School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Graduate Program in Food and Nutrition. Federal University of Piauí, Teresina-PI, Brazil.
Clin Ther. 2021 Dec;43(12):e346-e363. doi: 10.1016/j.clinthera.2021.10.002. Epub 2021 Nov 29.
Despite extensive research, findings regarding the effects of folic acid supplementation on inflammatory mediators have been controversial and inconclusive. This study therefore aimed to summarize the findings of all available clinical trials regarding the effects of folic acid supplementation on inflammatory biomarkers in adults.
A systematic search was conducted of PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and Google Scholar until April 2020. All randomized controlled trials that examined the influence of folic acid supplementation on C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were included. Pooled effect sizes were calculated based on the random effects model, and dose-response analysis was modeled by using a fractional polynomial model.
In total, 18 randomized controlled trials involving 2286 participants were analyzed. Folic acid supplementation significantly reduced serum levels of C-reactive protein (mean difference [MD], -0.21 mg/L; 95% CI, -0.41 to -0.01; n = 16), TNF-α (MD, -14.88 pg/mL; 95% CI, -23.68 to -6.09; n = 10), and IL-6 (MD, -0.93 pg/mL; 95% CI, -1.72 to -0.14; n = 11). Subgroup analyses suggested a significant reduction at doses ≤5 mg/d and studies longer than 12 weeks in duration. A significant nonlinear association was also found between folic acid dosage (P <0.001) and duration of administration (P <0.001) with serum TNF-α levels.
This meta-analysis indicates the beneficial effects of folic acid supplementation on pro-inflammatory cytokines. Further studies with a longer duration of administration, higher doses, and larger sample sizes should be performed exclusively on patients with chronic inflammatory disorders to elucidate the favorable role of folate intake on inflammatory biomarkers. International Prospective Register of Systematic Reviews identifier: CRD42021249947.
尽管进行了广泛的研究，但关于叶酸补充对炎症介质影响的研究结果仍存在争议且尚无定论。因此，本研究旨在总结所有关于叶酸补充对成人炎症生物标志物影响的临床试验结果。
系统检索了 PubMed/MEDLINE、Scopus、Web of Science、EMBASE 和 Google Scholar，检索时间截至 2020 年 4 月。纳入所有研究叶酸补充对 C 反应蛋白（CRP）、白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）影响的随机对照试验。基于随机效应模型计算合并效应量，并采用分数多项式模型进行剂量反应分析。
共纳入 18 项涉及 2286 名参与者的随机对照试验。叶酸补充可显著降低 CRP（平均差值 [MD]，-0.21 mg/L；95%置信区间 [CI]，-0.41 至 -0.01；n=16）、TNF-α（MD，-14.88 pg/mL；95%CI，-23.68 至 -6.09；n=10）和 IL-6（MD，-0.93 pg/mL；95%CI，-1.72 至 -0.14；n=11）的血清水平。亚组分析表明，剂量≤5 mg/d 和持续时间超过 12 周的研究中，叶酸补充的效果更显著。还发现血清 TNF-α水平与叶酸剂量（P<0.001）和给药时间（P<0.001）之间存在显著的非线性关系。
本荟萃分析表明，叶酸补充对促炎细胞因子具有有益作用。应该进行持续时间更长、剂量更高和样本量更大的研究，专门针对患有慢性炎症性疾病的患者，以阐明叶酸摄入对炎症生物标志物的有利作用。国际前瞻性系统评价注册中心登记号：CRD42021249947。
