Low folate has been causatively linked to depression, but research is contradictory. An association may arise due to chance, bias, confounding or reverse causality. A systematic review of observational studies which examined the association between depression and folate was conducted. 11 relevant studies (15 315 participants; three case–control studies, seven population surveys and one cohort study) examining the risk of depression in the presence of low folate were found. Pooling showed a significant relationship between folate status and depression (odds ratio (OR)pooled unadjusted = 1.55; 95% CI 1.26 to 1.91). This relationship remained after adjustment for potential confounding (OR)pooled adjusted = 1.42; 95% CI 1.10 to 1.83). Folate levels were also lower in depression. There is accumulating evidence that low folate status is associated with depression. Much of this evidence comes from case–control and cross-sectional studies. Cohort studies and definitive randomised-controlled trials to test the therapeutic benefit of folate are required to confirm or refute a causal relationship.
- MTHFR, methylene tetrahydrofolate reductase
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Competing interests: None declared.
Each of the authors has contributed to the conception, design, conduct and analysis of this study and to the writing of this paper. SG acted as lead reviewer and is the guarantor of this paper.