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

Aims: There are growing data and a continuing controversy over the efficacy of folic acid supplementation in stroke prevention. We conducted a meta-analysis based on relevant, up-to-date published randomised trials to further examine this issue. Methods: Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke with a fixed-effects model. Results: Overall, folic acid supplementation reduced the risk of stroke by 8% (n = 55,764; RR: 0.92; 95% CI: 0.861.00, p = 0.038). In the 10 trials with no or partial folic acid fortification (n = 43,426), the risk of stroke was reduced by 11% (0.89; 0.820.97, p = 0.010). Within these trials, a greater beneficial effect was observed among trials with a lower percent use of statins [= 80% (median); 0.77; 0.640.92, p = 0.005], and a meta-regression analysis also suggested a positive dose-response relationship between percent use of statins and log-RR for stroke associated with folic acid supplementation (p = 0.013). A daily dose of 0.40.8mg folic acid appeared to be adequate for stroke prevention in comparison with larger doses. In the remaining five trials conducted in populations with folic acid fortification (n = 12,338), folic acid supplementation had no effect on stroke risk (1.03; 0.881.21, p = 0.69). Conclusions: Our analysis indicated that folic acid supplementation is effective in stroke prevention in populations with no or partial folic acid fortification. In addition, a greater beneficial effect was observed among trials with a lower percent use of statins. Our findings underscore the importance of identifying target populations that can particularly benefit from folic acid therapy.