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

Abstract

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.

Intended and Unintended Benefits of Folic Acid Fortification—A Narrative Review

“…A collective analysis of six RCTs demonstrated that supplementation of folic acid resulted in a decrease in depression scores, as measured by the Beck Depression Inventory (WMD: −3.9; 95%CI: −5.3, −2.4). Additionally, it resulted in a lower depression score on the Hamilton Depression Inventory (WMD: −3.5; 95%CI: −4.6, −2.4); p < 0.001) compared to the control group [ 51 ]. A meta-analysis consisting of data from 15,315 participants (1769 subjects with depression and 13,546 control subjects) revealed a significant association between folate status and depression (pooled adjusted OR:1.42; 95%CI: 1.1, 1.83) [ 52 ].…”

The role of diet in managing menopausal symptoms: A narrative review

“…One meta‐analysis reported that vitamin B12 or folate decreased the risk of depression relapse and the onset of symptoms in at‐risk people (Almeida et al, 2015) and two meta‐analyses reported no significant benefit from combined B vitamin supplementation (Markun et al, 2021; Young et al, 2019), or vitamin B12 administered alone (Markun et al, 2021). Analysis of findings from folic acid supplementation trials has reported a benefit in improving depressive symptoms (Altaf et al, 2021; Khalili et al, 2022; Zheng et al, 2020), although the number of studies was small, sample sizes were generally small, a wide range of doses was used and significant heterogeneity was reported across studies. Results from a single RCT suggest that folic acid may be an effective adjunct to fluoxetine for treating depression in women (Venkatasubramanian et al, 2013), but no trials included women with a defined menopausal status.…”

Are probiotics beneficial for obese patients with major depressive disorder? Opinion for future implications and strategies

“…Probiotics consist of many types of microbes. The most commonly used microbes as probiotics are species from the genera Lactobacillus, Bifidobacterium, and Saccharomyces ( 16 ). Probiotics must be administered in a live state and in an effective dosage ( 15 ).…”

“…Some studies have found that probiotics can reduce symptoms of depression and improve the condition of patients ( 14 ). Gut probiotics can produce vitamins, such as vitamin B (Folic Acid and Pyridoxine), which, when deficient, may be involved in the etiology of depression and hinder the treatment of depression in patients ( 15 , 16 ). In addition, pyridoxine can also reduce symptoms of depression and anxiety ( 17 ).…”