Gnosis by Lesaffre webinar preview: Innovating Quatrefolic supplements for pregnancy and cognitive health

29 Sep 2022 --- Ahead of Gnosis by Lesaffre’s webinar on October 11 (15:00 CEST), which will focus on Quatrefolic as a supplement and the importance of innovating in the field. NutritionInsight sits down with the webinar’s speakers: Silvia Pisoni, global market manager at Gnosis, and Luca Tiano, professor in biochemistry at the University of Marche.

Folate is the generic term for vitamin B9, a critical nutrient during pregnancy. It consists of structurally-related compounds, including the synthetic folic acid form, food folates and the biologically active form 5-MethylTetraHydroFolate (5-MTHF).

“The terms ‘folate’ and ‘folic acid’ are often used interchangeably, causing considerable confusion. The bioavailability and metabolism of folates differ due to their respective chemical structures. All forms of folates, natural or synthetic, must be converted to exert their biological activity,” says Pisoni.

Folate is water-soluble in nature – therefore, people cannot synthesize folate, and the body can only store it to a limited extent. 

“Therefore, folate must be obtained from the diet or supplementation. Although naturally occurring folates are found in various foods, such as green leafy vegetables, sprouts, fruits, brewer’s yeast and animal liver, it is difficult for most people to get the daily recommended amount through food alone,” continues Pisoni.

Food folates can be oxidized by heat, light and metal ions so that cooking can reduce bioavailability, she adds.

The role of geneticsUnique genetic patterns play a role in the effectiveness of folic acid metabolization.
Meanwhile, Tiano explains that the 5-methyltetrahydrofolate (5-MTHF) present in Quatrefolic is completely bioequivalent to the bioactive form and does not need any activation so consumers can benefit independently of their genetic background.

Pisoni highlights the unique genetic patterns that play a role in the effectiveness of folic acid, due to polymorphisms of specific enzymes involved in the metabolization.

“Individuals expressing a form of polymorphism of the enzyme methylenetetrahydrofolate reductase (MTHFR), might be partially able to reduce folic acid and about 40% of the population presents this form polymorphism. So, the primary consequence of not understanding the difference is that if you are unaware you express this polymorphism and take folic acid for support, you may not experience all the benefits of folate supplementation,” she explains.

Gnosis also stresses that some people experience genetic variations that decrease the Dihydrofolate reductase (DHFR) activity.

“Folic acid is first reduced to dihydrofolate by the enzyme DHFR and then to tetrahydrofolate (THF). This rate-limiting step leads to DHFR’s weak activity in humans, with considerable inter-individual variations. High doses of FA lead to a rapid saturation or inhibition of the DHFR enzyme, resulting in an accumulation of un-metabolized FA (UMFA) and the UMFA syndrome,” Pisoni notes.

Tiano adds: “Folic acid in a synthetic form is widely used in supplements and fortified food, which might represent a risk for consumers due to potential accumulation of UMFA. On the contrary, dietary folate and Quatrefolic, the bioequivalent form 5-MTHF does not present a health risk.”

Beyond pregnancyFolate supplements are mainly targeted at pregnancy, although deficiency impacts health conditions beyond pregnancy, such as cardiovascular disease.
Even though folate supplements are of extra importance for pregnant and fertile women, the company stresses that folate impacts other health conditions beyond pregnancy. 

“One-carbon metabolism is a network of interrelated biochemical reactions that transfer one-carbon methyl groups from one compound to another. This process affects various physiological human conditions, from cardiovascular to pregnancy and mood and cognition health,” Pisoni stresses.

“The 5-MTHF supports the cycle by converting homocysteine (Hcy) to methionine – a byproduct of the one-carbon cycle. Perturbations of one-carbon metabolism, owing to low levels of 5-MTHF, critically contribute to increasing circulating Hcy levels, causing various areas of health to be compromised.”

High plasma level of homocysteine is a recognized risk factor for several diseases, including pregnancy, cardiovascular and neurological conditions.

Steps for governments
In recent years, there has been a significant amount of research investigating the biological role, behavior in the body and potential effect on human health from different folates.

“From governments, we expect more attention to advances in science, both on MTHFR polymorphism and the appearance of UMFA in circulation, supporting even more research and investigation,” says Pisoni.

“From consumers, we expect an increased interest in understanding why it is important to differentiate folates and how to respond to our body’s need for B9 supplementation properly.”

She adds that additional research is needed to assess folic acid supplementation on health when the current upper limit is exceeded (1,000 μg per day), as the 5-MTHF does not have any upper limit uptake.

“It is a great innovation considering its bioavailability and effective uptake independently of the genetic background of the consumer,” Tiano concludes.

By Beatrice Wihlander