Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis

Key PointsQuestionDoes vitamin D supplementation have any association with cardiovascular disease risk? FindingsIn this meta-analysis of randomized clinical trials that included more than 83000 participants, vitamin D supplementation was not associated with reduced risks of major adverse cardiovascular events, myocardial infarction, stroke, cardiovascular disease mortality, or all-cause mortality compared with placebo. MeaningThese results suggest that vitamin D supplementation may not confer cardiovascular protection and may not be indicated for this purpose. This meta-analysis of 21 randomized clinical trials examines the role of vitamin D supplementation in reducing cardiovascular events and all-cause mortality. ImportanceObservational studies have reported an association between low serum vitamin D levels and elevated risk of cardiovascular disease (CVD) events, but such studies cannot prove causation because of possible unmeasured confounding. ObjectiveWe conducted a meta-analysis of randomized clinical trials that tested the association of vitamin D supplementation with reduced CVD events and all-cause mortality. Data SourcesLiterature search through PubMed, the Cochrane Library, and Embase was completed by 2 reviewers from each database's inception to December 15, 2018. Study SelectionInclusion criteria were randomized clinical trials that reported the effect of long-term (>= 1 year) vitamin D supplementation on CVD events and all-cause mortality. Studies that did not include cardiovascular outcomes were excluded. Data Extraction and SynthesisData were abstracted independently by 2 authors. Random-effects models were used to report the risk ratios (RRs) and 95% CIs. Main Outcomes and MeasuresMajor adverse cardiovascular events was the primary outcome, and rates of myocardial infarction, stroke or cerebrovascular accident, CVD mortality, and all-cause mortality were the secondary end points. ResultsTwenty-one randomized clinical trials were included (including 83291 patients, of whom 41669 received vitamin D and 41622 received placebos). The mean (SD) age of trial participants was 65.8 (8.4) years; 61943 (74.4%) were female. Only 4 trials had prespecified CVD as a primary end point. Vitamin D supplementation compared with placebo was not associated with reduced major adverse cardiovascular events (RR, 1.00 [95% CI, 0.95-1.06]; P=.85) nor the secondary end points of myocardial infarction (RR, 1.00 [95% CI, 0.93-1.08]; P=.92), stroke (RR, 1.06 [95% CI, 0.98-1.15]; P=.16), CVD mortality (RR, 0.98 [95% CI, 0.90-1.07]; P=.68), or all-cause mortality (RR, 0.97 [95% CI, 0.93-1.02]; P=.23). Results were generally consistent by sex, baseline 25-hydroxyvitamin D level, vitamin D dosage, formulation (daily vs bolus dosing), and presence or absence of concurrent calcium administration. Conclusions and RelevanceIn this updated meta-analysis, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality), or all-cause mortality. The findings suggest that vitamin D supplementation does not confer cardiovascular protection and is not indicated for this purpose.