PT - JOURNAL ARTICLE AU - Zhao, Min AU - Wu, Guangliang AU - Li, Youbao AU - Wang, Xiaobin AU - Hou, Fan Fan AU - Xu, Xiping AU - Qin, Xianhui AU - Cai, Yefeng TI - Meta-analysis of folic acid efficacy trials in stroke prevention AID - 10.1212/WNL.0000000000003909 DP - 2017 May 09 TA - Neurology PG - 1830--1838 VI - 88 IP - 19 4099 - http://n.neurology.org/content/88/19/1830.short 4100 - http://n.neurology.org/content/88/19/1830.full SO - Neurology2017 May 09; 88 AB - Objective: To examine the efficacy and effect modifiers of folic acid supplementation in the prevention of stroke in regions without folic acid fortification based on relevant, up-to-date published randomized trials.Methods: Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke using a fixed effects model.Findings: Overall, folic acid supplementation significantly reduced the stroke risk by 11% (22 trials, n = 82,723; RR 0.89, 95% confidence interval [CI] 0.84–0.96). The effect was greater in low folate regions (2 trials, n = 24,020; Asia, 0.78, 0.67–0.90) compared to high folate regions (7 trials, n = 14,655; America, 1.05, 0.90–1.23), and among patients without folic acid fortification (11 trials, n = 49,957; 0.85; 0.77–0.94) compared with those with folic acid fortification (7 trials, n = 14,655; 1.05, 0.90–1.23). In further stratified analyses among trials without folic acid fortification, a larger beneficial effect was found in those trials that used a low dosage of folic acid (≤0.8 mg: 0.78, 0.69–0.88) or low baseline vitamin B12 levels (<384 pg/mL: 0.78, 0.68–0.89). In the corresponding comparison groups, the effect sizes were attenuated and insignificant (p for interaction <0.05 for both). Although the interaction tests were not significant, there might be a higher benefit in trials with a low dosage of vitamin B12, a low prevalence of statin use, but a high prevalence of hypertension.Conclusions: Folic acid supplementation could reduce the stroke risk in regions without folic acid fortification, particularly in trials using a relatively low dosage of folic acid and with low vitamin B12 levels.CI=confidence interval; CSPPT=China Stroke Primary Prevention Trial; CVD=cardiovascular disease; RCT=randomized controlled trial; RR=relative risk