Effect of folic acid, vitamin B12, and B6 supplementation on the risk of cardiovascular and cerebrovascular diseases: An updated meta-analysis of randomized controlled trials

Abstract Background Numerous studies indicated that B vitamin supplementation can reduce cardiovascular risk; nonetheless, available proof reported from individual studies have not been consistent, so we performed an updated meta-analysis of randomized controlled trials (RCTs) to evaluate the relationship between B vitamin supplementation and cardiovascular outcomes. Materials and method Relevant studies published before May 2022 were searched from the electronic databases of PubMed, Embase, the Cochrane Library, Chinese Biology Medicine, and the Chinese National Knowledge Infrastructure. Outcomes included major adverse cardiovascular event (MACE), myocardial infarction (MI), stroke, hospitalization for unstable angina, revascularization, total mortality, and cardiovascular death. The strength of the association was examined by risk ratio (RR) with 95% confidence interval (95% CI). Results A total of 17 RCTs involving 31,085 subjects were included in the meta-analysis. The combined supplementation of B vitamins had no significant effect on MACE based on eight RCTs (RR = 0.98, 95% CI = 0.92–1.04), MI based on 13 RCTs (RR = 1.00, 95% CI = 0.92–1.09), and revascularization based on 12 RCTs (RR = 1.02, 95% CI = 0.95–1.10). Ten studies showed that the combined supplementation of B vitamins reduced the risk of stroke by 12% (RR = 0.88, 95% CI = 0.81–0.97). Eleven studies showed that the combined supplementation of B vitamins had no significant effect on the total mortality (RR = 0.99, 95% CI = 0.94–1.05), and nine studies showed that the combined B vitamins had no significant effect on cardiovascular death (RR = 0.96, 95% CI = 0.88–1.05). Besides, with the extension of follow-up duration and those with a history of cardio-cerebrovascular diseases, supplementation of B vitamins could reduce the risk of stroke. Conclusion The supplementation of folic acid, Vitamin B6, and B12 is associated with a reduction in stroke, but not in total mortality, cardiovascular death, MACE, and MI.