In the world of rheumatoid arthritis, the subject of folic acid is forever tied to methotrexate. A discussion of one is incomplete without the other. In searching the medical literature for articles related to ‘rheumatoid arthritis and folate (folic acid)’, I discovered that most of the titles of the articles include mention of methotrexate.
Are folic acid and folinic acid effective against methotrexate side effects in RA patients?
Yes, according to the Cochrane Review updated in 2013 that included six randomized controlled trials involving 624 RA patients taking MTX (≤ 25 mg/week), of whom 385 also took low-dose folic acid (≤ 7 mg/week). Studies using higher doses of folic acid were excluded because the high dose is no longer recommended or used in clinical practice.
For patients supplemented with either folic or folinic acid while receiving MTX therapy for RA, a 26% relative (9% absolute) risk reduction was seen for the incidence of gastrointestinal side effects such as nausea, vomiting, or abdominal pain. Folic and folinic acid also appear to be protective against abnormal serum transaminase (liver enzyme) elevation caused by MTX, with a 76.9% relative (16% absolute) risk reduction, as well as reducing patient withdrawal from MTX for any reason by 60.8% relative (15.2% absolute) risk reduction.
Importantly, there was no significant reduction in MTX efficacy, as measured by disease activity measures such as tender and swollen joint counts or physician's global assessment scores.
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Folic Acid Use in Rheumatoid Arthritis