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

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Department of Clinical Biochemistry, Randers Central Hospital, Skovlyvej 1, 8900 Randers, Denmark. neh@rc.aaa.dk

    , ,

    Source

    The Journal of rheumatology 31:12 2004 Dec pg 2374-81

    MeSH

    Arthritis, Rheumatoid
    Biomarkers
    Dose-Response Relationship, Drug
    Drug Administration Schedule
    Drug Therapy, Combination
    Female
    Folic Acid
    Follow-Up Studies
    Homocysteine
    Humans
    Male
    Methotrexate
    Probability
    Prospective Studies
    Risk Assessment
    Sensitivity and Specificity
    Severity of Illness Index
    Single-Blind Method
    Treatment Outcome
    Vitamin B 12

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    15570637

    Citation

    Hornung, Nete, et al. "Folate, Homocysteine, and Cobalamin Status in Patients With Rheumatoid Arthritis Treated With Methotrexate, and the Effect of Low Dose Folic Acid Supplement." The Journal of Rheumatology, vol. 31, no. 12, 2004, pp. 2374-81.
    Hornung N, Ellingsen T, Stengaard-Pedersen K, et al. Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis treated with methotrexate, and the effect of low dose folic acid supplement. J Rheumatol. 2004;31(12):2374-81.
    Hornung, N., Ellingsen, T., Stengaard-Pedersen, K., & Poulsen, J. H. (2004). Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis treated with methotrexate, and the effect of low dose folic acid supplement. The Journal of Rheumatology, 31(12), pp. 2374-81.
    Hornung N, et al. Folate, Homocysteine, and Cobalamin Status in Patients With Rheumatoid Arthritis Treated With Methotrexate, and the Effect of Low Dose Folic Acid Supplement. J Rheumatol. 2004;31(12):2374-81. PubMed PMID: 15570637.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Folate, homocysteine, and cobalamin status in patients with rheumatoid arthritis treated with methotrexate, and the effect of low dose folic acid supplement. AU - Hornung,Nete, AU - Ellingsen,Torkell, AU - Stengaard-Pedersen,Kristian, AU - Poulsen,Jørgen H, PY - 2004/12/1/pubmed PY - 2005/3/11/medline PY - 2004/12/1/entrez SP - 2374 EP - 81 JF - The Journal of rheumatology JO - J. Rheumatol. VL - 31 IS - 12 N2 - 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. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/15570637/Folate_homocysteine_and_cobalamin_status_in_patients_with_rheumatoid_arthritis_treated_with_methotrexate_and_the_effect_of_low_dose_folic_acid_supplement_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=15570637 DB - PRIME DP - Unbound Medicine ER -