vitamin · for low mood
Folate
Your body needs it to make serotonin and dopamine, the chemicals that steady your mood.
Say that in clinical terms
Folate is essential for SAMe synthesis, the primary methyl donor for monoamine neurotransmitter production (serotonin, dopamine, norepinephrine). Low folate status impairs methylation and is strongly associated with depression.
How strong is the research?
1 paper read, 1 supporting.
Who was studied: Studied in people with depression that had not responded to antidepressants, who kept taking them alongside.
How much to take
daily
800–1000 mcg
L-methylfolate (5-MTHF) bypasses MTHFR polymorphisms. Often used as adjunct to antidepressant therapy. Do not exceed 1000mcg without medical guidance.
Before you take it
- NIH ODS Tolerable Upper Intake Level (UL) for synthetic/supplemental folate is 1,000 mcg/day for adults aged 19+; the UL does not apply to naturally occurring food folate.
- High folate intake can mask vitamin B12 deficiency by correcting megaloblastic anemia while neurological damage from B12 deficiency progresses; B12 status should be assessed before supplementing, particularly in older adults.
- Folate antagonizes methotrexate (used in cancer and autoimmune conditions); concomitant supplementation can reduce methotrexate's therapeutic efficacy and should not occur without medical supervision.
- Antiepileptic drugs (phenytoin, carbamazepine, valproate) can deplete folate; folate supplementation can in turn reduce phenytoin efficacy — clinical monitoring is required when taking anticonvulsant therapy.
- Sulfasalazine inhibits folate absorption; concurrent use may worsen folate status.
- High synthetic folic acid intake may accelerate progression of preneoplastic lesions and potentially increase colorectal cancer risk in susceptible individuals; this risk has not been established for natural food folate or 5-MTHF specifically.
- L-methylfolate at high doses (15 mg/day and above) has been associated with onset or exacerbation of manic or hypomanic symptoms; individuals with bipolar disorder or a personal/family history of mania should use under medical supervision when supplementing for mood-related indications.
When to take it
Best taken: morning
What we make of it
The trial used doses ten times what we list, alongside antidepressants, in treatment-resistant depression.
The detail
The biology is well established. But the trial tested 7.5 to 15 mg as an add-on for depression that had not responded to medication, and only the 15 mg arm worked. The 800 to 1,000 mcg we list has no support from that study and sits near the safe upper limit for synthetic folate. Cochrane has found insufficient evidence for folate on its own.