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1 December 1994 | Volume 121 Issue 11 | Pages 833-841
Objective: To determine the effect of two different weekly doses of folic acid on the toxicity and efficacy of low-dose methotrexate therapy for rheumatoid arthritis.
Design: Randomized, double-blind, placebo-controlled study.
Patients: 79 persons between 19 and 78 years of age who fulfilled the American Rheumatism Association's criteria for rheumatoid arthritis.
Intervention: Participants were randomly assigned to visually identical placebo or to 5 mg or 27.5 mg of folic acid each week.
Measurements: Duration, intensity, and clinical severity of toxic events; efficacy (indices of joint tenderness and swelling and grip strength); plasma and erythrocyte folate levels; and other laboratory variables.
Results: Folic acid supplementation at either dose did not affect the efficacy of methotrexate therapy as judged by joint indices and patient and physician assessments of disease. Patients given folic acid supplements had lower toxicity scores than did participants given placebo (P
Conclusions: Folic acid, an inexpensive vitamin, is safe in a broad range of doses and protects patients with rheumatoid arthritis who are taking methotrexate from toxicity while preserving the efficacy of methotrexate.
Author and Article Information
From the Birmingham Veteran's Administration Hospital and the University of Alabama at Birmingham, Birmingham, Alabama.
ARTICLE
Supplementation with Folic Acid during Methotrexate Therapy for Rheumatoid Arthritis: A Double-Blind, Placebo-controlled Trial
0.001). Low blood folate levels and increased mean corpuscular volumes were associated with substantial methotrexate toxicity, whereas daily dietary intakes of more than 900 nmol (400 µg) of folic acid were associated with little methotrexate toxicity.
Requests for Reprints: Sarah L. Morgan, MD, RD, 212 Webb, Department of Nutrition Sciences, U.A.B. Station, Birmingham, AL 35294-3360.
Acknowledgments: The authors thank their patient volunteers and their referring rheumatologists (faculty and fellows) for participating in the study and the staffs of the General Clinical Research Center, the Kirklin Clinic, and the University of Alabama at Birmingham Clinical Vitaminology Lab for assisting in the investigation.
Grant Support: In part by the National Institutes of Health Department of Research Resources Clinical Research Center grant RR-32-31S1; United States Public Health Service grants 5P01-CA-28103-10, 5P60-AR-20614, and AR-03555; and Veteran's Administration Merit Review Award AR-03555.
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