Beneficial effects of folic acid on inflammatory markers in the patients with metabolic syndrome: Meta-analysis and meta-regression of data from 511 participants in 10 randomized controlled trials

Previous clinical studies on the anti-inflammatory effects of folic acid (FA) in patients with metabolic syndrome (MetS) have shown controversial results. This study aimed to synthesize the evidence on the effect of FA on inflammatory marker levels in MetS patients. We screened PubMed, Embase, Medline, and the Cochrane Library (from inception to March 2022) to identify relevant randomized controlled trials (RCTs). DerSimonian and Laird random effects were used to estimate the pooled weighted mean difference (WMD) with 95% confidence interval (CI). Funnel plot, Egger's test, and the Begg-Mazumdar correlation test was used to assess publication bias. Subgroup analysis, meta-regression and sensitivity analysis were performed to find out possible sources of between-study heterogeneity. Ten RCTs with a total of 511 participants were included. The analysis showed that FA reduced high sensitivity C-reactive protein (hs-CRP) (WMD, -0.94; 95% CI, -1.56 to -0.32; P = 0.00), interleukin-6 (IL-6) (WMD, -0.39; 95% CI, -0.51 to -0.28; P = 0.00), and tumor necrosis factor-alpha (TNF-alpha) (WMD, -1.28; 95% CI, -1.88 to -0.68; P = 0.00), but did not decrease the C-reactive protein (CRP) (WMD, 0.10; 95% CI, -0.13 to 0.33; P = 0.38). Sensitivity analysis, subgroup analysis, and meta-regression showed that the effect sizes remained stable. Our findings suggest that FA supplementation could reduce inflammatory markers, such as hs-CRP, IL-6, TNF-alpha in patients with MetS. This study is registered with PROSPERO (CRD42021223843).