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Lorena Carboni, Scientific Communications Specialist, Gnosis by Lesaffre

Lorena Carboni Lorena Carboni

With a master’s degree in pharmaceutical chemistry and technology, Lorena Carboni specializes in natural ingredients’ scientific and clinical aspects, focusing on the one-carbon metabolites, including folate (5-MTHF), S-adenosylmethionine and glutathione, at Gnosis by Lesaffre. Over her 20-plus years in the nutraceutical and pharmaceutical industries, she proactively collaborates with universities and academic panels of experts on educational projects and publications.

Q: How does folate differ from folic acid?

A: Folate is the generic term given to vitamin B9, a water-soluble vitamin recognized as a critical nutrient during pregnancy, consisting 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.

People cannot synthesize folate, and due to its water-soluble nature, the body stores folate 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. Further, food folates can be oxidized (by heat, light, and/or metal ions), so cooking can reduce bioavailability.

Folic acid, the oxidized monoglutamate precursor form of folate and the standard recommended form, was synthesized in pure crystalline form in the 1940s. It can be found in many dietary supplements or added to fortified foods (e.g., cereal-based products, pasta, enriched bread, fruit juice, etc.). Folic acid does not occur in nature and has no biological functions. To be utilized, the body must metabolize and reduce it to 5-MTHF by a multi-step enzymatic conversion.

For some people, folic acid metabolization might not be entirely effective due to the unique genetic patterns of the enzyme methylenetetrahydrofolate reductase (MTHFR). Individuals expressing this polymorphism may be unable to reduce folic acid, and about 40 percent of the population presents a form of MTHFR polymorphism.

Finally, 5-MTHF is both the metabolic and active form of folate. It is the predominant and circulating form of folate in our body, and what we offer at Gnosis by Lesaffre as Quatrefolic, available in several finished products.

Q: What health conditions can be impacted by folate?

A: Growing scientific evidence confirms folate’s key role in one-carbon metabolism, the essential pathway supporting fetal development during pregnancy. Lesser known is that folate is vital for many functions, including cardiovascular health, mood, cognition and fertility.

Here is how 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. The 5-MTHF supports the cycle by converting homocysteine (Hcy) to methionine. Hcy is 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.

Q: How does Quatrefolic differ from what practitioners are already recommending?

A: We contend that clinically validated Quatrefolic, the glucosamine salt of 5-MethylTetraHydroFolate (5-MTHF), offers substantial advantages over folic acid, but also for a wider population. While folic acid must be first converted into 5-MTHF by a multi-enzymatic steps process, Quatrefolic is the biologically active form of folate that completely bypasses this metabolic route. This makes it immediately available but especially effective for 100 percent of people, including those with polymorphisms in folate-related enzymes, such as MTHFR polymorphism.

These genetic alterations can increase Hcy blood levels, increasing cardiovascular risks and inhibiting fertility and conception potential.

Q: Can you discuss the study published by The International Journal of Environmental Research and Public Health demonstrating Quatrefolic’s value in women undergoing assisted reproductive technologies (ART)?

A: ART represents widely used procedures for controlling and treating infertility. Reproductive success is highly influenced by the female pre-conceptional health, including nutrition and micronutrient levels, which may play a pivotal role in this initial phase. Unfortunately, most procedures remain unsuccessful.

This new retrospective study investigated the impact of supplementation with a vitamin B complex (5-MTHF as Quatrefolic plus vitamins B12 and B6) versus folic acid on pregnancy outcomes (clinical pregnancy, pregnancy loss and live birth) in infertile women undergoing ART. Results showed that the Quatrefolic group had a higher chance of clinical pregnancy and live birth than those supplementing with folic acid alone.

While further clinical trials are needed to elucidate the effects of folate, vitamin B12 and homocysteine pathway in improving pregnancy outcomes in women after ART, the authors noted that, if their findings were confirmed, this relatively inexpensive supplementation with vitamin B complex might be considered in clinical practice, particularly in women undergoing ART.

Q: What advice would you give practitioners on educating their patients regarding folate?

A: The scientific community has been trying to clarify the links between folate deficiency, the correct form of folate supplementation and the role of MTHFR polymorphism in human health. Nevertheless, the genetic test for the MTHFR polymorphism remains not recommended without symptoms and conditions that could be considered a major health risk, such as hyperhomocysteinemia, recurrent infertility and negative pregnancy outcomes. How can we strengthen the connection between the progress of science and medical practice? Folic acid is often suggested at a very high dosage to counteract the less efficient enzyme MTHFR. But with the biologically active form, like Quatrefolic, practitioners have an opportunity to overcome the issue and be sure to recommend the most active folate for 100 percent of their patients.