Levomefolic Acid

Levomefolic acid (INN) (also known as 5-MTHF, l-methylfolate and 5-methyltetrahydrofolate) is the natural, active form of folic acid used at the cellular level for DNA reproduction, the cysteine cycle and the regulation of homocysteine among other functions. The un-methylated form, folic acid (vitamin B₉), is a synthetic form of folate found in nutritional supplements. Synthetic folic acid is metabolized in the body into levomefolic acid. Approximately 10% of the general population (homozygous TT) lack the enzymes needed to receive any benefit from folic acid. Another 40% of the population (heterozygous CT) appear to convert only a limited amount of folic acid into levomefolic acid. They cannot fully process supplemental folic acid at RDA or higher dose levels. The remaining population do not have a known MTHFR polymorphism and can therefore metabolize folic acid more efficiently.

It is synthesized in the absorptive cells of the small intestine from polyglutamylated dietary folate. It is a methylated derivate of tetrahydrofolate (THF, H₄F). Levomefolic acid is generated by methylenetetrahydrofolate reductase (MTHFR) from 5,10-methylenetetrahydrofolate (5,10-CH₂-THF, MTHF) and used to recycle homocysteine back to methionine by 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) also known as methionine synthase (MS).

Levomefolic acid has been proposed for treatment of cardiovascular disease and advanced cancers such as breast and colorectal cancers. It bypasses several metabolic steps in the body and better binds thymidylate synthase with fDump, a metabolite of the drug fluorouracil.

Levomefolate calcium, a calcium salt of levomefolic acid, is sold under the brand names Metafolin and Deplin.