This supplement can help minimize many bothersome side effects from MTX.

Methotrexate is the leading disease-modifying anti-rheumatic drug (DMARD) given to people with rheumatoid arthritis (RA) and many other types of inflammatory arthritis. By reducing your immune system’s ability to produce cells that cause inflammation, methotrexate (MTX) reduces arthritis symptoms and, over time, the destruction of affected joints. MTX also boosts the release of adenosine, a highly anti-inflammatory chemical that is found in all human cells.

Unfortunately, MTX causes bothersome side effects in many people, but some of these can be lessened with a simple supplement of vitamin B9, also known as folate (usually taken as a folic acid supplement).

“It is impossible to predict who will suffer side effects [from methotrexate]. Because folic acid supplements have a very low risk of harm, recommending them to all patients starting MTX is a worthwhile investment in preventing side effects and increasing the likelihood that patients will stay on this often extremely effective rheumatoid arthritis medication,” says Amanda Steiman, MD, M.Sc, a rheumatologist at Sinai Health System/University Health Network in Toronto, Canada and an assistant professor of medicine at the University of Toronto.

Here’s more information about the importance of folic acid while taking methotrexate.

1. Why is my doctor recommending that I take folic acid?

Folic acid and folinic acid are forms of vitamin B9, which you need to keep your cells dividing and growing normally. Folic acid is also essential in the production of red blood cells. Methotrexate blocks some of the actions of folic acid, which can lead to side effects such as mouth sores, abdominal pain, liver problems, hair loss, and anemia. For some people, the side effects are bad enough that they stop taking their methotrexate.

2. Does folic acid really help reduce methotrexate side effects?

Yes. In 2013, a Cochrane review of six studies found that taking folic acid or folinic acid reduced the proportion of people on methotrexte experiencing stomach problems (from 35 percent to 25 percent), abnormal liver tests (from 21 percent to 5 percent), and mouth sores (from 22 percent to 16 percent, which was not a statistically significant difference).

Overall, fewer people dropped out of methotrexate treatment studies if they used folic acid (10 percent) than if they did not (25 percent).

3. But could taking folic acid keep my methotrexate from working?

No. Large doses of MTX are used to treat some cancers, and the drug’s anti-cancer activity results from its interference with folate. So cancer patients taking methotrexate should not take supplemental folic acid.

However, the actions of MTX on folic acid are not related to its ability to reduce inflammation and joint damage at the low doses used in treating rheumatoid arthritis, says rheumatologist Gabby Schmajuk, MD, MS, associate professor of medicine at the University of California San Francisco.

You can safely take folic acid without any impact on the efficacy of methotrexate.

4. Does my multivitamin give me enough folic acid?

Probably not enough if you’re on methotrexate for arthritis and trying to avoid side effects. The amount of folic acid in common multis is 400 micrograms for most adults, and up to 800 micrograms for women who are pregnant or planning to be.

But for arthritis patients, “we recommend taking a supplement with at least 1,000 micrograms, and some patients report fewer MTX side effects taking 2,000 micrograms or more,” says Dr. Schmajuk.

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