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The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15⁻1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80⁻2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision.

Background: Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality., Methods: In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488., Findings: We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and <30 nmol/L were 1.15 (1.00-1.29), 1.33 (1.16-1.51), and 1.67 (1.44-1.89), respectively. We observed similar results for cardiovascular mortality, but there was no significant linear association between 25(OH)D and cancer mortality. There was also no significantly increased mortality risk at high 25(OH)D levels up to 125 nmol/L., Interpretation: In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths.

Background/objectives: The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults., Methods/subjects: Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged ≥65 years. Sun exposure was assessed with a structured questionnaire (n=1012), vitamin D intake using a Food Frequency Questionnaire (n=596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n=2530)., Results: Serum 25(OH)D concentrations <50nmol/L were observed in 45% of the population; only 6% of these participants used vitamin D supplements. Sun exposure (being outside daily during summer: 66±25nmol/L vs not being outside daily during summer: 58±27nmol/L, P=0.02) and vitamin D intake (per unit μg/day during winter/spring: 3.1±0.75nmol/L, P<0.0001) were associated with higher 25(OH)D concentrations. Major allele carriers of SNPs related to DHCR7, CYP24A1, and GC, as well as CYP2R1 minor allele carriers had the highest 25(OH)D concentrations. Together, sun (R 2 =0.29), vitamin D intake (R 2 =0.24), and genes (R 2 =0.28) explained 35% (R 2 =0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BMI, education, alcohol consumption, smoking, physical activity, and self-rated health status (n=185)., Conclusion: The investigated determinants explained 35% of 25(OH)D status. Of the three main determinants under study, sun exposure still appeared to be an important determinant of serum 25(OH)D in older individuals, closely followed by genes, and vitamin D intake. Given the low frequency of vitamin D supplement use in this population, promoting supplement use may be an inexpensive, easy, and effective strategy to fight vitamin D deficiency., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance., Design, Setting, and Participants: Associations were studied using cross-sectional data of 776 (3 domains) up to 2722 (1 domain) Dutch community-dwelling older adults, aged 65 years or older., Measurements: Serum 25(OH)D, plasma glucose, and insulin concentrations were obtained. Cognitive performance was assessed with an extensive cognitive test battery. Prevalence ratios (PRs) were calculated to quantify the association between 25(OH)D and cognition; poor performance was defined as the worst 10% of the distribution of the cognitive scores., Results: The overall median MMSE score was 29 (IQR 28-30). Higher serum 25(OH)D was associated with better attention and working memory, PR 0.50 (95% CI 0.29-0.84) for the third serum 25(OH)D tertile, indicating a 50% lower probability of being a poor performer than participants in the lowest tertile. Beneficial trends were shown for 25(OH)D with executive function and episodic memory. Serum 25(OH)D was not associated with plasma glucose or insulin. Plasma insulin only modified the association between serum 25(OH)D and executive function (P for interaction: .001), suggesting that the improvement in executive function with high 25(OH)D concentrations is stronger in participants with high plasma insulin concentrations compared with those with low plasma insulin concentrations., Conclusion: Higher 25(OH)D concentrations significantly associated with better attention and working memory performance. This study does not demonstrate an interplay between serum 25(OH)D and glucose homeostasis in the association with cognitive performance., (Copyright © 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: several studies have been pointing towards a non-linear relationship between serum 25(OH)D and cardiovascular disease. Next to vitamin D deficiency, also higher levels of 25(OH)D have been reported to be associated with increased cardiovascular risk. We aimed to investigate the nature of the relationship between serum 25(OH)D and measures of arterial stiffness and arteriosclerosis in an elderly population., Design: cross-sectional., Setting/subjects: a subgroup of the B-PROOF study was included to determine associations between serum 25(OH)D and arterial stiffness and atherosclerosis (n = 567, 57% male, age 72.6 ± 5.6 years, mean serum 25(OH)D 54.6 ± 24.1 nmol/l)., Methods: carotid intima media thickness (IMT) was assessed using ultrasonography and pulse wave velocity (PWV) was determined with applanation tonometry. Associations were tested using multivariable restricted cubic spline functions and stratified linear regression analysis., Results: the associations between serum 25(OH)D and carotid IMT or PWV were non-linear. Spline functions demonstrated a difference between 25(OH)D deficient and sufficient individuals. In serum 25(OH)D sufficient participants (≥50 nmol/l; n = 287), a positive association with IMT and serum 25(OH)D was present (β 1.24; 95%CI [0.002; 2.473]). PWV levels were slightly lower in vitamin D deficient individuals, but the association with 25(OH)D was not significant., Conclusion: our study demonstrates that associations of serum 25(OH)D and PWV and IMT in an elderly population are not linear. In particular from serum 25(OH)D levels of 50 nmol/l and up, there is a slight increase of IMT with increasing 25(OH)D levels., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Summary: This study evaluated the yield of routine laboratory examination in a large population of older women in primary care. The prevalence of laboratory abnormalities was low and the clinical consequences in follow-up were limited. There was a weak association of laboratory abnormalities with osteoporosis but no association with vertebral fractures and recent fractures. Purpose: Most osteoporosis guidelines advice routine laboratory examination. We have investigated the yield of laboratory examinations in facture risk evaluation of elderly women in primary care. Methods: We assessed the prevalence of laboratory abnormalities and their association with risk factors for fractures, recent fractures, low bone mineral density (BMD), and prevalent vertebral fracture in 8996 women ≥ 65 years of age participating in a primary care fracture risk screening study. In a sample of 2208 of these participants, we also evaluated the medical consequences in the medical records during a follow-up period of ≥ 1 year. Results: Vitamin D deficiency (< 30 nmol/L) was present in 13% and insufficiency (< 50 nmol/L) in 43% of the study sample. The prevalence of other laboratory abnormalities (ESR, calcium, creatinine, FT4) was 4.6% in women with risk factors for fractures, 6.1% in women with low BMD (T-score ≤ − 2.5), 6.0% after a prevalent vertebral fracture, 5.2% after a recent fracture and 2.6% in the absence of important risk factors for fractures. Laboratory abnormalities other than vitamin D were associated with low BMD (OR 1.4, 95%CI 1.1–1.8) but not with prevalent vertebral fractures nor recent fractures. Low BMD was associated with renal failure (OR 2.0, 95%CI 1.3–3.4), vitamin D insufficiency (OR 1.2, 95%CI 1.0–1.3) and deficiency (OR 1.3, 95%CI 1.1–.5). In the follow-up period, 82% of the laboratory abnormalities did not result in a new diagnosis or treatment reported in the medical records. Conclusions: We identified a low prevalence of laboratory abnormalities in a primary care population of older women and the majority of these findings had no medical consequences. [ABSTRACT FROM AUTHOR]