Objectives The aim of the study was to investigate whether folic acid (FA) supplementation in patients with rheumatoid arthritis reduces methotrexate (MTX) toxicity.

Methods It was a prospective randomised study. Total of 53 patients with RA who had never used methotrexate before, were randomly assigned to receive either MTX alone (group 1) or MTX and 5 mg. folic acid (group 2). Patients were evaluated for treatment toxicity at three monthly intervals for two years.

Results 1. Significant increases in the hepatic transaminases, ALT and AST, occurred in group 1, over the trial period. 2. After 6 months an increased incidence of nausea in group 1, occurred (43% vs. 7%). 3. More patients withdrew from the study early because of side-effects in group 1 (39% vs. 18% p = 0,025).

Conclusion Our results indicate that it is inportant to continue FA supplementation long term to avoid patients discontinuing MTX treatment due to side-effects. They aslo suggest that FA supplementation can prevent the changes in AST and ALT.