Objective To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances.Design Systematic review and meta-analysis of observational studies and randomised controlled trials.Data sources Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators. Study selectionObservational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes.Data extraction Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849 412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30 716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics. ResultsIn the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements . In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D 3 supplementation and 1.04 (0.97 to 1.11) for vitamin D 2 supplementation . The effects observed for vitamin D 3 supplementation remained unchanged when grouped by various characteristics. However, for vitamin D 2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods. ConclusionsEvidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D 3 significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D 3 and D 2 have different effects on mortality risk.

Objective: The effects of vitamin D in the elderly are inconsistent. The aim of this study was to evaluate the association between vitamin D status and the metabolic syndrome (MetS) in the elderly, as well as between vitamin D status and the components of MetS (i.e. serum glucose, triglycerides (TG), HDL cholesterol (HDL-C), waist circumference (WC), and blood pressure (BP)). Methods: The study was embedded in the Rotterdam Study, a population-based cohort of middle-aged and elderly adults. We analyzed data from 3240 people (median age 71.2 years) who did not have type 2 diabetes mellitus at baseline.

Our findings suggest that higher dietary intake and higher blood concentrations of lutein are generally associated with better cardiometabolic health. However, evidence mainly comes from observational studies in adults, whereas large-scale intervention studies and studies of lutein during pregnancy and childhood are scarce.

Vitamin D deficiency is widely prevalent and has been associated with many diseases. It has been suggested that vitamin D has effects on the immune system and inhibits inflammation. The aim of our study was to investigate whether vitamin D has an inhibitory effect on systemic inflammation by assessing the association between serum levels of vitamin D and C-reactive protein. We studied the association between serum 25-hydroxyvitamin D and C-reactive protein through linear regression in 9,649 participants of the Rotterdam Study, an observational, prospective population-based cohort study. We used genetic variants related to vitamin D and CRP to compute a genetic risk score and perform bi-directional Mendelian randomization analysis. In linear regression adjusted for age, sex, cohort and other confounders, natural log-transformed CRP decreased with 0.06 (95% CI: -0.08, -0.03) unit per standard deviation increase in 25-hydroxyvitamin D. Bi-directional Mendelian randomization analyses showed no association between the vitamin D genetic risk score and lnCRP (Beta per SD = -0.018; p = 0.082) or the CRP genetic risk score and 25-hydroxyvitamin D (Beta per SD = 0.001; p = 0.998). In conclusion, higher levels of Vitamin D are associated with lower levels of C-reactive protein. In this study we did not find evidence for this to be the result of a causal relationship.

Atrial fibrillation (AF) is the most common chronic arrhythmia and it increases the risk of cardiovascular morbidity and mortality. Still there is not a complete understanding of its etiology and underlying pathways. Vitamin D might regulate renin-angiotensin-aldosterone system and might be involved in inflammation, both implicated in the pathophysiology of AF. The objective of this work was to investigate the association between vitamin D status with the risk of AF in the elderly. This study was conducted within the Rotterdam Study, a community-based cohort of middle-aged and elderly participants in Rotterdam, The Netherlands. We had 3,395 participants who were free of AF diagnosis at the start of our study and who had vitamin D data available. We analyzed the association between serum 25-hydroxivitamin D (25(OH)D) and incidence of AF using Cox regression models. Vitamin D deficiency was defined as serum 25(OH)D concentrations <50nmol/l, insufficiency between 50nmol/l and 75nmol/l, while serum 25(OH)D concentrations equal to and above 75nmol/l were considered as adequate. After mean follow-up of 12.0 years 263 (7.7%) participants were diagnosed with incident AF. Vitamin D status was not associated with AF in any of the 3 multivariate models tested (model adjusted for socio-demographic factors and life-style factors: HR per 10 unit increment in serum 25(OH)D 0.96, 95% CI: 0.91-1.02; HR for insufficiency: 0.82, 95%CI: 0.60-1.11,and HR for adequate status: 0.76, 95%CI: 0.52-1.12 compared to deficiency). This prospective cohort study does not support the hypothesis that vitamin D status is associated with AF.

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Smoking exposure is associated with pregnancy complications, as are levels of folate, vitamin B12, and homocysteine. In nonpregnant adults, smoking exposure is associated negatively with folate and vitamin B12 levels and positively with homocysteine levels. A complete overview of the literature on this topic in pregnant women is lacking. To evaluate evidence of associations of maternal smoking exposure during pregnancy and levels of folate, homocysteine, and vitamin B12 in pregnancy and in cord blood, we searched MEDLINE, Embase, CINAHL, Cochrane, Scopus, Web of Science, and reference lists of relevant studies until August 2017. We selected studies in pregnant women describing the association of passive or active smoking and levels of folate, homocysteine, and/or vitamin B12. Data were extracted by two independent reviewers. We included 32 studies of 2,015 identified references with a total of 37,822 participants and more than 6,000 smokers. Twenty-eight studies measured folate, 14 measured vitamin B12, and 13 measured homocysteine. Nineteen out of 28 studies assessing folate reported significantly lower levels in pregnant women exposed to smoking compared with those unexposed. Vitamin B12 levels were lower in smoking mothers in eight out of 14 studies. Homocysteine levels tended to be higher in mothers exposed to smoking. Smoking exposure during pregnancy is generally associated with lower folate and vitamin B12 levels and higher homocysteine levels. This may help raise further awareness about the consequences of smoking and the need to encourage stopping smoking in all, especially in pregnant women.

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