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This study aims, a systematic review and meta-analysis, to evaluate the effects of folic acid (folate) on patients with depression.

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.

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.

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.