OBJECTIVE

To investigate the effect of methotrexate (MTX) treatment of rheumatoid arthritis (RA) on folate metabolism, and to determine the effect of low dose folic acid on toxicity, efficacy, and folate status.

METHODS

A 52-week prospective study of 81 patients with RA treated with MTX and self-administered low dose folic acid; 38 patients were included prior to MTX therapy, 33 patients continued established MTX therapy, and 10 patients were excluded. Drug efficacy and side effects were monitored with biochemical and clinical indicators.

RESULTS

MTX treatment resulted in decreased concentrations of red blood cell (RBC) folate and a rise in plasma homocysteine. Intracellular concentrations of MTX were inversely correlated to RBC folate levels after treatment for a longer period (mean 41 months). Supplement with low dose folic acid prevented or diminished the influence of MTX on folate status and had a protective effect on MTX induced liver toxicity without changing the efficacy of MTX.

CONCLUSION

MTX interferes with folate and homocysteine metabolism, and the intracellular concentration of MTX may play a role. Our results indicate low dose folic acid supplementation has a beneficial effect on MTX toxicity.