MTHFR Mutations: Folic Acid Supplementations

Traditional Recommendation for MTHFR Mutations: Folic Acid Supplementation

Historically, folic acid supplementation has been the standard recommendation for addressing folate deficiencies, including for individuals with MTHFR gene mutations. It was traditionally thought to help alleviate folate insufficiency. However, recent research challenges this assumption. Below are key findings that highlight why folic acid may not be suitable for managing MTHFR mutations, alongside alternative recommendations.

Folic Acid Inhibits DHFR Gene

Folic acid interferes with the dihydrofolate reductase (DHFR) gene, which is essential for metabolising folic acid in the body. Studies show that folic acid competes with DHFR at high concentrations of 7,8-dihydrofolate (DHF) and inhibits it even at lower concentrations. This means that folic acid may not efficiently address folate deficiencies in people with MTHFR mutations, leading to unmetabolised folic acid building up in the bloodstream.

Unmetabolised Folic Acid and Immune Dysfunction

Unmetabolised folic acid poses significant health risks, especially at high intake levels. Studies have found that excessive folic acid intake can lead to unmetabolised folic acid circulating in the bloodstream, which can reduce immune function by lowering natural killer (NK) cell activity. Even individuals without MTHFR mutations may struggle to metabolise large amounts of folic acid. For instance, unmetabolised folic acid has been detected in the blood of people consuming doses exceeding 400 mcg daily.

In countries like the U.S., flour is fortified with folic acid, adding 140 mcg per 100 g of flour. Australia's guidelines are even higher, with around 250 mcg per 100 g of bread. Once the liver becomes saturated with folic acid, unmetabolised folic acid enters the bloodstream. This has also been observed in newborns, with research from Ireland showing that unmetabolised folic acid was present in cord blood at birth.

Folic Acid Blocking Natural Folates and Pseudo MTHFR

High concentrations of folic acid can block the absorption of natural folates in cells. This phenomenon, known as "pseudo MTHFR deficiency," has been demonstrated in animals and humans. In mice fed high-folic-acid diets, prolonged intake reduced MTHFR protein levels, causing metabolic dysfunction. The implications for humans with MTHFR mutations are concerning, as high folic acid intake may worsen metabolic imbalances rather than correct them.

Folic Acid and Cancer Risk

The potential link between folic acid supplementation and cancer risk has been debated for years. An early study from the 1940s found that folic acid supplementation accelerated leukemia progression in children. More recent large-scale clinical trials have shown a 67% increase in advanced colorectal adenomas and a doubling of the risk for multiple adenomas in patients supplemented with high doses of folic acid. Increased lung cancer risk has also been observed in patients with ischemic heart disease treated with folic acid supplements. The potential for MTHFR mutations to amplify these risks further emphasises the need for alternative treatments to folic acid.

5-MTHF as an Alternative to Folic Acid

5-methyltetrahydrofolate (5-MTHF), the bioactive form of folate, has emerged as a safer and more effective alternative to folic acid. Studies comparing 5-MTHF to folic acid have shown that 5-MTHF is more readily absorbed and metabolised by the body, even in individuals with MTHFR mutations. Unlike folic acid, 5-MTHF does not lead to the accumulation of unmetabolised folic acid and has been found to more effectively raise plasma folate levels and lower homocysteine levels. Given these advantages, 5-MTHF is increasingly being recognised as a preferable option for treating folate deficiencies, particularly in individuals with MTHFR mutations.

Conclusion

While folic acid has been the traditional treatment for folate deficiency, its inefficacy and potential harm in individuals with MTHFR mutations are becoming clearer. The research outlined above supports the use of 5-MTHF as a safer and more effective alternative to folic acid, especially in populations with MTHFR mutations. When considering folate supplementation, 5-MTHF offers the added benefits of avoiding unmetabolised folic acid accumulation, maintaining immune function, and lowering cancer risks, making it the superior choice.

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