Folic acid may have a role in managing depression for some people when taken along with prescription antidepressants. Still, more research is needed to understand this effect and what form of supplemental folate may be most effective.
Mechanistically, folate is involved in the generation of S-adenosylmethionine (SAMe), a compound that is important for synthesizing neurotransmitters like dopamine, norepinephrine, and serotonin. Additionally, low folate levels may lead to high homocysteine, which has been positively correlated with depression symptom severity.[1] Although research has generally been mixed regarding whether depression is associated with reduced folate status,[2][3][1] folate deficiency has been associated with an increased risk of depression and longer, more severe episodes of depression.[1]
Folic acid taken along with antidepressant medications, specifically selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs), may reduce depression symptoms and increase rates of remission compared to antidepressants alone.[4][5][6] However, supplementing with L-methylfolate (an active form of folate that can cross the blood-brain barrier) may be more effective than folic acid.[7][8]
Importantly, there is insufficient research to suggest that folic acid or L-methylfolate taken alone is effective for depression or to determine whether folic acid or L-methylfolate are effective when taken with other types of antidepressants (e.g., tricyclic antidepressants).
References
- ^Bender A, Hagan KE, Kingston NThe association of folate and depression: A meta-analysis.J Psychiatr Res.(2017-Dec)
- ^Gilbody S, Lightfoot T, Sheldon TIs low folate a risk factor for depression? A meta-analysis and exploration of heterogeneityJ Epidemiol Community Health.(2007 Jul)
- ^Petridou ET, Kousoulis AA, Michelakos T, Papathoma P, Dessypris N, Papadopoulos FC, Stefanadis CFolate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis.Aging Ment Health.(2016-Sep)
- ^Rabail Altaf, Irasema Gonzalez, Kimberley Rubino, Eric C Nemec 2ndFolate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysisComplement Ther Med.(2021 Sep)
- ^Zheng W, Li W, Qi H, Xiao L, Sim K, Ungvari GS, Lu XB, Huang X, Ning YP, Xiang YTAdjunctive folate for major mental disorders: A systematic review.J Affect Disord.(2020-Apr-15)
- ^Khalili P, Asbaghi O, Aghakhani L, Clark C, Haghighat NThe effects of folic acid supplementation on depression in adults: a systematic review and meta-analysis of randomized controlled trialsNutr Food Sci.(2022 Jul)
- ^Maruf AA, Poweleit EA, Brown LC, Strawn JR, Bousman CASystematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders.Pharmacopsychiatry.(2022-May)
- ^Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, Veronese N, Schuch F, Smith L, Solmi M, Carvalho AF, Vancampfort D, Berk M, Stubbs B, Sarris JThe efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trialsWorld Psychiatry.(2019 Oct)