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Are There Any Vitamins That Can Interfere With Folic Acid or Methotrexate?

By Robin Elizabeth Margolis

If you take methotrexate for a medical condition, folic acid can interfere with effectiveness of the drug, and methotrexate can create a folic acid deficiency. This negative interaction between the two substances produces a dilemma for doctors prescribing methotrexate. For anyone whose diet doesn’t provide enough vitamin B-12, a building block for red blood cells, taking the drug poses an additional risk. If the doctor tries to balance your methotrexate side effects by prescribing folic acid supplements, the additional folic acid can mask any dangerous vitamin B-12 deficiencies.

Folic Acid

Spinach, asparagus, turnip, beets, brussels sprouts, lima beans, soybeans, beef liver and many other foods contain folic acid, and you can take the vitamin in a tablet. The body utilizes folic acid for multiple purposes, including building DNA, a complex chemical found in the cells of the human body that directs their growth and development. For various reasons, pregnant women should ensure they are receiving enough folic acid in their diets.


Methotrexate, currently marketed as Trexall, is a folate antagonist, a chemical that blocks the body's use of folate to create new cells. This has made methotrexate a useful medication in fighting illnesses, such as cancer, in which cells grow abnormally. Doctors also prescribe the drug to treat arthritis and psoriasis and to terminate pregnancies. Patients taking the drug can develop folic acid deficiency, so physicians may ask patients to take folic acid if they are suffering from non-life-threatening illnesses, such as psoriasis. However, they cannot prescribe folic acid supplements if the patient has cancer, since the additional folic acid may diminish the effectiveness of methotrexate.

Vitamin B-12

Vitamin B-12 is used by the body to build red blood cells, keep nerves functioning and also to create DNA, the complex chemical found in every cell that serves as a blueprint for new cells. It is found in beef, yogurt, fish, milk and other foods. A vitamin B-12 deficiency can cause a dangerous form of anemia, resulting in a low red blood cell count. If you are taking folic acid supplements, the infusion of vitamin B-9 that you are getting from the folic acid supplements may mask a vitamin B-12 deficiency, leaving it undetected and untreated.

Balancing Act

Tell your doctor that you are taking folic acid supplements if you receive a prescription for methotrexate. If your physician prescribes folic acid supplements to combat a folic acid deficiency caused by methotrexate, ask your physician if you should be tested for a vitamin B-12 deficiency. Your physician can ensure that you receive the appropriate amounts of folic acid and vitamin B-12.

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