L-5-Methyltetrahydrofolate (L-5-MTHF)
Also known as: L-methylfolate, 5-MTHF, levomefolic acid, methylfolate, L-5-methyltetrahydrofolate calcium, 5-MTHF glucosamine salt, (6S)-5-MTHF, Quatrefolic, Metafolin
L-5-methyltetrahydrofolate is the main circulating form of folate and the form cells use directly for homocysteine remethylation, so it bypasses the MTHFR enzyme step that is less active in people carrying the common 677C>T variant. NIH ODS reports its bioavailability is equal to or greater than folic acid's. Supplements supply it as a calcium salt or a glucosamine salt (branded examples include Metafolin and Quatrefolic), and it is the folate of choice in methylation, prenatal, and mood-support formulas that want to avoid unmetabolized folic acid.
Research summary
Donates its methyl group to homocysteine via methionine synthase (B12-dependent) to regenerate methionine and tetrahydrofolate, feeding the SAMe methylation cycle.
Dosage
Daily amounts, of compound.
| Lowest studied | Typical range | Highest studied | Upper limit |
|---|---|---|---|
| 400 mcg | 400–1,000 mcg | 1,000 mcg | 1,000 mcg |
NIH ODS — UL of 1,000 mcg/day is set for folic acid from supplements and fortified foods; applied to this synthetic folate form as a conservative ceiling
Doses are mcg of L-5-MTHF salt as labeled; the folate content of the salt differs by form (calcium salt about 91 percent 5-MTHF by mass, glucosamine salt about 72 percent), so confirm the supplier's declared folate equivalence. FDA allows a 1.7 conversion factor to mcg DFE for 5-MTHF (or a supplier-established factor not above 1.7), so 400 mcg can be labeled up to 680 mcg DFE. Prescription L-methylfolate at 7.5 to 15 mg is a medical food regimen outside supplement dosing. Pair with vitamin B12.
Standardization: ≥98% (6S)-5-MTHF calcium or glucosamine salt; supplied neat or as 1% to 2% dilutions
Source material: synthetic
As supplied: Commonly supplied as a 1% to 2% dilution on a carrier for premixes (0.1 mg powder per mcg at 1%); neat salt is used at mg doses. Supplier dependent.
Forms of Folate
| Form | Typical dose | Element % | Formats | Price |
|---|---|---|---|---|
| L-5-Methyltetrahydrofolate (L-5-MTHF) | 400–1,000 mcg | — | Capsule, Tablet, Powder, Gummy, Liquid, Softgel | high |
| Folic Acid | 400–800 mcg | — | Capsule, Tablet, Powder, Gummy, Liquid, Softgel | low |
| Folinic Acid (Calcium Folinate) | 400–800 mcg | — | Capsule, Tablet, Powder, Liquid | high |
Format suitability
- Capsule
- Powder
- Tablet
- Softgel
- Gummy
- Liquid
The glucosamine salt is more water-soluble and stable than the calcium salt, which helps in liquids and gummies. Light- and oxygen-sensitive; protect and consider overage.
Formulation notes
Pair with methylcobalamin or cyanocobalamin. Same methotrexate and antiepileptic interactions as folic acid. Glucosamine-salt grades are typically shellfish-free (fermentation derived) but confirm allergen status.
- Has an upper limit
- Notable drug interactions
Sources
Related ingredients
Folic Acid
VitaminFolic acid is the fully oxidized, synthetic form of folate used in food fortification and most supplements.
Typical: 400–800 mcg
Vitamin B12 (Cyanocobalamin)
VitaminCyanocobalamin is the synthetic, highly stable form of vitamin B12 used in most supplements and fortified foods.
Typical: 100–1,000 mcg
Vitamin B12 (Methylcobalamin)
VitaminMethylcobalamin is one of the two coenzyme forms of vitamin B12 that the body uses directly, in this case for the methionine synthase reaction that recycles homocysteine and supports methylation.
Typical: 100–1,000 mcg
Folinic Acid (Calcium Folinate)
VitaminFolinic acid (5-formyltetrahydrofolate) is a reduced, metabolically active folate supplied as its calcium salt.
Typical: 400–800 mcg
Vitamin D3 (Cholecalciferol)
VitaminThe form of vitamin D the body makes from sunlight and the most effective supplemental form for raising blood levels.
Typical: 1,000–2,000 IU