of ascorbic acid deficiency on the urinary excretion of nitrate was investigated using a mutant strain of rats (osteogenic disorder syndrome rats; ODS rats) unable to synthesize ascorbic acid. The amount of urinary nitrate excreted by ODS rats with or without ascorbic acid supplementation were measured before and after the intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). Urinary nitrate excretion increased markedly after LPS injection. Urinary nitrate excretion by ODS rats not supplied with ascorbic acid was significantly less than that of those supplied with ascorbic acid both before and after LPS injection. These results show that ascorbic acid enhances both LPS-stimulated and constitutive nitrate production in vivo.

Topics: Adrenal Glands; Analysis of Variance; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Female; Kidney; Lipopolysaccharides; Liver; Nitrates; Rats; Rats, Mutant Strains; Spleen

The plasma concentration of vitamin C of 14 patients with tropical pyomyositis without clinical evidence of scurvy and that of II age and sex-matched controls was determined in order to ascertain whether or not there was a deficiency of the vitamin in this condition. The results show that the mean plasma concentrations of vitamin C of patients were slightly higher (15.9 +/- 6.4 g/l) than those of controls (12.0 +/- 4.5 g/l). The differences, however, were not statistically significant (P greater than 0.25). It is therefore concluded that lack of vitamin C does not play a part in the aetiology of tropical pyomyositis.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Myositis

We investigated the vitamin C (ascorbic acid) status in 1077 eastern Finnish men aged 54 years of age examined in the "Kuopio Ischaemic Heart Disease Risk Factor Study" in 1984-86. Dietary intake of ascorbic acid had a strong linear correlation to plasma ascorbic acid, and we found a clear seasonal variation in the plasma ascorbic acid levels: the highest values were found in August-September and again in April, and the lowest levels in November-January and in June. A true vitamin C depletion was found in 8.8% of the 1077 men studied, and, in addition, 16.5% had a mild vitamin C deprivation. The decreased plasma levels of this antioxidant vitamin may be associated with elevated blood pressure.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cohort Studies; Coronary Disease; Eating; Finland; Humans; Male; Middle Aged; Nutritional Status; Risk Factors; Seasons

Ascorbic acid (AA) metabolism was studied in control and iron-loaded guinea pigs. All animals were fed an AA-deficient diet and given a daily intraperitoneal (ip) dose of 10 mg sodium ascorbate. The control-diet formula contained 0.10 g Fe/kg diet; the experimental diet contained an additional 3.33 g Fe/kg diet as FeSO4. After 14 wk animals were injected (ip) with 9.25 x 10(3) Bq [1-14C]L-ascorbic acid. Blood was collected for 10 d and plasma specific activity of AA was determined. All animals were subsequently killed and selected tissues were analyzed for AA and iron concentrations. In spite of marked elevation of iron concentrations in plasma, spleen, and liver in experimental animals compared with controls, no differences in AA metabolism as determined by tissue AA concentrations and AA half-life, turnover rate, and body-pool size were evident. These results demonstrate that iron loading has no effect on the rate of AA catabolism in guinea pigs.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Guinea Pigs; Half-Life; Iron; Liver; Male; Models, Biological; Siderosis; Spleen

The effect of acute or chronic ascorbic acid deficiency on the activity of hepatic cholesterol 7 alpha-hydroxylase and fecal excretion of bile acids was investigated in ODS-od/od (OD) rats (a rat mutant unable to synthesize ascorbic acid) fed a purified basal diet or purified diets containing either cholesterol (2%) or polychlorinated biphenyl (PCB) (200 mg/kg). In OD rats, the dietary requirement of ascorbic acid to maintain normal growth and normal levels of cholesterol in serum and liver is about 300 mg of ascorbic acid/kg diet. In OD rats fed the basal diet, acute or chronic ascorbic acid deficiency did not affect the activity of hepatic cholesterol 7 alpha-hydroxylase and fecal excretion of bile acids. However, in OD rats fed diets containing either cholesterol or PCB, acute ascorbic acid deficiency caused a higher level of serum cholesterol, a lower activity of hepatic cholesterol 7 alpha-hydroxylase and a lower excretion of fecal bile acids than in OD rats fed a basal diet containing an adequate level of ascrobic acid. It is concluded that acute ascorbic acid deficiency causes a hypercholesterolemia due to the depression of bile acid synthesis in OD rats fed a purified diet with cholesterol or PCB.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Body Weight; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol, Dietary; Cytochrome P-450 Enzyme System; Diet; Feces; Lipid Metabolism; Liver; Male; Organ Size; Polychlorinated Biphenyls; Rats; Rats, Inbred Strains; Rats, Mutant Strains

The present study revealed ascorbic acid deficiency in the blood of many children with Down's syndrome. It also revealed a fairly definite connection between Vitamin C deficiency and diet in these patients and a similar link between ascorbic acid deficiency and this incidence of infections. Where necessary the prescription of Vitamin C for the prevention and treatment of recurring infection is therefore recommended, bearing in mind the valuable antioxidant properties of ascorbic acid that can be exploited in combating cell deterioration.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Diet; Down Syndrome; Female; Humans; Infant; Male

A study was made of the content of ubiquinone, vitamins A, E, ascorbic, dehydroascorbic and diketogulonic acids (DKGA), and malonic dialdehyde (MDA) in the liver, of the content of glutathione, the activity of superoxide dismutase (SOD) and glutathione reductase in red blood cells, of the content of vitamins A, E and ubiquinone in the spleen of C57Bl/6jG mice with inoculated leukemia La. It was found that in red blood cells of the animals with leukemia, the content of vitamin E and DKGA reduced, the MDA level increased, and the content of glutathione dropped whereas SOD activity rose. Application of the antioxidant complex of vitamins A, E, C appreciably improved the characteristics of enzymatic and non-enzymatic antioxidant protection of the liver and red blood cells of the leukemic animals without exerting any noticeable effect on the content of vitamin E and ubiquinone in the leukemic spleen tissue.

Topics: Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Erythrocyte Membrane; Leukemia, Experimental; Lipid Peroxidation; Liver; Mice; Mice, Inbred C57BL; Vitamin A; Vitamin A Deficiency; Vitamin E; Vitamin E Deficiency

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Fetus; L-Gulonolactone Oxidase; Liver; Liver Transplantation; Male; Microsomes, Liver; Rats; Rats, Inbred Strains; Rats, Mutant Strains; Reference Values; Spleen; Sugar Alcohol Dehydrogenases; Transplantation, Isogeneic

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; England; History, 20th Century; Humans; Hungary; Industrial Microbiology; Nobel Prize

The levels of vitamin C in plasma, mononuclear (MN) and polymorphonuclear (PMN) leucocytes were measured in healthy, free-living, young and elderly women on three occasions over an 8-10-week period: (a) at entry into the study, (b) following 5 weeks of dietary depletion of vitamin C, and (c) following 3 weeks of supplementation with 500 mg of vitamin C per day. The combined mean vitamin C levels (expressed as microgram/10(8) cells) in MN cells were higher than those found in PMN cells at all three times, although the difference was only statistically significant in the depleted state. There were no age-related differences in the levels of vitamin C in plasma, MN or PMN cells at any of the three times. Significant overall differences in vitamin C levels between the entry and depleted and the depleted and supplemented states were observed for plasma and PMN cells but not for MN cells, possibly indicating that plasma and PMN cells are more sensitive indicators of vitamin C status than MN cells. The mean levels of vitamin C found in plasma clearly do 'track' those found in MN and PMN cells. However, attempted correlations between plasma and MN, plasma and PMN, and MN and PMN vitamin C levels at each time proved to be non-significant. In addition, the changes in vitamin C levels from entry to depleted and from depleted to supplemented times were non-significant when comparing plasma to MN and plasma to PMN, whereas the MN vs PMN comparison indicated a significant change in vitamin C levels between the depleted and supplemented states.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Food, Fortified; Humans; Leukocytes, Mononuclear; Neutrophils

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Nutritional Requirements

Urine and blood levels of ascorbic acid (AA) were measured in healthy subjects (40), cases of cancer of the lung (74), stomach (32) and esophagus (12). AA levels were decreased in cancer patients, particularly, in those with gastric and esophageal tumors. A correlation between the decrease of AA level and the increase in blood concentrations of malonic and pyruvic acids was established. Administration of 1.5 g AA for 7 days was followed by blood-AA level returning practically to normal matched by decrease in lactate and pyruvate concentrations. Also, a correlation between postoperative complication frequency and AA deficit was shown. Correction of AA level was found to be an effective means of postoperative complication prevention.

Topics: Administration, Oral; Ascorbic Acid; Ascorbic Acid Deficiency; Combined Modality Therapy; Esophageal Neoplasms; Humans; Infusions, Intravenous; Lactates; Lactic Acid; Lung Neoplasms; Oxidation-Reduction; Preoperative Care; Pyruvates; Pyruvic Acid; Stomach Neoplasms

The effect of erythorbic acid (ErA) administration on activities of liver aniline hydroxylase, liver acid phosphatase, and serum alkaline phosphatase, and the content of liver cytochrome P-450 was studied to determine whether or not ErA would affect the availability of ascorbic acid (AsA) in normal and AsA-deficient guinea pigs. In experiment I, changes of the enzyme activities and liver cytochrome P-450 content in the guinea pigs administered AsA and/or ErA and sacrificed on days 4, 10, 16, and 30 were examined. Moreover, in experiment II, after 16 days of depletion of AsA, the guinea pigs were administered AsA and/or ErA. These animals were sacrificed on days 0, 4, and 20 of the repletion period, after which the activities of drug metabolic enzyme and phosphatases and content of cytochrome P-450 during recovery were observed. The enzyme activities and cytochrome P-450 content of AsA-supplemented guinea pigs were similar to those of ErA-supplemented animals and also similar to those of both AsA and ErA-supplemented guinea pigs throughout the experimental period. During the repletion of the AsA-depleted guinea pigs, there were no significant differences in these enzyme activities and cytochrome P-450 content among the animals administered AsA and/or ErA. These results suggested that ErA administration may not affect the AsA availability in the guinea pigs.

Topics: Acid Phosphatase; Alkaline Phosphatase; Aniline Hydroxylase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Guinea Pigs; Liver; Male

Whole blood ascorbate, plasma oxalate, serum cholesterol, and capillary fragility were measured at monthly intervals for 3 mth in 7 patients receiving continuous ambulatory peritoneal dialysis and 4 receiving haemodialysis, to whom ascorbate supplements had not been prescribed for at least 12 mth. Ascorbate supplements, 25 mg/day, were prescribed for the first month and 50 mg/day for the second month; in the final month patients received no supplements. Whole blood ascorbate was below normal in 6/11 patients at the start of the study but was normal in 10/11 patients when taking ascorbate 50 mg/day. No significant changes in plasma oxalate were observed with these doses of ascorbate, and correction of ascorbate deficiency had no effect on serum cholesterol, mean cell volume, or the results of capillary fragility tests. In a supplementary study, ascorbic acid 500 mg/day was administered for 3 wk to 11 patients. This resulted in a significant rise in mean plasma oxalate from 30.3 (SEM 3.5) to 48.4 (SEM 20.3) mumol/l.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Bilirubin; Capillary Fragility; Cholesterol; Creatinine; Female; Hemoglobins; Humans; Male; Middle Aged; Oxalates; Renal Dialysis; Triglycerides

The mutagenic effect of intraperitoneally injected K2Cr2O7 was significantly higher in vitamin C-deficient guinea pigs than in animals fed diet with high vitamin C content. Mutagenic and toxic effects of hexavalent chromium were more expressed in vitamin C-deficient guinea pigs administered K2Cr2O7 in drinking water: the number of micronuclei in polychromatic erythrocytes of bone marrow was increased, and the activity of O-demethylase and the levels of cytochromes P-450 and b5 in liver microsomes were decreased. In guinea pigs fed high vitamin C diet the same doses of bichromate in drinking water evoked no mutagenic changes in the bone marrow and no changes in microsomal enzymes in the liver. These results indicate that high intake of ascorbic acid in the diet reduces mutagenic effects of K2Cr2O7 and its toxic influence on drug metabolizing enzymes in hepatocytes. The protective effect ascorbic acid consists most probably in the enhanced extracellular and intracellular reduction of hexavalent chromium to the less toxic and less mutagenic trivalent chromium.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone Marrow; Chromates; Chromosome Aberrations; Guinea Pigs; Liver; Male; Micronucleus Tests; Mutagens; Potassium Compounds; Random Allocation

Ascorbic acid (AA) metabolism and requirements were studied in 11 adult nonpregnant women maintained in a metabolic unit and fed a formula diet devoid of AA for 54 d. After depletion for 24 d, the subjects received increasing supplements of AA in the presence or absence of 600 mg/d of erythorbic acid (EA). Various analytical procedures were used to measure AA concentrations in blood components. The depletion period resulted in a marked decrease in AA in all blood indices. During the study scorbutic signs developed in some of the subjects. AA supplements of 30 mg/d for 10 d failed to increase plasma ascorbate concentrations; 60 mg/d for 10 d produced a small increase; 90 mg/d resulted in a mean AA concentration of 29 mumol/L. EA did not present any adverse effects, but rather had a small sparing effect. Vitamin C requirements for adult nonsmoking, nonpregnant women would be marginally met by an intake of 60 mg/d of AA whereas 90 mg/d would provide an allowance for body storage.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Specimen Collection; Chromatography, High Pressure Liquid; Diet; Energy Metabolism; Female; Humans; Leukocytes; Nutritional Requirements; Nutritional Status

To further define the relation between smoking and vitamin C status, the dietary and serum vitamin C levels of 11,592 respondents in the second National Health and Nutrition Examination Survey (NHANES II) were analyzed. Smokers of 20 cigarettes daily had the lowest vitamin C dietary intake (79 mg, 95% CI:73, 84) and serum levels (0.82 mg/dl, 95% CI: 0.77, 0.86; 46.6 mumol/L, 95% CI: 43.7, 48.8), while smokers of 1-19 cigarettes daily had decreased vitamin C intake (97 mg; 95% CI: 90, 104 mg) and serum levels (0.97 mg/dl, 95% CI: 0.92, 1.03; 55.1 mumol/L, 95% CI: 52.2, 58.5) compared to respondents who had never smoked (109 mg, 95% CI: 105, 113 and 1.15 mg/dl, 95% CI: 1.11, 1.18; 65.3 mumol/L, 95% CI: 63.0, 67.0, respectively). This inverse association between both intake and serum levels of vitamin C and smoking was independent of age, sex, body weight, race, and alcoholic beverage consumption. Following further adjustment for dietary vitamin C intake, the negative correlation between cigarette smoking and serum vitamin C levels persisted. The risk of severe hypovitaminosis C (serum levels less than or equal to 0.2 mg/dl; 11.4 mumol/L) was increased in smokers, particularly when not accompanied by vitamin supplementation (odds ratio 3.0, 95% CI: 2.5, 3.6). These data suggest that even though smoking adversely affects preferences for vitamin C rich foods, the inverse association between smoking and serum vitamin C levels occurs independently of dietary intake.

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Female; Humans; Male; Middle Aged; Risk Factors; Smoking

The ascorbic acid content of guinea pig leukocytes is reduced by a factor of 16:1 between normal and scorbutic guinea pigs. Ascorbic acid deficiencies do not appear to affect phagocytic activity but do change leukocyte morphology. A deficiency of this vitamin appears to significantly interfere with the in vitro bactericidal effectiveness of circulating leukocytes against ingested, cell-associated, and extracellular bacterial cells of the oral pathogen, Actinomyces viscosus. Leukocytes from scorbutic guinea pigs killed 13% of ingested and cell-associated Actinomyces viscosus compared to 83% killed by normal leukocytes by both acridine orange staining and viable count. Degranulation resulted in extracellular killing in normal but not scorbutic leukocytes. This decreased bactericidal activity can be reversed by adding supplements of the vitamin to the diet of scorbutic animals. Chemotactic responses were much lower in vivo and absent in vitro in scorbutic leukocytes. The acridine orange staining technique is an excellent indicator of leukocyte health. This study supports the important role for ascorbic acid in leukocyte function and also discusses its probable protective and bactericidal activities related to oral pathogens.

Topics: Actinomyces; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Bactericidal Activity; Chemotaxis, Leukocyte; Guinea Pigs; In Vitro Techniques; Leukocytes; Microscopy, Fluorescence; Mouth; Neutrophils; Phagocytosis; Staining and Labeling

The plasma and tissue concentration of ascorbic acid (AA) is reduced in diabetes. This study was designed to investigate the mechanism and significance of this phenomenon. The low plasma AA concentration of diabetic rats can be normalized by dietary AA supplement (20-40 mg/day), a dosage approximately equal to the maximal synthetic rate of this substance in the rats. Treatment of diabetic rats with this regime prevented the decrease in activity of granulation tissue prolyl hydroxylase (PRLase), an AA-dependent enzyme required for maintaining the normal properties of collagen. The decreased plasma AA concentration and granulation tissue PRLase activity in diabetes can also be normalized by the aldose reductase inhibitor tolrestat. We conclude that in diabetic animals there is a true deficiency of AA that may be responsible for some of the changes of collagen observed in diabetes. Treatment with AA or an aldose reductase inhibitor may prevent some of the diabetic complications with underlying collagen abnormalities.

Topics: Aldehyde Reductase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Diabetes Mellitus, Experimental; Female; Granulation Tissue; Naphthalenes; Procollagen-Proline Dioxygenase; Rats; Rats, Inbred Strains; Sugar Alcohol Dehydrogenases

Concentrations of the vitamins B1, B2, B6, B12, C, folic acid, A, E and beta-carotene were determined in blood and 24-h dialysate in 44 CAPD patients. Twenty-five of these patients were studied during chronic treatment (mean 313 days, range 60-1034 days). Nineteen patients were studied during training. In a longitudinal study, 11 patients were analysed again after 77-507 (mean 238) days. In both patient groups a considerable portion of patients (11%-64%) had blood concentrations indicative of a deficiency of the vitamins B1, B6, C and folic acid. The average concentrations of these vitamins were normal in both groups. The only abnormal finding was the mean EGOT activity being deficient in patients on chronic treatment. Mean concentrations of vitamin A were above normal in both groups. In the longitudinal study a significant increase of vitamin B2 and a decrease of vitamin B6 in blood was found. When compared to 24-h excretion in normal urine, loss with 24-h dialysate was low for vitamin B1, normal to relatively high for vitamin B2 and B6, but extremely high for vitamin C and folic acid. The vitamins B12, A, E and carotenoids were hardly detectable in the dialysate. In ten other patients the effect of daily supplementation with 2 mg vitamin B6, 100 mg vitamin C and 400 micrograms folic acid was analysed during a 16-week period. In all patients a significant increase in blood concentrations was obtained. It is concluded that these dosages were sufficient to maintain a normal status of these vitamins in CAPD patients.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Cross-Sectional Studies; Female; Folic Acid; Folic Acid Deficiency; Humans; Longitudinal Studies; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Pyridoxine; Riboflavin; Thiamine; Thiamine Deficiency; Vitamin B 6 Deficiency

Airway responsiveness to histamine aerosol and lung prostaglandin generation were investigated in normal, partially vitamin C deficient and scorbutic guinea pigs. The ascorbic acid content of the lung expressed as microgram/100 mg wet weight lung parenchyma decreased from 22.1 +/- 1.8 (mean +/- SE) in the control group to 9.0 +/- 1.4 and 1.8 +/- 0.4 in tissues from partially ascorbic acid deficient and scorbutic animals, respectively. Guinea pigs on low and ascorbic acid deficient diets developed significant airway hyperresponsiveness to histamine aerosol after 3 and 4 weeks. Indomethacin (30 mg/Kg, i.p.) further increased the airway hyperresponsiveness in scorbutic animals but was without effect in control animals. Prostaglandin generation from different parts of the lung was significantly changed by the diets. However, airway hyperresponsiveness was not directly attributable to altered prostanoid generation. Scorbutic conditions did not alter the electrophysiological characteristics of airway smooth muscle namely, resting membrane potential and electrogenic sodium pump activity. In summary, ascorbic acid deficiency causes airway hyperresponsiveness to histamine in guinea pigs. This alteration seems not to be related to an altered prostaglandin generation by the lung or to the electrophysiological properties of airway smooth muscle.

Topics: Aerosols; Airway Resistance; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Histamine; Lung; Male; Membrane Potentials; Prostaglandins

In ascorbic acid-requiring species (human, guinea pig), elevations of circulating histamine occur as the result of marginal ascorbic acid status. Marginal ascorbic acid status during pregnancy is associated with preeclampsia, abruption, and prematurity. Furthermore, circulating histamine is known to be elevated in these complications perhaps as a result of placental dysfunction which diminishes normal placental histaminase. We hypothesized that women with preeclampsia and premature labor would have elevated histamine and the lowest concentrations of ascorbic acid. Plasma total whole blood histamine and ascorbic acid were surveyed in women in term (T) and preterm (PT) labor. Blood histamine was elevated in PT compared to T labor but so was plasma ascorbate, indicating that marginal ascorbate status does not cause the elevated circulating histamine observed in PT. However, marginal ascorbate status concomitant with reduced placental histaminase may contribute to further increases in circulating histamine and to any pathology which might result from elevated histamine. Regression analysis of histamine on ascorbate for T and PT labor revealed a significant inverse relationship between ascorbate and histamine only in PT labor (p less than 0.027). An unexpected finding was that a history of maternal cigarette smoking, to a degree which resulted in marginal ascorbic acid status, confounded the relationship between ascorbate and circulating histamine in T labor.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Histamine; Humans; Labor, Obstetric; Pregnancy; Smoking

560 pregnant women aged 20-30 were divided into 2 groups; 270 smokers (150 smoking 6-10 cigarettes a day and 120 smoking 12-20 cigarettes) and 270 nonsmokers. Their serum vitamin C level was measured repeatedly by the method of Roe and Kuethera from the 2nd to the 10th month. Nonsmokers had 1.037 mg vitamin C in their blood light smokers had .699 mg, and heavy smokers had .521 mg. The serum level of both smoker groups was statistically significant (p .001). The vitamin C level of light smokers was .8 mg, while that of heavy smokers was .6 mg%. The vitamin C level of all pregnant women tended to decrease somewhat as pregnancy progressed; however, this was statistically insignificant. Smoking of tobacco caused the decrease of serum vitamin C levels in pregnant women compared to nonsmokers. The decline of vitamin C levels was greater in those pregnant women who smokes more cigarettes per day.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Pregnancy; Pregnancy Complications; Smoking

Chronic vitamin C deficiency was induced in guinea pigs by restricting their vitamin C intake to 0.5 mg daily. This was just sufficient to prevent rapidly fatal scurvy and 55 per cent of the animals survived. In 16 weeks their serum ascorbic acid (SAA) fell to 0.16 +/- 0.06 mg/dl as compared to 0.73 +/- 0.11 in control animals receiving 5 mg vitamin C daily. There was a marked increase in serum cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides and total lipids. HDL-cholesterol was, however, decreased resulting in a shift of the LDL/HDL ratio from 1.13 +/- 0.16 in the control to 5.91 +/- 1.70 in the low vitamin C group. Cholesterol feeding (100 mg/day) by itself lowered the SAA significantly, besides producing hyperlipidemia. When the vitamin C intake was reduced to only 0.5 mg/day, the effects of cholesterol feeding were exaggerated; the magnitude of hyperlipidemia was now significantly greater than with simple cholesterol feeding. The LDL/HDL ratio rose to 19.02 +/- 3.32 from 1.13 +/- 0.16 in the normal guinea pigs. Chronic vitamin C deficiency seems to affect the blood lipid profile unfavourably which could promote atherogenesis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Chronic Disease; Guinea Pigs; Hyperlipidemias; Lipids; Male; Triglycerides

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cadmium; Cholesterol; Guinea Pigs; Microsomes, Liver

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Bronchitis; Chronic Disease; Female; Humans; Male; Middle Aged

Assessment of L-ascorbic acid requirement for prolonged survival in ODS (genotype: od/od) rats and their susceptibility to urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) were examined. In ODS rats without L-ascorbic acid synthesizing ability, the 50 ppm dietary total ascorbic acid (TAA) was insufficient to survive for 4 weeks, the 250 ppm dietary TAA was sufficient to survive for 36 weeks. In examination of BBN treatment, ODS rats--although showing a lower availability of TAA than the heterozygotes (+/od) and normal (+/+) rats with L-ascorbic acid synthesizing ability--were equally susceptible to bladder carcinogenesis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Butylhydroxybutylnitrosamine; Male; Rats; Urinary Bladder Neoplasms

Topics: Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiovascular Diseases; Chronic Disease; Czechoslovakia; Diet; Humans

Modulation of the flavin-containing monooxygenase (FMO) by varying the ascorbic acid and food intake was investigated. Hepatic activity of the FMO in ascorbic acid-deficient guinea pigs fed a restricted amount of diet which resulted in a 10-15% body weight loss, was 17% of that in animals fed restricted amounts of the adequate diet. FMO hepatic activity in ascorbic acid-supplemented guinea pigs on a food-restricted regimen was 176% of that found in animals fed the adequate diet ad libitum. This increase in activity was not related to stress. Alteration in the activity of this important drug-metabolizing enzyme system by a combination of ascorbic acid deficiency and reduced food intake could potentially alter the rate of metabolism of a great variety of pharmaceutical drugs and environmental chemicals.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Food Deprivation; Guinea Pigs; Liver; Male; Oxygenases; Tyrosine Transaminase

The effect of ascorbic acid deficiency and excessive ascorbic acid intake on serum and liver levels of cholesterol and lipids was investigated in ODS-od/od (OD) rats fed a normal diet, a cholesterol-containing diet or a polychlorinated biphenyl (PCB)-containing diet. The OD rat is a rat mutant unable to synthesize ascorbic acid. In OD rats, the dietary requirement of ascorbic acid to maintain normal growth and normal levels of cholesterol in serum and liver is about 300 mg of ascorbic acid/kg diet. In control (ODS-+/+) rats that can synthesize ascorbic acid, dietary addition of 0.5% cholesterol and 0.25% cholic acid caused elevation of cholesterol concentrations in serum and liver, elevation of total lipids in liver and reduction of the ratio of high density lipoprotein (HDL) cholesterol to total cholesterol in serum. Dietary addition of PCB (200 mg/kg diet) caused elevation of serum concentration of cholesterol and of the ratio of HDL-cholesterol to total cholesterol in serum. In OD rats fed a normal diet, ascorbic acid deficiency slightly elevated serum concentration of cholesterol, elevated liver concentration of cholesterol and reduced the ratio of HDL-cholesterol to total cholesterol in serum; and ascorbic acid excess did not affect serum and liver concentrations of cholesterol and the ratio of HDL-cholesterol to total cholesterol in serum. In OD rats fed a cholesterol-containing diet, ascorbic acid deficiency elevated serum and liver concentrations of cholesterol, and did not affect the ratio of HDL-cholesterol to total cholesterol in serum; and ascorbic acid excess did not affect serum and liver concentrations of cholesterol and the ratio of HDL-cholesterol to total cholesterol in serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholic Acid; Cholic Acids; Diet; Liver; Male; Organ Size; Polychlorinated Biphenyls; Rats; Rats, Mutant Strains

Marmosets can tolerate an ascorbic acid (AA) deficiency for several weeks without clinical symptoms. After being fed an AA-free diet for 3 months, nonspecific deficiency symptoms became obvious. Different dietary levels of AA resulted in corresponding serum ascorbate levels. The kidney threshold of AA in marmosets is comparable to that in humans. When the minimal AA requirement is defined as the amount that is necessary to maintain a serum AA level above the kidney threshold, then about 20 mg AA/kg body weight is needed. This intake was achieved in our trial with a diet containing 500 ppm AA. Thus, the AA requirement of marmosets is severalfold higher than the AA requirement of humans.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Callithrix; Callitrichinae; Male; Nutritional Requirements

The vitamin A, E and C nutritional status of 313 non institutionalized elderly people living in a small town and in an agricultural village of North Italy has been evaluated. From results obtained it is possible to say that all the population tested is at low risk for vitamin A deficiency, while 10-20% of people over 70 living in the small town have low levels of vitamin E. On the contrary, the nutritional status of ascorbic acid, where the levels are inadequate in more than 50% of the population, is worrying.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Italy; Lipids; Male; Middle Aged; Nutritional Status; Retinol-Binding Proteins; Vitamin A; Vitamin E; Vitamin E Deficiency; Zinc

Mild and severe retinal photic injuries were inflicted on 22 eyes of seven monkeys fed a vitamin C-deficient diet and four monkeys given a vitamin C-enriched diet. The retinal lesions were studied by fundus examination, fluorescein angiography, and light and electron microscopy. While the general cellular response to photic injury in the retina of scorbutic animals was not different qualitatively from that in the normal animals, scurvy appeared to cause more severe tissue damage, an exaggerated repair response, and more advanced retinal degeneration. In the four groups of eyes, representing mild and severe photic injury in normal and scorbutic animals, a continuous spectrum of changes was produced. The least damage occurred from mild photic injury in the normal animals, and the most detrimental insult resulted from severe photic injury in the scorbutic animals. We propose that the basic mechanism by which ascorbate mitigates retinal photic injury depends on its redox properties. Ascorbate functions as an antioxidant in the retina. It scavenges superoxide radicals and hydroxyl radicals, quenches singlet oxygen, and reduces hydrogen peroxide, all of which are formed in retinal photic injury. This hypothesis provides an explanation for the high level of ascorbate in the retina. The pathogenetic mechanisms that correspond to the three distinct phases of pathologic changes observed in retinal photic injury are characterized. In phase 1, single oxygen is generated in a photodynamic reaction that damages the photoreceptor elements and pigment epithelium. In phase 2, macrophages attracted from the systemic circulation invade the subretinal space, and a photo-oxidative reaction generates superoxide radicals, hydrogen peroxide, and hydroxyl radicals. These free radicals attack the photoreceptor cells and pigment epithelium to cause further retinal damage. In phase 3, macrophages remain in the subretinal space for as long as 8 months after injury, causing persistent disruption of the blood-retinal barrier. The photo-oxidative reaction appears to linger, resulting in chronic retinal degeneration. It is hypothesized that in some forms of age-related macular degeneration, patients suffer from repeated mild photic insult throughout their lifetime. Aging has been associated with subclinical scurvy, which leads to even greater susceptibility to photic injury. Although ascorbate moderates many biochemical functions of the body and helps the retina ameliorate photo-oxidativ

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Light; Macaca fascicularis; Oxidation-Reduction; Retina; Retinal Diseases

Studies were carried out on 10 rabbits divided into two groups. Group I was fed on a physiological diet, group II was given additionally 200 mg of cholesterol daily. After 2 weeks the rabbits were decapitated and, having prepared the tissues according to Zannoni, the level of vitamin C was determined in the plasma, liver and intestinal wall by the method of Roe-Kuenther. It was shown that the diet rich in cholesterol caused a decrease in the level of vitamin C in the organism. The level of ascorbic acid decreased by 57% in the liver and plasms, by 52% in the wall of the caecum, whereas by 30% in the wall of the jejunum. A high level of cholesterol in the organism seems to increase its demand for vitamin C.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cecum; Cholesterol, Dietary; Jejunum; Liver; Rabbits

Biochemical indices of AA clearly showed that the young men in this study were brought into various states of AA depletion and repletion according to their dietary AA intakes. While previous studies have postulated that supplemental intakes of AA may adversely affect body status of vitamins B6 and B12, we found no changes in the B vitamin status of the young men receiving varying AA intakes. Moderate AA supplementation (605 mg/day) showed no antagonistic effect on markers of vitamins B6 and B12. Blood markers of fat-soluble vitamins A and E and iron status were not affected by AA intakes. The propensity of the gingiva to become inflamed or bleed on probing was reduced after normal (65 mg/day) AA intakes as compared to deficient (5 mg/day) intakes and upon supplementary (605 mg/day) AA intakes as compared to normal intakes. The results suggest that AA status may influence early stages of gingival inflammation and crevicular bleeding, and warrant further study of the relationship between AA and periodontal health.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Gingival Diseases; Humans; Iron; Male; Nutritional Physiological Phenomena; Periodontal Diseases; Pyridoxine; Vitamin A; Vitamin B 12; Vitamin E

We investigated the association of dietary fatty acids and plasma antioxidative vitamins with blood pressure in 722 eastern Finnish men aged 54 years, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study in 1984-1986, who had no known hypertension nor any cerebrovascular disease. Allowing for the major anthropometric, dietary, medical and psychological determinants of blood pressure in a multivariate regression analysis, plasma ascorbic acid concentration had a moderate, independent inverse association (P less than 0.0001) and the estimated dietary intake of linolenic acid an inverse (P = 0.026) independent association with mean resting blood pressure. The marked elevation of blood pressure at the lowest levels of plasma vitamin C concentration supports the hypothesis of the role of antioxidants in the aetiology of hypertension.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Blood Pressure; Coronary Disease; Dietary Fats; Humans; Linolenic Acids; Male; Middle Aged; Prospective Studies; Regression Analysis; Risk Factors

Intra-adrenal ascorbic acid (AsA) concentrations exert a braking or modulating effect upon steroid release. Because changes in steroidogenesis are mediated through alterations in adenylate cyclase activity (ACL), the effect of varied AsA plasma concentrations on guinea pig adrenal ACL activity and plasma cortisol was studied. Forty-two male guinea pigs were randomly allocated to the following seven groups: controls, scorbutic, and groups given 0.1, 5, 10, 20 or 100 mg ascorbic acid/100 g body weight, respectively. Scorbutic animals had very low levels of AsA in comparison to control animals. Plasma AsA levels increased as AsA dose increased. The levels of AsA in the group given 0.1 mg AsA were higher than in controls. Basal adenylate cyclase activity did not vary significantly among animal groups. In contrast, values for NaF-stimulated ACL activity showed a progressive decrease with increasing AsA doses. A highly significant correlation was found between decreasing ACL activity and increasing plasma AsA concentrations. On the other hand, NaF-responsive ACL activity was higher in scorbutic animals than in any other group. Higher mean cortisol values were found in the scorbutic group than in the controls, correlating with high levels of NAF-stimulated ACL activity. Higher mean cortisol values were also found in the group given 0.1 mg AsA although ACL activity in this group was not affected. This finding, coupled with reduced ACL activity in these groups, is consistent with the inhibitory effect of a megadose of AsA on production of cortisol from the adrenal. The above data may suggest that differing plasma concentrations of AsA regulate in vivo steroidogenesis by altering the activity of the membrane-bound enzyme adenylate cyclase.

Topics: Adenylyl Cyclases; Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Hydrocortisone; Male; Sodium Fluoride

In 92 uremic patients under chronic hemodialysis without ascorbic acid supplementation, serum ascorbic acid was measured before hemodialysis and between two sessions. The results indicated a more serious ascorbic acid deficiency of patients than in previous studies. This difference might be explained by the highly specific enzymatic method applied in the present study, excluding any potential interference of various serum reducing substances.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Male; Middle Aged; Renal Dialysis

Vitamin C concentrations have been measured in the plasma of 200 mothers and their newborns as well as in amniotic fluid and breastmilk. Out of this group 19 mother-infant-pairs were taken as normal control group with no risk factors, complications or diseases during pregnancy or delivery or in the newborn infant. Vitamin C concentrations in plasma showed great variability. This is true for both the entire study group and the normal control group. A positive correlation was found between the vitamin C concentrations in maternal plasma at the time of admission to the obstetric unit and that in the second stage of labor immediately before delivery. Cord blood and newborn plasma vitamin C concentrations were nearly twice as high compared to maternal concentrations. They too correlate with the concentrations in the maternal plasma. A further correlation was found between maternal plasma and amniotic fluid at the time of delivery (ratio about 1:3). No more significant correlations of vitamin C concentrations have been found in the normal control group. Various diseases or risk factors in mother and/or child were shown to be associated with lower vitamin C concentrations. Vitamin C concentrations were considerably lower in all biological fluids in smokers and mothers with diabetes. Other statistical correlations will be shown and possible casualties will be discussed. In this study vitamin C concentrations in groups with abnormal states are documented only with small numbers of cases and are therefore considered as a basis for further more specific investigations.

Topics: Adolescent; Adult; Amniotic Fluid; Ascorbic Acid; Ascorbic Acid Deficiency; Colostrum; Female; Fetal Blood; Humans; Infant, Newborn; Maternal-Fetal Exchange; Middle Aged; Milk, Human; Pregnancy; Reference Values; Risk

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Immunity, Innate; Male; Military Personnel; Trace Elements

Ascorbic acid deficiency causes qualitative and quantitative differences in the guinea pig hepatic flavin-containing monooxygenase (FMO). Kinetic studies with purified FMO indicated no significant change in the apparent Km of dimethylaniline or NADPH in ascorbate-supplemented or -deficient animals. Following purification of ascorbate-deficient guinea pig FMO by DEAE-cellulose and blue agarose chromatography, exogenous FAD was required for 15% of the FMO microsomal activity recovered. In contrast, only 5% of the total microsomal enzyme recovered from ascorbate-supplemented animals required exogenous FAD. Furthermore, there was an enhanced sensitivity to time-dependent nonlinearity with the purified ascorbate-deficient guinea pig FMO. The degree of time-dependent nonlinearity was related to the concentration of substrate. Also, purified ascorbate-supplemented guinea pig FMO was stable for 4 weeks at -20 degrees, whereas the ascorbate-deficient enzyme was inactivated. A decrease in the quantity of ascorbate-deficient guinea pig FMO compared to ascorbate-supplemented was indicated by a marked reduction in total FMO activity recovered from blue agarose chromatography and reduced protein staining intensity with SDS-PAGE at 56,000 daltons.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Flavin-Adenine Dinucleotide; Guinea Pigs; Kinetics; Molecular Weight; Oxygenases

We investigated the requirement of ascorbic acid for the induction by polychlorinated biphenyls (PCB) of hepatic drug-metabolizing enzymes in ODS-od/od rat (OD rat) which is a rat mutant unable to synthesize ascorbic acid. ODS- +/+ rats (+/+ rat), which can synthesize ascorbic acid, were used as controls. In OD rats, the dietary requirement of ascorbic acid to maintain normal growth and prevent any signs of scurvy is about 300 mg of ascorbic acid per kilogram diet. In this study, dietary levels of ascorbic acid tested were 0, 50, 300, 1000 and 3000 mg ascorbic acid per kilogram diet with or without 200 mg of PCB per kilogram diet. Feeding PCB did not affect growth in rats of either genotype. When statistical analysis was done within groups fed diets without PCB, ascorbic acid deficiency caused significant decreases in body weight gain, hepatic activities of drug-metabolizing enzymes and level of hepatic cytochrome P-450. When OD rats were fed a diet without PCB, the supplementation of about 300 mg ascorbic per kilogram diet was sufficient to maintain normal activities of hepatic aminopyrine N-demethylase, aniline hydroxylase, cytochrome c reductase and reduction of cytochrome P-450 and a normal level of hepatic cytochrome P-450. However, when OD rats were fed a diet supplemented with 200 mg PCB per kilogram of diet, significantly higher activities of hepatic aminopyrine N-demethylase and aniline hydroxylase and significantly higher level of hepatic cytochrome P-450 were observed in OD rats fed a diet supplemented with 1000 mg or 3000 mg ascorbic acid per kilogram of diet than in rats fed a diet supplemented with 300 mg of ascorbic acid. It is concluded that the dietary requirement of ascorbic acid is increased severalfold by the administration of xenobiotics, such as PCB, for the maximum induction of hepatic drug metabolism.

Topics: Aminopyrine N-Demethylase; Aniline Hydroxylase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Enzyme Induction; Male; Microsomes, Liver; Mixed Function Oxygenases; NADH Dehydrogenase; Nutritional Requirements; Pharmaceutical Preparations; Polychlorinated Biphenyls; Rats; Rats, Mutant Strains

Wound contraction and scar contracture were studied in guinea pigs deficient (stage I) and nondeficient in vitamin C (stage II). Some vitamin C-deficient and some nondeficient animals were subjected to excision of an ellipse of skin measuring 40 X 20 mm in an area not containing panniculus carnosus. The wounds were approximated without undermining. In other animals, the same type of excision was carried out; however, the wounds were left unapproximated. Wound contraction was studied in the unapproximated group and scar contracture was studied in both groups for six months postoperatively. Scar contracture was found to be more significant in animals with unapproximated wounds who were on regular diets, implying a role for vitamin C in this process. Wound contraction was noted to take place in scorbutic and non-scorbutic groups at the same rate. These findings are in line with previous studies done in areas containing panniculus carnosus, implying that the role of this cutaneous muscle in contraction and contracture is not essential in either deficient or nondeficient states. Two animals also developed a remarkably thicker scar than their counterparts while in a deficient state. The relationship between vitamin C deficiency and the formation of hypertrophic scar in guinea pigs is postulated.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cicatrix; Contracture; Female; Guinea Pigs; Skin; Time Factors; Wound Healing

To determine if systemic levels of vitamin C influence periodontal health, changes in plaque accumulation, gingival health and periodontal probing depth were measured in healthy subjects housed for 3 months in a nutrition suite that provided controlled periods of ascorbic acid depletion and supplementation. Eleven healthy, nonsmoking men, aged 19 to 28 years, ate a rotating 7-day diet adequate in all nutrients except ascorbic acid. This basal diet, which contained less than 5 mg/day ascorbic acid, was supplemented with 60 mg/day ascorbic acid for 2 weeks, 0 mg/day ascorbic acid for 4 weeks, 600 mg/day ascorbic acid for 3 weeks and 0 mg/day ascorbic acid for 4 weeks. Plasma, urine and leukocyte ascorbate levels, Plaque Index, Gingival Index, Bleeding Index and probing depths were monitored throughout the study. A uniform oral hygiene program was maintained in which oral hygiene instructions were reinforced bi-weekly. Ascorbate concentrations in body fluids and leukocytes responded rapidly to changes in ascorbic acid intake. No mucosal pathoses or changes in plaque accumulation or probing depths were noted during any of the periods of depletion or supplementation. However, measures of gingival inflammation were directly related to the ascorbic acid status. The results suggest that ascorbic acid may influence early stages of gingivitis, particularly crevicular bleeding.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Gingival Hemorrhage; Humans; Leukocytes; Male; Oral Hygiene; Periodontal Index; Periodontium

There is considerable controversy about the soundness and relevance of so-called "megavitamin" therapy for various illnesses. In this article it is suggested that this disagreement is caused to a large extent by the use of two very different approaches to nutrition, which are referred to here as the "nutritional need" and "optimal intake" approaches. It is clear that a re-evaluation of the goals of nutrition is required, as nutritional recommendations deal mainly with the prevention of deficiency diseases and are not concerned with optimal levels of intake.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Deficiency Diseases; Diet; Enzymes; Humans; Nutritional Physiological Phenomena

Protection against the toxic effects of chronic alcohol consumption was observed in male guinea pigs maintained on a high-ascorbic-acid diet (vitamin C-deficient chow plus 2.0 mg ascorbic acid/ml drinking water) as compared to animals on a low-ascorbic-acid diet (vitamin C-deficient chow and from 0.025 to 0.050 mg ascorbic acid/ml drinking water). Alcohol was orally administered to the guinea pigs at a dose of 2.5 g/kg for up to 14 weeks. Levels of serum aspartate aminotransferase and serum alanine aminotransferase were significantly elevated in animals on the low-ascorbic-acid diet that received alcohol, 120 and 250%, respectively. In contrast, in animals on the high-ascorbic-acid diet that received alcohol, levels of alanine aminotransferase were not significantly elevated and levels of aspartate aminotransferase were elevated 50%. In addition, some of the animals on the low-ascorbic-acid diet that received alcohol for 12 to 14 weeks developed hepatic steatosis and necrosis, whereas none of the animals on the high-ascorbic-acid diet that received alcohol for the same length of time manifested these changes.

Topics: Administration, Oral; Alanine Transaminase; Alcoholic Intoxication; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Aspartate Aminotransferases; Body Weight; Cytochrome P-450 Enzyme System; Fatty Liver, Alcoholic; Guinea Pigs; Male; Organ Size; Oxygenases

The properties of N-nitroso compounds (NNC) and of vitamins C and E are briefly described. The author reviews the ability of vitamins C and E to inhibit NNC formation in chemical systems, in nitrite-preserved meat, in experimental animals and in humans. Dietary vitamins C and E both produced 30% to 60% inhibitions in most carcinogenesis experiments employing preformed carcinogens. Vitamin C reversed transformation in an in vitro system. Carcinogenicity tests of the vitamins are reviewed (vitamin C can promote bladder carcinogenesis). Intake of fresh fruits and vegetables (which contain vitamin C) is negatively correlated with cancer of the stomach, esophagus, larynx, mouth and cervix. For gastric and esophageal cancer, there is evidence that this association is due to an inhibition of in vivo NNC formation. Vitamin C is apparently not a useful treatment for cancer. The author supports the recommendation that fresh fruit and vegetable intake be increased to lower the risk of cancer.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinogens; Food Preservatives; Humans; Neoplasms; Nitrites; Nitroso Compounds; Vitamin E

Vitamin C intake, and serum and leukocyte ascorbate levels were assessed serially over 6 months in 137 outpatients with Crohn's disease. Vitamin C intake was low in 18% of males and 37% of females. Serum ascorbate levels were suboptimal in 11% of males and 18% of females. Leukocyte ascorbate levels were low in 26% of males and 49% of females. Serum ascorbate levels were more frequently below the reference range in patients who smoked, but neither the serum nor the leukocyte ascorbate levels were affected by Crohn's disease activity, the use of an oral contraceptive agent, or by taking prednisone or sulfasalazine. Monthly diet counseling sessions significantly increased vitamin C intake, led to more patients consuming a normal ascorbate intake, and to a normalization of serum ascorbate values. We did not establish the importance of these ascorbate abnormalities on the clinical course of Crohn's disease. We conclude that low serum or leukocyte ascorbate levels are relatively common in patients with active or inactive Crohn's disease; these abnormalities are due in part to the reduced intake of dietary ascorbate; and the ascorbate status in patients with Crohn's disease may be normalized by improving the dietary intake of vitamin C.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Counseling; Crohn Disease; Female; Humans; Male; Middle Aged; Nutritional Requirements; Random Allocation

The effect of erythorbic acid (ErA) on ascorbic acid (AsA) content in the tissues of normal and AsA-deficient guinea pigs was studied. The animals were sacrificed at varying intervals during the experimental period, and the liver, adrenal glands, spleen and kidneys were removed. The amounts of AsA and ErA in the tissues were measured by HPLC. The content of AsA in the tissues of the animals administered both AsA and ErA was lower than that of the animals administered only AsA. But the disappearance rate of AsA from the tissues of the AsA-deficient animals was similar to that of the animals administered only ErA. The amount of AsA in the tissues of the animals administered both AsA and ErA during the repletion period was lower than that of the animals administered only AsA. These results suggest that ErA administration may affect the amount of AsA in the tissues by inhibiting its tissue uptake or its storage in the tissues, and not by accerelating the catabolism of AsA in the tissues.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Availability; Body Weight; Chromatography, High Pressure Liquid; Guinea Pigs; Kidney; Liver; Male; Spleen

The antiscorbutic effect of dehydro-L-ascorbic acid (DAsA) was investigated in vitamin C-deficient guinea pigs. Male guinea pigs were fed vitamin C-deficient diets for 16 days to deplete body L-ascorbic acid (AsA) pools and then fed the deficient diet supplemented with DHA and/or AsA intraperitoneally for 14 days. During the repletion period, most of the animals injected with 0.5 mg DAsA/day developed scurvy, their body weights decreased and their mortality rate was higher than that of the other groups injected with 0.5 mg AsA/day or 5 mg DAsA/day. Injecting animals with 0.5 mg AsA/day resulted in the disappearance of the typical scorbutic symptoms and regaining of body weight. These data indicate that DAsA has considerably less antiscorbutic activity than AsA in vitamin C-deficient guinea pigs.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Dehydroascorbic Acid; Guinea Pigs; Kidney; Liver; Male; Scurvy; Spleen

The tissue distribution of L-ascorbic acid (AsA) and dehydro-L-ascorbic acid (DAsA) in guinea pigs injected with DAsA intravenously was examined using high-performance liquid chromatography. DAsA injected into guinea pigs fed normal diets containing AsA (control group) was readily taken into erythrocytes, and AsA contents of plasma and other tissues rapidly increased after DAsA injection. In animals fed vitamin C-deficient diets, DAsA was also detected in erythrocytes; however, the increase of AsA in their tissues was considerably less than that of control group. From these results, it was suggested that utilization of DAsA as AsA in vitamin C-deficient guinea pigs was less than that of control animals, and the reduction mechanism of DAsA to AsA in vitamin C-deficient guinea pigs may have differed from that of control groups.

Topics: Administration, Oral; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Chromatography, High Pressure Liquid; Dehydroascorbic Acid; Guinea Pigs; Injections, Intravenous; Male; Tissue Distribution

Topics: Alcoholism; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Male

The aim of this study was to ascertain the effects of ascorbic acid deficiency and supplementation on endurance and mitochondrial oxidative capacities in various tissues of guinea pigs. Endurance capacity was significantly reduced by ascorbic acid deficiency and supplementation. Oxidative capacities were reduced in heart, liver and brown adipose tissue but it seems as if skeletal muscle is protected against ascorbic acid deficiency and supplementation-induced oxidative damage. Skeletal muscle and liver but not heart appear to be susceptible to exercise-induced oxidative damage. To a certain extent oxidative capacities could be related to the glutathione status in the various tissues.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Glutathione; Glutathione Disulfide; Guinea Pigs; Male; Mitochondria, Heart; Mitochondria, Liver; Mitochondria, Muscle; Organ Specificity; Oxygen Consumption

We have previously found that ascorbic acid (AA) deficiency in guinea pigs enhances the pulmonary toxicity of nitrogen dioxide (NO2). The present study showed that exposure to NO2 (4.8 ppm, 3 hr) significantly increased lung lavage fluid protein (a sensitive indicator of pulmonary edema) only in guinea pigs fed rabbit chow (a diet not supplemented with vitamin C) for at least 7 days, at which time lung AA was about 50% of normal. The rabbit chow diet did not cause reduced body weight as did commercial synthetic scorbutic diets, even when they were supplemented with AA. After 14 days of feeding rabbit chow, lung AA was reduced to 15% of control. At this time, alpha-tocopherol (AT) in the same lungs was reduced to 85% of control, and lung nonprotein sulfhydryls (NPSH) were increased to 114% of control. Exposure of the guinea pigs to NO2 (4.5 ppm, 16 hr) increased wet lung weight and further altered the antioxidants in deficient (but not normally fed) animals in the following manner: NPSH content was increased to 130% of control, AT was decreased to 74% of control, and AA was increased from 15 to 50% of control. These findings suggest that depletion of AA in guinea pigs removes an important defense against NO2. The lung appears to be able to partially compensate for the dietary lack of antioxidant by accumulating AA from other tissues and by increasing NPSH concentrations. However, sufficient exposure to NO2 leads to oxidation of AT and pulmonary edema. Conditions in which NO2 produced edema were accompanied by only a slight consumption of AT, and no detectable oxidation of lung AA or NPSH.

Topics: Animal Feed; Animals; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Lung; Nitrogen Dioxide; Probability; Proteins; Sulfhydryl Compounds; Time Factors; Vitamin E

Female, adult guinea pigs were fed a low ascorbic acid diet ad libitum. Oral administrations of either estinyl (5 micrograms) or progestogen (250 micrograms) in combination with 5 mg of ascorbic acid (minimum requirement) daily for 21 d, resulted in significantly lower (P less than 0.05) concentrations of ascorbic acid in plasma, liver, adrenals and urine than in animals receiving only 5 mg of the vitamin. None of these animals showed any clinical signs of ascorbic acid deficiency. Clinical manifestations of scurvy were exhibited, however, when animals receiving no ascorbic acid supplement were treated with the steroid hormones for 7 d. All of these animals died by d 10. On the other hand, the animals receiving neither ascorbic acid nor the steroids remained free from any signs of scurvy, except one (out of six), which died by d 12. In vitro studies revealed a markedly higher rate of oxidation of ascorbic acid in the presence of either estinyl or progestogen than in untreated controls. These results were further supported by a higher level of plasma ceruloplasmin in animals receiving a combination of estrogen and progestogen than in animals receiving no hormones. An in vivo dose-related effect of ascorbic acid indicated that the steroid-mediated lowering effect of the vitamin status could be counteracted by increasing the dose of ascorbic acid from 5 to 10 mg/d for 2 wk. These results suggest that the interactions between oral contraceptive hormones and ascorbic acid may be of clinical importance only in the case of borderline intake of the vitamin.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Contraceptives, Oral, Combined; Estradiol Congeners; Female; Guinea Pigs; In Vitro Techniques; Liver; Oxidation-Reduction; Progesterone Congeners

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Platelets; Child; Child, Preschool; Hemoglobinopathies; Humans; Infant; Iron; Thalassemia

Since mice can synthesize ascorbic acid but man cannot, the ascorbate status in murine and human leukaemia was compared. The decline in plasma ascorbate concentration in both cases indicates that vitamin C deficiency occurs in malignancy. Analysis of tissue ascorbate values in mice also indicated that an enhanced rate of utilization of this vitamin occurs during malignancy, as does an increased rate of excretion, and both events may be responsible for vitamin C deficiency. The hepatic ascorbate values suggest an endeavour by the animals to compensate for the loss through increased synthesis and storage of the vitamin, at least in the early stages of the disease.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Kidney; Leukemia, Experimental; Leukemia, Lymphoid; Leukemia, Myeloid; Liver; Mice; Spleen; Tissue Distribution

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Mouth; Occupational Dentistry; Occupational Diseases; Periodontal Diseases

This paper provides indirect evidence that ascorbate nutriture affects plasma concentrations of complement component C1q in the guinea pig. C1q is a protein with a hydroxyproline-rich region similar in structure to collagen. It is essential for complement-mediated lysis of pathogens and may also facilitate phagocytic activity of macrophages and neutrophils. Since C1q is the only hydroxyproline-containing protein in the euglobulin fraction of plasma, it can be quantified indirectly by precipitating this fraction, hydrolyzing it and estimating hydroxyproline colorimetrically. We investigated the effect of ascorbate nutriture on protein-bound hydroxyproline (PBH) in the euglobulin fraction of plasma of young male guinea pigs. The animals had been depleted of ascorbate for 3 wk to produce scurvy and then repleted (6 wk) as follows: 0.5, 2.0 and 10.0 mg ascorbate/100 g body weight per d or 10 g ascorbate per liter of drinking water. PBH values were significantly correlated (P less than 0.001) with dietary ascorbate (+ 0.74) and with liver ascorbate (+ 0.75). Plasma PBH was significantly higher (P less than 0.01, Scheffé's test) in guinea pigs fed ample ascorbate (10.0 mg/100 g body weight per day) or tissue-saturating levels (10 g/L of drinking water) than in those fed adequate (2.0 mg/100 g body weight) or suboptimal (0.5 mg/100 g body weight) levels. These data are consistent with the known biochemical role of ascorbic acid in hydroxyproline biosynthesis and suggest a possible link between ascorbate and the immune response via C1q.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Proteins; Complement Activating Enzymes; Complement C1q; Diet; Guinea Pigs; Hydroxyproline; Liver; Male

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Guinea Pigs; Lathyrism; Male

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Exercise Test; Heart Rate; Humans; Male; Nutritional Requirements; Oxygen Consumption; Physical Exertion; Respiration; Riboflavin Deficiency; Vitamin B 6 Deficiency

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Brazil; Diet; Eating; Fruit; Humans; Nutrition Surveys; Vegetables

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Folic Acid; Folic Acid Deficiency; Humans; Pyridoxine; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin E; Vitamin E Deficiency; Vitamin K; Vitamin K Deficiency; Vitamins

Channel catfish fingerlings were fed purified diets containing 0 to 3000 mg/kg of ascorbic acid until external signs of scurvy were seen in the fish fed the ascorbic acid-deficient diet. At this time, resistance to bacterial infection, antibody production, complement activity and phagocytic activity were assessed for fish from the various dietary treatments. Mortality rates of fish experimentally infected with Edwardsiella ictaluri, the bacterium causing enteric septicemia in channel catfish, decreased with increases in dietary ascorbic acid doses, ranging from 100% for fish fed the ascorbic acid-deficient diet to 15% for fish fed 300 mg ascorbic acid per kilogram diet and 0 for fish fed 3000 mg ascorbic acid per kilogram diet. Antibody response to E. ictaluri antigen, hemolysis of sensitized sheep erythrocytes by complement activity and phagocytic engulfment of E. ictaluri by peripheral phagocytes were each impaired in fish fed the diet without supplemental ascorbic acid; intracellular bactericidal activity of the phagocytes was not affected by ascorbic acid deficiency. There were no differences in antibody production, complement activity, or phagocytic activities among fish fed diets containing 30-300 mg ascorbic acid/kg of diet. However, the dose level of 3000 mg ascorbic acid/kg significantly enhanced antibody production and complement activity.

Topics: Animal Nutritional Physiological Phenomena; Animals; Antibody Formation; Ascorbic Acid; Ascorbic Acid Deficiency; Complement System Proteins; Enterobacteriaceae Infections; Fish Diseases; Fishes; Immunity, Cellular; Immunity, Innate; Phagocytosis

The Dutch Nutrition Council recommends an average daily intake of at least 50 mg of vitamin C. In a Dutch centre for nursing and rehabilitation this amount in the food as consumed by 272 patients and as served by the kitchen was calculated to be below 20 mg. About half of the patients consumed additional food - rich in vitamin C - each day either bought or acquired. Symptoms pertaining to the disease scorbut, were observed in a considerable number of these patients, but these may also be caused by other diseases. Patients completely dependent on food served by the central kitchen, had very low values of plasma vitamin C, in contrast to patients who used extra fruit each day. Centres for nursing and rehabilitation are recommended to serve 150 ml vitamin C-rich fruit juice each day, thereby combining the advantages of providing enough fluid intake and preventing obstipation.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Chromatography, High Pressure Liquid; Humans; Nursing Homes; Nutritional Requirements; Scurvy

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Naval Medicine; Tropical Climate

Guinea pigs fed a normal diet show the expected diurnal variation in 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Vitamin C deficiency, however, suppresses the diurnal peak activity of reductase, due to a decrease in active (unphosphorylated) enzyme. Inhibition of reductase is paralleled by both a fall in hepatic cholesterol synthesis and a rise in serum cholesterol. Incubation of normal guinea pig hepatic microsomes with physiologic and supraphysiologic concentrations of sodium ascorbate also leads to a concentration-dependent inhibition of reductase activity. Thus, dietary extremes of vitamin C may exert similar effects on reductase activity and cholesterolgenesis. Moreover, the changes in enzyme activity induced by ascorbic acid appear to be due in part to a direct effect of the vitamin on the microsomally bound enzyme.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Circadian Rhythm; Guinea Pigs; Hydroxymethylglutaryl CoA Reductases; Liver; Male; Phosphorylation

This article suggests that atherosclerosis is a plurideficiency disease. Increasing only linoleic acid intake in daily nutrition to counteract atherosclerosis has failed to give satisfactory results. The use of lecithin affects the metabolism and transportation of cholesterol in the blood more efficiently than do the polyunsaturated fats. Furthermore, insufficient quantities of vitamins B6 and C in the blood contribute to lesions of the arterial endothelium, which are indistinguishable from the first stages of atherosclerosis. It is recommended, therefore, that these factors should be combined, and that, together with a sufficient quantity of polyunsaturated fatty acids, the daily diet be supplemented with adequate doses of lecithin, vitamin B6 (in B complex), and vitamin C.

Topics: Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Nutritional Physiological Phenomena; Phosphatidylcholines; Pyridoxine; Risk; Vitamin B 6 Deficiency

The amount of oral ascorbic acid that a patient can tolerate without diarrhea, increases somewhat proportionately to the "toxicity" of his disease. Clinically, in a disease ameliorated by ascorbate, there is a suppression of symptoms only with very high doses and approximately to that extent which a nonrate-limited, antioxidant free radical scavenger, might be expected to affect that disease process if all harmful free radicals and highly reactive oxidizing substances were quenched. In most pathologic processes, the rate at which free radicals and highly reactive oxidants are produced, exceeds the rate at which the ordinary rate-limited antioxidant free radical scavenging mechanisms can quench those free radicals and oxidants. When ascorbate acts as a scavenger, dehydroascorbate is formed; but if the ascorbate/dehydroascorbate (AA/DHA) ratio is kept high (the redox potential kept reducing) until the unstable dehydroascorbate undergoes hydrolysis or can be reduced back to ascorbate, the dehydroascorbate will do no harm. Since even at very high doses, ascorbate is virtually nontoxic, it may be given in the enormous doses necessary to quench almost all unwanted free radicals and oxidants. The wide spectrum of infectious diseases ameliorated by massive doses of ascorbate indicates some common pathologic processes in these diseases.

Topics: Acquired Immunodeficiency Syndrome; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Diarrhea; Dose-Response Relationship, Drug; Free Radicals; Glucosephosphate Dehydrogenase Deficiency; Humans; Infant; Kidney Calculi; Kinetics; Oxidation-Reduction; Scurvy; Sudden Infant Death

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Catalase; Child; Child, Preschool; Chronic Disease; Diabetes Mellitus, Type 1; Female; Humans; Male; Obesity

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Food-Processing Industry; Humans; Male; Middle Aged; Niacinamide; Occupational Diseases; Sucrose; Vitamin B Complex; Vitamin B Deficiency

With reference to a case of vitamin C deficiency in a strict vegetarian, the authors recall the clinical findings and current diagnostic procedures in scurvy. Serum and urine ascorbic acid assays are now available and established the diagnosis. Management rests upon vitamin C given in a curative dosage of 1 to 2 g per day for 15 days followed by a preventive dosage of 10 mg per day.

Topics: Adult; Anemia; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Humans; Male; Purpura; Scurvy

The influence of ascorbate deficiency and megadosage on the metabolism of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) was investigated in the guinea pig. After 21 days on a scorbutogenic diet, microsomal cytochrome P-450 and cytochrome b5 levels fell by 51 and 32%, respectively, while cytochrome c reductase activity remained constant. The activities of NDMA and NDEA dealkylase I were also depressed significantly. The Vmax of NDMA demethylase I and NDEA deethylase I was significantly depressed. Also, ascorbate deficiency significantly decreased the plasma clearance of both nitrosamines though the LD50 of neither were altered by ascorbate nutrition. Covalent binding of 14C from [14C]NDMA and [14C]NDEA to DNA obtained from liver slices was significantly lower in the deficient than in the control samples; megadosage appeared to have the opposite effect.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome b Group; Cytochrome P-450 Enzyme System; Cytochromes b5; Diethylnitrosamine; Dimethylnitrosamine; Guinea Pigs; Kinetics; Male; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Nitrosamines

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Kidney Failure, Chronic; Male; Oxalates; Oxalic Acid; Renal Dialysis

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Climate; Humans; Male; Naval Medicine; Time Factors; USSR; Weather

Leucocyte ascorbic acid levels failed to identify six of seven elderly patients shown to be deficient on an oral vitamin C saturation test. Compared to those with a normal saturation test, patients judged deficient had lower levels for triceps skinfold thickness, mean arm muscle circumference and Quetelet's index; there was a significant association with the habit of eating alone, and with a dietary intake of less than 30 mg of ascorbic acid daily (the recommended daily allowance in the U.K.). No significant difference was found in the values for haemoglobin, serum albumin or potassium concentrations between the two groups, and no association shown between a deficient saturation test and smoking, season, sublingual varicosities or an abnormal bleeding time.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Coagulation Tests; Diet; Feeding Behavior; Female; Humans; Leukocytes; Male; Skinfold Thickness

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Male; Middle Aged; Tuberculosis, Pulmonary

The purpose of this study was to evaluate the systemic effects of varying levels of orally administered ascorbic acid during wound healing in guinea pig oral mucosa. Forty five Murphy/Hartley guinea pigs were randomly placed into four groups and fed an ascorbic acid deficient diet for 2 weeks. Each group of animals then received a daily oral supplement of the following doses of ascorbic acid: 0.5 mg, 5.0 mg, 50 mg, and 250 mg. All animals were weighed twice a week. Twenty eight days later, a standardized wound was made in the premaxilla. On day 35, all animals were sacrificed. Blood samples were evaluated for levels of ascorbic acid. Thirty nine samples showed insignificant levels of vitamin C, 32 of which showed no ascorbic acid. Organ to body weight ratios were calculated and compared. Spleen to body weight ratios were not affected by different ascorbic acid levels. High levels of ascorbic acid caused a significant increase in adrenal gland to body weight ratios. Varying the levels of ascorbic acid did not affect growth prior to surgical wounding. Increased levels of ascorbic acid enhanced body weight recovery post surgically.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Dose-Response Relationship, Drug; Guinea Pigs; Kidney; Organ Size; Spleen; Wound Healing

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child, Preschool; Humans; Infant; Iron; Iron Deficiencies

Absorption of ascorbic acid was assessed by measuring its urinary excretion following the administration of a standard dose under pre-determined conditions. The absorption mechanism appeared to be a saturable one and with intakes of up to 1 g over 90 per cent of the subsequent urinary excretion occurred during the first 8 h. Significantly less ascorbic acid was absorbed by elderly persons than by young ones; after a 500 mg dose the mean urinary excretion by nine elderly females (mean age 82.6) was 25 mg and by six young females (mean age 21.8) 245 mg. It is suggested that impaired gastrointestinal absorption is an important factor in the aetiology of low blood concentrations of ascorbic acid in the elderly.

Topics: Adult; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Transport; Circadian Rhythm; Female; Humans; Intestinal Absorption; Male; Middle Aged; Sex Factors; Time Factors

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Citrus; Food Handling; Humans

There is evidence that H2O2 present in aqueous humor arises from ascorbic acid which is also present in this fluid, but the extent to which peroxide is derived from ascorbic acid is not known. We have measured the concentrations of H2O2 and ascorbic acid normally present in the aqueous humor of various species and also under conditions in which the level of ascorbic acid in the fluid was experimentally altered. In aqueous humor of rabbit and guinea pig the concentration of ascorbic acid was 10 times higher than that present in aqueous of rat and frog. Similarly, the concentration of H2O2 was four to 10 times higher in rabbit and guinea pig aqueous compared to that in rat and frog. Consistent with the higher concentration of ascorbic acid in posterior compared to anterior aqueous humor in the rabbit, the concentration of H2O2 was also significantly higher in the posterior aqueous. When ascorbic acid in rabbit aqueous humor was elevated by intraperitoneal administration of the compound, there was a significant increase in the level of H2O2 in both anterior and posterior aqueous humor. Moreover, when the level of ascorbic acid was lowered experimentally by placing guinea pigs on an ascorbic acid deficient diet, a 10-fold decrease in the level of both ascorbic acid and H2O2 was observed in the aqueous humor. Upon returning the animals to a normal diet, the concentrations of both compounds returned to control values. The direct correlation between the concentrations of ascorbic acid and H2O2 in aqueous humor suggests that ascorbic acid is the primary source of H2O2 in this fluid.

Topics: Animals; Anura; Aqueous Humor; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Guinea Pigs; Hydrogen Peroxide; Rabbits; Rats; Rats, Inbred Strains; Species Specificity

beta- Hydroxyaspartic acid is a rare amino acid, present in all vitamin K-dependent plasma proteins except prothrombin, and is formed by a post-translational hydroxylation of aspartic acid. We have now investigated whether this hydroxylation, like that of proline in collagen, is vitamin C-dependent. The vitamin K-dependent plasma proteins were isolated from normal and scorbutic guinea pig plasma by barium citrate adsorption and the beta- hydroxyaspartic acid content was determined. Compared with normal animals, scorbutic animals showed no significant reduction of beta- hydroxyaspartic acid content. In warfarin-treated animals there was a decreased content of both beta- hydroxyaspartic acid and gamma-carboxyglutamic acid in the barium citrate adsorbed fraction. It was concluded that the post-translational hydroxylation of aspartic acid is unlikely to be vitamin C-dependent.

Topics: 1-Carboxyglutamic Acid; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Aspartic Acid; Blood Coagulation; Blood Proteins; Guinea Pigs; Hydroxylation; Protein Processing, Post-Translational; Vitamin K; Warfarin

Ascorbic acid levels are commonly reported to be decreased in alcoholics. Although this deficiency could be due to dietary factors, there is evidence that ascorbic acid may be involved in the metabolism and acute effects of ethanol, possibly related to the pathogenesis of alcoholism. Therefore, we examined ethanol preference in guinea pigs receiving an ascorbate deficient vs a normal diet. Brain and spleen ascorbic acid levels were dramatically decreased, but ethanol preference was not altered by the acute dietary deficiency of this vitamin. In addition, an acute stressor (cold water swim), alone or in combination with ascorbate deficiency, had no effect on ethanol preference. At termination of the experiment, two measures of brain aminergic function (MAO activity and 3H-spiroperidol binding), purportedly altered by ethanol or ascorbic acid or both, were not associated with tissue ascorbate levels.

Topics: Alcohol Drinking; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Butyrophenones; Corpus Striatum; Ethanol; Food Preferences; Guinea Pigs; Male; Monoamine Oxidase; Receptors, Dopamine; Spiperone

The effect of ascorbic acid supplementation on physical working capacity was studied in young adolescent boys in which the concomitant biochemical riboflavin and pyridoxin deficiencies were corrected by medicamentous prophylaxis. After daily administration for two months of 70 mg ascorbic acid, the mean plasma vitamin C in the experimental group (n = 49) rose from 0.33 to 1.49 mg/dl (p less than 0.001) and the prevalence of deficient plasma vitamin C values (less than 0.20 mg/dl) decreased from 52.3 percent to zero. The improvement in vitamin C biochemical status was also accompanied by a statistically significant increase in VO2 max. (p less than 0.01). There were no significant changes neither in the mean plasma vitamin C values nor in the mean VO2 max. in the control group subjects (n = 42). The increase in VO2 max. in the experimental group was primarily the result of an increase of VO2 max. in subjects with initially lower values. When data from both experimental and control groups were pooled together, a positive and significant association was found between VO2 max. and the increase of plasma vitamin C values below 1.0 mg/dl. No further increase in VO2 max. was observed when vitamin C plasma values reached 1.0 mg/dl or more. The two regression lines crossed at X = 0.86 mg/dl. This cut off point of plasma vitamin C level corresponds to a dietary intake of about 80 mg of ascorbic acid per day. The results of this study are in agreement with the suggested optimal ascorbic acid daily intake obtained by kinetic studies with (1-14C) ascorbic acid.

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Erythrocytes; Hematocrit; Hemoglobins; Humans; Male; Oxygen Consumption; Physical Fitness; Pyridoxine; Riboflavin; Transferrin; Yugoslavia

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Female; Humans; Infant; Nutritional Requirements; Pregnancy

The effects of long-term chronic ascorbic acid deficiency and excessive ascorbic acid consumption on bile acid metabolism and biliary lipid composition were studied in guinea pigs. Male, weanling guinea pigs were fed a cereal-based scorbutigenic diet for 19 or 21 weeks. Ascorbic acid was administered either orally at 0.15 (group A) or 2.0 (group B) mg/100 g body weight, or it was mixed in the diet at levels of 500 (group C), 16-22 (group D), or 20,000 mg/kg (group E). Chronic ascorbic acid deficiency (groups A and D) caused depression of hepatic cytochrome P-450 levels and elevation of plasma cholesterol. Excessive ascorbate consumption did not alter these parameters relative to control levels. In contrast to results obtained in guinea pigs fed low or high amounts of ascorbate for 7-9 weeks, prolonged consumption of inadequate or excessive ascorbate resulted in little or no change in bile acid metabolism and biliary lipid composition except that bile acid pool size was increased 12% as a result of excessive ascorbate ingestion. Results of the present study suggest that there may be important differences in the guinea pig's metabolic response to ascorbic acid deficiency and ascorbic acid excess, depending on the length of the experimental period.

Topics: Administration, Oral; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Body Weight; Cholesterol; Cytochrome P-450 Enzyme System; Guinea Pigs; Male; Microsomes, Liver

Periodontal disease is one of the most prevalent health problems in the world and is the major cause of tooth loss in the adult population. Its two major subdivisions are gingivitis where disease is confined to the gingiva, and periodontitis where disease is present both in the gingiva and the supporting periodontal tissues. During the first stage there is a vasculitis of vessels subjacent to the junctional epithelium which is followed by exudation of fluid from the gingival sulcus and migration of leukocytes. There is variable expression of this stage throughout the mouth with new areas of involvement appearing in place of healed areas. Mast cells which are present in the gingival connective tissues may participate in this inflammatory response by liberating histamine. Ascorbic acid deficiency has been shown to be a conditioning factor in the development of gingivitis. When humans are placed on ascorbic acid deficient diets there is increased edema, redness and swelling of the gingiva. These changes have been attributed to deficient collagen production by gingival blood vessels. However, this may be due to an antihistamine role of ascorbic acid. This vitamin may act to directly detoxify histamine or effect a change in the level of enzymes responsible for histamine metabolism. This could occur through the influence of ascorbic acid in altering cyclic AMP (c-AMP) levels. Such changes in the level of this regulatory molecule could result in increased histamine-N-methyl transferase and other enzymes responsible for the breakdown of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dental Plaque; Female; Gingiva; Gingivitis; Guinea Pigs; Histamine; Humans; Oral Hygiene; Pregnancy; Rats

Topics: Amino Acids; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Proteins; Brain; Histidine; Liver; Macaca nemestrina; Male; Organ Specificity; Protein-Energy Malnutrition

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Male; Nicotine; Smoking

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Guinea Pigs; Humans; Methylene Blue; Microsomes, Liver; NADH Dehydrogenase; Oxidoreductases, N-Demethylating; Poisoning; Sulfones

Endogenous levels of ascorbic acid may play a role in regulating the biosynthesis of cyclooxygenase metabolites in lungs of male guinea pigs. The in vitro biosyntheses of prostaglandins, prostacyclin and thromboxane were examined using isolated microsomal membranes from control and ascorbic acid deficient guinea pigs, under conditions in which the substrate concentration ( [3H]-arachidonic acid) was varied from 10-100 microM. Maintenance of guinea pigs for two weeks on an ascorbic acid deficient diet did not alter lung/body weight ratios, nor protein content of the lungs. Lung microsomes from ascorbic acid deficient guinea pigs demonstrated a greater biosynthesis of total cyclooxygenase metabolites at low substrate concentrations. A significant increase in the PGF2 alpha synthesis was observed in the scorbutic microsomes at 20 microM arachidonic acid. At higher substrate concentrations the production of PGF2 alpha was significantly reduced in ascorbic acid deficient animals. By contrast, biosynthesis of thromboxane or prostacyclin in treated animals was not significantly different from control microsomes. At a substrate concentration of 100 microM, there was equivalent synthesis of total cyclooxygenase metabolites in control and vitamin C deficient animals. The changes in prostaglandin biosynthesis were not due to an interaction of ascorbic acid with glutathione levels in the lung. These results support the hypothesis that ascorbic acid may modulate cyclooxygenase activity in the lung in a substrate dependent nature.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Guinea Pigs; Kinetics; Lung; Male; Microsomes; Organ Size; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Sulfhydryl Compounds

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Male; Middle Aged; Mouth Diseases; Orthomolecular Therapy

Topics: Adolescent; Adrenal Glands; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Catecholamines; Chronic Disease; Humans; Middle Aged; Recurrence; Stomatitis, Aphthous; Sympathetic Nervous System

Only a weak association between periodontal disease and ascorbic acid deficiency has been shown in the analysis of nutritional and periodontal health data collected from a representative sample of the US population. Intake of ascorbic acid in amounts larger than those recommended by the dietary standards does not seem to be associated with better periodontal health. The results of this study also suggest that dental practitioners are better advised to concentrate on plaque control rather than vitamin C supplements to prevent and control periodontal disease in their patients.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Humans; Middle Aged; Periodontal Diseases; Periodontium; United States

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Gastrointestinal Neoplasms; Humans; Neoplasms; Neoplasms, Experimental

Topics: Ascorbate Oxidase; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Chemical Analysis; Chlorides; Colorimetry; Ferric Compounds; Humans; Hydrogen-Ion Concentration; Oxidation-Reduction; Time Factors; Triazines

Collagen production by cultured human lung fibroblasts was examined when the cells were made deficient in ascorbate. Cells grown in the absence of ascorbate produced 30% less collagen during a 6-h labeling period than cells incubated with as little as 1 microgram/ml ascorbate during the labeling period. Cells grown without ascorbate produced under-hydroxylated collagen which was subject to increased intracellular degradation from a basal level of 16% to an enhanced level of 49% of all newly synthesized collagen. The likely mechanism for increased intracellular degradation is the inability of under-hydroxylated collagen to assume a triple-helical conformation causing it to be susceptible to intracellular degradation. Measurement of collagen production by enzyme linked immunoassay (ELISA) using antibodies directed against triple-helical determinants of collagen showed that both types I and III collagens were affected. In contrast, another connective tissue component, fibronectin, was not affected. Analysis by ELISA showed a greater decrease in collagen production than did analysis by the collagenase method, suggesting that some non-helical collagen chains (detected by collagenase but not by ELISA) were secreted in the absence of ascorbate. These results provide a mechanism to account, in part, for the deficiency of collagen in connective tissues which occurs in a state of ascorbate deficiency.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cells, Cultured; Collagen; Fibroblasts; Humans; Hydroxyproline; Kinetics; Lung; Proline

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Scurvy

Topics: Adrenal Glands; Animals; Ascariasis; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Larva; Liver; Male; Stimulation, Chemical; Vitamin A

Threonic acid is a major breakdown product of ascorbic acid used as a food additive. When administered orally to guinea-pigs (100 mg/kg body weight) for periods of 4 or 28 days, it produced a significant fall in the ascorbic acid concentration of certain organs but was without effect on other physiological and biochemical characteristics. The lifespan of scorbutic guinea-pigs was significantly reduced by dietary threonic acid (100 mg/kg body weight). The results indicate that threonic acid may modify the metabolism of ascorbic acid in guinea-pigs.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Butyrates; Drug Interactions; Food Additives; Guinea Pigs; Hydroxybutyrates; Longevity; Male; Organ Size; Time Factors; Tissue Distribution

Studies were carried out to characterize the response of hepatic mixed function oxidase (MFO) activity to chronic ascorbic acid deficiency and excessive ascorbic acid intake in the guinea pig. When guinea pigs were fed excessive ascorbic acid, there was a small increase in hepatic cytochrome P-450 which was unaccompanied by any alteration in drug-metabolizing enzyme activity. Similarly, induction of MFO activity by phenobarbital was not modified by excessive ascorbic acid administration. Chronic ascorbic acid deficiency resulted in depressed metabolism of aniline, aminopyrine, ethoxycoumarin and benzphetamine, but not of ethylmorphine, in comparison with animals fed diets containing control and/or excessive amounts of ascorbic acid. In contrast to the metabolism of all drugs studied, the 7 alpha-hydroxylation of cholesterol was depressed by both inadequate and excessive vitamin C intake, demonstrating the unique sensitivity of cholesterol 7 alpha-hydroxylase to dietary ascorbate.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Benzphetamine; Cytochrome P-450 Enzyme System; Diet; Dose-Response Relationship, Drug; Enzyme Induction; Guinea Pigs; Kinetics; Liver; Male; Mixed Function Oxygenases; Oxidoreductases; Phenobarbital

The effect of peritoneal dialysis on plasma ascorbate levels was investigated in 32 patients suffering from end-stage renal disease. Our studies demonstrated a high peritoneal clearance of ascorbic acid resulting in a significant loss into the dialysate. The quantity of ascorbic acid lost by patients undergoing peritoneal dialysis was proportional to the predialysis ascorbic acid levels. Since the ascorbic acid lost from the plasma during peritoneal dialysis is not adequately replaced by dietary consumption of vitamin C, patients undergoing chronic peritoneal dialysis should receive ascorbic acid supplementation as an important part of their therapeutic regimen.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Kidney Diseases; Male; Middle Aged; Peritoneal Dialysis

Liver carnitine level decreased from 249 +/- 16.1 nmoles/g (mean +/- SEM) control value to 148 +/- 9.8 nmoles/g (59.4%) in ascorbic acid deficient guinea-pigs, while in the underfed ('pair-fed') group it decreased to 181 +/- 14.1 nmoles/g (72.6%). Underfeeding also resulted in lower ascorbic acid levels; the depression of carnitine in the underfed animals could be prevented by an overdose (200 mg daily) of ascorbic acid.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carnitine; Food Deprivation; Guinea Pigs; Liver; Male; Muscles

A study of vitamin C requirements was undertaken in the village of Keneba, The Gambia, during the rainy season, when the intake of vitamin C-rich foods is very low. The effect of four supplementary levels of vitamin C (0, 24, 47 and 60 mg/day), together with a milk and biscuit food supplement which provided 34 mg vitamin C/day, was studied for a five-week period. Plasma ascorbate increased from 0.25 to 0.72 mg/dl; buffy coat ascorbate increased from 14.7 to 24.3 micrograms/10(8) cells and breast milk ascorbate increased from 3.4 to 5.5 mg/dl as intake increased from 34 to 103 mg/dl. Breast milk ascorbate approached a plateau at the high intakes. A fasting plasma ascorbate of at least 0.3 mg/dl in 97.5% of the population of lactating women in Keneba would require a daily vitamin C intake of about 117 mg. No differences between vitamin C supplementation levels were observed with respect to changes in plasma iron, total iron-binding capacity or its percentage saturation. Whole blood histamine levels showed a slight downward trend as the vitamin C intake increased.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Gambia; Histamine; Humans; Iron; Lactation; Milk, Human; Pregnancy; Rural Population; Tea

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diabetes Mellitus; Glucose; Guinea Pigs; Humans; Lipid Metabolism; Rats

Measurements of pentane and ethane as indices of in vivo lipid peroxidation were made on samples of breath from vitamin C-sufficient and vitamin C-deficient guinea pigs injected with 23 microliters carbon tetrachloride (CCl4)/100 g body wt. Vitamin C-deficient animals produced significantly more pentane and ethane after CCl4 treatment than did vitamin C-sufficient guinea pigs. Pretreatment of vitamin C-deficient animals with 75 mg ascorbic acid/100 g body wt significantly lowered both pentane and ethane evolution. Protection against in vivo lipid peroxidation similar to that provided by ascorbic acid was also found when vitamin C-deficient guinea pigs were pretreated with isoascorbic acid, reduced glutathione, alpha-tocopherol or beta-carotene. When animals were pretreated with the radical scavenger mannitol, a protective effect was also observed as measured by pentane evolution.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carbon Tetrachloride Poisoning; Ethane; Guinea Pigs; Lipid Peroxides; Male; Pentanes; Time Factors

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Benzene; Child; Humans; Motivation; Otorhinolaryngologic Diseases; Pharyngitis; Substance-Related Disorders

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Interferons; Multiple Sclerosis; Virus Diseases

Serum and liver ceruloplasmin levels rose markedly in guinea pigs with acute scurvy and with chronic latent scurvy. Their increase in the former condition can be attributed to the general stress reaction, but the increase in ceruloplasmin levels in concentration may have a stimulant effect on the ceruloplasmin, when the oxidation of Fe2+ to Fe3+ is potentiated, may obstruct the binding of iron to protoporphyrin and prevent formation of the haeme of cytochrome P 450 and b5.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Ceruloplasmin; Cytochrome b Group; Cytochrome P-450 Enzyme System; Cytochromes b5; Guinea Pigs; Iron; Liver; Male

The cholesterol content of the high-density plasma lipoproteins (d over 1.1 g.cm-3) of guinea-pigs with experimental vitamin C deficiency, followed by realimentation with suboptimal (1 mg/animal per day) or optimal (10 mg/animal per day) doses of L-ascorbic acid for 6-9 weeks in the continued presence of an elevated alimentary cholesterol intake (0.5 g/kg diet), did not exceed 5% of the total plasma cholesterol concentration and did not alter significantly with changes in the degree of vitamin C saturation of the organism. The maximum total body tissue cholesterol concentrations were found in C-deficient guinea-pigs (plasma, adrenals) and in the group with partial vitamin C deficiency (liver, brain); the lowest values were found in the group whose organism was fully saturated with vitamin C. Under conditions of a raised cholesterol intake, ascorbic acid stimulated its elimination from the organism, but did not affect the proportion of plasma cholesterol bound in high-density lipoproteins.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain Chemistry; Cholesterol; Cholesterol, Dietary; Guinea Pigs; Lipoproteins, HDL; Liver; Male

The effect of dietary vitamin C on the reduction of cytochrome c and cytochrome P-450 by NADPH-cytochrome P-450 reductase was determined in guinea pig liver microsomes. Acute vitamin C deficiency decreased hepatic microsomal cytochrome P-450 content 21% and the rate of cytochrome P-450 reduction 66% without affecting cytochrome c reduction. However, the vitamin status of the animals did not affect the enhancement in cytochrome P-450 reduction produced by the addition of a type I substrate to the reaction mixture. The results suggest that vitamin C deficiency selectivity affects the transfer of electron from NADPH to cytochrome P-450 and that this effect does not result from a change in the spin state of cytochrome P-450.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Benzphetamine; Cytochrome c Group; Cytochrome P-450 Enzyme System; Cytochrome Reductases; Guinea Pigs; Male; Microsomes, Liver; NADH Dehydrogenase; Oxidation-Reduction; Phenethylamines

The possible interrelations between ascorbic acid, cholesterol and plasma triglycerides were studied in the residents of an old people's home. The study lasted about five months, from autumn to spring, and concerned 100 people in good health, both males and females, whose age varied from 70 to 84. Old people's diets proved well balanced and varied to such an extent as to supply them with a satisfying amount of calories and vitamin C. The results of this study showed that the average plasma levels of ascorbic acid [1] approached the lower level of normal values (587 +/- 34 micrograms %), [2] depended on sex (in fact it was significantly lower in males) (p less than 0.01), and [3] depended on diets which varied according to the different seasons when drawings were made (p less than 0.01). Moreover, in all cases there was a significantly negative correlation between ascorbic acid and cholesterol (p less than 0.05), whereas no significant correlation seemed to exist between ascorbic acid and triglycerides. On the contrary, a significant positive correlation between cholesterol and triglycerides was observed (p less than 0.01). The above-mentioned correlations seem to be valid only for males. This study confirmed by partial 3 variant correlations, produced results that point out the risk of hypercholesterolemia connected with chronic hypovitaminosis C, a characteristic feature of old age.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Female; Humans; Male; Seasons; Sex Factors; Triglycerides

The activity of the cholesterol 7 alpha-hydroxylating system containing cyto-chrome P-450 is depressed in the liver of guinea-pigs with chronic marginal vitamin C deficiency. Slowing-down of this rate-limiting reaction of cholesterol transformation to bile acids causes cholesterol accumulation in the liver, blood plasma and arteries, increase in the index total: HDL cholesterol, prolongation of plasma cholesterol half-life, increase in the index cholesterol: bile acids in the gall-bladder bile, cholesterol gallstone formation and atheromatous changes on coronary arteries in guinea-pigs with long-lasting marginal vitamin C deficiency. The most effective means for preventing these changes are vitamin C doses ensuring maximal steady-state levels of ascorbate in the tissues. In most of hypercholesterolemic persons with a low vitamin C status, the administration of ascorbic acid in doses 500-1000 mg per day lowers total cholesterol concentration in blood plasma. This effect may be reinforced through a simultaneous administration of bile acids sequestrants, such as cholestyramine or pectin. In every form of hypercholesterolemia therapy (dietary and/or pharmacological), an adequate vitamin C supply should be ensured in doses capable of creating maximal steady-state levels of ascorbate in human tissues.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Drug Synergism; Humans; Hypercholesterolemia; Pectins; Spleen; Time Factors

The postoperative ascorbic acid requirements of 63 surgical patients were assessed by measurement of buffy layer leucocyte ascorbic acid and the ascorbic acid content of white blood cells. There was a significant reduction in ascorbic acid levels following surgery. The postoperative changes were unrelated to the extent of surgical trauma or the volume of blood transfused during surgery but there was a significant correlation between postoperative ascorbic acid measurements and white blood cell counts. It appears that postoperative leucocytosis and release by the bone marrow of white blood cells with a low ascorbic acid content may partly account for the postoperative changes in buffy layer and white blood cell ascorbic acid measurements. However, surgical operations were followed by an authentic increase in ascorbic acid requirements, and there was a 42 per cent reduction in circulating white blood cell ascorbic acid levels on the third postoperative day. The findings of this study create an argument for the use of ascorbic acid supplements in surgical patients although it is unlikely that postoperative changes in leucocyte ascorbic acid have pathologic significance in wound repair.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Blood Cell Count; Erythrocyte Count; Humans; Leukocyte Count; Leukocytes; Nutritional Requirements; Postoperative Complications; Postoperative Period; Surgical Procedures, Operative

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Orthomolecular Therapy

Topics: Adrenal Cortex; Aging; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Rats; Rats, Inbred Strains

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Castration; Estrogens; Female; Guinea Pigs; Periodontal Diseases; Periodontium

Topics: 2,6-Dichloroindophenol; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Indophenol

Studies in animal models suggest that ascorbic deficiency impairs T-cell-mediated immunity. We studied five normal volunteers hospitalized on a metabolic unit and consuming a strictly controlled diet deficient in ascorbic acid I) after a 5-wk control period of ascorbic acid supplementation (75 mg/day) and 2) after a 9-wk period of no supplementation. Three of the subjects were restudied after a 5-wk period of ascorbic acid supplementation after the deficient period. At the end of both control periods ascorbic acid levels in plasma ranged from 0.9 to 1.3 mg/dl and in leukocytes from 19 to 30 microgram/10(8) cells. At the end of the deficient period levels of ascorbic acid in plasma ranged from 0.09 to 0.15 mg/dl and in leukocytes from 6.2 to 10 microgram/10(8) cells, levels at or below those frequently found in frank scurvy. None of the T-cell parameters tested including mitogen responsiveness to phytohemagglutinin and percentage of T-cells bearing receptors for IgM (helper cells) and IgG (suppressor cells) was different in the deficient period compared to the control periods. One patient with spontaneous scurvy (plasma ascorbic acid 0.07 mg/dl, leukocytic ascorbic acid 4.9 microgram/10(8) cells) was studied at the time of admission and after vigorous ascorbic acid repletion. All T-cell parameters after repletion were unchanged from admission. We conclude that in man ascorbic acid deficiency, even at the scorbutic level, does not alter T-cell numbers or impair in vitro T-cell function.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Leukocytes; Male; Middle Aged; Phytohemagglutinins; Receptors, Immunologic; Scurvy; T-Lymphocytes

Possible interactions between folic acid (folate) and ascorbic acid (AA) have been suspected because megaloblastic anemia is occasionally observed in scorbutic patients, and it may or may not respond to folate treatment. Male weanling guinea pigs were fed diets containing high levels of folate and AA or diets deficient in one or both vitamins. A total of 36 animals, including 9 controls, were studied. When anorexia began to appear in the deficient groups, all animals were killed by exsanguination, and tissue samples (blood, liver, adrenal, kidney, spleen, and intestinal mucosa) were removed for AA and folate analyses. Folate and AA deficiency lowered tissue folate and AA levels, respectively. AA deficiency, either alone or in combination with folate restriction, did not affect tissue folate levels, nor did AA deficiency significantly exacerbate the anemia and leukopenia caused by folate deficiency. However, there was an unexpected decrease in AA levels in the liver and adrenal glands with folate deficiency. Although AA does not appear to be needed for normal folate metabolism, the lower AA levels associated with a folate deficiency are indicative of an interaction between the two vitamins.

Topics: Anemia, Megaloblastic; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Folic Acid; Folic Acid Deficiency; Guinea Pigs; Hematocrit; Hemoglobins; Leukopenia; Male; Organ Specificity; Tissue Distribution

The influence of experimentally induced subclinical ascorbic acid deficiency upon antipyrine metabolism was assessed in five healthy male volunteers maintained in a hospital metabolic ward and fed a controlled diet deficient in ascorbic acid. Antipyrine pharmacokinetic parameters were determined four times during the study: at the end of an initial control period, after 28 and 63 days of depletion, and at the end of a second control period. No differences in antipyrine metabolism were observed despite the fact that the subjects had plasma ascorbate levels indicative of vitamin C deficiency (i.e., plasma levels less than 0.3 mg/dl) for 5 days (28 day-depletion) or 40 days (63 day-depletion). This experiment demonstrates that pronounced ascorbic acid deficiency of relatively short duration does not alter antipyrine metabolism in man.

Topics: Adult; Antipyrine; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Kinetics; Leukocytes; Male; Middle Aged; Saliva; Time Factors

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Cataract Extraction; Female; Humans; Hyphema; Postoperative Complications; Retinal Hemorrhage

The incidence of ascorbic acid (AA) deficiency and its effect on serum ferritin concentration relative to body iron stores was studied in 61 unchelated patients with beta-thalassaemia major. Thirty-nine (64%) of patients had subnormal leucocyte ascorbate concentrations without clinical evidence of scurvy. The lowest leucocyte ascorbate concentrations tended to occur in the most transfused patients. No correlation was found between the units transfused and serum ferritin concentration in the AA-deficient patients but a close correlation (r = +0.82; p less than 0.005) existed for the AA-replete group. Similarly a close correlation (r = +0.77; p less than 0.005) was obtained between liver iron concentration and serum ferritin in AA-replete patients but only a weak correlation (r = +0.385; p less than 0.025) existed for the AA-deficient group. When AA-deficient patients were treated with ascorbic acid, serum iron and percentage saturation of iron binding capacity rose significantly; serum ferritin rose in 13 of 21 patients despite the simultaneous commencement of desferrioxamine therapy. In contrast all three measurements tended to fall in AA-replete patients with ascorbic acid and desferrioxamine therapy. Thus, AA deficiency is commonly present in beta-thalassaemia patients with iron overload and may give rise to inappropriate serum ferritin concentrations in relation to body iron stores.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Female; Ferritins; Humans; Iron; Liver; Male; Thalassemia; Transaminases

The results of an epidemiological study using the case-control method on 150 oesophageal cancer cases, observed at the IIIrd Surgical Department in Padua and on 150 controls are presented. The results show that alcohol an maize flour (corn meal) are two aetiopathogenetic factors of verified statistical significance in oesophageal carcinoma in the Veneto population. This confirms other studies among populations with a high risk of oesophageal cancer.

Topics: Adult; Aged; Alcohol Drinking; Ascorbic Acid; Ascorbic Acid Deficiency; Esophageal Neoplasms; Feeding Behavior; Female; Humans; Italy; Male; Middle Aged; Smoking; Vitamin A; Vitamin A Deficiency; Zea mays; Zinc

Guinea pigs fed an ascorbic acid-deficient diet develop scurvy because of the absence of the enzyme L-gulonolactone oxidase. In theory if this enzyme is provided and its substrate L-gulonolactone is present at adequate concentrations ascorbic acid will be synthesized and the development of scurvy prevented. Using this model we tested whether a viable segment of intestine could be used to contain the administered enzyme and act as an artificial organ for the production of ascorbic acid. A surgical procedure was developed to prepare an externalized pouch of intestine with its circulation left intact. When enzyme is inserted in this intestinal bag it is not toxic and not antigenic in some animals, whereas, enzyme injected intraperitoneally is clearly antigenic. Synthesis of ascorbic acid by this artificial organ could not, however, be detected by elevation of plasma concentrations of the vitamin.

Topics: Animals; Artificial Organs; Ascorbic Acid; Ascorbic Acid Deficiency; Bioprosthesis; Disease Models, Animal; Evaluation Studies as Topic; Guinea Pigs; Intestine, Small; L-Gulonolactone Oxidase; Male; Scurvy; Sugar Alcohol Dehydrogenases

A systematic study of vitamin C blood levels in patients with cancer and an evaluation of their modifications when the patients were orally treated with daily large doses of ascorbic acid (5g/day) have been carried out. For excluding any interference on intestinal vitamin C absorption, all patients with digestive tract cancer have been excluded. Our first results concern 24 lung cancer and 35 bladder cancer patients, operable or not, of different sex and age. The study has shown hypovitaminosis C subclinic conditions for the greater part of subjects: in fact the average haematic rate of ascorbic acid approaches to lower level of physiologic range, appearing very low particularly for the younger patients. Periodic haematic dosages of vitamin C of unoperable and operated patients treated with large doses of ascorbic acid, have shown a rapid increase of its blood concentration which frequently has been very over 1500 micrograms%, the higher level of normal range. These high vitamin haematic levels, generally constant during the time, appear usefull in increasing the defence reactions of the cancerous patient.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Urinary Bladder Neoplasms

Plasma and buffy-coat vitamin C were estimated in 158 samples from 139 lung-cancer patients, at all stages of the disease. Most samples showed hypovitaminosis C in both estimations: 64% had plasma, and 25% buffy-coat values below the thresholds for incipient clinical scurvy (0.3 mg% and 10 micrograms/10(8) cells respectively). Levels were diet-dependent and could be increased by oral supplements. Levels were low both in tumour-bearing patients and in those clinically free of disease after resection. The latter had particularly low values during the first 6 months, indicating the utilization of vitamin C in surgical repair. The vitamin C content of 13 primary lung tumours was assayed: tumours had a higher vitamin C content (mean 111.6 +/- 55.1 micrograms/g tissue) than normal lung (58.5 +/- 20.4 micrograms/g). Mononuclear cells from normal individuals show a higher vitamin C content than polymorphs, but in lung-cancer patients the expected correlation of buffy-coat vitamin C with the proportion of lymphocytes in peripheral blood was obscured by an inverse correlation in patients with relative lymphocytosis (greater than or equal to 25% lymphocytes), confirmed by an inverse correlation of the proportion of lymphocytes in peripheral blood with mononuclear-cell vitamin C in 14 patients in whom this was measured. These correlations were unaffected by controlling for plasma values, and indicate the utilization of vitamin C in lymphocyte-related anti-tumour mechanisms. Vitamin C is necessary for phagocytosis and for the expression of cell-mediated immunity. In view of the increasing circumstantial evidence that immune mechanisms exert some measure of control on tumour extension and metastasis in man, the effect of supplementation with vitamin C in lung-cancer patients on survival should be tested in a clinical trial.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma, Bronchogenic; Diet; Female; Humans; Immunity, Innate; Leukocyte Count; Leukocytes; Lung Neoplasms; Lymphocytes; Male; Middle Aged; Seasons

The relationship between the metabolic changes in tissue ascorbic acid (AA) and the release of 11-hydroxy corticosteroids (cortisol) into the blood of male and female guineapigs fed on vitamin C-deficient diet, has been investigated. The animals received the diet for 30 and 36 days (males and females respectively) during which tissue AA and Corticol concentrations were analysed at six-day intervals. Bodyweight and adrenal weights were also recorded. When guineapigs are deprived of vitamin C in their diet, tissue cortisol and ascorbic acid concentrations undergo concurrent metabolic changes. There is a close association between the metabolic changes in adrenal cortisol secretion and ascorbic acid release into the plasma as shown by the regression and correlation values. Adrenal ascorbic acid concentration falls as cortisol secretion into the plasma increases. These results indicate that adrenal ascorbic acid operates a modulating role over the production of adrenal steroids during stress in guineapigs.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Female; Guinea Pigs; Hydrocortisone; Leukocytes; Liver; Male; Sex Factors

The long-term maintenances of guinea pigs on diets with (a) lack of vitamin C, (b) lack of lysine, methionine and threonine or (c) with a deficiency of all the above nutrients led to the development of oesophageal hyperplasia and atrophic gastritis. These dietary insufficiences were found to favour oesophageal and gastric cancer production by NPIP with a greatly shortened tumour induction time. It seems likely that the observed features of NPIP carcinogenesis depend on the alteration of the chemistry and biochemistry of these organs provoked by the low intake of the above-mentioned nutrients.

Topics: Amino Acids; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinogens; Esophageal Neoplasms; Female; Guinea Pigs; Male; Neoplasms, Experimental; Nitrosamines; Probability; Stomach Neoplasms

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Male; Organ Specificity; Vitamin E

The effect of desferrioxamine on the reduction of tissue iron and the corresponding level of tissue ascorbic acid have been investigated in female guinea pigs on Vitamin C deficient diet. Plasma and liver AA concentrations were measured after stopping treatment (day 0) and on the following 24 days. Vitamin C intake with the diet enhances rapid absorption of iron into the tissue with corresponding increased catabolism of tissue ascorbic acid. Desferrioxamine reduced tissue iron concentrations without causing pronounced loss of liver ascorbic acid. It is concluded that alterations in tissue ascorbic acid are caused by iron overload in guinea pigs without the pronounced involvement of desferrioxamine.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Deferoxamine; Dose-Response Relationship, Drug; Female; Ferrous Compounds; Guinea Pigs; Iron; Liver

The excretion of AsS and total vitamin C into urine after oral administration of AsS to humans was investigated. When 10 mmol of AsS was administered to the subjects, the excretion of AsS into urine continued for 60 hr in males and 48 hr in females. The average amount excreted per hour was less than 5 mg. These results differed from those for AsA and DAsA orally administered to humans. The determination of vitamin C after oral administration of AsS to the subjects consisting of ten males and six females showed no vitamin C effect in humans, similarly to the case with the guinea pig and the rhesus monkey.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Male; Sex Factors

Half-lives of ascorbate depletion in 9 organs proved the same in guinea pigs receiving minimum maintenance dose of ascorbic acid (0.5 mg/animal/day) during 15 weeks of the pre-experimental period, as in those on very high doses (0.5% ascorbic acid in diet = 300 mg/kg body weight/day). The survival on the ascorbate-free diet proved longer in guinea pigs receiving high vitamin C doses (0.5% in diet) for 7 months previously, than in those with a tenfold lower vitamin C supply (0.05% in diet). Permanently high vitamin C intake does not induce induce systemic conditioning in adult guinea pigs.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Guinea Pigs; Half-Life; Kinetics; Male; Tissue Distribution

An hypothesis is proposed relating the possible role of vitamin deficiency as an etiologic factor contributing to periodontal disease in diabetes. The hypothesis is based upon the following: (1) transport of ascorbate across cell membranes may be impaired by glucose, but facilitated by insulin; (2) glucose utilization is significantly accelerated by sublethal concentrations of endotoxin; (3) endotoxin-induced histamine sensitivity of tissue is enhanced by ascorbic deficiency; and (4) ascorbic acid deficiency alters mucosal barrier function. The interrelationship of these factors is discussed.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Diabetes Complications; Diabetes Mellitus; Endotoxins; Glucose; Histamine Release; Humans; Periodontal Diseases

The addition of Zn2+ inhibited lysine hydroxylation markedly less effectively than it did proline hydroxylation in chick embryo tendon cells, 3T6 fibroblasts and lysyl hydroxylase-deficient Ehlers-Danlos Syndrome Type VI fibroblasts. With low Zn2+ concentrations, a similar difference was also seen in chick embryo cartilage cells, whereas with high concentrations both hydroxylations were affected to the same extent in this cell type. Ascorbate deficiency likewise had a much less effect on lysine than proline hydroxylation when studied with 3T6 fibroblasts. As these two effectors involve quite different mechanisms, it is suggested that relative insensitivity to inhibition may be a property of lysine hydroxylation seen in many cell types with a number of agents. Studies on the mechanism of the difference in the inhibition indicates that the phenomenon is probably not due to differences in the kinetic constants of Zn2+ and ascorbate for the two enzymes. Neither is it probably to any major extent due to delayed procollagen triple helix formation nor a difference in the location of the two hydroxylases within the cisternae of the rough endoplasmic reticulum. The difference similarly cannot be explained solely by an excess of lysyl hydroxylase in the cell. It may thus be due either to some other intracellular property or to the combined effect of several factors.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cartilage; Cells, Cultured; Chick Embryo; Chickens; Collagen; Ehlers-Danlos Syndrome; Fibroblasts; Kinetics; Mice; Mixed Function Oxygenases; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; Procollagen-Proline Dioxygenase; Skin; Tendons; Zinc

Aged men and women with ischaemic heart disease had higher total triglyceride levels than controls, and also lower mean percentage cholesterol levels in the high-density lipoprotein fraction. Subnormal levels of leucocyte ascorbic acid were found in 15/25 patients. In men, but not in women, the initial leucocyte ascorbic acid levels were correlated positively with HDL-cholesterol concentrations. After six weeks treatment with ascorbic acid, the mean HDL-cholesterol concentration had increased not only in all men, but also in those women with IHD. Furthermore, total serum cholesterol and LDL-cholesterol concentrations were reduced in men with IHD, but triglyceride levels were not significantly changed; whereas in women with IHD both total serum and VLDL-triglycerides were reduced. Ascorbic acid deficiency appears to contribute to disorders of lipoprotein metabolism in the aged. Latent ascorbic acid deficiency may be one of several preventable 'risk' factors contributing to the present epidemic of IHD in the western world.

Topics: Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Coronary Disease; Female; Humans; Leukocytes; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Male; Sex Factors; Triglycerides

The influence of chronic ascorbic acid (AA) deficiency and excessive ascorbate consumption on bile acid metabolism, liver and plasma cholesterol levels, hepatic microsomal cytochromes and biliary lipid composition was investigated. Male weanling guinea pigs were fed a cereal-based scorbutigenic diet supplemented with four levels of AA for 7 weeks: deficient, 15 and 30 mg/kg; control, 500 mg/kg; and excess, 20,000 mg/kg. Bile acid kinetic parameters were determined following the intraperitoneal administration of [24-14C] chenodeoxycholic acid. Dietary extremes of AA caused similar alterations in the parameters studied. Relative to the control group, the deficient and excess groups exhibited reduced cytochrome P-450 concentration, lower cholesterol 7 alpha-hydroxylase activity, lower bile acid turnover rate, prolonged bile acid half-life and increased plasma and liver cholesterol concentrations. Deficient and excess groups also exhibited lower biliary cholesterol saturation (i.e., increased bile acid-neutral sterol ratios) than controls. Urinary bile acid excretion was 2- to 3-fold higher in excess guinea pigs than in the other three groups. The data demonstrate the exceptional susceptibility of cholesterol 7 alpha-hydroxylase activity to alteration by dietary extremes of AA, resulting in marked inhibition of bile acid synthesis and elevation of cholesterol levels by both inadequate and excessive AA intake.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile; Bile Acids and Salts; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cytochromes; Guinea Pigs; Kinetics; Male; Microsomes, Liver

Topics: Anemia, Hypochromic; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Chronic Disease; Drug Combinations; Female; Ferrous Compounds; Hemoglobins; Humans; Infant; Iron Deficiencies; Male

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Guinea Pigs; Humans; L-Gulonolactone Oxidase; Lactones; Metabolism, Inborn Errors; Nutritional Requirements; Sugar Alcohol Dehydrogenases

Topics: Animals; Aorta, Thoracic; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Male

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Balneology; Cholangitis; Cholecystitis; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Vitamin B Complex; Vitamin B Deficiency

Guinea pigs formed gallstones when fed chow supplemented with cholesterol and cholic acid. Although the stones contained little or no cholesterol the changes in biliary bile acid and lipid composition were similar to those observed in other rodents under conditions of cholesterol gallstone formation. Addition of cholestyramine to chow had a midly lithogenic effect. Hypovitaminosis C in animals given cholesterol and cholic acid resulted in an increase of the cholesterol content of the gallstones. The composition of biliary bile acids was markedly changed. Reductive formation of deoxycholic acid decreased and oxidative formation of ketonic bile acid increased. The results show that vitamin C may influence the redox state of the intestinal microorganisms microorganisms responsible for these conversions.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholelithiasis; Cholesterol; Cholesterol, Dietary; Cholestyramine Resin; Cholic Acid; Cholic Acids; Diet, Atherogenic; Female; Guinea Pigs; Hot Temperature; Male

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Diet; Guinea Pigs; Hydroxymethylglutaryl CoA Reductases; Intestinal Mucosa; Liver; Male; Steroid Hydroxylases

Topics: Aflatoxins; Age Factors; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carbohydrate Metabolism; Female; Liver; Male; Oxidoreductases, O-Demethylating; Rats; Rats, Inbred Strains; Sex Factors

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cadmium; Guinea Pigs; Intestinal Absorption; Male; Zinc

Topics: Administration, Oral; Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Deferoxamine; Female; Guinea Pigs; Hemosiderosis; Humans; Injections, Subcutaneous; Iron; Male; Scurvy; Thalassemia; Transfusion Reaction

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Iron; Scurvy; Thalassemia; Transfusion Reaction

Prolyl and lysyl hydroxylase activities in cultures of human skin fibroblasts from fetal to 94-yr-old donors were measured. In contrast to earlier studies with whole skin, neither prolyl nor lysyl hydroxylase activity was found related to donor age. Prolyl hydroxylase activity increased 3- to 6-fold when cell extracts were incubated with ascorbate and other hydroxylation cofactors before assay. A similar increase in prolyl hydroxylase activity occurred when cells were incubated with ascorbate. Lysyl hydroxylase activity remained unaltered under these conditions.

Topics: Adolescent; Adult; Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Cells, Cultured; Child; Child, Preschool; Collagen; Fibroblasts; Humans; Hydroxylation; Infant; Infant, Newborn; Middle Aged; Mixed Function Oxygenases; Procollagen; Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; Procollagen-Proline Dioxygenase; Skin

Previously we have observed increased specific activities of several lysosomal hydrolases in scorbutic guinea pigs and thus the specificity of this effect was examined in guinea pigs marginally deficient in ascorbic acid (AA). Guinea pigs were fed an AA-deficient diet for 2 weeks to deplete body AA pools and then fed a stock diet containing 0.5 mg AA/g diet or the deficient diet plus oral administration of 10 mg AA/day, 1 mg AA/100 g body weight or 0.5 mg AA/100 g body weight each day. Animal were periodically killed during the 12-week experiment and lysosomes isolated from individual livers and analyzed. Serum and brain AA declined when AA was withheld, returned to normal when the stock diet or 10 mg AA were fed but remained at low levels on administation of 1.0 mg or 0.5 mg AA/100 g body weight. Brain norepinephrine followed a similar pattern to brain AA and was opposite to the pattern observed for dopamine. In guinea pigs receiving 1 mg AA/100 g body weight, amine concentrations slowly returned to normal after 8 weeks. Serum hexosaminidase and lysosomal cathepsins A and B were unchanged during the experiment, whereas lysosomal hexosaminidase and acid phosphatase were significantly higher when the experiment was terminated.

Topics: Acid Phosphatase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; beta-N-Acetylhexosaminidases; Carboxypeptidases; Cathepsin A; Cathepsin B; Cathepsins; Dose-Response Relationship, Drug; Guinea Pigs; Hexosaminidases; Liver; Lysosomes; Male

The regulatory functions of vitamins are described with particular reference to their importance in the metabolic processes of ageing. Although clear hypovitaminosis is uncommon, slight vitamin deficiencies are often encountered in the clinical practice. They cause a speed up of the organism deterioration. The nutritional requirement and the effect of vitamin A, B1, B6, B12, are rapidly reviewed. More attention is paid to the data about vitamin C, D and E. Vitamin C deficiency in elderly, especially in the hospitalized ones; whereas a high content of ascorbic acid in necessary in order to extend the life length and to achieve a good self-sufficiency. Also the deficiency of vitamin D and of its metabolites is frequent in the aged due to both a lower uptake and a scarce exposure to the sunlight. Low levels of vitamin D cause a worsening of bone tissue and consequent demineralization (osteomalacia and osteoporosis). Some aspects of ageing can be prevented by the supply of vitamin E, particularly the impaired bone trophism. The anti-oxidant power of tocopherol could also interfere some pathogenetic processes of ageing.

Topics: Adolescent; Adult; Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; C-Peptide; Calcifediol; Child; Child, Preschool; Humans; Hydroxycholecalciferols; Insulin; Middle Aged; Osteomalacia; Osteoporosis; Prediabetic State; Vitamin D Deficiency; Vitamin E

The hematic level of ascorbic acid was significantly lower with respect to that of healthy subjects in 55 patients with hemorrhagic ocular diseases. Experiments on albino guinea pigs showed that an induced hypovitaminosis C (2 weeks of scorbutigenic diet followed by a maintenance dose of 0,5 mg of ascorbic acid) caused the appearance of widespread retina hemorrhages and a significant decrease of the blood ascorbate levels with respect to the control groups. The present results suggest that a prolonged insufficient dietary intake of ascorbic acid may give rise to hemorrhagic ocular pathologies in humans.

Topics: Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Eye Diseases; Female; Guinea Pigs; Hemorrhage; Humans; Male; Middle Aged

1. Pregnant guinea-pigs receiving a low dose of L-ascorbic acid (0.2 mg/100 g body-weight per d) developed a hypercholesterolaemia in the third trimester of pregnancy, whereas no change in serum cholesterol levels was observed in pregnant animals receiving a higher dose of the vitamin (2 mg/100 g body-weight per d). 2. Pregnancy in the group of guinea-pigs receiving the higher dose of L-ascorbic acid was associated with an increased biliary secretion of bile acids. No change was observed in the biliary secretion of bile acids in pregnant animals receiving the lower dose of L-ascorbic acid, but these animals secreted significantly more cholesterol. 3. Changes in the biliary secretion of cholesterol and bile acids in the pregnant guinea-pig according to L-ascorbic acid intake were reflected in the composition of the gall-bladder bile. Thus, the gall-bladder bile of guinea-pigs receiving the lower dose of L-ascorbic acid contained more cholesterol, while the gall-bladder bile of those animals receiving the higher dose of the vitamin had a higher content of bile acids. 4. The increased cholesterol content of the gall-bladder of pregnant guinea-pigs receiving the lower dose of L-ascorbic acid resulted in decreased bile acid:cholesterol and phospholipid:cholesterol values, conditions predisposing to cholelithiasis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile; Bile Acids and Salts; Cholelithiasis; Cholesterol; Female; Guinea Pigs; Phospholipids; Pregnancy; Pregnancy, Animal

Tissue ascorbic acid (AA) contents of approximately 12 and 100% saturation respectively were produced in two groups of guinea-pigs. The 'low-AA' group had a significantly lower muscle carnitine concentrations than the 'high-AA' group. There was no concomitant emergence of the symptoms customarily regarded as characteristic of hypovitaminosis C. It is concluded that muscle carnitine (beta-OH-gamma-(trimethyl-amino)butyric acid) is a highly-sensitive indicator of tissue AA contents; this could account for the lassitude and fatique reported to precede the emergence of frank scurvy in man.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carnitine; Diet; Guinea Pigs; Male; Muscles

The distribution of ascorbic acid has been compared in the fore-, mid- and hind-brains of guinea-pigs maintained on a scorbutogenic diet alone, or the diet with supplementary Vitamin C, or the supplemented diet and a terminal convulsant dose of leptazol after 27 days. At the beginning of the investigation, mid-brain ascorbic acid concentrations were similar in both sexes and highest in the mid-brain. After 27 days on the supplemented diet, levels of ascorbic acid were raised in all three brain sections and were still highest in the mid-brains. In the scorbutic group, ascorbic acid concentrations had not changed from control levels in the mid-brain, but had fallen in the other two sections. In a dose-range of 40-60 mg/kg, leptazol caused an increase in convulsive index, and progressive depletion of brain ascorbic acid. No change occurred in fore-brain ascorbic acid, a reduction took place in the hindbrain, and the greatest fall occurred in the mid-brain. It is concluded that ascorbic acid plays an essential role in mid-brain metabolism, and that the convulsant effect of leptazol is influenced by an interaction with brain ascorbic acid.

Topics: Animals; Appetite Regulation; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Dose-Response Relationship, Drug; Female; Guinea Pigs; Male; Pentylenetetrazole; Seizures; Sex Factors

Topics: Aminolevulinic Acid; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Cytochromes; Diet; Guinea Pigs; Heme; In Vitro Techniques; Male; Microsomes, Liver; Pharmaceutical Preparations; Porphyrins; Proteins

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dialysis; Drug Implants; Guinea Pigs; L-Gulonolactone Oxidase; Lactones; Male; Sugar Alcohol Dehydrogenases; Tissue Distribution

The ascorbic acid level of the leukocytes in patients with coronary artery disease was compared to the ascorbic acid level of the leukocytes in patients without coronary artery disease as demonstrated by coronary arteriography. The leukocyte ascorbic acid level was found significantly lower in patients with coronary arteriography. The leukocyte ascorbic acid level was found significantly lower in patients with coronary atherosclerosis (P < 0.001). There was also significant difference in the leukocyte ascorbic acid levels among patients with abnormal coronary arteriograms who smoked compared to those who did not. The anatomical changes secondary to atherosclerotic disease, and mainly those changes related to the ground substance, have been shown to be the changes that have been observed in patients with ascorbic acid deficiency. From the present study, with its limitations, it is suggested that ascorbic acid may play a role in the pathogenesis of atherosclerosis, and although not implicated as an etiological factor in coronary artery disease, it suggests that a closer look at its possible role in the pathogenesis and progression of coronary artery disease is warranted.

Topics: Adult; Aged; Aging; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiac Catheterization; Coronary Disease; Female; Humans; Leukocytes; Male; Middle Aged; Sex Factors; Smoking

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Ferritins; Guinea Pigs; Iron; Liver; Male; Spleen

Although interaction of vitamin C, copper and iron have been studied in several species, little is known about these interactions in species which require the vitamin in the diet. Young male Hartley guinea pigs were fed a basal diet, or a basal diet and supplemented daily with vitamin C, p.o. Pharmacologic doses (25 mg per 100 g BW per day) of vitamin C resulted in two-to-three-fold decreases in liver copper, when compared with those receiving normal (0.5 mg per 100 g BW per day) intakes. Under conditions of vitamin C deficiency, serum copper and ceruloplasmin were elevated along with liver copper. Serum and hepatic iron levels, hepatic microsomal cytochrome P-450 and cytochrome b5, and blood heme parameters all appeared to be directly related to vitamin C intake, i.e. the iron and heme parameters increased as the vitamin dose increased. These data are consistent with the hypothesis that interaction between vitamin C, copper and iron influence normal heme formation through the oxidation/reduction of iron and/or by regulating iron absorption and availability at the gut level.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Copper; Guinea Pigs; Iron; Liver; Male

The status of vitamin B1, B2, B6 and C was investigated in 656 hospital inpatients by means of a dietary interview, biochemical studies, and clinical investigation. The daily intake was lower than the Recommended Dietary Allowance for vitamin B1 in 57%, B2 in 47%, B6 in 53%, and C in 9% of the patients; it was less than half the Recommended Dietary Allowance in 19, 12, 15, and 3%, respectively. A biochemical deficiency was observed in 25% of the patients for vitamin B1, in 11% for B2, in 25% for B6, and in 14% for C. On the basis of the parameters selected for this study, the biochemical vitamin status, the dietary vitamin intake, and the clinical symptoms correlated significantly with each other except in the case of vitamin B6.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Female; France; Humans; Inpatients; Male; Middle Aged; Nutritional Requirements; Pregnancy; Pyridoxine; Riboflavin; Riboflavin Deficiency; Thiamine; Thiamine Deficiency

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Female; Ferritins; Guinea Pigs; Hemosiderin; Iron; Liver; Spleen

A clinical description and discussion of eight cases of cephalhematomas in young squirrel monkeys suspected of being ascorbic acid-deficient is presented.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cebidae; Hematoma; Monkey Diseases; Saimiri; Skull

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cyclic GMP; Cysteine; Dehydroascorbic Acid; Dithiothreitol; Guanylate Cyclase; Guinea Pigs; Spleen; Time Factors

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cells, Cultured; Cytochrome P-450 Enzyme System; Cytochromes; Heme; Kinetics; Lactones; Liver; Liver Regeneration; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Rats; Sugar Alcohol Dehydrogenases

Eight male Cynomolgus monkeys were fed an ascorbic acid-free total liquid diet until plasma levels decreased from a mean of 1.1 mg/dl to 0.04 mg/dl at 8 weeks. They showed no visible signs of scurvy. The animals were then given a daily oral dose of 10 mg ascorbic acid/kg body weight for 4 weeks, when the experiment was ended. Four of the animals were given, in addition, 200 mg erythorbic acid/kg body weight orally each day. In all animals repletion was accomplished in two to three weeks using return to initial plasma ascorbic acid levels as the criterion. During deficiency, blood cellular elements were found to be more resistant to depletion than plasma. For erythrocytes, this may be explained at least partially by the observation that in vitro uptake of ascorbic acid tended to be related inversely to blood ascorbic acid levels. However, no such relationship was seen in leucocytes or platelets. Other measurements made on blood did not vary in response to changing ascorbic acid levels. These include serum cholesterol; erythrocyte, leucocyte, or platelet counts; leucocyte differential; hemoglobin concentration; and hematocrit. Urinary hydroxyproline/creatinine ratios were also unchanged. Erythorbic acid, a stereoisomer of ascorbic acid and a common food additive, has been cited as a possible interferent in the determination of whole blood or plasma ascorbic acid, since in the guinea pig it is absorbed from the gut and no commonly used ascorbic acid analysis can distinguish between the isomers. Under conditions of the present experiment, however, no elevation of apparent whole blood or plasma ascorbic acid was produced by inclusion of high levels of erythorbic acid in the diet. Animals given erythorbic acid in addition to ascorbic acid during repletion did not differ from those given ascorbic acid alone in any aspect mentioned above.

Topics: Administration, Oral; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Cell Count; Blood Cells; Blood Platelets; Cholesterol; Creatinine; Erythrocytes; Haplorhini; Hematocrit; Hemoglobins; Hydroxyproline; Leukocytes; Macaca; Macaca fascicularis; Male; Stereoisomerism

1. Plasma tyrosine and urinary p-hydroxyphenyl lactic acid (PHPLA) and p-hydroxyphenyl acetic acid (PHPAA) were studied in thirty patients with marasmus and twenty normal controls in the same age group. 2. In the control group conventional tyrosyluria was not observed but 30% of the group excreted high levels of PHPAA. In the group with marasmus, plasma tyrosine and urinary PHPLA and PHPAA values were signigificantly higher than the control values. However only 13.3% of the patients were considered to have conventional tyrosyluria and 52.3% were found to excrete high levels of PHPAA. 3. Administration of ascorbic acid resulted in a reduction of PHPLA excretion while it had no effect on PHPAA excretion. 4. It was inferred that (a) tyrosyluria in marasmus is due to the reduced activity of the hepatic enzyme 4-hydroxyphenyl pyruvate: oxygen oxidoreductase (hydroxylating, decarboxylating) (PHPAA-oxidase; EC 1.13.11.27) due to the deficiency of ascorbic acid and (b) high excretion of PHPAA is related to age and nutrition of the child and is unaffected by the administration of ascorbic acid. 5. It was further inferred that urinary excretion of PHPLA is a reliable index of tyrosyluria.

Topics: 4-Hydroxyphenylpyruvate Dioxygenase; Ascorbic Acid; Ascorbic Acid Deficiency; Child, Preschool; Dietary Proteins; Humans; Infant; Lactates; Liver; Phenylacetates; Phenylpropionates; Protein-Energy Malnutrition; Tyrosine

Plasma ascorbic acid (PAA) in normal Labrador Retriever dogs less than one year of age averaged 1.22 +/- 0.05 mg/dl (x +/- sem) and was significantly higher than the value of 0.89 +/- 0.03, for Labrador Retrievers two years of age and older. No significant diurnal variation in PAA was observed. Oral or intravenous administration of 0.5 or 1.0 g of ascorbic acid (AA) elevated PAA for less than 8 hours. Injection of ACTH caused a significant decline in PAA for the initial 2 days, with variable results thereafter. Labrador Retriever puppies fed a ration high in protein, energy and calcium developed the typical skeletal diseases of overnutrition, including hypertrophic osteodystrophy (HOD). The addition or oral AA (0.5 g twice daily) had no ameliorating effect on the skeletal lesions. Instead AA supplementation resulted in relatively higher serum calcium values which, presumably by enhanced hypercalcitoninism, decreased bone resorption. Thus, AA treatment of dogs with HOD is contraindicated, as it can only aggravate the osseous lesions of HOD. The decreased PAA reported in dogs with HOD is interpreted to be the result of stress from pain.

Topics: Adrenocorticotropic Hormone; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Bone Diseases, Developmental; Calcium; Cortisone; Dog Diseases; Dogs; Humerus

1. This study tested the hypothesis that black death, the ascorbic acid (AsA) related disease of penaeid shrimp, is related to collagen underhydroxylation. 2. Collagen measured as hydroxyproline (HYP) in healthy Penaeus californiensis (Holmes) and P. stylirostris (Stimpson) of a wide range of masses were determined. The results revealed a logarithmic relationship between total body collagen HYP and body weight fitting the equation y = 90x1.18 where y = total collagenous HYP (microgram) and x = body weight (g). 3. Shrimp tissues most subject to mechanical trauma (subcutis, hindgut and gills) had the highest collagenous HYP levels and were most consistently and severely affected by an ascorbic acid (AsA) deficiency disease. 4. Prolyl hydroxylase (PH) activity was demonstrated in tissues of P. californiensis and P. stylirostris by hydroxylation of [3,4-3H]proline. 5. AsA was required for shrimp PH activity using a chicken embryo substrate. 6. Nutritional trials revealed that dietary AsA was required for proline hydroxylation in collagen formation in P. californiensis.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Collagen; Decapoda; Diet; Hydroxyproline; Procollagen-Proline Dioxygenase

Tooth germs grown in ascorbate deficient medium for up to 20 days underwent progressive and widespread changes. Proliferation and differentiation of preameloblasts and preodontoblasts progressed normally. Newly differentiated odontoblasts, however, became vacuolated when they began secreting: this suggested a metabolic disturbance. Failure to maintain differentiated odontoblasts, ameloblasts and pulpal cells resulted in aberrant dentin matrix, cessation of dentin production, and finally overall structural collapse with loss of normal morphology. Biochemical studies then were undertaken to define the lesion involved. The relative rate of collagen synthesis in ascorbate deficient cultures was comparable to that of ascorbate supplemented cultures, but the collagen was found to be underhydroxylated. In this state it would be unstable at 37 degrees and subject to preferential degradation. This correlates with the observation that a major fraction of the hydroxyproline in the scorbutic cultures was found in the medium as small molecular weight peptides. The overall effect of ascorbate deficiency was to deprive the tooth germ of the normal quality and quantity of collagen resulting in the characteristic histological and structural abnormalities observed. Flattening and deterioration due to structural failure most likely resulted from abnormal extracellular matrix synthesis in the supportive pulp and dentin due to the aberrant collagen.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Hydroxyproline; Mice; Odontoblasts; Odontogenesis; Proline; Tooth Germ

Vitamin C stimulates the formation of PGE1 in human platelets. The effect occurs over the physiologically relevant range of concentrations. PGE1 is required for T lymphocyte function and plays a major part in the regulation of immune responses. PGE1 is also important in the regulation of collagen and ground substance metabolism, in cholesterol metabolism and in regulation of responsiveness to insulin. It is proposed that defective formation of PGE1 could account for many of the features of scurvy and for many of the reported therapeutic effects of vitamin C. If correct, vitamin C will be of value only in conjunction with an adequate supply of dihomogammalinolenic acid, the precursor of PGE1. Essential fatty acids, pyridoxine and zinc are all required to achieve this.

Topics: Animals; Arachidonic Acids; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Platelets; Cats; Cholesterol; Collagen; Dental Caries; Drug Therapy, Combination; Glycosaminoglycans; Humans; Linolenic Acids; Neoplasms; Platelet Aggregation; Prostaglandins E; Salivation; Scurvy; Sjogren's Syndrome; Stimulation, Chemical

A case of scurvy presenting in a patient with Crohn's disease is reported. A normal response to replacement therapy is seen. Vitamin C (ascorbic acid) deficiency was found in 7 out of 10 patients with clinically quiescent Crohn's disease, 4 of whom had an adequate oral intake of vitamin C. There was no significant difference in oral intake between patients with Crohn's disease and matched controls but there was a significant difference (P less than 0.001) in leucocyte ascorbic acid levels. It is recommended that patients with Crohn's disease be screened for vitamin C deficiency and receive prophylactic vitamin C supplements daily.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Crohn Disease; Female; Humans; Leukocytes; Male; Scurvy

Topics: Aminopyrine N-Demethylase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Guinea Pigs; Heme; Liver; Male; Microsomes, Liver; Mixed Function Oxygenases; Pharmaceutical Preparations; Time Factors

1. The synthesis of collagen in several tissues, including the C1q component of complement in serum, was measured in vitamin C-deficient and control guinea pigs by incorporating labelled proline into hydroxyproline in vivo. 2. Of the tissues examined, by far the greatest specific effect of vitamin C deficiency was observed in skin. Bone was second in order of sensitivity; skeletal muscle, lung, heart and kidney exhibited only small effects, which were difficult to distinguish from those of inanition, while liver, C1q, and the ethanol-soluble components of serum were virtually insensitive. The effect on urinary hydroxyproline was also extremely small. 3. The lack of sensitivity of C1q confirms previous conclusions (BATES, LEVENE, OLDROYD and LACHMANN 1978), based on total protein bound hydroxyproline levels and total C1 activity in plasma. Since C1q, which turns over rapidly, is insensitive, the high sensitivity of "repair" tissues to vitamin C deficiency is unlikely to be connected with their high turnover rate. Differential concentration of vitamin C by different tissues seems more likely to be the critical factor.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Proteins; Body Weight; Collagen; Complement C1; Guinea Pigs; Hydroxyproline; Liver; Organ Size; Proline; Spleen

In scorbutic guinea pigs fed an ascorbic acid-deficient diet for 18 days, the ascorbic acid contents of the liver and plasma were less than 4% those of the control animals, while the content in the brain was about one-third that of the controls. In normal animals, the concentration of ascrobic acid was highest (7.55 +/- 1.46 micrograms of ascorbic acid/mg protein) in the S3 fraction and was also fairly high (5.37 +/- 0.91) in the P2p fraction (cytoplasm of nerve terminals). During ascorbic acid deficiency, the contents in the P2p and microsome fractions decreased slightly faster than those in other fractions. Even after 18 days' deficiency, no significant change was found in the acetylcholine content of the brain.

Topics: Acetylcholine; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Guinea Pigs; Liver; Male; Subcellular Fractions

1. The age-related decrease in hydroxyproline : creatinine ratio in young guinea pigs was significantly smaller in vitamin C-deficient animals than in pair-fed controls. The same was true for proline : creatinine and total amino nitrogen : creatinine ratios, but hydroxyproline : total amino nitrogen and proline : total amino nitrogen ratios were not significantly affected by deficiency. 2. Although the proline : hydroxyproline ratio was unaffected in unfractionated urine, acute or chronic deficiency produced a small but significant increase in this ratio in collagenase digests of the acetone-insoluble fraction. 3. In scorbutic animals, therefore, collagen probably turns over more rapidly than in animals matched for inanition. Some at least, of this increase could represent the rapid turnover of underhydroxylated nascent collagen. Because it contains the degradation products from collagen from many tissues, differing widely in sensitivity to vitamin C status, the urine is unlikely, however, to provide a specific and sensitive functional index of vitamin C status.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Creatinine; Guinea Pigs; Hydroxyproline; Male; Nitrogen; Proline

Sterol balance techniques have been used to determine the effect of short-term ascorbic acid (AA) deprivation on bile acid excretion in the guinea pig. The effects of a brief (2-week) AA deficiency on bile acid pool sizes and the activity of the rate controlling enzyme in bile acid biosynthesis have been determined. It was found that, while food intake and body weight were not affected by the short-term AA deficiency, liver AA levels had fallen to 25% of control levels. At the same time, the rate of excretion of bile acids and the size of the bile acid pool were both reduced by about 50% in guinea pigs deficient in AA. These results were supported by a decrease in the activity of cholesterol 7 alpha-hydroxylase in the deficient animals. It is concluded that an AA deficiency will significantly impair bile acid metabolism independent of any side effects of clinical scurvy.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Feces; Guinea Pigs; Male; Steroids; Triglycerides

Brush border sucrase and alkaline phosphatase activities are considerably enhanced in the intestine of ascorbic acid deficient guinea-pigs. Similar increase in the uptake of D-glucose and L-alanine also occurs in chronic vitamin C deficiency. However the permeability of D-glucose and L-alanine in the intestine of animals fed with large doses of vitamin C is severely depressed, with a reduction in the levels of sucrase and alkaline phosphatase activities.

Topics: Alanine; Alkaline Phosphatase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Transport; Cell Membrane; Glucose; Guinea Pigs; Intestinal Absorption; Intestinal Mucosa; Male; Microvilli; Sucrase

Ascorbic acid status of thirty-nine white children with developmental disabilities, ages three to nineteen years, is reported. Mean daily ascorbic acid intakes were calculated from three-day food records. Biochemical assessment consisted of fasting serum levels and a 6-hr. load test. Nine children served as a control group for the load test only. Mean dietary intakes for the vitamin were 204 per cent of the allowance. The mean serum ascorbic acid value was 1.3 mg. per deciliter. Only two children had levels at the unacceptable deficient level. Following load tests, ten children were identified as low excretors (less than 17 per cent), nine were moderate excretors (17 to 23 per cent), and the rest were high excretors (above 23 per cent). All of the normal children were high excretors. Two of three children with low ascorbic acid intakes (below 66 per cent of the recommended allowance) were verified as deficient by their fasting serum levels and urinary recovery after a load.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Female; Humans; Intellectual Disability; Male; Mental Disorders; Neurocognitive Disorders; Neurotic Disorders; Nutritional Requirements

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Scandinavian and Nordic Countries; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Scandinavian and Nordic Countries; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamins

Homo sapiens' gene pool contains a defective gene for the synthesis of the active enzyme protein, L-gulonolactone oxidase(GLO). The absence of GLO in the human liver blocks the normal mammalian conversion of blood sugar into ascorbate, leading to the potentially-fatal "inborn error of carbohydrate metabolism", the genetic disease, Hypoascorbemia (in the older nomenclature- scurvy). To survive, humans need exogenous sources of daily ascorbate. Most mammals have the intact gene for GLO synthesis and produce generous daily amounts of the liver metabolite, ascorbate; for instance, an unstressed 70 Kg goat is capable of producing over 13 grams of ascorbate daily and much more under stress. The recommended dietary allowance of 45 milligrams of ascorbate a day for human adults, now proposed and used by nutritionists, is grossly inadequate to restore Homo sapiens to a normal mammalian ascorbate physiology. To correct fully this human genetic defect and banish epidemic chronic subclinical scurvy requires daily intakes of ascorbate equivalent to, at least, the amounts synthesized by the other mammals. Humans kept on a long term regime of full correction of this birth defect show great salutary benefits in health maintenance, disease therapy and slowing of the aging process. This can be regarded as the creation of a new and more robust, longer-living, tough human sub-species, Homo sapiens ascorbicus, by the biochemical reversal of a primate mutation occurring some 60 million years ago. Some of the practical benefits and pathways of future clinical research are discussed.

Topics: Aging; Alcohol Oxidoreductases; Ascorbic Acid; Ascorbic Acid Deficiency; Genes; Heart Diseases; Humans; Neoplasms; Substance-Related Disorders; Sudden Infant Death; Virus Diseases

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Female; Galvanic Skin Response; Guinea Pigs

A definition is given for the terms of latent and borderline vitamin deficiency, and the vitamin requirement and optimal vitamin supply, respectively, are discussed in relation to these two terms. The upper limit of the latent vitamin deficiency status can be used to define the optimal intake of vitamins, whereas the lower limit indicates the minimum requirement. The impact on health of a latent vitamin deficiency lies in the risk of falling into a manifest vitamin deficiency during sudden stress, whereas, in borderline vitamin deficiency status, some health functions are affected so that a problem of public health may arise and countermeasures should be taken.

Topics: Adolescent; Adult; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Nutritional Requirements; Sex Factors; Vitamins

Willow ptarmigan chicks raised on a diet containing 265 mg ascorbic acid/kg develop scury-like symptoms and die by 4 weeks of age. If blueberry plants are given as an ad libitum supplement to this diet, the malady is prevented. We have described the clinical, pathological and histological changes which accompany this malnutrition and conclude that they are in accord with the description of scurvy in guinea pig and man. Biochemical determination of ascorbic acid synthesis in the kidney of ptarmigan chicks indicated a rate of synthesis five times that found in livers of growing white rats. Blueberry plants and many other plants found in the natural diet of ptarmigan chicks contain 2,000 to 5,000 mg ascorbic acid/kg dry weight. Feeding experiments showed that the pathological signs were avoided and that already afflicted chicks recovered if the vitamin C content of the diet was raised to 750 mg/kg dry weight of food. Since the food intake of the chicks was 5 to 8 g/day the daily requirement of external vitamin C is about 150 mg/kg body weight. To our knowledge this is the first example of an animal which, while producing vitamin C itself, requires substantial amounts of external vitamin C to survive.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Behavior, Animal; Birds; Nutritional Requirements; Osteochondritis; Osteochondrodysplasias; Scurvy; Tibia

Following initial weight gain, reduction in appetite and pronounced weight loss occurred in scorbutic unsupplemented guinea-pigs. Hepatic ascorbic acid levels were significantly reduced and cholesterol concentration increased in the liver. Fenfluramine administration caused immediate loss of weight and appetite in the scorbutic guinea-pigs, these changes being more pronounced in the males. Hepatic ascorbic acid, cholesterol and triglycerides were reduced to lower levels in the fenfluramine-treated scorbutic animals than in the scorbutic guinea-pigs receiving diet alone. In contrast, weight and appetite increased in vitamin-C-supplemented animals while they were receiving fenfluramine. Their hepatic cholesterol and triglyceride levels became significantly reduced. It has been shown that supplementary vitamin C can inhibit the anti-obesity and anorectic actions of fenfluramine and counteract its effect in raising tissue cholesterol.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cholesterol; Disease Models, Animal; Female; Fenfluramine; Growth; Guinea Pigs; Lipid Metabolism; Liver; Male; Obesity; Sex Factors; Triglycerides

Increasing doses of fenfluramine were given to female guinea-pigs on a scorbutogenic diet with or without Ascorbic Acid (AA) supplementation. AA alone increased weight and appetite, hepatic and plasma AA. AA deficiency reduced weight after an initial rise. 10 mg/kg fenfluramine in association with the diet produced a gain in weight. Larger doses caused weight loss and reduced appetite. These effects were prevented by AA supplementation. Fenfluramine reduced hepatic and plasma AA significantly in comparison with the animals receiving the diet alone, or the diet with AA supplementation in the absence of fenfluramine administration. It is concluded that AA release plays an important role in the anti-obesity and anorectic actions of fenfluramine.

Topics: Animals; Appetite; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Female; Fenfluramine; Guinea Pigs; Liver; Obesity

Vitamin C over the concentration range 10 to 100 microgram/ml (5.7-57 x 10-5 M) caused a dose dependent and highly significant enhancement of conversion of 14C-dihomogammalinolenic acid (DGLA) to prostaglandin (PG) E1 and to thromboxane (Tx) B1 by human platelets. Vitamin C had no effect on conversion of 14C-arachidonic acid to PGE2 and TxB2. The concentration range is relevant to physiology: in some cells which concentrate the vitamin, such as polymorphonbuclear leucocytes and the adrenal cortex, vitamin C concentrations may be substantially higher than 100 microgram/ml. Vitamin C can therefore selectively enhance the formation of cyclo-oxygenase generated products from DGLA without changing formation of those from AA. This effect can account for a number of the known actions of vitamin C including its effect on the immune system. The implications of this finding are discussed.

Topics: 8,11,14-Eicosatrienoic Acid; Arachidonic Acids; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Platelets; Fatty Acids, Unsaturated; Humans; In Vitro Techniques; Prostaglandins; Prostaglandins E; Thromboxane B2

The activity of the red blood cell enzymes transketolase, glutathione reductase, and aspartate transaminase, and their activation by the coenzymes thiamine, riboflavin, and pyridoxine, the pyruvate tolerance test, the leucocyte vitamin C concentration, and the activity in serum of gamma-glutamyl transferase were measured in a series of 35 patients with alcohol-related illness. The incidence of thiamine deficiency was 31% as assessed by the activation of transketolase, and 55% as assessed by the pyruvate tolerance test. The incidence of riboflavin deficiency was 23% and of ascorbic acid deficiency 91%. No cases of pyridoxine deficiency were detected. The pyruvate tolerance test was found to be a more sensitive test of thiamine deficiency than the transketolase activation, and the activation of red blood cell aspartate transaminase was found to be a poor indicator of pyridoxine deficiency. There was a poor correlation of the gamma-glutamyl transferase activity with the degree of vitamin deficiency, suggesting that alcohol exposure is only partly responsible for the observed vitamin deficiency.

Topics: Adult; Aged; Alcoholism; Ascorbic Acid; Ascorbic Acid Deficiency; Erythrocytes; Female; gamma-Glutamyltransferase; Humans; Leukocytes; Male; Middle Aged; Pyruvates; Transketolase; Vitamin B Deficiency

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Female; Humans; Hyperlipidemias; Leukocytes; Male; Middle Aged; Triglycerides

Topics: Animals; Antipyrine; Ascorbic Acid; Ascorbic Acid Deficiency; Half-Life; Haplorhini; Ketamine; Macaca fascicularis; Pharmaceutical Preparations; Sleep; Stereoisomerism

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Female; Humans; Male; Middle Aged; Orthomolecular Therapy

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Microscopy, Electron; Muscles

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Infant; Infant Food; Infant Nutritional Physiological Phenomena; Scurvy; Sudden Infant Death

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Infant; Sudden Infant Death

1 Antipyrine plasma half-life and clearance rates were studied in 19 elderly patients shortly after admission to a geriatric ward and again 2 weeks after a course of dietary supplementation with Vitamins A, B complex, C and D. 2 Antipyrine half-life fell and clearance increased in the nine who had sub-clinical evidence of ascorbic acid deficiency. No correlation was found with other indices of nutritional status. 3 Vitamin supplementation in elderly people with no demonstrable deficiencies did not alter the metabolism of antipyrine.

Topics: Aged; Antipyrine; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Blood Proteins; Humans; Kinetics; Leukocytes; Urea; Vitamin A; Vitamins

Male guinea pigs fed a vitamin C-deficient diet for 3 weeks had lower concentrations of cholesteryl esters in their adrenals than did control animals fed the recommended intake of the vitamin. Not all esters were affected to the same degree, and the fatty acid profiles of the esters from control and deficient guinea pigs differed; there was proportionately more palmitic and linoleic acids and less docosatetraenoic acid [22:4 (n-6)] in the deficient guinea pig adrenal esters. [Fatty acids are designated as X:Y (n-Z), where X and Y are the numbers of carbon atoms and olefinic bonds in the acid and Z is the number of carbon atoms after the terminal olefinic bond.] A 100-fold excess of vitamin C in the diet also resulted in lower concentrations of adrenal cholesteryl esters than did the control diet, but they were not as low as in the deficient animals. Fatty acid profiles were similar for esters from control and excessively supplemented guinea pigs. Vitamin C deficiency apparently imposes a long term stress which results in a depletion of adrenal cholesteryl esters, possibly specific esters, to meet the requirements for glucocorticoid synthesis.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol Esters; Diet; Fatty Acids; Guinea Pigs; Male

Topics: Adult; Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Male; Middle Aged; Nicotinic Acids; Nutritional Requirements; Thiamine; Thiamine Deficiency; Vitamin A; Vitamin A Deficiency; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin E; Vitamin E Deficiency; Vitamins

Topics: Amino Acids; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Dietary Proteins; Guinea Pigs; Male; Protein Binding; Protein Deficiency; Rats; Time Factors; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamins

Effects of L-ascorbate 2-sulfate (AAS) on lipid metabolism were studied in guinea pigs maintained on diet I with sufficient L-ascorbic acid (AA) supplement or on diet II without AA supplement. AAS(300 mg/kg) inhibited an increase in serum and liver levels of lipids to a greater degree than AA (175 mg/kg), a reference compond, in hyperlipidemic guinea pigs induced by cholesterol feeding with diets I or II. AAS also induced a decrease in serum and liver levels of lipids in guinea pigs which had been previously maintained for 6 weeks on diet II containing 1.0% cholesterol. AA administration significantly increased AA level in various organs of animals maintained on both the diets containing cholesterol. It also rectified the AA level lowered by previous maintenance on diet II containing cholesterol. AAS showed a slight AA replacing effect on the AA level. Both AA and AAS exerted preventive and curative effects on several symptoms due to chronic AA deficiency.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Depression, Chemical; Guinea Pigs; Hyperlipidemias; Lipid Metabolism; Lipids; Male; Time Factors

The effects of L-ascorbic acid deficiency on guinea pig hepatic and brain lysosomal hydrolases were examined. In general, hepatic beta-N-acetylhexosaminidase, beta-D-glucoronidase, alpha-D-galactosidase, alpha-D-mannosidase, and acid phosphatase were elevated in scorbutic animals. This appears to be independent of the starved state. Brain beta-D-glucoronidase and acid phosphatase followed a similar pattern to that observed with the liver enzymes, but brain beta-N-acetylhexosaminidase was not affected by L-ascorbic acid decreased the activity of hepatic beta-N-acetylhexosaminiadase was unaffected by dietary treatments although the activity of beta-N-acetylhexosaminidase A tended to increase in the scorbutic animals. Subcellular fractions were obtained from the three groups of animals and the recoveries of protein, beta-N-acetylhexosaminidase, and glucose-6-phosphatase estimated.

Topics: Acid Phosphatase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Glycoside Hydrolases; Guinea Pigs; Hydrolases; Liver; Lysosomes; Male; Subcellular Fractions

Topics: Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Chronic Disease; Guinea Pigs; Humans; Nutritional Requirements; Rats

Tetracosactrin (Synacthen) tests were performed on 19 elderly women who had leucocyte ascorbic acid (LAA) levels of less than 15 microgram/108 WBC. 9 were then given a daily dose of 200 mg ascorbic acid orally for 2 weeks while the other 10 were left untreated. Following this, tetracosactrin tests were repeated in both groups. All initial plasm cortisol responses to tetracosactrin were within normal limits. Treatment with ascorbic acid produced no changes in these. This suggests that the low LAA levels often found in old people do not result in adrenal insufficiency.

Topics: Adrenal Glands; Adrenal Insufficiency; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Cosyntropin; Female; Humans; Hydrocortisone

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Horse Diseases; Horses

Biochemical deficiency of thiamine, vitamin B6, ascorbic acid or nicotinic acid occurred in 71% and 88% of patients with fulminant hepatic failure (FHF) and decompensated chronic liver disease (DCLD) respectively. Transient high plasma vitamin B6 concentrations in FHF were followed by low levels later in the illness. Although patients with DCLD of alcoholic aetiology tended to have lower circulating levels of vitamins than those with non-alcoholic DCLD, the prevalence of abnormally low concentrations did not differ. Decreased dietary nutrient intake and alcohol appeared to be less important determinants of biochemical vitamin deficiency than the presence of liver disease per se. Finally, urinary excretion of these vitamins or their major metabolites in patients with severe liver disease correlated poorly with circulating levels of vitamins.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Liver Diseases; Nicotinic Acids; Pyridoxine; Thiamine; Thiamine Deficiency; Vitamin B 6 Deficiency

Vitamin C status was studied, by means of leucocyte ascorbic acid concentrations, in 67 cases of idiopathic hemochromatosis subdivided into 44 untreated and 25 treated cases (2 patients belonging to both subgroups) and compared to 31 normal subjects and 37 alcoholic cirrhosis patients. The control groups exhibited the following mean levels (+/- SEM): 34.4 +/- 1.9 microgram/10(8) WBC in normals and 22.0 +/- 1.8 microgram/10(8) WBC in alcoholic cirrhosis. In idiopathic hemochromatosis the mean levels were: for the untreated group 19.5 +/- 1.7 microgram/10(8) WBC and for the treated group 34.3 +/- 2.3 microgram/10(8) WBC. These results (1) affirm an important vitamin C deficiency in the untreated disease; (2) suggest that iron overload is the main causal factor in view of the striking difference--to date unreported--between untreated and treated cases of idiopathic hemochromatosis. Besides its possible theoretical interests, this vitamin C deficiency is responsible in idiopathic hemochromatosis for a significant underestimation of the desferrioxamine-induced urinary iron excretion.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Hemochromatosis; Humans; Iron; Leukocytes; Liver Cirrhosis, Alcoholic; Liver Function Tests; Male; Middle Aged

The vitamin C status of 186 elderly subjects living at home and institutionalised in hospital, residential accommodation and sheltered dwelling was studied. Subjects from hospital and home receiving multivitamin supplements regularly were grouped separately. Ascorbic acid deficiency (plasma ascorbic acid less than or equal to 0.3 mg/100 ml) was noted in 47.2, 39.0, 46.2 and 47.4 per cent subjects of home, hospital, residential accommodation and sheltered dwelling, respectively. All subjects receiving multi-vitamin had plasma ascorbic acid (PAA) levels greater than or equal to 0.3 mg/100 ml. The mean levels of PAA appeared higher in females than males and the percentage incidence of low vitamin C status was higher in males than females in the majority of the groups. Leucocyte ascorbic acid (LAA) levels were measured in only 26 subjects of residential accommodation and of these 38.5 per cent had low LAA levels (less than 15 microgram/10(8) cells). The biochemical vitamin C deficiency was not accompanied by any recognised clinical manifestation.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Homes for the Aged; Humans; Leukocytes; Male; Northern Ireland; Sex Factors

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Infant; Sudden Infant Death

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Heparin; Lipase; Lipids; Lipoprotein Lipase; Male; Triglycerides

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Australia; Humans; Infant

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Guinea Pigs; Male

Indices of nutritional state were measured in 105 surgical patients. The indices were chosen to give information on protein-calorie malnutrition, anaemia, vitamin deficiency. Abnormal values for the various indices were common in the group as a whole and most frequent (50%) in patients who were still in hospital more than a week after major surgery. These patients had a high frequency of anaemia, vitamin deficiency, weight-loss, loss of arm-muscle bulk, and low plasma levels of transferrin and albumin. These abnormalities had gone almost entirely unrecognised, even in patients with sepsis after major surgery, who would benefit from improvement in nutritional state.

Topics: Adolescent; Adult; Aged; Anemia; Anthropometry; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Body Weight; England; Female; Folic Acid; Hemoglobins; Humans; Male; Middle Aged; Nutritional Requirements; Protein-Energy Malnutrition; Serum Albumin; Surgical Procedures, Operative; Transferrin; Vitamin B Complex; Vitamin B Deficiency

Some aspects of adrenocortical function were investigated in young male guinea pigs fed an ascorbic acid (AsA)-deficient diet for 7 days, followed by 0.1 mg AsA/100 g body weight/day for 4 days; pair-fed guinea pigs served as controls. Ninety minutes prior to killine, all guinea pigs received either an adrenocorticotropic hormone (ACTH) or saline injection, and 30 minutes prior to killing, all were injected with 20 muCi 45Ca/100 g body weight intraperitoneally. AsA restriction alone caused an 89% reduction in adrenal AsA concentration, but growth rate, adrenal weight and plasma ACTH were not different from those of pair-fed controls. Adrenal radiocalcium uptake, adrenal calcium content and plasma corticosteroids were similar in saline-treated guinea pigs restricted in AsA and the ACTH-treated controls, all of which were significantly higher than the values observed in saline-injected controls. Similar responses of the ACTH-treated controls and the saline-treated mildly deficient guinea pigs indicated that, at the adrenal AsA levels achieved (4.45 to 7.02 mg/100 g tissue), adrenal calcium and plasma corticosteroids increased significantly without the mediation of ACTH.

Topics: Adrenal Cortex Hormones; Adrenal Glands; Adrenocorticotropic Hormone; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Calcium; Guinea Pigs; Male; Organ Size

One-third of a group of young children admitted to hospital had levels of ascorbic acid indicative of a deficiency state. The average haemoglobin of these children was 91g/1, and there was also evidence of iron deficiency.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child, Hospitalized; Child, Preschool; Ethnicity; Female; Hemoglobins; Humans; Infant; Leukocytes; Male; New Zealand

The vitamin C status of 35 men, over 70 years of age from a residential home has been studied by measuring the plasma and leucocyte vitamin C levels and by assessing the intake of vitamin C. The mean plasma vitamin C level of the group was 16 +/- 15 mumol/l which was significantly lower (P less than 0.005) than that of a similar group of elderly men living alone (26 +/- 20 mumol/l). The mean leucocyte vitamin C levels of the two groups did not differ significantly. Twenty-nine (83 percent) of the institution group had plasma vitamin C levels below 23 mumol/l and 13 men (37 percent) had leucocyte vitamin C levels below 10 microgram/10(8)WBC. The residents who supplemented the institution diet with their own fresh fruit supplies had higher plasma and leucocyte vitamin C levels than the men who did not (P less than 0.01). Some clinical signs possible related to vitamin C deficiency were recorded but these could not later be statistically related to either plasma or leucocyte vitamin C levels. A case is made for vitamin C supplementation of puddings in institutional meals for the elderly.

Topics: Aged; Alcohol Drinking; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Fruit; Homes for the Aged; Humans; Leukocytes; Male; New Zealand; Scurvy

A group of young children who had low levels of leucocyte ascorbic acid had iron status assessed. Those children with low ascorbic acid had also concomitant low iron saturation of their blood. The significance of these findings is discussed.

Topics: Anemia, Hypochromic; Ascorbic Acid; Ascorbic Acid Deficiency; Child, Preschool; Humans; Infant; Iron; Leukocytes

It is well known that glycolytic and hexose monophosphate shunt activities of leukocytes increase during phagocytosis. The relevance of these metabolic changes to particle uptake and particle destruction is also well established. In the present study, these metabolic activities were studied to assess the phagocytic function of leukocytes isolated from ascorbic acid deficient guinea pigs. Glycolytic activity which provides the necessary energy for particle uptake was found to be decreased in both resting and phagocytizing leukocytes for ascorbic acid deficient guinea pigs. The direct oxidation of glucose through the hexose monophosphate shunt (HMS) was stimulated to a significantly lesser extent during phagocytosis in ascorbic acid deficient leukocytes. There was a progressive decline in phagocytosis induced shunt activity of leukocytes as the deficiency of ascorbic acid progressed. These findings show that particle uptake (as indicated by glycolytic activity) as well as particle destruction (as indicated by HMS activity) by leukocytes are impaired in ascorbic acid deficiency. Bactericidal capacity of leukocytes against Escherichia coli was also found to be low in ascorbic acid deficient guinea pigs as compared to those in the pair-fed control group.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Bactericidal Activity; Escherichia coli; Glycolysis; Guinea Pigs; Hexosephosphates; Male; Neutrophils; Phagocytosis

Topics: 4-Aminobenzoic Acid; Acetyltransferases; Aminopyrine N-Demethylase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Cytosol; Glucuronosyltransferase; Glutathione Transferase; Guinea Pigs; Kidney; Liver; Lung; Male; Microsomes; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Organ Size

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Humans; Liver; Microsomes, Liver; Pharmaceutical Preparations

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Rabbits; Radiation Injuries, Experimental; Radiation-Protective Agents; Ultraviolet Rays

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Breast Neoplasms; Female; Humans; Hydroxyproline; Lipid Metabolism; Neoplasm Metastasis; Neoplasms; Thiamine Deficiency; Vitamin A; Vitamin A Deficiency

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Canada; Humans; Infant

Topics: 5-Aminolevulinate Synthetase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Ferrochelatase; Guinea Pigs; Heme; Liver; Male; Porphobilinogen Synthase

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Hospitalization; Hospitals, Special; Humans; Leukocytes; Smoking

1. Plasma and buffy-coat vitamin C, urinary proline, hydroxyproline, creatinine and total amino acid concentrations were meausred in 23 healthy elderly subjects at intervals of 3 months. 2. There was a strong positive correlation between plasma vitamin C and buffy-coat vititamin C. 3. There were not significant correlations between plasma or buffy-coat vitamin CPAMIN C. 3. There were not significant correlations between plasma or buffy-coat vitamin C and total urinary hydroxyproline, whether expressed on a creatinine basis or on a total amino acid basis. Similarly, no significant correlations could be detected involving the proline/hydroxyproline ratio in urine hydrolysates. 4. There was a significant negative correlation between plasma or buffy-coat vitamin C and total urinary proline, when expressed per unit of total urinary proline, when expressed per unit of total urinary proline, when expressed per unit of total amino acids in the hydrolysates. This correlation was not observed with unhydrolysed urine, and it appeared to reside in the diffusible fraction, part of whose proline could be liberated by prolidase digestion. In addition, in the man, there was some evidence for a positive correlation between plasma or buffy-coat vitamin C and the ratio of total urinary amino acids to creatinine. 5. These results support the view that poor vitamin C status in elderly humans may be associated with a defect in collagen proline hydroxylation, reflected by increased excretion of proline-rich, collagen-derived peptides. If this interpretation is correct, it indicates a potential defect in connective tissue repair, and could form the basis of a functional test for subclinical vitamin C deficiency.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Creatinine; Female; Humans; Hydroxyproline; Male; Proline

The growth of tumours in guinea-pigs was observed for 20 weeks after placing them on various doses of vitamin C. Complete tumour regression occurred in 55% of those animals receiving 0-3 mg/kg/day ascorbic acid, whereas animals given 10 mg/kg/day showed tumour inhibition but no regression. In contrast, tumours in animals maintained on 1 g/kg/day ascorbic acid grew without sign of retardation. When increased amounts of ascorbic acid were restored to the diet of scorbutic tumour-bearing animals, tumours which had not regressed responded with enhanced growth. Likewise, animals previously maintained on 10 mg/kg ascorbic acid responded in turn to the additional vitamin with enhanced tumour growth. In contrast, all tumour-bearing animals maintained on 1 g/kh ascorbic acid died within 3 weeks when this dose was replaced with 0-3 mg/kg.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Fibrosarcoma; Guinea Pigs; Liposarcoma; Male; Neoplasms, Experimental; Sarcoma, Experimental

There is a certain presumptive evidence for believing than AA has functions other than the simple prevention of classical scurvy; whether these extra-antiscorbutic functions are attributable to AA itself, or to one or more of its metabolites, is not known. Tissue saturation with AA would appear to provide a good insurance against defects in these extra-antiscorbutic areas. ttissue saturation is attainable by a daily intake of 100-150 mg in man; there are no compelling reasons for using megadoses of AA and the emphasis should be on the avoidance of chronic hypovitaminosis C. There is suggestive evidence that megadoses of AA could be physiologically disadvantageous--particularly with regard to in-utero exposure and in persons exposed to high environmental levels of toxic metals.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Common Cold; Humans; Longevity; Metals; Scurvy

Five experiments were carried out in which various levels of calcium and ascorbic acid or citric acid were fed to adult male chickens, young chickens, or young coturnix. Observations were made on body weight, feed efficiency, plasma calcium and tibia mineral content. One percent dietary ascorbic acid had no adverse effect on body weight, tibia ash or tibia calcium content of adult male chickens over a 224-day period, even at calcium levels as low as 0.026% of the diet. In growing chicks, body weight and plasma calcium and tibia mineral content varied with the calcium level of the diet, but were not influenced by ascorbic acid even at 0.65% of the diet. Citric acid at the same molar level was also ineffective in altering calcium metabolism in growing chickens. Growing coturnix showed differences in growth and tibia ash content with 0.4% and 0.85% calcium, but there were no pronounced effects caused by dietary ascorbic acid. There is no evidence in this work that these relatively high levels of ascorbic acid or citric acid have any adverse effect on calcium metabolism because of their chelating properties.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Bone and Bones; Calcium; Calcium, Dietary; Chelating Agents; Chickens; Citrates; Coturnix; Diet; Female; Hypocalcemia; Male; Minerals; Mortality; Quail; Species Specificity

The addition of 0.5% of ascorbic acid to the lithogenic diet of golden hamsters whose body pool was labelled with 26-14C-cholesterol, lowered the formation of gallstones, the cholesterol concentration and half-life in blood plasma and in the liver, and accelerated cholesterol transformation to bile acids.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholelithiasis; Cholesterol; Cricetinae; Liver; Male; Mesocricetus

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholelithiasis; Cholesterol; Cholesterol, Dietary; Gallbladder; Guinea Pigs; Male; Phospholipids

Topics: Amino Acids; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Dietary Proteins; Guinea Pigs; Liver; Tissue Distribution

In 92 patients with various chronic affections of the gastro-intestinal tract vitamins C and B1 content in the blood and urine was measured. As controls 17 healthy persons were examined. Patients with gastro-intestinal affections were found to show a statistically significant fall of the vitamins C and B1 level in the blood and urine at all seasons of the year (winter, spring, summer and fall). But their decline is most intensive with exacerbation of the ailment and then the presence of the pain syndrome is attended by a steeper drop in the level of these vitamins. A course-wise parenteral administration of the vitamins C and B1 results in their statistically significant rise in the blood and urine, their level, however, remaining below that in healthy persons.

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Chronic Disease; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Nutritional Requirements; Thiamine; Thiamine Deficiency

The decrease of tyrosine hydroxylase activity in adrenal homogenate in scurvy was recovered after the administration of ascorbic acid. The causes of the increase in the enzyme activity after the administration of ascorbic acid have been studied. 1. No significant elevation in the enzyme activity was observed after the administration of reserpine to the scortutic guinea pig. 2. A dose of metal chelating agent, alpha, alpha'-dipyridyl, prevented the ascorbic acid-induced or reserpine-induced increase in enzyme activity in the scorbutic and the non-scorbutic guinea pigs, respectively. 3. Tyrosine hydroxylase activity was partially recovered by the administration of FeSO4 to the scorbutic guinea pig. From these results, it became clear that the induction of tyrosine hydroxylase which was not observed in scurvy was due to the deficiency of Fe2+. These results suggested that ascorbic acid affected the induction of this enzyme via Fe2+.

Topics: 2,2'-Dipyridyl; Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Catecholamines; Ferrous Compounds; Guinea Pigs; Male; Reserpine; Tyrosine 3-Monooxygenase

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Evaluation Studies as Topic; Humans; Methods; Tongue

Experiments were conducted to determine the nature of the effect of dietary ascorbic acid on selenium nutrition in the chick. Results showed that ascorbic acid resulted in increased activities of the selenium-containing enzyme glutathione peroxidase in plasma, accompanied by an apparent reduction in the dietary selenium requirement of the vitamin E-deficient chick. The ascorbic acid contents of plasma, liver, kidney and adrenals were not affected by selenium or vitamin E deficiencies, indicating that selenium-vitamin E deficient chicks are not rendered scrobutic. Absorption experiments using ligated duodenal loops or oral doses indicated that dietary ascorbic acid promoted the enteric absorption of selenium but did not affect the absorption of vitamin E. These results support the hypothesis previously reported that factors which inhibit the oxidation of dietary selenium promote its absorption and, perhaps, its post-absorptive utilization in metabolically active components of the cell.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Chickens; Dose-Response Relationship, Drug; Duodenum; Glutathione Peroxidase; Intestinal Absorption; Nutritional Requirements; Oxidation-Reduction; Scurvy; Selenium; Vitamin E; Vitamin E Deficiency

Guinea pigs were fed a vitamin C-deficient diet and at various time periods thereafter their peritoneal cells were tested for biological activity. The serum levels of vitamin C in the deficient animals indicated a progressive state of ascorbic acid deficiency with time and this correlated well with clinical signs and symptoms of scurvy. Fewer macrophages were obtained from the peritoneal cavities of deficient animals and in structural appearance under the phase contrast and light microscope they were smaller in size. They showed no significant impairment in phagocytosis of bacterial cells. The macrophages, however, exhibited significantly reduced migration on glass as compared to the normal cells. In vitro addition of vitamin C partially reversed this reduced migration.

Topics: Animals; Ascitic Fluid; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cell Movement; Dose-Response Relationship, Drug; Female; Glass; Guinea Pigs; Macrophages; Phagocytosis; Staphylococcus aureus

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Female; Guinea Pigs; Male; Pentylenetetrazole; Seizures

Previous in vivo studies indicate that hepatic microsomal drug metabolism decreases in ascorbic acid deficiency and is augmented when high supplements of the vitamin are given to guinea pigs. Kinetic studies with O-demethylase indicate no significant change in the apparent Km of p-nitroanisole in normal, ascorbic acid-deficient animals, or in animals given high supplements of ascorbic acid. The decrease in drug metabolism activity caused by ascorbic acid deficiency is not due to increased lipid peroxidation, nor was phosphatidyl choline significantly altered quantitatively or qualitatively in microsomes from ascorbic acid-deficient animals. Microsomal cytochrome P-450 prepared from ascorbic acid-deficient livers is less stable to sonication, dialysis and treatment with metal chelators. The decrease in cytochrome P-450 and O-demethylase activity associated with dialysis could be prevented by the addition of ascorbic acid. The molar ratio of microsomal ascorbic acid to cytochrome P-450 (plus P-420) is in the order of 2:1. This ratio is maintained during ascorbic acid deficiency in liver and adrenal tissue, during dialysis, on storage and with a partial purification of the cytochrome, which suggests a close association between ascorbic acid and the cytochrome. In addition, ascorbic acid protects cytochrome P-450 and aniline hydroxy lase activity from inhibition by ferrous iron chelators such as alpha, alpha'-dipyridyl. The chelator binds to cytochrome P-450 and prevents formation of the reduced cytochrome P-450-CO spectrum; it in turn gives a reduced spectrum with the cytochrome at 450 nm. These studies suggest that there is an interaction between ascorbic acid and cytochrome P-450 involving the reduced form of the heme iron.

Topics: Animals; Animals, Newborn; Ascorbic Acid; Ascorbic Acid Deficiency; Chelating Agents; Cytochrome P-450 Enzyme System; Electron Transport; Guinea Pigs; In Vitro Techniques; Lipid Metabolism; Male; Microsomes, Liver; Nitroanisole O-Demethylase; Pharmaceutical Preparations; Phospholipids

A significant correlation between liver ascorbic acid (AA) and total bile acids or liver bile acids has been established in guinea-pigs by direct determination of the bile acids, confirming an earlier hypothesis. The oxidation of cholesterol to bile acids is dependent on the AA status, but it cannot be further stimulated by AA when the animals are already on an adequate intake of the vitamin. This suggests that AA has a hypocholesterolaemic effect over a limited range of AA status.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholesterol; Fatty Acids, Nonesterified; Gallbladder; Guinea Pigs; Intestine, Small; Liver; Male; Organ Specificity; Triglycerides

Cholesterol 7alpha-hydroxylase activity was assayed in liver microsomes from guinea pigs supplemented with ascorbate and from guinea pigs in a state of ascorbate deficiency. A mass fragmentographic method was used by which the 7alpha-hydroxylation of endogenous cholesterol could be measured. The 7alpha-hydroxylation was markedly reduced in the ascorbate-deficient animals as compared to animals treated with ascorbate. Addition of ascorbate to the incubations did not increase this activity. 11- and 12-Hydroxylation of laurate as well as 25- and 26-hydroxylation of 5beta-cholestane-3alpha, 7alpha-diol were not significantly affected by the ascorbate status of animals. In the presence of excess NADPH-cytochrome P-450 reductase and a phospholipid, partially purified cytochrome P-450 from the microsomal fraction of liver of an ascorbate-deficient guinea pig had a much lower capacity to 7alpha-hydroxylate [4-14C]cholesterol than a corresponding system containing cytochrome P-450 from liver of an ascorbate-supplemented guinea pig. It is suggested that ascorbate affects the synthesis or breakdown of the 7alpha-hydroxylating system, in particular the cytochrome P-450 component.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol 7-alpha-Hydroxylase; Cytochrome P-450 Enzyme System; Female; Guinea Pigs; Liver; Microsomes, Liver; Steroid Hydroxylases; Subcellular Fractions

Fifty percent of the ascorbic acid content of sliced rat lung was released from the tissue to the media within a few minutes by either washing or incubating the slices with Krebs-phosphate solution. Measurement of the lactate dehydrogenase and potassium content of the medium after incubating lung slices for 5 min showed that about 20% of the cells were damaged by slicing. Sephadex chromatography of tissue extracts prepared from washed lung slices showed that none of the ascorbic acid in these slices were bound to protein. Also, metabolic poisons were shown to deplete the ascorbic acid content of washed lung slices. Approx. 57% of the lung ascorbic acid of guinea pigs that had been supplemented with ascorbic acid and 78% of the lung ascorbic acid of ascorbic acid-deficient guinea pigs were found in the medium when lung slices from these animals were incubated with Krebs-phosphate solution. These results were taken to indicate the presence of an extracellular pool of ascorbic acid in lung which is maintained even during scurvy.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cyanides; DNA; Extracellular Space; Fluorides; Guinea Pigs; L-Lactate Dehydrogenase; Lung; Male; Potassium; Proteins; Rats

Blood was obtained from 11 healthy voluteers, mixed with two standard types of anticoagulant used in blood transfusion centres and stored for 21-28 days at 4 degrees C. Leucocyte ascorbic acid (LAA) fell to deficient levels after 7 days in all cases. There were no corresponding changes in plasma ascorbic acid (PAA) levels. LAA and PAA were measured before, during and after surgery in 5 control patients who underwent definitive operations for benign peptic ulceration and in 4 patients under-going surgery for bleeding peptic ulceration. The average amount of blood administered to the latter group was 10 units. There was a fall in LAA and PAA in both groups of patients after operation. This fall had returned to normal by 7 days in the controls, but the LAA remained at a deficient level at 7 days in the patients who had bled. Deficient ascorbic acid in stored blood may contribute to low leucocyte ascorbic acid levels in patients after blood transfusion and may contribute to the increased complication rate when surgery is undertaken in these patients.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Preservation; Female; Humans; Leukocytes; Male; Peptic Ulcer; Peptic Ulcer Hemorrhage; Stomach Ulcer; Transfusion Reaction

Topics: Abortion, Habitual; Abortion, Spontaneous; Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Copper; Female; Follow-Up Studies; Humans; Pregnancy

There is increasing evidence that the liver microsomal drug metabolizing system is affected by various vitamins such as ascorbic acid, riboflavin, and alpha-tocopherol. In regard to ascorbic acid deficiency there is a decrease in the quantity of hepatic microsomal electron transport components such as cytochrome P-450 and NADPH-cytochrome P-450 reductase, as well as decreases in a variety of drug enzyme reactions such as N-demethylation, O-demethylation, and steroid hydroxylation. In addition, young animals given high supplements of vitamin C have increased quantities of electron transport components and overall drug metabolism activities. Kinetic studies indicate no change in the apparent Km of N-demethylase, O-demethylase or hydroxylase for drug substrates in animals depleted or given high amounts of the vitamin. However, there are qualitative changes in both type I and II substrate-cytochrome P-450 binding. Ascorbic acid is not involved in microsomal lipid peroxidation or in any qualitative or quantitative change in phosphatidylcholine. Replenishing vitamin C-deficient animals with ascorbic acid required 3 to 7 days for the electron transport components and drug metabolism activities to return to normal levels. Induction with phenobarbital and 3-methylcholanthrene is not impaired in the deficient animal since drug metabolism activities are induced to the same extent as normal controls; however, the administration of delta-aminolevulinic acid, a precursor of heme synthesis, to deficient animals caused an increase in the quantity of cytochrome P-450. The effects of riboflavin deficiency on electron transport components and drug metabolism activities have been noted only in adult animals after prolonged periods of deficiency. Decreases in drug metabolism activities occur with both type I (aminopyrine and ethylmorphine) and type II (aniline) substrates. As was found with ascorbic acid deficiency, drug enzyme induction occurred to the same extent with phenobarbital in deficient and normal animals. In addition, it required from 10 to 15 days for the drug metabolism activities to return to normal levels when deficient animals were replenished with riboflavin. The effect of vitamin E on drug metabolism is specific in N-demethylase activities decrease while O-demethylase activities are not affected in the deficient state. This vitamin differs from ascorbic acid and riboflavin in that several laboratories have reported no quantitative decrease in cytochrome P-45

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Cytochrome P-450 Enzyme System; Cytochrome Reductases; Disease Models, Animal; Enzyme Induction; Guinea Pigs; Kinetics; Liver; Microsomes, Liver; Mixed Function Oxygenases; Oxidoreductases; Oxidoreductases, N-Demethylating; Phenobarbital; Riboflavin Deficiency; Vitamin E Deficiency

Leucocyte ascorbic acid (LAA) levels were measured in 138 patients with liver disease. Significantly reduced levels were found in 37 patients with alcoholic liver disease (P less than 0-01) and 25 patients with primary biliary cirrhosis (P less than 0-05). In the primary biliary cirrhosis patients, cholestyramine therapy was associated with significantly lower levels of the vitamin (P less than 0-05). Liver ascorbic acid measured in Menghini needle biopsies in 20 patients was significantly correlated with LAA (r=0-807, P less than 0-001). No significant correlation was found between LAA and haematological indices, conventional liver function tests, or cholesterol levels in any group of patients. Patients with LAA levels below 100 nM/10(8) WBC had significantly higher antipyrine half-lives (mean=28-3 h) than patients with LAA levels above this level (mean=18-6 h) (P less than 0-05). Delayed drug metabolism related to low LAA should be considered when drugs metabolised by the liver are prescribed for patients with alcoholic liver disease or primary biliary cirrhosis.

Topics: Alcoholism; Ascorbic Acid; Ascorbic Acid Deficiency; Cholestyramine Resin; Humans; Leukocytes; Liver; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Function Tests

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Black People; Child; Disease Models, Animal; Guinea Pigs; Hemosiderosis; Humans; Iron; Leukocytes; Liver; Oxalates; South Africa; Thalassemia

Topics: Aging; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Male; Organ Specificity

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Citrus; Flavonoids; Guinea Pigs; Hesperidin

Topics: Alcoholism; Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Humans; Liver Cirrhosis; Pyridoxal Phosphate; Thiamine; Thiamine Deficiency; Vitamin B 6 Deficiency

Three guinea pigs fed a vitamin C-free diet manifested no symptoms of scurvy even after 4-8 months, normally increased in body weight and excreted quantities of ascorbic acid in urine far exceeding the total body pool of ascorbic acid. The course of healing subsequent to experimental trauma in one of these animals proved to be entirely normal and vitamin C concentration in its liver after 8 months of a scorbutogenic regimen was found to be more than twice that in guinea pigs with a daily intake of 10 mg ascorbic acid. It is evident that certain guinea pigs are capable to synthesize ascorbic acid that fully covers the needs of the organism. However, the freqency of occurence of such guinea pigs appears to be extremely small.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Guinea Pigs; Male; Rats; Sex Factors; Species Specificity; Tissue Distribution; Wound Healing

A dietary survey using the five day record method was carried out on 35 elderly men living alone in the Christchurch area. The mean calculated intake of vitamin C for these men was 31 mg/day. These dietary intakes of vitamin C were significantly correlated with both plasma vitamin C levels and with leucocyte vitamin C levels. Twelve men (34 percent) with lowered dietary intakes of vitamin C were in the range for asymptomatic scurvy. The mean calculated intake of thiamine was 1.05 mg/day. The mean TPP effect was 12.9 percent (n = 27). Dietary intakes of thiamine showed a significant inverse relationship with TPP effect. Eight subjects (23 percent) who too, less than the Australian dietary allowance had an elevated TPP effect. By both dietary and biochemical methods there was evidence of subclinical vitamin C and thiamine deficiencies in more than a quarter of these men.

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Humans; Leukocytes; Male; New Zealand; Thiamine; Thiamine Deficiency; Thiamine Pyrophosphate

Previous work supporting the vitamin A dependency of adrenal function in rats neglected to take into account a secondary effect of the deficiency, a decrease in hepatic ascorbic acid biosynthesis. Vitamin A-depleted rats maintained on a diet free of ascorbate had a decrease in the activity of adrenal 3 beta-hydroxysteroid dehydrogenase, and extensive adrenocortical degeneration. The use of an ascorbate supplement prevented the symptoms. The results suggest that previous evidence for direct involvement of vitamin A in steroidogenesis may have been due to the production of a secondary deficiency, a chronic scorbutic condition.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Corticosterone; Hydroxysteroid Dehydrogenases; Male; Progesterone Reductase; Rats; Vitamin A Deficiency

Topics: Adolescent; Adult; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Female; Humans; Male; Middle Aged; Nutrition Disorders

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Child; Child, Preschool; Female; Humans; Infant; Male

Guinea-pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair-fed animals did not exhibit these changes. The alpha-methyl-p-tyrosine (alpha MpT)-induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair-fed animals, but restored in guinea-pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of alpha MpT) showed a decrease in both pair-fed and ascorbic acid deficient animals. The noradrenaline of the heart exhibited a similar tendency. The alpha MpT-induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without alpha MpT administration) decreased. Pair-fed animals showed a similar tendency. The striatal concentration of homovanillic acid (HVA) was diminished in both pair-fed and ascorbic acid deficient guinea-pigs. The cerebral content of 5-hydroxyindoleacetic acid showed a decrease in pair-fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under-nutrition without ascorbic acid deficiency (pair-feeding) diminishes the turnover of cerebral noradrenaline, 5-hydroxytryptamine and striatal dopamine.

Topics: Alkaline Phosphatase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Cerebellum; Diet; Dopamine; Guinea Pigs; Homovanillic Acid; Hydroxyindoleacetic Acid; Leukocytes; Methyltyrosines; Myocardium; Norepinephrine; Serotonin; Time Factors

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Avitaminosis; Contraceptives, Oral; Female; Humans; Pyridoxine; Riboflavin; Riboflavin Deficiency; Vitamin A; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Contraceptives, Oral; Female; Humans

Those organochlorine pesticides which possess both high lipoid solubility and high resistance to biodegradation are prone to accumulation in animal tissues and produce relatively long-term effects as toxicants. Such compounds, typified by DDT, Dieldrin, and Lindane, are profound inducers of hepatic microsomal enzymes, including parts of the glucuronic acid and ascorbic acid biosynthetic pathways. Consequently, administering such pesticides to rats in accompanied by enhanced formation and excretion of D-glucuronic acid and L-ascorbic acid, or D-glucaric acid in the case of guinea pigs. Secondarily, the efficiency in biodegrading the pesticides is reduced in ascorbic-acid-deficient guinea pigs with correspondingly greater residue accumulation in tissue. This would aggravate chronic toxic effects of the compounds. Finally, the capacity of the liver to adapt to the presence of such toxicants through enhanced microsomal enzymatic levels appears to be sensitive to its ascorbate status. Impaired enzyme induction is apparent quite early during ascorbic acid depletion in guinea pigs. The enhanced turnover of ascorbate produced by such pesticides, the poor enzymatic adaptation to them during ascorbate depletion and the dependency of the oxidase system upon adequate ascorbate, all point to the central significance of ascorbate status in the liver, and possibly other tissues, as a determinant of their chronic toxicity.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cytochrome P-450 Enzyme System; DDT; Dieldrin; Enzyme Induction; Female; Glucuronates; Guinea Pigs; Hexachlorocyclohexane; Insecticides; Liver; Liver Glycogen; Rats

The effects of ascorbic acid deficiency on growth and calcification of bone were studied in whole 18-day fetal rat radii and ulnae cultured in a chemically defined medium. Ascorbic acid deficiency decreased the formation of labeled hydroxyporline from labeled proline in both bone shafts and cartilage ends while incorporation of tryptophan was maintained. Dry weights and collagen content of bone and cartilage were decreased, but calcification was not affected. The optimun initial concentration of ascorbic acid for collagen synthesis was 200 mug/ml. The effect of ascorbic acid was not antagonized by glucoascorbic acid or replaced by dithiothreitol. Decreased collagen synthesis in ascorbic acid deficiency could not be ascribed to loss of available peptidyl proline hydorxylase. Formation of underhydroxylated collagen and its release into the medium accounted for much of the decrease in hydroxylated collagen in ascorbic acid deficient bones. Nevertheless, the total newly synthesized collagen, as measured by collagenase digestion, was still decreased. Similar effects were exerted by alpha, alpha'-dipyridyl which also inhibited general protein synthesis. Ascorbic acid did not stimulate proline incorporation into collagen in the presence of alpha, alpha'-dipyridyl.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bone and Bones; Calcification, Physiologic; Calcium; Cartilage; Chromatography; Collagen; Dithiothreitol; Fetus; Glucose; Hydroxylation; Hydroxyproline; Microbial Collagenase; Organ Culture Techniques; Organ Size; Procollagen-Proline Dioxygenase; Protein Biosynthesis; Pyridines; Rats; Tryptophan

Topics: Agglutination Tests; Animals; Antibodies, Bacterial; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Cell Count; Body Weight; Brucella abortus; Brucella Vaccine; Complement Fixation Tests; Female; Guinea Pigs; Immunity; Injections, Intramuscular; Organ Size; Reticulocytes; Spleen

A chronic deficiency of ascorbic acid was induced in guinea pig. The level of catecholamines, copper and the activities of ceruplasmin, catecholamine oxidase, monoamineoxidase and acetylcholinesterase were checked in brain, liver and serum. Also the levels of ascorbic acid and glutathione were measured in the organs of ascorbic acid-deficient animals. The most important changes due to the ascorbic acid deficiency were observed in the brain were monoamineoxidase, catecholamineoxidase, acetylcholinesterase and the concentration of catecholamines were altered. The statement that brain is the organ most affected by the ascorbic acid deficiency is discussed.

Topics: Acetylcholinesterase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Catechol Oxidase; Catecholamines; Ceruloplasmin; Copper; Dopamine; Glutathione; Guinea Pigs; Liver; Male; Monoamine Oxidase; Norepinephrine

Topics: Aminopyrine N-Demethylase; Aniline Hydroxylase; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Cytochrome Reductases; Cytochromes; Diet; Fetus; Guinea Pigs; Kinetics; Liver; Microsomes, Liver; Nitroanisole O-Demethylase; Pharmaceutical Preparations

Topics: Adrenal Glands; Aminolevulinic Acid; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Collagen; Cycloheximide; Cytochrome P-450 Enzyme System; Cytochromes; Dactinomycin; Guinea Pigs; Iron; Kidney Cortex; Liver; Phenobarbital; Spleen

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Collagen; Diet; Epithelial Cells; Epithelium; Feeding Behavior; Guinea Pigs; Male; Mouth Mucosa; Permeability; Tongue

The maximal response of a selection of ascorbic-acid-dependent parameters to a range of intakes of ascorbic acid has been shown to occur at virtually one level of intake in the present experiments. Further, this response occurred with intakes that produced only 1/2 saturation or less of tissues with ascorbic acid. Excessive intakes did not enhance effects, and, as in the case of serum copper levels, may have a detrimental effect. In view of the known factors that may influence requirements and the intralaboratory variability in experimental conditions, the more reasonable approach to the interpretation of dose response data is likely to relate the response to the accompanying degree of tissue saturation, rather than to an absolute level of ascorbic acid intake.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Cholesterol; Dose-Response Relationship, Drug; Glycine; Guinea Pigs; Hematocrit; Hemoglobins; Hydroxyproline; Iron; Male; Organ Size; Organ Specificity; Phospholipids; Proline; Tooth; Wound Healing

Guinea pigs were fed a control (0.05%) or a high (0.5%) ascorbic acid diet during the last half of pregnancy. When the pups were tested at 5 and 10 days of life the ones from the high-ascorbic-acid group demonstrated a marked increase in 14CO2 excretion, compared with the control pups, following an intraperitoneal injection of 14C-labeled ascorbic acid. When the animals were weaned to an ascorbic-acid-deficient diet signs of scurvy appeared earlier in the pups from the high vitamin C group and their survival was shorter. When excretion of labeled CO2 in both groups was correlated with the day of onset of scurvy signs, a linear correlation was found between these two parameters, suggesting that the earlier appearance of signs of scurvy in the experimental pups is secondary to an increased rate of ascorbic acid catabolism.

Topics: Animals; Animals, Newborn; Ascorbic Acid; Ascorbic Acid Deficiency; Birth Weight; Body Weight; Carbon Dioxide; Diet; Feeding Behavior; Female; Fertility; Guinea Pigs; Maternal-Fetal Exchange; Nutritional Requirements; Pregnancy; Pregnancy, Animal

Latent chronic ascorbic acid deficiency provokes in guinea pigs a metabolic disorder in the liver, causing an impaired cholesterol transformation to its principal catabolic product, bile acids. This metabolic disorder induces hypercholesterolemia and accumulation of cholesterol in the liver and slows the release of cholesterol from the circulation. Ascorbic acid probably intervenes into the biosynthesis of bile acids at the stage of 7 alpha-hydroxylation of the cholesterol nucleus. High doses of ascorbic acid significantly stimulate cholesterol transformation to bile acids in guinea pigs and decrease plasma cholesterol concentration in humans.

Topics: Aged; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Cholesterol; Cholesterol, Dietary; Female; Guinea Pigs; Humans; Hypercholesterolemia; Kinetics; Liver; Male; Middle Aged; Spleen

Although vitamin C nutritional status in man may be determined on the basis of dietary intake findings and on clinical signs of a dietary deprivation, biochemical measurements represent the most objective approach. Without the availability of a functional biochemical procedure that relates to vitamin C status, information concerning inadequacies in this nutrient has been derived mainly from measuring ascorbate levels in serum (plasma), leukocytes, blood, and urine. The measurement of serum levels of ascorbic acid is the most commonly used and practical procedure for determining vitamin C nutritional status in individuals or population groups. Although leukocyte ascorbate levels provide information concerning the body stores of the vitamin, the measurement is technically more difficult to perform, and, hence, its use is largely confined to clinical situations as an aid in the diagnosis of scurvy. The clinical diagnosis of scurvy can be aided also by information on the urinary levels of ascorbic acid and the use of vitamin C loading or saturation tests. With recognized limitations, ascorbic acid can be measured in biological samples with the use of automated or manual colorimetric and fluorometric procedures. Nutrition surveys conducted in Canada and the United States have indicated vitamin C deficits among certain population groups.

Topics: Adolescent; Adult; Age Factors; Ascorbic Acid; Ascorbic Acid Deficiency; Australia; Canada; Child; Child, Preschool; Europe; Female; Humans; Infant; Leukocytes; Male; Nutrition Surveys; Nutritional Requirements; Scurvy; Sex Factors; United States

Topics: Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Chick Embryo; Chickens; Diet; Embryo, Mammalian; Embryo, Nonmammalian; Eye; Female; Guinea Pigs; Humans; Liver; Myocardium; Nutritional Requirements; Pregnancy; Scurvy; Tongue

Topics: Administration, Oral; Ascorbic Acid; Ascorbic Acid Deficiency; Crohn Disease; Fistula; Gastrointestinal Diseases; Humans; Kidney Tubules; Leukocytes

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Chondroitin; Enzyme Inhibitors; Guinea Pigs; Hyaluronoglucosaminidase

Three feeding studies on the vitamin C requirements of channel catfish were conducted with practical and semipurified diets. In a long-duration study in which fish achieved almost a 4,000% increase in weight, 50 mg of l-ascorbic acid/kg diet was required for maximal growth and food efficiency. A diet stability study revealed that excessive losses in activity of l-ascorbic acid occurred when practical diets were stored for 16 weeks at 20 degrees. The typical scoliosis condition associated with severe vitamin C deficiency in fish occurred in the nonsupplemented groups in the study with practical diets. Severe growth reductions were obtained from fish fed nonsupplemented semi-purified diets, yet no incidences of spinal abnormalities were noted.

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Dose-Response Relationship, Drug; Drug Stability; Fishes; Hematocrit; Nutritional Requirements; Scoliosis; Spinal Diseases

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Drug Combinations; Humans; Phenylbutazone

The physiological mechanism to prevent and control abnormal bleeding is dependent on three vitamins (C, K, and Q). Two of these are unequivocally established as essential for hemostasis while the existence of the third (Q) is supported by experimental evidence and by clinical and therapeutic observations (Quick 1972; Quick 1974). The interrelationship of these three vitamins has remained moot except for clue observations. Both vitamins C and K have a key structure in their molecules which supplies a redox mechanism, ascorbic acid and 2-methyl, 1,4-naphthoquinone, respectively. Both vitamins are concerned with growth. Lack of vitamin C, which clinically is the basic defect of scurvy, does not appear to cause a defect in blood coagulation while vitamin K affects the clotting mechanism by being essential for the production of four distinct clotting factors: prothrombin, factors VII, IX and X. In this presentation an attempt is made to correlate the action of the vitamin K-dependent clotting factors grouping them in a diagram to show how two systems of thrombin formation exist, one being essentially intrinsic, the second extrinsic requiring tissue thromboplastin and factor VII. The possible interlocking of vitamin Q in this mechanism is presented.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Coagulation; Blood Coagulation Factors; Factor VII; Humans; Lampreys; Models, Biological; Oxidation-Reduction; Prothrombin Time; Thromboplastin; Vitamin K; Vitamins

Subclinical vitamin C deficiency frequently occurs in Black mineworkers, in spite of an apparently adequate daily intake. A study was undertaken to establish the minimum rate of supplementation that would effectively reduce the incidence of subclinical vitamin C deficiency. Two levels of supplementation were tested in relation to a control group. It was found that a supplementation rate of at least 235 mg/head/day is required to maintain reasonably adequate serum levels. It was also found that effective control measures are required to ensure that the supplement is added to the magou, the staple beverage of the miners. It is strongly recommended that the intake of every Black mineworker be supplemented at a rate of 200 - 250 mg/day.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Black or African American; Black People; Botswana; Humans; Lesotho; Malawi; Male; Mining; Mozambique; Occupational Medicine; South Africa

Topics: Age Factors; Aging; Amyloid; Amyloidosis; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Free Radicals; Humans; Molecular Conformation; Protein Denaturation; Proteins; Time Factors; Vitamin E

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Burns; Child; Contraceptives, Oral; Depression; Female; Folic Acid; Folic Acid Deficiency; Humans; Infant; Infections; Leg Ulcer; Pyridoxine; Scurvy; Vitamin B 12 Deficiency; Vitamin D; Vitamin D Deficiency; Vitamins; Wound Healing; Zinc

Hypertyrosinemia tyrosine concentration in whole blood greater than 0.42 mmol/l or 7.5 mg/dl is prevalent among lnuit newborn of the Canadian Eastern Arctic. The rate was 14.8 per 100 newborn between January 1970 and December 1972 (first survey period) and 6.2/100 between January 1973 and September 1974 (second survey period); the corresponding rates among Indian newborn of Nouveau Quebec were 2.6 and 2.2%. Among Anglo-Saxons the rate was less than 0.5% and in French Canada it commonly exceeded 0.94%. Serum concentrations of ascorbic acid were low (less than or equal to 0.25 mg/dl) in the pregnant and age-matched adult lnuit when measured by Nutrition Canada during the first survey period. The percentages of inuit children (up to 4 years old) and pregnant women at "high risk" for scurvy (serum concentration of ascorbic acid less than 0.2 mg/dl) were 14.8 and 47.1, respectively; the corresponding national percentages were 3.0 and 2.2, respectively. Deficiency of ascorbic acid in pregnant women is probably the cause of the unusual prevalence of neonatal hypertyrosinemia among the native Arctic and subarctic peoples because ascorbic acid is required to maintain optimal activity of p-hydroxyphenylpyruvic acid hydroxylase and to permit normal oxidation of tyrosine.

Topics: Adolescent; Adult; Arctic Regions; Ascorbic Acid; Ascorbic Acid Deficiency; Canada; Child; Child, Preschool; Diet; Female; Health Surveys; Humans; Indians, North American; Infant; Infant Nutrition Disorders; Infant, Newborn; Inuit; Male; Pregnancy; Quebec; Tyrosine

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Male; Middle Aged; Pneumonia

Topics: Acidosis; Adrenocortical Hyperfunction; Ascorbic Acid; Ascorbic Acid Deficiency; Peptic Ulcer; Postoperative Care; Postoperative Complications; Preoperative Care

Topics: Abortion, Spontaneous; Ascorbic Acid; Ascorbic Acid Deficiency; Congenital Abnormalities; Female; Fetal Death; Humans; Infant, Newborn; Nutritional Requirements; Pregnancy; Pregnancy Complications

Topics: Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Food Service, Hospital; Humans; Length of Stay; Vitamin D; Vitamin D Deficiency; Vitamins

Topics: Adult; Aged; Aging; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Diet; Food Analysis; Food Service, Hospital; Humans; Long-Term Care; Nutritional Requirements

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Brain; Brain Chemistry; Dopamine; Dose-Response Relationship, Drug; Fluorescence; Guinea Pigs; Histocytochemistry; Hydroxydopamines; In Vitro Techniques; Iris; Male; Methyltyrosines; Myocardium; Nerve Degeneration; Neurons; Norepinephrine; Tritium; Tyrosine 3-Monooxygenase

Topics: Aminopyrine N-Demethylase; Animals; Anisoles; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Cytochrome Reductases; Dose-Response Relationship, Drug; Edetic Acid; Electron Transport; Guinea Pigs; Indicators and Reagents; Kinetics; Male; Methyltransferases; Microsomes, Liver; NADP; Nitro Compounds; Oxidation-Reduction; Pharmaceutical Preparations; Proteins; Stimulation, Chemical; Thiourea; Weaning

Topics: Analgesics; Animals; Anticonvulsants; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinogens; Central Nervous System; Histamine H1 Antagonists; Hormones; Humans; Hypnotics and Sedatives; Lysosomes; Microsomes, Liver; Muscle Relaxants, Central; Oxidation-Reduction; Pharmaceutical Preparations; Vitamins

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Enzyme Repression; Haplorhini; In Vitro Techniques; Lipoprotein Lipase; Myocardium; Papio; Stimulation, Chemical

Topics: Adult; Ascites; Ascorbic Acid; Ascorbic Acid Deficiency; Cardiomegaly; Edema; Female; Humans; Leg; Scurvy

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Aspirin; Barbiturates; Common Cold; Humans; Hypercholesterolemia; Phenylbutazone; Pressure Ulcer; Tetracycline

In a study of the vitamin C status of 50 patients with malignant disease, 46 had leucocyte levels less than the lower limit of the normal range (18-50,μg/10(8) W.B.C.) and of these 30 had very low levels (< 12.5 μg/10(8) W.B.C.). Physical signs compatible with subclinical scurvy were frequently recorded and there was a significant decrease in capillary fragility in those with the lowest levels. Most patients had an inadequate dietary intake of ascorbic acid-containing foods and this was felt to be the major factor in producing the vitamin depletion.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Bronchial Neoplasms; Capillary Fragility; Colonic Neoplasms; Diet; Humans; Leukocytes; Lymphatic Diseases; Neoplasms; Rectal Neoplasms; Scurvy; Stomach Neoplasms

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Humans; Leukocytes; Scurvy; Tyrosine

Topics: Acute Disease; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Oxytetracycline; Penicillins; Pneumonia; Streptomycin

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Black or African American; Black People; Botswana; Carotenoids; Diet; Humans; Mining; Mozambique; Occupational Medicine; Serum Albumin; South Africa; Time Factors; Vitamin A; Vitamin A Deficiency

Topics: Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cholelithiasis; Cholesterol; Disease Models, Animal; Edema; Female; Gallbladder; Guinea Pigs; Humans; Liver

Topics: Age Factors; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Common Cold; Female; Guinea Pigs; Humans; Leukocytes; Male; Sex Factors

Topics: Adrenal Glands; Analysis of Variance; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cytochrome P-450 Enzyme System; Cytochromes; Diet; Guinea Pigs; Kidney; Liver; Microsomes; Microsomes, Liver; Spleen

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Dentistry

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Diet; Guinea Pigs; Incisor; Male; Odontoblasts; Time Factors; Tooth Eruption

Topics: Adrenal Glands; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Brain Chemistry; Brain Stem; Diencephalon; Discrimination Learning; Guinea Pigs; Liver; Male

Topics: Adolescent; Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Australia; Avitaminosis; Carotenoids; Child; Child, Preschool; Erythrocytes; Ethnicity; Female; Folic Acid; Humans; Infant; Male; Middle Aged; Native Hawaiian or Other Pacific Islander; Pyridoxine; Riboflavin; Thiamine; Vitamin A; Vitamin E; Vitamins

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Platelets; Crohn Disease; Diet; Esophageal Fistula; Humans; Ileum; Leukocytes

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Carbon Dioxide; Carbon Radioisotopes; Dose-Response Relationship, Drug; Feces; Guinea Pigs; Male; Time Factors; Urine

Topics: Anemia, Macrocytic; Ascorbic Acid; Ascorbic Acid Deficiency; Contraceptives, Oral; Depression; Female; Folic Acid Deficiency; Glutathione Reductase; Humans; Pyridoxine; Riboflavin Deficiency; Vitamin A; Vitamin B 12 Deficiency; Vitamin B 6 Deficiency; Vitamins

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Guinea Pigs; Pentylenetetrazole; Seizures

Topics: Administration, Oral; Adrenal Glands; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Autoradiography; Carbon Radioisotopes; Central Nervous System; Guinea Pigs; Lens, Crystalline; Male; Organ Specificity; Oxidation-Reduction; Pancreas; Pituitary Gland; Species Specificity; Structure-Activity Relationship; Testis; Time Factors

Topics: Administration, Topical; Adrenergic Agonists; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Cocaine; Dose-Response Relationship, Drug; Epinephrine; Ganglia, Sympathetic; Ganglionectomy; Guinea Pigs; Humans; Injections, Intravenous; Iris; Male; Monoamine Oxidase Inhibitors; Pargyline; Pupil; Receptors, Adrenergic

Topics: Animals; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Coronary Disease; Humans

Topics: Aged; Arteriosclerosis; Ascorbic Acid; Ascorbic Acid Deficiency; Cholesterol; Coronary Disease; Female; Humans; Male; Middle Aged; Thrombosis

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Chronic Disease; Deficiency Diseases; Female; Humans; Male; Middle Aged; Niacinamide; Pneumonia; Pyridoxine; Seasons; Vitamin B 6 Deficiency

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Gingival Hyperplasia; Humans; Male; Middle Aged; Phenytoin

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Coloring Agents; Oral Health

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Aspartate Aminotransferases; Child; Child Nutritional Physiological Phenomena; Clinical Enzyme Tests; Gingival Diseases; Glutathione Reductase; Humans; Nutrition Surveys; Oral Hemorrhage; Riboflavin; Riboflavin Deficiency; Seasons; Stomatitis

Topics: Alcohol Oxidoreductases; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Body Weight; Female; Guinea Pigs; Liver; Male; Sex Factors; Time Factors

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Fruit; Gingival Hyperplasia; Haplorhini; Monkey Diseases; Nutritional Requirements; Oral Hemorrhage; Stress, Physiological; Vitamins

Topics: Aeromonas; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bacterial Infections; Body Weight; Environment; Eukaryota; Fish Diseases; Fisheries; Fishes; Gills; Kidney; Liver; Lordosis; Nutritional Requirements; Pigmentation Disorders; Scoliosis

Cholesterol accumulates in the blood serum and in the liver of guinea pigs with chronic latent vitamin C deficiency. The reason for this is the decreased rate of transformation of cholesterol to bile acids in the liver of animals deficient in vitamin C. A significant direct correlation exists between the vitamin C concentration in the liver and the rate of cholesterol transformation to bile acids.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Biotransformation; Carbon Dioxide; Carbon Isotopes; Cholesterol; Guinea Pigs; Liver; Male; Spleen

Topics: Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Humans; Vitamin A Deficiency; Vitamin B Deficiency; Vitamins

Topics: Adrenal Glands; Animals; Aorta; Ascorbic Acid; Ascorbic Acid Deficiency; Bile Acids and Salts; Brain; Carbon Dioxide; Carbon Isotopes; Cholesterol; Digestive System; Guinea Pigs; Kidney; Kinetics; Liver; Lung; Male; Muscles; Oxidation-Reduction; Skin; Spleen; Testis; Time Factors; Urine