Efficacy of folic acid supplementation in stroke prevention: a meta-analysis

Background: The efficacy of treatments that lower homocysteine concentrations in reducing the risk of cardiovascular disease remains controversial. Our aim was to do a meta-analysis of relevant randomised trials to assess the efficacy of folic acid supplementation in the prevention of stroke. Methods: We collected data from eight randomised trials of folic acid that had stroke reported as one of the endpoints. Relative risk (RR) was used as a measure of the effect of folic acid supplementation on the risk of stroke with a random effect model. The analysis was further stratified by factors that could affect the treatment effects. Findings: Folic acid supplementation significantly reduced the risk of stroke by 18% (RR 0·82, 95% CI 0·68-1·00; p=0·045). In the stratified analyses, a greater beneficial effect was seen in those trials with a treatment duration of more than 36 months (0·71, 0·57-0·87; p=0·001), a decrease in the concentration of homocysteine of more than 20% (0·77, 0·63-0·94; p=0·012), no fortification or partly fortified grain (0·75, 0·62-0·91; p=0·003), and no history of stroke (0·75, 0·62-0·90; p=0·002). In the corresponding comparison groups, the estimated RRs were attenuated and insignificant. Interpretation: Our findings indicate that folic acid supplementation can effectively reduce the risk of stroke in primary prevention.