Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis treated with methotrexate, and the effect of low dose folic acid supplement.
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.


CONCLUSIONS
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.
Hornung
Nete
N
Department of Clinical Biochemistry, Randers Central Hospital, Skovlyvej 1, 8900 Randers, Denmark. neh@rc.aaa.dk
Ellingsen
Torkell
T
Stengaard-Pedersen
Kristian
K
Poulsen
Jørgen H
JH
D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016037:Single-Blind Method; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000097:blood*
D015415:Biomarkers; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12; D008727:Methotrexate