Beneficial effects of folic acid supplementation on lipid markers in adults: A GRADE-assessed systematic review and dose-response meta-analysis of data from 21,787 participants in 34 randomized controlled trials

Folic acid supplementation has received considerable attention in the literature, yet there is a large discrepancy in its effects on lipid markers in adults. Therefore, this systematic review and meta-analysis of 38 randomized controlled trials (RCTs) evaluated the effects of folic acid supplementation on triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations in a cohort of 21,787 participants. A systematic search current as of March 2021 was performed in PubMed/Medline, Scopus, Web of Science, and Embase using relevant keywords to identify eligible studies. A fix or random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence intervals (CIs). Thirty-four RCTs were included in this meta-analysis. The pooled analysis revealed that serum TG (WMD: -9.78 mg/dL; 95% CI: -15.5 to -4.00; p = 0.001, I-2=0.0%, p = 0.965) and TC (WMD: -3.96 mg/dL; 95% CI: -6.71 to -1.21; p = 0.005, I-2=46.9%, p = 0.001) concentrations were significantly reduced following folic acid supplementation compared to placebo. However, folic acid supplementation did not affect serum concentrations of LDL (WMD: -0.97 mg/dL; 95% CI: -6.82 to 4.89; p = 0.746, I-2=60.6%, p < 0.001) or HDL cholesterol (WMD: 0.44 mg/dL; 95% CI: -0.53 to 1.41; p = 0.378, I-2= 0.0%, p = 0.831). A significant dose-response relationship was observed between the dose of folic acid supplementation and serum concentrations of HDL cholesterols (r = 2.22, p = 0.047). Folic acid supplementation reduced serum concentrations of TG and TC without affecting LDL or HDL cholesterols. Future large RCTs on various populations are needed to show further beneficial effects of folic acid supplementation on lipid profile.