Gnosis by Lesaffre sheds light on “newest generation” of folate amid widespread confusion
03 Dec 2021 --- Consumers and practitioners alike often lack understanding of the nuances between folic acid, folate and their various forms. This is according to Silvia Pisoni, global market manager of Gnosis by Lesaffre, who speaks to NutritionInsight ahead of an upcoming webinar about how this market is developing.
“Even today, the terms folate and folic acid are often mistaken and used interchangeably, both by practitioners and consumers, often causing considerable confusion,” she argues.
For example, many practitioners still recommend folic acid as the standard for folate supplementation without making the differentiation between its various forms.
Meeting the folate family
Pisoni explains that folate is the generic term given to vitamin B9, recognized as one of the mandatory vitamin supplements during pregnancy, and essential for a range of other conditions, like cardiovascular health, fertility, mood and cognition.
Folate includes a group of structurally related compounds like:
- Naturally occurring folates in foods, which exist in many chemical forms, predominantly in the polyglutamate form.
- Folic acid, the commercially synthesized form added in dietary supplements and fortified foods.
- The biologically active form 5-methyltetrahydrofolate (5-MTHF), also available in small amounts in foods and as food ingredients.
Metabolizing makes all the difference
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.
For example, folic acid – the oxidized monoglutamate precursor form of folate – must be metabolized and reduced to the enzyme methylenetetrahydrofolate (5-MTHF) by a multi-step enzymatic conversion to be used by the human body.
For some people, metabolization of folic acid might not be totally effective due to unique genetic patterns of the enzyme methylenetetrahydrofolate reductase (MTHFR).
“Individuals expressing this polymorphism may have a variation in their ability to reduce folic acid. The incidence of people presenting a form of polymorphism MTHFR is about 40% worldwide,” explains Pisoni.
However, folic acid continues to be a widely discussed nutrient, with the UK government set to make certain flour fortification guidelines mandatory. Quatrefolic is positioned as the fourth generation of folate.
A new generation of folate
In the folate space, Gnosis by Lesaffre offers Quatrefolic, the glucosamine salt of 5-MTHF. It’s formulated as an already active form of folate. Pisoni emphasizes that 5-MTHF is the predominant and circulating form of folate in the body.
“Quatrefolic has a significant advantage over previous generations of folates. Thanks to its high solubility and bioavailability, Quatrefolic delivers a ‘finished’ folate directly used by the organism without any specific form of metabolism,” explains Pisoni.
She continues that it seems to be the ideal choice as it is suitable for anyone, regardless of whether they express MTHFR polymorphisms.
Shifting approaches
Quatrefolic was introduced to the market in 2011, but Pisoni has seen major changes in the interceding decade.
“Back in the day, folate supplementation was solely considered for pregnancy. Thanks to worldwide studies and scientific advances, the importance of the role of the one-carbon metabolism in our general health has changed this view, expanding folate’s place.”
Additionally, the correlation between its essential role and the importance of ensuring adequate folate levels has been paramount in highlighting the risks associated with folate deficiencies.
“Today, the knowledge around its different forms, their mechanisms of action and the wide range of benefits continues to gain recognition,” Pisoni explains. 5-MTHF is the both the metabolic and active form of folate.
Beyond pregnancy
While folate is frequently recognized for its role in pregnancy, its role in other key functions is often overlooked.
Pisoni notes that consumers tend to be more conscientious of their health as a whole and the importance of taking proactive measures to secure it, especially in the wake of the COVID-19 pandemic.
“The growing body of scientific evidence confirms folate’s key role in one-carbon metabolism, which is the essential pathway that not only supports the fetus development during pregnancy but is also key for many functions including cardiovascular health, mood health and fertility.”
Folate is also considered an important ingredient in infant formula, with DSM’s Metafolin INF recently gaining regulatory approval in the EU, US and Mexico. See the story on page 50.
Looking ahead, Pisoni anticipates that scientific advances will help spur further health claims in the coming years that could help enlarge the spectrum of vitamin B9 benefits.
On December 9, Pisoni and other experts will present a free webinar further exploring Quatrefolic’s actions on polymorphic metabolisms and the benefits and claims that it provides for various folate needs. Registration is open here.
By Katherine Durrell
To contact our editorial team please email us at editorial@cnsmedia.com

Subscribe now to receive the latest news directly into your inbox.