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: 0.86-1.00, 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; 0.82-0.97, 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; 0.64-0.92, 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 0.4-0.8mg 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; 0.88-1.21, 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.
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