Synopsis

Source of validity: Scientific
Rating (out of 5): 4

Vitamin B9, particularly in the form of 5-methyltetrahydrofolate (5-MTHF), is scientifically validated for use in conjunction with certain chemotherapy agents, most notably methotrexate. Methotrexate works by inhibiting dihydrofolate reductase, thus interfering with folate metabolism and DNA synthesis, which is particularly effective in rapidly dividing cancer cells. However, this mechanism also affects normal, healthy cells and can result in significant side effects such as myelosuppression, mucositis, and gastrointestinal toxicity.

To mitigate these adverse effects, folinic acid (also called leucovorin, a reduced form of folate related to 5-MTHF) is routinely administered as "leucovorin rescue" therapy. While folinic acid is more commonly used, 5-MTHF has also been investigated as a potential alternative due to its ability to bypass certain metabolic blocks and directly participate in methylation and nucleotide synthesis. Clinical studies have demonstrated that supplementation with reduced folates, including 5-MTHF, can protect healthy tissues from the toxic effects of antifolate chemotherapy without compromising anti-cancer efficacy.

Current evidence is strongest for folinic acid, but 5-MTHF is recognized as a valid substitute, especially in patients with genetic polymorphisms (such as MTHFR mutations) that impair folate metabolism. Overall, the use of reduced folates in chemotherapy is well-supported by clinical guidelines and research, reflecting a scientific rather than traditional rationale.

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