Decreased serum levels of 1,25-(OH)2 vitamin D during 1 year of sunlight deprivation in the Antarctic

French Antarctic territories harbor bases that are devoted to scientific and technical work. Living and working conditions during 1-year sojourns in such an environment are quite acceptable, but the confinement and the drop in ultraviolet B radiation exposure during winter months raise the problem of preservation of normal vitamin D status. Seasonal variations in 25-hydroxyvitamin D [25(OH)D] levels have been well documented, but the effect of sunshine deprivation on 1,25 dihydroxyvitamin D [1,25(OH)₂D] levels is quite controversial. The aim of this study was to address this question under the exceptional conditions of lack of sunshine exposure. Fifteen male Caucasian subjects participating in a 1-year mission in Antarctica were investigated. They were subjected to seven blood samplings, one before and six during their sojourn. Serum levels of 25(OH)D, 1,25(OH)₂D, osteocalcin, and ICTP were measured. We found that levels of 25(OH)D and 1,25(OH)₂D significantly decreased in these subjects during the mission, minimum levels being observed 10 months after their departure from France. ICTP concentrations did not change throughout this study, but osteocalcin levels were found to be higher at the end of the sojourn than before departure, which could argue for the existence of bone remodeling changes. Further studies are now needed to fully investigate bone metabolism changes and to address the question of vitamin D supplementation during this kind of sojourn.     

Vitamin D status is not associated with inflammatory cytokine levels during experimental human endotoxaemia

Vitamin D has been shown to modulate innate immune responses in vitro and ex vivo; however, human in‐vivo data are lacking. At high latitudes, seasonal vitamin D deficiency is common due to alternating ultraviolet (UV)‐B radiation exposure. In the present study, we investigated whether levels of 25 hydroxyvitamin D₃ [25(OH)D₃] and its active metabolite 1,25 dihydroxyvitamin D₃ [1,25(OH)₂D₃] are subject to seasonal variation and whether plasma levels of these vitamin D metabolites correlate with the in‐vivo cytokine response during experimental human endotoxaemia [administration of lipopolysaccharide (LPS) in healthy volunteers]. Plasma levels of 25(OH)D₃ and 1,25(OH)₂D₃ were determined in samples obtained just prior to administration of an intravenous bolus of 2 ng/kg LPS (derived from Escherichia coli O:113) in 112 healthy male volunteers. In the same subjects, plasma levels of the inflammatory cytokines tumour necrosis factor (TNF)‐α, interleukin (IL)‐6 and IL‐10 were analysed serially after endotoxin administration. Plasma levels of 1,25(OH)₂D₃, but not 25(OH)D₃, were subject to significant seasonal variation, with lower levels in autumn and winter. 25(OH)D₃ and 1,25(OH)₂D₃ levels did not correlate with plasma cytokine responses. Furthermore, 25(OH)D₃ deficient subjects (< 50 nmol/l) displayed an identical cytokine response compared with sufficient subjects. In conclusion, plasma levels of vitamin D are not correlated with the LPS‐induced TNF, IL‐6 and IL‐10 cytokine response in humans in vivo. These findings question the direct role of vitamin D in modulation of the innate immune response.     

The D‐vitamin metabolite 1,25(OH)2D in serum is associated with disease activity and Anti‐Citrullinated Protein Antibodies in active and treatment naïve,early Rheumatoid Arthritis Patients

Rationale

Sufficient levels of vitamin D seem to be essential for proper immune function, and low levels might be associated to disease activity in Rheumatoid Arthritis (RA ). Most studies investigate only 25OHD and not the physiologically active vitamin D metabolite, 1,25(OH )₂D.

Objective

To investigate associations between serum level of vitamin D metabolites and disease activity parameters in 160 inflammatory active and treatment naïve early RA patients. Serum level of vitamin D metabolites (25OHD ₂, 25OHD ₃ and 1,25(OH )₂D) was measured by isotope dilution mass spectrometry and radio‐immunoassays at baseline. Disease characteristics were gender, number of tender joints, number of swollen joints, DAS 28‐CRP , HAQ , VAS ‐scores, CRP , erosive status (Total Sharp Score; TSS ), ACPA and IgM‐RF ‐status. Associations were evaluated using Spearman's and Wilcoxon rank‐sum tests. The study was registered in clinical trials; trial registration number: NCT 00209859.

Findings

Statistically significant inverse associations were found between the active metabolite 1,25(OH )₂D and DAS 28‐CRP (P  = 0.004, rho = −0.23), HAQ (P  = 0.005, rho = −0.22), CRP (P  = 0.001, rho = −0.25), VAS _{patient‐pain} (P  = 0.008, rho = −0.21), and a positive association was found to ACPA ‐status (P  = 0.04).

Conclusion

The vitamin D metabolite 1,25(OH )₂D was inversely associated with disease activity and positively associated with ACPA in treatment naïve and inflammatory active early RA . The results indicate that in RA , both the degree of inflammatory activity, and the diagnostic sensitivity and specificity might affect—or might be affected by the level of vitamin 1,25(OH )₂D.

     

Inflammation and vitamin D: the infection connection

Introduction

Inflammation is believed to be a contributing factor to many chronic diseases. The influence of vitamin D deficiency on inflammation is being explored but studies have not demonstrated a causative effect.

Methods

Low serum 25(OH)D is also found in healthy persons exposed to adequate sunlight. Despite increased vitamin D supplementation inflammatory diseases are increasing. The current method of determining vitamin D status may be at fault. The level of 25(OH)D does not always reflect the level of 1,25(OH)2D. Assessment of both metabolites often reveals elevated 1,25(OH)2D, indicating abnormal vitamin D endocrine function.

Findings

This article reviews vitamin D's influence on the immune system, examines the myths regarding vitamin D photosynthesis, discusses ways to accurately assess vitamin D status, describes the risks of supplementation, explains the effect of persistent infection on vitamin D metabolism and presents a novel immunotherapy which provides evidence of an infection connection to inflammation.

Conclusion

Some authorities now believe that low 25(OH)D is a consequence of chronic inflammation rather than the cause. Research points to a bacterial etiology pathogenesis for an inflammatory disease process which results in high 1,25(OH)2D and low 25(OH)D. Immunotherapy, directed at eradicating persistent intracellular pathogens, corrects dysregulated vitamin D metabolism and resolves inflammatory symptoms.     

Rapid effect of prednisolone on serum 1,25-dihydroxycholecalciferol levels in hypercalcemic sarcoidosis

We have studied a hypercalcemic patient with sarcoidosis and advanced renal failure. Bone biopsy and urinary cAMP excretion indicated suppression of parathyroid function. 1,25(OH)2D levels were moderately elevated and dropped to low normal levels during prednisolone treatment. Discontinuation of prednisolone treatment caused deterioration of renal function and hypercalcemia, 1,25(OH)2D serum levels being within the normal range. Our data demonstrate the rapid speed at which prednisolone causes a drop in serum 1,25(OH)2D level. Since hypercalcemia was observed both during periods of hypercalciuria and normal serum 1,25(OH)2D levels, increased sensitivity to active vitamin D seems likely. There was no significant correlation between 25(OH)D, 24,25(OH)2D or 25,26(OH)2D. Furthermore there was no correlation between any of these three metabolites and either 1,25(OH)2D or serum calcium.     

Anti-adipogenic effects of 1,25-dihydroxyvitamin D3 are mediated by the maintenance of the wingless-type MMTV integration site/β-catenin pathway

1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D, was found to have anti-adipogenic activity, however, its mechanism of action has not been fully elucidated. In this study, 3T3-L1 preadipocytes were differentiated in the presence and absence of 1,25(OH)2D3, and the expression of the genes and proteins of the wingless-type MMTV integration site (WNT)/β-catenin pathway were analyzed. While the expression of the members of the WNT/β-catenin pathway were significantly downregulated during the adipogenesis of untreated 3T3-L1 cells, 1,25(OH)2D3 treatment was found to maintain the WNT/β-catenin pathway. Among the members of the WNT/β-catenin pathway, the levels of WNT10B and disheveled (DVL)2 as well as the phosphorylation of glycogen synthase kinase (GSK)3β were maintained by 1,25(OH)2D3 treatment. The levels of nuclear β-catenin, which were downregulated during adipogenesis, were also maintained by 1,25(OH)2D3 treatment. The results of this study suggested that the anti-adipogenic effect of 1,25(OH)2D3 was mediated by the maintenance of the WNT/β-catenin pathway, which was normally downregulated during adipogenesis.     

The increase in skin 7-dehydrocholesterol induced by an hypocholesterolemic agent is associated with elevated 25-hydroxyvitamin D3 plasma level

Vitamin D3 is generated in skin by UV irradiation of 7-dehydrocholesterol (7-DEHC). Whether the 7-DEHC amount in skin affects vitamin D3 formation, and thereby the plasma level of 25-hydroxyvitamin D3 (25[OH]D3) is not known. In the present work we report on the influence on vitamin D and Ca metabolism of a new hypocholesterolemic agent, HCG-917 (0-2-[hydroxy-3-]N-(2-chlorophenyl)-N-piperazinyl-1-[propyl]-4-chloro-benz-aldoxim-hydrochloride) which inhibits 7-DEHC reductase and thereby increases skin 7-DEHC. Rats were treated with HCG 917 (0.3 and 5.0 mg/kg, orally) for 13 days. HCG 917 caused a dose-dependent decrease in cholesterol and concomitant accumulation of 7-DEHC in plasma and skin. In skin, 7-DEHC was: control: 1.05±0.20; HCG 917, 0.3 mg/kg: 1.41±0.22; HCG 917, 5.0 mg/kg: 2.35±0.35 mg/g. At a dose of 0.3 mg/kg, HCG 917 had no significant influence on the plasma level of neither 25(OH)D3 nor 1,25(OH)2D3. However, at a dose of 5.0 mg/kg, HCG 917 induced a significant increase in plasma 25(OH)D3 (control: 36.2±2.2; HCG 917 5.0 mg/kg: 57.6±6.5 nmol/l) and a slight but not significant rise in 1,25(OH)2D3. Calcium balance studies indicated that HCG 917 did not influence intestinal Ca absorption nor urinary Ca excretion. At a dose of 5.0 mg/kg HCG 917 slightly induced a decrease in total plasma Ca. In conclusion, HCG 917 treatment can induce a significant rise in skin 7-DEHC with an increase in plasma 25(OH)D3. These results suggest that variation in the skin level of 7-DEHC can directly influence the cutaneous production of vitamin D3 and thereby the vitamin D status of the organism.     

Long-term therapy with cyclosporin A does not influence serum concentrations of vitamin D metabolites in patients with multiple sclerosis

Summary Animal studies have shown that cyclosporin A (CyA) stimulates renal 25-hydroxyvitamin D₃ [25(OH)D₃]-1-hydroxylase activity; in contrast, studies in renal transplant recipients indirectly suggest that CyA reduces 1,25-dihydroxyvitamin D₃ [1,25 (OH)₂D₃] production. To clarify the effect of CyA on vitamin D metabolite concentrations, we measured parameters of calcium metabolism in 37 CyA-treated patients (median trough whole blood levels 171–222 ng/ml) with multiple sclerosis and initially normal kidney function. The patients participated in a randomized double-blind study to assess the efficacy of CyA in multiple sclerosis. An age- and sex-matched control group (n = 39) received azathioprine (Aza). Measurements were made at the end of a 2-year treatment period. The 1,25(OH)₂D₃ serum concentrations were not significantly different between the two groups, although they were numerically lower in CyA-treated patients [median (range), 28.4 pg/ml (7.8–85.9) vs 41.0 pg/ml (9.2–105.1) in Aza-treated patients]. The 25(OH)D₃ levels were comparable in both groups. There was no correlation between the 25(OH)D₃ and 1,25(OH)₂D₃ concentrations. The renal function in both groups was stable in the last 6 months of the study. At the end of the study period, the endogenous creatinine clearance was significantly lower in the CyA-treated group (85 ± 17 ml/min versus 99 ± 22 in the Aza-treated group, P < 0.05). The carboxyterminal parathyroid hormone (C-PTH) was within the normal range in both groups, although CyA-treated patients had significantly higher concentrations (P<0.01). The urinary excretion of mineral ions, cations and protein was similar in both groups. Our data suggest that long-term treatment with CyA does not cause clinically important alterations of vitamin D metabolism in humans. Subtle differences in the concentrations of 1,25(OH)₂D₃ and C-PTH between CyA- and Aza-treated patients result presumably from a slight impairment of renal function through CyA.Abbreviations CyA cyclosporin A - Aza azathioprine - 25(OH)D₃ 25-hydroxyvitamin D₃ - 1,25(OH)₂D₃ 1,25-dihydroxyvitamin D₃ - PTH parathyroid hormone - C-PTH carboxyterminal-PTH - AP alkaline phosphatase - Ccr endogenous creatinine clearance - gamma-GT gamma-glutamyltransferase     

Inhibition of tumor invasiveness by 1-alpha-25-dihydroxy-vitamin D coupled to a decline in protein kinase A activity and an increase in cytoskeletal organization

The capacity of cloned metastatic Lewis lung carcinoma cells (LLC-LN7) to invade through reconstituted basement membrane-coated filters was reduced after incubation with 1,25-dihydroxyvitamin D [1,25(OH)D]. This was observed at doses as low as 10 m 1,25(OH)D. The 1,25(OH)D-treated cells also had reduced levels of protein kinase A (PKA) activity and an increase in the level of polymerized actin, properties that have previously been demonstrated for less metastatic LLC variants. In addition, levels of the intermediate filament protein vimentin increased in 1,25(OH)D-treated LLC-LN7 tumor cells. In contrast, the levels and distribution of tubulin were not affected by 1,25(OH)D. The possibility that the decline in PKA activity was involved in the 1,25(OH)D modulation of the cytoskeletal components was evaluated. To accomplish this, LLC-7 transfectants whose PKA levels were blocked due to expression of a mutated PKA R subunit (LN7-REV) were incubated with 1,25(OH)D and their levels of F-actin were measured. In the absence of 1,25(OH)D treatment, the PKA-defective LN7-REV cells had an increased level of polymerized actin as compared to the wild-type LLC-LN7 cells. This level of F-actin was minimally affected by 1,25(OH)D, suggesting that PKA activity is required for 1,25(OH)D modulation of actin polymerization. These studies show that 1,25(OH)D can reduce PKA activity in tumor cells, and that this reduction in PKA may be an intermediate signal through which 1,25(OH)D affects the cytoskeleton and diminishes tumor invasiveness.     

Serum 25-hydroxyvitamin D levels in early and advanced breast cancer

BACKGROUND: Laboratory and epidemiological studies have implicated vitamin D deficiency in the pathogenesis of breast cancer. 1,25-Dihydroxyvitamin D (1,25(OH)(2)D) promotes differentiation and apoptosis, and potently inhibits proliferation of malignant breast epithelial cells in culture. Serum levels of 1,25(OH)(2)D are higher in normal women than in patients with primary breast cancer. AIM: To clarify the role of vitamin D in breast cancer progression by comparing the levels of serum vitamin D in patients with early and in those with advanced breast cancer. METHODS: Circulating levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and calcium were measured prospectively in 279 Caucasian women with invasive breast cancer, 204 women with early-stage disease and 75 women with locally advanced or metastatic disease. RESULTS: Patients with early-stage breast cancer had significantly higher circulating levels of 25(OH)D (p<0.005) and significantly lower PTH (p<0.001) levels than those with advanced disease. Calcium levels did not differ significantly (p = 0.74). CONCLUSION: Serum levels of 25(OH)D are significantly higher in patients with early-stage breast cancer than in those with locally advanced or metastatic disease.     

Inhibition of tropoelastin expression by 1,25-dihydroxyvitamin D3.

Elastin production is modulated by steroid hormones and is dependent on calcium. Because vitamin D3 is involved in the regulation of calcium metabolism and influences the expression of various extracellular matrix proteins, we investigated whether vitamin D3 influences tropoelastin expression. Three elastin-producing, bovine cell types, auricular chondroblasts, nuchal ligament fibroblasts and arterial smooth muscle cells, were treated with the principal active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), and with 24,25 dihydroxyvitamin D3 (24,25[OH]2D3). Tropoelastin levels in culture media and cell layers, as measured by an enzyme-linked immunoassay, decreased in a dose and exposure dependent manner after treatment with 1,25(OH)2D3; 24,25(OH)2D3 had no effect on tropoelastin production relative to solvent-treated controls. The maximal effective dose of 1,25(OH)2D3 was 10(-7) M for 48 hr, which resulted in a severalfold reduction of tropoelastin production, and decreased tropoelastin levels were detected at 8 hr after treatment. Reduction of tropoelastin protein production was paralleled by a decrease of equal magnitude in the steady-state levels of tropoelastin mRNA. Vitamin D3 metabolites had no effect on DNA or total protein synthesis. These results suggest that vitamin D3 may be an important modulator of elastin expression.     

Vitamin D Deficiency in Adult Sickle Cell Patients

Introduction

Vitamin D levels in adult black Americans with sickle cell disease (SCD) are comparatively lower than those found in the general population of black Americans. The objectives of this study were to examine the prevalence of Vitamin D deficiency (VDD) in adults with various subtypes of sickle cell disease and identify risk factors for vitamin D deficiency.

Parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentration in elderly patients

Summary In 50 patients of a geriatric hospital (33 women, aged 65–96 years, mean age 80 years, and 17 men, aged 68–91, mean age 78.3 years) calcium, albumin, phosphate, urea, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined. Forty patients with serum creatinine levels up to 1.4 mg/dl (124 mol/l) and 10 patients with creatinine concentrations 1.5 mg/dl (132mol/l) were evaluated. In patients with normal creatinine, a positive correlation was found between parathyroid hormone and age (r=0.41;P<0.01). In patients with elevated creatinine, negative correlations were found in 1,25-dihydroxyvitamin D and calcium (r=–0.724;P<0.05), 1,25dihydroxyvitamin D and creatinine (r=–0.79;P<0.01) and 1,25-dihydroxyvitamin D and phosphate (r=–0.87;P< 0.002). The best correlation was observed in patients with elevated serum creatinine for 1,25-dihydroxyvitamin D and phosphate (r=–0.91;P< 0.001). The results suggest that low levels of calcium and phosphate stimulate the 1-hydroxylation of 25-hydroxyvitamin D even in advanced age and that the calcium metabolism of these patients is frequently disturbed. Nineteen patients had low levels of 25-hydroxyvitamin D, indicating an insufficient supply of vitamin D or rare exposure to sunlight. In 49 of 50 patients, one ore more of the parameters of calcium metabolism were outside the normal range.Abbreviations 25-OH-D 25-hydroxyvitamin D - 1,25(OH)₂D 1,25-dihydroxyvitamin D - PTH parathyroid hormone Supported by the Deutsche Forschungsgemeinschaft (Schm 405–407)     

Prevalence of Vitamin D Deficiency in Korean Children Presenting with Nonspecific Lower-Extremity Pain

Purpose

Although interest in the role played by vitamin D in bone health is increasing, little is known about the role of this vitamin in musculoskeletal pain in children. This study aimed to assess the prevalence of vitamin D deficiency in children presenting with nonspecific lower extremity pains.

Materials and Methods

From 2011 to 2012, 183 children underwent evaluation for nonspecific lower-extremity pains. Patients with valid causes, such as fractures or transient synovitis, were excluded, as were those with underlying medical conditions, such as cerebral palsy and metabolic disease. Ultimately, 140 patients met the inclusion criteria. Levels of serum 25-hydroxy vitamin D [25-(OH)D], the ideal indicator of vitamin D status, were measured in these children.

Results

Eighty-seven boys (62.1%) and 53 girls (37.9%) were included. The mean age at presentation was 5.2 years (range, 2-15). Serum 25-(OH)D levels were <10 ng/mL in 5.7% of patients, 10 to <20 ng/mL in 51.4%, 20 to <30 ng/mL in 37.9%, and ≥30 ng/mL in only 5.0%. Most patients visited the hospital in the winter (41.4%) (summer, 12.9%), and serum 25-(OH)D levels were also lowest in the winter (17.2±5.5 ng/mL).

Conclusion

This study found a high prevalence of vitamin D deficiency or insufficiency in Korean children with nonspecific lower-extremity pains, indicating a positive association between vitamin D deficiency and growing pains. More attention should be directed toward vitamin D and its role in the optimization of bone health.     

Substrate-product relation of 1-hydroxylase activity in primary hyperparathyroidism

The synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)2D), is thought to be relatively insensitive to the serum concentration of its precursor, 25-hydroxyvitamin D (25-OH-D). We compared the effect of oral administration of 25-OH-D3 (50 micrograms per day for one month) on serum concentrations of calcium, phosphate, parathyroid hormone, 25-OH-D, and 1,25-(OH)2D in five healthy adults and in six patients with primary hyperparathyroidism. In normal adults the mean (+/- S.D.) serum level of 25-OH-D rose from 18 +/- 9 to 136 +/- 47 ng per milliliter; no significant changes were observed in the other serum levels. In contrast, comparable increases in the levels of circulating 25-OH-D in patients with primary hyperparathyroidism caused a consistent slight rise in serum calcium and phosphate levels, a partial suppression of parathyroid hormone, and a sharp increase in the level of 1,25-(OH)2D. During this period a significant positive correlation was found between serum concentrations of 25-OH-D and 1,25-(OH)2D (P less than 0.001). These results provide evidence that in patients with primary hyperparathyroidism, levels of circulating 1,25-(OH)2D may be more dependent on the prevailing serum concentrations of 25-OH-D than they are in normal adults.     

25-hydroxyvitamin D concentration, vitamin D intake and joint symptoms in postmenopausal women

Introduction

Low 25-hydroxyvitamin D (25(OH) D) concentrations have been associated with radiologic worsening of osteoarthritis in some reports. However, the results are mixed and few studies have evaluated associations between 25(OH) D concentrations and both total vitamin D intake and clinical joint symptoms.

Study design

Cross-sectional analyses of information from a subset of 1993 postmenopausal women obtained at baseline entry in the Women's Health Initiative Calcium plus Vitamin D clinical trial.

Main Outcome Measures

25(OH) D concentration, total vitamin D intake (diet plus supplements), presence and severity of joint pain and joint swelling.

Results

The 25(OH) D levels were commonly low with 53% having deficient (<50 nmol/L) and only 17% having sufficient (>72 nmol/L) levels. Joint pain (reported by 74%) and joint swelling (reported by 34%) were also commonly reported. 25(OH) D concentrations were modestly correlated with total vitamin D intake (R = 0.29, p < 0.0001); however, considerable variability in 25(OH) D concentrations for a given vitamin D intake was seen. In adjusted linear regression models, lower serum 25(OH) D concentrations were associated with higher average joint pain score (P = 0.01 for trend) with differences most apparent in the lowest 25(OH) D levels sextile.

Conclusions

Relatively low 25(OH) D levels and a high frequency of joint symptoms were common in this population of postmenopausal women. Total vitamin D intake was only modestly associated with 25(OH) D. Low serum 25(OH) D concentrations were associated with higher joint pain scores. These findings can inform the design of future intervention trials.     

1,25-Dihydroxyvitamin D3-Differentiated Human Promyelocytic Leukaemia Cells (HL-60) Can Kill Antibody-Coated Tumour Cells (K562)

The active metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), was tested for the ability to differentiate promyelocytic leukaemia cells (HL-60) and histiocytic lymphoma cells (U937) into cytotoxic effector cells against K562 leukaemia cells. A concentration of 10(-6) M 1,25(OH)2D3 differentiated HL-60 cells into substrate-adherent monocyte-like cells with cytolytic activity against antibody-coated K562 cells. These differentiated HL-60 cells were not able to lyse uncoated K562 cells in an 18-h Cr-release assay. Similar treatment of the U937 cells with 1,25(OH)2D3 did not make them cytolytic towards K562 cells. These data indicate that 1,25(OH)2D3 can differentiate HL-60 cells to mature monocytes with cytolytic activity against antibody-coated leukaemia cells.     

EMAS position statement: Vitamin D and postmenopausal health

Introduction

There is emerging evidence on the widespread tissue effects of vitamin D.

Aims

To formulate a position statement on the role of vitamin D in postmenopausal women.

Materials and methods

Literature review and consensus of expert opinion.

Results and conclusions

Epidemiological and prospective studies have related vitamin D deficiency with not only osteoporosis but also cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However the evidence is robust for skeletal but not nonskeletal outcomes where data from large prospective studies are lacking. The major natural source of vitamin D is cutaneous synthesis through exposure to sunlight with a small amount from the diet in animal-based foods such as fatty fish, eggs and milk. Vitamin D status is determined by measuring serum 25-hydroxyvitamin D [25(OH)D] levels. Optimal serum 25(OH)D levels are in the region of 30–90 ng/mL (75–225 nmol/L) though there is no international consensus. Levels vary according to time of the year (lower in the winter), latitude, altitude, air pollution, skin pigmentation, use of sunscreens and clothing coverage. Risk factors for low serum 25(OH)D levels include: obesity, malabsorption syndromes, medication use (e.g. anticonvulsants, antiretrovirals), skin aging, low sun exposure and those in residential care. Fortified foods do not necessarily provide sufficient amounts of vitamin D. Regular sunlight exposure (without sunscreens) for 15 min, 3–4 times a week, in the middle of the day in summer generate healthy levels. The recommended daily allowance is 600 IU/day increasing to 800 IU/day in those aged 71 years and older. Supplementation can be undertaken with either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) with monitoring depending on the dose used and the presence of concomitant medical conditions such as renal disease.