Siobhan Muldowney

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.

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.

Vitamin D status of Irish adults: findings from the National Adult Nutrition Survey

Previous national nutrition surveys in Irish adults did not include blood samples; thus, representative serum 25-hydroxyvitamin D (25(OH)D) data are lacking. In the present study, we characterised serum 25(OH)D concentrations in Irish adults from the recent National Adult Nutrition Survey, and determined the impact of vitamin D supplement use and season on serum 25(OH)D concentrations. Of the total representative sample (n 1500, aged 18+ years), blood samples were available for 1132 adults. Serum 25(OH)D was measured via immunoassay. Vitamin D-containing supplement use was assessed by questionnaire and food diary. Concentrations of serum 25(OH)D were compared by season and in supplement users and non-users. Year-round prevalence rates for serum 25(OH)D concentration < 30, < 40, < 50 and < 75 nmol/l were 6.7, 21.9, 40.1 and 75.6 %, respectively (11.1, 31.1, 55.0 and 84.0 % in winter, respectively). Supplement users had significantly higher serum 25(OH)D concentrations compared to non-users. However, 7.5 % of users had winter serum 25(OH)D < 30 nmol/l. Only 1.3 % had serum 25(OH)D concentrations >125 nmol/l. These first nationally representative serum 25(OH)D data for Irish adults show that while only 6.7 % had serum 25(OH)D < 30 nmol/l (vitamin D deficiency) throughout the year, 40.1 % had levels considered by the Institute of Medicine as being inadequate for bone health. These prevalence estimates were much higher during winter time. While vitamin D supplement use has benefits in terms of vitamin D status, at present rates of usage (17.5 % of Irish adults), it will have only very limited impact at a population level. Food-based strategies, including fortified foods, need to be explored.

Vitamin D and cardiometabolic health: a review of the evidence.

The cardiometabolic syndrome (MetS) is a clustering of related metabolic abnormalities including abdominal adiposity, insulin resistance, hypertension, dyslipidaemia and increased inflammatory and thrombotic markers, which is linked to increased risk of type 2 diabetes, CVD and overall mortality. Several cross-sectional and prospective studies have shown an association between low vitamin D status, as indicated by concentrations of serum 25-hydroxyvitamin D (s25(OH)D), and increased prevalence of the MetS and individual CVD risk factors. These epidemiological observations are supported by mechanistic studies but experimental data are limited. The available data from intervention studies are largely confounded as most vitamin D supplementation trials were mainly carried out to explore the role of Ca in CVD and include Ca in the treatment arms. Inadequate consideration of seasonal effects on s25(OH)D concentrations is also a common design flaw in most studies. Further complications arise from shared risk factors such as adiposity and ageing, which predispose individuals to exhibit both a more pronounced risk profile and relatively lower s25(OH)D concentrations. In conclusion, while epidemiological associations are promising and a rationale for low vitamin D status as a potentially modifiable risk factor for CVD is supported by mechanistic data, suitable experimental data from appropriately designed trials are just beginning to emerge. As yet, this body of literature is too immature to draw firm conclusions on the role of vitamin D in CVD prevention. Carefully controlled vitamin D trials in well-described population groups using intervention doses that are titrated against target s25(OH)D concentrations could yield potentially valuable outcomes that may have a positive impact on CVD risk modification.

Relationships between vitamin D status and cardio-metabolic risk factors in young European adults.

Background/Aims: To explore associations between vitamin D and cardiovascular disease risk factors in young European adults. Methods: This was a cross-sectional analysis of serum 25-hydroxyvitamin D [s25(OH)D], intact parathyroid hormone (iPTH) and biomarkers of cardiovascular disease risk in 195 healthy 20- to 40-year-olds (109 women) with a BMI between 27.5 and 32.5 from Iceland (64°N; n = 82), Ireland (51°N; n = 37) and Spain (42°N; n = 76) during mid-late winter. Results: The median s25(OH)D was 52.8 nmol/l (IQR 38.1–69.9) or 21.1 ng/ml (IQR 15.2–28.0) with a latitude-dependent gradient (p ≤ 0.0001): Iceland, 41.7 nmol/l (IQR 32.7–54.2) or 16.7 ng/ml (IQR 13.1–21.7); Ireland, 52.9 nmol/l (IQR 35.3–68.6) or 21.2 ng/ml (IQR 14.1–27.4), and Spain, 67.1 nmol/l (IQR 47.1–87.1) or 26.8 ng/ml (IQR 18.8–34.8). Eleven percent of Icelandic participants had s25(OH)D concentrations <25 nmol/l (10 ng/ml) and 66% of Icelandic, 43% of Irish, and 30% of Spanish volunteers had concentrations <50 nmol/l (20 ng/ml), respectively. Overall, 17% met 3 or more of the NCEP/ATP III criteria for cardio-metabolic syndrome (MetS). Participants in the lowest third of s25(OH)D [≤42.5 nmol/l (17 ng/ml)] were more likely to have MetS (OR 2.49, p = 0.045) and elevated TAG (OR 3.46, p = 0.019). Individuals with iPTH concentrations in the lowest third [2.34 pmol/l (22.2 pg/ml)] were more likely to have elevated fasting TAG (OR 4.17, p = 0.039), insulin (OR 3.15, p = 0.029) and HOMA-IR (OR 2.15, p = 0.031), and they were less likely to have elevated IL-6 (OR 0.24, p = 0.003). Conclusion: There were interactions between s25(OH)D, iPTH and cardio-metabolic risk factors which, given the increasing prevalence of overweight and obesity and a low vitamin D status among adults, require randomised controlled vitamin D intervention studies in overweight persons.

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.

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.

No effect of vitamin D supplementation on circulating concentrations of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in adults aged 20–40 and ≥64 years

Tissue matrix metalloproteinases participate in extracellular matrix remodelling and degradation. Increased expression of MMP-9 and its inhibitor TIMP-1 are linked to unfavourable cardiovascular conditions, including inflammatory damage leading to increased plaque instability. Vitamin D insufficiency is associated with higher MMP-9 concentrations, while vitamin D supplementation has been shown to decrease circulating MMP-9 and TIMP-1 concentrations in vitamin D-deficient adults. The effect of vitamin D supplementation (0, 5, 10 and 15mg cholecalciferol/d) on MMP-9 and TIMP-1 concentrations was investigated in two randomised placebo-controlled double-blind 22-week intervention studies in men and women aged 20–40 years (n 215; during winter 2006–7) and ‡ 64 years (n 215; during winter 2007–8) from Cork and Coleraine. Fasting serum levels of MMP-9, TIMP-1 and 25-hydroxyvitamin D (25(OH)D) were measured by ELISA at baseline and end point.