Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexate therapy of rheumatoid arthritis and psoriatic arthritis patients

Clin Exp Rheumatol. 1995 Jul-Aug;13(4):459-63.


Objective: To compare folic acid (FA) levels in patients being treated with methotrexate (MTX) with those of untreated patients in order to investigate potential folate depletion by MTX and its possible relationship to the drug's efficacy.

Methods: In 33 patients on low-dose MTX therapy and in 24 controls, FA and cyanocobalamin (B12) levels were determined in serum and red blood cells (RBC). In addition, MTX levels in the RBC and serum were measured, and clinical and laboratory measures of disease activity were evaluated.

Results: MTX treated patients had lower FA levels than controls (median 4.36 vs 7.37 ng/ml, p < 0.001). A significant correlation between serum FA and MTX/RBC (p < 0.01) and between the weekly dose and MTX/RBC (p < 0.01) was seen. There was apparently no correlation between FA and the cumulative total MTX. MTX patients had lower B12/RBC levels than the controls (p < 0.001); the serum levels of B12 were not different. Clinical features, ESR and CRP did not correlate with FA, B12 or MTX levels.

Conclusions: The degree of folate depletion during MTX therapy depends primarily upon the weekly administered dose. Folate depletion may be related to B12 deficiency in RBC. Since FA levels were not related to parameters of disease activity it is conceivable that MTX does not exert its action in RA primarily by inhibiting dihydrofolatereductase. Therefore, additional folate compounds, if necessary, should not lead to a reduction in the efficacy of MTX.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Arthritis, Psoriatic / blood
  • Arthritis, Psoriatic / drug therapy*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Erythrocytes / metabolism*
  • Female
  • Folic Acid / blood*
  • Humans
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / blood
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Vitamin B 12 / blood*


  • Folic Acid
  • Vitamin B 12
  • Methotrexate