The effects of folic acid supplementation on depression in adults: a systematic review and meta-analysis of randomized controlled trials

Purpose: This study aims, a systematic review and meta-analysis, to evaluate the effects of folic acid (folate) on patients with depression. Design/methodology/approach: Related articles were found by searching PubMed, SCOPUS, Web of science and Cochrane’s Library, from inception to January 2022. Weighted mean differences (WMD) were pooled using a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods. Findings: Pooled analysis of six randomized controlled trials revealed that folic acid supplementation decreased the depression score in the Beck Depression Inventory (WMD: −3.9; 95% CI: −5.3 to −2.4, p < 0.001) compared with control group, without heterogeneity (I2 = 0.0%, p = 1.000). It also lowered the depression score in the Hamilton (HAM) Depression Inventory (WMD: −3.5 mg/dL; 95% CI: −4.6 to −2.4, p < 0.001) compared with control group, with moderate heterogeneity (I2 = 71.8%, p = 0.007). Moreover, subgroup analysis showed that the folic acid supplementation reduced HAM in all subgroups. Meta-regression analysis demonstrated that there is no evidence of a significant linear relationship between dose and duration of folic acid supplementation and changes in HAM. Also, based on the non-linear dose response, no evidence of a relationship between dose and duration of folic acid supplementation and changes in HAM was found. Originality/value: Folic acid supplementation could possibly have an effect on lowering depression in patients. However, the clinical trials thus far are insufficient for clinical guidelines and practice.