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 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, à immediately bioavailable to react with homocysteine to avoid the possibility to incur in hyperhomocysteinemia.

Quatrefolic®: mechanisms of action

Main Components of the Folate Biochemical Cycle. Abbreviations: DHFR = dihydrofolate reductase; MTHFR = methylenetetrahydrofolate reductase.


  • 1 - Biosynthesis of nucleotides for incorporation into DNA and RNA;
  • 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 catalyses the formation of 5-methylfolate needed for methylation reactions;
  • 5 - Dihydrofolate reductase enzyme.
Folate biochemical cycle

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

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

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 anaemia 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 the first symptoms of vitamin B12 deficiency, such as anaemia, while 5-methyltetrahydrofolate supplementation does not. Actually, folic acid supplementation may activate the synthesis of purine and pyrimidine through pathway 1 correcting anaemia, although vitamin B12 is absent; on the contrary pathway, 2 remains blocked leading to a nerve and cognitive deterioration that may continue unchecked.

One Carbon Metabolism

Folate-dependent one carbon metabolism and the role of nutritional compounds in regulating biochemical pathways in our bodies are the focus of recent and future investigative research. Often referred to as the Methylation Cycle, this life critical process is a network of interrelated biochemical reactions that involves the transfer of one carbon methyl groups from one compound to another. Folate and methionine are the key components of the Methylation Cycle and are required for normal healthy cellular function.

This process occurs in all cells of the body and it is crucial for a variety of functions, including detoxification, energy production, immune function, maintaining and regulating genes, mood balancing and controlling inflammation. Therefore, maintaining the balance and levels of folate, vitamin B12 and S-Adenosyl methionine (SAMe) can be critical to support various cellular processes, which influence the development, prevention, and treatment of various disease states.

Quatrefolic®, the most bioavailable form of folate, can be the preferred choice for active folate supplementation in synergy with SAMe to support and regulate the methylation cycle.

Newsletter - Quatrefolic

Love reading? Get our newsletter!

For exclusive content, opportunities, events and new product announcements – plus a few surprises.