Folate (Vitamin B9) for Mood Stabilization
L-methylfolate has some support as an add-on to antidepressants, particularly in people with low folate status.
Overview
Verdict
How It Works
Dosing & Protocol
Typical dose
- Recommended dose
- Adjunct to antidepressant treatment: 500 mcg/day folic acid, or 7.5-15 mg/day L-methylfolate in the trials of methylfolate augmentation
- Expected timeframe
- 8-12 weeks
Protocol
- form
- Folic acid for general repletion; L-methylfolate (5-MTHF) at 7.5-15 mg/day is what the augmentation trials used, and those doses are far above nutritional intakes
- duration
- 8-12 weeks as an adjunct; this is not a standalone treatment
- co factor
- Take consistently, with or without food. Evidence is mixed. Low folate status is associated with depression and with poorer response to SSRIs, and folate is a cofactor in synthesis of serotonin, dopamine and noradrenaline via tetrahydrobiopterin, so the rationale is sound. Randomised trials of L-methylfolate 15 mg/day added to an SSRI in partial responders showed improved response rates, while trials of plain folic acid as an adjunct have been inconsistent and the FolATED trial found no benefit. This works, if at all, as augmentation in people who have not fully responded - not as a first-line antidepressant, and not for mood stabilisation in bipolar disorder, where it has no established role.
- titration
- Methylfolate augmentation trials found 15 mg/day effective where 7.5 mg/day was not, so if used, use the studied dose. Check vitamin B12 before starting
- starting dose
- 500 mcg/day folic acid alongside existing antidepressant treatment, or 15 mg/day L-methylfolate where the methylfolate augmentation protocol is being followed
Evidence
What the studies say
No studies are yet linked to both Folate (Vitamin B9) and Mood Stabilization.
Safety
Caveats
Do not stop or replace prescribed antidepressant or mood-stabilising treatment - this is an adjunct only, and in bipolar disorder there is no evidence for folate as a mood stabiliser while stopping lithium or an antipsychotic carries serious relapse risk. Suicidal thoughts, inability to function or psychotic symptoms need urgent medical care. Check vitamin B12 before starting folate: folate corrects the anaemia of B12 deficiency while irreversible spinal cord degeneration progresses, and B12 deficiency itself causes low mood. Safety ceiling: the tolerable upper intake level for supplemental folic acid is 1000 mcg (1 mg) per day; the 7.5-15 mg methylfolate doses used in augmentation trials far exceed it and should only be taken under psychiatric supervision. Folate antagonises methotrexate, and lowers phenytoin, phenobarbital and primidone levels, risking seizures. In pregnancy 400 mcg daily is recommended, 5 mg where risk is higher.
Less likely to help if
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