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

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.