5MTHF

5-Methyl-tetrahydrofolate (5-MTHF), also known as L-5-MTHF, is the bioactive form of folate in humans and the predominant circulating folate in plasma. It participates directly in one-carbon metabolism and does not require initial activation to the methylated form to function in cellular processes.

In folate metabolism, dietary and gut-derived folates are converted to tetrahydrofolate (THF) derivatives. The enzyme methylenetetrahydrofolate reductase (MTHFR) converts 5,10-methylene THF to 5-MTHF, which then donates a methyl group to homocysteine via methionine synthase, with vitamin B12 as a cofactor, forming methionine. Methionine can be converted to S-adenosylmethionine (SAM), a universal methyl donor for numerous methylation reactions, including DNA, proteins, and lipids. 5-MTHF also contributes to the synthesis of purines and thymidylate, essential for DNA replication and repair.

Physiologically, 5-MTHF is the major circulating form of folate and can cross the placenta, supporting fetal development. It is used in dietary supplements and sometimes in fortified foods to ensure adequate folate status, particularly for individuals who have reduced MTHFR activity or prefer to bypass the need for folic acid activation.

Supplement forms include calcium L-5-MTHF (calcium salt) and dipotassium salts, marketed under various brand names (one well-known example is Metafolin). Safety is generally favorable at recommended doses; excessive folate can mask vitamin B12 deficiency and may interact with certain drugs such as anticonvulsants and methotrexate.

See also: folate, folic acid, MTHFR, one-carbon metabolism.