Synopsis

Source of validity: Scientific
Rating (out of 5): 2

L-5-methyltetrahydrofolate glucosamine salt (5-MTHF) is a bioactive form of folate, the naturally occurring form of vitamin B9. There is a scientific rationale for its use in supporting or treating peripheral neuropathy, although the overall quality and quantity of evidence is moderate to low (hence a score of 2). Folate is critical for homocysteine metabolism; elevated homocysteine levels are associated with neurotoxicity and may contribute to nerve damage. 5-MTHF is used instead of synthetic folic acid, especially in individuals with genetic polymorphisms (e.g., MTHFR mutations) that reduce their ability to convert folic acid to its active form. Some clinical studies and case reports suggest that supplementation with B vitamins—including folate, B12, and B6—can help reduce symptoms of peripheral neuropathy, particularly in cases related to deficiencies or elevated homocysteine. 5-MTHF may be preferred over folic acid due to better bioavailability and fewer metabolic bottlenecks. However, most studies use combinations of B vitamins, and the specific contribution of 5-MTHF alone is not well defined. There is limited direct evidence from randomized controlled trials that 5-MTHF monotherapy significantly improves neuropathy outcomes. In summary, the use of 5-MTHF for peripheral neuropathy is supported by plausible mechanisms and some indirect clinical evidence, but high-quality, large-scale studies are lacking. Its use is most justified in individuals with folate deficiency or genetic polymorphisms affecting folate metabolism.

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