Levomefolic Acid

Absorption

Absorbed in the proximal small intestines via the active proton-coupled folate transporter (PCFT) that transports both oxidized and reduced folic acids. Passive diffusion also occurs at the proximal and distal portions of the small intestines . A single oral dose of 906nmol of levomefolic acid in healthy females resulted in the mean peak plasma concentration of 39.4nmol/L .

Toxicity

Overdose of levomefolic acid is unlikely to cause clinically significant adverse events.

The Uses of Levomefolic Acid

As a natural, active form of folic acid, Levomefolic Acid can be used at the cellular level for DNA reproduction, the cysteine cycle and the regulation of homocysteine among other functions. It is a coenzymated form of folic acid and a more bioavailable alternative in dietary supple

The Uses of Levomefolic Acid

A 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. It is a coenzymated form of folic acid. It has been proposed for treatment of cardiovascular disease.

Background

Levomefolic acid (INN) is the metabolite of folic acid (Vitamin B9) and it is a predominant active form of folate found in foods and in the blood circulation, accounting for 98% of folates in human plasma . It is transported across the membranes including the blood-brain barrier into various tissues where it plays an essential role in the DNA synthesis, cysteine cycle and regulation of homocysteine, where it methylates homocysteine and forms methionine and tetrahydrofolate (THF). Levomefolate is approved as a food additive and is designated a GRAS (generally regarded as safe) compound . It is available commercially as a crystalline form of the calcium salt (Metafolin(R)), which has the stability required for use as a supplement . Supplementation of levomefolic acid is desired over folic acid due to reduced potential for masking vitamin B12 deficiency symptoms.

Indications

For the treatment and prevention of folate deficiency and for use as an antidote against folic acid antagonists. Contained in oral contraceptives to reduce the risk of neural tube defects arising from folic acid deficiency for pregnant women who conceived during use or shortly after the discontinuation of the product. Being studied for use as a treatment for cardiovascular diseases and adjunct therapy for patients undergoing antidepressant pharmacotherapy .

Definition

ChEBI: 5-methyltetrahydrofolic acid is a tetrahydrofolic acid that is 5,6,7,8-tetrahydrofolic acid substituted by a methyl group at position 5. It has a role as a human metabolite. It is functionally related to a 5,6,7,8-tetrahydrofolic acid. It is a conjugate acid of a 5-methyltetrahydrofolate(2-).

Pharmacokinetics

Levomefolic acid is an active metabolite of folic acid and a methyl group donor in one-carbon metabolism reactions. It regulates important cellular functions such as DNA biosynthesis, gene expression regulation, amino acid synthesis and metabolism, and myelin synthesis and repair. As a only form of folate that can cross the blood-brain barrier, it acts as a cofactor in the production of monoamine neurotransmitters such as dopamine, serotonin and norepinephrine . Levomefolic acid is also involved in red blood cell formation .

Metabolism

Levomefolic acid is further converted into tetrahydrofolate (THF) via the vitamin B12-dependent enzyme methionine synthase before effective polyglutamylation by folylpolyglutamate synthetase (FPG). Polyglumate forms of folic acids are more effective substrates for associated enzymes in folate-dependent reactions.