Suggested Use: Take 1 or 2 capsules daily with meals, or as recommended by your healthcare practitioner.
Humans cannot synthesize folates. They must obtain them from dietary sources. 5-methyl-tetrahydrofolate (5-MTHF) is the predominant form of dietary folate and the only species normally found in the circulation, and thus it is the folate normally transported into peripheral tissues for use in cellular metabolism.1 Quatrefolic® is (6S)-5-methylfolate, a stable and highly-soluble form of 5-MTHF. Folic acid (FA), in contrast, is a synthetic, oxidized form of the vitamin that has been conventionally used for supplementation and food fortification. Folic acid lacks coenzyme activity and must be reduced to the metabolically active tetrahydrofolate (THF) form within the cell.
Cellular metabolism of L-methylfolate begins with conversion to unsubstituted THF in what is known as the “methylation cycle.” This conversion occurs via reaction of ingested 5-MTHF with vitamin B12- dependent methyltransferase and homocysteine to form methionine and THF, which subsequently becomes polyglutamated.2 There is some evidence, however, that the metabolic capacity of intestinal cells to reduce FA may be limited or compromised in a substantial percentage of individuals. If FA is ingested in higher doses by such individuals, unmetabolized FA may appear in the circulation.3 4 5 Although the clinical relevance of this remains unknown, the presence of unmetabolized FA may be a concern because it can enter cells, with potential of effects on folate-related cellular functions, such as synthesis of DNA and RNA.
Quatrefolic is a fourth-generation folate, stabilized as a salt of glucosamine, and has greater than 99% purity. Quatrefolic is estimated to be 100 times more soluble than the commonly used calcium salt of 5-MTHF.6 Because 5-MTHF has demonstrated bioequivalence with folic acid, supplementation with the natural folate derivative is thought to confer the beneficial effects associated with folic acid, but without the potential disadvantages of accumulation of unmetabolized folic acid or masking of vitamin B-12 deficiency.2
Quatrefolic® is a registered trademark of Gnosis S.p.A.
Pietrzik K, Bailey L, Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48. Pentieva K, McNulty H, Reichert R, et al. The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. J Nutr. 2004 Mar;134(3):580–5. Perry J, Chanarin I. Intestinal absorption of reduced folate compounds in man. Br J Haematol. 1970;18: 329–39. Kelly P, McPartlin J, Goggin M, Weir DG, Scott JM. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr. 1997;65:1790–5. Fohr IP, Prinz-Langenohl R, Brönstrup A, et al. 5, 10-Methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women. Am J Clin Nutr. 2002;75:275–82. Gnosis USA, Inc. Quatrefolic Solubility Statement. Data on file.