Incremental cholecalciferol supplementation up to 15 µg/d throughout winter at 51-55° N has no effect on biomarkers of cardiovascular risk in healthy young and older adults.

Two separate, identical, double-blind, randomized, placebo-controlled intervention studies were carried out in the south and north of Ireland (51-55°N). Men and women aged 20-40 y (n = 202) and ≥64 y (n = 192) received cholecalciferol at doses of 0 (P), 5 (D3-5), 10 (D3-10), or 15 (D3-15) µg/d (0-600 IU) during wintertime. Serum 25-hydroxyvitamin D [s25(OH)D], intact parathyroid hormone, systolic and diastolic blood pressure, fasting lipids, glucose and insulin, HOMA-IR, high-sensitivity CRP, matrix metalloproteinase-9, and its inhibitor (tissue inhibitor metalloproteinase-1) were measured at baseline (October) and 22 wk later at endpoint (March). Vitamin D receptor Fok I and Taq I genotypes were analyzed and dietary intakes of vitamin D and calcium were assessed. In young adults, s25(OH)D decreased from baseline to endpoint (P < 0.001), except in the D3-15 group, who maintained the baseline concentration of ~70 nmol/L. Older adults had lower s25(OH)D at baseline (median, 54.2 nmol/L) and concentrations increased in the D3-10 and D3-15 groups (P < 0.001). There were no significant effects of supplementation on cardiovascular disease (CVD) risk biomarkers in either age group. Fasting glucose and total and HDL cholesterol were lower (P < 0.05) in older adults with the Fok 1 ff genotype than in those with FF or Ff. Putative effects of vitamin D on cardio-metabolic health will only be evident at higher intakes than the current RDA and possibly in individuals at particular risk of low s25(OH)D and/or CVD risk.

Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults.

There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity. Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation, results have been equivocal. The aim of this randomised, placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol (25(OH)D) response to 15 µg cholecalciferol per d in healthy young and older Irish adults. A total of 110 young adults (20-40 years) and 102 older adults ( ≥ 64 years) completed the 22-week intervention with >85 % compliance. The change in 25(OH)D from baseline was calculated. Anthropometric measures of adiposity taken at baseline included height, weight and waist circumference (WC), along with skinfold thickness measurements to estimate fat mass (FM). FM was subsequently expressed as FM (kg), FM (%), FM index (FMI (FM kg/height m2)) and as a percentage ratio to fat-free mass (FFM). In older adults, vitamin D status was inversely associated with BMI (kg/m2), WC (cm), FM (kg and %), FMI (kg/m2) and FM:FFM (%) at baseline (r - 0·33, - 0·36, - 0·33, - 0·30, - 0·33 and - 0·27, respectively, all P values < 0·01). BMI in older adults was also negatively associated with the change in 25(OH)D following supplementation (ß - 1·27, CI - 2·37, - 0·16, P = 0·026); however, no such associations were apparent in younger adults. Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes.

Maintenance of wintertime vitamin D status with cholecalciferol supplementation is not associated with alterations in serum cytokine concentrations among apparently healthy younger or older adults.

Epidemiological studies have shown that low vitamin D status results in impaired immune function and is associated with the prevalence of autoimmune and inflammatory conditions. Vitamin D supplementation has been shown to reduce circulating concentrations of inflammatory markers in such conditions. However, the possible beneficial effect of vitamin D supplementation in the general population, particularly for those individuals living at high latitudes where hypovitaminosis D is common during wintertime, remains unclear. The aim of this study was to assess the effect of vitamin D supplementation using doses of 5, 10, and 15 µg/d cholecalciferol (D3) compared with placebo on cytokine concentrations throughout winter in apparently healthy younger (aged 20-40 y) and older (aged ≥64 y) adults. A total of 211 younger and 202 older adults completed the 22-wk intervention (from October to March) with >85% compliance. Serum concentrations of 25-hydroxycholecalciferol [25(OH)D3], high sensitivity C-reactive protein, IL-6, IL-10, soluble CD40 ligand, TGFß, TNFα, and fibrinogen were measured using ELISA. 25(OH)D3 concentrations significantly decreased in the placebo and 5 and 10/d µg D3 groups in the younger cohort and in the placebo group in the older cohort. Whereas 15 µg/d D3 supplementation maintained 25(OH)D3 concentrations in the younger cohort (baseline, 75.9 nmol/L; postintervention, 69.0 nmol/L) and significantly increased concentrations in the older cohort (baseline, 55.1 nmol/L; postintervention, 73.9 nmol/L), it had no significant effect on cytokine concentrations (ANCOVA, P > 0.05). The long-term effects of low vitamin D status remain to be elucidated and optimization of vitamin D status in otherwise healthy individuals may potentially have lasting beneficial effects on the immune system.

Cholecalciferol supplementation throughout winter does not affect markers of bone turnover in healthy young and elderly adults.

Although there have been several studies of the effect of vitamin D status on bone turnover in the elderly, the findings are unclear, and, furthermore, to date very few have investigated this in young adults. The objective of these randomized, placebo-controlled, double-blind, 2-center intervention studies was to investigate the effect of cholecalciferol supplementation (0, 5, 10, and 15 microg cholecalciferol/d) throughout winter time on indices of vitamin D status and bone turnover in young (aged 20-40 y; n = 215) and elderly (aged > or = 64 y; n = 204) adults, with relatively high mean calcium intakes of 976 and 874 mg/d, respectively. Fasting serum concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, bone-specific alkaline phosphatase, and carboxyterminal collagen crosslinks were measured by enzyme immunoassays at baseline and endpoint. Fok I and Taq I vitamin D receptor (VDR) genotypes were determined by real-time PCR. Endpoint serum 25(OH)D increased (P < 0.0001) in a dose-related manner with increasing supplemental cholecalciferol (up to 15 microg/d) in 20-40-y olds and up to 10 microg/d in > or = 64-y olds. Endpoint serum PTH was lower (P < 0.05) in the 3 cholecalciferol-supplemented groups compared with that in the placebo group in > or = 64-y olds, but cholecalciferol supplementation did not affect other markers in either cohort and there was no significant interaction with VDR genotype. In conclusion, cholecalciferol supplementation alone throughout winter did not affect bone turnover markers in apparently healthy young and elderly adults, even when stratified by VDR genotype.

Vitamin D deficiency and insufficiency in pregnant women: a longitudinal study.

Maternal vitamin D insufficiency is associated with childhood rickets and longer-term problems including schizophrenia and type 1 diabetes. Whilst maternal vitamin D insufficiency is common in mothers with highly pigmented skin, little is known about vitamin D status of Caucasian pregnant women. The aim was to investigate vitamin D status in healthy Caucasian pregnant women and a group of age-matched non-pregnant controls living at 54-55 degrees N. In a longitudinal study, plasma 25-hydroxyvitamin D (25(OH)D) was assessed in ninety-nine pregnant women at 12, 20 and 35 weeks of gestation, and in thirty-eight non-pregnant women sampled concurrently. Plasma 25(OH)D concentrations were lower in pregnant women compared to non-pregnant women (P < 0.0001). Of the pregnant women, 35, 44 and 16 % were classified as vitamin D deficient (25(OH)D < 25 nmol/l), and 96, 96 and 75 % were classified as vitamin D insufficient (25(OH)D < 50 nmol/l) at 12, 20 and 35 weeks gestation, respectively. Vitamin D status was higher in pregnant women who reported taking multivitamin supplements at 12 (P < 0.0001), 20 (P = 0.001) and 35 (P = 0.001) weeks gestation than in non-supplement users. Vitamin D insufficiency is evident in pregnant women living at 54-55 degrees N. Women reporting use of vitamin D-containing supplements had higher vitamin D status, however, vitamin D insufficiency was still evident even in the face of supplement use. Given the potential consequences of hypovitaminosis D on health outcomes, vitamin D supplementation, perhaps at higher doses than currently available, is needed to improve maternal vitamin D nutriture.

Estimation of the dietary requirement for vitamin D in free-living adults >=64 y of age.

BACKGROUND: Older adults may be more prone to developing vitamin D deficiency than younger adults. Dietary requirements for vitamin D in older adults are based on limited evidence. OBJECTIVE: The objective was to establish the dietary intake of vitamin D required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above various cutoffs between 25 and 80 nmol/L during wintertime, which accounted for the effect of summer sunshine exposure and diet. DESIGN: A randomized, placebo-controlled, double-blind, 22-wk intervention was conducted in men and women aged >/=64 y (n = 225) at supplemental levels of 0, 5, 10, and 15 microg vitamin D(3)/d from October 2007 to March 2008. RESULTS: Clear dose-related increments (P < 0.0001) in serum 25(OH)D were observed with increasing supplemental vitamin D(3) intakes. The slope of the relation between total vitamin D intake and serum 25(OH)D was 1.97 nmol . L(-1) . microg intake(-1). The vitamin D intake that maintained serum 25(OH)D concentrations >25 nmol/L in 97.5% of the sample was 8.6 microg/d. Intakes were 7.9 and 11.4 microg/d in those who reported a minimum of 15 min daily summer sunshine exposure or less, respectively. The intakes required to maintain serum 25(OH)D concentrations of >37.5, >50, and >80 nmol/L in 97.5% of the sample were 17.2, 24.7, and 38.7 microg/d, respectively. CONCLUSION: To ensure that the vitamin D requirement is met by the vast majority (>97.5%) of adults aged >/=64 y during winter, between 7.9 and 42.8 microg vitamin D/d is required, depending on summer sun exposure and the threshold of adequacy of 25(OH)D. This trial was registered at http://www.controlled-trials.com/ISRCTN20236112 as ISRCTN registration no. ISRCTN20236112.

Estimation of the dietary requirement for vitamin D in healthy adults.

BACKGROUND: Knowledge gaps have contributed to considerable variation among international dietary recommendations for vitamin D. OBJECTIVE: We aimed to establish the distribution of dietary vitamin D required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above several proposed cutoffs (ie, 25, 37.5, 50, and 80 nmol/L) during wintertime after adjustment for the effect of summer sunshine exposure and diet. DESIGN: A randomized, placebo-controlled, double-blind 22-wk intervention study was conducted in men and women aged 20-40 y (n = 238) by using different supplemental doses (0, 5, 10, and 15 microg/d) of vitamin D(3) throughout the winter. Serum 25(OH)D concentrations were measured by using enzyme-linked immunoassay at baseline (October 2006) and endpoint (March 2007). RESULTS: There were clear dose-related increments (P < 0.0001) in serum 25(OH)D with increasing supplemental vitamin D(3). The slope of the relation between vitamin D intake and serum 25(OH)D was 1.96 nmol x L(-1) x microg(-1) intake. The vitamin D intake that maintained serum 25(OH)D concentrations of >25 nmol/L in 97.5% of the sample was 8.7 microg/d. This intake ranged from 7.2 microg/d in those who enjoyed sunshine exposure, 8.8 microg/d in those who sometimes had sun exposure, and 12.3 microg/d in those who avoided sunshine. Vitamin D intakes required to maintain serum 25(OH)D concentrations of >37.5, >50, and >80 nmol/L in 97.5% of the sample were 19.9, 28.0, and 41.1 microg/d, respectively. CONCLUSION: The range of vitamin D intakes required to ensure maintenance of wintertime vitamin D status [as defined by incremental cutoffs of serum 25(OH)D] in the vast majority (>97.5%) of 20-40-y-old adults, considering a variety of sun exposure preferences, is between 7.2 and 41.1 microg/d.