Effect of supplementation with folic acid and B vitamins on cardiovascular outcomes: a meta-analysis of randomised controlled trials

Background

There is an increasing amount of data over the effect of folic acid and B vitamins (vitamin B6 and B12) on cardiovascular disease, but whether supplementation with folic acid and B vitamins can reduce the risk of cardiovascular disease among middle-aged and elderly patients remains unclear. We conducted this meta-analysis to assess the efficacy of folic acid supplementation in the prevention of cardiovascular disease.

Methods

We searched PubMed and Web of Science for randomised controlled trials published between Jan 1, 1980, and Sept 1, 2015. We used relative risk (RR) with 95% CIs as a measure of effect of folic acid supplementation on the risk of cardiovascular disease. Data were independently extracted and sorted by two investigators to assess their quality. The results were pooled with a randomised-effects model using Stata 12.0 software. We used forest plots to analyse the effect of B vitamins as well as folic acid.

Findings

We included 22 randomised controlled trials reporting data on 79?564 participants. All participants were aged 45 years or older (ie, middle-aged or elderly). Supplementation with both folic acid and B vitamins together was not associated with any significant reduction in the risk of cardiovascular events (RR 0·98, 95% CI 0·92 to 1·03, p=0·353), myocardial infarction (1·00, 0·93 to 1·08, p=0·940), or total mortality (1·00, 0·94 to 1·06, p=0·778). However, a beneficial effect was observed for stroke, with supplementation with folic acid and B vitamins reducing the risk by 12% (RR 0·88, 95% CI 0·80 to 0·97, p=0·001). Moreover, we found that folic acid only could reduce the risk of cardiovascular events by 11% (RR 0·89, 95% CI 0·80 to 0·98, p=0·016) and the risk of stroke by 20% (0·80, 0·69 to 0·93, p=0·003). The level of homocysteine was reduced by 0·72 μmol/L (95% CI ?1·00 to ?0·44, p<0·0001).

Interpretation

Supplementation with folic acid with or without B vitamins is more beneficial for stroke than for other cardiovascular outcomes in middle-aged and elderly patients.

Funding

2012 Chinese Nutrition Society Nutrition Research Foundation—DSM Research Fund (2014-014); the Research Program of Shaanxi Soft Science (2015KRM117); the National High-Level Talents Special Support Plan (“Thousands of People Plan”); Shaanxi Provincial Youth Star of Science and Technology in 2016; and the Basic Scientific Research Funding of Xi'an Jiaotong University (SK2015007).