Levomefolic acid (INN) (also known as 5-MTHF, l-methylfolate and 5-methyltetrahydrofolate) is the 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 form of folate found in a variety of foods and can be isolated or synthesized for use in nutritional supplements. Folic acid is metabolized in the body into levomefolic acid. Approximately 10% of Caucasian and Asian populations (homozygous TT) have 70% less activity in 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.
Levomefolic acid (and folic acid in turn) 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 (a registered trademark of Merck KGaA) and Deplin (trademark of Pamlab, LLC).
MTHFR metabolism: folate cycle, methionine cycle, trans-sulfuration and hyperhomocysteinemia
Commercial use of levomefolic acid in pharmaceutical products began in Europe in the early part of this decade[clarification needed] and have now[when?] appeared in the United States. Supplementation of folate/folic acid has potential to impact prenatal care, homocysteine management, and the treatment of depression, dementia and cardiovascular concerns.
Prenatal care: low folate status has been linked to neural tube defects, recurrent pregnancy loss, low birth weight and a variety of age-related high risk complications of pregnancy.
Homocysteine management: elevated homocysteine is frequently linked to the presence of the MTHFRpolymorphism.
Depression: folate status has been linked to the performance of SSRI drugs. Many patients have required folate supplementation in order to adequately respond to standard treatment protocol.
Dementia: folate status has been linked to the efficacy of neural transmitters and cognitive performance. Only active, levomefolic acid can cross the blood brain barrier.
Diabetic neuropathy: folate status has been shown to have a substantial impact upon wound care.
5-MTHF is widely available as over-the-counter nutritional supplements or as pharmaceutical preparations.
In March 2012, Merck & Cie of Switzerland, Pamlab LLC (maker of Metanx and Cerefolin, Neevo DHA, and Deplin), and South Alabama Medical Science Foundation (SAMSF) (the plaintiffs) filed a complaint in the United States District Court for the Eastern District of Texas against four defendants - Macoven Pharmaceuticals (owned by Pernix Therapeutics), Gnosis SpA of Italy, Gnosis U.S.A and Gnosis Bioresearch Switzerland. The plaintiffs alleged that the defendants infringed on several of the plaintiffs' patents. The Macoven products named in the suit are: "Vitaciric-B", "ALZ-NAC", "PNV DHA", and l-methylfolate calcium (levomefolate calcium).