Study Tackles Tough Questions about Folic Acid Supplementation for Rheumatoid Arthritis

Methotrexate (MTX) is the gold standard for rheumatoid arthritis (RA) treatment, but there is a perception among many patients—and, in some cases, primary care physicians—that MTX is highly toxic and comes with devastating side effects. This perception is perhaps due to the fact that higher doses of MTX can be used to treat leukemia and certain other types of cancer. (MTX was developed as a cancer treatment.) For RA patients, a typical dose is between 10 mg and 25 mg of MTX per week. Doses to treat cancer can be hundreds of times larger.

Still, MTX does pose some side effect challenges; almost three in four RA patients report at least one side effect, which can include the usual suspects—nausea, vomiting, and headaches—but can also include hair loss and mouth sores. MTX works by stopping malignant (or cancerous) cells from rapidly multiplying and spreading by blocking their access to folate, a form of vitamin B, which these cells need to survive. This affects healthy cells as well, which explains the side effects. Thus, RA treatment generally also includes a dose of folic acid, which can minimize or eliminate these side effects. But how much folic acid should patients take?

This is an important question in treating RA, because 30% to 50% of patients stop taking the drug due to its toxicity. There is general agreement and reasonable evidence that 5 mg — 10mg of folic acid per week is enough, but the recent trend in rheumatology over the past few years has been to increase the dosage, in most cases to 25 mg/week.

But the folic acid dosage is important for another reason as well: Although folic acid counteracts some of the negative side effects experienced by patients taking MTX to treat their rheumatoid arthritis, researchers have posited it may also reduce the effectiveness of MTX therapy. Several studies have suggested that this is indeed a possibility. A new study in Arthritis Research and Therapy sheds some light on this question.

The study suggests that increased dosages of folic acid do not offer additional benefit, though higher dosages also create no harm.

There remains a controversy on the effect of folic acid on the efficacy of MTX. The study had the inherent limitation of not having a placebo arm. However, according to the study authors, the results suggest that “any reduction in efficacy (if it occurs) does not have a dose—response effect.” In other words, the effectiveness of MTX declined over time in both groups who were given the standard dosage of folic acid and those given elevated dosages. “Our results support the postulation that folic acid merely serves to correct the intracellular folate deficiency with

MTX,” the authors noted.