Synopsis

Source of validity: Scientific
Rating (out of 5): 3

Folic acid, the synthetic form of folate (vitamin B9), has been investigated for its role in supporting or treating depression. Scientific evidence suggests that folate deficiency is relatively common in people with depression, and low folate levels have been associated with poorer response to antidepressant treatments. Several clinical studies and meta-analyses indicate that supplementation with folic acid or its active form, L-methylfolate, may improve the efficacy of antidepressant medications, particularly in individuals with documented folate deficiency or certain genetic polymorphisms affecting folate metabolism (such as MTHFR mutations).

However, the overall evidence is mixed. While some randomized controlled trials and systematic reviews report modest improvements in depressive symptoms with folic acid or L-methylfolate supplementation, others do not find significant benefits, especially in people with normal baseline folate levels. The most consistent findings support the use of L-methylfolate as an adjunct to antidepressant therapy, rather than as a standalone treatment. Current clinical guidelines do not recommend routine folic acid supplementation for depression in the general population, but it may be considered in select cases, such as treatment-resistant depression with low folate status.

In summary, there is scientific rationale and moderate evidence (rated 3/5) supporting the adjunctive use of folic acid—especially L-methylfolate—in some individuals with depression, but it is not universally effective and should be targeted to those with specific deficiencies or risk factors.

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