L-Methylfolate

L‑Methylfolate (5‑methyltetrahydrofolate, 5‑MTHF) is the biologically active, methyl‑donating form of folate that circulates in human plasma. It bypasses the genetic polymorphism of the enzyme methylenetetrahydrofolate reductase (MTHFR) and directly participates in one‑carbon metabolism, supporting DNA synthesis, neurotransmitter production, and methyl-group transfer reactions throughout the body.

• L‑Methylfolate is the L‑isomer of 5‑methyltetrahydrofolic acid, a tetrahydropteridine derivative.
• IUPAC name: (6S)-5‑Methyltetrahydrofolic acid (L‑form).
• Molecular formula: C₂₀H₂₃N₇O₆.
• Molar mass: 459.44 g·mol⁻¹.
• Key structural features: a pteridine ring fused to a para‑aminobenzoic acid (PABA) moiety, a reduced pteridine ring (tetrahydro), and a methyl group at the 5‑position of the pteridine ring.
• Solubility and Stability: The molecule is water‑soluble, with a pKa ≈ 6.3 (acidic) and a log P ≈ -0.8, indicating high hydrophilicity. Its stability is limited; it is prone to oxidation, thus formulations often include antioxidants (e.g., ascorbic acid) and are packaged in opaque, airtight containers.

• Production: L‑Methylfolate is produced primarily by microbial fermentation (e.g., Corynebacterium or Lactobacillus spp.) followed by purification, or by chemical synthesis from folic acid via enzymatic methylation using S‑adenosyl‑methionine as a methyl donor.
• Natural Sources: Natural dietary sources (leafy greens, legumes) contain folate, which is converted to L‑methylfolate in the gut and liver, but the amount is variable and influenced by MTHFR genotype.
• Supplement Quality: High‑quality supplements are typically produced under GMP (Good Manufacturing Practice) conditions, with verification of >95 % purity by HPLC and absence of heavy metals.
• Product Considerations: Look for products that provide a certificate of analysis, stability data, and, when applicable, certification of vegan or allergen‑free status.