Is Folate (5-MTHF / Methylfolate) Safe with Methotrexate?
Free · No account · based on published sources including NIH ODS, FDA drug labels, and peer-reviewed literature
Avoid methylfolate (L-5-MTHF) supplements during methotrexate chemotherapy unless explicitly directed by your oncologist. Do not self-substitute methylfolate for prescribed leucovorin rescue protocols.
Why this interaction occurs
Methylfolate, the active form of folate, can directly bypass methotrexate's inhibition of the folate cycle. This may significantly antagonize the cytotoxic effect of methotrexate in cancer treatment, compromising therapeutic outcomes.
Evidence
Evidence level: moderate.
Reported safety data
The FDA’s adverse event reporting system (FAERS) has received 499,559 reports mentioning Methotrexate. This reflects reported cases involving the medication in general — not confirmed causation, and not specific to the Methotrexate + supplement combination on this page.
FAERS reports are voluntary and cannot prove that a drug caused an event. Do not use report counts to assess the safety of this specific drug-supplement pair.
Frequently asked questions
Related interactions
All Folate (5-MTHF / Methylfolate) interactions → · All Methotrexate interactions →
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Educational only — not medical advice.
Always confirm with your doctor or pharmacist.