MTHFR polymorphism and 5-MTHF bypassing effect

Supplementation with Quatrefolic by Gnosis Lesaffre may be the best option to avoid blood folate deficiencies and guarantee the right percentage amount of 5-MTHF in pregnancy

Folate metabolism, from folic acid to active 5-methyltetrahydrofolate (5-MTHF), and the biological role of these molecules in our body are not always known and understood, even if these aspects are under the limelight of current clinical research trends.

Gnosis by Lesaffre with a brand-dedicated tool to Quatrefolic, the glucosamine salt of 5-MTHF, has released a clear infographic to explain why the body needs a folate that can immediately be used by cells without any kind of metabolisation: very often, more than expected, people are not able to properly metabolise folic acid and food folate, because they have polymorphic defects with the methylenetetrahydrofolate reductase (MTHFR) enzyme (www.quatrefolic.com/news.php?p=142) .

A very recent in vitro study on J. Clin. Med. 2020, “Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate” , published by Vidmar Golja M. et al. has evaluated the effect of folate deprivation and supplementation of Folic acid (FA) or 5-methyltetrahydrofolate (5-Me-THF or 5-MTHF) on cell growth and proliferation of human lymphoblastoid cells lines (LCLs), with diverse methylenetetrahydrofolate reductase enzyme (MTHFR) activity.

FA and 5-Me-THF are the most commonly available folate supplements worldwide [38], but there is limited research on their bioavailability, their effects on growth and proliferation of the cells, and on their influence on intracellular concentrations of key folate-homocysteine metabolites. Polymorphisms in the MTHFR gene influence the levels of biologically active folate, with numerous clinical studies demonstrated a significant association between MTHFR polymorphisms and various diseases, such as serious congenital birth defect, cardiovascular diseases, neuronal development diseases, and also psychiatric disorders.

In the group with normal MTHFR activity cells, FA treatment significantly increased the concentration of biologically active folate, while in the group with low MTHFR activity cells, the change was not statistically different compared to untreated control cells. When cells were exposed to the equimolar concentration of 5-MTHF, high intracellular concentrations of the biologically active form were determined in both subgroups.

Adapted from Vidmar Golja M. et al. 2020 Cell lines with predicted low MTHFR activity (n = 15). 5-MTHF is more effective in increasing metabolic activity then FA at concentrations higher than 6.25 nM and up to 50 nM

As reported by the study, “These results demonstrate that polymorphisms influencing the enzyme activity of MTHFR are associated with intracellular concentrations of the methylated form of folates and we provide evidence that 5-MTHF can bypass folate insufficiency due to MTHFR deficiency”.

Silvia Pisoni, Senior Marketing Manager of Gnosis by Lesaffre commented: “More and more, scientific evaluations clarify the difference between the various folates and their real biological activity. Supplementation with Quatrefolic may be the best option to avoid blood folate deficiencies and guarantee the right percentage amount of 5-MTHF (also known as L-methylfolate) in pregnancy, and when folate supplementation is recommended, as it provides the "natural" and “bioactive” dose of folate, without metabolisation by MTHFR.

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