calcitriol and Vitamin-D-Deficiency

Delayed deterioration associated with cerebral vasospasm (CVS) is a feared complication after spontaneous subarachnoid hemorrhage (SAH) and is one of the leading causes of death in patients with intracranial hemorrhage. The pathophysiology of vasospasm is complex and not fully understood, involving multiple inflammatory pathways in addition to vasoconstriction induced ischemia. Current treatment with anti-inflammatory or vasodilatory medications has been met with limited success and has not led to a decrease in vasospastic associated mortality prompting continued investigation of potential treatment options. The active form of vitamin D, 1,25-dihydroxyvitamin D

Topics: Animals; Humans; Risk Factors; Subarachnoid Hemorrhage; Vasospasm, Intracranial; Vitamin D; Vitamin D Deficiency

increasing evidence suggests that besides the several metabolic, endocrine, and immune functions of 1alpha,25-dihydroxyvitamin D (1,25(OH)2D), the neuronal effects of 1,25(OH)2D should also be considered an essential contributor to the development of cognition in the early years and its maintenance in aging. The developmental disabilities induced by vitamin D deficiency (VDD) include neurological disorders (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia) characterized by cognitive dysfunction. On the other hand, VDD has frequently been associated with dementia of aging and neurodegenerative diseases (e.g., Alzheimer's, Parkinson's disease).. various cells (i.e., neurons, astrocytes, and microglia) within the central nervous system (CNS) express vitamin D receptors (VDR). Moreover, some of them are capable of synthesizing and catabolizing 1,25(OH)2D via 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1) and 25-hydroxyvitamin D 24-hydroxylase (CYP24A1) enzymes, respectively. Both 1,25(OH)2D and 25-hydroxyvitamin D were determined from different areas of the brain and their uneven distribution suggests that vitamin D signaling might have a paracrine or autocrine nature in the CNS. Although both cholecalciferol and 25-hydroxyvitamin D pass the blood-brain barrier, the influence of supplementation has not yet demonstrated to have a direct impact on neuronal functions. So, this review summarizes the existing evidence for the action of vitamin D on cognitive function in animal models and humans and discusses the possible pitfalls of therapeutic clinical translation.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; Blood-Brain Barrier; Brain; Cognitive Dysfunction; Disease Models, Animal; Humans; Neuroglia; Receptors, Calcitriol; Signal Transduction; Vitamin D; Vitamin D Deficiency; Vitamin D3 24-Hydroxylase

The essential biological action of vitamin D is regulation of calcium and phosphorus metabolism and preserving bone health. In recent years there have been reports about the extraskeletal actions of vitamin D and its role in the regulation of immune system. Vitamin D supplementation appears to reduce the incidence of cardiovascular diseases, cancer, and infections and be able to reduce all-cause mortality. Deficiency of vitamin D has been found to correlate with the increased incidence of autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis. Autoimmune thyroid diseases (AITD), including Graves' disease, Hashimoto's thyroiditis are relatively common autoimmune disorders affecting more than 5% of general population. It has been shown that vitamin D receptors (VDR) and 1-alpha hydroxylase are expressed in papillary thyroid cancer and normal thyroid tissue, suggesting local synthesis of 1,25(OH)2D in the thyroid. While VDR gene polymorphism has been found in much research to be associated with AITDs, very few studies have examined the impact of vitamin D deficiency on the incidence of AITDs in humans with conflicting results. This review focuses on the association between vitamin D and autoimmune thyroid diseases and summarizes the results of vitamin D supplementation studies in patients with AITD.

Topics: Graves Disease; Hashimoto Disease; Humans; Receptors, Calcitriol; Thyroiditis, Autoimmune; Vitamin D; Vitamin D Deficiency; Vitamins

Vitamin D is an endocrine regulator of calcium and bone metabolism. Yet, its effects include other systems, such as innate and adaptive immunity. Unique to pregnancy, circulating 1,25-dihydroxyvitamin D (1,25[OH]2D) increases early on to concentrations that are 2-3 times prepregnant values. At no other time during the lifecycle is the conversion of 25-hydroxyvitamin D (25[OH]D) to 1,25(OH)2D directly related and optimized at ≥100 nmol/L. Vitamin D deficiency appears to affect pregnancy outcomes, yet randomized controlled trials of vitamin D supplementation achieve mixed results depending on when supplementation is initiated during pregnancy, the dose and dosing interval, and the degree of deficiency at the onset of pregnancy. Analysis of trials on an intention-to-treat basis as opposed to the use of 25(OH)D as the intermediary biomarker of vitamin D metabolism yields differing results, with treatment effects often noted only in the most deficient women. Immediately after delivery, maternal circulating 1,25(OH)2D concentrations return to prepregnancy baseline, at a time when a breastfeeding woman has increased demands of calcium, beyond what was needed during the last trimester of pregnancy, making one question why 1,25(OH)2D increases so significantly during pregnancy. Is it to serve as an immune modulator? The vitamin D content of mother's milk is directly related to maternal vitamin D status, and if a woman was deficient during pregnancy, her milk will be deficient unless she is taking higher doses of vitamin D. Because of this relative "deficiency," there is a recommendation that all breastfed infants receive 400 IU vitamin D3/day starting a few days after birth. The alternative - maternal supplementation with 6,400 IU vitamin D3/day, effective in safely raising maternal circulating vitamin D, that of her breast milk, and effective in achieving sufficiency in her recipient breastfeeding infant - remains a viable option. Additional research is needed to understand vitamin D's influence on pregnancy health and the effect of maternal supplementation on breast milk's immune signaling.

Topics: Adaptive Immunity; Adult; Breast Feeding; Dietary Supplements; Female; Humans; Immunity, Innate; Infant Nutritional Physiological Phenomena; Infant, Newborn; Lactation; Maternal Nutritional Physiological Phenomena; Milk, Human; Pregnancy; Pregnancy Complications; Pregnancy Trimesters; Vitamin D; Vitamin D Deficiency

The association between circulating levels of vitamin D and the incidence of chronic diseases is known. The identification of vitamin D as a biomarker of physiological/pathological ageing could contribute to expanding current knowledge of its involvement in healthy ageing.. According to PRISMA guidelines, a systematic review was conducted on cohorts studying the role of 25OH-Vitamin D [25(OH)D] and 1,25(OH). Twenty cohorts from 24 articles were selected for this review. Inverse associations were found between low 25(OH)D levels and all-cause mortality, respiratory and cardiovascular events, as well as markers relating to hip and non-vertebral fractures. Associations between 1,25(OH). This systematic review pinpoints peculiar aspects of vitamin D as a multidimensional predictor of ill health in the ageing process. Further well-designed controlled trials to investigate whether vitamin D supplement results in superior outcomes are warranted in the future.

Topics: Age Factors; Aging; Biomarkers; Cause of Death; Female; Health Status; Health Status Indicators; Humans; Male; Middle Aged; Prognosis; Risk Assessment; Risk Factors; Vitamin D; Vitamin D Deficiency

Dysregulated mineral metabolism is a nearly universal sequalae of acute kidney injury (AKI). Abnormalities in circulating mineral metabolites observed in patients with AKI include hypocalcemia, hyperparathyroidism, hyperphosphatemia, decreased vitamin D metabolite levels, and increased fibroblast growth factor 23 levels. We review the pathophysiology of dysregulated mineral metabolism in AKI with a focus on calcium, phosphate, parathyroid hormone, and vitamin D metabolites. We discuss how mineral metabolite levels can serve as novel prognostic markers for incident AKI and other related outcomes in various clinical settings. Finally, we discuss how vitamin D metabolites potentially could be used as novel therapeutic agents for AKI prevention and treatment.

Topics: Acute Kidney Injury; Animals; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hyperparathyroidism; Hyperphosphatemia; Hypocalcemia; Klotho Proteins; Membrane Proteins; Minerals; Parathyroid Hormone; Renal Replacement Therapy; Vitamin D; Vitamin D Deficiency

Bone fracture, cardiovascular events, and mortality are three outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD), and the umbrella concept originally described for dialysis patients. The reported association of serum phosphorus or fibroblast growth factor 23 (FGF23) levels with renal outcome suggests that the fourth relevant outcome of CKD-MBD in predialysis patients is renal outcome. We found that proteinuria of 2+ or greater with a dipstick test was associated with low vitamin D status due to urinary loss of 25-hydroxyvitamin D (25D). Moreover, active vitamin D or its analogues decrease proteinuria. Given our finding that maxacalcitol does not repress renin, the reduction of proteinuria by this agent is likely due to direct upregulation of the nephrin and podocin in podocytes. Moreover, this agent downregulates the mesenchymal marker desmin in podocytes and blocks transforming growth factor-beta autoinduction, leading to attenuation of renal fibrosis in a unilateral ureteral obstructive (UUO) model. These facts are reminiscent of the suppression of epithelial-mesenchymal transition (EMT) by vitamin D. EMT blockage may explain our finding that vitamin D prescription in renal transplant recipients is associated with a lower incidence of cancer. We also reported that low vitamin D status and high FGF23 levels predict a worse renal outcome. However, administration of massive doses of 25D exacerbates renal fibrosis in UUO kidneys in 1alpha-hydroxylase knockout mice. Moreover, FGF23 inhibits 1alpha-hydroxylase in proximal tubules and monocytes. Taken together, local 1,25(OH)

Topics: Animals; Awards and Prizes; Biomarkers; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Progression; Epithelial-Mesenchymal Transition; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Kidney; Kidney Failure, Chronic; Phosphorus; Prognosis; Proteinuria; Risk Factors; Vitamin D; Vitamin D Deficiency

Hypovitaminosis D in childhood is a re-emerging public health problem in developed countries. New life style habits, current "epidemics" of obesity in children and adolescents worldwide, and other preventable risk factors may play a role in favoring the occurrence of vitamin D deficiency. In addition to skeletal consequences, hypovitaminosis D has been found to be involved in the development of serious health extra-skeletal problems in childhood, including atopy and autoimmunity. The increasing concerns about the global health impact of vitamin D deficiency make further research necessary to fill the gaps of knowledge in this field, and particularly to establish universally accepted "normal" serum 25(OH)D levels in the pediatric population, and to improve strategies for the screening, prevention and treatment of hypovitaminosis D. This review discusses the key points of hypovitaminosis D in childhood in the light of new knowledge, and highlights the limitations of current strategies to control this condition.

Topics: Adolescent; Bone Diseases; Child; Child, Preschool; Dermatitis, Atopic; Developed Countries; Diabetes Mellitus, Type 1; Diet; Dietary Supplements; Humans; Infant; Infant Food; Nutritional Status; Polymorphism, Single Nucleotide; Reference Values; Rickets; Risk Factors; Sunlight; Vitamin D; Vitamin D Deficiency

Inflammatory bowel disease [IBD], including ulcerative colitis and Crohn's disease, is a chronic and unpredictable condition characterised by alternating periods of remission interspersed with relapses. In recent years, accumulating support for an immunomodulating effect of vitamin D on both the innate and the adaptive immune systems has been presented. Through the vitamin D receptor, the active form of vitamin D, 1,25[OH]2D, induces antimicrobial peptide secretion, decreases dendritic cell activity, and promotes Th2 and regulatory T cell development and activity. In addition, vitamin D promotes an increased ratio of anti-inflammatory cytokines to pro-inflammatory cytokines. Studies in IBD point to a role for vitamin D in ameliorating disease outcome. Suboptimal circulating levels of 25-hydroxyvitamin D are common in IBD and appear to be associated with an increased risk of flares, IBD-related hospitalisations and surgeries, an inadequate response to tumour necrosis factor [TNF] inhibitors, a deterioration in quality of life, and low bone mineral density. With only few available randomised double-blind, placebo-controlled studies investigating therapeutic effects of vitamin D related to IBD, further research is necessary to determine the true therapeutic potential of vitamin D, as well as to define its optimal range in serum to achieve and maintain quiescence of disease. This review aims to summarise the latest knowledge on the extraskeletal effects of vitamin D in IBD, and outlines the potential deleterious consequences of vitamin D deficiency in this patient cohort.

Topics: Adaptive Immunity; Biological Products; Dietary Supplements; Humans; Immunity, Innate; Inflammatory Bowel Diseases; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Topics: Autoimmune Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Humans; Incidence; Neurodegenerative Diseases; Osteoporosis; Racial Groups; Sarcopenia; Survival Analysis; Vitamin D; Vitamin D Deficiency

In the UAE and the Gulf region in general, there are several intricate public health issues in the context of vitamin D deficiency that needs to be addressed. Changes in lifestyle such as diet, lack of exercise, cultural habits, avoiding sun exposure due to excessive heat, and other risk factors predispose those who live in GULF countries, such as Emiratis likely to becoming vitamin D deficient. Consequently, the prevalence of vitamin D deficiency is high, and new guidelines are needed to overcome this major public health issue. Peer-reviewed papers related to guidelines and those vitamin D-related papers relevant to the Middle-Eastern region were extracted from multiple research databases using key words according to the general guidelines from the Preferred Reporting Items for Systematic Analysis. This guideline was prepared focusing on the United Arab Emirate and the Gulf populations, to overcome the high incidence of vitamin D deficiency and to improve overall health. We recommend the following vitamin D supplementations for different groups of people: (A) Breastfed infants supplement with 400 IU/day up to age 6 months, and 400-600 IU/day between 6 and 12 months, depending on daily intake of total vitamin D and sun exposure; (B) for children and adolescents of age 1-18 years supplement with 600-1000 IU/day depending on the body weight; (C) adults greater than 18 years', supplementation with 1000-2000 IU/day is recommended, while, (D) the elderly (over 65 years) should be supplemented with 2000 IU/day, throughout the year; (E) pregnant and breast feed women, 2000 IU/day from the first trimester of pregnancy. (F) Premature infants, supplementation of 400-800 IU/daystart from the first days of life. (G) For obese, individuals and those with metabolic syndrome, supplementation of 2000 IU/day (H) For individuals with dark skin complexions and for night workers, supplementation of 1000-2000 IU/day (25-50μg/day), throughout the year, depending on body weight. The goal of supplementation is to achieve and longer term maintenance of serum 25(OH)D concentration of 30-50ng/mL.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cholecalciferol; Ergocalciferols; Female; Humans; Infant; Infant, Premature; Middle Aged; Pregnancy; United Arab Emirates; Vitamin D; Vitamin D Deficiency

Vitamin D has emerged as a key regulator of innate immune responses to pathogen threat. The hormonal form of vitamin D signals through a nuclear receptor transcription factor and regulates gene transcription. Several papers have shown that vitamin D signaling is active both upstream and downstream of pattern recognition receptors, vanguards of innate immune responses. Crohn's disease (CD) is a relapsing-recurring inflammatory bowel disease (IBD) that arises from dysregulated intestinal innate immunity. Indeed, genetic studies have identified several CD susceptibility markers linked to mechanisms of innate immune responses to infection. Interest in links between vitamin D deficiency and CD has grown substantially, particularly in the last five years. While a number of studies have consistently revealed an association between CD and vitamin D deficiency, recent experimental work has uncovered a compelling mechanistic basis for the contribution of vitamin D deficiency to the pathogenesis of the disease. Moreover, a number of intervention trials have provided generally solid evidence that robust vitamin D supplementation may be of therapeutic benefit to patients with CD. This review summarizes these laboratory and clinical findings.

Topics: Clinical Trials as Topic; Crohn Disease; Dietary Supplements; Gene Expression Regulation; Humans; Immunity, Innate; Interleukin-1beta; Nod2 Signaling Adaptor Protein; Receptors, Calcitriol; Signal Transduction; Transcription, Genetic; Vitamin D; Vitamin D Deficiency; Vitamin D Response Element

Topics: Calcium; Cardiovascular Diseases; Clinical Trials as Topic; Dietary Supplements; Humans; Renin-Angiotensin System; Risk Factors; Survival Analysis; Ultraviolet Rays; Vascular Calcification; Vitamin D; Vitamin D Deficiency

In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD). Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

Topics: Animals; Biomarkers; Humans; Macular Degeneration; Prognosis; Risk Assessment; Risk Factors; Vitamin D; Vitamin D Deficiency

The free hormone hypothesis postulates that only the nonbound fraction (the free fraction) of hormones that otherwise circulate in blood bound to their carrier proteins is able to enter cells and exert their biologic effects. For the vitamin D metabolites less than 1% (0.4% for 1,25(OH)

Topics: Humans; Vitamin D; Vitamin D Deficiency

Vitamin D is best known for its influence on skeletal health. There is growing recognition, however, that vitamin D has nonskeletal actions, which could have important implications for understanding the consequences of vitamin D deficiency. In epidemiologic studies, vitamin D deficiency has been consistently associated with an increased risk for cardiovascular disease and hypertension. Disruption of vitamin D signaling in animal models promotes hypertension, cardiac hypertrophy, and atherosclerosis. This evidence has led to the initiation of prospective randomized trials of vitamin D supplementation in individuals at risk for cardiovascular disease. The results of these trials should help to guide strategies for screening and management of vitamin D deficiency in the clinic and at the population level.

Topics: Animals; Cardiovascular Diseases; Cholecalciferol; Dietary Supplements; Humans; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Risk Factors; Vitamin D; Vitamin D Deficiency

Despite adherence to evidence-based guidelines, heart failure [HF] still results in 5-year mortality rates of 50%, indicating a need to implement additional preventive/intervention strategies. This review summarizes data on alterations in the calciotropic and phosphaturic hormones 1,25-dihydroxyvitamin D [1,25(OH)

Topics: Age Factors; Animals; Biomarkers; Calcium, Dietary; Dietary Supplements; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Heart Failure; Humans; Kidney Diseases; Male; Phosphorus, Dietary; Risk Factors; Sedentary Behavior; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Vitamin D through its active form 1a-25-dihydroxyvtamin D [1,25(OH)2D] is a secosteroid hormone that plays a key role in mineral metabolism. Recent years have witnessed a significant scientific interest on vitamin D and expanded its actions to include immune modulation, cell differentiation and proliferation and inflammation regulation. As our understanding of the many functions of vitamin D has grown, the presence of vitamin D deficiency has become one of the most prevalent micronutrient deficiencies worldwide. Concomitantly, non-alcoholic fatty liver disease (NAFLD) has become the most common form of chronic liver disease in western countries. NAFLD and vitamin D deficiency often coexist and epidemiologic evidence has shown that both of these conditions share several cardiometabolic risk factors. In this article we provide an overview of the epidemiology and pathophysiology linking NAFLD and vitamin D deficiency, as well as the available evidence on the clinical utility of vitamin D supplementation in NAFLD.

Topics: Animals; Biomarkers; Dietary Supplements; Humans; Liver; Non-alcoholic Fatty Liver Disease; Risk Assessment; Risk Factors; Vitamin D; Vitamin D Deficiency

The potential beneficial effects of supplementing vitamin D or treatment with pharmacological doses of vitamin D in the prevention or cure of diseases like type 1 (T1D) or type 2 diabetes (T2D) remains the subject of debate. Data from epidemiological and association studies clearly indicate a correlation between vitamin D deficiency and a higher prevalence of both forms of diabetes. In animal models, vitamin D deficiency predisposes to type 1 and type 2 diabetes, whereas high doses of vitamin D or its active hormonal form, 1,25-dihydroxyvitamin D, prevent disease. Large scale, randomized, blinded prospective studies however, remain lacking. Here we discuss the current literature on a role for vitamin D in diabetes. We propose, in particular, to avoid vitamin D deficiency in individuals at risk of developing T1D or T2D. Applying international guidelines on supplementation of vitamin D using small daily doses of vitamin D (500-1000IU) may contribute to reduce the burden of diabetes by preventing vitamin D deficiency. Any other recommendations are at present not supported by data.

Topics: Animals; Causality; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Risk Factors; Vitamin D; Vitamin D Deficiency

Various kinds of immune cells-including macrophages, dendritic cells, T cells and B cells- express the vitamin D receptor and 1α-hydroxylase (CYP27B1), the enzyme necessary for the conversion of circulating 25-hydroxyvitamin D into its active form, 1,25-dihydroxyvitamin D. It suggests that vitamin D has a regulatory role on innate and adaptive immune responses. Vitamin D has been recently shown to promote antimicrobial responses through the production of antibacterial peptides, and stimulation of the autophagic activity in macrophages. Recent epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of several infectious diseases. Here, we review the essential roles of vitamin D in modulating the immune system and discuss the protective effects of vitamin D supplementation in diverse infections.

Topics: Animals; Humans; Immune System; Receptors, Calcitriol; T-Lymphocytes; Vitamin D; Vitamin D Deficiency; Vitamins

Deficiency of 1,25(OH)2 vitamin D is inevitable in CKD, and is part of a cascade of bone and mineral abnormalities that result in secondary hyperparathyroidism. The widespread acceptance of calcitriol therapy as the treatment paradigm, has resulted in an overall neglect of vitamin D deficiency, as defined by low serum 25(OH)D levels Recent research has greatly enhanced our understanding of the disordered vitamin D metabolism seen in CKD. Furthermore vitamin D has been implicated in numerous disease states, beyond its traditional role in regulating bone and mineral metabolism. Low serum 25(OH)D levels have been linked to numerous adverse clinical outcomes in health and CKD. Additionally, the recognition of extra-renal, autocrine 1,25(OH)2D synthesis, present in many tissues, has refocused attention on the therapeutic potential of correcting low serum 25(OH)D levels. In this review we examine the physiology of disordered vitamin D metabolism in CKD, the clinical associations of low 25(OH)D levels in CKD, and discuss the rationale for vitamin D replacement in current clinical practice.

Topics: Autocrine Communication; Calcitriol; Humans; Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

Vitamin D appears to have significant effects on both innate and acquired immunity and deficiency may be associated with both susceptibility and disease severity in some autoimmune conditions. There has been little focus on the potential immunomodulatory role of vitamin D in AS. This study systematically reviews the evidence for an association between vitamin D deficiency and disease susceptibility and severity in AS.. A systematic review was conducted using Medline, EMBASE, Web of Science and conference abstracts of the European League Against Rheumatism (2002-13), British Society for Rheumatology (1993-2013) and ACR (2006-13).. Fifteen original articles and five conference abstracts met the criteria for inclusion. All were cross-sectional in design. Seven of 11 studies identified lower concentrations of 25-hydroxyvitamin D (25OHD) in AS patients compared with healthy controls. A significant inverse correlation between 25OHD and disease activity was observed in 5 of 11 studies. The majority of studies that failed to demonstrate significant findings used inappropriate statistical methods.. Cross-sectional studies using appropriate statistical analyses have highlighted that AS is associated with lower vitamin D concentrations. Within groups of AS patients there is some evidence that low vitamin D concentrations are associated with higher disease activity. However, there are insufficient published data to support an immunomodulatory role for vitamin D in AS. Further study with a longitudinal design is required to understand whether optimizing vitamin D in AS has potential as a disease-modifying intervention.

Topics: Cross-Sectional Studies; Disease Susceptibility; Humans; Spondylitis, Ankylosing; Vitamin D; Vitamin D Deficiency

At the beginning of the 20th century, the discovery of vitamin D by Sir EV McCollum allowed a better comprehension of its origin and its role, and made it possible to cure rickets, a largely prevalent disease at that time. The main role of vitamin D3 is to maintain calcium and phosphate homeostasis through the action of 1,25-dihydroxyvitamin D3, its active form. This underlies physiological functions related to calcium and phosphate, such as bone mineralization or muscle function. Progress in basic research for the last 40 years led to the discovery of the main hydroxylation steps that produce and catabolize the active form of vitamin D. It also uncovered the molecular aspects of vitamin D action, from its nuclear receptor, VDR, to the various target genes of this hormone. Recent progress in human genetics pointed out mutations in genes involved in vitamin D metabolism and 1,25-dihydroxyvitamin D3 actions. It also helped to understand the role of the major actors that control vitamin D production and effects, through 1,25-dihydroxyvitamin D3 actions on phosphate and calcium homeostasis, and on bone biology. Genetical engineering targeting the whole animal or defined tissues or cell types have yielded many mouse models in the past decades. When targeted to tissues important for vitamin D metabolism and activity, these models allowed a more detailed comprehension of vitamin effects on calcium and phosphorus homeostasis.

Topics: Animals; Calcium; Cytochrome P-450 Enzyme System; Humans; Intestinal Absorption; Kidney; Mice; Models, Animal; Osteogenesis; Parathyroid Glands; Phosphates; Receptors, Calcitriol; Rickets; Signal Transduction; TRPV Cation Channels; Vitamin D; Vitamin D Deficiency

The development of autoimmune disease is based on the interaction of genetic susceptibility and environmental causes. Environmental factors include infectious and non-infectious agents, with some of these factors being implicated in several autoimmune diseases. Vitamin D is now believed to play a role in the development (or prevention) of several autoimmune diseases, based on its immunomodulatory properties. As well, the increasing incidence of autoimmune disease as one moves away from the equator, may be due to the lack of sunlight, which is crucial for the maintenance of normal vitamin D levels. A deficiency in vitamin D levels or vitamin D receptors is commonly indicated in autoimmune diseases, with multiple sclerosis (MS) being one of the best-studied and well-known examples. However, the role of vitamin D in other autoimmune diseases is not well defined, including autoimmune liver diseases such as primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis. This review will examine the role of vitamin D as an immunomodulator, followed by a comparison of vitamin D in MS versus autoimmune liver disease. From this comparison, it will become clear that vitamin D likely plays a role in the development of autoimmune liver disease, but this area requires further investigation.

Topics: Autoimmune Diseases; Cell Proliferation; Cytokines; Genotype; Humans; Immunomodulation; Liver Diseases; Multiple Sclerosis; Polymorphism, Single Nucleotide; Receptors, Calcitriol; T-Lymphocytes; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

Vitamin D activity requires an adequate vitamin D status as indicated by the serum level of 25-hydroxyvitamin D and appropriate expression of genes coding for vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase, the enzyme which converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Vitamin D deficiency contributes to the aetiology of osteomalacia and osteoporosis. The key element of osteomalacia, or rickets in children, is a delay in mineralization. It can be resolved by normalisation of plasma calcium and phosphate homeostasis independently of vitamin D activity. The well characterised endocrine pathway of vitamin D metabolism generates plasma 1,25-dihydroxyvitamin D and these endocrine activities are solely responsible for vitamin D regulating plasma calcium and phosphate homeostasis and protection against osteomalacia. In contrast, a large body of clinical data indicate that an adequate serum 25-hydroxyvitamin D level improves bone mineral density protecting against osteoporosis and reducing fracture risk. Recent research demonstrates that the three major bone cell types have the capability to metabolise 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D to activate the vitamin D receptor and modulate gene expression. Dietary calcium intake interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on bone through the endocrine system when calcium intake is inadequate or an anabolic action through a bone autocrine or paracrine system when calcium intake is sufficient.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Bone and Bones; Bone Density; Calcification, Physiologic; Calcium; Child; Gene Expression Regulation; Humans; Osteomalacia; Osteoporosis; Phosphates; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Vitamin D is a fat-soluble precursor of the circulating 25-hydroxyvitamin D₃ (25(OH)D₃)which can be converted by the 1α-hydroxylase (1α(OH)ase) enzyme into the bioactive hormonal metabolite 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), generally known to promote bone mineralization through its ability to enhance calcium absorption from the gut. Importantly, in humans, vitamin D is mainly derived from endogenous production of vitamin D₃ from ultraviolet (UV) radiation exposure to the skin while a small part (<10%) is obtained via dietary intake of dairy products and fatty fish (1). Taking these factors into account, geographic distribution and seasonality, skin pigmentation, age, and lifestyle may predispose certain populations to be at a higher risk of developing vitamin D insufficiency or deficiency (2). The first valid reports correlating the importance of an adequate vitamin D status to optimal human health originate from the early part of the 20th century, when vitamin D was described to prevent and treat the bone disease rickets. Since then, the findings that vitamin D receptors (VDR) are present in many body tissues and that vitamin D metabolizing enzymes can be found in various cells outside the kidney, including the intestine, prostate, immune cells, and within the skin itself (reviewed in reference 3), have revolutionized the vitamin D business. In this review, we will mainly focus on vitamin D as a component of immune regulation and on the role of vitamin D in antigen-specific and non-specific therapies with potential relevance for type 1 diabetes (T1D).

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; Dendritic Cells; Diabetes Mellitus, Type 1; Humans; Immunomodulation; Immunotherapy; Insulin-Secreting Cells; Receptors, Calcitriol; T-Lymphocytes; T-Lymphocytes, Regulatory; Vitamin D; Vitamin D Deficiency

Immunomodulatory actions of vitamin D have been recognised for over a quarter of a century, but it is only in the last few years that the significance of this to normal human physiology has become apparent. Two key factors have underpinned this revised perspective. Firstly, there are increasing data linking vitamin insufficiency with prevalent immune disorders. Improved awareness of low circulating levels of precursor 25-hydroxyvitamin D in populations across the globe has prompted epidemiological investigations of health problems associated with vitamin D insufficiency. Prominent among these are autoimmune diseases such as multiple sclerosis, type 1 diabetes and Crohn's disease, but more recent studies indicate that infections such as tuberculosis may also be linked to low 25-hydroxyvitamin D levels. The second factor expanding the link between vitamin D and the immune system is our improved knowledge of the mechanisms that facilitate this association. It is now clear that cells from the immune system contain all the machinery needed to convert 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D, and for subsequent responses to 1,25-dihydroxyvitamin D. Mechanisms such as this are important for promoting antimicrobial responses to pathogens in macrophages, and for regulating the maturation of antigen-presenting dendritic cells. The latter may be a key pathway by which vitamin D controls T-lymphocyte (T-cell) function. However, T-cells also exhibit direct responses to 1,25-dihydroxyvitamin D, notably the development of suppressor regulatory T-cells. Collectively these observations suggest that vitamin D is a key factor linking innate and adaptive immunity, and both of these functions may be compromised under conditions of vitamin D insufficiency.

Topics: Autoimmune Diseases; Dendritic Cells; Humans; Immunity; Immunologic Factors; Infections; Macrophages; T-Lymphocytes; Vitamin D; Vitamin D Deficiency

The objective of this review is to consider the mechanisms by which vitamin D affects muscle and the evidence that vitamin D status is important for muscle performance and fall prevention in older adults. Vitamin D receptors have been identified in human skeletal-muscle cells. Activation of these receptors by 1,25-dihydroxyvitamin D is involved in the action of vitamin D on the myocyte. Several studies have examined the effect of supplemental vitamin D on muscle strength, balance and falls. Among those examining muscle strength, results have been either positive for vitamin D or null. A recent meta-analysis of seventeen such trials revealed no significant effect of vitamin D overall, but a significant improvement in strength was observed in the trials in which the mean starting level of 25-hydroxyvitamin D was 25 nmol/l or below. Evidence for an effect of vitamin D on balance, measured as sway, is less abundant but more consistently positive. Many trials have evaluated the effect of supplemental vitamin D on falls. Overall, there is about a 20% lower risk of falling with supplementation. One meta-analysis considered the vitamin D dose administered and concluded that doses up through 15 μg (600 IU) were ineffective and doses of 17·5-25 μg/d (700-1000 IU/d) significantly lowered fall risk. The minimal 25-hydroxyvitamin D level needed for benefit was 60 nmol/l.

Topics: Accidental Falls; Aged; Dietary Supplements; Humans; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Postural Balance; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

The population-based association between low vitamin D status and increased cancer risk can be inconsistent, but it is now generally accepted. These relationships link low serum 25OHD (25-hydroxyvitamin D) levels to cancer, whereas cell-based studies show that the metabolite 1,25(OH)2D (1,25-dihydroxyvitamin D) is a biologically active metabolite that works through vitamin D receptor to regulate gene transcription. In the present review we discuss the literature relevant to the molecular events that may account for the beneficial impact of vitamin D on cancer prevention or treatment. These data show that although vitamin D-induced growth arrest and apoptosis of tumour cells or their non-neoplastic progenitors are plausible mechanisms, other chemoprotective mechanisms are also worthy of consideration. These alternative mechanisms include enhancing DNA repair, antioxidant protection and immunomodulation. In addition, other cell targets, such as the stromal cells, endothelial cells and cells of the immune system, may be regulated by 1,25(OH)2D and contribute to vitamin D-mediated cancer prevention.

Topics: Gene Expression Regulation; Humans; Neoplasms; Receptors, Calcitriol; Signal Transduction; Vitamin D; Vitamin D Deficiency; Vitamins

Throughout evolution, sunlight-produced vitamin D in the skin has been critically important for health. Vitamin D, known as the sunshine vitamin, is actually a hormone. Once it is produced in the skin or ingested from the diet, it is converted sequentially in the liver and kidneys to its biologically active form 1,25-dihydroxyvitamin D. This hormone interacts with its receptor in the small intestine to increase the efficiency of intestinal calcium and phosphate absorption for the maintenance of the skeleton throughout life. Vitamin D deficiency during the first few years of life results in a flattened pelvis, making it difficult for childbirth. Vitamin D deficiency causes osteopenia and osteoporosis, increasing risk of fracture. Essentially, every tissue and cell in the body has a vitamin D receptor. Therefore, vitamin D deficiency has been linked to increased risk for preeclampsia, requiring a cesarean section for birthing, multiple sclerosis, rheumatoid arthritis, types I and II diabetes, heart disease, dementia, deadly cancers, and infectious diseases. Therefore, sensible sun exposure along with vitamin D supplementation of at least 2000 IU/d for adults and 1000 IU/d for children is essential to maximize their health.

Topics: Adolescent; Adult; Aged; Calcium; Child; Child, Preschool; Diet; Dietary Supplements; Female; Health; Humans; Infant; Infant, Newborn; Male; Middle Aged; Models, Biological; Receptors, Calcitriol; Skin; Sunlight; Vitamin D; Vitamin D Deficiency; Vitamins

Considering that the vitamin D receptor as well as the 1-α-hydroxylase enzyme that converts 25-hydroxyvitamin D (25(OH)D) to its active form 1,25-dihydroxyvitamin D have been found in tissues throughout the body, it is likely that vitamin D is important for more than the calcium balance. Accordingly, low serum levels of 25(OH)D have been associated with mortality, cardiovascular disease, type 2 diabetes, hypertension and obesity. Low serum levels of 25(OH)D have also been associated with an unfavourable lipid profile, which could possible explain the relation with cardiovascular disease and mortality. However, the relation between vitamin D and lipids have so far received little attention and is therefore the main focus of the present review. A PubMed search identified 22 cross-sectional studies where serum levels of 25(OH)D and lipids were related and that included a minimum of 500 subjects, and 10 placebo-controlled double-blind intervention studies with vitamin D where more than 50 subjects were included. In all the cross-sectional studies serum 25(OH)D was positively associated with high-density lipoprotein cholesterol (HDL-C) resulting in a favourable low-density lipoprotein cholesterol (LDL-C) (or total cholesterol) to HDL-C ratio. There was also a uniform agreement between studies on a negative relation between serum 25(OH)D and triglycerides (TG). On the other hand, the intervention studies gave divergent results, with some showing a positive and some a negative effect of vitamin D supplementation. However, none of the intervention studies were specifically designed for evaluating the relation between vitamin D and lipids, none had hyperlipemia as an inclusion criterion, and none were sufficiently powered. In only one study was a significant effect seen with an 8% (0.28 mmol/L) increase in serum LDL-C and a 16% (0.22 mmol/L) decrease in serum TG in those given vitamin D as compared to the placebo group. Accordingly, the effect of vitamin D supplementation on serum lipids is at present uncertain. Considering the numerous other promising vitamins and minerals that when properly tested have been disappointing, one should wait for the results of forthcoming vitamin D intervention studies before drawing conclusions on potential beneficial effects of vitamin D.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypertension; Male; Obesity; Randomized Controlled Trials as Topic; Triglycerides; Vitamin D; Vitamin D Deficiency

Humans acquire vitamin D through skin photosynthesis and digestive intake. Two hydroxylations are needed to obtain the bioactive compound, the first produces 25-hydroxyvitamin D [25(OH)D], and the second 1,25-dihydroxyvitamin D [1,25(OH)2D]. There is no consensus regarding the appropriate cut-off level to define the normal serum 25(OH)D range. Experimental, epidemiological and clinical studies have related low vitamin D status with longevity. Although some results are controversial, low serum 25(OH)D levels have been linked to all-cause, cardiovascular, cancer and infectious related mortality. Throughout life span a significant proportion of human beings display insufficient (20-30 ng/mL) or deficient (<20 ng/mL) serum 25(OH)D levels. Appropriate lifestyle changes, such as regular short exposures to sunlight (15 min a day), and an adequate diet that includes vitamin D rich components, are not always easily accomplished. Studies relating to vitamin D supplementation have methodological limitations or are based on relatively low doses. Therefore, dosages used for vitamin D supplementation should be higher than those traditionally suggested. In this sense, there is an urgent need for prospective controlled studies using high daily vitamin D doses (2,000 IU or higher) including cardiovascular, cancer, infectious and other endpoints. Relationship between vitamin D and health outcomes is not linear, and there are probably various optimal vitamin D levels influencing different endpoints.

Topics: Bone Density Conservation Agents; Diet; Dietary Supplements; Evidence-Based Medicine; Global Health; Humans; Longevity; Risk Assessment; Risk Factors; Sunlight; Vitamin D; Vitamin D Deficiency

Type 1 (T1D) and type 2 (T2D) diabetes are considered multifactorial diseases in which both genetic predisposition and environmental factors participate in their development. Many cellular, preclinical, and observational studies support a role for vitamin D in the pathogenesis of both types of diabetes including: (1) T1D and T2D patients have a higher incidence of hypovitaminosis D; (2) pancreatic tissue (more specifically the insulin-producing beta-cells) as well as numerous cell types of the immune system express the vitamin D receptor (VDR) and vitamin D-binding protein (DBP); and (3) some allelic variations in genes involved in vitamin D metabolism and VDR are associated with glucose (in)tolerance, insulin secretion, and sensitivity, as well as inflammation. Moreover, pharmacologic doses of 1,25-dihydroxyvitamin D (1,25(OH)(2)D), the active form of vitamin D, prevent insulitis and T1D in nonobese diabetic (NOD) mice and other models of T1D, possibly by immune modulation as well as by direct effects on beta-cell function. In T2D, vitamin D supplementation can increase insulin sensitivity and decrease inflammation. This article reviews the role of vitamin D in the pathogenesis of T1D and T2D, focusing on the therapeutic potential for vitamin D in the prevention/intervention of T1D and T2D as well as its complications.

Topics: Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Genetic Predisposition to Disease; Glucose Intolerance; Humans; Immune System; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Male; Mice; Pancreatitis; Rats; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

Historically vitamin D is known to be essential for normal bone growth and quality, and thus appropriate dietary vitamin D supplementation can eliminate vitamin D deficiency childhood rickets and adult osteomalacia. In spite of many government and medical associations' worldwide guidelines for the reference daily intake (RDI) of vitamin D, scientists and nutritionists from many countries agree that at present about half of elderly North Americans and Western Europeans and probably also of the rest of the world are not receiving enough vitamin D to maintain healthy bone. In addition, over the past decade there has been a dramatic increase in our understanding of the many biological actions that result from vitamin D acting through its daughter steroid hormone, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] in collaboration with its cognate vitamin D receptor (VDR). Consequently, evidence has accumulated that beside intestine and bone, there are five additional physiological systems where the VDR with 1alpha,25(OH)(2)D generates biological responses. These include the immune system (both the innate and adaptive), pancreas and metabolic homeostasis, heart-cardiovascular, muscle and brain systems as well as the control of the cell cycle, and thus of the disease process of cancer. Acting through the VDR, 1alpha,25(OH)(2)D(3) can produce a wide array of favorable biological effects that collectively are projected to contribute to the improvement of human health. Responsible medicine demands that worldwide vitamin D nutritional guidelines reflect current scientific knowledge about vitamin D's spectrum of activities. Thus, worldwide vitamin D nutritional policy is now at a crossroads. This paper presents several proposed policy changes with regard to the amount of vitamin D daily intake that if implemented will maximize vitamin D's contribution to reducing the frequency of many diseases, which would then increase the quality and longevity of life and significantly reduce the cost of medical care worldwide.

Topics: Aged; Bone and Bones; Bone Development; Dietary Supplements; Forecasting; Humans; Male; Public Policy; Receptors, Calcitriol; Rickets; Vitamin D; Vitamin D Deficiency

Fibroblast growth factor 23 (FGF23) is a circulating hormone that is synthesized by osteocytes and osteoblasts. This glycosylated peptide controls phosphate balance by modulating urinary phosphate excretion and indirectly intestinal phosphate absorption by reducing expression of the renal and intestinal sodium phosphate transporters. In a feedback loop, 1,25-dihydroxyvitamin D and phosphate intake control FGF23 production. FGF23 is inactivated by cleavage by a still unidentified enzyme. FGF23 cleavage occurs within cells and probably in the circulation. Klotho, a protein expressed at the cell surface of few organs, forms complexes with FGF receptors, which increases their affinity for FGF23. Klotho is also released into the plasma and urine by an enzymatic cleavage. FGF23 plays a central role in vitamin D metabolism: It inhibits calcitriol synthesis in the kidney and stimulates the catabolism of active vitamin D sterols. In turn, calcitriol stimulates FGF23 and Klotho expression. In chronic kidney diseases, FGF23 concentration increases as GFR declines, whereas Klotho tissue expression decreases. The modifications of FGF23 and Klotho expression are probably involved in the genesis of hyperparathyroidism and the resistance to vitamin D receptor (VDR) activation in chronic kidney disease. Low vitamin D, high FGF23 concentrations, and defects in VDR activation are associated with similar risks, which evoke the possibility that potential FGF23 toxicity might be partly mediated by FGF23-induced decrease in calcitriol or 25-hydroxyvitamin D. Conversely, VDR activators could be used to modulate Klotho or FGF23 expression.

Topics: Animals; Chronic Disease; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Glucuronidase; Homeostasis; Humans; Kidney; Kidney Diseases; Klotho Proteins; Phosphorus, Dietary; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

It is true to say that it is just over the past decade and even more so in this new decade that it has become appreciated how vitally important vitamin D is for optimum health. This 'sunshine' vitamin could justifiably be called 'the nutrient of this decade'. Until recently, vitamin D was known primarily for its role in bone health. However, as a result of advances in research this perspective has changed. While it is true to say that the classic function of vitamin D is to control calcium and vitamin D metabolism, we now know that the importance of vitamin D spreads far wider than just bone health. There is much ongoing research with regard to its emerging role in immunopathology, as a potent inhibitor of cellular growth, stimulator of insulin secretion, modulator of immune function and inhibitor of renin production. This review discusses the current evidence with regard to the clinical consequences of vitamin D deficiency and underscores the fact that physicians should be vigilant in searching for and treating this preventable and treatable condition. Furthermore, this review highlights the fact that the time is opportune for rheumatologists to agree upon clinical guidelines to advise practitioners as to when and in which patients to check for, what target vitamin D level to aim for and how best to treat vitamin D deficiency.

Topics: Biomarkers; Dietary Supplements; Humans; Osteomalacia; Parathyroid Hormone; Prevalence; Vitamin D; Vitamin D Deficiency

A compromised vitamin D status, characterized by low 25-hydroxyvitamin D (25-(OH)D) serum levels, and a nutritional calcium deficit are widely encountered in European and North American countries, independent of age or gender. Both conditions are linked to the pathogenesis of many degenerative, malignant, inflammatory and metabolic diseases. Studies on tissue-specific expression and activity of vitamin D metabolizing enzymes, 25-(OH)D-1 alpha-hydroxylase and 25-(OH)D-24-hydroxylase, and of the extracellular calcium-sensing receptor (CaR) have led to the understanding of how, in non-renal tissues and cellular systems, locally produced 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) and extracellular Ca(2+) act jointly as key regulators of cellular proliferation, differentiation and function. Impairment of cooperative signalling from the 1,25-(OH)(2)D(3)-activated vitamin D receptor (VDR) and from the CaR in vitamin D and calcium insufficiency causes cellular dysfunction in many organs and biological systems, and, therefore, increases the risk of diseases, particularly of osteoporosis, colorectal and breast cancer, inflammatory bowel disease, insulin-dependent diabetes mellitus type I, metabolic syndrome, diabetes mellitus type II, hypertension and cardiovascular disease. Understanding the underlying molecular and cellular processes provides a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases worldwide.

Topics: Autoimmune Diseases; Calcium; Calcium, Dietary; Cardiovascular Diseases; Chronic Disease; Gene Expression Regulation; Humans; Metabolic Diseases; Neoplasms; S100 Calcium Binding Protein G; Vitamin D; Vitamin D Deficiency

Chronic kidney disease is associated with an increased risk of cardiovascular disease. Vitamin D deficiency is common in patients with chronic kidney disease. In epidemiological studies, vitamin D deficiency and absence of treatment with vitamin D is associated with increased cardiovascular mortality. Several possible mechanisms may explain how vitamin D can influence the development of cardiovascular disease. Clinical intervention studies are needed to clarify whether treatment with vitamin D decreases the risk of cardiovascular disease in chronic kidney disease.

Topics: Animals; Calcinosis; Cardiovascular Diseases; Heart Failure; Humans; Kidney Failure, Chronic; Renal Dialysis; Risk Factors; Vascular Diseases; Vitamin D; Vitamin D Deficiency

Vitamin D, the sunshine vitamin, is now recognized not only for its importance in promoting bone health in children and adults but also for other health benefits, including reducing the risk of chronic diseases such as autoimmune diseases, common cancer, and cardiovascular disease. Vitamin D made in the skin or ingested in the diet is biologically inert and requires 2 successive hydroxylations first in the liver on carbon 25 to form 25-hydroxyvitamin D [25(OH)D], and then in the kidney for a hydroxylation on carbon 1 to form the biologically active form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. With the identification of 25(OH)D and 1,25(OH)(2)D, methods were developed to measure these metabolites in the circulation. Serum 25(OH)D is the barometer for vitamin D status. Serum 1,25(OH)(2)D provides no information about vitamin D status and is often normal or even increased as the result of secondary hyperparathyroidism associated with vitamin D deficiency. Most experts agree that 25(OH)D of <20 ng/mL is considered to be vitamin D deficiency, whereas a 25(OH)D of 21-29 ng/mL is considered to be insufficient. The goal should be to maintain both children and adults at a level >30 ng/mL to take full advantage of all the health benefits that vitamin D provides.

Topics: Binding, Competitive; Humans; Radioimmunoassay; Vitamin D; Vitamin D Deficiency

Topics: Humans; Vitamin D; Vitamin D Deficiency

Serum calcium (Ca) level is tightly regulated by parathyroid hormone (PTH) and 1,25-dihydoxyvitamin D in human. In practice, however, one should take a look at background factors that have significant effects on Ca and its regulating hormones. Among them vitamin D insufficiency, magnesium (Mg) depletion and treatment with bisphosphonates, glucocorticoids and anticonvulsants are most important.

Topics: Bone Density Conservation Agents; Diagnosis, Differential; Diphosphonates; Glucocorticoids; Humans; Hypocalcemia; Magnesium Deficiency; Parathyroid Hormone; Vitamin D; Vitamin D Deficiency

Recent studies have added new dimensions to the fund of knowledge on vitamin D. In addition to the classic role of vitamin D in preventing rickets and osteomalacia, a preventive effect against osteoporotic fractures has been convincingly established, and abundant evidence suggests a role in preventing malignancies and autoimmune diseases. Serum 25-OH-vitamin D assay is a simple test for evaluating vitamin D status. However, recent review articles indicate that current reference ranges for serum 25-OH-vitamin D are too low. An appropriate lower normal limit may be between 50-100 nmol/l (20-40 ng/ml). Standard supplement dosages may fail to provide concentrations above this range.

Topics: Fractures, Bone; Humans; Osteomalacia; Osteoporosis; Rickets; Risk Factors; Vitamin D; Vitamin D Deficiency

Topics: Addison Disease; Calcitonin; Calcium; Diagnosis, Differential; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Hyperthyroidism; Hypocalcemia; Hypoparathyroidism; Parathyroid Hormone; Prognosis; Vitamin D; Vitamin D Deficiency

There is evidence from both observational studies and clinical trials that calcium malnutrition and hypovitaminosis D are predisposing conditions for various common chronic diseases. In addition to skeletal disorders, calcium and vitamin D deficits increase the risk of malignancies, particularly of colon, breast and prostate gland, of chronic inflammatory and autoimmune diseases (e.g. insulin-dependent diabetes mellitus, inflammatory bowel disease, multiple sclerosis), as well as of metabolic disorders (metabolic syndrome, hypertension). The aim of the present review was to provide improved understanding of the molecular and cellular processes by which deficits in calcium and vitamin D cause specific changes in cell and organ functions and thereby increase the risk for chronic diseases of different aetiology. 1,25-Dihydroxyvitamin D(3) and extracellular Ca(++) are both key regulators of proliferation, differentiation and function at the cellular level. However, the efficiency of vitamin D receptor-mediated intracellular signalling is limited by the negative effects of hypovitaminosis D on extrarenal 25-hydroxyvitamin D-1alpha-hydroxylase activity and thus on the production of 1,25-dihydroxyvitamin D(3). Calcium malnutrition eventually causes a decrease in calcium concentration in extracellular fluid compartments, resulting in organ-specific modulation of calcium-sensing receptor activity. Hence, attenuation of signal transduction from the ligand-activated vitamin D receptor and calcium-sensing receptor seems to be the prime mechanism by which calcium and vitamin D insufficiencies cause perturbation of cellular functions in bone, kidney, intestine, mammary and prostate glands, endocrine pancreas, vascular endothelium, and, importantly, in the immune system. The wide range of diseases associated with deficits in calcium and vitamin D in combination with the high prevalence of these conditions represents a special challenge for preventive medicine.

Topics: Autoimmune Diseases; Calcium; Calcium, Dietary; Chronic Disease; Communicable Diseases; Humans; Hypertension; Musculoskeletal Diseases; Neoplasms; Osteoporosis; Prevalence; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency/insufficiency, which is clinically represented by low 25(OH)D concentration, is frequently seen in patients with CKD stage 3 and 4. Although its cause is unknown, hypovitaminosis D is partly associated with low 1,25(OH)2D in these patients, possibly leading to advancement of renal osteodystrophy. Recently, in United States, K/DOQI (Kidney disease outcomes quality initiative) guideline indicated that vitamin D deficiency/insufficiency of 25(OH)D concentration less than 30 ng/mL should be treated by supplementation of ergocalciferol. A Japanese guideline to treat vitamin D deficiency/insufficiency should be urgently established.

Topics: Biomarkers; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Severity of Illness Index; Vitamin D; Vitamin D Deficiency

Topics: Calcitriol; Calcium; Cytochrome P-450 Enzyme System; Gene Expression Regulation, Enzymologic; Humans; Interferon-gamma; Kidney Tubules, Proximal; Macrophages; Parathyroid Hormone; Receptors, Calcitriol; Steroid Hydroxylases; Vitamin D; Vitamin D Deficiency; Vitamin D3 24-Hydroxylase

Although both vitamin D deficiency and obesity are highly prevalent in the UAE, the role of vitamin D metabolites in mediating obesity-related adverse health effects is not clear. We aimed to assess the role of vitamin D metabolites as potential mediators in the association between obesity, inflammation and metabolic risk factors.. 277 participants who were part of a randomized controlled trial had their assessment that included clinical, anthropometric and physical activity data at baseline and at 6 months. Blood and urine samples were taken for measurements of serum 25(OH)D, 25(OH)D metabolites including 25(OH)D3), 25(OH)D2), 1,25(OH)2D3, 3-Epi-D3), metabolic and inflammatory markers and related biochemical variables. Multiple regression analysis used to assess the role of 25(OH)D metabolites in mediating the effect of increasing body mass index (BMI) on inflammation and metabolic risk factors.. Overall, 277 participants with complete 6 months follow up with a mean (±SD) age of 41 ± 12 and 204 (74%) female were included in the study. Blood pressure, inflammatory, metabolic and lipid profile markers significantly increased in overweight and obese subjects compared to subjects with normal BMI both at baseline and at 6 months (p < 0.05). 25(OH)D revealed significant association with age, gender, HbA1c and type 2 diabetes (p < 0.05). No statistically significant changes in any of 25(OH)D metabolites assessed. Multivariate analysis revealed significant and independent associations between BMI and important inflammatory and metabolic risk factors (p < 0.05). No similar association observed with 25(OH)D metabolites.. Although we found significant association between 25(OH)D and prevalence of type 2 diabetes, we found no evidence however to support a role of 25(OH)D metabolites in mediating the effect of BMI on inflammatory or metabolic risk factors.

Topics: 25-Hydroxyvitamin D 2; Adult; Body Mass Index; Calcifediol; Calcitriol; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Multivariate Analysis; Obesity; Risk Factors; Vitamin D; Vitamin D Deficiency

Vitamin D inadequacy is pervasive in the oldest-old. Many vitamin D metabolites are available for supplementation, their effects on the recovery of adequate serum levels remain unknown. We investigate the effects of supplementation with cholecalciferol (D3) and calcifediol (25D3) on serum levels of 25(OH)D, 1-25(OH)D, bone and inflammatory markers, ultimately identifying clinical predictors of successful treatment. Sixty-seven oldest-old individuals were randomized to weekly administration of 150 mcg of 25D3 or D3, from hospital admission to 7 months after discharge. Supplementation of 25D3 and D3 were associated with increasing serum levels of 25(OH)D (

Topics: Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcifediol; Cholecalciferol; Dietary Supplements; Drug Administration Schedule; Female; Hand Strength; Hospitalization; Humans; Male; Parathyroid Hormone; Polypharmacy; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is common in peritoneal dialysis (PD) patients, so its supplementation has been advocated as potentially beneficial.. Double-blind, placebo-controlled, randomized clinical trial. Subjects on PD treated with high calcium peritoneal dialysate (Ca 3.5 mEq/l) and serum levels of 25-hydroxi vitamin D (25D) < 20 ng/ml were randomized to receive cholecalciferol (4800 IU/daily) or placebo for 16 weeks. The outcome measures were the effects on the osteogenic biomarkers osteoprotegerin (primary endpoint), intact fibroblast growth factor-23 (iFGF23), osteocalcin, osteopontin, iPTH, 1,25-dyhydroxivitamin D (1,25D), and interleukin-6.. Fifty-eight subjects were randomly assigned. Baseline characteristics were similar in both groups. Cholecalciferol supplemented subjects had a significant increase in serum 25D (from 11.4 ± 5.0 to 28.3 ± 10.3 ng/ml), 1,25D and iFGF23 compared with placebo group. iFGF23 levels increased an average of 10,875 pg/ml per month (95% CI 11,778-88,414) in the cholecalciferol group and was unchanged in the placebo group (2829 pg/ml, 95% CI - 2181 to 14,972). Extremely high iFGF23 levels (> 30,000 pg/ml) were observed in 74% of subjects receiving cholecalciferol although iFGF23 returned to baseline values after 32 weeks of withdrawal. The observed changes in iFGF23 correlated with 1,25D levels and were not modified by other variables. No difference was observed between groups in osteoprotegerin or other osteogenic biomarkers levels.. Cholecalciferol supplementation increases serum 25D levels in subjects on PD exposed to high calcium dialysate, yet it induces an exponential increase of iFGF23 in most patients, which disappear after withdrawal of supplementation and may be a major concern for this maneuver.

Topics: Adult; Aged; Biomarkers; Carotid Intima-Media Thickness; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Interleukin-6; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin; Parathyroid Hormone; Peritoneal Dialysis; Prospective Studies; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

Results of animal models and cross-sectional cohort studies have suggested a beneficial role for vitamin D in male reproduction.. Determine the effect of vitamin D and calcium supplementation on semen quality in infertile men with serum 25-hydroxyvitamin-D (25OHD) levels ≤50 nmol/L.. A single-center, triple-blinded, randomized clinical trial.. A total of 1427 infertile men were screened to include 330; 1002 men did not meet inclusion criteria and 95 did not wish to participate.. The active group received cholecalciferol 300,000 IU initially, then 1400 IU cholecalciferol and 500 mg of calcium daily for 150 days; the other group received placebo.. Serum concentrations of 25OHD and 1,25-dihydroxyvitamin D3 were significantly higher in men in the treatment group compared with the placebo group. Vitamin D supplementation was not associated with changes in semen parameters, although spontaneous pregnancies tended to be higher in couples in which the man was in the treatment group [7.3% vs 2.4%, Δ5.0% (-0.6%; 10.5%)]. Vitamin D treatment in a subgroup of oligozoospermic men increased the chance for a live birth compared with placebo [35.6% vs 18.3%, Δ17.3% (1.6%; 32.9%)]. Moreover, serum inhibin B levels were higher in men deficient in vitamin D who were randomly assigned to receive high-dose vitamin D [193 pg/mL vs 143 pg/mL, Δ49 pg/mL (8; 91 pg/mL)]; however, the increase in sperm concentration was not significantly higher than in the placebo group (P = 0.07).. High-dose vitamin D supplementation did not improve semen quality in vitamin D-insufficient infertile men. The positive impact of vitamin D supplementation on live birth rate and serum inhibin B in oligozoospermic and vitamin D-deficient men may be of clinical importance and warrant verification by others.

Topics: Adult; Calcium; Cholecalciferol; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Infertility, Male; Male; Middle Aged; Oligospermia; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Semen Analysis; Sperm Count; Sperm Motility; Vitamin D; Vitamin D Deficiency

Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH). Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH). TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health.. NCT01751646 (ATN 109) and NCT01769469 (ATN 117).

Topics: Adolescent; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Black or African American; Bone and Bones; Bone Density; Cohort Studies; Emtricitabine; Female; HIV; HIV Infections; Humans; Male; Parathyroid Hormone; Pre-Exposure Prophylaxis; Tenofovir; Vitamin D; Vitamin D Deficiency; White People; Young Adult

Previous in vitro and in vivo studies indicate that enzymes that synthesize and metabolize vitamin D are magnesium dependent. Recent observational studies found that magnesium intake significantly interacted with vitamin D in relation to vitamin D status and risk of mortality. According to NHANES, 79% of US adults do not meet their Recommended Dietary Allowance of magnesium.. The aim of this study was to test the hypothesis that magnesium supplementation differentially affects vitamin D metabolism dependent on baseline 25-hydroxyvitamin D [25(OH)D] concentration.. The study included 180 participants aged 40-85 y and is a National Cancer Institute independently funded ancillary study, nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), which enrolled 250 participants. The PPCCT is a double-blind 2 × 2 factorial randomized controlled trial conducted in the Vanderbilt University Medical Center. Doses for both magnesium and placebo were customized based on baseline dietary intakes. Subjects were randomly assigned to treatments using a permuted-block randomization algorithm. Changes in plasma 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2 [25(OH)D2], 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by liquid chromatography-mass spectrometry.. The relations between magnesium treatment and plasma concentrations of 25(OH)D3, 25(OH)D2, and 24,25(OH)2D3 were significantly different dependent on the baseline concentrations of 25(OH)D, and significant interactions persisted after Bonferroni corrections. Magnesium supplementation increased the 25(OH)D3 concentration when baseline 25(OH)D concentrations were close to 30 ng/mL, but decreased it when baseline 25(OH)D was higher (from ∼30 to 50 ng/mL). Magnesium treatment significantly affected 24,25(OH)2D3 concentration when baseline 25(OH)D concentration was 50 ng/mL but not 30 ng/mL. On the other hand, magnesium treatment increased 25(OH)D2 as baseline 25(OH)D increased.. Our findings suggest that optimal magnesium status may be important for optimizing 25(OH)D status. This trial was registered at clinicaltrials.gov as NCT03265483.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Aged; Calcifediol; Calcitriol; Dietary Supplements; Ergocalciferols; Female; Humans; Kidney; Magnesium; Magnesium Deficiency; Male; Middle Aged; Nutritional Status; Placebos; Vitamin D; Vitamin D Deficiency

Deficiency of vitamin D is very common in obese people and treatment by oral supplementation is not effective in all patients. This exploratory pilot study investigated the influence of different doses of short-term ultraviolet B irradiation on serum 25-hydroxyvitamin-D. Participants with skin types II and III (Fitzpatrick skin classification) were assigned to six groups including four intervention groups receiving irradiation (three groups of obese and one group of normal weight subjects) and two control groups without treatment (obese and normal weight). Intervention groups received three sessions of whole body UVB irradiation of three different doses (cumulative doses over three sessions: 0.28, 0.70, 1.75 minimal erythema dose) within 1 week of intervention. Serum 25D and 1,25D were measured at baseline and after irradiation. Outcome differences between groups were analyzed using a linear model.. Serum 25D levels increased significantly in obese (+23.6 and +26.7%, respectively, p = 0.01) and normal weight (+15.6%, p = 0.02) intervention groups who received medium and high doses of ultraviolet B irradiation compared to control groups (+3.5 and -4.0%, respectively, p = 1.0). The increase in obese patients was 51.4% greater compared to normal weight controls irradiated with equal ultraviolet B doses. Low-level ultraviolet irradiation did not result in a significant change in serum 25D (+7.0%, p = 0.61). We did not detect any significant differences of 1,25D between groups (p = 0.25).. The current study indicates that short-term ultraviolet B irradiation increases 25D levels in obese patients.

Topics: Adult; Calcifediol; Female; Humans; Male; Middle Aged; Obesity; Pilot Projects; Ultraviolet Rays; Ultraviolet Therapy; Vitamin D; Vitamin D Deficiency

Vitamin D (VitD) deficiency is a health problem prevalent not only in the elderly but also in young adults. The primary objective of our observational pilot study "MUVY" (Mood, UVR, Vitamin D in Young women) was to test both the short-term and long-term effects of a series of three suberythemal UV radiation (UVR) exposures on the VitD status and well-being of young healthy women during winter in a repeat measure design.. 20 healthy young women (Fitzpatrick skin types I-III, aged 21-25 years) received three full body broad band UVR exposures with an escalating erythemally weighted dose schedule during one week in winter, and completed self-report questionnaires monitoring symptoms of depression (Beck Depression Inventory, BDI) and affective state/well-being (Profile of Mood States, POMS) at baseline and three days after the last UVR exposure. 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in serum at baseline, and at study days 8, 36 and 50.. Mean baseline 25(OH)D level was 54.3 nmol/L (standard deviation (s.d.) = 24.1), with seven women having VitD deficient status. Relevant symptoms of depression, as indicated by low BDI total scores (0-8), were absent. After the three UVR exposures the increment of 25(OH)D was an average of 13.9 nmol/L (95% confidence interval (CI) = 9.4-18.4) and 26.2 pmol/L (95%CI = 7.2-45.1) for 1,25(OH)2D. Δ25(OH)D, and corresponding baseline levels were significantly and inversely associated (rho = -0.493, p = 0.027). Only 25(OH)D remained significantly increased above baseline for at least six weeks after the last UVR exposure. A strong inverse correlation of the POMS subscale "Vigor/Activity" and the increment in 1,25(OH)2D was found (rho = -0.739, p<0.001) at day 8.. Three suberythemal whole body UVR exposures during one week are a simple and suitable method for improving 25(OH)D levels during winter, for at least six weeks, and especially in young women with VitD deficient status.. German Clinical Trials Register (Deutsches Register Kinischer Studien) DRKS00009274.

Topics: Adult; Female; Humans; Pilot Projects; Seasons; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency; Whole-Body Irradiation; Women's Health; Young Adult

Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23.. Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks.. ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events.. Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD.

Topics: 24,25-Dihydroxyvitamin D 3; Aged; Calcifediol; Calcium; Creatinine; Delayed-Action Preparations; Double-Blind Method; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

Little is known about the changes in calciotropic hormones during puberty and their relationship to bone mass during this critical period for skeletal accretion.. Investigate changes in calciotropic hormones, IGF-1, body composition, and their associations with bone metabolism in adolescents.. Post hoc analyses were performed from data on 335 healthy school children, ages 10-17 years, with hypovitaminosis D who participated in a vitamin D randomized controlled trial. Baseline serum biochemistries; hormonal studies; densitometry at the spine, hip, and total body; and body composition were used. ANOVA and regression analyses were implemented to evaluate changes in variables of interest across pubertal stages, within and between genders.. Bone mass and body composition parameters increased substantially across Tanner stages in both genders. Serum calcium, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D levels did not vary by Tanner stages in both genders. Conversely, serum phosphorus, alkaline phosphatase, IGF-1, PTH, and osteocalcin peaked for the most part at Tanner stage II in girls and stage III in boys. 1,25-Dihydroxyvitamin D correlations with bone mass were not consistent, whereas IGF-1 was the most robust correlate of bone mass at several skeletal sites in early Tanner stages in both genders (R = 0.3-0.6).. Serum phosphorus, alkaline phosphatase, IGF-1, PTH, and osteocalcin, but not calcium or 1,25-dihydroxyvitamin D, increased significantly in early puberty, with gender difference except for PTH, peaking earlier in girls than in boys. IGF-1 is a robust predictor of bone mass, an effect mediated in large part by increments in lean mass.

Topics: Adolescent; Alkaline Phosphatase; Body Composition; Bone Density; Child; Female; Humans; Insulin-Like Growth Factor I; Male; Osteocalcin; Parathyroid Hormone; Phosphorus; Puberty; Vitamin D; Vitamin D Deficiency

In several low latitude countries, vitamin D deficiency is emerging as a public health issue. Adequate vitamin D is essential for bone health in rapidly growing children. In the Thai population, little is known about serum 25-hydroxyvitamin D [25(OH)D] status of infants and children. Moreover, the association between 25(OH)D and the biological active form of 1,25-dihydroxyvitamin D [1,25(OH)]2D is not clear. The specific aims of this study were to characterize circulating serum 25(OH)D, 1,25(OH)2D and their determinants including parathyroid hormone (PTH), age, sex, height and body mass index (BMI) in 529 school-aged Thai children aged 6-14 y. Adjusted linear regression analysis was performed to examine the impact of age and BMI, and its interaction with sex, on serum 25(OH)D concentrations and 1,25(OH)2D concentrations. Serum 25(OH)D, 1,25(OH)2D and PTH concentrations (geometric mean ± geometric SD) were 72.7±1.2 nmol/L, 199.1±1.3 pmol/L and 35.0±1.5 ng/L, respectively. Only 4% (21 of 529) participants had a serum 25(OH)D level below 50 nmol/L. There was statistically significant evidence for an interaction between sex and age with regard to 25(OH)D concentrations. Specifically, 25(OH)D concentrations were 19% higher in males. Moreover, females experienced a statistically significant 4% decline in serum 25(OH)D levels for each increasing year of age (P = 0.001); no decline was seen in male participants with increasing age (P = 0.93). When BMI, age, sex, height and serum 25(OH)D were individually regressed on 1,25(OH)2D, height and sex were associated with 1,25(OH)2D with females exhibiting statistically significantly higher serum 1,25(OH)2D levels compared with males (P<0.001). Serum 1,25(OH)2D among our sample of children exhibiting fairly sufficient vitamin D status were higher than previous reports suggesting an adaptive mechanism to maximize calcium absorption.

Topics: Adolescent; Age Factors; Body Height; Body Mass Index; Calcium, Dietary; Child; Female; Humans; Male; Parathyroid Hormone; Schools; Sex Factors; Socioeconomic Factors; Students; Thailand; Vitamin D; Vitamin D Deficiency

Declines in 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels and physical functioning follow the course of chronic kidney disease (CKD). Although the molecular actions of vitamin D in skeletal muscle are well known, and muscle weakness and atrophy are observed in vitamin D-deficient states, there is little information regarding vitamin D and muscle function and size in CKD.. To examine associations of vitamin D with physical performance (PF) and muscle size.. Cross-sectional.. CKD clinic.. Twenty-six patients (61 ± 13 years, 92% men) with CKD stage 3 or 4.. Gait speed, 6-minute walk, sit-to-stand time, 1-legged balance, and thigh muscle cross-sectional area (MCSA), measured by magnetic resonance imaging (MRI).. Overall, 73% were 25-hydroxyvitamin D (25(OH)D) deficient (n = 10) or insufficient (n = 9) (Kidney Disease Outcomes Quality Initiative guidelines). 25(OH)D level was associated with normal gait speed only (r = 0.41, P = .04). Normal and fast gait speed, the distance walked in 6 minutes, and sit-to-stand time were best explained by 1,25(OH)₂D and body mass index (P < .05 for all) and 1-legged stand by 1,25(OH)₂D (r = 0.40, P < .05) only. There were no associations of age, estimated glomerular filtration rate (eGFR), intact parathyroid hormone (iPTH), or albumin with any PF measures. MCSA was associated with eGFR (r = 0.54, P < .01) only. Variance in MCSA was best explained by a model containing 1,25(OH)₂D, plasma Ca²⁺, and daily physical activity (by accelerometry) (P < .05 for all). Once these variables were in the model, there was no contribution of eGFR.. These results suggest that 1,25(OH)₂D is a determinant of PF and muscle size in patients with stage 3 and 4 CKD.

Topics: Adult; Aged; Aged, 80 and over; Anatomy, Cross-Sectional; Calcium; Double-Blind Method; Female; Humans; Kidney Failure, Chronic; Magnetic Resonance Imaging; Male; Middle Aged; Motor Activity; Multivariate Analysis; Muscle, Skeletal; Parathyroid Hormone; Regression Analysis; Serum Albumin; Vitamin D; Vitamin D Deficiency

Fibroblast growth factor 23 is a phosphate- and vitamin D-regulating hormone. The objective of this study was to determine the effect of ergocalciferol administration on fibroblast growth factor 23 levels in healthy vitamin D-deficient subjects.. In this 12-week trial conducted in a clinical research center, 18- to 45-year-old subjects (n=90) with 25-hydroxyvitamin D levels ≤20 ng/ml (by chemiluminescent immunoassay) were randomized to weekly ergocalciferol treatment of 50,000 international units or placebo, while consuming a self-selected diet. Changes in fibroblast growth factor 23, 25-hydroxyvitamin D (by liquid chromatography/tandem mass spectroscopy), 1,25-dihydroxyvitamin D, parathyroid hormone, and serum phosphate were measured.. Mean 25-hydroxyvitamin D (P<0.0001), 1,25-dihydroxyvitamin D (P=0.01), and fibroblast growth factor 23 (P=0.003) increased in the treatment versus placebo group. In the treatment group, 25-hydroxyvitamin D increased from 18 ± 7 to 40 ± 12 ng/ml at week 4 (P<0.0001) and remained stable at 43 ± 12 ng/ml at week 12 (P<0.0001); 1,25-dihydroxyvitamin D increased from 42 ± 17 to 52 ± 18 pg/ml at week 4 (P<0.001) and then remained stable, and fibroblast growth factor 23 increased from 43 ± 17 to 60 ± 33 pg/ml at week 8 (P=0.001) and 74 ± 42 pg/ml at week 12 (P<0.0001). Urinary phosphate excretion increased within the treatment group, but parathyroid hormone and serum phosphate were unchanged.. Ergocalciferol administration increases circulating fibroblast growth factor 23. When measuring fibroblast growth factor 23, concurrent 25-hydroxyvitamin D measurements should be obtained, because vitamin D deficiency may lower circulating fibroblast growth factor 23 levels.

Topics: Adult; Biomarkers; Boston; Chi-Square Distribution; Chromatography, Liquid; Dietary Supplements; Ergocalciferols; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Immunoassay; Linear Models; Male; Multivariate Analysis; Parathyroid Hormone; Phosphates; Tandem Mass Spectrometry; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Effects of vitamin D repletion in young people with low vitamin D status have not been investigated so far.. We evaluated the effect of a single massive dose of cholecalciferol on calcium metabolism at 3, 15, and 30 d, compared to baseline.. We conducted a prospective intervention study in an ambulatory care setting.. Forty-eight young subjects with vitamin D deficiency participated in the study.. A single oral dose of 600,000 IU of cholecalciferol was administered to each subject.. We evaluated serum changes of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, calcium, and PTH induced by a single load of cholecalciferol.. The 25(OH)D level was 15.8 ± 6.5 ng/ml at baseline and became 77.2 ± 30.5 ng/ml at 3 d (P < 0.001) and 62.4 ± 26.1 ng/ml at 30 d (P < 0.001). PTH levels concomitantly decreased from 53.0 ± 20.1 to 38.6 ± 17.2 pg/ml at 3 d and to 43.4 ± 14.0 pg/ml at 30 d (P < 0.001 for both). The trends were maintained in a subgroup followed up to 90 d (P < 0.001). Mean serum Ca and P significantly increased compared to baseline, whereas serum Mg decreased at 3 d. 1,25-Dihydroxyvitamin D significantly increased from 46.8 ± 18.9 to 97.8 ± 38.3 pg/ml at 3 d (P < 0.001) and to 59.5 ± 27.3 pg/ml at 60 d (P < 0.05).. A single oral dose of 600,000 IU of cholecalciferol rapidly enhances 25(OH)D and reduces PTH in young people with vitamin D deficiency.

Topics: Administration, Oral; Adult; Calcium; Cholecalciferol; Dose-Response Relationship, Drug; Female; Hormones; Humans; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Vitamin D; Vitamin D Deficiency; Young Adult

Children suffering severe burns develop progressive vitamin D deficiency because of inability of burned skin to produce normal quantities of vitamin D(3) and lack of vitamin D supplementation on discharge. Our study was designed to determine whether a daily supplement of a standard multivitamin tablet containing vitamin D(2) 400 IU (10 microg) for 6 months would raise serum levels of 25-hydroxyvitamin D [25(OH)D] to normal. We recruited eight burned children, ages 5-18, whose families were deemed reliable by the research staff. These children were given a daily multivitamin tablet in the hospital for 3 months in the presence of a member of the research staff and then given the remainder at home. At 6 months, the subjects returned for measurements of serum levels of 25(OH)D,1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact parathyroid hormone (iPTH), Ca, P, albumin, and total protein as well as bone mass by dual energy X-ray absorptiometry. Serum 25(OH)D levels were compared to a group of seven age-matched burned children studied at an earlier date without the vitamin supplement but with the same method of determination of 25(OH)D at 6 months post-burn. In addition, the chewable vitamins were analyzed for vitamin D(2) content by high performance liquid chromatography. Serum concentration of 25(OH)D was 21 +/- 11(SD) ng/ml (sufficient range 30-100) with only one of the eight children having a value in the sufficient range. In comparison, the unsupplemented burn patients had mean serum 25(OH)D level of 16 +/- 7, P = 0.33 versus supplemented. Serum levels of 1,25(OH)(2)D, iPTH, Ca, P, albumin, and total protein were all normal in the supplemented group. Vitamin D(2) content of the chewable tablets after being saponified and extracted was 460 +/- 20 IU. Bone mineral content of the total body and lumbar spine, as well as lumbar spine bone density, failed to increase as expected in the supplemented group. No correlations were found between serum 25(OH)D levels and age, length of stay, percent body surface area burn or third-degree burn. Supplementation of burned children with a standard multivitamin tablet stated to contain 400 IU of vitamin D(2) failed to correct the vitamin D insufficiency.

Topics: Adolescent; Blood Proteins; Bone Density; Burns; Calcium; Child; Child, Preschool; Dietary Supplements; Ergocalciferols; Female; Humans; Lumbar Vertebrae; Male; Parathyroid Hormone; Phosphates; Serum Albumin; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

The authors' previous investigations have disclosed low serum 25-hydroxyvitamin D (25-OHD) concentrations in 45 patients during long-term hospitalization following stroke (mean 5.9 ng/mL). This 25-OHD deficiency resulted from sunlight deprivation.. To evaluate the efficacy of sunlight exposure in increasing serum 25-OHD, in reducing the severity of osteoporosis in bone mineral density (BMD), and in decreasing the risk of hip fractures in chronically hospitalized, disabled stroke patients.. In a 12-month randomized and prospective study of stroke patients, 129 received regular sunlight exposure for 12 months, and the remaining 129 (sunlight-deprived) did not.. At baseline, patients of both groups showed vitamin D deficiency. BMD increased by 3.1% in the sunlight-exposed group and decreased by 3.3% in the sunlight-deprived group (p = 0.0001). 25-OHD level increased by fourfold in the sunlight-exposed group. Six patients sustained hip fractures on the hemiplegic side in the sunlight-deprived group, and one hip fracture occurred among the sunlight-exposed group (p = 0421; odds ratio = 6.1).. Sunlight exposure can increase the BMD of vitamin D-deficient bone by increasing 25-OHD concentration.

Topics: Aged; Bone Density; Calcium; Female; Fractures, Bone; Heliotherapy; Humans; Male; Osteoporosis; Parathyroid Hormone; Prospective Studies; Stroke; Vitamin D; Vitamin D Deficiency

Topics: Calcifediol; Celiac Disease; Child; Child, Preschool; Female; Humans; Male; Vitamin D; Vitamin D Deficiency

Sarcopenia increases with age, and an underlying mechanism needs to be determined to help with designing more effective treatments. This study aimed to determine whether 1,25(OH)

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Aging; Animals; Cellular Senescence; GATA4 Transcription Factor; Mice; NF-kappa B; Polycomb Repressive Complex 1; Sarcopenia; Transcription Factor RelA; Vitamin D Deficiency

Emerging observational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, the relationship between vitamin D level and OA and the role of vitamin D supplementation in the prevention of knee OA are controversial. To address these issues, we analyzed the articular cartilage phenotype of 6- and 12-month-old wild-type and 1α(OH)ase

Topics: Aging; Animals; Cartilage, Articular; Chondrocytes; Down-Regulation; Mice; Osteoarthritis, Knee; Sirtuin 1; Vitamin D; Vitamin D Deficiency

A growing body of scientific works investigating the physio-pathological mechanisms behind cardiovascular disease has suggested that vitamin D deficiency could play a key role on its development. However, it remains unclear whether its active form (1,25-dihydroxyvitamin D [1,25(OH). A total of 73 adults (~53% women; 54 ± 5 years old) were included in the current cross-sectional study. A sex-specific cardiometabolic risk score (MetScore) was calculated for each subject based on clinical parameters (i.e., waist circumference, systolic and diastolic blood pressure, plasma glucose, high-density lipoprotein cholesterol, and triglycerides) according to the International Diabetes Federation's clinical criteria. Plasma levels of 1,25(OH). No significant association was detected between 1,25(OH). In summary, the present results suggest that 1,25(OH)

Topics: Adult; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Risk Factors; Vitamin D; Vitamin D Deficiency; Waist Circumference

Vitamin D deficiency is a pandemic disorder affecting over 1 billion of subjects worldwide. Calcitriol (1,25(OH)2D) represents the perpetrator of the several systemic effects of vitamin D, including the anti-inflammatory, antithrombotic and anti-atherosclerotic actions, potentially preventing acute cardiovascular ischemic events. Variability in the transformation of vitamin D into 1,25(OH)2D has been suggested to modulate its cardioprotective benefits, however, the determinants of the levels of calcitriol and their impact on the cardiovascular risk have been seldom addressed and were, therefore, the aim of the present study.. A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included. The levels of 25 and 1,25(OH)2 D were assessed at admission by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc) and LIAISON® XL. Hypovitaminosis D was defined as 25(OH)D < 10 ng/ml, whereas calcitriol deficiency as 1,25(OH)2D < 19.9 pg/ml. We included in our study 228 patients, divided according to median values of 1,25(OH)2D (

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Biomarkers; Coronary Angiography; Female; Heart Disease Risk Factors; Humans; Immunoassay; Inflammation Mediators; Italy; Male; Middle Aged; Prevalence; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is associated with poor cancer outcome in humans, and administration of vitamin D or its analogs decreases tumor progression and metastasis in animal models. Using the mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) model of mammary cancer, we previously demonstrated a significant acceleration of carcinogenesis in animals on a low vitamin D diet and a reduction in spontaneous lung metastases when mice received vitamin D through perfusion. We investigate here the action mechanism for vitamin D in lung metastasis in the same non-immunodeficient model and demonstrate that it involves the control of epithelial to mesenchymal transition as well as interactions between chemokine C-X-C motif chemokine 12 (CXCL12) and its receptor C-X-C chemokine receptor type 4 (CXCR4). In vitro, 10-9M vitamin D treatment modifies the phenotype of MMTV-PyMT primary mammary tumor cells and significantly decreases their invasiveness and mammosphere formation capacity by 40% and 50%, respectively. Vitamin D treatment also inhibits phospho-signal transducer and activator of transcription 3 (p-STAT3), zinc finger E-box-binding homeobox 1 (Zeb1), and vimentin by 52%, 75%, and 77%, respectively, and increases E-cadherin by 87%. In vivo, dietary vitamin D deficiency maintains high levels of Zeb1 and p-STAT3 in cells from primary mammary tumors and increases CXCL12 expression in lung stroma by 64%. In lung metastases, vitamin D deficiency increases CXCL12/CXCR4 co-localization by a factor of 2.5. These findings indicate an involvement of vitamin D in mammary cancer "seed" (primary tumor cell) and "soil" (metastatic site) and link vitamin D deficiency to epithelial-to-mesenchymal transition (EMT), CXCL12/CXCR4 signaling, and accelerated metastasis, suggesting vitamin D repleteness in breast cancer patients could enhance the efficacy of co-administered therapies in preventing spread to distant organs.

Topics: Animals; Cell Line, Tumor; Chemokine CXCL12; Epithelial-Mesenchymal Transition; Female; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Neoplasm Invasiveness; Receptors, CXCR4; Signal Transduction; Vitamin D; Vitamin D Deficiency

Topics: Causality; COVID-19; Humans; Risk Factors; SARS-CoV-2; Vitamin D; Vitamin D Deficiency; Vitamins

Vitamin D has a crucial role in cancer control and prevention. For its activity, VDR (vitamin D receptor) and its heterodimer RXR (Retinoid X receptor) are equally important in the cell. This ligand (vitamin D) and receptors (VDR-RXR) complex together triggers downstream DNA damage response in the cell and thus counters cancer in blood. 137 patients and 60 disease free controls were recruited for this study. The levels of vitamin D in patient and controls were analysed and compared using ELISA. The mRNA expression of the two receptor genes; VDR and RXR was also assessed by RT-PCR, to see their role in haematological malignancies. Their expression levels were corelated with the vitamin D levels in individuals to understand their mutual contribution in blood cancer prevention. The results confirmed a highly significant correlation between vitamin D levels of patients and controls (p < 0.001). The study also revealed that age of patients is a critical factor in determining the relative risk of blood cancer (p < 0.001), its types (leukaemia and lymphoma) and subtypes. Also, the mRNA expression of VDR showed a positive and non-significant relationship with vitamin D levels and RXR expression (p > 0.05). Based on our findings, and studies on other diseases it can be inferred that Vitamin D deficiency and dysregulation of its associated receptors may lead to cancer initiation and/or progression by failing to trigger the cellular DNA damage repair machinery.

Topics: Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; DNA Damage; DNA Repair; Female; Gene Expression; Humans; Leukemia; Lymphoma; Male; Middle Aged; Receptors, Calcitriol; Retinoid X Receptors; RNA, Messenger; Vitamin D; Vitamin D Deficiency; Young Adult

Vitamin D deficiency in pregnancy is reported as a prevalent public health problem.. We aimed to evaluate, in pregnant Canadian women, 1) vitamin D intake, 2) maternal and cord serum 25-hydroxycholecalciferol [25(OH)D] and maternal 1,25-dihydroxycholecalciferol [1,25(OH)2D], and 3) factors associated with maternal serum 25(OH)D.. Women (n = 187; mean prepregnancy BMI 24.4 kg/m2, mean age 31 y) recruited to the Be Healthy in Pregnancy study provided fasting blood samples and nutrient intake at 12-17 (early) and 36-38 (late) weeks of gestation, and cord blood. Vitamin D intakes (Nutritionist Pro™) and serum 25(OH)D and 1,25(OH)2D concentrations (LC-tandem MS) were measured.. Vitamin D intake was comparable in early and late pregnancy [median (IQR) = 586 (459, 859) compared with 689 (544, 974) IU/d; P = 0.83], with 71% consumed as supplements. Serum 25(OH)D was significantly higher in late pregnancy (mean ± SD: 103.1 ± 29.3 nmol/L) than in early pregnancy (82.5 ± 22.5 nmol/L; P < 0.001) and no vitamin D deficiency (<30 nmol/L) occurred. Serum 1,25(OH)2D concentrations were significantly higher in late pregnancy (101.1 ± 26.9 pmol/L) than in early pregnancy (82.2 ± 19.2 pmol/L, P < 0.001, n = 84). Cord serum 25(OH)D concentrations averaged 55% of maternal concentrations. In adjusted multivariate analyses, maternal vitamin D status in early pregnancy was positively associated with summer season (est.β: 13.07; 95% CI: 5.46, 20.69; P < 0.001) and supplement intake (est.β: 0.01; 95% CI: 0.00, 0.01; P < 0.001); and in late pregnancy with summer season (est.β: 24.4; 95% CI: 15.6, 33.2; P < 0.001), nonmilk dairy intake (est.β: 0.17; 95% CI: 0.02, 0.32; P = 0.029), and supplement intake (est.β: 0.01; 95% CI: 0.00, 0.01; P = 0.04).. Summer season and recommended vitamin D intakes supported adequate vitamin D status throughout pregnancy and in cord blood at >50 nmol/L in healthy Canadian pregnant women. This trial was registered at clinicaltrials.gov as NCT01693510.

Topics: Adult; Canada; Dairy Products; Diet; Dietary Supplements; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Maternal Nutritional Physiological Phenomena; Nutritional Status; Pregnancy; Pregnancy Complications; Seasons; Vitamin D; Vitamin D Deficiency

Obesity has been regarded to be protective against fracture in spite of its association with low levels of vitamin D. Vitamin D is the key regulator of bone metabolism and its deficiency contributes to higher level of parathyroid hormone (PTH), leading to the activation of bone turnover.. We studied 161 subjects of which 65 were young healthy subjects and 96 were elderly subjects. We measured creatinine, 25(OH)D, 1,25(OH)2D, PTH, albumin, and calcium plasma levels, we evaluated physical activity, and we calculated BMI. A sub-cohort of elderly subjects also underwent DXA scans.. Overweight and obese subjects, as well as underweight ones, had lower levels of vitamin D but normal serum concentrations of 1,25(OH)2D and PTH was higher in underweight and obese subjects. Moreover, we found a nonlinear relationship between body mass index (BMI) and PTH with a significant U-shaped exponential regression. Regardless of BMI, 25(OH)D mean levels were higher in subjects who practice physical activity.. These findings suggest that physical activity and BMI had a significant effect on the metabolism of bone and vitamin D, but the effect of BMI was different in underweight, normal weight or obese subjects. In obesity the real vitamin D deficiency could be estimate by serum 1,25(OH)2D concentrations whose lower levels contribute to the higher PTH production and consequently to bone loss and to a greater fracture risk.

Topics: Adiposity; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Bone Density; Exercise; Female; Humans; Male; Middle Aged; Obesity; Osteoporotic Fractures; Prevalence; Retrospective Studies; Risk Assessment; Risk Factors; Rome; Vitamin D; Vitamin D Deficiency

The association between low vitamin D status and the development of type 2 diabetes mellitus is well established; however, intervention trials that increased serum vitamin D (through ultraviolet B exposure or dietary supplementation) provide mixed outcomes. Recent evidence suggests that metabolites directly related to vitamin D receptor activation-1α,25-dihydroxyvitamin D

Topics: Adult; Aged; Asian People; Calcifediol; Diabetes Mellitus, Type 2; Female; Glucose; Homeostasis; Humans; Insulin Resistance; Insulin Secretion; Intra-Abdominal Fat; Male; Middle Aged; Oxygen; Oxygen Consumption; Triglycerides; Vitamin D; Vitamin D Deficiency

Vitamin A and D deficiency is prevalent in pregnant women worldwide. Both vitamins are involved in fetal skeletal development. A positive association between maternal vitamin D levels and offspring bone mineral density (BMD) at adulthood has been observed. The impact of maternal vitamin A status in pregnancy on offspring peak bone mass remains unclear.. Forty-one mother-child pairs were recruited from a population-based prospective cohort study in Trondheim, Norway, where pregnant women were followed from gestational week 17. Their term-born infants were followed from birth (1986-88). Regression analyses were performed for vitamin A (retinol), 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in maternal serum (gestational weeks 17, 33, 37) and cord blood. Offspring BMD and spine trabecular bone score (TBS), a measure of bone quality, were analyzed by dual x-ray absorptiometry at 26 years. Average levels during pregnancy of retinol, 25(OH)D and 1,25(OH)2D were 1.66 (0.32) μmol/L, 59.0 (20.6) nmol/L, and 251.3 (62.4) pmol/L, respectively. 1,25(OH)2D levels were similar in those with 25(OH)D levels <30 and >75 nmol/L. After adjustment for maternal age, BMI, smoking, and education, and offspring birth weight, maternal serum retinol was positively associated with offspring spine BMD [mean change 30.8 (CI 7.6, 54.0) mg/cm2 per 0.2 μmol/L retinol], and with offspring TBS, although non-significant (p = 0.08). No associations were found between maternal 25(OH)D and 1,25(OH)2D levels and offspring bone parameters. Vitamin levels in cord blood were not associated with offspring BMD or TBS.. This is the first study to show an association between maternal vitamin A status and offspring peak bone mass. Our findings may imply increase future risk for osteoporotic fracture in offspring of mothers with suboptimal vitamin A level. No associations were observed between 25(OH)D and 1,25(OH)2D and offspring BMD.

Topics: Absorptiometry, Photon; Adult; Bone Density; Female; Follow-Up Studies; Humans; Male; Norway; Osteoporotic Fractures; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prospective Studies; Risk Assessment; Risk Factors; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH). We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH). We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH). Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)

Topics: Animals; Case-Control Studies; Disease Models, Animal; Down-Regulation; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Insulin-Like Growth Factor I; Kidney; Kidney Function Tests; Male; Mice; Mice, Inbred C57BL; Parathyroid Hormone; Sepsis; Signal Transduction; Vitamin D; Vitamin D Deficiency

Opinions are conflicting about the epidemiology of vitamin D deficiency. This population-based study investigated cross-sectionally the associations of 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol) with indices of mineral homeostasis. Study cohort consisted of 979 persons of the Moli-Sani study, both sexes, ages ≥35 years. Data collection included serum calcidiol by different assays, serum calcitriol, serum parathyroid hormone, serum and urine calcium, and phosphorus. Prevalence of mild-to-moderate calcidiol deficiency (10-19 ng/mL) was 36.4% and did not associate with hypocalcemia or hyperparathyroidism. Prevalence of severe calcidiol deficiency (<10 ng/mL) was 16.8% and associated with hyperparathyroidism only (odds ratio = 8.81, 95% confidence interval = 2.4/32.9). Prevalence of calcitriol deficiency (<18 pg/mL) was 3.1% and associated with hypocalcemia (29.1, 7.4/114.5) but not hyperparathyroidism. In ANOVA along concentration strata, lower calcidiol associated with higher parathyroid hormone only (

Topics: Adult; Aged; Biomarkers; Calcium; Cross-Sectional Studies; Female; Homeostasis; Humans; Hyperparathyroidism; Hypocalcemia; Italy; Male; Middle Aged; Parathyroid Hormone; Prevalence; Prospective Studies; Severity of Illness Index; Vitamin D; Vitamin D Deficiency

The commonest cause of rickets worldwide is vitamin D deficiency, but studies from sub-Saharan Africa describe an endemic vitamin D-independent form that responds to dietary calcium enrichment. The extent to which calcium-deficiency rickets is the dominant form across sub-Saharan Africa and in other low-latitude areas is unknown. We aimed to characterise the clinical and biochemical features of young children with rickets in a densely populated urban informal settlement in Kenya. Because malnutrition may mask the clinical features of rickets, we also looked for biochemical indices of risk in children with varying degrees of acute malnutrition. Twenty one children with rickets, aged 3 to 24 months, were identified on the basis of clinical and radiologic features, along with 22 community controls, and 41 children with either severe or moderate acute malnutrition. Most children with rickets had wrist widening (100%) and rachitic rosary (90%), as opposed to lower limb features (19%). Developmental delay (52%), acute malnutrition (71%), and stunting (62%) were common. Compared to controls, there were no differences in calcium intake, but most (71%) had serum 25-hydroxyvitamin D levels below 30 nmol/L. These results suggest that rickets in young children in urban Kenya is usually driven by vitamin D deficiency, and vitamin D supplementation is likely to be required for full recovery. Wasting was associated with lower calcium (p = .001), phosphate (p < .001), 25-hydroxyvitamin D (p = .049), and 1,25-dihydroxyvitamin D (p = 0.022) levels, the clinical significance of which remain unclear.

Topics: Calcium; Calcium, Dietary; Child, Preschool; Dietary Supplements; Female; Humans; Infant; Kenya; Male; Malnutrition; Phosphates; Rickets; Urban Population; Vitamin D; Vitamin D Deficiency; Wasting Syndrome

Topics: Drug Information Services; Guidelines as Topic; Humans; Unnecessary Procedures; Vitamin D; Vitamin D Deficiency

Recent studies have shown a relationship between vitamin D status and growth hormone (GH) and insulin-like growth factor 1 (IGF1). The objective of this study was to assess vitamin D status in children with GH deficiency due to pituitary stalk interruption syndrome (PSIS) and to investigate the relationship between 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25 (OH). A retrospective single-center study of 25OHD and 1,25(OH)

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Female; Human Growth Hormone; Humans; Hypopituitarism; Infant; Male; Retrospective Studies; Syndrome; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency (low plasma 25-hydroxyvitamin D [25D] concentration) is often reported in tuberculosis. Adjunctive vitamin D has been tested for its potential to improve treatment outcomes, but has proven largely ineffective. To better understand vitamin D in tuberculosis, we investigated determinants of 25D and its immunologically active form, 1,25-dihydroxyvitamin D (1,25D), their inter-relationship in tuberculosis, longitudinal changes and association with outcome.. In a prospective observational study of adults with smear-positive pulmonary tuberculosis in Sabah, Malaysia, we measured serial 25D, 1,25D, vitamin D-binding protein (VDBP), albumin, calcium, parathyroid hormone, chest x-ray, week 8 sputum smear/culture and end-of-treatment outcome. Healthy control subjects were enrolled for comparison.. 1,25D was elevated in 172 adults with tuberculosis (mean 229.0 pmol/L, 95% confidence interval: 215.4 - 242.6) compared with 95 controls (153.9, 138.4-169.4, p < 0.001), directly proportional to radiological severity (p < 0.001), and fell rapidly within one week of treatment commencement. Tuberculosis patients with higher baseline 1,25D achieved significantly higher percentage weight gain over time, including when controlling for baseline weight, however persistently elevated 1,25D was associated with worse residual x-ray changes and lower end-of-treatment BMI. 1,25D was inversely associated with PTH (p < 0.001), consistent with the extra-renal origin of the 1,25D. 25D did not differ between tuberculosis patients (mean 63.9 nmol/L, 95% CI: 60.6 - 67.3) and controls (61.3, 57.2- 65.3, p = 0.24), and was unassociated with outcomes. Among tuberculosis patients in multivariable analyses, sex, age and VDBP were associated with 25D, and age and albumin with 1,25D. 1,25-dihydroxyvitamin was not significantly asscociated with 25D. Vitamin D deficiency <25 nmol/L was uncommon, occurring in only five TB patients; 1,25D was elevated in three of them.. In an equatorial setting, high extra-renal production of 1,25D was seen in tuberculosis, including in individuals with 25D in the deficient range; however, severe 25D deficiency was uncommon. Baseline elevation of 1,25D, a marker of macrophage activation, was associated with better weight gain but persistent elevation of 1,25D was associated with worse radiological and BMI outcomes. 1,25D warrants testing in larger datasets including TB patients less responsive to treatment, such as multi-drug resistant TB, to test its utility as a marker of tuberculosis severity and treatment response.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Female; Humans; Malaysia; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Treatment Outcome; Tuberculosis, Pulmonary; Vitamin D; Vitamin D Deficiency; Young Adult

Our recent studies demonstrated that intestinal epithelial vitamin D receptor (VDR) signaling plays a critical role in regulating colonic inflammation by protecting epithelial barrier integrity. Epithelial VDR is downregulated in colitis, but how mucosal inflammation affects local 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] production is unknown. Here we showed that cytochrome P450 27b1 (Cyp27b1), a cytochrome P450 enzyme necessary for 1,25(OH)2D3 biosynthesis, is highly induced in colonic mucosa in inflammatory response. Although VDR is reduced in colon biopsies from patients with ulcerative colitis, Cyp27b1 is markedly upregulated in these samples. Colon mucosal Cyp27b1 was also markedly induced in an experimental colitis mouse model, and this local Cyp27b1 induction and colonic inflammation required the presence of commensal bacteria. Vitamin D deficiency further exaggerated colonic Cyp27b1 induction and aggravated colonic inflammation in mice. In HCT116 cells, lipopolysaccharide or tumor necrosis factor-α treatment induced Cyp27b1 in time- and dose-dependent manners, and the induced Cyp27b1 was enzymatically active. The inflammation-induced upregulation of Cyp27b1 was mediated by nuclear factor κB. Collectively these data suggest that induction of colonic epithelial Cyp27b1, which is expected to increase local production of 1,25(OH)2D3, is a protective mechanism that partially compensates for the downregulation of epithelial VDR during colonic inflammation. Increased local 1,25(OH)2D3 maintains 1,25(OH)2D3-VDR signaling to protect the mucosal barrier and reduce colonic inflammation.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; Colitis; Colon; Enzyme Induction; HCT116 Cells; Humans; Inflammation; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Microbiota; Receptors, Calcitriol; Signal Transduction; Vitamin D; Vitamin D Deficiency

We examined whether measures of vitamin D were associated with transitioning to systemic lupus erythematosus (SLE) in individuals at risk for SLE.. 436 individuals who reported having a relative with SLE but who did not have SLE themselves were evaluated at baseline and again an average of 6.3 (±3.9) years later. Fifty-six individuals transitioned to SLE (≥4 cumulative American College of Rheumatology criteria). 25-Hydroxyvitamin D (25[OH]D) levels were measured by ELISA. Six single-nucleotide polymorphisms in four vitamin D genes were genotyped. Generalised estimating equations, adjusting for correlation within families, were used to test associations between the vitamin D variables and the outcome of transitioning to SLE.. Mean baseline 25[OH]D levels (p=0.42) and vitamin D supplementation (p=0.65) were not different between those who did and did not transition to SLE. Vitamin D deficiency (25[OH]D <20 ng/mL) was greater in those who transitioned compared with those who did not transition to SLE (46% vs 33%, p=0.05). The association between 25[OH]D and SLE was modified by CYP24A1 rs4809959, where for each additional minor allele increased 25[OH]D was associated with decreased SLE risk: zero minor alleles (adjusted OR: 1.03, CI 0.98 to 1.09), one minor allele (adjusted OR: 1.01, CI 0.97 to 1.05) and two minor alleles (adjusted OR: 0.91, CI 0.84 to 0.98). Similarly, vitamin D deficiency significantly increased the risk of transitioning to SLE in those with two minor alleles at rs4809959 (adjusted OR: 4.90, CI 1.33 to 18.04).. Vitamin D status and CYP24A1 may have a combined role in the transition to SLE in individuals at increased genetic risk for SLE.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adult; Aged; Alleles; Female; Genetic Predisposition to Disease; Humans; Longitudinal Studies; Lupus Erythematosus, Systemic; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Risk Factors; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamin D3 24-Hydroxylase

This study examined the characteristics of biochemical parameters, bone diseases, and vascular calcification in Korean patients with chronic kidney disease (CKD) not yet on dialysis. Serum levels of fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D3 (25D), and 1,25-dihydroxyvitamin D3 (1,25D); lumbar spine, total hip, and femur neck bone mineral densities; and brachial-to-ankle pulse wave velocity (baPWV) representing vascular calcification were measured at baseline for 2,238 CKD patients in the KoreaN Cohort Study for Outcomes in Patients With CKD (KNOW-CKD). Increases in serum FGF23 and iPTH preceded changes in serum calcium and phosphate, similar to Western populations. However, the 25D and 1,25D levels decreased earlier than serum FGF23 or iPTH increased, with a decreased estimated glomerular filtration rate (eGFR) in Korean CKD patients. Vitamin D deficiency occurred in 76.7% of patients with CKD stage 1. Bone mineral densities were lowest in CKD stage 5 (lumbar spine, -0.64 ± 1.67; total hip, -0.49 ± 1.21; femur neck, -1.02 ± 1.25). Osteoporosis was more prevalent in patients with higher CKD stages. The mean baPWV, abdominal aortic calcification (AAC), and coronary calcium score also increased, with declined eGFR. In conclusion, a decline in serum vitamin D levels was observed in early CKD stages before significant increases of FGF23 and iPTH in the Korean CKD population compared with that in Western populations. Increased bone disease and vascular calcification occurred in early-stage CKD.

Topics: Adult; Aged; Asian People; Bone Density; Bone Diseases; Calcitriol; Calcium; Cohort Studies; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Humans; Male; Middle Aged; Parathyroid Hormone; Phosphates; Pulse Wave Analysis; Renal Insufficiency, Chronic; Republic of Korea; Severity of Illness Index; Vitamin D; Vitamin D Deficiency

The best repletion and maintenance dosing regimens with cholecalciferol in vitamin D-deficient HIV-1 patients remain unknown. Protease inhibitors (PIs) have been shown to inhibit vitamin D 1α- and 25α-hydroxylation in hepatocyte and monocyte cultures. We therefore evaluated the effect of a single high dose of cholecalciferol in vitamin D-deficient HIV-1 postmenopausal women undergoing treatment with highly active anti-retroviral therapy (cART), with and without PIs. Forty HIV-1 postmenopausal women treated with cART, with hypovitaminosis D (<20 ng/ml), were enrolled. We measured serum changes of 25-hydroxyvitamin D [25(OH)D]; 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone (PTH), serum calcium, and urinary calcium excretion following a loading dose of 600,000 IU of cholecalciferol after 3, 30, 60, 90, and 120 days. Patients were divided into two groups, whether or not they were taking PI. A significant increase in mean 25(OH)D and 1,25(OH)2D levels at day 3 and throughout the entire observation period was found in both groups (p < 0.001). PTH levels concomitantly decreased in both groups (p < 0.001). Mean albumin-adjusted serum calcium increases with respect to baseline were significant only at day 3 and day 30 for both groups (p < 0.01). Considering remaining parameters, there were no significant differences between the groups at any time, by two-way RM ANOVA. An oral dose of 600,000 IU of cholecalciferol in HIV-1 postmenopausal women rapidly increases 25(OH)D and 1,25(OH)2D levels reducing PTH levels, regardless of the presence of PIs in the cART scheme.

Topics: Cholecalciferol; Female; HIV Infections; Humans; Parathyroid Hormone; Pilot Projects; Postmenopause; Protease Inhibitors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Blood levels of 25-hydroxyvitamin D [25(OH) D] are reduced in patients with nephrotic syndrome (NS). The lowering is thought to be due to urinary loss of vitamin D binding protein (DBP). A link between vitamin D deficiency and bone disease or markers of mineral metabolism has not yet been shown in NS. We hypothesized that alterations in bioavailable vitamin D levels might be linked to these abnormalities in NS.. We measured circulating levels of 25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)2 D], DBP, serum albumin and intact parathyroid hormone (iPTH) in 106 adults with sporadic idiopathic NS and 40 healthy controls. Bioavailable vitamin D was calculated from previously validated formulae. Bone mineral density (BMD) was measured at left hip (neck of femur) by DEXA.. Compared to healthy controls, total and bioavailable 25(OH)D levels were significantly reduced in patients with NS as compared to healthy controls. Among the nephrotic patients, BMD was positively correlated with bioavailable 25(OH)D (r = 0.358; P = 0.0002) but not with total 25(OH)D (r = 0.174; P = 0.079). Total 1,25(OH)2 D and bioavailable 1,25(OH)2 D did not correlate with BMD (r = 0.131; P =  0.206 and r = 0.107, P = 0.295). Bioavailable 25(OH)D levels showed a strong inverse correlation with iPTH on univariate (r = -0.457; P < 0.0001) and multivariate (β=-0.453, P < 0.0001) analyses.. We conclude that bioavailable 25(OH)D is a better measure of vitamin D status with respect of BMD and mineral metabolism in patients of nephrotic syndrome.

Topics: Absorptiometry, Photon; Adolescent; Adult; Aged; Biomarkers; Bone Density; Bone Remodeling; Case-Control Studies; Cross-Sectional Studies; Down-Regulation; Female; Femur Neck; Humans; Male; Middle Aged; Multivariate Analysis; Nephrotic Syndrome; Parathyroid Hormone; Predictive Value of Tests; Serum Albumin; Serum Albumin, Human; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Young Adult

Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20-100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation.. Multicenter longitudinal study of children (2-18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later.. Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D < 20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D < 20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p < 0.01) in children supplemented with vitamin D.. In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2-4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Dietary Supplements; Female; Humans; Incidence; Linear Models; Logistic Models; Longitudinal Studies; Male; Midwestern United States; Multivariate Analysis; Nephrotic Syndrome; Odds Ratio; Parathyroid Hormone; Prospective Studies; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

To determine the interrelationships between body composition, glycemic control and vitamin D status in an ambulatory population with diabetes (DM) and chronic kidney disease (CKD).. Adult (18-80 years) patients (n=60) with DM and stage 1-4 CKD were recruited from the Northern Alberta Renal Program. Outcome variables included body composition (absolute/regional fat (FM)/lean soft tissue/total mass, percent fat/lean/fat-free (FFM) mass), glycemic control (glycated hemoglobin (HbA1c)), vitamin D intake (dietary/supplemental) and vitamin D status (25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D)) measured by validated methodologies. Sarcopenia was determined as an appendicular skeletal mass/height(2) less than 7.26 kg/m(2) (males) and 5.45 kg/m(2) (females).. Suboptimal HbA1c (>7%), 25(OH)D (<50 nmol/l) and 1,25(OH)2D (<43 pmol/l) concentrations were present in 57, 8 and 11% of participants. Ten percent of subjects had sarcopenia. Gender/age/DM type, not CKD, significantly influenced regional/whole body composition. Females, older participants and those with type 2 DM had higher %FM. No significant interrelationships between vitamin D status and glycemic control were observed (P>0.05). Serum 25(OH)D concentrations were inversely associated with arm lean soft tissue/FFM/total mass, weight, appendicular skeletal mass, lean soft tissue/height(2), FFM/height(2), appendicular skeletal mass/height(2) and body mass index (P<0.05). Sarcopenia occurred more frequently in patients with 25(OH)D concentrations ⩾100 nmol/l. Regional/whole body %FM was inversely related to 1,25(OH)2D, not 25(OH)D.. Body composition, not glycemic control, is associated with vitamin D status in an ambulatory population of adults with DM and CKD.

Topics: Adult; Aged; Alberta; Blood Glucose; Body Composition; Body Mass Index; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Sarcopenia; Vitamin D; Vitamin D Deficiency

Topics: Blood Chemical Analysis; Humans; Mass Screening; Medical Overuse; Military Medicine; United States; Vitamin D; Vitamin D Deficiency

In chronic kidney disease (CKD) a deficiency of 1,25-dihydroxyvitamin D is common. The aim of this review was to compare vitamin D status after oral supplementation of vitamin D3 to that of serial suberythemal irradiation in end-stage kidney disease (ESKD) patients.. Ninety-five patients, with a mean age of 62 (range=35-82) years, were treated with a mean dose of 35,000 (20,000-60,000) IU vitamin D3 per week for a period of 18 months. Fourteen patients, with a mean age of 51 (range=41-57) years, were whole-body UVB irradiated for over 6 months. From 3 hemodialysis patients skin biopsies were performed.. With oral supplementation 25(OH)D3 increased by 60%. With UV irradiation 25(OH)D3 increased by 400%. Gene expression analysis demonstrated an improvement in the vitamin D receptor (VDR) by 0.65 fold, in 1-alpha-hydroxylase (CYP27B1) by 1.0 fold, and in 25-hydroxylase (CYP2R) by 1.2 fold.. Serial suberythemal UVB irradiation of patients with CKD on dialysis is capable to improve serum 25(OH)D3 and 1,25(OH)2D3 by enhancing the skin's ability to activate vitamin D.

Topics: Adult; Aged; Aged, 80 and over; Calcifediol; Calcitriol; Cholecalciferol; Dietary Supplements; Humans; Kidney Failure, Chronic; Male; Middle Aged; Receptors, Calcitriol; Renal Dialysis; Renal Insufficiency, Chronic; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency; Vitamin D3 24-Hydroxylase

The role of vitamin D deficiency in coronary artery disease (CAD) progression is uncertain. Chronic inflammation in epicardial adipose tissue (EAT) has been implicated in the pathogenesis of CAD. However, the molecular mechanism underlying vitamin D deficiency-enhanced inflammation in the EAT of diseased coronary arteries remains unknown. We examined a mechanistic link between 1,25-dihydroxyvitamin D-mediated suppression of nuclear factor-κB (NF-κB) transporter, karyopherin α4 (KPNA4) expression and NF-κB activation in preadipocytes. Furthermore, we determined whether vitamin D deficiency accelerates CAD progression by increasing KPNA4 and nuclear NF-κB levels in EAT.. Nuclear protein levels were detected by immunofluorescence and Western blot. Exogenous KPNA4 was transported into cells by a transfection approach and constituted lentiviral vector. Swine were administered vitamin D-deficient or vitamin D-sufficient hypercholesterolemic diet. After 1 year, the histopathology of coronary arteries and nuclear protein expression of EAT were assessed. 1,25-dihydroxyvitamin D inhibited NF-κB activation and reduced KPNA4 levels through increased vitamin D receptor expression. Exogenous KPNA4 rescued 1,25-dihydroxyvitamin D-dependent suppression of NF-κB nuclear translocation and activation. Vitamin D deficiency caused extensive CAD progression and advanced atherosclerotic plaques, which are linked to increased KPNA4 and nuclear NF-κB levels in the EAT.. 1,25-dihydroxyvitamin D attenuates NF-κB activation by targeting KPNA4. Vitamin D deficiency accelerates CAD progression at least, in part, through enhanced chronic inflammation of EAT by upregulation of KPNA4, which enhances NF-κB activation. These novel findings provide mechanistic evidence that vitamin D supplementation could be beneficial for the prevention and treatment of CAD.

Topics: Active Transport, Cell Nucleus; Adipocytes; Adipose Tissue; alpha Karyopherins; Animals; Cells, Cultured; Coronary Artery Disease; Disease Models, Animal; Disease Progression; Hypercholesterolemia; Receptors, Calcitriol; RNA Interference; Swine; Swine, Miniature; Time Factors; Transcription Factor RelA; Transfection; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is endemic in children with CKD. We sought to investigate the association of genetic disposition, environmental factors, vitamin D supplementation, and renal function on vitamin D status in children with CKD.. Serum 25-hydroxy-vitamin D, 1,25-dihydroxy-vitamin D, and 24,25-dihydroxy-vitamin D concentrations were measured cross-sectionally in 500 children from 12 European countries with CKD stages 3-5. All patients were participants of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study, had CKD stage 3-5, and were age 6-18 years old. Patients were genotyped for single-nucleotide polymorphisms in the genes encoding 25-hydroxylase, vitamin D binding protein, 7-dehydrocholesterol reductase, and 24-hydroxylase. Associations of genetic status, season, local solar radiation, oral vitamin D supplementation, and disease-associated factors with vitamin D status were assessed.. Two thirds of patients were vitamin D deficient (25-hydroxy-vitamin D <16 ng/ml). 25-Hydroxy-vitamin D concentrations varied with season and were twofold higher in vitamin D-supplemented patients (21.6 [14.1] versus 10.4 [10.1] ng/ml; P<0.001). Glomerulopathy, albuminuria, and girls were associated with lower 25-hydroxy-vitamin D levels. 24,25-dihydroxy-vitamin D levels were closely correlated with 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D (r=0.87 and r=0.55; both P<0.001). 24,25-dihydroxy-vitamin D concentrations were higher with higher c-terminal fibroblast growth factor 23 and inversely correlated with intact parathyroid hormone. Whereas 25-hydroxy-vitamin D levels were independent of renal function, 24,25-dihydroxy-vitamin D levels were lower with lower eGFR. Vitamin D deficiency was more prevalent in Turkey than in other European regions independent of supplementation status and disease-related factors. Single-nucleotide polymorphisms in the vitamin D binding protein gene were independently associated with lower 25-hydroxy-vitamin D and higher 24,25-dihydroxy-vitamin D.. Disease-related factors and vitamin D supplementation are the main correlates of vitamin D status in children with CKD. Variants in the vitamin D binding protein showed weak associations with the vitamin D status.

Topics: Adolescent; Albuminuria; Child; Cholestanetriol 26-Monooxygenase; Cross-Sectional Studies; Dietary Supplements; Europe; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Oxidoreductases Acting on CH-CH Group Donors; Parathyroid Hormone; Polymorphism, Single Nucleotide; Seasons; Sex Factors; Sunlight; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamin D3 24-Hydroxylase; Vitamins

Vitamin D has immunomodulatory properties and seems to reduce the risk of infections. Whether low vitamin D concentrations are independent risk factors for nosocomial postoperative infections in surgical patients remains to be studied in detail.. In 3,340 consecutive cardiac surgical patients, we investigated the association of circulating 25-hydroxyvitamin D (25OHD; indicator of nutritional vitamin D status) and 1,25-dihydroxyvitamin D (1,25[OH]2D; active vitamin D hormone) with nosocomicial infections. The primary endpoint was a composite of thoracic wound infection, sepsis, and broncho-pulmonary infection. Vitamin D status was measured on the last preoperative day. Infections were assessed until discharge. Logistic regression analysis was used to examine the association between vitamin D metabolite concentrations and the composite endpoint.. The primary endpoint was reached by 5.6% (n = 186). In patients who reached and did not reach the endpoint, in-hospital mortality was 13.4% and 1.5%, respectively (P<0.001). Median (IQR) 25OHD and 1,25(OH)2D concentrations were 43. 2 (29.7-61.9) nmol/l and 58.0 (38.5-77.5) pmol/l, respectively. Compared with the highest 1,25(OH)2D quintile (>81.0 pmol/l), the multivariable-adjusted odds ratio of infection was 2.57 (95%CI:1.47-4.49) for the lowest 1,25(OH)2D quintile (<31.5 pmol/l) and 1.85 (95%CI:1.05-3.25) for the second lowest quintile (31.5-49.0 pmol/l). There was no significant association between 25OHD concentrations and the primary endpoint.. Our data indicate an independent association of low 1,25(OH)2D levels with the risk of postoperative infections in cardiac surgical patients. Future studies should pay more attention on the clinical relevance of circulating 1,25(OH)2D and its regulation.

Topics: Aged; Anti-Bacterial Agents; Cardiac Surgical Procedures; Critical Care; Cross Infection; Female; Heart Diseases; Heart Transplantation; Hospital Mortality; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Period; Prospective Studies; Regression Analysis; Risk; Vitamin D; Vitamin D Deficiency

CYP27B1 converts 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3, playing a vital role in calcium homeostasis and bone growth. Vitamin D-dependent rickets type 1 (VDDR-1) is a rare autosomal recessive disorder caused by mutations in CYP27B1.. The objective of the study was an enzymatic and structural analysis of mutations in a patient with calcipenic rickets. Design, Setting, Patient, and Intervention: Two siblings presented with calcipenic rickets and normal 1,25-dihydroxyvitamin D3 levels. CYP27B1 gene analysis showed compound heterozygous mutations confirming VDDR-1. We studied wild-type CYP27B1 and mutations H441Y and R459L by computational homology modeling, molecular dynamics simulations, and functional studies using a luciferase assay. The patients were successfully treated with calcitriol.. The main outcomes of the study were novel mutations leading to a severe loss of CYP27B1 activities for metabolism of 25-hydroxyvitamin D3.. Mitochondrial cytochrome P450s require adrenodoxin (FDX1) and adrenodoxin reductase. We created models of CYP27B1-FDX1 complex, which revealed negative effects of mutations H441Y and R459L. Upon structural analysis, near-identical folds, protein contact areas, and orientations of heme/iron-sulfur cluster suggested that both mutations may destabilize the CYP27B1-FDX1 complex by negating directional interactions with adrenodoxin. This system is highly sensitive to small local changes modulating the binding/dissociation of adrenodoxin, and electron-transporting efficiency might change with mutations at the surface. Functional assays confirmed this hypothesis and showed severe loss of activity of CYP27B1 by both mutations.. This is the first report of mutations in CYP27B1 causing VDDR-1 by affecting protein-protein interactions with FDX1 that results in reduced CYP27B1 activities. Detailed characterization of mutations in CYP27B1 is required for understanding the novel molecular mechanisms causing VDDR-1.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adrenodoxin; Amino Acid Sequence; Biomarkers; Familial Hypophosphatemic Rickets; Female; Humans; Infant; Infant, Newborn; Male; Mutation; Prognosis; Sequence Homology, Amino Acid; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency and vitamin D receptor gene polymorphisms are known to be significantly associated with high myopia. Whether this genetic variant may impact primary open-angle glaucoma is largely unknown. This study investigated whether vitamin D receptor gene polymorphisms are altered in primary open-angle glaucoma subjects carrying the risk allele, and whether vitamin D deficiency is an important factor in the development of glaucoma.. Seventy-three POAG patients and 71 age-matched controls from the Han population were enrolled. Serum levels of 1a, 25-Dihydroxyvitamin D3 were measured by enzyme-linked immunoabsorbent assay. Vitamin D receptor polymorphisms (Cdx-2, Fok I, Bsm I and Taq I) were analyzed using real-time polymerase-chain reaction high resolution melting analysis.. Serum levels of 1a, 25-Dihydroxyvitamin in primary open-angle glaucoma patients were lower than in age-matched controls. Statistical analysis revealed a significant difference in the allelic frequencies of the BsmI and TaqI genotypes between primary open-angle glaucoma patients and age-matched controls, while other polymorphisms did not show any significant differences.. Vitamin D deficiency and the presence of the BsmI 'B' allele and the TaqI 't' allele are relevant risk factors in the development of glaucoma.. Clinical Trials.gov: NCT02539745 . The study was registered retrospectively on August 3rd, 2015. The first participant was enrolled on July 4th, 2013.

Topics: Aged; Alleles; Case-Control Studies; CDX2 Transcription Factor; Female; Gene Frequency; Genotype; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Calcitriol; Retrospective Studies; Risk Factors; Vitamin D; Vitamin D Deficiency

Topics: Aged; Biomarkers; Colon; Colonoscopy; Diverticulosis, Colonic; Female; Humans; Male; Predictive Value of Tests; Retrospective Studies; Severity of Illness Index; Vitamin D; Vitamin D Deficiency

It is well established that the mitochondria of proximal convoluted tubule cells of the kidney are the site of production of circulating 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The production of 1,25(OH)2D3 at this site is tightly regulated. Parathyroid hormone markedly stimulates 1,25(OH)2D3 production, whereas 1,25(OH)2D3 itself suppresses production. The mechanism of suppression by 1,25(OH)2D3 has not yet been elucidated. We have now found that in the absence of vitamin D (vitamin D deficiency), the vitamin D receptor (VDR) is found in the interior of the apical brush border of the proximal tubule cells. This is unique for the proximal tubule cells, since this has not been observed in the distal tubule cells or in other epithelial cells, such as intestinal mucosa. Administration of 1,25(OH)2D3 to vitamin D-deficient rats results in the movement of VDR from the brush border to the cytoplasm and nucleus presumably bound to reabsorbed 1,25(OH)2D3. The VDR bound to 1,25(OH)2D3 suppresses expression of 25-hydroxyvitamin D3 1α-hydroxylase and stimulates the 25-hydroxyvitamin D3 24-hydroxylase. Thus, VDR in the apical brush border of the proximal convoluted tubule cells serves to "sense" the level of circulating 1,25(OH)2D3 and modulates the activity of the 1α-hydroxylase and the 24-hydroxylase accordingly.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Active Transport, Cell Nucleus; Animals; Calcium; Cell Nucleus; Gene Expression Regulation; Kidney Tubules, Proximal; Male; Protein Transport; Rats; Rats, Sprague-Dawley; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency; Vitamin D3 24-Hydroxylase

Burn patients are at risk of vitamin D (VD) deficiency and may benefit from its pleiotropic effects as soon as acute phase. Aim of this observational study was to assess effects of a cholecalciferol (VD3) bolus on VD status in adult burn patients (Group B, GB) after admission, compared to healthy subjects (Group H, GH).. Both groups received an oral dose of 100,000 IU VD3. Blood samples were collected before (D0) and 7 days (D7) after bolus to measure 250H-D, 1,25(OH)2-D, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Albumin (ALB) and VD binding protein (DBP) were measured and used to calculate free 25OH-D level. Data were expressed as median (min-max) or proportions.. A total of 49 subjects were included: 29 in GH and 20 in GB. At D0, prevalence of VD deficiency was higher in GB: 25OH-D was 21.5 (10.1-46.3) ng/ml in GH vs 11 (1.8-31.4) ng/ml in GB. DBP and ALB were lower in GB. At D7, DBP was stable in both groups while ALB decreased in GB. 25OH-D increased by 66.6 (13.5-260.3)% in GH. In GB, changes in 25OH-D extended from -36.7% to 333.3% with a median increase of 33.1%. Similar changes were observed in each group for free 25OH-D. High FGF23 levels were observed in GB.. This study highlighted the differences in VD status and in response to a high dose VD3 in burn patients when compared to healthy patients. Pitfalls in VD status assessment are numerous during acute burn care: 25OH-D measurement needs cautious interpretation and interest of free 25OH-D is still questionable. They should not prevent burn patients to receive VD supplements during acute care. Higher doses than general recommendations should probably be considered.

Topics: Adolescent; Adult; Aged; Burns; Case-Control Studies; Cholecalciferol; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Male; Middle Aged; Parathyroid Hormone; Serum Albumin; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamins; Young Adult

Hypovitaminosis D is a common syndrome with well-established risk factors. Only recently, however, are the expansive implications of vitamin D deficiency becoming recognized, including cardiovascular complications, cancer, and dementia. The increased attention to the role of vitamin D has made its assessment more crucial in comprehensive patient management.

Topics: Dementia; Diet; Dietary Supplements; Humans; Muscle Weakness; Neoplasms; Sunlight; Vitamin D; Vitamin D Deficiency

Vitamin D3 has transcriptome- and genome-wide effects and activates, via the binding of its metabolite 1α,25-dihydroxyvitamin D3 to the transcription factor vitamin D receptor (VDR), several hundred target genes. Using samples from a 5-month vitamin D3 intervention study (VitDmet), we recently reported that the expression of 12 VDR target genes in peripheral blood mononuclear cells (PBMCs) as well as 12 biochemical and clinical parameters of the study participants are significantly triggered by vitamin D3. In this study, we performed a more focused selection of further 12 VDR target genes and demonstrated that changes of their mRNA expression in PBMCs of VitDmet subjects significantly correlate with alterations of 25-hydroxyvitamin D3 serum levels. Network and self-organizing map analysis of these datasets together with that of the other 24 parameters was followed by relevance calculations and identified changes in parathyroid hormone serum levels and the expression of the newly selected genes STS, BCL6, ITGAM, LRRC25, LPGAT1 and TREM1 as well as of the previously reported genes DUSP10 and CD14 as the most relevant parameters for describing vitamin D responsiveness in vivo. Moreover, parameter relevance ranking allowed the segregation of study subjects into high and low responders. Due to the long intervention period the vitamin D response was not too prominent on the level of transcriptional activation. Therefore, we performed in the separate VitDbol trial a short-term but high dose stimulation with a vitamin D3 bolus. In PBMCs of VitDbol subjects we observed direct transcriptional effects on the selected VDR target genes, such as an up to 2.1-fold increase already one day after supplementation onset. In conclusion, both long-term and short-term vitamin D3 supplementation studies allow monitoring the vitamin D responsiveness of human individuals and represent new types of human in vivo vitamin D3 investigations.

Topics: Biomarkers; Chromatin Immunoprecipitation; Dietary Supplements; Female; Gene Expression Regulation; Gene Regulatory Networks; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Multigene Family; Real-Time Polymerase Chain Reaction; Receptors, Calcitriol; Signal Transduction; Vitamin D; Vitamin D Deficiency; Vitamins

Essential hypertension is a polygenic disorder with a complex and multifactorial nature. Although no single gene is responsible, multiple genes provide incremental contributions to this disorder. Vitamin D is a primary regulator of calcium homeostasis. Epidemiological and clinical studies appear to point to a role for vitamin D in hypertension but direct experimental evidence is lacking. Sprague-Dawley rats were made vitamin D deficient by feeding a purified vitamin D-deficient diet and eliminating all sources of ultraviolet light. Vitamin D deficiency was confirmed by very low serum calcium levels. Blood pressure was measured in conscious rats non-invasively with a volume pressure recording system. Vitamin D deficiency results in elevated blood pressures independent of serum calcium concentration. The administration of 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and a less calcemic analog, 2-methylene-19-nor-20(S)-1α-hydroxyl-bishomopregnacalciferol (2MbisP) significantly reduced blood pressure in these rats. Thus, vitamin D status is one of the determining factors regulating blood pressure.

Topics: Animals; Blood Pressure; Female; Hypertension; Hypocalcemia; Male; Rats; Rats, Sprague-Dawley; Vitamin D; Vitamin D Deficiency

Topics: Antineoplastic Agents; Apoptosis; Bexarotene; CD4-Positive T-Lymphocytes; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Humans; Mycosis Fungoides; Receptors, Calcitriol; Retinoid X Receptors; Sezary Syndrome; Skin Neoplasms; Tetrahydronaphthalenes; Vitamin D; Vitamin D Deficiency

Low circulating 25-hydroxyvitamin D [25(OH)D] and high sodium intake are both associated with progressive albuminuria and renal function loss in CKD. Both vitamin D and sodium intake interact with the renin-angiotensin-aldosterone system. We investigated whether plasma 25(OH)D or 1,25-dihydroxyvitamin D [1,25(OH)2D] is associated with developing increased albuminuria or reduced renal function and whether these associations depend on sodium intake.. Baseline plasma 25(OH)D and 1,25(OH)2D were measured by liquid chromatography tandem mass spectrometry, and sodium intake was assessed by 24-hour urine collections in the general population-based Prevention of Renal and Vascular End-Stage Disease cohort (n=5051). Two primary outcomes were development of urinary albumin excretion >30 mg/24 h and eGFR (creatinine/cystatin C-based CKD Epidemiology Collaboration) <60 ml/min per 1.73 m(2). Participants with CKD at baseline were excluded. In Cox regression analyses, we assessed associations of vitamin D with developing increased albuminuria or reduced eGFR and potential interaction with sodium intake.. During a median follow-up of 10.4 (6.2-11.4) years, 641 (13%) participants developed increased albuminuria, and 268 (5%) participants developed reduced eGFR. Plasma 25(OH)D was inversely associated with increased albuminuria (fully adjusted hazard ratio [HR] per SD higher, 0.86; 95% confidence interval [95% CI], 0.78 to 0.95; P=0.003) but not reduced eGFR (HR, 0.99; 95% CI, 0.87 to 1.12; P=0.85). There was interaction between 25(OH)D and sodium intake for risk of developing increased albuminuria (P interaction =0.03). In participants with high sodium intake, risk of developing increased albuminuria was inversely associated with 25(OH)D (lowest versus highest quartile: adjusted HR, 1.81; 95% CI, 1.20 to 2.73, P<0.01), whereas this association was nonsignificant in participants with low sodium intake (HR, 1.29; 95% CI, 0.94 to 1.77; P=0.12). Plasma 1,25(OH)2D was not significantly associated with increased albuminuria or reduced eGFR.. Low plasma 25(OH)D is associated with higher risk of developing increased albuminuria, particularly in individuals with high sodium intake, but not of developing reduced eGFR. Plasma 1,25(OH)2D is not associated with risk of developing increased albuminuria or reduced eGFR.

Topics: Adult; Aged; Albuminuria; Biomarkers; Chi-Square Distribution; Chromatography, Liquid; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Multivariate Analysis; Netherlands; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Factors; Sodium, Dietary; Tandem Mass Spectrometry; Time Factors; Urinalysis; Vitamin D; Vitamin D Deficiency

Vitamin (vit) D deficiency and preterm birth (PTB) are more prevalent among African American (AA) women compared to caucasian (Cau) women. Because vit D is important in regulating cell-mediated immune responses, vit D insufficiency or deficiency during pregnancy may enhance inflammation in pregnant women and increase the risk of PTB. In this study, circulatory levels of 25-hydroxy (OH) and 1,25-dihydroxy (OH)2 vit D were measured using chemiluminescence and radioimmunoassay techniques, respectively, in AA (n = 108) and Cau (n = 84) women who delivered at term and preterm. The results from this study suggest that the serum levels of the 25-(OH) vit D concentrations tend to decrease (P = .06) in the Cau women who delivered at preterm compared to those delivering at term. However, the 25-(OH) vit D levels in Cau and AA between term and preterm deliveries were not significantly different. The serum levels of 1,25-(OH)2 vit D were found to be significantly lower in AA women compared to Cau women (P < .02) at term, and in the Cau (P < .01) and AA (P < .04) women delivering at preterm compared to those delivering at term. One-way analysis of variance demonstrated that 1,25-(OH)2 vit D levels were significantly lower in participants delivering at preterm (<34 weeks and between 34 and 37 weeks) compared to those delivering at term (>37 weeks).These results suggest that low levels of serum 1,25-(OH)2 vit D are associated with PTB, and vit D can potentially be used as a novel diagnostic marker in the detection of PTB.

Topics: Adult; Biomarkers; Black or African American; Case-Control Studies; Female; Humans; Infant, Newborn; Pregnancy; Premature Birth; Retrospective Studies; Vitamin D; Vitamin D Deficiency; White People; Young Adult

Plasma exchange is used in the treatment of diseases mediated by pathogenic circulating proteins, or for transplant desensitization. Its non-targeted nature results in the depletion of physiologically important molecules, and it is often complicated by hypocalcaemia.. To determine the effects of plasma exchange on vitamin D binding protein (DBP) and associated vitamin D metabolites.. Single-centre prospective cohort study of 11 patients.. DBP and vitamin D metabolites were measured before and immediately after five plasma exchanges, and 7 and 28 days after discontinuation of plasma exchange.. Plasma exchange reduced plasma DBP concentration from 196.9 ± 53.2 to 98.5 ± 34 μg/ml (P = 0.0001), 1,25-dihydroxyvitamin D from 103 ± 52 to 42 ± 4 pmol/l (P = 0.003) and 25-hydroxyvitamin D from 49.7 ± 29 to 22 ± 9.4 nmol/l (P = 0.0017), through their removal in effluent. After 7 days, DBP and 1,25-dihydroxyvitamin D were not significantly different from baseline, but 25-hydroxyvitamin D remained significantly lower after 7 days (26.4 ± 9.8 nmol/l, P = 0.02) and 28 days (30.8 ± 15.5 nmol/l, P = 0.048). Corrected calcium decreased from 2.23 ± 0.11 to 1.98 ± 0.08 mmol/l (P = 0.0007) immediately after five treatments. Plasma calcium was significantly associated with 1,25-dihydroxyvitamin D (r(2) = 0.79, P < 0.0001).. Plasma exchange induced an acute reversible decrease in plasma 1,25-dihydroxyvitamin D, DBP, calcium and a sustained decrease in plasma 25-hydroxyvitamin D.

Topics: Adult; Aged; Calcium; Female; Humans; Male; Middle Aged; Plasma Exchange; Prospective Studies; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

In children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess and 1,25-dihyroxyvitamin D deficiency across the spectrum of predialysis CKD. This study characterized circulating concentrations of fibroblast growth factor 23 and 1,25-dihyroxyvitamin D, and investigated their interrelationships and associations with GFR and secondary hyperparathyroidism in children with CKD who were enrolled in the Chronic Kidney Disease in Children observational cohort study.. Plasma fibroblast growth factor 23 concentrations and determinants of mineral metabolism were measured in 464 children ages 1-16 years with predialysis CKD. GFR was measured by plasma disappearance of iohexol in 70% of participants and estimated by the Chronic Kidney Disease in Children estimating equation using serum creatinine and cystatin C concentrations in the remainder of the participants. Participants were grouped according to CKD stage and by 10-ml/min categories of GFR.. Median GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57; range=15-109). Plasma fibroblast growth factor 23 concentration was above the normal range in 67% of participants (with higher levels observed among participants with lower GFR) before higher levels of serum parathyroid hormone and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34% higher in participants with glomerular disease than in participants with nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher GFR, but thereafter they became higher in parallel with fibroblast growth factor 23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in those participants with low GFR values, high fibroblast growth factor 23 levels, 25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism was present in 55% of participants with GFR<50 ml/min per 1.73 m(2).. In children with predialysis CKD, high plasma fibroblast growth factor 23 is the earliest detectable abnormality in mineral metabolism, and levels are highest in glomerular diseases.

Topics: Adolescent; Age Factors; Biomarkers; Calcium; Canada; Child; Child, Preschool; Creatinine; Cross-Sectional Studies; Cystatin C; Early Diagnosis; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular Filtration Rate; Humans; Hyperparathyroidism, Secondary; Infant; Kidney; Parathyroid Hormone; Phosphorus; Predictive Value of Tests; Renal Insufficiency, Chronic; Severity of Illness Index; United States; Vitamin D; Vitamin D Deficiency

Elevation of serum proinflammatory advanced glycation end products (AGEs) is involved in the pathogenesis of polycystic ovary syndrome (PCOS). The soluble receptor for AGEs (sRAGE) acts as a decoy by binding circulating AGEs. Vitamin D supplementation attenuates the deposition of AGEs in the vascular system of diabetic animals and improves some metabolic aspects of vitamin D-deficient women with PCOS. Additionally, serum anti-Mullerian hormone (AMH) is elevated in women with PCOS, reflecting abnormal ovarian folliculogenesis.. The objective of the study was to evaluate the effect of 1,25 dihydroxyvitamin D3 (vit D3) supplementation on serum sRAGE and AMH in vitamin D-deficient women with PCOS. DESIGN, SETTINGS, PARTICIPANTS, AND INTERVENTION: Sixty-seven women with (n = 22) or without (control; n = 45) PCOS who were diagnosed with vitamin D deficiency were enrolled. Fifty-one women were replaced with oral vit D3 for 8 weeks (16 with PCOS and 35 controls) and 16 women were not treated (six with PCOS and 10 controls). Serum 25-hydroxyvitamin D (25 OH-D), sRAGE, and AMH concentrations were measured at baseline and after vit D3 supplementation in the treated group and 8 weeks apart in the nontreated group.. Changes in serum sRAGE and AMH concentrations after vit D3 replacement were measured.. In all participants, there was a negative correlation between body mass index and serum sRAGE levels (r = -0.3, P = .01). In women with PCOS, but not in controls, vit D3 increased serum sRAGE (P = .03) and decreased serum AMH levels (P < .001). The increase in serum sRAGE positively correlated with the increase in serum 25 OH-D after supplementation in women with PCOS (r = 0.6, P = .01).. In women with PCOS, vit D3 might exert a protective effect against the inflammatory action of AGEs by increasing circulating sRAGE. The normalization in serum AMH induced by vit D3 replacement suggests an improvement in folliculogenesis.

Topics: Adult; Anti-Mullerian Hormone; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Polycystic Ovary Syndrome; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency has been frequently reported in advanced liver disease. However, its influence on alcoholic liver disease (ALD) has been poorly elucidated. We investigated the association of vitamin D with clinical, biological, and histological parameters and survival in ALD patients. Furthermore, we explored the effect of vitamin D treatment on ALD patient peripheral blood mononuclear cells (PBMCs), and in a murine experimental model of ALD.. Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined in 324 Caucasian ALD patients and 201 healthy controls. In vitro experiments on vitamin D pre-treated PBMCs evaluated TNFα production by ELISA in culture supernatants. Mice were submitted to an ethanol-fed diet and some of them were orally supplemented three times per week with 1,25(OH)2D.. Severe deficiency in 25(OH)D (<10 ng/ml) was significantly associated with higher aspartate aminotransferase levels (p=1.00 × 10(-3)), increased hepatic venous pressure gradient (p=5.80 × 10(-6)), MELD (p=2.50 × 10(-4)), and Child-Pugh scores (p=8.50 × 10(-7)). Furthermore, in multivariable analysis, a low 25(OH)D concentration was associated with cirrhosis (OR=2.13, 95% CI=1.18-3.84, p=0.013) and mortality (HR=4.33, 95% CI=1.47-12.78, p=7.94 × 10(-3)) at one year. In addition, in vitro, 1,25(OH)2D pretreatment decreased TNFα production by stimulated PBMCs of ALD patients (p=3.00 × 10(-3)), while in vivo, it decreased hepatic TNFα expression in ethanol-fed mice (p=0.04).. Low 25(OH)D levels are associated with increased liver damage and mortality in ALD. Our results suggest that vitamin D might be both a biomarker of severity and a potential therapeutic target in ALD.

Topics: Adult; Animals; Biomarkers; Case-Control Studies; Disease Models, Animal; Female; Humans; Leukocytes, Mononuclear; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Male; Mice; Mice, Inbred C57BL; Middle Aged; Prognosis; Prospective Studies; Risk Factors; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency

Epidemiology has linked vitamin D deficiency with preeclampsia in humans. We hypothesized that low vitamin D status in pregnant mice may lead to symptoms of preeclampsia. Female BL6 mice were raised on vitamin D-sufficient or -deficient diets from weeks 4 of age and then mated with vitamin D-sufficient BL6 males at week 8. The resulting pregnant mice were either allowed to deliver pups and monitored for blood pressure (BP) and weight of offspring or euthanized at day 14 or 18 of gestation (E14 or E18) for analysis of serum, placental/kidney tissues, and fetuses. At E14 serum concentrations of 25-hydroxyvitamin D (30.1 ± 5.0 vs 1.8 ± 0.6 ng/mL, P < .001) and 1,25-dihydroxyvitamin D (119.5 ± 18.7 vs 37.4 ± 5.1 pg/mL, P < .01) were higher in sufficient vs deficient pregnant mice. At E14 BP was significantly elevated in vitamin D-deficient pregnant mice relative to vitamin D-sufficient mice for both systolic BP (124.89 ± 2.28 vs 105.34 ± 3.61 mm Hg, P < .001) and mean arterial pressure (115.33 ± 1.93 vs 89.33 ± 5.02 mm Hg, P < .001). This elevation continued through pregnancy until 7 days postpartum (PP7) but returned to baseline by PP14. Analysis of maternal kidneys showed increased expression of mRNA for renin and the angiotensin II receptor (3- and 4-fold, respectively) in vitamin D-deficient vs -sufficient mice at E14. Histological analysis of E14 placentas from vitamin D-deficient mice showed decreased vascular diameter within the labyrinth region. E14 and E18 fetuses from vitamin D-deficient mice were larger than those from vitamin D-sufficient mothers. However, by PP14 pups from vitamin D-deficient mothers weighed significantly less than those from vitamin D-sufficient mothers. Resupplementation of vitamin D periconceptually partially reversed the effects of vitamin D deficiency. These data provide further evidence that low vitamin D status may predispose pregnant women to dysregulated placental development and elevated blood pressure.

Topics: Animals; Blood Pressure; Female; Fetal Development; Immunohistochemistry; Mice; Mice, Inbred C57BL; Placenta; Pregnancy; Real-Time Polymerase Chain Reaction; Receptors, Angiotensin; Vitamin D; Vitamin D Deficiency

The effect of a single large oral dose of vitamin D on muscle function in young people with vitamin D deficiency has not been investigated so far.. We evaluated the effect of a single oral dose of 600,000 IU of cholecalciferol on muscle strength.. Eighteen young women with vitamin D deficiency received a single oral dose of 600,000 IU of cholecalciferol. We evaluated changes in maximal voluntary contraction (MVC) and speed of contraction (S) in response to cholecalciferol by using an hand held dynamometer at 3, 15, 30, 60 and 90 days, compared to baseline.. We observed no significant change in MVC and S values, a significant increase of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and a significant decrease in serum parathyroid hormone (PTH) (p<0.001 for all). A significant correlation was found between MVC and S and serum phosphorus (P) after supplementation (p<0.02 and p<0.05, respectively). Conversely, we observed no association between the parameters of muscle strength and 25(OH)D, ionized calcium (Ca2+), PTH and 1,25(OH)2D.. A single dose of 600,000 IU of cholecalciferol does not directly enhance handgrip strength in young women with vitamin D deficiency. More studies are needed on the indirect effect of the hormone on muscle.

Topics: Adult; Cholecalciferol; Dietary Supplements; Female; Hand Strength; Humans; Muscle Contraction; Parathyroid Hormone; Phosphorus; Prospective Studies; Vitamin D; Vitamin D Deficiency

The active form of vitamin D [1,25-dihydroxycholecalciferol, 1,25(OH)2D3] and the vitamin D receptor (VDR) regulate susceptibility to experimental colitis. The effect of the bacterial microflora on the susceptibility of C57BL/6 mice to dextran sodium sulfate-induced colitis was determined. Mice that cannot produce 1,25(OH)2D3 [Cyp27b1 (Cyp) knockout (KO)], VDR KO as well as their wild-type littermates were used. Cyp KO and VDR KO mice had more bacteria from the Bacteroidetes and Proteobacteria phyla and fewer bacteria from the Firmicutes and Deferribacteres phyla in the feces compared with wild-type. In particular, there were more beneficial bacteria, including the Lactobacillaceae and Lachnospiraceae families, in feces from Cyp KO and VDR KO mice than in feces from wild-type. Helicobacteraceae family member numbers were elevated in Cyp KO compared with wild-type mice. Depletion of the gut bacterial flora using antibiotics protected mice from colitis. 1,25(OH)2D3 treatment (1.25 μg/100 g diet) of Cyp KO mice decreased colitis severity and reduced the numbers of Helicobacteraceae in the feces compared with the numbers in the feces of untreated Cyp KO mice. The mechanisms by which the dysbiosis occurs in VDR KO and Cyp KO mice included lower expression of E-cadherin on gut epithelial and immune cells and fewer tolerogenic dendritic cells that resulted in more gut inflammation in VDR and Cyp KO mice compared with wild-type mice. Increased host inflammation has been shown to provide pathogens with substrates to out-compete more beneficial bacterial species. Our data demonstrate that vitamin D regulates the gut microbiome and that 1,25(OH)2D3 or VDR deficiency results in dysbiosis, leading to greater susceptibility to injury in the gut.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Cadherins; Colitis; Dendritic Cells; Dextran Sulfate; Feces; Female; Immune System; Inflammation; Intestinal Mucosa; Intestines; Male; Metagenome; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Topics: Child; Child, Preschool; Familial Hypophosphatemic Rickets; Female; Humans; Male; Vitamin D; Vitamin D Deficiency

Prior studies of vitamin D metabolism in Crohn's disease (CD) did not include controls or examine changes following diagnosis. This study examined associations among 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and parathyroid hormone (PTH) levels in incident pediatric CD, compared with controls, and following diagnosis.. Serum vitamin D and PTH were measured at diagnosis (n = 78), 6, 12, and a median of 43 months (n = 52) later in CD participants, and once in 221 controls. Multivariate regression was used to examine baseline associations and quasi-least squares regression to assess subsequent changes.. At diagnosis, 42% of CD participants were 25(OH)D-deficient (<20 ng/mL). The odds ratio for deficiency was 2.1 (95% confidence interval [CI]: 1.1, 3.9; P < 0.05) vs. controls, adjusted for age, race, and season. 1,25(OH)(2)D was lower in CD vs. controls (P < 0.05), adjusted for 25(OH)D, tumor necrosis factor alpha (TNF-α), and PTH. TNF-α was associated with lower 1,25(OH)(2)D (P < 0.05), and the positive association between PTH and 1,25(OH)(2)D in controls was absent in CD (interaction P = 0.02). Among participants with 25(OH)D <30 ng/mL, CD was associated with lower PTH (P < 0.05) vs. controls. Following diagnosis, 25(OH)D and 1,25(OH)(2)D improved (P < 0.001). At the final visit, 3% were 25(OH)D-deficient, PTH was no longer low relative to 25(OH)D, and 1,25(OH)(2)D was significantly elevated (P < 0.001) compared with controls.. Incident CD was associated with 25(OH)D and 1,25(OH)2D deficiency and a relative hypoparathyroidism that resolved following diagnosis. Inflammatory cytokine suppression of PTH and renal 1-α-hyroxylase may contribute to these alterations.

Topics: Adolescent; Adult; Body Composition; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Crohn Disease; Female; Follow-Up Studies; Humans; Male; Parathyroid Hormone; Prognosis; South Carolina; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency; Young Adult

Recent studies in the Middle East have shown an increased incidence of vitamin D deficiency across this region of year-round sunlight. There is scarcity of information, however, as to the levels of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of vitamin D, and its associations with cardiometabolic parameters in an Arab cohort and this study aims to fill this gap. In a cross-sectional study, 33 male and 43 female (22 children and 54 adults, total 76) Saudis with previously established low levels of serum 25-hydroxyvitamin D [25(OH)D] (<50 ng/ml or 20 nmol/l) were recruited. Anthropometrics were obtained and fasting blood samples were taken for a routine measurement of glucose, lipid profile, calcium, and albumin, while serum 25(OH)D, 1,25-(OH)2D, and intact PTH were quantified using specific ELISAs. Serum calcium, intact PTH, and 1,25(OH)2D were all within the normal range in both children and adults in both genders. In all subjects, serum 1,25(OH)2D was not associated with intact PTH, while circulating 1,25(OH)D inversely correlated with systolic blood pressure (p=0.01) and waist circumference (p=0.04). Thus, vitamin D deficient Saudi children and adults with normal levels of 1,25-(OH)2D also had normal circulating calcium and PTH. This study suggests that local cutoffs should be set that will be of clinical significance in the identification of those at true risk for harder end-points, such as secondary hyperparathyroidism and bone-related diseases.

Topics: Adult; Blood Pressure; Body Mass Index; Child; Female; Health; Humans; Linear Models; Male; Parathyroid Hormone; Saudi Arabia; Systole; Vitamin D; Vitamin D Deficiency

Several trials have reported an increased risk of fractures and falls after intermittent high-dose vitamin D. Treatment with loading doses of vitamin D may increase 1,25(OH)(2) vitamin D catabolism through changes in calcium/phosphate homeostasis and fibroblast growth factor-23 (FGF-23).. The aim was to determine the effects of high-dose vitamin D on circulating concentrations of 1,25(OH)(2) vitamin D and FGF-23 in patients with osteoporosis and vitamin D insufficiency.. We carried out a prospective study of 45 subjects with vitamin D deficiency/insufficiency treated with a bolus dose of 300 000 IU of vitamin D(2) im. Blood samples were obtained at baseline and 1, 2, and 3 months after treatment.. Changes in 1,25(OH)(2)-vitamin D and FGF-23 were measured.. Loading dose of vitamin D(2) increased 1,25(OH)(2)-vitamin D(2) at 3 months, with a mean [SD] of 41 [56] pmol/L at baseline and 162.3 [137.8] pmol/L at 3 months (P < .001). FGF-23 increased significantly at all time points with a peak at 3 months, with percent change from baseline (mean [SEM]) of 50% [48%] at 3 months (P < .01). There was a positive correlation between FGF-23 and serum phosphate (r = 0.36, P = .024) and calcium (r = 0.532, P < .001) and a negative correlation between total 1,25(OH)(2)-vitamin D and FGF-23 (r = -0.32, P = .036) at 3 months.. High-dose vitamin D increases 1,25(OH)(2)-vitamin D and FGF-23 concentration. Further studies are required to determine whether adjusting vitamin D dose and frequency to minimize increases in FGF-23 may prevent the adverse outcomes associated with high-dose intermittent vitamin D supplementation.

Topics: Aged; Alendronate; Bone Density; Bone Density Conservation Agents; Ergocalciferols; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Male; Middle Aged; Osteoporosis; Postmenopause; Vitamin D; Vitamin D Deficiency

There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.. The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.. Men aged 40-79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.. QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.. A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.. Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.

Topics: Absorptiometry, Photon; Adult; Aged; Aging; Biomarkers; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Calcaneus; Calcitriol; Collagen Type I; Hip Joint; Humans; Life Style; Lumbar Vertebrae; Male; Middle Aged; Parathyroid Hormone; Peptides; Surveys and Questionnaires; Ultrasonography; Vitamin D; Vitamin D Deficiency; White People

Data regarding the prevalence of 25-hydroxyvitamin D (25(OH)D) insufficiency in patients with nephrolithiasis, and the effects of vitamin D supplementation on parathyroid hormone (PTH) are few and conflicting. In this article, we examined the prevalence of vitamin D insufficiency and deficiency in 236 recurrent kidney stone formers and the correlation of vitamin D levels with other parameters of stone formation. The prevalent stone composition was calcium oxalate (80.4%) and uric acid (16.45%). One third of stone formers had vitamin D insufficiency and a quarter of them high PTH levels (PTH >7.5 pmol/l) with normal serum (total and ionized) calcium values. Predictor of high PTH was low 25(OH)D level (r = 0.989, r(2) = 0.977, p < 0.001). Stone formers with hypercalciuria had higher 25(OH)D values (72.26 ± 4.21 vs. 59.29 ± 1.76, p = 0.0013) compared to stone formers with urine calcium within normal ranges. Further studies are needed in order to better define the consequences of vitamin D insufficiency and to evaluate the impact of the therapeutic interventions in this cohort.

Topics: Biomarkers; Comorbidity; Female; Humans; Kidney Calculi; Male; Middle Aged; Ontario; Prevalence; Recurrence; Risk Factors; Vitamin D; Vitamin D Deficiency

Few large studies have assessed changes in calcitropic hormones and maternal 25-hydroxyvitamin D (25(OH)D) status across pregnancy, and how this may impact maternal bone turnover and neonatal hormone status. We aimed to identify determinants of 25(OH)D, parathyroid hormone (PTH), and calcitriol across pregnancy in a longitudinal study of 168 pregnant adolescents (≤18 years of age). Maternal 25(OH)D, PTH, and calcitriol were assessed at mid-gestation (∼26 weeks), delivery, and in cord blood. Data were related to measures of maternal anthropometrics, dietary intake, physical activity, and bone turnover markers. Approximately 50% of teens and their infants had serum 25(OH)D ≤ 20 ng/mL; 25(OH)D was lower in African Americans versus whites (p < 0.001). PTH increased across gestation (p < 0.001). Elevated PTH (≥60 pg/mL) was detected in 25% of adolescents at delivery, and was associated with increased concentrations of serum N-telopeptide (NTX) (p = 0.028). PTH and calcitriol did not significantly differ across the range of Ca intake consumed (257-3220 mg/d). In the group as a whole, PTH was inversely associated with 25(OH)D in maternal circulation at mid-gestation (p = 0.023) and at delivery (p = 0.019). However, when the cohort was partitioned by 25(OH)D status, this relationship was only present in those with 25(OH)D ≤ 20 ng/mL, suggestive of a threshold below which 25(OH)D impacts PTH during pregnancy. Mid-gestation 25(OH)D was inversely associated with calcitriol at delivery (p = 0.023), irrespective of Ca intake. Neonatal PTH and calcitriol were significantly lower than (p < 0.001), but unrelated to maternal concentrations. These findings indicate that maternal 25(OH)D status plays a role in calcitropic hormone regulation in pregnant adolescents.

Topics: Adolescent; Biomarkers; Bone Remodeling; Calcitriol; Diet; Dietary Supplements; Female; Hormones; Humans; Infant, Newborn; Longitudinal Studies; Parathyroid Hormone; Pregnancy; Prevalence; Vitamin D; Vitamin D Deficiency

The aim of this study was to determine the prevalence of vitamin D deficiency in hemodialysis (HD) patients and the relationship between seasonal variations in vitamin D levels and vascular calcification.. As a prospective observational study, we analyzed 289 HD patients. We have assessed serum 25-hydroxyvitamin D (25D) levels at the end of the summer (September) and winter (March) and analyzed the data to reveal the association of serum 25D level with vascular calcification scores (VCS) at the end of the summer, when vitamin D levels were found to peak. Plan X-ray images of lateral lumbar spine from all subjects were studied for calculation of semiquantitative VCS as described by Kauppila.. The prevalence of 25D deficiency was 86.2% at the end of the summer and increased to 96.2% at the end of the winter. Female gender and diabetes were associated with vitamin D deficiency. According to univariate analysis, 25D levels were inversely related to vascular calcification. However, after correcting for confounding factors, this relationship lost statistical significance. Multivariate analysis showed that age, systolic blood pressure, and LDL-cholesterol levels were directly associated with a higher VCS.. Vitamin D deficiency was highly prevalent in HD patients with marked seasonal variation. However, low 25D levels could not be identified as an independent predictor of vascular calcification in these patients.

Topics: Adult; Aged; Biomarkers; Chi-Square Distribution; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prevalence; Prospective Studies; Radiography; Renal Dialysis; Republic of Korea; Risk Assessment; Risk Factors; Seasons; Vascular Calcification; Vitamin D; Vitamin D Deficiency

Reports of clinical rickets are particularly evident in minority infants and children, but only limited analyses of vitamin D are available in this demographic group.. We sought to characterize circulating 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and their determinants, including circulating parathyroid hormone (PTH), total alkaline phosphatase activity (ALP), calcium, and phosphorus, in minority infants and children.. We obtained demographic information and blood samples for measurement of PTH, ALP, 25(OH)D, and 1,25(OH)(2)D in >750 6-mo- to 3-y-old children. Dietary intake data were obtained and analyzed.. The mean (±SD) 25(OH)D concentration was 66 ± 22 nmol/L (26.3 ± 8.7 ng/dL). A total of 15% of children had 25(OH)D concentrations less than the recommended target threshold of 50 nmol/L. Combined elevations of PTH and ALP occurred in only 2.5% of children. Determinants of 25(OH)D included vitamin D intake, age (decreasing with age), skin type (greater concentrations in lighter-skinned children than in darker-skinned children), formula use (higher intakes), season (greater concentrations in the summer and fall than in the winter and spring), and, inversely, PTH. The mean 1,25(OH)(2)D concentration was 158 ± 58 pmol/L (60.6 ± 22.5 pg/mL), which was consistent with a reference range of 41-274 pmol/L or 15.7-105.5 pg/mL. Determinants for 1,25(OH)(2)D were age (decreasing with age), sex (greater concentrations in girls than in boys), skin type (greater concentrations in lighter-skinned children than in darker-skinned children), and, inversely, serum calcium and phosphorus.. Although 15% of subjects were vitamin D insufficient, only 2.5% of subjects had elevations of both PTH and ALP. The greater 25(OH)D concentrations observed with formula use confirm that dietary vitamin D fortification is effective in this demographic group. Circulating 1,25(OH)(2)D is higher in infants than in older children and adults and, in contrast to 25(OH)D, is not directly correlated with nutrient intakes.

Topics: Age Factors; Alkaline Phosphatase; Calcium; Catchment Area, Health; Child, Preschool; Diet; Female; Humans; Hyperparathyroidism; Infant; Male; Minority Groups; Parathyroid Hormone; Phosphorus; Prevalence; Reference Values; Seasons; Sex Factors; Skin Pigmentation; Urban Population; Vitamin D; Vitamin D Deficiency; Vitamins

Here we determined if vitamin D deficiency is more common in children with chronic kidney disease compared to healthy children. In addition, we sought to identify disease-specific risk factors for this deficiency, as well as its metabolic consequences. We found that nearly half of 182 patients (ages 5 to 21) with kidney disease (stages 2 to 5) and a third of age-matched 276 healthy children were 25-hydroxyvitamin D deficient (<20 ng/ml). The risk of deficiency was significantly greater in advanced disease. Focal segmental glomerulosclerosis and low albumin were significantly associated with lower 25-hydroxyvitamin D, which, in turn, was associated with significantly higher intact parathyroid hormone levels. We found that 25-hydroxyvitamin D levels were positively associated with 1,25-dihydroxyvitamin D, the relationship being greatest in advanced disease (significant interaction), and inversely related to those of inflammatory markers C-reactive protein and IL-6. The association with C-reactive protein persisted when adjusted for the severity of kidney disease. Thus, lower 25-hydroxyvitamin D may contribute to hyperparathyroidism, inflammation, and lower 1,25-dihydroxyvitamin D in children and adolescents, especially those with advanced kidney disease.

Topics: Adolescent; C-Reactive Protein; Case-Control Studies; Child; Child, Preschool; Female; Humans; Hyperparathyroidism, Secondary; Inflammation; Interleukin-6; Male; Parathyroid Hormone; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Young Adult

Topics: Adolescent; Breast Feeding; Dietary Supplements; Female; Humans; Hypocalcemia; Infant; Italy; Male; Rickets; Risk Factors; Vitamin D; Vitamin D Deficiency

Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D-binding protein) associates more strongly with measures of mineral metabolism than total levels, we identified 94 patients with previously measured 25(OH)D and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) from a cohort of incident hemodialysis patients. Vitamin D-binding protein was measured from stored serum samples. Bioavailable 25(OH)D and 1,25(OH)(2)D were determined using previously validated formulae. Associations with demographic factors and measures of mineral metabolism were examined. When compared with whites, black patients had lower levels of total, but not bioavailable, 25(OH)D. Bioavailable, but not total, 25(OH)D and 1,25(OH)(2)D were each significantly correlated with serum calcium. In univariate and multivariate regression analysis, only bioavailable 25(OH)D was significantly associated with parathyroid hormone levels. Hence, bioavailable vitamin D levels are better correlated with measures of mineral metabolism than total levels in patients on hemodialysis.

Topics: Aged; Biological Availability; Biomarkers; Black or African American; Bone and Bones; Bone Remodeling; Calcium; Female; Humans; Incidence; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Multivariate Analysis; Parathyroid Hormone; Renal Dialysis; Retrospective Studies; United States; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; White People

This retrospective data analysis was undertaken to examine the biochemical differences between renal stone formers with normocalcemic hyperparathyroidism (NHPT) and those with normal parathyroid hormone (PTH) levels. Our goal was to ascertain whether 25-hydroxyvitamin D (25(OH)D) status related to PTH levels in this patient cohort. Our findings among 74 patients with NHPT indicate that stone formers with NHPT had significantly lower 25(OH)D levels compared to 192 controls (p = 0.0001) and that 25(OH)D is positively correlated with 1,25-dihydroxyvitamin D values (R = 0.736, p = 0.015). Sequential measurements (after 3 - 5 years), among 11 patients with NHPT who did not receive vitamin D (VitD) preparations, showed a significant increase in urinary calcium (3.43 ± 1.96 vs. 5.72 ± 3.95, p = 0.0426) without a significant change in PTH levels. VitD supplementation, to 3 patients resulted in significant PTH decrease (11.8 ± 1.8 vs. 9.8 ± 1.3, p = 0.003). Prospective studies are needed to confirm the role of vitamin supplementation in renal stone formers with NHPT.

Topics: Biomarkers; Calcium; Chi-Square Distribution; Dietary Supplements; Female; Humans; Hyperparathyroidism; Kidney Calculi; Male; Middle Aged; Ontario; Parathyroid Hormone; Recurrence; Retrospective Studies; Time Factors; Vitamin D; Vitamin D Deficiency; Vitamins

Elevated fibroblast growth factor 23 (FGF-23) concentrations associate with left ventricular hypertrophy (LVH) and adverse outcomes in adult patients with chronic kidney disease. We hypothesized that similar associations are present in pediatric patients on maintenance hemodialysis.. In this retrospective study of 26 young patients on chronic hemodialysis, aged 6-21 years, cardiac structure and geometry were measured by echocardiography, and circulating levels of FGF-23 and calciotropic hormones were obtained.. FGF-23 levels were uniformly elevated in all patients from three- to 835-fold above the upper limit of normal. The average LV mass index (LVMI) was 43 ± 13 g/m(2.7) and reflected LVH in 55 % of patients. Log-transformed FGF-23 concentrations correlated with LVMI (p = 0.03) and were independently associated with the interventricular septal thickness Z-score (p < 0.001). Concentric LVH was associated with the highest FGF-23 concentrations and the highest LVMI measurements (p < 0.001). Each 1 standard deviation increase in log-transformed FGF-23 levels was associated with a 17 % increase in LVMI.. FGF-23 levels are strongly associated with increased LVMI and with prevalent LVH in pediatric hemodialysis patients. Our cross-sectional findings provide observational evidence supporting the hypothesis linking FGF-23 to cardiac hypertrophy in patients with chronic kidney disease.

Topics: Adolescent; Age Factors; Biomarkers; Calcium; Child; Comorbidity; Cross-Sectional Studies; Echocardiography, Doppler; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Florida; Humans; Hypertrophy, Left Ventricular; Multivariate Analysis; Parathyroid Hormone; Phosphates; Prevalence; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Up-Regulation; Vitamin D; Vitamin D Deficiency; Young Adult

Klotho(-/-) mice display disturbed Ca(2+) and vitamin D homeostasis. Renal cytochrome p450 27b1 (Cyp27b1), the enzyme that catalyzes the hydrolysis to 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), is increased in klotho(-/-) mice, and a 1,25(OH)(2)D(3)-deficient diet partially normalized Ca(2+) homeostasis in these klotho(-/-) mice. The aim of the present study was to further delineate the interplay between 1,25(OH)(2)D(3) and klotho and their relative contribution to the Ca(2+) homeostasis of klotho(-/-) mice.. Double-klotho(-/-)/Cyp27b1(-/-) mice were generated and mice aged 8-12 weeks were housed in metabolic cages to collect 24-h urine. Blood samples were taken and the animals were sacrificed, and the kidney and duodenum tissues were sampled for RNA extraction. The bone was fixed in 10% v/v formalin and analysed by microcomputed tomography (μCT) scans.. Klotho(-/-)/Cyp27b1(-/-) mice, like Cyp27b1(-/-) mice, displayed significantly decreased serum total calcium concentrations compared with wild-type mice (1.44 ± 0.03 and 2.25 ± 0.02 mM) along with normal urinary total calcium excretion. Hyperphosphataemia of klotho(-/-) mice normalized to wild-type levels in klotho(-/-)/Cyp27b1(-/-) mice. The mRNA levels of duodenal transient receptor potential vanilloid subtype 6 (TRPV6) and calcium-binding protein-D(9K), and renal calbindin-D(28K) and NCX1 were significantly reduced in the double knockouts compared with wild-type or klotho(-/-) mice. Elevated TRPV5 protein levels in klotho(-/-) mice normalized to wild type in klotho(-/-)/Cyp27b1(-/-) mice, but were decreased in Cyp27b1(-/-) mice. μCT scans showed that klotho(-/-)/Cyp27b1(-/-) mice, as Cyp27b1(-/-) mice, display significant bone hypomineralization and severely decreased bone mass. Klotho(-/-) mice show a reduced bone mass and increased trabecular numbers.. Klotho(-/-)/Cyp27b1(-/-) mice resemble Cyp27b1(-/-) mice. Since 1,25(OH)(2)D(3) is absent in these mice, our results imply that Ca(2+) homeostasis in klotho(-/-) mice is affected by their excessive 1,25(OH)(2)D(3) levels.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; Blotting, Western; Bone and Bones; Calcium; Duodenum; Glucuronidase; Homeostasis; Immunohistochemistry; Klotho Proteins; Mice; Mice, Knockout; Phosphates; Real-Time Polymerase Chain Reaction; TRPV Cation Channels; Vitamin D; Vitamin D Deficiency

Renal impairment is a risk factor for poor clinical outcome in cardiac surgical patients and low circulating levels of the vitamin D hormone 1,25-dihydroxyvitamin D (1,25[OH](2)D) may contribute to this risk.. We investigated the association between glomerular filtration rate (GFR) and 1,25(OH)(2)D in 151 heart transplant recipients and 59 other cardiac surgical patients in postoperative week 1 and at postoperative month 1. GFR estimates (eGFR) were calculated from cystatin C (CysC) and serum creatinine (SCr)-based formulas.. With both formulas, linear models provided a better fit between eGFR and circulating 1,25(OH)(2)D than nonlinear models. Nonetheless, the association between 1,25(OH)(2)D and eGFR in the early postoperative period was stronger with the CysC-based formula (r = 0.560; P <0.001) than with the SCr-based equation (r = 0.386; P <0.001). CysC-eGFR and SCr-eGFR displayed considerably lack of agreement in the early postoperative period, especially in heart transplant recipients.. There is a relatively close association between CysC-eGFR and circulating 1,25(OH)(2)D in cardiac surgical patients. Data underline the importance of preserved kidney function in cardiac surgery for adequate circulating 1,25(OH)(2)D levels. The SCr-based formula is probably too imprecise for estimating GFR in the early postoperative period correctly.

Topics: Adult; Aged; Biomarkers; Cardiac Surgical Procedures; Creatinine; Cystatin C; Female; Glomerular Filtration Rate; Heart Transplantation; Humans; Kidney; Kidney Diseases; Linear Models; Male; Middle Aged; Models, Biological; Nonlinear Dynamics; Risk Factors; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

The classic role of vitamin D in the regulation of calcium and phosphate metabolism, and its effects on bone health, are well established. More recently a critical role in immunity and respiratory health has been proposed. This arises from evidence for the capacity to generate the active metabolite, 1α,25-dihydroxyvitamin D3 (1,25(OH)D3), locally in many tissues beyond the kidney; expression of the vitamin D receptor (VDR) in immune and structural cells not involved in calcium-phosphate homeostasis; and control by 1,25(OH)D3 of the transcription of genes associated with numerous different biological processes through its nuclear VDR. Abnormalities in the vitamin D axis, including a high prevalence of vitamin D insufficiency worldwide, now appear important in a wide range of pulmonary diseases including viral and bacterial respiratory infection, asthma, chronic obstructive pulmonary disease, and cancer. Actions of vitamin D on innate immune responses, for example, production of antimicrobial peptides and autophagy, and on adaptive immune responses, for example, promoting regulatory lymphocytes, are believed to underpin these associations.

Topics: Calcitriol; Calcium Channels; Humans; Immunity, Innate; Lung Diseases; Prevalence; Receptors, Calcitriol; Transcription, Genetic; United Kingdom; Vitamin D; Vitamin D Deficiency

Low vitamin D concentrations are detected in patients suffering from various clinical conditions which are characterized also by inflammation and immune activation.We investigated whether vitamin D levels in patients with coronary artery disease (CAD) are related to markers of immune activation.. Serum concentrations of 25-hydroxyvitamin D[25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH) 2 D] and the immune activation markers neopterin and high sensitivity C-reactive protein (hsCRP) were measured in 2015 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography.. Serum concentrations of 25(OH)D and 1,25(OH) 2 D did not differ between patients with CAD [mean } SD:25(OH)D: 17.4 } 9.4 μ g/L; 1,25(OH) 2 D: 34.4 } 13.3 ng/L] and controls [25(OH)D: 18.4 } 11.7 μ g/L; 1,25(OH) 2 D: 35.3 } 12.7ng/L; Welch ’ s t-test: p = n.s.] but CAD patients had higher neopterin (8.6 } 7.4 nmol/L) and hsCRP (9.6 } 19.6 mg/L) concentrations compared to controls (neopterin: 7.5 } 4.8 nmol/L;p = 0.0004; hsCRP: 5.4 } 10.0 mg/L; p < 0.0001). There was an inverse correlation between serum 25(OH)D or 1,25(OH) 2 D concentrations and serum neopterin [Spearman ’ s rank correlation:25(OH)D: r s = – 0.183; 1,25(OH)2D: r s = – 0.230] and hsCRP [25(OH)D: r s = – 0.142; 1,25(OH) 2 D: r s = – 0.130; allp < 0.0001] concentrations.. Our results indicate increased inflammatory processes in patients with low vitamin D status. Further studies should clarify the underlying mechanisms for the observed associations of vitamin D status and inflammatory parameters.

Topics: Aged; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Humans; Immune System; Inflammation; Middle Aged; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is an increasingly recognized comorbidity in patients with both type 1 (T1D) and type 2 diabetes, particularly associated with the presence of diabetic nephropathy.. Because we have previously reported enhanced excretion of megalin in the urine of T1D patients with microalbuminuria, we hypothesized that concurrent urinary loss of the megalin ligand, vitamin D binding protein, might contribute mechanistically to vitamin D deficiency.. Examining a study cohort of 115 subjects with T1D, aged 14-40 yr, along with 55 age-matched healthy control subjects, we measured plasma and urine concentrations of vitamin D binding protein (VDBP) along with serum concentrations of total calcium, parathyroid hormone, 25-hydroxyvitamin D, and 1, 25-dihydroxyvitamin D; these results were compared between groups and investigated for relationships with metabolic control status or with albuminuria.. Between-group differences in urinary VDBP concentration were the main outcome measures.. A marked increase in the urinary excretion of VDBP was apparent in subjects with T1D, compared with control subjects. Using multivariate regression modeling, significant correlates of urinary VDBP excretion included microalbuminuria (P = 0.004), glycosylated hemoglobin (P = 0.010), continuous glucose monitoring system average capillary glucose (P = 0.047), and serum 1,25(OH)(2)D concentrations (P = 0.037). Vitamin D deficiency or insufficiency was slightly more prevalent in diabetic subjects with albuminuria, coincident with the increase in urine VDBP excretion.. These findings suggest that, theoretically, exaggerated urinary loss of VDBP in T1D, particularly in persons with albuminuria, could contribute mechanistically to vitamin D deficiency in this disease.

Topics: Adolescent; Adult; Blood Glucose; Calcium; Diabetes Mellitus, Type 1; Female; Humans; Male; Parathyroid Hormone; Regression Analysis; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

We tested the hypothesis that vascular endothelial function, assessed by endothelium-dependent dilation, is related to serum vitamin D status among middle-aged and older adults without clinical disease, and that this is linked to inflammation. Brachial artery flow-mediated dilation, a measure of endothelium-dependent dilation, was lower (P<0.01) in vitamin D-insufficient (3.7 ± 0.2%; serum 25-hydroxyvitamin D [25(OH)D]: 20 to 29 ng/mL; 62 ± 1 years of age; n = 31; mean± SE) and vitamin D-deficient (3.2 ± 0.3%; 25(OH)D: <20 ng/mL; 63 ± 2 years of age; n = 22) versus vitamin D-sufficient (4.6 ± 0.4%; 25(OH)D: >29 ng/mL; 61 ± 1 years of age; n = 22) subjects, whereas endothelium-independent dilation (brachial dilation to sublingual nitroglycerine) did not differ (P = 0.45). Among all subjects, brachial flow-mediated dilation was positively related to serum 25(OH)D (%Δ: r = 0.35; P<0.01) but not 1,25-dihydroxyvitamin D (r = -0.06; P = 0.61), the active form of vitamin D. Vascular endothelial cell expression of the proinflammatory transcription factor nuclear factor κB was greater in deficient versus sufficient subjects (0.59 ± 0.07 versus 0.44 ± 0.05; P<0.05), and inhibition of nuclear factor κB (4 days oral salsalate) improved flow-mediated dilation to a greater extent in subjects with lower versus higher 25(OH)D (+3.7 ± 0.6 versus +2.0 ± 0.2%; P<0.05). Endothelial cell expression of the downstream proinflammatory cytokine interleukin-6 also was higher in deficient versus sufficient subjects (0.67 ± 0.08 versus 0.47 ± 0.05; P<0.01) and inversely related to serum 25(OH)D level (r = -0.62; P<0.01), whereas vitamin D receptor and 1-α hydroxylase, the 25(OH)D to 1,25-dihydroxyvitamin D converting enzyme, were lower (P<0.05). Inadequate serum 25(OH)D is associated with vascular endothelial dysfunction among healthy middle-aged/older adults, and this is mediated in part by nuclear factor κB-related inflammation. Reduced vitamin D receptor and 1-α hydroxylase may be molecular mechanisms linking vitamin D insufficiency to endothelial dysfunction.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Aged; Brachial Artery; Endothelium, Vascular; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; NF-kappa B; Nitroglycerin; Receptors, Calcitriol; Salicylates; Vascular Diseases; Vasodilation; Vitamin D; Vitamin D Deficiency

Hypovitaminosis D is highly prevalent in adult kidney-transplanted patients. The knowledge of vitamin D status in kidney-transplanted children and adolescents is sparse. The present study investigated the vitamin D status of a cohort of kidney-transplanted children and adolescents, and the association between vitamin D status and plasma concentrations of PTH, ionized calcium, and phosphate. The study included 35 patients with a functioning graft. Their mean age was 12.0 yr, and the mean graft age was 2.8 yr. Forty percent of the patients were vitamin D insufficient (P-25-hydroxyvitamin D 40-75 nm), and 14% were deficient (P-25-hydroxyvitamin D < 40 nm). S-25-hydroxyvitamin D was inversely associated with PTH (p = 0.02) and positively associated with S-1,25-dihydroxyvitamin D (p = 0.02). There was no significant association between S-1,25-dihydroxyvitamin D and PTH. In conclusion, we found hypovitaminosis D in 54% of the study population despite the fact that samples were collected in spring and summer months. Hypovitaminosis D was associated with adverse effects on PTH and 1,25-dihydroxyvitamin D. Our data suggest that it is warranted to monitor vitamin D status of kidney-transplanted children and adolescents and indicate that correction of hypovitaminosis D might have favorable effects on calcium-phosphate metabolism.

Topics: Adolescent; Age Distribution; Anthropometry; Child; Child, Preschool; Cross-Sectional Studies; Female; Follow-Up Studies; Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Male; Parathyroid Hormone; Prevalence; Severity of Illness Index; Sex Distribution; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Both, anemia and vitamin D deficiency are prevalent in patients with heart failure. According to recent evidence, vitamin D may stimulate erythropoiesis. We measured circulating 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH](2)D) and hemoglobin (Hb) in a cross-sectional study in 364 end-stage heart failure patients awaiting cardiac transplantation, of whom 52.6% met the criteria for anemia (Hb < 13 g/dl in males and <12 g/dl in females). None of the patients were on erythrocyte-stimulating agents. Of the study cohort, 87.8% had 25(OH)D concentrations below 50 nmol/l. The mean Hb concentrations were significantly reduced in the lower tertiles of 25(OH)D and 1,25(OH)(2)D (P < 0.001). In multivariate-adjusted logistic regression analyses, the odds ratios for anemia of the lowest tertile of 25(OH)D (<18 nmol/l) and 1,25(OH)(2)D (<40 pmol/l) were 2.69 (1.46-5.00) and 4.08 (2.18-7.62) compared with their respective highest tertile (>32 nmol/l and >70 pmol/l). Patients with severe dual deficiency of 25(OH)D and 1,25(OH)(2)D had an odds ratio for anemia of 9.87 (95% CI 3.59-27.1) compared with patients in the highest tertile for both vitamin D metabolites. Circulating 1,25(OH)(2)D was directly related to circulating 25(OH)D levels and kidney function (P < 0.001), and inversely associated with C-reactive protein (P = 0.020). Our data demonstrate that vitamin D deficiency is independently associated with low Hb values and anemia in end-stage heart failure. Circulating 1,25(OH)(2)D is a better predictor of anemia than circulating 25(OH)D. Prospective randomized studies with administration of vitamin D (metabolites) will have to clarify if the association of vitamin D deficiency with anemia is causal.

Topics: Adult; Aged; Anemia; C-Reactive Protein; Cross-Sectional Studies; Female; Heart Failure; Hemoglobins; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Severity of Illness Index; Vitamin D; Vitamin D Deficiency

Topics: Calcifediol; Clinical Laboratory Techniques; Diagnosis, Differential; Dietary Supplements; Ergocalciferols; Humans; Malabsorption Syndromes; Osteoporosis; Polymorphism, Genetic; Receptors, Calcitriol; Reference Values; Renal Insufficiency; Sarcoidosis; Sunscreening Agents; Vitamin D; Vitamin D Deficiency

The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium-vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH)(2)D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH)(2)D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH)(2)D levels and increased bone turnover markers.

Topics: Adult; Bariatric Surgery; Biomarkers; Bone Density; Bone Resorption; Dietary Supplements; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Obesity; Parathyroid Hormone; Postoperative Complications; Prospective Studies; Vitamin D; Vitamin D Deficiency; Weight Loss

Multiple pathways converge to result in the overexpression of T(h)17 cells in the absence of either vitamin D or the vitamin D receptor (VDR). CD4(+) T cells from VDR knockout (KO) mice have a more activated phenotype than their wild-type (WT) counterparts and readily develop into T(h)17 cells under a variety of in vitro conditions. Vitamin D-deficient CD4(+) T cells also overproduced IL-17 in vitro and 1,25 dihydroxyvitamin D(3) inhibited the development of T(h)17 cells in CD4(+) T-cell cultures. Conversely, the induction of inducible (i) Tregs was lower in VDR KO CD4(+) T cells than WT and the VDR KO iTregs were refractory to IL-6 inhibition. Host-specific effects of the VDR were evident on in vivo development of naive T cells. Development of naive WT CD4(+) T cells in the VDR KO host resulted in the overexpression of IL-17 and more severe experimental inflammatory bowel disease (IBD). The increased expression of T(h)17 cells in the VDR KO mice was associated with a reduction in tolerogenic CD103(+) dendritic cells. The data collectively demonstrate that T(h)17 and iTreg cells are direct and indirect targets of vitamin D. The increased propensity for development of T(h)17 cells in the VDR KO host results in more severe IBD.

Topics: Animals; CD4-Positive T-Lymphocytes; Dendritic Cells; Immune Tolerance; Inflammation; Inflammatory Bowel Diseases; Interleukin-17; Interleukin-6; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Calcitriol; Signal Transduction; T-Lymphocytes, Regulatory; Th17 Cells; Vitamin D; Vitamin D Deficiency

Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However, because studies examining the associations of all three chronic conditions with circulating 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) are limited, we examined these associations in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian PLCO participants selected as controls in previous nested case-control studies of 25(OH)D and 1,25(OH)(2)D were included in this analysis. Diabetes, CHD and hypertension prevalence, risk factors for these conditions and intake of vitamin D and Ca were collected from a baseline questionnaire. Results indicated that serum levels of 25(OH)D were low (< 50 nmol/l) in 29 % and very low (< 37 nmol/l) in 11 % of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30 and 10 %, respectively. After adjustment for confounding by sex, geographical location, educational level, smoking history, BMI, physical activity, total dietary energy and vitamin D and Ca intake, only diabetes was significantly associated with lower 25(OH)D and 1,25(OH)(2)D levels. Caucasians who had 25(OH)D ≥ 80 nmol/l were half as likely to have diabetes (OR 0·5 (95 % CI 0·3, 0·9)) compared with those who had 25(OH)D < 37 nmol/l. Those in the highest quartile of 1,25(OH)(2)D (≥ 103 pmol/l) were less than half as likely to have diabetes (OR 0·3 (95 % CI 0·1, 0·7)) than those in the lowest quartile (< 72 pmol/l). In conclusion, the independent associations of 25(OH)D and 1,25(OH)(2)D with diabetes prevalence in a large population are new findings, and thus warrant confirmation in larger, prospective studies.

Topics: Aged; Chronic Disease; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Female; Heart Diseases; Humans; Hypertension; Male; Middle Aged; Prevalence; Risk Factors; Surveys and Questionnaires; United States; Vitamin D; Vitamin D Deficiency; White People

The last decade has seen a substantial increase in clinical interest in vitamin D deficiency and of laboratory testing for vitamin D status. Many clinical laboratories in the United States have seen requests for vitamin D testing increase 100% or more in the last 5 years. The most common laboratory test to assess vitamin D nutritional status is total 25-hydroxyvitamin D serum concentrations. Laboratory professionals are often confronted with challenges related to vitamin D testing, including controversy over optimal and target vitamin D concentrations, variable reference ranges across marketed assays and reference laboratories, lack of standardization of vitamin D assays, and misordering of 1,25-dihydroxyvitamin D testing. This article presents a common clinical case scenario regarding vitamin D and an up-to-date discussion and review of the literature on vitamin D testing.

Topics: Humans; Male; Middle Aged; Pathology, Clinical; Reference Values; Referral and Consultation; Vitamin D; Vitamin D Deficiency

Vitamin D3 is known to induce regulatory T (Treg) cells by rendering antigen-presenting cells tolerogenic, its direct effect on human naturally occurring Treg cells is unclear. Here, we investigated if and how 1,25-dihydroxyvitamin D(3) [1,25(OH)2D3] can directly affect the proliferation and function of human naturally occurring Treg cells in vitro. First, we demonstrated that these Treg cells express vitamin D receptors that were up-regulated following anti-CD3/CD28-bead stimulation. 1,25(OH)2D3 inhibited proliferation of Treg cells even when exogenous interleukin-2 was provided. Treg cells were more susceptible to the inhibitory effect of 1,25(OH)2D3 than conventional T cells(.) 1,25(OH)2D3 neither affected the anergic state nor the suppressive function of Treg cells but induced a subtle increase in interleukin-10-secreting cells. The cell-division-inhibiting effect of 1,25(OH)2D3 on Treg cells was also demonstrated in vivo by supplementing vitamin D-deficient HIV-1-infected patients with 2000 IU cholecalciferol (vitamin D3). Increased serum 1,25(OH)2D3 levels were associated with a drop in the number and percentage of Treg cells, which may be attributed to a decrease in the proliferating Foxp3+ Treg cell population. In conclusion, 1,25(OH)2D3 directly affects Treg cell growth and promotes interleukin-10 production without apparent effects on activation status and suppressive phenotype whereas in vivo, high serum 1,25(OH)2D3 levels are associated with reduced Treg cell proliferation and a reduced number of Treg cells.

Topics: Antigen Presentation; Antigen-Presenting Cells; Cell Proliferation; Cells, Cultured; HIV Infections; Humans; Interleukin-10; Interleukin-2; Lymphocyte Activation; Receptors, Calcitriol; T-Lymphocytes, Regulatory; Vitamin D; Vitamin D Deficiency

Patients taking antiepileptic drugs (AEDs) have an increased incidence of fractures. This study investigated chronic AED use and physical contributors to falls risk using an AED-discordant, twin and sibling matched-pair approach, and assessed clinically relevant subgroups: AED polytherapy; longer-duration AED; and falls history.. Twenty-nine same-sex (mean age 44.9 years, 59% female), ambulatory, community-dwelling twin and sibling pairs, discordant for AED exposure (and AED-indication), were recruited. Validated clinical and laboratory tests of strength, gait, and balance were performed. Relevant AED levels, and fasting serum samples for 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and immunoreactive parathyroid hormone (iPTH) levels were taken.. There were significant mean within-pair differences in tests of static and dynamic balance, with the AED user having poorer balance function than the AED nonuser. No difference was seen in lower limb strength or gait measures. Increased duration of AED therapy and AED polytherapy were independent predictors of increased sway. No significant within-pair differences were seen in fasting serum levels of 1,25(OH)(2)D, 25OHD and iPTH after Bonferroni correction.. Balance performance is impaired in AED users compared to their matched nonuser siblings. Pairs where the AED users took AED polytherapy, or had a longer duration of AED use, had more impaired balance performance. These balance deficits may contribute to the increased rate of fractures in this population.

Topics: Accidental Falls; Adult; Anticonvulsants; Diseases in Twins; Drug Therapy, Combination; Epilepsy; Female; Fractures, Bone; Gait; Humans; Male; Muscle Strength; Parathyroid Hormone; Postural Balance; Risk Factors; Siblings; Vitamin D; Vitamin D Deficiency

Topics: Aged; Aged, 80 and over; Female; Frail Elderly; Humans; Immunologic Factors; Institutionalization; Japan; Male; Pneumonia; Risk Factors; Tuberculin Test; Vitamin D; Vitamin D Deficiency

Vitamin D has a number of pleiotropic effects in a variety of tissues, in addition to its well-known effects on mineral metabolism. To determine whether it has an effect on erythropoiesis, we studied the association of the components of the vitamin D axis with the prevalence and severity of anemia in chronic kidney disease. We measured the concentrations of 25-hydroxyvitamin D (25D), 1,25-dihydroxyvitamin D (1,25D), and hemoglobin in a cross-sectional study of 1661 subjects in SEEK, a multi-center cohort study of chronic kidney disease patients in the United States, of whom 41% met the criteria for anemia. The mean hemoglobin concentrations significantly decreased with decreasing tertiles of 25D and 1,25D. These linear trends remained significant after adjustment for age, gender, ethnicity, eGFR, diabetes, and parathyroid hormone. In similarly adjusted models, the lowest tertiles of 25D and 1,25D were independently associated with 2.8- and 2.0-fold increased prevalence of anemia compared with their respective highest tertiles. Patients with severe dual deficiency of 25D and 1,25D had a 5.4-fold prevalence of anemia compared with those replete in both. Our study shows that 25D and 1,25D deficiency are independently associated with decreased hemoglobin levels and anemia in chronic kidney disease. Whether this association is causal requires further study.

Topics: Anemia; Bone and Bones; Calcinosis; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus; Dihydroxycholecalciferols; Hemoglobins; Humans; Kidney Failure, Chronic; Parathyroid Hormone; Prevalence; Renal Insufficiency, Chronic; United States; Vitamin D; Vitamin D Deficiency

Globally, cardiovascular disease (CVD) is the number one cause of death, being responsible for approximately 30% of deaths worldwide. Urbanization and a westernized lifestyle are thought to play a major role in the development of CVD. There is accumulating evidence that vitamin D is a nonclassical risk factor for CVD. The active vitamin D metabolite, 1,25-dihydroxyvitamin D, which is synthesized from its precursor 25-hydroxyvitamin D (25[OH]D), down-regulates several negative and up-regulates various protective pathways in the heart and vasculature. First randomized trials demonstrate that vitamin D supplementation leads to vasodilatation and suppresses cardiovascular risk markers such as triglycerides and the inflammation marker tumor necrosis factor-α. Solar UV-B radiation is the major source of vitamin D for humans. Consequently, the vitamin D status is largely influenced by season, geographic latitude, daily outdoor activities, and the percentage of body surface exposed to solar UV-B. A significant proportion of individuals in Europe and North America have vitamin D concentrations in the deficiency range (25[OH]D<25 nmol/l). Available data indicate that low solar UV-B exposure and/or low 25(OH)D concentrations are associated with an increased risk of CVD. Large nonrandomized studies indicate that CVD mortality is more than twice as high in older individuals with deficient 25(OH)D concentrations compared with those individuals who have adequate 25(OH)D concentrations (>75 nmol/l). Together, experimental and epidemiological evidence does support a plausible role for improving vitamin D status in CVD prevention in the population at large. Nevertheless, future randomised clinical trials are needed to evaluate whether vitamin D is effective with respect to primary, secondary, and/or tertiary prevention of CVD.

Topics: Animals; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Mice; Risk Factors; Seasons; Sunlight; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency

Renal osteodystrophy (ROD) is the skeletal complication of chronic kidney disease. Secondary hyperparathyroidism and 125 dihydroxy vitamin D3 deficiency are the major causative factors in ROD. Musculoskeletal problems remain among the main limitations of the quality of life of renal failure patients. In this report, a 60-year-old male with four extremity fractures due to a minor trauma was presented. The patient had been receiving haemodialysis for seven years due to hypertensive nephropathy. Our case emphasises the importance of multispecialty approach to the investigation and treatment of patients with ROD.

Topics: Chronic Kidney Disease-Mineral and Bone Disorder; Elbow Injuries; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Shoulder Fractures; Tibial Fractures; Vitamin D; Vitamin D Deficiency

Vitamin D insufficiency is a global health issue. Although classically associated with rickets, low vitamin D levels have also been linked to aberrant immune function and associated health problems such as inflammatory bowel disease (IBD). To test the hypothesis that impaired vitamin D status predisposes to IBD, 8-wk-old C57BL/6 mice were raised from weaning on vitamin D-deficient or vitamin D-sufficient diets and then treated with dextran sodium sulphate (DSS) to induce colitis. Vitamin D-deficient mice showed decreased serum levels of precursor 25-hydroxyvitamin D(3) (2.5 +/- 0.1 vs. 24.4 +/- 1.8 ng/ml) and active 1,25-dihydroxyvitamin D(3) (28.8 +/- 3.1 vs. 45.6 +/- 4.2 pg/ml), greater DSS-induced weight loss (9 vs. 5%), increased colitis (4.71 +/- 0.85 vs. 1.57 +/- 0.18), and splenomegaly relative to mice on vitamin D-sufficient chow. DNA array analysis of colon tissue (n = 4 mice) identified 27 genes consistently (P < 0.05) up-regulated or down-regulated more than 2-fold in vitamin D-deficient vs. vitamin D-sufficient mice, in the absence of DSS-induced colitis. This included angiogenin-4, an antimicrobial protein involved in host containment of enteric bacteria. Immunohistochemistry confirmed that colonic angiogenin-4 protein was significantly decreased in vitamin D-deficient mice even in the absence of colitis. Moreover, the same animals showed elevated levels (50-fold) of bacteria in colonic tissue. These data show for the first time that simple vitamin D deficiency predisposes mice to colitis via dysregulated colonic antimicrobial activity and impaired homeostasis of enteric bacteria. This may be a pivotal mechanism linking vitamin D status with IBD in humans.

Topics: Animals; Colitis; Colon; Dextran Sulfate; DNA, Bacterial; Flow Cytometry; Immunohistochemistry; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; Ribonuclease, Pancreatic; Splenomegaly; Vitamin D; Vitamin D Deficiency; Weight Loss

Vitamin D deficiency has been associated with chronic heart failure (CHF). We evaluated vitamin D levels in relationship with New York Heart Association (NYHA) classes, N-terminal pro-brain natriuretic peptide (NT-proBNP) values and left ventricular (LV) measures in ≥60 year old patients with stable CHF. Differently from previous investigations, LV function was assessed by transthoracic echocardiography, to provide easily reproducible results.. The study was performed at geographic latitude 44° N, from March to May and from September to November 2008. Acute HF and diseases or drugs altering vitamin D status were exclusion criteria. NYHA scores and 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D and NT-proBNP concentrations were assessed in 90 (45 F, 45 M) Caucasian patients with CHF secondary to hypertension and/or coronary artery disease. Vitamin D levels were also measured in 31 subjects without heart disease (controls). LV echocardiography was performed in 52 (26 F, 26 M) representative patients. Vitamin D concentrations were significantly lower in CHF cases than in controls. Among subject with CHF, 97.8% presented vitamin D deficiency (25(OH)D<75 nmol/L), being severe (<25 nmol/L) in 66.7%. LV end-diastolic and end-systolic diameters were significantly longer, LV end-diastolic and end-systolic volumes bigger and fractional shortening lower in CHF patients with 25(OH)D<25 nmol/L than with 25(OH)D≥25 nmol/L (p<0.05). Log-values of 25(OH)D were negatively correlated with LV end-systolic diameter and volume (r=-0.28; p<0.05). On subgroup analysis, these results persisted only in male patients.. In elderly CHF patients, vitamin D deficiency was highly prevalent and often severe. This first addressed echocardiography study showed a sex-specific association between vitamin D deficiency and LV dilation. Since further echocardiography data are easily obtainable, larger investigations are demanded.

Topics: Aged; Aged, 80 and over; Chronic Disease; Echocardiography; Female; Heart Failure; Heart Ventricles; Humans; Male; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is associated with many adverse health outcomes. There are several well established environmental predictors of vitamin D concentrations, yet studies of the genetic determinants of vitamin D concentrations are in their infancy. Our objective was to conduct a pilot genome-wide association (GWA) study of 25-hydroxyvitamin D (25[OH]D) and 1,25-dihydroxyvitamin D (1,25[OH](2)D) concentrations in a subset of 229 Hispanic subjects, followed by replication genotyping of 50 single nucleotide polymorphisms (SNPs) in the entire sample of 1190 Hispanics from San Antonio, Texas and San Luis Valley, Colorado. Of the 309,200 SNPs that met all quality control criteria, three SNPs in high linkage disequilibrium (LD) with each other were significantly associated with 1,25[OH](2)D (rs6680429, rs9970802, and rs10889028) at a Bonferroni corrected P-value threshold of 1.62 × 10(-7), however none met the threshold for 25[OH]D. Of the 50 SNPs selected for replication genotyping, five for 25[OH]D (rs2806508, rs10141935, rs4778359, rs1507023, and rs9937918) and eight for 1,25[OH](2)D (rs6680429, rs1348864, rs4559029, rs12667374, rs7781309, rs10505337, rs2486443, and rs2154175) were replicated in the entire sample of Hispanics (P<0.01). In conclusion, we identified several SNPs that were associated with vitamin D metabolite concentrations in Hispanics. These candidate polymorphisms merit further investigation in independent populations and other ethnicities.

Topics: Adult; Colorado; Female; Genome-Wide Association Study; Hispanic or Latino; Humans; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Single Nucleotide; Texas; Vitamin D; Vitamin D Deficiency

Vitamin D insufficiency is common in the United States, with low levels linked in some studies to higher cancer incidence, including non-Hodgkin's lymphoma (NHL). Recent data also suggest that vitamin D insufficiency is related to inferior prognosis in some cancers, although there are no data for NHL.. We tested the hypothesis that circulating 25-hydroxyvitamin D [25(OH)D] levels are predictive of event-free survival (EFS) and overall survival (OS) in a prospective cohort of 983 newly diagnosed patients with NHL. 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels were measured by liquid chromatography-tandem mass spectrometry.. Mean age at diagnosis was 62 years (range, 19 to 94 years); 44% of patients had insufficient 25(OH)D levels (< 25 ng/mL) within 120 days of diagnosis. Median follow-up was 34.8 months; 404 events and 193 deaths (168 from lymphoma) occurred. After adjusting for known prognostic factors and treatment, 25(OH)D insufficient patients with diffuse large B-cell lymphoma (DLBCL) had inferior EFS (hazard ratio [HR], 1.41; 95% CI, 0.98 to 2.04) and OS (HR, 1.99; 95% CI, 1.27 to 3.13); 25(OH)D insufficient patients with T-cell lymphoma also had inferior EFS (HR, 1.94; 95% CI, 1.04 to 3.61) and OS (HR, 2.38; 95% CI, 1.04 to 5.41). There were no associations with EFS for the other NHL subtypes. Among patients with DLBCL and T-cell lymphoma, higher 1,25(OH)(2)D levels were associated with better EFS and OS, suggesting that any putative tumor 1-α-hydroxylase activity did not explain the 25(OH)D associations.. 25(OH)D insufficiency was associated with inferior EFS and OS in DLBCL and T-cell lymphoma. Whether normalizing vitamin D levels in these patients improves outcomes will require testing in future trials.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Chi-Square Distribution; Chromatography, Liquid; Disease-Free Survival; Female; Humans; Iowa; Kaplan-Meier Estimate; Lymphoma, Non-Hodgkin; Male; Middle Aged; Minnesota; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Tandem Mass Spectrometry; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Young Adult

The objectives were to determine the prevalence of vitamin D deficiency [25(OH)D < 10 ng/ml] in pediatric renal transplant (RTx) recipients, compared with controls and identify correlates of changes in 25(OH)D and intact parathyroid hormone (iPTH) levels following transplantation. Serum 25(OH)D, 1,25(OH)(2)D, and iPTH were measured once in 275 healthy controls and at transplantation, and 3 and 12 months posttransplantation in 58 RTx recipients. Multivariate logistic regression models determined the odds ratio (OR) of vitamin D deficiency in RTx recipients vs. controls adjusted for age, sex, race, and season. Generalized estimating equations were used to assess changes following transplantation. At transplantation, 22% of nonblack and 27% of black RTx recipients were vitamin D deficient. The adjusted OR of vitamin D deficiency was greater in RTx recipients (p < 0.001) compared with controls; however, the transplant association was greater in nonblack vs. black individuals (interaction p = 0.02). Overall, 25(OH)D levels did not change significantly following transplantation. Younger age (p < 0.01), nonblack race (p < 0.001), visits in nonwinter months (p < 0.001), and supplementation with ≥400 IU/day ergo/cholecalciferol (p < 0.001) were associated with increases (or lesser declines) in 25(OH)D following transplantation. Increases in 25(OH)D levels (p < 0.001) and vitamin D supplementation (p < 0.01) were associated with greater reductions in iPTH levels following transplantation, independent of 1,25(OH)(2)D levels.

Topics: Adolescent; Age Factors; Biomarkers; Black or African American; Case-Control Studies; Chi-Square Distribution; Child; Child, Preschool; Dietary Supplements; Female; Humans; Hyperparathyroidism; Kidney Transplantation; Logistic Models; Male; Odds Ratio; Ohio; Parathyroid Hormone; Philadelphia; Prevalence; Risk Assessment; Risk Factors; Seasons; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Young Adult

For decades the vitamin D biological system has been considered almost exclusively as the master integrator of calcium-phosphate homeostasis and bone metabolism. More recently, the discovery that many human tissues and cells, which do not directly participate in mineral ion homeostasis, express the vitamin D receptor (VDR) and are able to convert the circulating pro-hormone 25-hydroxyvitamin D in its active form, 1,25-dihydroxyvitamin D, has provided new insights into the biological function of this peculiar endocrine system. Several reports have highlighted a variety of human diseases possibly related to vitamin D insufficiency or deficiency (respectively defined as 25-hydroxyvitamin D serum levels lower than 30 or lower than 20 ng/ml). In particular, experimental and observational studies, including those published in this journal issue, support the concept that vitamin D deficiency is involved in the pathogenesis of congestive heart failure, a disabling condition affecting over 15 million of patients worldwide. Considering that circulating levels of 25-hydroxyvitamin D represent the accepted clinical indicator of individual vitamin D status, the measurement of this pro-hormone can be regarded as an appropriate and cost-effective screening tool in patients with chronic heart failure.

Topics: Animals; Heart Failure; Humans; Receptors, Calcitriol; Renin-Angiotensin System; Vitamin D; Vitamin D Deficiency

Vitamin D compounds possessing A rings prohibited from flipping to the alternative chair form (i.e., analogues 2 and 26) were synthesized. The bicyclic fragment 22 consisting of the fused cyclohexane and dihydropyran rings was constructed via the ring-closing metathesis route. Also, a homologous synthon 23 with an attached dihydropyran ring was successfully synthesized using this strategy. The carbonyl deprotection in 22 yielded cyclohexanone 5 that was subjected to Julia coupling with the anion of the phenylthiazoline sulfone 25. In the resulting isomeric 19-norvitamins 2 and 26, their A rings can exist only in the alpha- and beta-conformation. The analogue 26 was 300 times more active in binding to the vitamin D receptor protein, 30 times more effective in causing HL-60 differentiation, and 10 times more active in transcription. These results confirm that the beta-chair form of the vitamin D ring A is necessary for the binding to the receptor.

Topics: Animals; Bone and Bones; Calcitriol; Calcium; Cell Differentiation; HL-60 Cells; Humans; Male; Molecular Conformation; Norsteroids; Rats; Rats, Sprague-Dawley; Receptors, Calcitriol; Structure-Activity Relationship; Vitamin D Deficiency

Serum 25(OH)D levels decline without sunlight exposure. We studied 120 expeditioners to Antarctica to determine the skeletal and hormonal responses to sunlight deprivation. With emerging vitamin D insufficiency, serum calcium decreased, PTH increased, and bone loss at the proximal femur was observed. Baseline serum 25(OH)D levels >100 nmol/L prevented vitamin D insufficiency.. Vitamin D stores deplete without adequate sunlight exposure unless supplementation is provided. We studied 120 healthy adults who spent a year in Antarctica as a model for sunlight deprivation to define the timing and magnitude of the skeletal and hormonal responses to emerging vitamin D insufficiency.. Fasting blood samples were assessed at baseline, 6 and 12 months for serum 25-hydroxyvitamin D (25(OH)D), osteocalcin (OC), bone formation (P1NP) and resorption (CTx), PTH and calcium. Lumbar spine and proximal femur BMD was measured using DXA. Differences over time were determined using repeated measures ANOVA. Percent changes were expressed as (Delta value/(value A + value B)/2) x 100. Relationships between outcome measures were determined using Spearman's correlations.. Vitamin D insufficiency (<50 nmol/L) was observed in 85% of expeditioners by 6 months when serum calcium decreased and PTH increased (p < 0.01). By 12 months, OC increased by 7.4 +/- 3.0% (p < 0.05), and BMD decreased by 1.0 +/- 2.0% at the total proximal femur (p < 0.05). For those with vitamin D sufficiency at baseline (>50 nmol/L), sunlight deprivation produced vitamin D insufficiency within 4 months unless baseline values were >100 nmol/L.. Supplementation may be necessary for expeditioners with limited access to UV light.

Topics: Adult; Analysis of Variance; Antarctic Regions; Biomarkers; Bone and Bones; Bone Resorption; Dietary Supplements; Fasting; Female; Humans; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Prospective Studies; Sunlight; Vitamin D; Vitamin D Deficiency; Young Adult

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D) enhances innate immunity by inducing the cathelicidin antimicrobial peptide (hCAP). In monocytes/macrophages, this occurs primarily in response to activation of TLR, that induce expression of the vitamin D receptor and localized synthesis of 1,25(OH)(2)D from precursor 25-hydroxyvitamin D(3) (25OHD). To clarify the relationship between vitamin D and innate immunity, we assessed changes in hCAP expression in vivo and ex vivo in human subjects attending a bone clinic (n = 50). Of these, 38% were vitamin D-insufficient (<75 nM 25OHD) and received supplementation with vitamin D (50,000 IU vitamin D(2) twice weekly for 5 wk). Baseline 25OHD status or vitamin D supplementation had no effect on circulating levels of hCAP. Therefore, ex vivo changes in hCAP for each subject were assessed using peripheral blood monocytes cultured with 10% autologous serum (n = 28). Under these vitamin D "insufficient" conditions the TLR2/1 ligand 19 kDa lipopeptide or the TLR4 ligand LPS, monocytes showed increased expression of the vitamin D-activating enzyme CYP27b1 (5- and 5.5-fold, respectively, both p < 0.01) but decreased expression of hCAP mRNA (10-fold and 30-fold, both p < 0.001). Following treatment with 19 kDa, expression of hCAP: 1) correlated with 25OHD levels in serum culture supplements (R = 0.649, p < 0.001); 2) was significantly enhanced by exogenous 25OHD (5 nM); and 3) was significantly enhanced with serum from vivo vitamin D-supplemented patients. These data suggest that a key role of vitamin D in innate immunity is to maintain localized production of antibacterial hCAP following TLR activation of monocytes.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Antimicrobial Cationic Peptides; Cathelicidins; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Humans; Immunity, Innate; Male; Middle Aged; Monocytes; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-Like Receptor 4; Vitamin D; Vitamin D Deficiency

Cardiovascular disease is the leading cause of death among those with diabetes mellitus. Vitamin D deficiency is associated with an increased risk of cardiovascular disease in this population. To determine the mechanism by which vitamin D deficiency mediates accelerated cardiovascular disease in patients with diabetes mellitus, we investigated the effects of active vitamin D on macrophage cholesterol deposition.. We obtained macrophages from 76 obese, diabetic, hypertensive patients with vitamin D deficiency (25-hydroxyvitamin D <80 nmol/L; group A) and 4 control groups: obese, diabetic, hypertensive patients with normal vitamin D (group B; n=15); obese, nondiabetic, hypertensive patients with vitamin D deficiency (group C; n=25); and nonobese, nondiabetic, nonhypertensive patients with vitamin D deficiency (group D; n=10) or sufficiency (group E; n=10). Macrophages from the same patients in all groups were cultured in vitamin D-deficient or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] -supplemented media and exposed to modified low-density lipoprotein cholesterol. 1,25(OH)(2)D(3) suppressed foam cell formation by reducing acetylated or oxidized low-density lipoprotein cholesterol uptake in diabetic subjects only. Conversely, deletion of the vitamin D receptor in macrophages from diabetic patients accelerated foam cell formation induced by modified LDL. 1,25(OH)(2)D(3) downregulation of c-Jun N-terminal kinase activation reduced peroxisome proliferated-activated receptor-gamma expression, suppressed CD36 expression, and prevented oxidized low-density lipoprotein-derived cholesterol uptake. In addition, 1,25(OH)(2)D(3) suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1 expression, and prevented oxidized and acetylated low-density lipoprotein-derived cholesterol uptake.. These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.

Topics: Adult; Animals; CD36 Antigens; Cells, Cultured; Cholesterol; Diabetes Mellitus, Type 2; Female; Foam Cells; Humans; JNK Mitogen-Activated Protein Kinases; Lipoproteins, LDL; Macrophages; Male; Mice; Mice, Mutant Strains; Middle Aged; Obesity; PPAR gamma; Receptors, Calcitriol; Scavenger Receptors, Class A; Signal Transduction; Vitamin D; Vitamin D Deficiency

Institutionalized older people have a high risk of bone fractures due to osteoporosis. In addition, chronic kidney disease (CKD) is highly prevalent in older people living in residential homes. Secondary hyperparathyroidism, poor calcium intake and deficiency of 1,25-dihydroxyvitamin D may lead to decreased bone mass in people with CKD. The present cross-sectional study assessed the relationship between markers of bone mineral metabolism and kidney function in a residential care home population.. Older subjects were recruited from residential care homes and kidney function stratified by the estimated glomerular filtration rate (GFR). Parathyroid hormone (PTH), 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 188 residents not receiving vitamin D/calcium treatment [mean age 85 (range 68- 100) years, 75% female] and in 52 residents receiving vitamin D/calcium supplementation.. Amongst those not receiving vitamin D/calcium, median PTH increased with declining GFR (P < 0.0001), particularly as GFR (mL/min/1.73 m(2)) fell below 45. PTH concentration was suppressed by increasing 25-hydroxyvitamin D (P < 0.0001), but not 1,25-dihydroxyvitamin D (P > 0.05) concentration. Nearly all residents (92%) had 25-hydroxyvitamin D deficiency or insufficiency and this was uninfluenced by kidney function (P > 0.05). Concentration of 1,25-dihydroxyvitamin D declined with worsening renal function (P < 0.0004) but 1,25-dihydroxyvitamin D deficiency was prevalent at all stages of kidney disease, including amongst residents receiving vitamin D/calcium supplementation.. Vitamin D deficiency and secondary hyperparathyroidism are common in this population irrespective of renal function. However, as GFR falls below 45, the prevalence of secondary hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency increases. Unidentified CKD appears to exacerbate secondary hyperparathyroidism in this at risk population.

Topics: Aged; Aged, 80 and over; Bone and Bones; Bone Density; Chronic Disease; Cross-Sectional Studies; Dietary Supplements; Female; Glomerular Filtration Rate; Humans; Hyperparathyroidism, Secondary; Kidney Diseases; Male; Parathyroid Hormone; Residential Facilities; Vitamin D; Vitamin D Deficiency

It is known that vitamin D has many functions besides involvement in calcium metabolism. It has recently been recognized that vitamin D deficiency is associated with mortality, especially in cardiovascular disease (CVD). Vitamin D deficiency is common in end-stage renal disease, but develops from the early stage of chronic kidney disease (CKD). So we investigated whether the serum level of the activated form of vitamin D (1,25-dihydroxyvitamin D) affected mortality in patients with CKD stages 3 and 4.. Between January 1, 1995, and June 30, 2006 we measured serum 1,25-dihydroxyvitamin D In 226 patients with CKD stages 3 and 4 and classified the results into two groups depending on whether the level was below (group I) or above (group II) 20 pg/ml. We ended the follow-up period on December 31, 2006. We compared all-cause and cardiovascular mortality between the two groups. We also examined predictors of mortality by using Cox proportional regression analysis.. Two-hundred and twenty-six patients (67 men and 159 women, mean age 67.0) were registered in this study, and groups 1 and 2 comprised 84 and 142 patients, respectively. During the follow-up period 43 patients died. CVD was the major cause of death, followed by infectious disease. The Kaplan-Meier survival curve revealed that all-cause mortality was significantly higher in group I, but a significant difference between CVD mortality in the two groups was not demonstrated. By Cox proportional regression analysis, group I was related to all-cause mortality, but this was not proved to be an independent predictor.. The results suggested that serum level of 1,25-dihydroxyvitamin D was associated with all-cause mortality in patients with CKD stages 3 and 4.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Communicable Diseases; Disease Progression; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Assessment; Severity of Illness Index; Time Factors; Vitamin D; Vitamin D Deficiency

Although severe deficiency of bioactive vitamin D (1,25OH2D) causes rickets, mild insufficiency of the hormone, known as hypovitaminosis D, is responsible for the occurrence of secondary hyperparathyroidism and osteoporosis. To clarify the pathophysiology of the disease, we studied the negative feedback effect of 1,25OH2D and its precursor 25OHD on the transcriptional activity of parathyroid hormone (PTH) gene using the PT-r parathyroid cell line. We found that PT-r cells express endogenous 1alpha-hydroxylase as well as PTH mRNAs. We also found the potent suppressive effect of physiological concentration of 25OHD on the transcriptional activity of PTH gene. A similar effect was obtained with 1,25OH2D but only with pharmacological concentration. Interestingly, the effect of 25OHD was completely abolished when the cells were treated with 1alpha-hydroxylase inhibitor ketoconazole. These results suggest that the negative feedback regulation of vitamin D on PTH gene transcription occurs not by the end-product 1,25OH2D but by its prohormone 25OHD via intracellular activation by 1alpha-hydroxylase within the parathyroid cells.

Topics: Animals; Base Sequence; Cell Line; Cloning, Molecular; Enzyme Inhibitors; Feedback, Physiological; Genetic Vectors; Humans; Hyperparathyroidism, Secondary; Ketoconazole; Luciferases; Molecular Sequence Data; Parathyroid Glands; Parathyroid Hormone; Plasmids; Promoter Regions, Genetic; Rats; Reverse Transcriptase Polymerase Chain Reaction; Steroid Hydroxylases; Transcription, Genetic; Vitamin D; Vitamin D Deficiency

The effects of vitamin D (VD) deficiency on calcium (Ca) metabolism during pregnancy were evaluated in rats fed VD-repleted (VD-repleted rats) and VD-depleted (VD-depleted rats) diets. In the VD-depleted rats, the plasma concentrations of 1,25-dihydroxyvitamin D and Ca decreased severely, whereas the parathyroid hormone concentrations increased. The Ca contents of the feces of the VD-depleted rats were higher than those of the VD-repleted rats. The fetal Ca contents of the VD-repleted and VD-depleted rats increased continuously, but that of the VD-depleted rats was lower. These data reveal that VD deficiency during pregnancy induces severe hypocalcemia due to reduced intestinal absorption of Ca and elevated fetal demand for Ca.

Topics: Animals; Calcium; Feces; Female; Femur; Fetal Development; Parathyroid Hormone; Pregnancy; Pregnancy Complications; Rats; Rats, Sprague-Dawley; Vitamin D; Vitamin D Deficiency

Serum 25-hydroxyvitamin D [25(OH)D] concentrations serve as a biomarker for vitamin D stores. Prior studies have not examined the risk factors for low vitamin D concentrations in a multiethnic sample of US youth across a broad age range.. The objective was to determine the prevalence of and factors associated with low concentrations of 25(OH)D in children and adolescents.. Serum 25(OH)D concentrations were measured in 382 healthy children aged 6-21 y living in the northeastern United States. Dietary and supplemental vitamin D intake was assessed by interview. Fat and lean mass were assessed by dual-energy X-ray absorptiometry. Multivariable ordinal logistic regression was used to determine factors associated with decreased concentrations of 25(OH)D.. The median concentration of 25(OH)D was 28 ng/mL (interquartile range: 19-35 ng/mL), and 55% of subjects had 25(OH)D concentrations <30 ng/mL. 25(OH)D concentrations were inversely correlated with parathyroid hormone concentrations (Spearman's r=-0.31, P<0.001) but were not significantly correlated with 1,25-dihydroxyvitamin D concentrations. In the multivariable model, older age (P<0.001), black race [odds ratio (OR): 14.2; 95% CI: 8.53, 23.5], wintertime study visit (OR: 3.55; 95% CI: 2.29, 5.50), and total daily vitamin D intake <200 IU (OR: 1.58; 95% CI: 1.02, 2.46) were associated with low vitamin D concentrations. Fat and lean mass were not independently associated with vitamin D status in this healthy-weight sample.. Low serum 25(OH)D concentrations are prevalent in otherwise healthy children and adolescents in the northeastern United States and are related to low vitamin D intake, race, and season.

Topics: Absorptiometry, Photon; Adolescent; Adult; Alkaline Phosphatase; Body Composition; Child; Cross-Sectional Studies; Female; Humans; Logistic Models; Male; Multivariate Analysis; Parathyroid Hormone; Risk Factors; Seasons; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. To investigate the relation between blood levels of 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) with hemodialysis outcomes, we measured baseline vitamin D levels in a cross-sectional analysis of 825 consecutive patients from within a prospective cohort of incident US hemodialysis patients. Of these patients, 78% were considered vitamin D deficient with 18% considered severely deficient. Calcium, phosphorus, and parathyroid hormone levels correlated poorly with 25D and 1,25D concentrations. To test the association between baseline vitamin D levels and 90-day mortality, we selected the next 175 consecutive participants who died within 90 days and compared them to the 750 patients who survived in a nested case-control analysis. While low vitamin D levels were associated with increased mortality, significant interaction was noted between vitamin D levels, subsequent active vitamin D therapy, and survival. Compared to patients with the highest 25D or 1,25D levels who received therapy, untreated deficient patients were at significantly increased risk for early mortality. Our study shows that among incident hemodialysis patients, vitamin D deficiency is common, correlates poorly with other components of mineral metabolism and is associated with increased early mortality.

Topics: Aged; Calcium; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Female; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Parathyroid Hormone; Phosphorus; Prospective Studies; Renal Dialysis; Risk Factors; Survival Analysis; Vitamin D; Vitamin D Deficiency

Primary hyperparathyroidism (PHPT) is associated with reduced plasma 25-hydroxyvitamin D (P-25OHD) and usually increased plasma 1alpha,25-dihydroxyvitamin D (P-1,25(OH)2D). Parathyroid tissue expresses the vitamin D receptor and it is thought that circulating 1,25(OH)2D participate in the regulation of parathyroid cell proliferation, differentiation and secretion.. To investigate the relations between circulating levels of 1,25(OH)2D and 25OHD respectively and parathyroid adenoma weight (AW), plasma-parathyroid hormone (P-PTH) and PTH secretion expressed as P-PTH/AW.. Cross-sectional study.. One hundred and seventy-one consecutive hypercalcaemic caucasian patients aged 19-87 years (median 63, 84% females) with surgically proven parathyroid adenoma.. A weak positive correlation was found between P-25OHD and P-1,25(OH)2D (r=0.24, P<0.005). AW depended on sex and body mass index. Following adjustment, it was correlated positively to P-PTH, calcium (Ca) and alkaline phosphatase (AP) and inversely to plasma phosphate in a multiple regression model. AW was not associated with vitamin D metabolites. Preoperative P-PTH correlated positively to plasma levels of Ca and AP, but inversely to phosphate and 25OHD (P<0.001) levels. P-PTH was not associated with P-1,25(OH)2D (P=0.65). The P-PTH:AW ratio correlated inversely to P-25OHD (P<0.05), but showed no relations to plasma levels of Ca, phosphate or 1,25(OH)2D (P=0.22).. In this material, low levels of 25OHD were related to higher levels of P-PTH and higher PTH:AW ratios in patients with PHPT suggesting that vitamin D deficiency increase PTH secretion activity. Neither PTH secretion nor AW was associated with circulating levels of 1,25(OH)2D.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Organ Size; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Vitamin D; Vitamin D Deficiency

Topics: Biomarkers; Calcium; Deficiency Diseases; Humans; Milk Hypersensitivity; Parathyroid Hormone; Phosphates; Rickets; Vitamin D; Vitamin D Deficiency

Children and adolescents with the high bone turnover comprise a high risk population for vitamin D insufficiency. A sample of 178 clinically healthy children aged 3 to 18 years who came from public schools and lived in North West of Greece participated in the study. They were grouped into three age groups (I: 3-10, II: 11-14 and III: 15-18 years of age). Blood samples were taken during winter and summer months for determining calciotropic hormones, calcium, phosphate and biochemical markers of bone synthesis.A high percentage (47%) of the subjects aged 15-18 years was found to have 25OHD <10 ng/ml in winter but much less (13-14%) of the younger ages (13-14 years), while in the summer they were all >10 ng/ml. The prevalence was even higher in the girls of the older group accompanied by lower Pi concentrations again in winter (win:1.19+/-0.03, sum:1.93+/-0.03 mmol/l, p < 0.001). The 24,25(OH)(2)D levels were changing in parallel to 25OHD, but again in the older subjects, during winter, they were by 2/3 lower than the summer ones (0.73+/-0.10 vs. 2.41+/-0.20 ng/ml, p < 0.001). No significant differences were found between seasons and groups in the 1,25(OH)(2)D levels. The biochemical markers of bone synthesis, osteocalcin (OC) and total alkaline phosphatase (ALP), were found significantly lower in the girls of the older group both in winter and summer respectively. Even in a sunny country like Greece the adolescents living in an urban area are in high risk for vitamin D deficiency during winter. Supplementation with vitamin D of milk, of popular beverages and perhaps some foods would be of help.

Topics: 24,25-Dihydroxyvitamin D 3; Adolescent; Adolescent Development; Alkaline Phosphatase; Calcium; Child; Child Development; Child, Preschool; Female; Greece; Humans; Male; Osteocalcin; Phosphates; Seasons; Vitamin D; Vitamin D Deficiency

Synthesis of vitamin D takes place in the skin under the effect of sunlight. The Indian subcontinent is situated between 8.4 degrees N and 37.6 degrees N latitudes and has adequate sunshine throughout the year. Thus, it has been presumed that Indians are vitamin D sufficient. We measured serum 25-hydroxy vitamin D [25(OH)D] ( n=92) and 1,25-dihydroxy vitamin D [1, 25(OH)(2)D] ( n=65) levels in healthy hospital staff, using (125)I radioimmunoassay. Serum intact parathyroid hormone (PTH) concentration was estimated by immunoradiometric assay. Bone mineral density was estimated using a dual energy X-ray absorptiometer (Hologic QDR 4500A). Using a serum 25(OH)D level of 15 ng/ml as a cutoff, 66.3% (61/92) of the subjects were found to be vitamin D deficient. Of these, 20.6% (19/92) subjects had severe vitamin D deficiency (<5 ng/ml), 27.2% (25/92) had moderate vitamin D deficiency (5-9.9 ng/ml), while 18.5% (17/92) had mild vitamin D deficiency (10-14.9 ng/ml). When a serum 25(OH)D level of 20 ng/ml was used as a cutoff, 78.3% subjects were diagnosed to be vitamin D deficient/insufficient. The serum 1,25(OH)(2)D level was within the normal range (40.6+/-20.1 pg/ml; mean +/- SD). Mean (+/-SD) serum intact PTH, estimated in a limited number of subjects (n=15), was 72.3 (+/-21.0) pg/ml (range 36-100 pg/ml). There was a significant correlation between daily sun exposure and 25(OH)D levels (r=0.731, P<0.001). The serum 25(OH)D level correlated with BMD at the femoral neck and Ward's triangle (r=0.50, P=0.020 and r=0.46, P=0.037, respectively). Our findings show that vitamin D deficiency is common in urban north Indian hospital staff. The possible reasons include inadequate sunlight exposure and skin pigmentation in Indians. The serum 1,25(OH)(2)D level is not a good indicator of vitamin D deficiency. A low serum 25(OH)D level is possibly one of the reasons for lower bone mineral density among Indians.

Topics: Absorptiometry, Photon; Adult; Bone Density; Calcitriol; Calcium, Dietary; Female; Humans; Immunoradiometric Assay; India; Male; Middle Aged; Parathyroid Hormone; Radioimmunoassay; Vitamin D; Vitamin D Deficiency

The prevalence of vitamin D insufficiency, its etiology, and associated sequelae among acutely injured burn patients is unknown.. This study assessed vitamin D and endocrine status, as well as the effect of anabolic agents, in pediatric patients who had sustained burns in excess of 25% total body surface area (TBSA).. Sixty-nine patients with a mean TBSA burn of 50.6+/-2.2% (range 27% to 94%) and full thickness injury of 41.3+/-3.0% (range 0% to 94%) were studied. Subjects ranged in age from 0.6 to 18 years (mean, 5.8+/-0.6 years). Main outcome measures Blood samples were obtained for serum 25-hydroxyvitamin D (D25), 1,25-dihydroxyvitamin D (D1,25), albumin, cortisol, triiodothyronine (T3), tetraiodothyronine (T(4)), thyroid stimulating hormone (TSH), and parathormone (PTH).. Two hundred eighty morning blood samples of D25 and D1,25 demonstrated that 45% and 26.2% were low and 8.9% and 11% were very low, respectively. At least one low D25 or D1,25 level occurred in 62.3% of all subjects. Very low levels were noted in 23.2% of all patients. There was an increased incidence of hyperparathyroidism in patients with very low serum D25. Vitamin D25 and D1,25 levels were lower in subjects with larger burns or inhalation injury, as well as those treated with thyroxine or oxandrolone. Serum albumin, cortisol, T(4), and TSH were not correlated with concentration of vitamin D.. Demonstration of a high incidence of low serum vitamin D indicates vitamin D status may be significantly compromised in burned children. It is unclear why vitamin D deficiency exists in this population. The most effective way to improve vitamin D status remains elusive at this time.

Topics: Adolescent; Anabolic Agents; Burns; Child; Child, Preschool; Ergocalciferols; Growth Hormone; Humans; Hydrocortisone; Incidence; Infant; Oxandrolone; Parathyroid Hormone; Prevalence; Serum Albumin; Thyrotropin; Thyroxine; Trauma Severity Indices; Triiodothyronine; Vitamin D; Vitamin D Deficiency

Hereditary vitamin D-resistant rickets (HVDRR) is a genetic disorder caused by mutations in the vitamin D receptor, which lead to resistance to 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)]. We found that the A ring-modified analogues, 2alpha-(3-hydroxypropyl)- and 2alpha-(3-hydroxypropoxy)-1alpha,25(OH)(2)D(3), (O1C3 and O2C3) can bind better than the natural hormone to the mutant VDR (R274A), which similar to the HVDRR mutant, R274L, had lost the hydrogen bond to the 1alpha-hydroxyl group of 1alpha,25(OH)(2)D(3).

Topics: Hydrogen Bonding; Hypophosphatemia, Familial; Mutation; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Two new vitamin D analogues, (22R)- and (22S)-22-ethyl-1,25-dihydroxy-23,24-didehydro-24a,24b-dihomo-20-epivitamin D(3) (3 and 4), were rationally designed on the basis of the active space group concept previously proposed by us. The 22R ethyl group of 3 restricts the mobility of the side chain to active space regions, whereas the 22S ethyl group of 4 confines the side chain to an inactive region. The double bond at C(23) further restricts the side chain flexibility. These compounds (3 and 4) were synthesized using ortho ester Claisen rearrangement as the key step. As expected, the 22R isomer 3 has nearly 100 times higher efficacy than 1,25-dihydroxyvitamin D(3) (1) in cell differentiation, although its affinity for the vitamin D receptor (VDR) was one-seventh of that of 1. The 22S isomer 4 has significantly lower efficacy than 3. A docking study in combination with site-directed mutation analysis revealed that two carbon elongated side chain analogue 3 could be fitted in the ligand binding pocket of the VDR by adopting a stable conformation.

Topics: Animals; Calcium; Cell Differentiation; COS Cells; Crystallography, X-Ray; HL-60 Cells; Humans; Ligands; Models, Molecular; Molecular Conformation; Mutagenesis, Site-Directed; Rats; Receptors, Calcitriol; Stereoisomerism; Structure-Activity Relationship; Transcription, Genetic; Transcriptional Activation; Vitamin D; Vitamin D Deficiency

To compare the vitamin D status of 34 children, 9-24 months old, living in an area of Delhi renowned for high levels of atmospheric pollution (Mori Gate), with a comparable age matched group of children from a less polluted (Gurgaon) area of the city.. Serum concentrations of calcium, alkaline phosphatase (ALP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured. Haze scores, regarded as a surrogate marker of solar UVB radiation reaching ground level, were measured in both areas.. Mean 25(OH)D of children in the Mori Gate area was 12.4 (7) ng/ml, compared with 27.1 (7) ng/ml in children living in the Gurgaon area (p < 0.001). The median ALP (p < 0.05) and mean PTH (p < 0.001) concentrations were higher in children living in the Mori Gate area than in the Gurgaon area. The mean haze score in the Mori Gate area (2.1 (0.5)) was significantly lower (p < 0.05) than in the Gurgaon area (2.7 (0.4)), indicating less solar UVB reaching the ground in Mori Gate.. We suggest that children living in areas of high atmospheric pollution are at risk of developing vitamin D deficiency rickets and should be offered vitamin D supplements.

Topics: Air Pollution; Biomarkers; Cross-Sectional Studies; Environmental Pollutants; Female; Humans; India; Infant; Male; Risk Factors; Urban Health; Vitamin D; Vitamin D Deficiency

We report three children presenting with hypocalcemia, hyperphosphatemia, elevated levels of parathyroid hormone, low concentrations of 25(OH)-vitamin D, normal to elevated concentrations of 1,25(OH)2-vitamin D, and normal radiographs. Although these findings led to consideration of parathyroid hormone resistance, clinical and biochemical findings remained normal after discontinuation of therapy, suggesting a variation of vitamin D deficiency.

Topics: Calcium; Child, Preschool; Female; Genetic Variation; Humans; Hypocalcemia; Infant; Male; Parathyroid Hormone; Phosphates; Vitamin D; Vitamin D Deficiency

calcium and vitamin D deficiency are common in elderly people and lead to increased bone loss, with an enhanced risk of osteoporotic fractures. Although hip fractures are a serious consequence, few therapeutic measures are given for primary or secondary prevention. A combination of calcium and vitamin D may not be the most effective treatment for all patients.. to investigate the effects of hypovitaminosis D on the calcium-parathyroid hormone endocrine axis, bone mineral density and fracture type, and the optimal role of combination calcium and vitamin D therapy after hip fracture in elderly patients.. a population-based, prospective cohort study.. 150 elderly subjects were recruited from the fast-track orthogeriatric rehabilitation ward within 7 days of surgery for hip fracture. This ward accepts people who live at home and are independent in activities of daily living. All subjects had a baseline medical examination, biochemical tests (parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) and were referred for bone densitometry.. at 68%, the prevalence of hypovitaminosis D (25-hydroxyvitamin D<30 nmol/l) was high. However, only half the patients had evidence of secondary hyperparathyroidism, the rest having a low to normal level of parathyroid hormone ('functional hypoparathyroidism'). Patients with secondary hyperparathyroidism and hypovitaminosis D had a higher mean corrected calcium, higher 1,25-dihydroxyvitamin D, lower hip bone mineral density and an excess of extracapsular over intracapsular fractures than the 'functional hypoparathyroid' group (P<0.01).. there is a high prevalence of hypovitaminosis D in active, elderly people living at home who present with a hip fracture. However, secondary hyperparathyroidism occurs in only half of these patients. This subgroup attempts to maintain calcium homeostasis but does so at the expense of increased bone turnover, leading to amplified hip bone loss and an excess of extracapsular over intracapsular fractures. Combination calcium and vitamin D treatment may be effective in preventing a second hip fracture in these patients, but its role in patients with hypovitaminosis D without secondary hyperparathyroidism and 'vitamin D-replete' subjects needs further evaluation.

Topics: Aged; Aged, 80 and over; Bone Density; Calcium; Femur Neck; Hip Fractures; Humans; Hypoparathyroidism; Lumbar Vertebrae; Parathyroid Hormone; Prevalence; Prospective Studies; United Kingdom; Vitamin D; Vitamin D Deficiency

To test the hypothesis that muscle weakness associated with aging is in part due to low serum levels of vitamin D, we investigated the relationship between muscle strength and serum levels of vitamin D metabolites in ambulatory elderly people who were not receiving vitamin D supplementation. We enrolled 319 ambulatory elderly subjects (103 women: mean age 74.2, age range 65-86; 216 men: mean age 76.6, age range 66-95) between April and August 1995. The study design was cross-sectional. Muscle strength was measured as leg extension power in watts (LEP). Mean 25-hydroxyvitamin D serum concentrations were higher in male participants at 36.2 ng/ml (range 3.0-85.0) versus 27.4 ng/ml (range 5.0-88.0) in female subjects (p = 0.008). We found 12 percent of female and 18 percent of male subjects with 25-hydroxyvitamin D values below the lower threshold (< 12 ng/ml). Mean 1,25-dihydroxyvitamin D levels were similar in both sexes: 39.8 pg/ml (range 15.0-73.0) in women and 37.9 pg/ml (range 13.0-69.0) in men. LEP declined with age in women and men (f: r = -0.35, p = 0.001; m: r = -0.48, p < 0.0001). Men were significantly stronger than women (p < 0.0001). In men both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D showed pairwise correlation with LEP (r = 0.24; p = 0.0004/r = 0.14; p = 0.045). In women only 1,25-hydroxyvitamin D was significantly correlated with LEP (r = 0.22; p = 0.03). In ANCOVA, including all participants, explaining LEP by sex (p < 0.0001), age (p < 0.0001), BMI (p = 0.013), 1,25-dihydroxyvitamin D (p = 0.02), 25-hydroxyvitamin D (p = 0.18) and iPTH (p = 0.82), all factors showed significant effects except 25-hydoxyvitamin D and iPTH (r2 of the whole model: 0.41). In conclusion our results support the view that, in concert with other factors, deficiency of both 25-hydroxyvitamin D and 1,25-hydroxyvitamin D contributes to the age-related decline in muscle strength. Modest, but significant relationships between 1,25-dihydroxyvitamin D and muscle strength in both sexes, and 25-hydroxyvitamin D in male participants could be documented. Whether the impact of vitamin D on calcium homeostasis and bone mineral density or directly on the muscle tissue level is more important for prevention of hip fractures remains unclear. Further prospective and comparative treatment studies should be performed, in order to evaluate whether and in which dose requirements, vitamin D supplementation can improve muscle strength in the elderly.

Topics: Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Humans; Isometric Contraction; Male; Parathyroid Hormone; Sex Factors; Vitamin D; Vitamin D Deficiency

Vitamin D insufficiency is still a concern in countries where there is no routine food supplementation, such as France. A low vitamin D status is clearly associated with an increased risk of fracture in the elderly, but the long-term consequences of latent vitamin D insufficiency in young people and adults are not known. We fed 26 growing pigs a high calcium diet (1.1%) with a 1000 IU cholecalciferol/kg diet (controls), or without vitamin D (0D) for 4 months. We then analyzed the overall impact of low vitamin D status on osteotropic hormones (calcitriol and immunoreactive parathyroid hormone), plasma markers of bone remodeling (alkaline phosphatase [ALP] activity, carboxyterminal propeptide of type I procollagen [PICP], osteocalcin, hydroxyproline), whole bone parameters (ash content, bending moment), histomorphometry, and the populations of marrow osteoblastic and osteoclastic precursors by ex vivo cultures. The fall in plasma 25-dihydroxyvitamin [25(OH)D] in the 0D pigs indicated severe depletion of their vitamin D stores. However, they remained normocalcemic, were mildly hyperparathyroid after 2 months of vitamin D deprivation, and showed only a slight decrease in plasma calcitriol. The bone mineral content and bending moment of metatarsals decreased and they had increased osteoblastic (+59%, p < 0.05 0D vs. controls) and osteoclastic (+31%, p < 0.1 0D vs. controls) surfaces. This was not paralleled by increased bone turnover, because plasma hydroxyproline and ALP were unchanged and PICP and osteocalcin were decreased. The adherent fraction of bone marrow cells showed a great increase in the number of total stromal colony-forming units (CFU-F; +93%, p < 0.05 0D vs. controls) and in the percent of ALP(+) CFU-F (+58%, p < 0.01 0D vs. controls) in cultures from 0D pigs. More tartrate-resistant acid phosphatase-positive (TRAP(+)) multinucleated cells were generated in cultures of nonadherent marrow cells from 0D pigs, and the area of resorption was 345% greater than in controls. Thus, vitamin D deprivation caused only moderate hormonal changes in growing pigs fed a high-calcium diet, but affected their bone characteristics and greatly enhanced the pool of osteoblasts and osteoclasts by stimulating the commitment of their precursors in bone marrow.

Topics: Animals; Bone and Bones; Bone Remodeling; Calcium; Female; Hematopoietic Stem Cells; Immunohistochemistry; Osteoclasts; Stromal Cells; Swine; Vitamin D; Vitamin D Deficiency

A line of mice deficient in vitamin D binding protein (DBP) was generated by targeted mutagenesis to establish a model for analysis of DBP's biological functions in vitamin D metabolism and action. On vitamin D-replete diets, DBP-/- mice had low levels of total serum vitamin D metabolites but were otherwise normal. When maintained on vitamin D-deficient diets for a brief period, the DBP-/-, but not DBP+/+, mice developed secondary hyperparathyroidism and the accompanying bone changes associated with vitamin D deficiency. DBP markedly prolonged the serum half-life of 25(OH)D and less dramatically prolonged the half-life of vitamin D by slowing its hepatic uptake and increasing the efficiency of its conversion to 25(OH)D in the liver. After an overload of vitamin D, DBP-/- mice were unexpectedly less susceptible to hypercalcemia and its toxic effects. Peak steady-state mRNA levels of the vitamin D-dependent calbindin-D9K gene were induced by 1,25(OH)2D more rapidly in the DBP-/- mice. Thus, the role of DBP is to maintain stable serum stores of vitamin D metabolites and modulate the rates of its bioavailability, activation, and end-organ responsiveness. These properties may have evolved to stabilize and maintain serum levels of vitamin D in environments with variable vitamin D availability.

Topics: Animals; Bone Diseases; Calbindins; Calcifediol; Calcification, Physiologic; Gene Targeting; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney; Liver; Mice; Mice, Knockout; Parathyroid Hormone; RNA, Messenger; S100 Calcium Binding Protein G; Transcriptional Activation; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

To assess the influence of immobilization upon vitamin D status and bone mass in chronically hospitalized, disabled, elderly patients following stroke.. cross-sectional study.. Department of geriatric neurology in a Japanese hospital.. 129 chronically hospitalized, disabled, elderly stroke patients and 28 age-matched controls.. We observed a deficiency of both 1,25-dihydroxyvitamin D (1,25-[OH]2D; 24.3 pg/ml) and 25-hydroxyvitamin D concentrations (25-OHD; 11.7 ng/ml) in stroke patients compared with controls. A high serum ionized calcium (mean; 2.648 mEq/l) was an independent determinant of the Barthel index (66) and 1,25-[OH]2D. When the patients were categorized into three groups by 25-OHD level (deficient, insufficient and sufficient), there was no difference in the mean 1,25-[OH]2D levels. Parathyroid hormone levels were normal or low and did not correlate with 25-OHD. Serum bone turnover variables and bone mineral density (BMD) of the second metacarpal in patients were significantly decreased compared to control subjects. Independent determinants of BMD included Barthel index, 25-OHD and 1,25-[OH]2D.. 1,25-[OH]2D deficiency in immobilized stroke patients is not caused by substrate (25-OHD) deficiency but by hypercalcaemia. Immobilization-induced hypercalcaemia may inhibit parathyroid hormone secretion and thus 1,25-[OH]2D production, resulting in decreased BMD. Immobilization itself also may be responsible for decreased BMD. Exogenous 1,25-[OH]2D (calcitriol) rather than dietary vitamin D supplementation may be required in disabled elderly stroke patients who have a deficiency of 1,25-[OH]2D in order to prevent hip fractures, which frequently occur in this population.

Topics: Aged; Bone and Bones; Bone Density; Calcium; Cerebrovascular Disorders; Cross-Sectional Studies; Disabled Persons; Female; Hospitalization; Humans; Immobilization; Japan; Long-Term Care; Male; Parathyroid Hormone; Reference Values; Risk Factors; Vitamin D; Vitamin D Deficiency

Peak bone mass attained after skeletal growth is a major determinant of the risk of developing osteoporosis later in life, hence the importance of nutritional factors that contribute to bone mass gain during infancy and adolescence. An adequate supply of vitamin D is essential for normal bone homeostasis. This study was undertaken to determine what the levels are of 25-hydroxyvitamin D (25(OH)D) that may be considered desirable in children and to assess if normal children maintain these levels throughout the year. Vitamin D metabolites and parathyroid hormone (PTH) serum levels were measured in 21 children in March and October, prior to and after the administration of a daily supplement of 25(OH)D (40 microg for 7 consecutive days). There were inverse correlations between basal 25(OH)D levels and supplementation-induced changes in serum 1,25(OH)2D (r = 0.57, p < 0.05) and PTH (r = 0.41, p < 0.05). When basal levels of 25(OH)D were below 20 ng/ml, the supplement induced an increase in serum 1,25(OH)2D; with basal 25(OH)D under 10-12 ng/ml, the supplement also decreased serum PTH. The lowest serum level of 25(OH)D in 43 normal children studied in summer was 13 ng/ml. Those results suggested that the lowest limit for desirable levels of 25(OH)D in children was somewhere between 12 and 20 ng/ml. However, 31% of 51 normal children studied in winter had levels below 12 ng/ml, and 80% had levels lower than 20 ng/ml. Those children are likely to have suboptimal bioavailability of vitamin D, which might hamper their achievement of an adequate peak bone mass. Since cutaneous synthesis of vitamin D is rather limited in winter, oral vitamin D supplementation should be considered.

Topics: Administration, Oral; Bone Density; Child; Cross-Sectional Studies; Female; Humans; Male; Osteoporosis; Parathyroid Hormone; Seasons; Surveys and Questionnaires; Vitamin D; Vitamin D Deficiency

Although sun protection is advocated for skin cancer prevention, sunlight is also important in generation of vitamin D in the skin. There is concern that sun protection may result in an abnormally low level of vitamin D.. To assess the risk of vitamin D deficiency in a sunlight-deprived population, we studied eight ambulatory patients with xeroderma pigmentosum (XP) who practiced intensive sun protection during a chemoprevention study of oral isotretinoin.. We surveyed the patients to determine the extent of sun protection and vitamin D intake and measured the serum levels of two vitamin D metabolites (25-hydroxyvitamin D [25-OHD] and 1,25-dihydroxyvitamin D [1,25-(OH)2D]), calcium, and parathyroid hormone during 6 years.. The patients all wore protective clothing and sunscreens when outdoors. Estimated mean vitamin D intake was normal. The mean values of serum 25-OHD were low normal, but 1,25-(OH)2D, calcium, ionized calcium and parathyroid hormone levels were normal. Lack of seasonal variation in serum 25-OHD indicated rigorous photoprotection.. Despite rigorous sun protection normal vitamin D levels can be maintained in ambulatory patients with XP.

Topics: Administration, Oral; Adolescent; Adult; Ambulatory Care; Calcium; Chemoprevention; Dihydroxycholecalciferols; Female; Follow-Up Studies; Humans; Isotretinoin; Keratolytic Agents; Male; Middle Aged; Parathyroid Hormone; Protective Clothing; Risk Factors; Seasons; Skin; Sunlight; Sunscreening Agents; Vitamin D; Vitamin D Deficiency; Xeroderma Pigmentosum

The hormonal form of vitamin D appears to be a physiological regulator of the epidermogenesis. While its differentiation-promoting effect is well accepted, there are conflicting reports of its action on keratinocyte proliferation. This study evaluates the specific changes induced by vitamin D treatment in the epidermis of rats nutritionally deprived of vitamin D by cell size analysis, acridine orange flowcytometry, and the immunohistochemical detection of proteins related to the different stages of differentiation (epidermal calcium binding protein and suprabasal keratins recognized by KL1 antibody) The total keratinocyte and isolated keratinocyte subpopulations were studied. Vitamin D deficiency was associated in the total population with a lower percentage of actively proliferating cells and with a lack of differentiation markers. Study of the isolated cell populations demonstrated, however, that small cells were actively proliferating, whereas they were mainly in the resting stage in the normal epidermis. Treatment with vitamin D dramatically increased cell proliferation and stimulated the appearance of differentiation markers. Some of the observed effects, such as an increase in proliferation and the appearance of epidermal calcium binding protein, were due to the normalisation of the vitamin D deficiency-induced hypocalcemia, whereas the expression of suprabasal keratins was directly dependent on vitamin D. We conclude that the action of vitamin D on the epidermis is associated with increases in both proliferation and differentiation of keratinocytes. Vitamin D itself and its resulting action on calcium homeostasis appear to contribute to the observed effects.

Topics: Animals; Body Weight; Calcium; Calcium-Binding Proteins; Cell Cycle; Cell Differentiation; Cell Division; Cell Size; Epidermal Cells; Epidermis; Flow Cytometry; Hydroxycholecalciferols; Keratinocytes; Male; Rats; Rats, Wistar; Vitamin D; Vitamin D Deficiency