ascorbic-acid and Bone-Diseases

Hemodialysis (HD) patients often have inadequate nutrition, especially with respect to ascorbic acid (AA). It is reported that every HD session may cause a 50%- 75% decrease in plasma AA levels. Some studies have shown that supplementation of AA can change the outcome of chronic kidney disease-mineral bone disorders (CKD-MBD), but the effect of AA on HD patients with CKD-MBD remains controversial. Consequently, we decided to perform a meta-analysis to evaluate the efficacy of AA supplementation in CKD-MBD patients requiring dialysis.. A search was conducted using Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and VIP information database up to April 2018 for all English and Chinese language publications. The main indicators of our study were changes in serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) levels after AA treatment. The efficacy of AA was evaluated by weighted mean difference (WMD) and confidence intervals (CI). Cardiovascular events, mortality and adverse events reported during the experiment were also noted.. In total, 371 patients in six studies were involved in this meta-analysis. Compared to placebo, AA treatment had no positive effect on serum P (353 patients; WMD = -0.05; 95% CI, -0.3 to 0.2; I2 = 28%) or PTH levels (275 patients; WMD = -17.04; 95%CI, -63.79 to 29.72; I2 = 75%). The pooled mean difference of the change of Ca levels from baseline was higher in the AA therapy group versus placebo (353 patients; WMD = 0.15; 95% CI, 0.01 to 0.3; I2 = 0%). No side effects were observed.. Our systematic review and meta-analysis does not support prescription of AA to HD patients with CKD-MBD. AA had no positive effect on CKD-MBD patients as it couldn't influence the serum P or PTH levels but did raise serum Ca levels in the short-term.

Topics: Ascorbic Acid; Bone Diseases; Calcium; Humans; Kidney Failure, Chronic; Minerals; Parathyroid Hormone; Phosphorus; Randomized Controlled Trials as Topic; Renal Dialysis

Vitamin C, traditionally associated with scurvy, is an important nutrient for maintaining bone health. It is essential in the production of collagen in bone matrix. It also scavenges free radicals detrimental to bone health.. This review aims to assess the current evidence of the bone-sparing effects of vitamin C derived from cell, animal and human studies.. Cell studies showed that vitamin C was able to induce osteoblast and osteoclast formation. However, high-dose vitamin C might increase oxidative stress and subsequently lead to cell death. Vitamin C-deficient animals showed impaired bone health due to increased osteoclast formation and decreased bone formation. Vitamin C supplementation was able to prevent bone loss in several animal models of bone loss. Human studies generally showed a positive relationship between vitamin C and bone health, indicated by bone mineral density, fracture probability and bone turnover markers. Some studies suggested that the relationship between vitamin C and bone health could be U-shaped, more prominent in certain subgroups and different between dietary and supplemental form. However, most of the studies were observational, thus could not confirm causality. One clinical trial was performed, but it was not a randomized controlled trial, thus confounding factors could not be excluded.. vitamin C may exert beneficial effects on bone, but more rigorous studies and clinical trials should be performed to validate this claim.

Topics: Animals; Ascorbic Acid; Bone and Bones; Bone Density; Bone Diseases; Cell Differentiation; Dose-Response Relationship, Drug; Humans; Observational Studies as Topic; Osteoblasts; Osteoclasts; Oxidative Stress

Topics: Animals; Ascorbic Acid; Bone Diseases; Dog Diseases; Dogs; Hip Dislocation, Congenital; Hip Dysplasia, Canine; Osteochondritis; Scurvy

Topics: Alkaline Phosphatase; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Bone Development; Bone Diseases; Bone Matrix; Bone Resorption; Calcium; Calcium, Dietary; Collagen; Deficiency Diseases; Dietary Proteins; Exostoses; Fluorine; Haplorhini; Hexosamines; Humans; Nutritional Physiological Phenomena; Rabbits

Topics: Animals; Ascorbic Acid; Bacteria; Bone Diseases; Chemical Phenomena; Chemistry; Collagen; Collagen Diseases; Endocrine System Diseases; Glycosides; Humans; Hydroxylation; Hydroxylysine; Hydroxyproline; Isomerism; Peptide Hydrolases; Plants; Polyribosomes; Procollagen-Proline Dioxygenase; Proline; Protein Precursors

Large populations consume fluoride-contaminated water, especially in developing countries. The toxic effects of fluorosis take three forms: clinical, skeletal and dental. Research thus far indicates that the manifestations of fluorosis are irreversible. However, it has been observed that the ingestion of calcium, vitamin C or vitamin D, individually, is effective in protection from fluoride toxicity to a certain extent. Therefore, a double blind control trial was conducted to examine the effect of a combination of calcium, vitamin D3 and ascorbic acid supplementation in fluorosis-affected children. In the present study, 25 children were selected from an area consuming water containing 4.5 p.p.m. of fluoride, All the children were in the age group 6-12 years and weighed 18-30 kg. They were graded for clinical, radiological and dental fluorosis and relevant biochemical parameters. Grade I skeletal fluorosis and all grades of the manifestation of dental and clinical fluorosis were observed. The children were given ascorbic acid, calcium and vitamin D3 well below the toxic dosages in a double blind manner using lactose as a placebo. Follow up revealed a significant improvement in dental, clinical and skeletal fluorosis and relevant biochemical parameters in these children. Thus, the study indicated that fluorosis can be reversed, at least in children, by a therapeutic regimen that is fairly cheap, simple and easily available and without any side effects.

Topics: Ascorbic Acid; Bone Diseases; Calcium; Child; Cholecalciferol; Double-Blind Method; Drug Monitoring; Drug Therapy, Combination; Fluoride Poisoning; Fluorosis, Dental; Humans; Radiography; Severity of Illness Index

Three hundred and sixteen patients diagnosed as skeletal fluorosis roentgenologically and having no other diseases were divided randomly into 2 groups, matchable in sex distribution, age, functional state and X-ray findings. In the treated group every patient took 200mg vitamin C twice a day, while in the control group placebo tablets. The duration of treatment was 3 months. The therapeutic effect was evaluated by measuring the joint angle and power of gripping and studying the X-ray film and electromyogram. 38 kinds of biochemical parameters were measured simultaneously with a MCA-3 autobiochemical analyser. The results were as follows, (1) The total effective rate in the treated group was 12.84%, chi 2 = 0.556, P > 0.05, so there is no obvious effect in treating skeletal fluorosis with vitamin C. (2) The electromyogram in the treated group showed a recovering rate of 20.00%, chi 2 = 5.9, P > 0.01. It is further shown that there is no effect in treating skeletal fluorosis with vitamin C. (3) 38 kinds of biochemical parameters measured simultaneously and the X-ray findings also showed that vitamin C is not effective. Thus the validity of using vitamin C as the drug of first choice to treat skeletal fluorosis is to be queried.

Topics: Adult; Ascorbic Acid; Bone Diseases; Female; Fluoride Poisoning; Humans; Male; Middle Aged

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

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

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

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

The effects of a large ascorbic acid dose on cytochrome P4501A1 gene expression induced by cigarette smoke exposure was studied in Osteogenic Disorder Shionogi rats, which lack ascorbic acid biosynthesis. The rats were divided into four groups and were administered either a minimal amount (4 mg/day, 4S and 4C) or a large amount (40 mg/day, 40S and 40C) of ascorbic acid. The 4S group and 40S group were daily exposed to cigarette smoke for 2 hours, while the 4C group and 40C group were not. At the end of the 25-day experiment, the rats were killed. The cytochrome P4501A1 mRNA level both in the liver and lung was measured by a competitive reverse transcription-polymerase chain reaction method. When a minimal amount of ascorbic acid was administered, the cytochrome P4501A1 mRNA increased in the liver of the cigarette smoke-exposed group (4S) compared with the control group (4C). On the other hand, when a large amount of ascorbic acid was administered, this increase was not observed in the cigarette smoke-induced group (40S) in liver. On the other hand, in lung, an increased mRNA level in 4S group was not decreased by large ascorbic acid administration (40S). This is the first direct mRNA-level evidence of the effects of a large ascorbic acid dose on the gene expression stimulated by cigarette smoke.

Topics: Animals; Ascorbic Acid; Bone Diseases; Cytochrome P-450 CYP1A1; Gene Expression Regulation, Enzymologic; Liver; Lung; Male; Rats; Rats, Mutant Strains; RNA, Messenger; Smoking

Rats with hereditary defects in ascorbic acid (AsA) synthesis (ODS rats) subjected to AsA-deficiency for 3 weeks showed reductions of plasma alkaline phosphatase and dry and ash weights of the tibia, but no body weight alteration. In accordance with the chemical changes, bone loss and decrease of bone formation by AsA deficiency but not by malnutrition were observed in contact microradiographs of the tibia and by a tetracycline double labeling technique, respectively. The mechanical properties of femora measured by a three point-bending procedure were also altered by AsA deficiency for 3 weeks and showed decreases of 59% in toughness, 32% in strength, 32% in ductility and 22% in stiffness. The biomechanical changes by AsA deficiency were greater than the chemical changes in bone, indicating the usefulness of measuring mechanical properties as a sensitive method for the evaluation of the bone status. The second moment of the area of the femur was not changed by AsA deficiency. These results suggest that AsA deficiency in ODS rats causes marked bone loss and reduction in bone formation, which is accompanied by a greater reduction in biomechanics of the femur without causing macroarchitectural changes.

Topics: Animals; Ascorbic Acid; Body Weight; Bone and Bones; Bone Diseases; Disease Models, Animal; Femur; L-Gulonolactone Oxidase; Male; Rats; Rats, Inbred Strains; Sugar Alcohol Dehydrogenases; Tibia; Time Factors

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

Topics: Aging; Ascorbic Acid; Beverages; Bone Diseases; Citrates; Citric Acid; Diabetes Mellitus; Drug Synergism; Fruit; Hemosiderosis; Humans; Iron; Neoplasms; Oxidative Stress

Topics: Adolescent; Adult; Ascorbic Acid; Back Pain; Bone Diseases; Child; Fractures, Bone; Humans; Muscular Diseases; Neoplasms; Osteogenesis Imperfecta; Pain

A colony of Wistar rats with a hereditary defect in L-ascorbic acid-synthesizing ability was established. This rat, like primates and guinea pigs, lacks L-gulonolactone oxidase (EC 1.1.3.8) which catalyzes the last step of L-ascorbic acid biosynthesis. When L-ascorbic acid was added to their drinking water, the rats grew almost normally and were fertile. These mutant rats should be useful not only for nutritional and pharmacological studies on vitamin C, but also for genetic studies on the lack of this enzyme.

Topics: Animals; Ascorbic Acid; Bone Diseases; L-Gulonolactone Oxidase; Microsomes, Liver; Osteogenesis; Rats; Rats, Inbred Strains; Rats, Mutant Strains; Sugar Alcohol Dehydrogenases

Topics: Alopecia; Anemia; Animals; Ascorbic Acid; Bone and Bones; Bone Diseases; Calcium; Copper; Deficiency Diseases; Diet; Electron Transport Complex IV; Iron; Liver; Myocardium; Phosphorus; Rabbits

Topics: Animals; Ascorbic Acid; Bone Diseases; Carbon Isotopes; Cartilage; Chemical Phenomena; Chemistry; Chick Embryo; Collagen; Collagen Diseases; Connective Tissue; Connective Tissue Cells; Galactose; Glycine; Hydroxyproline; In Vitro Techniques; Ketoglutaric Acids; Proline; RNA, Messenger; RNA, Transfer

Topics: Ascorbic Acid; Blood Glucose; Blood Proteins; Bone Diseases; Celiac Disease; Cholesterol; Esophageal Diseases; Fats; Feces; Female; Gastrectomy; Gastrointestinal Motility; Glucose Tolerance Test; Hemostasis; Humans; Intestinal Absorption; Iodine; Jejunum; Malabsorption Syndromes; Male; Nitrogen; Radiography; Vitamin A Deficiency; Vitamin K; Water-Electrolyte Balance; Xylose

Topics: Ascorbic Acid; Bone Diseases; Child; Humans; Male; Metaplasia; Radiography

Topics: Adolescent; Ascorbic Acid; Body Height; Bone Diseases; Child; Child, Preschool; Creatine; Female; Glycosaminoglycans; Hexosamines; Humans; Infant; Male; Monosaccharides

Topics: Acidosis, Renal Tubular; Adult; Aluminum; Ascorbic Acid; Bone Diseases; Calcium; Calcium Metabolism Disorders; Female; Humans; Hyperparathyroidism; Kidney Diseases; Kidney Failure, Chronic; Osteitis Fibrosa Cystica; Osteomalacia; Vitamin D; Vitamin D Deficiency

Topics: Ascorbic Acid; Bone Diseases; Calcinosis; Diagnosis, Differential; Ergocalciferols; Fractures, Bone; Humans; Infant; Osteoporosis; Radiography; Rickets; Scurvy; Streptomycin; Vitamin A

Topics: Aminopyrine; Ascorbic Acid; Bone Diseases; Caffeine; Disease; Joint Diseases; Muscle Relaxants, Central; Muscle Relaxation; Muscles; Muscular Diseases; Vitamins

Topics: Animals; Ascorbic Acid; Bone Diseases; Cholestanes; Diet; Hematologic Diseases; Lactose; Rats; Vitamin D; Vitamins

Topics: Animals; Ascorbic Acid; Bone Diseases; Bone Diseases, Developmental; Bone Diseases, Metabolic; Dog Diseases; Dogs; Medical Records