5-MTHF Folate (Quatrefolic)

400mcg

The biologically active form of folate - directly utilisable without MTHFR enzyme conversion. Standard folic acid requires two conversion steps; ~40% of people have MTHFR variants reducing efficiency. Quatrefolic bypasses this. Essential for DNA synthesis, homocysteine clearance, and neural tube formation.

Category Micronutrients
Dose 400mcg
Form Glucosamine salt of (6S)-5-methyltetrahydrofolate - Gnosis Quatrefolic
Evidence Level Strong - clinically superior to folic acid for MTHFR variants

Mechanism

5-methyltetrahydrofolate (5-MTHF) is the predominant circulating form of folate and the direct substrate for methionine synthase - donating its methyl group to convert homocysteine to methionine (with methylcobalamin B12 as cofactor). This regenerates methionine for the SAM cycle and clears potentially harmful homocysteine from the bloodstream.

Standard folic acid (the form in most supplements) requires two MTHFR enzyme steps to reach 5-MTHF. MTHFR C677T - a common SNP present in ~40% of individuals - significantly reduces this conversion efficiency, meaning folic acid supplementation leaves many people with inadequate active folate despite nominally meeting NRV targets. Quatrefolic is the (6S)-5-MTHF glucosamine salt - the stereochemically pure, bioidentical active form that bypasses MTHFR entirely.

Key Benefits

  • Directly bioactive - no MTHFR conversion required
  • Clears homocysteine via methionine synthase with B12
  • Critical for DNA synthesis and cell division
  • Bypasses MTHFR C677T conversion impairment (~40% of people)
  • 400mcg = 200% UK NRV

The Research

Peer-reviewed human trials supporting this ingredient at this dose.

Scaglione F, Panzavolta G. (2014). Xenobiotica. 44(5):480-8.Folate, folic acid and 5-methyltetrahydrofolate are not the same thing.PubMed →
Prinz-Langenohl R, et al. (2009). Br J Pharmacol. 158(8):2014-21.[6S]-5-methyltetrahydrofolate increases plasma folate more effectively than folic acid in MTHFR variants.PubMed →
Greenberg JA, et al. (2011). Rev Obstet Gynecol. 4(2):52-9.Folic acid supplementation and pregnancy: more than just neural tube defect prevention.PubMed →
In the formula

5-MTHF Folate (Quatrefolic)

400mcg

Glucosamine salt of (6S)-5-methyltetrahydrofolate - Gnosis Quatrefolic

When to take it

Any time of day. 5-MTHF is the active folate form - directly utilisable without MTHFR-mediated conversion. Particularly important for the ~40% of people with MTHFR C677T polymorphism.