RESEARCH - Effect of MTX on folate metabolism & effect of folic acid supplementation

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J Rheumatol. 2004 Dec;31(12):2374-81.

Folate, homocysteine, and cobalamin status in patients with rheumatoid

arthritis treated with methotrexate, and the effect of low dose folic

Acid supplement.

Hornung N, Ellingsen T, Stengaard-Pedersen K, Poulsen JH.

Department of Clinical Biochemistry, Randers Central Hospital, Randers,

Denmark.

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.

PMID: 15570637

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Mayo Clinic in Rochester

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s Hopkins Medicine

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