5-MTHF

5-MTHF (also known as 5-methyltetrahydrofolate) is the biologically active form of folate (vitamin B9). It is the primary form of folate used at the cellular level for DNA reproduction, the cysteine cycle, and homocysteine regulation. Unlike synthetic folic acid, 5-MTHF doesn't require conversion in the body, making it more bioavailable, especially for individuals with genetic variations affecting folate metabolism. ## Identification and Chemistry 5-MTHF is generated by methylenetetrahydrofolate reductase (MTHFR) from 5,10-methylenetetrahydrofolate. It functions, in concert with vitamin B12, as a methyl-group donor involved in converting homocysteine to methionine[1][5]. This methylation process is vital for many bodily functions, including serotonin, melatonin, and DNA synthesis[8]. The compound has a molecular weight of approximately 459.463 and chemical formula C20H25N7O6[1]. It is water-soluble and primarily excreted via the kidneys[5]. ## Clinical Applications 5-MTHF is used therapeutically for: - Reducing homocysteine levels in hyperhomocysteinemia[3][7][8] - Supporting neural tube development during pregnancy[4][7] - Improving vascular endothelial function[6][8] - Supporting individuals with MTHFR gene polymorphisms (affecting up to one-third of the population)[2][4] - Addressing folate deficiency[3] - Supporting patients with major depressive disorder who have folate deficiency[3] - Supporting patients with schizophrenia who have hyperhomocysteinemia related to folate deficiency[3] Research suggests 5-MTHF may also play roles in preventing cervical dysplasia, protecting against neoplasia in ulcerative colitis, treating vitiligo, reducing gingival inflammation, and addressing certain neurological, cognitive, and psychiatric conditions[8]. ## Advantages Over Folic Acid 5-MTHF offers significant advantages over synthetic folic acid: - Directly bioavailable without requiring enzymatic conversion[2][4][5] - Suitable for individuals with MTHFR gene variants who cannot efficiently convert folic acid[2][4] - Achieves higher peak plasma concentrations (129 ng/ml vs. 14.1 ng/ml for folic acid)[5] - Rapidly improves endothelial function and reduces vascular superoxide production[6] ## Formulations 5-MTHF is available as a medical food, dietary supplement, and in various pharmaceutical formulations. Commercial products include Quatrefolic (a glucosamine salt of 5-MTHF)[2] and branded medications like Deplin, Elfolate, L-Methylfolate Forte, and XaQuil XR[3].

Brand names

DeplinElfolateL-Methylfolate ForteXaQuil XRQuatrefolic

Other names

5-methyltetrahydrofolatebiologically active form of folatevitamin B9