Methotrexate and the MTHFR enzyme
Methotrexate influences folic acid metabolism. This is because polyglutamated methotrexate (a conversion product) inhibits the activity of two enzymes (dihydrofolate reductase and thymidylate synthase) that play a role in the folic acid cycle.
Besides methotrexate, folic acid metabolism is also influenced by the enzyme MTHFR. As a result, genetic variations that lead to an underactive MTHFR enzyme could influence the efficacy and toxicity of methotrexate.
Incidentally, the toxicity of methotrexate can be reduced by administering folinic acid and this is a standard procedure in ordinary, everyday practice.
The activity of the enzyme MTHFR can vary considerably depending on your genetic predisposition, which means the efficacy of methotrexate can also differ from person to person, as can the risk of side effects.
Information about your genetic predisposition may therefore provide grounds for extra vigilance during a treatment with methotrexate.