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Background: Evidence is limited and inconsistent regarding vitamin D and heart failure (HF) risk in people with type 2 diabetes (T2D), among whom vitamin D insufficiency or deficiency is common., Objectives: This study aimed to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with HF risk among individuals with T2D, in observational and Mendelian randomization (MR) frameworks., Methods: Observational analyses were performed among 15,226 T2D participants aged 40-72 y from the UK Biobank. HF incidence was ascertained through electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between serum 25(OH)D and HF risk among people with T2D. MR analyses were conducted among 11,260 unrelated participants with T2D. A weighted genetic risk score for genetically predicted 25(OH)D concentration was instrumented using 62 confirmed genome-wide variants., Results: The mean ± standard deviation of serum 25(OH)D was 43.4 ± 20.4 nmol/L. During a median follow-up of 11.3 y, 836 incident HF events occurred. Serum 25(OH)D was nonlinearly and inversely associated with HF and the decreasing risk tended to plateau at around 50 nmol/L. Comparing those with 25(OH)D <25 nmol/L, the multivariable-adjusted HR (95% CI) was 0.67 (0.54, 0.83) for participants with 25(OH)D of 50.0-74.9 nmol/L and was 0.71 (0.52, 0.98) for 25(OH)D >75 nmol/L. In MR analysis, each 7% increment in genetically predicted 25(OH)D was associated with 36% lower risk of HF among people with T2D (HR: 0.64, 95% CI: 0.41, 0.99)., Conclusions: Higher serum 25(OH)D was associated with lower HF risk among individuals with T2D and the MR analysis suggested a potential causal relationship. These findings indicate a role of maintaining adequate vitamin D status in the prevention of HF among individuals with T2D., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Evidence on the association between serum 25-hydroxyvitamin D [25(OH)D] and infections among patients with type 2 diabetes (T2D), a group susceptible to vitamin D deficiency and infections, is limited., Objectives: We aimed to examine this association in individuals with T2D, and to evaluate whether genetic variants in vitamin D receptor (VDR) would modify this association., Methods: This study included 19,851 participants with T2D from United Kingdom Biobank. Infections were identified by linkage to hospital inpatient and death registers. Negative binomial regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs), with adjustment of potential confounders., Results: In patients with T2D, the incidence rate of infections was 29.3/1000 person-y. Compared with those with 25(OH)D of 50.0-74.9 nmol/L, the multivariable-adjusted IRRs and 95% CIs of total infections, pneumonia, gastrointestinal infections, and sepsis were 1.44 (1.31, 1.59), 1.49 (1.27, 1.75), 1.47 (1.22, 1.78), and 1.41 (1.14, 1.73), respectively, in patients with 25(OH)D <25.0 nmol/L. Nonlinear inverse associations between 25(OH)D concentrations and the risks of total infections (P-overall < 0.001; P-nonlinear = 0.002) and gastrointestinal infections (P-overall < 0.001; P-nonlinear = 0.040) were observed, with a threshold effect at ∼50.0 nmol/L. The vitamin D-infection association was not modified by genetic variants in VDR (all P-interaction > 0.050)., Conclusions: In patients with T2D, lower serum 25(OH)D concentration (<50 nmol/L) was associated with higher risks of infections, regardless of genetic variants in VDR. Notably, nonlinear inverse associations between 25(OH)D concentrations and the risks of infections were found, with a threshold effect at ∼50.0 nmol/L. These findings highlighted the importance of maintaining adequate vitamin D in reducing the risk of infections in patients with T2D., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Prior studies on vitamin D and dementia outcomes yielded mixed results and had several important limitations., Objectives: We aimed to assess the associations of both serum vitamin D status and supplementation with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD) incidence., Methods: With a prospective cohort study design, we comprehensively assessed the associations of vitamin D and multivitamin supplementation, as well as vitamin D deficiency {25-hydroxyvitamin D [25(OH)D] <30 nmol/L}, and insufficiency [25(OH)D 30 to <50 nmol/L], with the 14-year incidence of all-cause dementia, AD, and VD in 269,229 participants, aged 55 to 69, from the UK Biobank., Results: Although 5.0% reported regular vitamin D use and 19.8% reported multivitamin use, the majority of participants exhibited either vitamin D deficiency (18.3%) or insufficiency (34.0%). However, vitamin D deficiency was less prevalent among users of vitamin D (6.9%) or multivitamin preparations (9.5%) than among nonusers (21.5%). Adjusted Cox regression models demonstrated 19% to 25% increased risk of all 3 dementia outcomes for those with vitamin D deficiency [hazard ratio (HR) 95% confidence interval (CI)]: 1.25 (1.16, 1.34) for all-cause dementia; 1.19 (1.07-1.31) for AD; 1.24 (1.08-1.43) for VD] and 10% to 15% increased risk of those with vitamin D insufficiency [HR (95% CI): 1.11 (1.05, 1.18) for all-cause dementia; 1.10 (1.02-1.19) for AD; 1.15 (1.03-1.29) for VD]. Regular users of vitamin D and multivitamins had 17% and 14% lower risk of AD [HR (95% CI): 0.83 (0.71, 0.98)] and VD [HR (95% CI): 0.86 (0.75, 0.98)] incidence, respectively., Conclusions: Although our findings indicate the potential benefits of vitamin D supplementation for dementia prevention, randomized controlled trials are essential for definitive evidence., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether 25(OH)D concentrations in children and female adults may be influenced by inflammation and thus require adjustment when estimating the population prevalence of vitamin D deficiency., Objectives: We examined correlations between inflammation biomarkers, CRP or alpha-1-acid glycoprotein (AGP), and serum 25(OH)D concentrations among preschool children (PSC; 6-59 mo) and nonpregnant females of reproductive age (FRA; 15-49 y)., Methods: We analyzed cross-sectional data from 6 nationally representative nutrition surveys (Afghanistan, Cambodia, Pakistan, UK, USA, and Vietnam) conducted among PSC (n = 9880) and FRA (n = 14,749) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Rank correlations between CRP or AGP and 25(OH)D concentrations were examined while taking into account complex survey design effects., Results: Among both PSC and FRA, correlations between inflammation and vitamin D biomarkers were weak and inconsistent across surveys. For PSC, correlation coefficients between CRP and 25(OH)D concentrations ranged from -0.04 to 0.08, and correlations between AGP and 25(OH)D ranged from 0.01 to 0.05. Correlation coefficients between CRP and 25(OH)D for FRA ranged from -0.11 to 0.14, and correlations between AGP and 25(OH)D concentrations ranged from -0.05 to 0.01., Conclusions: Based on the weak and inconsistent correlations between CRP or AGP and 25(OH)D, there is no rationale to adjust for these inflammation biomarkers when estimating population prevalence of vitamin D deficiency in PSC or FRA., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Vitamin D insufficiency is associated with risks of cardiovascular diseases (CVD) and cancer in observational studies, but evidence for benefits with vitamin D supplementation is limited., Objectives: To investigate the effects of vitamin D3 supplementation on CVD and cancer incidences., Methods: The study was a 5-year, randomized, placebo-controlled trial among 2495 male participants ≥60 years and post-menopausal female participants ≥65 years from a general Finnish population who were free of prior CVD or cancer. The study had 3 arms: placebo, 1600 IU/day, or 3200 IU/day vitamin D3. Follow-up was by annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person investigations. The primary endpoints were incident major CVD and invasive cancer. Secondary endpoints included the individual components of the primary CVD endpoint (myocardial infarction, stroke, and CVD mortality), site-specific cancers, and cancer death., Results: During the follow-up, there were 41 (4.9%), 42 (5.0%), and 36 (4.3%) major CVD events in the placebo, 1600 IU/d (compared with placebo: HR: 0.97; 95% CI: 0.63-1.49; P = 0.89), and 3200 IU/d (HR: 0.84; 95% CI: 0.54-1.31; P = 0.44) arms, respectively. Invasive cancer was diagnosed in 41 (4.9%), 48 (5.8%), and 40 (4.8%) participants in the placebo, 1600 IU/d (HR: 1.14; 95% CI: 0.75-1.72; P = 0.55), and 3200 IU/d (HR: 0.95; 95% CI: 0.61-1.47; P = 0.81) arms, respectively. There were no significant differences in the secondary endpoints or total mortality. In the subcohort, the mean baseline serum 25-hydroxyvitamin D concentration was 75 nmol/L (SD, 18 nmol/L). After 12 months, the concentrations were 73 nmol/L (SD, 18 nmol/L), 100 nmol/L (SD, 21 nmol/L), and 120 nmol/L (SD, 22 nmol/L) in the placebo, 1600 IU/d, and 3200 IU/d arms, respectively., Conclusions: Vitamin D3 supplementation did not lower the incidences of major CVD events or invasive cancer among older adults, possibly due to sufficient vitamin D status in most participants at baseline., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The prevalence of vitamin D deficiency (VDD) may be high in countries with abundant sun exposure year-round, but nationally representative data are lacking., Objective: We examined the prevalence and distribution of VDD by individual and environmental characteristics in a nationally representative sample of Colombian children, pregnant women, and adult nonpregnant women., Methods: Using the 2015 Colombian National Nutrition Survey, we defined VDD and low vitamin D (LVD) as serum 25-hydroxyvitamin D [25(OH)D] <30 nmol/L and <50 nmol/L, respectively, in 31,841 children aged 1 to <18 y, 1262 pregnant women, and 7170 nonpregnant women aged 18-49 y. Within each group, we compared VDD and LVD prevalence by levels of sociodemographic, anthropometric, and geographic factors using adjusted prevalence ratios with 95% CIs from multivariable Poisson regression., Results: The mean ± SE 25(OH)D was 65.1 ± 0.4 nmol/L. The prevalence ± SE of VDD and LVD was 3.1% ± 0.3% and 23.9% ± 0.8%, respectively. Pregnant women had the highest VDD prevalence at 6.7% ± 1.5%, whereas toddlers had the highest prevalence of LVD at 42.5% ± 1.8%. Altitude was one of the strongest correlates of VDD and LVD, with every 100 m above sea level related to a 4% increase in LVD prevalence (P <0.0001). Among children, VDD was positively associated with BMI-for-age Z >1 and maternal education. Among pregnant women, VDD was positively related to education. Among adult nonpregnant women, VDD was associated with BMI and household wealth., Conclusion: The prevalence of VDD and LVD in Colombian women and children is nonnegligible; some age groups are disproportionately affected. Altitude was a strong predictor of vitamin D status in this tropical setting. VDD was positively related to indicators of higher socioeconomic status., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Vitamin D is important for bone health; in 2014 it was the fifth most commonly ordered laboratory test among Medicare Part B payments., Objectives: The aim of this study was to describe vitamin D status in the US population in 2011-2014 and trends from 2003 to 2014., Methods: We used serum 25-hydroxyvitamin D data from NHANES 2011-2014 (n = 16,180), and estimated the prevalence at risk of deficiency (<30 nmol/L) or prevalence at risk of inadequacy (30-49 nmol/L) by age, sex, race and Hispanic origin, and dietary intake of vitamin D. We also present trends between 2003 and 2014., Results: In 2011-2014, the percentage aged ≥1 y at risk of vitamin D deficiency or inadequacy was 5.0% (95% CI: 4.1%, 6.2%) and 18.3% (95% CI: 16.2%, 20.6%). The prevalence of at risk of deficiency was lowest among children aged 1-5 y (0.5%; 95% CI: 0.3%, 1.1%), peaked among adults aged 20-39 y (7.6%; 95% CI: 6.0%, 9.6%), and fell to 2.9% (95% CI: 2.0%, 4.0%) among adults aged ≥60 y; the prevalence of at risk of inadequacy was similar. The prevalence of at risk of deficiency was higher among non-Hispanic black (17.5%; 95% CI: 15.2%, 20.0%) than among non-Hispanic Asian (7.6%; 95% CI: 5.9%, 9.9%), non-Hispanic white (2.1%; 95% CI: 1.5%, 2.7%), and Hispanic (5.9%; 95% CI: 4.4%, 7.8%) persons; the prevalence of at risk of inadequacy was similar. Persons with higher vitamin D dietary intake or who used supplements had lower prevalences of at risk of deficiency or inadequacy. From 2003 to 2014 there was no change in the risk of vitamin D deficiency; the risk of inadequacy declined from 21.0% (95% CI: 17.9%, 24.5%) to 17.7% (95% CI: 16.0%, 19.7%)., Conclusion: The prevalence of at risk of vitamin D deficiency in the United States remained stable from 2003 to 2014; at risk of inadequacy declined. Differences in vitamin D status by race and Hispanic origin warrant additional investigation., (Published by Oxford University Press on behalf of the American Society for Nutrition 2019.)

Background: Vitamin D deficiency is associated with renal progression in chronic kidney disease. Moreover, improvement of clinical outcomes after vitamin D supplementation has been reported in the diabetic and chronic kidney disease population., Objective: We investigated the association between renal hyperfiltration (RHF) and vitamin D status in a relatively healthy population., Design: Data were retrieved from the Korean NHANES, a nationwide population-based cross-sectional study from 2008 to 2015. Overall, 33,210 subjects with normal renal function were included in the final analysis. Severe vitamin D deficiency was defined as serum 25-hydroxyvitamin D concentration <10 ng/mL. RHF was defined as estimated glomerular filtration rate with residual in the >95th percentile after adjustment for age, sex, height, weight, and history of hypertension or diabetes., Results: The mean ± SD age of subjects was 48.1 ± 15.9 y, and the number of women was 18,779 (56.5%). Estimated glomerular filtration rate was negatively associated with serum 25-hydroxyvitamin D concentrations in multivariable linear regression analysis (β: -0.02; 95% CI: -0.02, -0.01; P < 0.001). Furthermore, 1637 (4.9%) subjects were categorized into the RHF group, and the prevalence of RHF was significantly higher in the severe vitamin D deficiency group than in the sufficiency group (5.8% compared with 5.0%, P < 0.001). In a multivariable logistic regression model, severe vitamin D deficiency was a significant risk factor for RHF (OR: 2.41; 95% CI, 1.72, 3.43; P < 0.001)., Conclusions: Severe vitamin D deficiency is significantly associated with increasing prevalence of RHF in a relatively healthy adult population.

Background: Associations of vitamin D with perinatal outcomes are inconsistent and few studies have considered the wider calcium metabolic system., Objectives: We aimed to explore functional vitamin D deficiency in pregnancy by investigating associations between vitamin D status, parathyroid hormone (PTH), and perinatal outcomes., Design: SCOPE (Screening for Pregnancy Endpoints) Ireland is a prospective cohort study of low-risk, nulliparous pregnant women. We measured serum 25-hydroxyvitamin D [25(OH)D] and PTH at 15 wk of gestation in 1754 participants., Results: Mean ± SD 25(OH)D was 56.6 ± 25.8 nmol/L (22.7 ± 10.3 ng/mL) and geometric mean (95% CI) PTH was 7.84 pg/mL (7.7, 8.0 pg/mL) [0.86 pmol/L (0.85, 0.88 pmol/L)]. PTH was elevated in 34.3% of women who had 25(OH)D <30 nmol/L and in 13.9% of those with 25(OH)D ≥75 nmol/L. Whereas 17% had 25(OH)D <30 nmol/L, 5.5% had functional vitamin D deficiency, defined as 25(OH)D <30 nmol/L with elevated PTH. Elevated mean arterial pressure (MAP), gestational hypertension, pre-eclampsia, and small-for-gestational-age (SGA) birth were confirmed in 9.2%, 11.9%, 3.8%, and 10.6% of participants, respectively. In fully adjusted regression models, neither low 25(OH)D nor elevated PTH alone increased the risk of any individual outcome. The prevalence of elevated MAP (19.1% compared with 9.7%) and SGA (16.0% compared with 6.7%) were highest (P < 0.05) in those with functional vitamin D deficiency compared with the reference group [25(OH)D ≥75 nmol/L and normal PTH]. The adjusted prevalence ratio (PR) and RR (95% CIs) for elevated MAP and SGA were 1.83 (1.02, 3.27) and 1.53 (0.80, 2.93), respectively. There was no effect of functional vitamin D deficiency on the risk of gestational hypertension (adjusted RR: 1.00; 95% CI: 0.60, 1.67) or pre-eclampsia (adjusted RR: 1.17; 95% CI: 0.32, 4.20)., Conclusion: The concept of functional vitamin D deficiency, reflecting calcium metabolic stress, should be considered in studies of vitamin D in pregnancy. The SCOPE pregnancy cohort is registered at http://www.anzctr.org.au as ACTRN12607000551493.

Background: A previous study indicated that 31% of the elderly in Taiwan have a vitamin D deficiency. Vitamin D adequacy has been associated with physical performance in the elderly., Objectives: The first aim of the current study was to identify the determinants for vitamin D deficiency. The second aim was to evaluate the association between vitamin D status and physical performance., Design: A total of 5664 community-dwelling participants aged ≥55 y were recruited since 2008. Plasma total 25-hydroxyvitamin D concentrations were originally determined by ELISA and calibrated to a chemiluminescence measurement. Physical performance was assessed by handgrip strength, the Short Physical Performance Battery, timed up and go, a 6-min walk test, and single-leg stands. Multiple linear regression and logistic regression were used to estimate the cross-sectional associations., Results: Vitamin D inadequacy (<50 nmol/L) was related to higher education (P-trend < 0.01), body mass index [(BMI; in kg/m 2 ) ORs (95% CIs) for ≥30 compared with 18.5 to <25 were 1.78 (1.14, 2.78) for men and 1.53 (1.11, 2.11) for women], and vegetable intake [fourth compared with first quartile, 1.58 (1.15, 2.18) for men and 2.38 (1.82, 3.12) for women]. Higher intakes of fish [fourth compared with first quartile, 0.44 (0.33, 0.59) for men and 0.27 (0.21, 0.36) for women] and milk [fourth compared with first quartile, 0.46 (0.31, 0.69) for men and 0.69 (0.49, 0.95) for women] were associated with lower risk of vitamin D inadequacy. Few subjects had 25-hydroxyvitamin D concentrations <30 nmol/L. Above that concentration, there was no dose-effect relation with physical performance except for single-leg stands., Conclusions: The factors associated with vitamin D inadequacy in Taiwan were higher education, higher BMI, and lower fish and milk intakes. No dose-effect relation existed between vitamin D concentration and physical performance except for single-leg stands. This study was registered at www.clinicaltrials.gov as NCT02677831., (© 2016 American Society for Nutrition.)

Background: Vitamin D deficiency impairs fertility in animal models, but the role of vitamin D in human fertility or treatment of infertility is less clear., Objective: We examined the association between circulating 25-hydroxyvitamin D [25(OH)D] concentrations and the outcome in women undergoing assisted reproduction technologies (ARTs)., Design: We randomly selected 100 women undergoing infertility treatment with ART enrolled in an ongoing prospective cohort study who underwent 168 treatment cycles. Serum 25(OH)D concentrations were measured in samples collected from women between days 3 and 9 of gonadotropin treatment. Generalized linear mixed models were used to evaluate the association of 25(OH)D concentrations with ART outcomes while adjusting for potential confounders and accounting for repeated treatment cycles per woman., Results: Median (range) serum 25(OH)D concentrations were 86.5 (33.5-155.5) nmol/L. Ninety-one percent of participants consumed multivitamins. Serum 25(OH)D concentrations were positively related to fertilization rate. The adjusted fertilization rate for women in increasing quartiles of serum 25(OH)D were 0.62 (95% CI: 0.51, 0.72), 0.53 (95% CI: 0.43, 0.63), 0.67 (95% CI: 0.56, 0.76), and 0.73 (95% CI: 0.63, 0.80), respectively (P-trend = 0.03). This association persisted when analyses were restricted to women with serum 25(OH)D between 50 and 125 nmol/L when models were further adjusted for season of blood draw and when analyses were restricted to the first treatment cycle. However, 25(OH)D concentrations were unrelated to probability of pregnancy (P-trend = 0.83) or live birth after ART (P-trend = 0.47)., Conclusion: Vitamin D may be associated with higher fertilization rates, but this apparent benefit does not translate into higher probability of pregnancy or live birth. This trial was registered at www.clinicaltrials.gov as NCT00011713., (© 2016 American Society for Nutrition.)

Background: Despite numerous animal studies that have illustrated the impact of additional vitamin D in the diet of hens on the resulting egg vitamin D content, the effect of the consumption of such eggs on vitamin D status of healthy individuals has not, to our knowledge, been tested., Objective: We performed a randomized controlled trial (RCT) to investigate the effect of the consumption of vitamin D-enhanced eggs (produced by feeding hens at the maximum concentration of vitamin D3 or serum 25-hydroxyvitamin D [25(OH)D3] lawfully allowed in feed) on winter serum 25(OH)D in healthy adults., Design: We conducted an 8-wk winter RCT in adults aged 45-70 y (n = 55) who were stratified into 3 groups and were requested to consume ≤2 eggs/wk (control group, in which status was expected to decline), 7 vitamin D3-enhanced eggs/wk, or seven 25(OH)D3-enhanced eggs/wk. Serum 25(OH)D was the primary outcome., Results: Although there was no significant difference (P > 0.1; ANOVA) in the mean preintervention serum 25(OH)D in the 3 groups, it was ∼7-8 nmol/L lower in the control group than in the 2 groups who consumed vitamin D-enhanced eggs. With the use of an ANCOVA, in which baseline 25(OH)D was accounted for, vitamin D3-egg and 25(OH)D3-egg groups were shown to have had significantly higher (P ≤ 0.005) postintervention serum 25(OH)D than in the control group. With the use of a within-group analysis, it was shown that, although serum 25(OH)D in the control group significantly decreased over winter (mean ± SD: -6.4 ± 6.7 nmol/L; P = 0.001), there was no change in the 2 groups who consumed vitamin D-enhanced eggs (P > 0.1 for both)., Conclusion: Weekly consumption of 7 vitamin D-enhanced eggs has an important impact on winter vitamin D status in adults. This trial was registered at clinicaltrials.gov as NCT02678364., (© 2016 American Society for Nutrition.)

Background: Temporal trends in the US population's vitamin D status have been uncertain because of nonstandardized serum 25-hydroxyvitamin D [25(OH)D] measurements., Objective: To accurately assess vitamin D status trends among those aged ≥12 y, we used data from the cross-sectional NHANESs., Design: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring 25(OH)D (sum of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3), calibrated to standard reference materials, was used to predict LC-MS/MS-equivalent concentrations from radioimmunoassay data (1988-2006 surveys; n = 38,700) and to measure LC-MS/MS concentrations (2007-2010 surveys; n = 12,446). Weighted arithmetic means and the prevalence of 25(OH)D above or below cutoff concentrations were calculated to evaluate long-term trends., Results: Overall, mean predicted 25(OH)D showed no time trend from 1988 to 2006, but during 2007-2010 the mean measured 25(OH)D was 5-6 nmol/L higher. Those groups who showed the largest 25(OH)D increases (7-11 nmol/L) were older, female, non-Hispanic white, and vitamin D supplement users. During 1988-2010, the proportions of persons with 25(OH)D <40 nmol/L were 14-18% (overall), 46-60% (non-Hispanic blacks), 21-28% (Mexican Americans), and 6-10% (non-Hispanic whites)., Conclusions: An accurate method for measuring 25(OH)D showed stable mean concentrations in the US population (1988-2006) and recent modest increases (2007-2010). Although it is unclear to what extent supplement usage compared with different laboratory methods explain the increases in 25(OH)D, the use of higher vitamin D supplement dosages coincided with the increase. Marked race-ethnic differences in 25(OH)D concentrations were apparent. These data provide the first standardized information about temporal trends in the vitamin D status of the US population., (© 2016 American Society for Nutrition.)

Background: Maternal vitamin D deficiency during pregnancy may affect fetal outcomes., Objective: The objective of this study was to examine whether maternal 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy affect fetal growth patterns and birth outcomes., Design: This was a population-based prospective cohort in Rotterdam, Netherlands in 7098 mothers and their offspring. We measured 25(OH)D concentrations at a median gestational age of 20.3 wk (range: 18.5-23.3 wk). Vitamin D concentrations were analyzed continuously and in quartiles. Fetal head circumference and body length and weight were estimated by repeated ultrasounds, and preterm birth (gestational age <37 wk) and small size for gestational age (less than the fifth percentile) were determined., Results: Adjusted multivariate regression analyses showed that, compared with mothers with second-trimester 25(OH)D concentrations in the highest quartile, those with 25(OH)D concentrations in the lower quartiles had offspring with third-trimester fetal growth restriction, leading to a smaller head circumference, shorter body length, and lower body weight at birth (all P < 0.05). Mothers who had 25(OH)D concentrations in the lowest quartile had an increased risk of preterm delivery (OR: 1.72; 95% CI: 1.14, 2.60) and children who were small for gestational age (OR: 2.07; 95% CI: 1.33, 3.22). The estimated population attributable risk of 25(OH)D concentrations <50 nmol/L for preterm birth or small size for gestational age were 17.3% and 22.6%, respectively. The observed associations were not based on extreme 25(OH)D deficiency, but presented within the common ranges., Conclusions: Low maternal 25(OH)D concentrations are associated with proportional fetal growth restriction and with an increased risk of preterm birth and small size for gestational age at birth. Further studies are needed to investigate the causality of these associations and the potential for public health interventions., (© 2016 American Society for Nutrition.)

Background: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys., Objective: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe., Design: The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography-tandem mass spectrometry on biobanked sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n= 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data., Results: An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October-March) and summer (April-November) periods, respectively. According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations., Conclusions: Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency in the majority of the European population., (© 2016 American Society for Nutrition.)

Background: To our knowledge, no studies have reported on the long-term variability of vitamin D status in adolescents., Objective: To determine whether tracking of vitamin D status occurs in healthy adolescents, we assessed the variability of 25-hydroxyvitamin D [25(OH)D] every 2 y over a 10-y period in a longitudinal cohort of adolescents living in Johannesburg, South Africa (latitude 26°S)., Design: Healthy adolescents who had blood samples available on ≥3 occasions between 11 and 20 y of age were included in the study. Of the cohort of 504 children, 99 met the criteria. The mean 25(OH)D concentration at each time point was measured, and the individual 25(OH)D z scores based on year 11 values were used as the reference. All 25(OH)D concentrations for a subject were measured in a single assay., Results: No significant correlation was found between 25(OH)D in the earlier and later years of adolescence, although significant correlations were found between year 11 and year 13 (r = 0.71, P < 0.0001) and between years 15, 17, and 20 (r ≥ 0.65, P < 0.0001). The percentage of adolescents whose 25(OH)D concentration changed by >20 nmol/L from year 11 was calculated for all age groups: 12% of the cohort had a change of >20 nmol/L at 13 y of age compared with 46% at 20 y of age. Just more than one-half (53%) of the cohort changed their category of vitamin D status between the ages of 11 and 20 y, and one-third of adolescents changed from being replete to insufficient over the same period., Conclusions: The data suggest that the measurement of 25(OH)D at a single time point does not reflect the long-term vitamin D status of an adolescent. These findings may cast doubt on the veracity of those studies that suggest an association of vitamin D status with various disease states in which vitamin D status was measured only once.

Background: The role of maternal 25-hydroxyvitamin D [25(OH)D] in fetal development is uncertain, and findings of observational studies have been inconsistent. Most studies have assessed 25(OH)D only one time during pregnancy, but to our knowledge, the tracking of an individual's 25(OH)D during pregnancy has not been assessed previously., Objective: We determined the tracking of serum 25(OH)D from early to late pregnancy and factors that influence this., Design: The Southampton Women's Survey is a prospective mother-offspring birth-cohort study. Lifestyle, diet, and 25(OH)D status were assessed at 11 and 34 wk of gestation. A Fourier transformation was used to model the seasonal variation in 25(OH)D for early and late pregnancy separately, and the difference between the measured and seasonally modeled 25(OH)D was calculated to generate a season-corrected 25(OH)D. Tracking was assessed with the use of the Pearson correlation coefficient, and multivariate linear regression was used to determine factors associated with the change in season-corrected 25(OH)D., Results: A total of 1753 women had 25(OH)D measured in both early and late pregnancy. There was a moderate correlation between season-corrected 25(OH)D measurements at 11 and 34 wk of gestation (r = 0.53, P < 0.0001; n = 1753). Vitamin D supplementation was the strongest predictor of tracking; in comparison with women who never used supplements, the discontinuation of supplementation after 11 wk was associated with a reduction in season-corrected 25(OH)D (β = -7.3 nmol/L; P < 0.001), whereas the commencement (β = 12.6 nmol/L; P < 0.001) or continuation (β = 6.6 nmol/L; P < 0.001) of supplementation was associated with increases in season-corrected 25(OH)D. Higher pregnancy weight gain was associated with a reduction in season-corrected 25(OH)D (β = -0.4 nmol · L(-1) · kg(-1); P = 0.015), whereas greater physical activity (β = 0.4 nmol/L per h/wk; P = 0.011) was associated with increases., Conclusions: There is a moderate tracking of 25(OH)D status through pregnancy; factors such as vitamin D supplementation, weight gain, and physical activity are associated with changes in season-corrected 25(OH)D from early to late gestation. These findings have implications for study designs and analyses and approaches to intervention studies and clinical care., (© 2015 American Society for Nutrition.)

Background: Vitamin D and iron deficiencies frequently co-exist. It is now appreciated that mechanistic interactions between iron and vitamin D metabolism may underlie these associations., Objective: We examined interrelations between iron and vitamin D status and their regulatory hormones in pregnant adolescents, who are a group at risk of both suboptimal vitamin D and suboptimal iron status., Design: The trial was a prospective longitudinal study of 158 pregnant adolescents (aged ≤18 y). Maternal circulating biomarkers of vitamin D and iron were determined at midgestation (∼25 wk) and delivery (∼40 wk). Linear regression was used to assess associations between vitamin D and iron status indicators. Bivariate and multivariate logistic regressions were used to generate the OR of anemia as a function of vitamin D status. A mediation analysis was performed to examine direct and indirect relations between vitamin D status, hemoglobin, and erythropoietin in maternal serum., Results: Maternal 25-hydroxyvitamin D [25(OH)D] was positively associated with maternal hemoglobin at both midgestation and at delivery (P < 0.01 for both). After adjustment for age at enrollment and race, the odds of anemia at delivery was 8 times greater in adolescents with delivery 25(OH)D concentrations <50 nmol/L than in those with 25(OH)D concentrations ≥50 nmol/L (P <0.001). Maternal 25(OH)D was inversely associated with erythropoietin at both midgestation (P <0.05) and delivery (P <0.001). The significant relation observed between 25(OH)D and hemoglobin could be explained by a direct relation between 25(OH)D and hemoglobin and an indirect relation that was mediated by erythropoietin., Conclusions: In this group of pregnant adolescents, suboptimal vitamin D status was associated with increased risk of iron insufficiency and vice versa. These findings emphasize the need for screening for multiple nutrient deficiencies during pregnancy and greater attention to overlapping metabolic pathways when selecting prenatal supplementation regimens., (© 2015 American Society for Nutrition.)

Background: Miscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy., Objective: We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage., Design: In a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58)., Results: The adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage., Conclusions: We found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900., (© 2015 American Society for Nutrition.)

Background: Vitamin D supplementation is recommended for breastfed infants. Maternal supplementation beginning in gestation is a potential alternative, but its efficacy in maintaining infant 25-hydroxyvitamin D [25(OH)D] concentration after birth is unknown., Objectives: We determined the effect of 3 doses of maternal vitamin D supplementation beginning in gestation and continued in lactation on infant serum 25(OH)D and compared the prevalence of infant serum 25(OH)D cutoffs (>30, >40, >50, and >75 nmol/L) by dose at 8 wk of age., Design: Pregnant women (n = 226) were randomly allocated to receive 10, 25, or 50 μg vitamin D₃/d from 13 to 24 wk of gestation until 8 wk postpartum, with no infant supplementation. Mother and infant blood was collected at 8 wk postpartum., Results: At 8 wk postpartum, mean [nmol/L (95% CI)] infant 25(OH)D at 8 wk was higher in the 50-μg/d [75 (67, 83)] than in the 25-μg/d [52 (45, 58)] or 10-μg/d [45 (38, 52)] vitamin D groups (P < 0.05). Fewer infants born to mothers in the 50-μg/d group had a 25(OH)D concentration <30 nmol/L (indicative of deficiency) than infants in the 25- and 10-μg/d groups, respectively (2% compared with 16% and 43%; P < 0.05). Fewer than 15% of infants in the 10- or 25-μg/d groups achieved a 25(OH)D concentration >75 nmol/L compared with 44% in the 50-μg/d group (P < 0.05). Almost all infants (∼98%, n = 44) born to mothers in the 50-μg/d group achieved a 25(OH)D concentration >30 nmol/L. At 8 wk postpartum, mean maternal 25(OH)D concentration was higher in the 50-μg/d [88 (84, 91)] than in the 25-μg/d [78 (74, 81)] or 10-μg/d [69 (66, 73)] groups (P < 0.05)., Conclusions: Maternal supplementation beginning in gestation with 50 μg vitamin D₃/d protects 98% of unsupplemented breastfed infants against 25(OH)D deficiency (<30 nmol/L) to at least 8 wk, whereas 10 or 25 μg vitamin D/d protects only 57% and 84% of infants, respectively., (© 2015 American Society for Nutrition.)

Background: More than one-fifth of the United Kingdom population has poor vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] concentration <25 nmol/L), particularly individuals with low sun exposure or poor dietary intake., Objective: We identified the fortification vehicle and concentration most likely to safely increase population vitamin D intakes and vitamin D status., Design: Wheat flour and milk were identified as primary fortification vehicles for their universal consumption in population groups most at risk of vitamin D deficiency including children aged 18-36 mo, females aged 15-49 y, and adults aged ≥65 y. With the use of data from the first 2 y (2008-2010) of the National Diet and Nutrition Survey Rolling Program, we simulated the effect of fortifying wheat flour and milk with vitamin D on United Kingdom food consumption. Empirically derived equations for the relation between vitamin D intake and the serum 25(OH)D concentration were used to estimate the population serum 25(OH)D concentration for each fortification scenario., Results: At a simulated fortification of 10 μg vitamin D/100 g wheat flour, the proportion of at-risk groups estimated to have vitamin D intakes below United Kingdom Reference Nutrient Intakes was reduced from 93% to 50%, with no individual exceeding the United Kingdom Tolerable Upper Intake Level; the 2.5th percentile of the population winter serum 25(OH)D concentration rose from 20 to 27 nmol/L after fortification. The simulation of the fortification of wheat flour at this concentration was more effective than that of the fortification of milk (at concentrations between 0.25 and 7 mg vitamin D/100 L milk) or of the fortification of milk and flour combined., Conclusion: To our knowledge, this study provides new evidence that vitamin D fortification of wheat flour could be a viable option for safely improving vitamin D intakes and the status of United Kingdom population groups at risk of deficiency without increasing risk of exceeding current reference thresholds., (© 2015 American Society for Nutrition.)

Background: The vitamin D-endocrine system is thought to play a role in physiologic processes that range from mineral metabolism to immune function. Serum 25-hydroxyvitamin D [25(OH)D] is the accepted biomarker for vitamin D status. Skin color is a key determinant of circulating 25(OH)D concentrations, and genes responsible for melanin content have been shown to be under strong evolutionary selection in populations living in temperate zones. Little is known about the effect of latitude on mean concentrations of 25(OH)D in dark-skinned populations., Objective: The objective was to describe the distribution of 25(OH)D and its subcomponents in 5 population samples of African origin from the United States, Jamaica, Ghana, South Africa, and the Seychelles., Design: Participants were drawn from the Modeling of the Epidemiologic Transition Study, a cross-sectional observational study in 2500 adults, ages 25-45 y, enrolled between January 2010 and December 2011. Five hundred participants, ∼50% of whom were female, were enrolled in each of 5 study sites: Chicago, IL (latitude: 41°N); Kingston, Jamaica (17°N); Kumasi, Ghana (6°N); Victoria, Seychelles (4°S); and Cape Town, South Africa (34°S). All participants had an ancestry primarily of African origin; participants from the Seychelles trace their history to East Africa., Results: A negative correlation between 25(OH)D and distance from the equator was observed across population samples. The frequency distribution of 25(OH)D in Ghana was almost perfectly normal (Gaussian), with progressively lower means and increasing skewness observed at higher latitudes., Conclusions: It is widely assumed that lighter skin color in populations outside the tropics resulted from positive selection, driven in part by the relation between sun exposure, skin melanin content, and 25(OH)D production. Our findings show that robust compensatory mechanisms exist that create tolerance for wide variation in circulating concentrations of 25(OH)D across populations, suggesting a more complex evolutionary relation between skin color and the vitamin D pathway., (© 2014 American Society for Nutrition.)

Background: Vitamin D status is currently diagnosed by measuring serum 25-hydroxyvitamin D [25(OH)D]., Objective: This study aimed to develop a risk profile that can be used to easily identify older individuals at high risk of vitamin D deficiency., Design: This study was performed within the Longitudinal Aging Study Amsterdam, an ongoing cohort study in a representative sample of the Dutch older population (n = 1509 for the development sample and n = 1100 for the validation sample). Prediction models for serum 25(OH)D concentrations <50 and <30 nmol/L were developed by using backward logistic regression. Risk scores were calculated by dividing the individual regression coefficients by the regression coefficient with the lowest β to create simple scores., Results: Serum 25(OH)D concentrations <50 and <30 nmol/L were present in 46.2% and 17.5% of participants, respectively. The model for the prediction of concentrations <50 nmol/L consisted of 13 easily assessable predictors, whereas the model for concentrations <30 nmol/L contained 10 predictors. The resulting areas under the curve (AUCs) were 0.78 and 0.80, respectively. The AUC in the external validation data set was 0.71 for the <50-nmol/L model. At a cutoff of 58 in total risk score (range: 8-97), the model predicted concentrations <50 nmol/L with a sensitivity of 61% and a specificity of 82%, whereas these values were 61% and 84%, respectively, at a cutoff of 110 in the total risk score (range: 6-204) in the model for concentrations <30 nmol/L., Conclusions: Two total risk scores, including 13 or 10 predictors that can easily be assessed, were developed and are able to predict serum 25(OH)D concentrations <50 and <30 nmol/L accurately. These risk scores may be useful in clinical practice to identify persons at risk of vitamin D deficiency.

Background: Vitamin D deficiency is an important health issue, particularly among people residing in northern countries. Low concentrations of 25-hydroxyvitamin D [25(OH)D] have been linked to several health conditions., Objective: The objective was to determine the association between plasma 25(OH)D and pulmonary function and the effect modifications of sex and body mass index (BMI) in adults., Design: A cross-sectional study included 3359 adults aged ≥18 y who participated in the Canadian Health Measures Survey, and a 2-stage multiple linear regression analysis was conducted., Results: Overall, 26% of the adults had a plasma 25(OH)D concentration <50 nmol/L, which is considered deficient (ie, hypovitaminosis D). This deficiency was more prevalent among men than among women (30% compared with 23%). Regression analysis showed that deficient plasma 25(OH)D was associated with lower mean residual forced vital capacity and forced expiratory volume in 1 s in men after adjustment for covariates. When further stratified by BMI, the associations were more marked in overweight and obese men. Vitamin D deficiency associated with pulmonary function was not statistically significant in normal-weight men or in women, regardless of BMI categories. Similar results were obtained when plasma 25(OH)D was examined as a continuous variable in the models., Conclusions: Hypovitaminosis D may be a risk factor for lung dysfunction, especially for overweight and obese men. Further research is necessary to determine the mechanism of the interrelation between vitamin D, adiposity, and pulmonary function.

Background: The role of vitamin D in breast cancer prevention is equivocal. Saudi Arabian women may be at greater risk of vitamin D deficiency because of a darker skin type and a greater likelihood of reduced ultraviolet B radiation exposure. Data regarding the vitamin D status of Saudi Arabian women and its relation to breast cancer risk are lacking., Objective: The purpose of this research was to evaluate the association between circulating concentrations of 25-hydroxyvitamin D [25(OH)D] and breast cancer risk in Saudi Arabian women., Design: A case-control study was conducted among 120 breast cancer cases and 120 controls. The study population was drawn from patients admitted to King Fahd Hospital in Jeddah, Saudi Arabia, from June to August 2009. Participants completed questionnaires on diet and medical history, and serum samples were collected from all women to measure circulating 25(OH)D concentrations., Results: The participants had a mean age of 47.8 y and a mean body mass index (BMI; in kg/m(2)) of 30.0. Breast cancer cases had significantly lower (mean ± SD) serum concentrations of 25(OH)D (9.4 ± 6.4 ng/mL) than did controls (15.4 ± 12.3 ng/mL; P = 0.001). In comparison with those in the highest category of vitamin D status for this population (≥20 ng/mL), the adjusted ORs (95% CIs) for invasive breast cancer were 6.1 (2.4, 15.1) for women with a serum 25(OH)D concentration <10 ng/mL and 4.0 (1.6, 10.4) for women with a serum concentration of ≥10 to <20 ng/mL (P-trend = 0.0001)., Conclusion: An inverse association exists between serum 25(OH)D concentrations and breast cancer risk in Saudi Arabian women. This trial was registered at clinicaltrials.gov as NCT01817231.

Background: Recent studies suggest an association between 25-hydroxyvitamin D [25(OH)D] and type 2 diabetes (T2D) risk. However, prospective studies investigating the relation between vitamin D inadequacy and incidence of T2D incorporating obesity and dynamic measures of insulin resistance (IR) and pancreatic β cell function are limited., Objective: We tested the hypothesis that baseline 25(OH)D is associated with the incidence of T2D in high-risk subjects for up to 5 y of follow-up, independently of obesity, baseline IR, and β cell function., Design: We recruited 1080 nondiabetic Korean subjects [mean ± SD age: 49.5 ± 11.4 y] based on the presence of one or more risk factors for T2D, including obesity, hypertension, dyslipidemia, and/or family history of T2D. We measured anthropometric and biochemical indicators, HOMA2-IR, and the insulinogenic index (IGI; calculated as change in insulin at 30 min/change in glucose at 30 min) from a 75-g oral-glucose-tolerance test., Results: Of the participants, 10.5% had a serum 25(OH)D deficiency (<10 ng/mL), 51.6% had an insufficiency (10.0-19.9 ng/mL), and 38.0% had a sufficiency (≥20 ng/mL), and the incidence of T2D at 32.3 ± 15.6 mo (±SD) declined accordingly: 15.9%, 10.2%, and 5.4%, respectively (P < 0.001). After adjustment for age, sex, blood pressure, lifestyles, family history, season, parathyroid hormone, and high-sensitivity C-reactive protein, the participants with 25(OH)D deficiency had an increased risk of T2D independently of BMI, HOMA2-IR, and IGI; the HRs were 2.06 (95% CI: 1.22, 3.49) for 25(OH)D 10-19.9 ng/mL compared with ≥20 ng/mL and 3.23 (95% CI: 1.66, 6.30) for 25(OH)D <10 ng/mL compared with ≥20 ng/mL., Conclusion: The current prospective study suggests that vitamin D metabolism may play a role in T2D pathogenesis independently of known risk factors. This trial was registered at clinicaltrials.gov as NCT01508481.

Background: There are questions about the appropriate method for the accurate estimation of the population prevalence of nutrient inadequacy on the basis of a biomarker of nutrient status (BNS)., Objective: We determined the applicability of a statistical probability method to a BNS, specifically serum 25-hydroxyvitamin D [25(OH)D]. The ability to meet required statistical assumptions was the central focus., Design: Data on serum 25(OH)D concentrations in adults aged 19-70 y from the 2005-2006 NHANES were used (n = 3871). An Institute of Medicine report provided reference values. We analyzed key assumptions of symmetry, differences in variance, and the independence of distributions. We also corrected observed distributions for within-person variability (WPV). Estimates of vitamin D inadequacy were determined., Results: We showed that the BNS [serum 25(OH)D] met the criteria to use the method for the estimation of the prevalence of inadequacy. The difference between observations corrected compared with uncorrected for WPV was small for serum 25(OH)D but, nonetheless, showed enhanced accuracy because of correction. The method estimated a 19% prevalence of inadequacy in this sample, whereas misclassification inherent in the use of the more traditional 97.5th percentile high-end cutoff inflated the prevalence of inadequacy (36%)., Conclusions: When the prevalence of nutrient inadequacy for a population is estimated by using serum 25(OH)D as an example of a BNS, a statistical probability method is appropriate and more accurate in comparison with a high-end cutoff. Contrary to a common misunderstanding, the method does not overlook segments of the population. The accuracy of population estimates of inadequacy is enhanced by the correction of observed measures for WPV.

Background: Early menarche is a risk factor for cardiometabolic disease and cancer. Latitude, which influences sun exposure, is inversely related to age at menarche. This association might be related to vitamin D, but to our knowledge it has not been investigated in prospective epidemiologic studies., Objective: We studied the association between vitamin D status and the occurrence of menarche in a prospective study in girls from Bogota, Colombia., Design: We measured plasma 25-hydroxyvitamin D [25(OH)D] concentrations in a random sample of 242 girls (mean ± SD age: 8.8 ± 1.6 y) and followed them for a median of 30 mo. Girls were asked periodically about the occurrence and date of menarche. Baseline 25(OH)D concentrations were categorized as <50 nmol/L (deficient), ≥50 and <75 nmol/L, or ≥75 nmol/L (sufficient). The incidence of menarche was compared between groups by using time-to-event analyses., Results: A total of 57% of girls in the vitamin D-deficient group reached menarche during follow-up compared with 23% of girls in the vitamin D-sufficient group (P-trend = 0.0004). The estimated mean (±SE) ages at menarche in the same groups were 11.8 ± 0.2 y and 12.6 ± 0.2 y, respectively (P = 0.0009). After adjustment for baseline age and BMI-for-age z score in a Cox proportional hazards model, the probability of menarche was twice as high in vitamin D-deficient girls than in girls who were vitamin D-sufficient (HR: 2.05; 95% CI: 1.03, 4.07; P = 0.04). Similar results were obtained in girls aged ≥9 y at baseline (HR: 2.39; 95% CI: 1.14, 5.00; P = 0.02)., Conclusion: Vitamin D deficiency is associated with earlier menarche.

Background: Metabolic consequences of vitamin D deficiency have become a recent research focus. Maternal vitamin D status is thought to influence musculoskeletal health in children, but its relation with offspring metabolic risk is not known., Objective: We aimed to examine the association between maternal vitamin D status and anthropometric variables, body composition, and cardiovascular risk markers in Indian children., Design: Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 28-32 wk gestation in 568 women who delivered at Holdsworth Memorial Hospital, Mysore, India. Anthropometric variables, glucose and insulin concentrations, blood pressure, and fasting lipid concentrations were measured in the offspring at 5 and 9.5 y of age. Muscle-grip strength was measured by using a hand-held dynamometer at age 9.5 y. Arm-muscle area was calculated as a measure of muscle mass. Fasting insulin resistance was calculated by using the homeostasis model assessment equation., Results: Sixty-seven percent of women had vitamin D deficiency [serum 25(OH)D concentration <50 nmol/L]. At ages 5 and 9.5 y, children born to vitamin D-deficient mothers had smaller arm-muscle area in comparison with children born to mothers without deficiency (P < 0.05). There was no difference in grip strength between offspring of women with and without vitamin D deficiency. At 9.5 y, children of vitamin D-deficient mothers had higher fasting insulin resistance than did children of nondeficient women (P = 0.04). There were no associations between maternal vitamin D status and other offspring risk factors at either age., Conclusion: Intrauterine exposure to low 25(OH)D concentrations is associated with less muscle mass and higher insulin resistance in children.

Background: Serum 25-hydroxyvitamin D [25(OH)D] concentrations can be affected by several environmental and individual factors. It is not clear to what extent genetic influences play a role in determining vitamin D status. Thus far, studies on the heritability of vitamin D have provided conflicting results., Objective: We estimated the heritability of vitamin D concentrations and the effect of season on heritability estimates., Design: We measured serum 25(OH)D concentrations in 510 middle-aged, male twins (310 monozygotic and 200 dizygotic twins) selected from the Vietnam Era Twin Registry. Generalized estimating equations were used to test the association between 25(OH)D and other study factors. Structural equation modeling was used to estimate the heritability of 25(OH)D., Results: The twins' mean (±SD) age was 55 ± 2.8 y. The mean (±SD) 25(OH)D concentration was 38.4 ± 23.3 ng/mL with a substantial seasonal variation (a 6.1-ng/mL lower value during the winter than during the summer, P = 0.003). Approximately 70% of the variation in 25(OH)D concentrations during the winter was explained by genetic factors. However, in the summer, 25(OH)D concentrations were not heritable. During the summer, 53% of the variation in 25(OH)D concentrations was due to shared environmental factors, and 47% of the variation in 25(OH)D concentrations was due to unique environmental factors., Conclusions: Serum 25(OH)D concentrations are highly heritable during the winter season only. In the summer, environmental conditions (eg, sun exposure) prevail over genetic backgrounds in determining serum 25(OH)D concentrations. This trial was registered at clinicaltrials.gov as NCT00017836.

Background: Despite increased awareness of the adverse health effects of low vitamin D status, few studies have evaluated 25-hydroxyvitamin D [25(OH)D] status in young children., Objectives: We aimed to assess vitamin D status on the basis of 25(OH)D and its relation with parathyroid hormone (PTH) and to identify possible predictors of 25(OH)D status in young children living in a country with minimal vitamin D fortification., Design: Serum 25(OH)D and PTH concentrations were measured in a cross-sectional sample of children aged 12-22 mo [n = 193 for 25(OH)D, n = 144 for PTH] living in Dunedin, New Zealand (latitude: 45 degrees S). Anthropometric, dietary, and sociodemographic data were collected., Results: The majority of children sampled in the summer (94%; 47 of 50) had 25(OH)D >50 nmol/L; however, nearly 80% of children sampled in the winter (43 of 55) had serum concentrations < or =50 nmol/L. In season-adjusted multivariate analysis, breastfeeding and higher levels of education were independently associated with lower 25(OH)D concentrations, whereas male sex and cigarette-smoke exposure were positively associated with 25(OH)D (all P < 0.05). Fractional polynomial regression was used to describe the nonlinear relation between serum PTH and 25(OH)D (P < 0.001). When 25(OH)D concentrations were >60-65 nmol/L, a plateau in PTH was evident., Conclusions: Seasonal variation in 25(OH)D concentration implies that postsummer vitamin D stores were insufficient to maintain status >50 nmol/L year-round. Examination of the predictors of 25(OH)D in our model shows few modifiable risk factors, and thus effective dietary strategies may be required if future research determines that children with 25(OH)D concentrations <50 nmol/L are at significant health risk. This trial was registered at www.actr.org.au as ACTRN12605000487617.

An increase in the incidence and an earlier onset of coronary artery disease is expected because of the increased prevalence of childhood obesity. Comorbidities of obesity, such as dyslipidemia, insulin resistance syndrome, hypertension, associated nutritional deficiencies, and a sedentary lifestyle or associated lifestyle factors such as tobacco smoke exposure, are likely to account for this increase because these are all independent risk factors for accelerated atherosclerosis. Because clinical atherosclerotic cardiovascular disease does not manifest in obese children, assessment of the subclinical markers of atherosclerosis may help in the evaluation of the progression of atherosclerosis, in further stratification of risk, and in monitoring the effects of intervention. Furthermore, because multiple risk factors with poorly understood interplay might be present in obese children, assessment of the vasculature directly, and perhaps the assignment of a "vascular age," may be a useful method to quantify the "end organ" effect of exposure to these various risks. Obese children may show favorable changes in their behaviors that result in an improvement in clinically measurable risk factors with various clinic-based and behavior modification therapies, but the vascular benefits of such interventions need to be studied further. Broad social, cultural, legislative, and policy changes that support healthy lifestyles within families and communities need to be implemented to decrease the prevalence of childhood obesity and its cardiovascular consequences in communities. The effect of risk factor modification on the vasculature will continue to be a resource for the direction of evidence-based therapy in obese children.

Background: Vegans and other vegetarians who limit their intake of animal products may be at greater risk of vitamin D deficiency than nonvegetarians, because foods providing the highest amount of vitamin D per gram naturally are all from animal sources, and fortification with vitamin D currently occurs in few foods., Objective: We assessed serum 25-hydroxyvitamin D [s25(OH)D] concentrations and factors affecting them in vegetarians, partial vegetarians, and nonvegetarians in a sample of calibration study subjects from the Adventist Health Study-2., Design: Food-frequency questionnaires and sun-exposure data were obtained from 199 black and 229 non-Hispanic white adults. We compared s25(OH)D concentration, dietary and supplemental vitamin D intake, and sun exposure in the different dietary groups., Results: We found no significant difference in s25(OH)D by vegetarian status for either white or black subjects. Among whites, dietary vitamin D intake and sun behavior were different between vegetarian groups, but there was no difference in skin type distribution. Among blacks, no significant differences were observed for any of these variables between vegetarian groups. The mean (+/-SD) s25(OH)D was higher in whites (77.1 +/- 10.33 nmol/L) than in blacks (50.7 +/- 27.4 nmol/L) (P < 0.0001)., Conclusions: s25(OH)D concentrations were not associated with vegetarian status. Other factors, such as vitamin D supplementation, degree of skin pigmentation, and amount and intensity of sun exposure have greater influence on s25(OH)D than does diet.

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.

Background: Racial differences in cardiovascular risk factors do not fully explain the higher prevalence of lower-extremity peripheral arterial disease (PAD) in black adults., Objective: We sought to determine whether any of this excess risk may be explained by vitamin D status, which has been widely documented to be lower in blacks than in whites., Design: This population-based cross-sectional study included 2987 white and 866 black persons aged >or=40 y from the 2001-2004 National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial pressure index of <0.90 in either leg., Results: Mean (+/-SEM) 25-hydroxyvitamin D [25(OH)D] concentrations were significantly lower in black than in white adults (39.2 +/- 1.0 and 63.7 +/- 1.1 nmol/L, respectively; P < 0.001). Adjusted odds ratios for PAD decreased in a dose-dependent fashion with increasing quartiles of 25(OH)D in white adults [1.00 (referent), 0.86, 0.67, and 0.53; P for trend < 0.001]. In black adults, the association was nonlinear; models with cubic splines suggested evidence of greater odds for PAD and a trend for lower odds for PAD at the lowest and highest concentrations of 25(OH)D, respectively. After adjustment for racial differences in socioeconomic status and for traditional and novel risk factors, odds for PAD in black compared with white adults were reduced from 2.11 (95% CI: 1.55, 2.87) to 1.67 (1.11, 2.51). After additional adjustment for 25(OH)D, the odds were further reduced to 1.33 (0.84, 2.10)., Conclusions: Racial differences in vitamin D status may explain nearly one-third of the excess risk of PAD in black compared with white adults. Additional research is needed to confirm these findings.

Vitamin D deficiency occurs in the United States in exclusively breastfed infants who have high levels of skin pigmentation, inadequate vitamin D supplementation, and insufficient sunlight exposure. I review serum 25-hydroxyvitamin D [25(OH)D] concentrations and functional outcomes of vitamin deficiency in young children and breastfed and nonbreastfed infants. These outcomes include the presence or absence of vitamin D deficiency rickets, bone mineral content, and serum parathyroid hormone concentration. Daily vitamin D supplements of 400 IU/L keep serum 25(OH)D concentrations higher than 50 nmol/L and prevent rickets in infants and young children. The available evidence is not sufficient to support the use of bone mineral content or parathyroid hormone concentrations in infants and young children as functional outcomes to define deficient or sufficient levels of 25(OH)D. I therefore propose a research agenda to establish the functional definitions of vitamin D sufficiency or deficiency in infants and young children.

This article describes the information currently available in the National Nutrition Monitoring System that is relevant to assessing the vitamin D status of US population groups, the strengths and limitations of this information, and selected results of vitamin D nutritional status assessments. The National Health and Nutrition Examination Survey (NHANES) provides information on vitamin D intakes only from 1988 to 1994. NHANES collected information on supplement use and circulating 25-hydroxyvitamin D [25(OH)D] concentrations from 1988 through current surveys. The National Nutrient Database for Standard Reference started providing limited data on the vitamin D content of foods in 2002 and continues to update these values. The Food Label and Package Survey provides 2006-2007 label information on vitamin D fortification of marketed foods. Despite limitations in the available data and controversies about appropriate criteria for evaluating vitamin D status among population groups, we can make some useful comparisons of vitamin D status among life-stage groups. In general, males have higher vitamin D intakes and 25(OH)D concentrations than do females. Children tend to have higher vitamin D status than adults. The increasing use of multivitamin-mineral dietary supplements in younger to older adults is not associated with a corresponding increase in serum 25(OH)D concentrations. In general, leaner individuals have higher circulating concentrations of 25(OH)D and supplement use than do heavier individuals. Finally, non-Hispanic whites tend to have higher vitamin D status than do non-Hispanic blacks and Mexican Americans.

The field of vitamin D public health research has a pressing need to define sensitive and specific predictors of vitamin D status that can be used to determine whether an individual or population has a supply of vitamin D that is sufficient to meet requirements. The aim of this review is to highlight the considerations needed when evaluating evidence of the relations between vitamin D biomarkers and functional or health outcomes across the life cycle. It draws attention to the importance of distinguishing between biomarkers of supply, function, and outcome and of considering the many factors that could influence interpretation, such as life stage, ethnicity, body mass index, liver and kidney function, and dietary calcium and phosphorus intake. The vitamin D biomarkers that have shown the most utility to date are the plasma concentration of 25-hydroxyvitamin D (supply), the plasma concentration of parathyroid hormone (function), and the presence or absence of rickets (outcome). However, a single biomarker of vitamin D status or threshold value is unlikely to be valid in all situations. The field therefore needs research to refine existing biomarkers or establish new indicators that take the many factors into account and to identify useful functional biomarkers of vitamin D status for infants, children, women of reproductive age, and specific ethnic groups. However, evidence using the biomarkers currently available shows that frank vitamin D deficiency is a major public health problem in many parts of the world that requires urgent attention.

Background: Little is known about vitamin D status in breast cancer survivors. This issue is important because vitamin D influences pathways related to carcinogenesis., Objective: The objective of this report was to describe and understand vitamin D status in a breast cancer survivor cohort., Design: Data are from the Health, Eating, Activity, and Lifestyle study. With the use of a cross-sectional design, we examined serum concentrations of 25-hydroxyvitamin D [25(OH)D] in 790 breast cancer survivors from western Washington state, New Mexico, and Los Angeles County. Cancer treatment data were obtained from Surveillance, Epidemiology, and End Results registries and medical records. Fasting blood, anthropometry, and lifestyle habits were collected after diagnosis and treatment. We examined distributions of 25(OH)D by race-ethnicity, season, geography, and clinical characteristics. Multivariate regression tested associations between 25(OH)D and stage of disease., Results: Five hundred ninety-seven (75.6%) of the women had low serum 25(OH)D, suggesting vitamin D insufficiency or frank deficiency. The overall mean (+/-SD) was 24.8 +/- 10.4 ng/mL, but it was lower for African Americans (18.1 +/- 8.7 ng/mL) and Hispanics (22.1 +/- 9.2 ng/mL). Women with localized (n = 424) or regional (n = 182) breast cancer had lower serum 25(OH)D than did women with in situ disease (n = 184) (P = 0.05 and P = 0.03, respectively). Multivariate regression models controlled for age, body mass index (in kg/m(2)), race-ethnicity, geography, season, physical activity, diet, and cancer treatments showed that stage of disease independently predicted serum 25(OH)D (P = 0.02)., Conclusions: In these breast cancer survivors, the prevalence of vitamin D insufficiency was high. Clinicians might consider monitoring vitamin D status in breast cancer patients, together with appropriate treatments, if necessary.