Vitamin B9, specifically as calcium methyltetrahydrofolate (the active form of folate), is used in the context of chemotherapy, particularly with drugs like methotrexate and pemetrexed, to reduce toxicity and side effects. The scientific basis for this practice is well established. Methotrexate and similar antimetabolite chemotherapeutics inhibit dihydrofolate reductase, blocking folate metabolism and thus DNA synthesis, which helps kill rapidly dividing cancer cells but also affects normal cells, leading to side effects like mucositis, myelosuppression, and gastrointestinal toxicity.

Supplementing with folate (as leucovorin/folinic acid or active forms like methyltetrahydrofolate) can "rescue" normal cells from excessive toxicity without significantly reducing the anticancer efficacy of methotrexate. This is called "leucovorin rescue" and is a standard part of high-dose methotrexate regimens. Calcium methyltetrahydrofolate, as a direct-acting folate, can fulfill a similar role, especially in patients with genetic polymorphisms (such as MTHFR) that impair conversion of folic acid to active forms.

Numerous clinical studies and oncology guidelines support the use of active folate supplementation to mitigate chemotherapy side effects, particularly with antifolate drugs. However, routine folate supplementation outside this specific context is not universally recommended, as it may interfere with the efficacy of some chemotherapeutics if not carefully managed.