Folate 5-MTHF — Supplements
Bioactive methylated form of folate bypassing MTHFR enzyme for optimal methylation and DNA synthesis.
Overview
5-Methyltetrahydrofolate (5-MTHF) is the biologically active, methylated form of folate that directly participates in one-carbon metabolism without requiring conversion by MTHFR (methylenetetrahydrofolate reductase). This is clinically significant because up to 40% of the population carries MTHFR polymorphisms (C677T or A1298C) that reduce enzymatic conversion of folic acid to active 5-MTHF. Folate is essential for DNA synthesis, methylation reactions, homocysteine metabolism, and neural tube development. 5-MTHF supplementation effectively raises folate status regardless of MTHFR genotype.
Indications
- Homocysteine reduction and methylation support
- Neural tube defect prevention (preconception/prenatal)
- MTHFR polymorphism management
- DNA synthesis and cell division support
- Mood and cognitive support (adjunctive to antidepressants)
Mechanism of Action
5-MTHF donates its methyl group to homocysteine via methionine synthase (B12-dependent), regenerating methionine
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| 5-MTHF (Methylfolate) | 1,000 mcg | Once daily | Preferred over folic acid for individuals with MTHFR polymorphisms |
Evidence Grade
GRADE C
Safety & Contraindications
- High-dose folate may mask vitamin B12 deficiency (megaloblastic anemia); always co-supplement B12
- 5-MTHF does not interfere with methotrexate efficacy (unlike folic acid)
- Generally well tolerated; rare reports of GI upset or insomnia
- Excessive folate may theoretically promote growth of pre-existing neoplastic cells