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 into methionine. The lack of this conversion has been associated with various pathologies and diseases.

Conversion of tetrahydrofolic acid into 5-methyltetrahydrofolate is mediated by the action of the enzyme methylentetrahydrofolate reductase. In individuals with a genetic defect of the methylentetrahydrofolate reductase (MTHFR) this enzyme conversion is limited, consequently it will predispose these individuals to an increased risk for certain disease conditions.

Supplementation with 5-methyltetrahydrofolate is preferable to the one with folic acid, as it is immediately bioavailable to react with homocysteine to avoid the possibility to incur in hyperhomocysteinemia.

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.

Folate Cycle

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 the product respect to folic acid.

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

Once formed, 5-methyltetrahydrofolate reacts with homocysteine by a single enzyme regulated by vitamin B12, leading to a recycling production of tetrahydrofolic acid.

If vitamin B12 is deficient, the folate present in cells becomes "metabolically trapped" and 5-methyltetrahydrofolate is piled up in the cells, resulting in a persistent impairment of purine and pyrimidine biosynthesis (pathway 1) and in a methylation cycle block (pathway 2), leading to megaloblastic anemia and neurological damage progress.

Vitamin B12 deficiency is common in old age and may not be easy to recognise. Folic acid intake by supplementation may mask first symptoms of vitamin B12 deficiency, such as anemia, while 5-methyltetrahydrofolate supplementation does not. Actually folic acid supplementation may activate synthesis of purine and pyrimidine through pathway 1 correcting anemia, although vitamin B12 is absent; on the contrary the pathway 2 remains blocked leading to a nerve and cognitive deterioration that may continue unchecked.

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