Levomefolic acid

Levomefolic acid (INN) or metafolin (5-methyltetrahydrofolic acid) 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.

Commercial use
Commercial use of levomefolic acid in pharmaceutical products began in Europe in the early part of this decade and have now appeared in the U.S. This approach to folate supplementation 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 MTHFR polymorphism.


 * 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.

Brands
Oral doses of levomefolic acid have been developed in Germany and are marketed under the brand name Metafolin.


 * Cerefolin NAC (5.6 mg) – Nutritional requirements of individuals under a physician's treatment for neurovascular oxidative stress or hyperhomocysteinemia, with particular emphasis for those individuals diagnosed with or at risk for mild to moderate cognitive impairment, vascular dementia, Alzheimer's disease or recurrent or ischemic.


 * Deplin (7.5 mg or 15 mg) – Dietary management of suboptimal folate levels in depressed patients.


 * Metanx (2.8 mg) – Dietary management of endothelial dysfunction in patients with diabetic peripheral neuropathy.


 * Néevo and NeevoDHA (1 mg) – Dietary management of those women under a physician's treatment for vitamin deficiency throughout pregnancy, postnatal and the lactating periods. Néevo is specifically indicated for: patients with high risk pregnancies, older OB patients, and patients unable to fully metabolize folic acid.


 * Zervalx (1 mg) – Dietary management of the following patient conditions: preconception hyperhomocysteinemia; intermediate to higher-risk pregnancies that require an increased dietary folate intake; hemolytic, megaloblastic or sickle cell anemia complicated by folate deficiency; and methotrexate induced plasma hyperhomocysteinemia.