Folic acid: Gnosis reports more research into metabolism benefits of Quatrefolic 5-MTHF

The debate over folates continues to create international interest with relevant studies that analyze the differences between them, Gnosis notes. These differences include their metabolic fate, efficacy and safety, in particular between 5-MTHF, the biologically active form, and folic acid, the synthetic derivative.

The potential role of uncontrolled consumption of folic acid by general populations through supplements or fortified foods, after the mandatory fortification of white flour operated in some countries including the US, is of crucial interest, Gnosis says.

Published data suggest that a direct correlation exists between folic acid intake and the presence of detectable amounts of unmetabolized folic acid in the blood, with health consequences that are still not clear, Gnosis reports. It also points to “mounting evidence” in two publications from this year suggesting that folic acid can impair transport of 5-MTHF.

Silvia Pisoni, Marketing Manager of Gnosis SpA, comments on the findings of the studies: “Even more clinical investigations suggest reconsidering the role of folic acid supplementation for its potential unexpected effects. The best form of folate administration has been recognized as 5-MTHF, the metabolic active reduced form of folate, suitable for the human body because it avoids any accumulation of UMFA in the blood.”

“Quatrefolic is the most bioavailable brand of 5-MTHF in the market, clinically tested for safety and efficacy,” Pisoni adds.

Studies detailed
One study pointed to by Gnosis, by Page et al., showed that folic acid disturbs 5-MTHF metabolism, lowering its levels in breast milk. Breast milk total folate, UMFA contents and their relationship with folic acid supplement use and doses were determined in a cohort of Canadian mothers who were enrolled in the MIREC (Maternal Infant Research on Environmental Chemicals).

UMFA was detectable in the milk of 96.1 percent of the women in the study. Total daily folic acid intake from supplements was associated with breast folate concentration and species. Breast milk total folate was 18 percent higher in supplement users than in nonusers, a difference driven by women consuming more than 400 micrograms of folic acid per day.

In addition, 5-MTHF was 19 percent lower and unmetabolized folic acid was 126 percent higher in supplement users than in non-users. Women who consumed more than 400 micrograms of folic acid per day had proportionally lower 5-MTHF and higher unmetabolized folic acid than women who consumed 400 micrograms or less of folic acid per day.

The research group concluded that intakes exceeding the recommended folic acid intake of 400 micrograms per day is supraphysiologic with no clear benefit. Therefore, higher-dose folic acid supplement use may not be warranted, especially in populations for whom folic acid fortification is mandatory.

It is notable that lactating Canadian women who consume folic acid from both folic acid-enriched foods and vitamin supplements are likely to exceed the Tolerable Upper Intake Level of folic acid per day, Gnosis notes. The presence of unmetabolized folic acid in the circulation is reportedly nearly ubiquitous in areas where folic acid fortification is permitted.

The second paper cited by Gnosis, authored by Smith et al., shows that folic acid inhibits 5-MTHF uptake into vascular cells. Under folate deficiency, elevated plasma levels of homocysteine were held responsible for endothelial cell injury and cardiovascular disease. However, there is probably an important direct role for reduced-folate 5-MTHF in maintaining vascular tissue integrity and functionality.

According to the results, folic acid has the ability to inhibit the uptake of the naturally occurring, bioactive folate 5-MTHF in endothelial cells through a mechanism that presumably involves interaction with the folate transporter PCFT. As folic acid consumption leads to unmetabolized folic acid in the plasma, this might affect endothelial cell folate status, which is of potential concern.

The study provides Gnosis’ initial necessary proof of concept that unmetabolized folic acid interferes with endothelial cell uptake of the circulating bioactive folate 5-MTHF, and compromises intracellular folate pools. This is because it occurs in the plasma of subjects taking oral folic acid supplementation, according to Gnosis.

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