Department of Cardiology, Peking University First Hospital, Beijing, China.
Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clin Nutr. 2024 Jul;43(7):1706-1716. doi: 10.1016/j.clnu.2024.05.034. Epub 2024 May 28.
BACKGROUND & AIMS: The AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical trials, and an additional 13 folate trials have been published since then. This meta-analysis aims to fill in critical evidence gaps by comprehensively evaluating 21 published trials with particular attention given to identifying the true influences through stratification.
PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 4, 2023. This study included all randomized controlled trials (RCTs) of folic acid with stroke as one of the reporting endpoints. Relative risks and 95% confidence intervals were used to assess the association between folic acid supplementation and the risk of stroke in a random-effects model.
Results from the 21 pooled RCTs totaling 115,559 participants showed that folic acid supplementation significantly reduced the risk of stroke by 10% (RR 0.90, 95%CI 0.83 to 0.98). Subgroup analyses showed that folic acid efficacy was greater in areas without fortified grain or with partially-fortified grain (RR = 0.83, 95% CI 0.75 to 0.93; RR = 1.04 in areas with grain fortification, P-interaction = 0.003). In this group, folic acid supplementation was most efficacious in those without a history of stroke or myocardial infarction (RR = 0.77, 95% CI 0.68 to 0.86; RR = 0.94 for participants with a history of stroke or myocardial infarction, P-interaction = 0.008). The efficacy of folic acid remained consistent regardless of baseline folate levels, folic acid dosage, baseline vitamin B12 levels, vitamin B12 dosage, homocysteine reduction, intervention duration, and whether folic acid was taken alone or in combination (all P-interaction>0.05). All 21 trials were free of attrition bias and reporting bias, and there was no significant publication bias.
This is by far the largest meta-analysis of RCTs regarding folic acid supplementation and stroke, demonstrating the overall benefit of folic acid for stroke prevention. Grain fortification and history of stroke or myocardial infarction may be the most important influences on the efficacy of folic acid for stroke prevention.
美国心脏协会/美国卒中协会的一级预防指南已近十年。目前关于叶酸补充的建议仅基于 8 项临床试验，此后又发表了 13 项叶酸试验。本荟萃分析旨在通过全面评估 21 项已发表试验来填补关键证据空白，特别关注通过分层确定真实影响。
从建库到 2023 年 4 月 4 日，检索了 PubMed、Cochrane 对照试验中心注册库和 Embase。本研究纳入了所有以卒中为报告终点之一的叶酸随机对照试验（RCT）。采用随机效应模型，使用相对风险和 95%置信区间评估叶酸补充与卒中风险之间的关联。
来自 21 项汇总 RCT 的结果共纳入了 115559 名参与者，结果表明叶酸补充可使卒中风险降低 10%（RR 0.90，95%CI 0.83 至 0.98）。亚组分析显示，在无强化谷物或部分强化谷物地区，叶酸的疗效更大（RR=0.83，95%CI 0.75 至 0.93；RR=1.04 在谷物强化地区，P 交互=0.003）。在该组中，无卒中或心肌梗死病史的患者中，叶酸补充的疗效最佳（RR=0.77，95%CI 0.68 至 0.86；RR=0.94 有卒中或心肌梗死病史的患者，P 交互=0.008）。无论基线叶酸水平、叶酸剂量、基线维生素 B12 水平、维生素 B12 剂量、同型半胱氨酸降低、干预持续时间以及叶酸单独使用还是联合使用，叶酸的疗效均保持一致（所有 P 交互值>0.05）。所有 21 项试验均无失访偏倚和报告偏倚，且无明显发表偏倚。
这是迄今为止关于叶酸补充与卒中的最大 RCT 荟萃分析，证明了叶酸在预防卒中方面的总体益处。谷物强化和卒中或心肌梗死史可能是影响叶酸预防卒中疗效的最重要因素。
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