Association between B Vitamins Supplementation and Risk of Cardiovascular Outcomes: A Cumulative Meta-Analysis of Randomized Controlled Trials

Background: Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs) investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base. Methodology and Principal Findings: In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR) was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE) occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI) occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93-1.03; P = 0.37), total mortality (RR, 1.01; 95% CI: 0.97-1.05; P = 0.77), cardiac death (RR, 0.96; 95% CI: 0.90-1.02; P = 0.21), MI (RR, 0.99; 95% CI: 0.93-1.06; P = 0.82), or stroke (RR, 0.94; 95% CI: 0.85-1.03; P = 0.18). Conclusion/Significance: B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.