Featured article | May 2025
Folate and Its Significance in Depressive Disorders and Suicidality: A Comprehensive Narrative Review
Liwinski T & Lang UE
The article explores the role of folate in the onset, progression, and treatment of depressive disorders and suicidality. It highlights the potential benefits of folate/folic acid and its active form, L-methylfolate, as adjunct therapies in depression, particularly for individuals with folate deficiencies.
Discussed in the article:
- Standard antidepressant treatments have limited success, with many patients not achieving remission.
- Low levels of serum and red blood cell folate are common in individuals with depression.
- Folate plays a crucial role in central nervous system functions and neurotransmitter synthesis.
- Studies of folic acid and L-methylfolate show benefit as adjunct therapies for depression.
- The roles of the one-carbon cycle (a network of biochemical pathways that transfer methyl groups), folate–homocysteine balance, immune function, NMDA receptor activity, and gut microbiome in mood regulation.
Dosing information:
- L-methylfolate (25 mg/day) was as effective as amitriptyline (150 mg/day) in treating mild-to-moderate depression.
- Patients with major depressive disorder and RBC folate deficiency who received 15 mg/day of L-methylfolate alongside antidepressants experienced significantly greater improvements in depressive symptoms compared to those receiving placebo.
- After an average of 95 days of treatment with L-methylfolate (7.5 or 15 mg/day), 67.9% of patients responded and 45.7% achieved remission, with notable improvements in depression severity, daily functioning, and medication satisfaction.
- Use of 1 mg/day of folic acid was associated with a 43% lower hazard of suicide events (HR 0.57). Each additional month of treatment further reduced suicide risk by 5% (HR 0.95 per month).
“Depressed individuals often exhibit low levels of serum and red blood cell folate.”
