Does sulphasalazine cause folate deficiency in rheumatoid arthritis?

Scand J Rheumatol. 1985;14(3):265-70. doi: 10.3109/03009748509100404.


Sulphasalazine impairs folic acid absorption and metabolism but rarely leads to folate deficiency in inflammatory bowel disease (IBD). In rheumatoid arthritis (RA), however, serum and red cell folate concentrations are often low and sulphasalazine might stress folate metabolism. In a prospective study, 2 g sulphasalazine was compared with 500 mg penicillamine daily in 30 patients over 24 weeks. Pre-treatment serum and red cell folate concentrations were low-normal. Improvements in disease activity and haemoglobin occurred in both treatment groups, but MCV increased only in patients taking sulphasalazine. Serum and red cell folate concentrations did not change in either group. Increased MCV with sulphasalazine might therefore reflect reticulocytosis secondary to drug-induced haemolysis. The mechanisms by which sulphasalazine antagonizes folate metabolism are dose-dependent and, consequently, higher doses might precipitate folate deficiency.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Arthritis, Rheumatoid / drug therapy*
  • Erythrocyte Indices / drug effects
  • Folic Acid Deficiency / chemically induced*
  • Humans
  • Penicillamine / therapeutic use
  • Sulfasalazine / adverse effects*
  • Sulfasalazine / therapeutic use


  • Sulfasalazine
  • Penicillamine