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5-MTHF (Quatrefolic)

Ingredient common name

5-MTHF; Active folate; Vitamin B9

Supports women’s reproductive health*
Promotes heart and blood vessel health*
Enhances mood* 

Patented ingredient name

Gnosis USA, Inc.

Grown in

Dietary sources
Spinach, collard greens, kale, Swiss chard, asparagus, broccoli, Brussels sprouts, avocado, papaya, oranges, grapefruit, strawberries, lentils, peas/split peas, and beans (pinto, kidney, black, etc.)
  • Stabilized by glucosamine (not derived from shellfish)
  • This form passes the gastric barrier and is absorbed mainly in the small intestine by a carrier-mediated mechanism, which ensures higher folate uptake
  • Created by Gnosis, the technology leader in active folate supplementation
  • Contains only the active isomer form of 5-MTHF
  • Identity (HPLC)
  • Specific rotation
  • Heavy metals
  • Microbes

Contained In

Clinical References

Pregnancy and Fetal Development

Rai V, Yadav U, Kumar P, et al. Maternal methylenetetrahydrofolate reductase C677T polymorphism and Down Syndrome risk: a meta-analysis from 34 studies. PLoS One 2014;9(9):e108552.

Obeid R, Holzgreve W, Pietrzik K. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects? J Perinat Med 2013;41(5):469-483.

Seremak-Mrozikiewicz A, Drews K, Kurzawinska G, et al. The significance of 1793G>A polymorphism in MTHFR gene in women with first trimester recurrent miscarriages. Neuro Endocrinol Lett 2010;31(5):717-723.

Centers for Disease Control and Prevention (CDC). CDC grand rounds: additional opportunities to prevent neural tube defects with folic acid fortification. MMWR Morb Mortal Wkly Rep 2010;59(31):980-984.

Forges T, Monnier-Barbarino P, Alberto J, et al. Impact of folate and homocysteine metabolism on human reproductive health. Hum Reprod Update 2007;13(3):225-238.

Houghton L, Sherwood K, Pawlosky R, et al. [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr 2006;83(4):842-850.George L, Mills J, Johansson A, et al. Plasma folate levels and risk of spontaneous abortion. JAMA 2002;288(15):1867-1873.

Cognitive Function/Mood

Mitchell E, Conus N, Kaput J. B vitamin polymorphisms and behavior: Evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neurosci Biobehav Rev 2014;47:307-320.

Lewis S, Araya R, Leary S, et al. Folic acid supplementation during pregnancy may protect against depression 21 months after pregnancy, an effect modified by MTHFR C677T genotype. Eur J Clin Nutr 2012;66(1):97-103.

Ginsberg L, Oubre A, Daoud Y. L-methylfolate Plus SSRI or SNRI from treatment Initiation compared to SSRI or SNRI monotherapy . . . . Innov Clin Neurosci 2011;8(1):19-28.

Morris M, Jacques P, Rosenberg I, Selhub J. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in . . . cognitive test performance in American seniors. Am J Clin Nutr 2010;91(6):1733-1744.

Blood Pressure Support

Cagnacci A, Cannoletta M, Volpe A. High-dose short-term folate administration modifies ambulatory blood pressure in postmenopausal women. A placebo-controlled study. Eur J Clin Nutr 2009;63(10):1266-1268.


Ambrosino P, Lupoli R, Di Minno A, et al. Cyclic supplementation of 5-MTHF is effective for the correction of hyperhomocysteinemia. Nutr Res 2015;35(6):489-495.

Akoglu B, Schrott M, Bolouri H, et al. The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study. Eur J Clin Nutr 2008;62(6):796-801.

Genetic Polymorphisms

Tsang B, Devine O, Cordero A, et al. Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: A systematic review and meta-analysis of trials and observational studies. Am J Clin Nutr 2015;101(6):1286-1294.


Scaglione F, Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica 2014;44(5):480-488.

EFSA Positive Scientific Opinion. Scientific Opinion on (6S)-5-methyltetrahydrofolic acid, glucosamine salt as a source of folate added for nutritional purposes to food supplements. EFSA Journal 2013.

Pietrzik K, Bailey L, Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 2010;49(8):535-548.