FOLIC-ACID SUPPLEMENTATION PREVENTS DEFICIENT BLOOD FOLATE LEVELS ANDHYPERHOMOCYSTEINEMIA DURING LONG-TERM, LOW-DOSE METHOTREXATE THERAPY FOR RHEUMATOID-ARTHRITIS - IMPLICATIONS FOR CARDIOVASCULAR-DISEASE PREVENTION

Objective. To determine the effect of longterm methotrexate (MTX) ther apy and folic acid supplementation on folate nutriture and homocystein e levels in patients with rheumatoid arthritis. Methods. A double blin d, placebo controlled trial lasting one rear was conducted at one acad emic medical center. A total of 79 patients taking low dose MTX were f ollowed up to one year. The patients were randomized to receive placeb o or 5 or 27.5 mg folic acid supplementation per week. Results. plasma and erythrocyte folate levels and plasma homocysteine levels were det ermined. The folate nutriture of patients taking low dose MTX declined without folic acid supplementation. Plasma homocysteine levels increa sed significantly over a one year period in the placebo group. Low fol ate nutriture and hyperhomocysteinemia occurred with greater frequency in the placebo group than in the folic acid supplemented groups. Conc lusion. For longterm, low dose MTX therapy, there are now at least 3 r easons to consider supplementation with folic acid (a low cost prescri ption): (1) to prevent MTX toxicity, (2) to prevent or treat folate de ficiency, and (3) to prevent hyperhomocysteinemia, considered by many investigators to be a risk factor for cardiovascular disease.