Folate supplementation as a beneficial add‐on treatment in relieving depressive symptoms: A meta‐analysis of meta‐analyses

Abstract The results of meta‐analyses investigating the role of folate on depression are conflicting. The aim of this umbrella meta‐analysis was to obtain an overall effect and give a concise and resolving conclusion. International scientific databases including PubMed, Scopus, and Web of Science were searched up to Oct 2023. All observational and interventional meta‐analyses investigating the role of folate in depression were included in the study. Random‐effects model was employed to obtain pooled results. I 2 statistics and Cochrane Q test were used to assess the between‐study heterogeneity. The quality of included meta‐analyses was evaluated using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR2) questionnaire. Overall 11 studies were included, of which 8 studies went under quantitative evaluation. The results indicated that folate supplementation significantly relieved depression symptoms (SMD: −0.42; 95% CI: −0.57, −0.27, p < .001; I 2 = 0.0%, p‐heterogeneity = 0.554) (WMD: −3.20; 95% CI: −4.00, −2.41, p < .001, I 2 = 14.8%, p‐heterogeneity = 0.318) with low levels of heterogeneity. Also, based on observational studies, folate insufficiency significantly increased the odds ratio of depression by 35% (OR:1.35; 95% CI: 1.27, 1.42, p < .001, I 2 = 8.7%, p ‐heterogeneity = 0.350). The findings support the fact that folate supplementation could be suggested as an efficacious and adjuvant agent in the alleviation of depression symptoms along with routine medications.