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Why Can't I Take Folic Acid the Same Day As Methotrexate?

author image Stephen Christensen
Stephen Christensen started writing health-related articles in 1976 and his work has appeared in diverse publications including professional journals, “Birds and Blooms” magazine, poetry anthologies and children's books. He received his medical degree from the University of Utah School of Medicine and completed a three-year residency in family medicine at McKay-Dee Hospital Center in Ogden, Utah.
Why Can't I Take Folic Acid the Same Day As Methotrexate?
Folic acid is the synthetic form of folate.

Methotrexate is a strong medication used to treat a wide array of conditions, including rheumatoid arthritis, psoriasis and various cancers, such as leukemia, lymphoma and bone cancer. It is also employed in the treatment of ectopic pregnancy, a condition in which the pregnancy is growing outside the womb. This medication works by interfering with the production of the genetic materials DNA and RNA, which are needed for cell growth and division. As a result, methotrexate is toxic to rapidly dividing cells. Folic acid -- the synthetic form of the B vitamin folate -- can interfere with the action of methotrexate.

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Folate naturally occurs in high concentrations in dark green leafy vegetables, such as kale, spinach and chard. Liver, kidney and brewer’s yeast also contain large amounts of this B vitamin. Folate from your diet is eventually converted to its active form -- tetrahydrofolic acid. Tetrahydrofolic acid is required to manufacture the building blocks used to produce DNA and RNA. Without DNA and RNA, your cells cannot grow and reproduce.

Methotrexate Actions

Methotrexate blocks the conversion of folate to tetrahydrofolic acid. This inhibition reduces the amount of active folate in your cells, thereby disrupting production of DNA and RNA. Doctors exploit this property of methotrexate to disrupt the reproduction of cancer cells, overstimulated immune cells or even the cells of an embryo that has implanted in a dangerous location.

Folic Acid Supplementation

Methotrexate’s interference with the action of folate is responsible for both its benefits and side effects. Your healthy cells need folate to grow and divide, too, but methotrexate is indiscriminate in its anti-folate activities. Methotrexate's interference with healthy cells can lead to side effects, such as mouth soreness, a low white blood cell count, hair loss and birth defects. Therefore, your doctor may advise you to take a folic acid supplement to counteract methotrexate’s effects on your healthy tissues. However, if you take folic acid on the same day as your methotrexate dose, the folic acid might lessen the effectiveness of the medicine.


The frequency of administration and dosage of methotrexate varies, depending on what condition you have that is being treated with this medicine. If you are taking methotrexate, ask your doctor if you should take folic acid supplements -- and when to take them in relationship to your methotrexate dose.

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