Levomefolic acid (5-MTHF) (5-MTHF)

Levomefolic acid, also known as 5-methyltetrahydrofolate (5-MTHF), is the primary biologically active form of folate found in the human body and circulation (PubChem CID 135398501). It is a critical component of the one-carbon metabolism cycle, serving as the primary methyl donor for the conversion of homocysteine to methionine via the enzyme methionine synthase (DrugBank DB06695). Unlike synthetic folic acid, levomefolic acid does not require enzymatic reduction by dihydrofolate reductase or methylenetetrahydrofolate reductase (MTHFR), making it particularly effective in individuals with MTHFR genetic polymorphisms (StatPearls NBK554487). It is essential for DNA synthesis, repair, and methylation, as well as the synthesis of key neurotransmitters like serotonin, dopamine, and norepinephrine (PubMed PMID 24351014). Clinically, it is utilized as a medical food or supplement to manage folate deficiency, hyperhomocysteinemia, and as an adjunct therapy for major depressive disorder to enhance the efficacy of antidepressants (NIH Folate Fact Sheet). Its ability to cross the blood-brain barrier allows it to directly influence central nervous system function, distinguishing it from other folate forms (PubMed PMID 24351014).

Other names

5-MethyltetrahydrofolateL-methylfolate5-methyl-5,6,7,8-tetrahydrofolic acidMetafolinDeplinQuatrefolic

Levomefolic acid acts as a methyl donor in the conversion of homocysteine to methionine and serves as a precursor for tetrahydrobiopterin (BH4) synthesis, which is a necessary cofactor for the production of monoamine neurotransmitters (DrugBank DB06695, PubMed PMID 24351014).