The 4th generation

Quatrefolic® represents an innovative dietary ingredient designed to act as a nutrient in all areas where folic acid and folate supplementation has been recommended and allowed. The terms folic acid and folate are often used interchangeably for the water-soluble B-complex vitamin, essential for the maintenance of cellular functions and health. Folate deficiency is one of the most common vitamin deficiencies and eating folate-rich foods may not provide the recommended daily dosage; thus the need for supplementation. Quatrefolic® is the glucosamine salt of (6S)-5-methyltetrahydrofolate and is structurally analogous to the reduced and active form of folic acid. Developed by Gnosis S.p.A, it represents the fourth generation folate providing greater stability, higher water solubility and multiple ingredient formulation flexibility compared to 5-methyltetrahydrofolate calcium salt guaranteeing an improved bioavailability.


Choosing Quatrefolic® as a source of folate presents several advantages both for manufacturer of dietary ingredients and for the consumer of supplements:

  • Provides the active form of folate, 5-methyltetrahydrofolate, naturally present in the body and available for its biological action.
  • Has been recognized GRAS. Gnosis has undertaken several in-vitro and in-vivo preclinical and clinical studies to characterize and guarantee the safety profile of the product.
  • Is a Gnosis proprietary product with pending patent and trademark applications guaranteeing a wide range of use and covering all areas of folate application.
  • Is produced according to cGMP, guaranteeing a reproducible quality profile.
  • Glucosamine, as a salt of (6S)-5-methyltetrahydrofolate does not come from animal sources and the product is suitable for vegetarian consumption.
  • Higher bioavailability and improved water solubility showed by Quatrefolic® respect to calcium salt open new perspectives and uses for combinations and formulations with vitamins and minerals both for dietary supplements and Food & Beverage industry.

Mechanism of action

The mechanism of action of Quatrefolic® is related to the action of 5-methyltetrahydrofolate the active part of the proprietary ingredient.

5-methyltetrahydrofolate derives from tetrahydrofolic acid, through a series of metabolic reactions. Tetrahydrofolic acid acts as a coenzyme in several vital metabolic reactions participating in the transfer as acceptors and donors of various one-carbon fragments, involved in the biosynthesis of nucleotides purines and pyrimidines and in the metabolism of several important amino acids.

In concert with vitamin B12, folate coenzymes allow the conversion of the amino acid homocysteine to methionine, the lack of this conversion has been associated with various pathologies and diseases.

Conversion of tetrahydrofolic acid to 5-methyltetrahydrofolate is mediated by the action of the enzyme methylentetrahydrofolate reductase. In individuals with a genetic defect of methylentetrahydrofolate reductase enzyme conversion is limited, predisposing these individuals for an increased risk for certain disease conditions.

Supplementation with 5-methyltetrahydrofolate might be preferable to folic acid, being it is immediately available to react with homocysteine to avoid the possibility of hyperhomocysteineamia.


Main Components of the Folate Biochemical Cycle


Abbreviations: DHFR = dihydrofolate reductase; MTHFR = methylenetetrahydrofolate reductase.
Pathway 1:
Biosynthesis of nucleotides for incorporation into DNA and RNA;
Pathway 2:
Remethylation of homocysteine to form methionine (vitamin B12 serves as a coenzyme in this reaction);
3 - Methylation of substrates, including DNA, RNA, phospholipids, and proteins;
4 - MTHFR, which catalyzes the formation of 5-methylfolate needed for methylation reactions;
5 - Dihydrofolate reductase enzyme.

As a direct source of (6S)-5-methyltetrahydrofolate Quatrefolic® is unlikely to mask vitamin B12 >

Quatrefolic® supplementation allows 5-methyltetrahydrofolate to be immediately bioavailable for its biological action without being metabolized in the body.

Quatrefolic® is unlikely to mask vitamin B12 resulting in tangible advantages and more safe profile of product respect to folic acid.

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