Open Access Peer-reviewed

The Effect of Methotrexate in Rheumatoid Arthritis Patients is Reduced by Tea Consumption

Ehab M. Mikhael1,, Samer I. Mohammed1

1University of Baghdad, College of Pharmacy, Clinical Pharmacy Department, Bagdad,Iraq

American Journal of Pharmacological Sciences. 2013, 1(4), 53-55. DOI: 10.12691/ajps-1-4-2
Published online: August 25, 2017


Rheumatoid arthritis (RA) is a common inflammatory disease. Methotrexate (MTX) is the most important drug for RA treatment; it acts as anti inflammatory drug by increasing adenosine level. Adenosine receptor antagonists reduce the anti inflammatory effect of MTX. Tea is a popular drink in Iraq contain large amount of caffeine, this study aimed to evaluate the effect of tea consumption on the response to MTX in RA patients. A cross-sectional study was conducted in Baghdad Teaching Hospital, Rheumatology Unit from September 2012 to April 2013. A total of 25 RA patients (5 males and 20 females) who were treated by using MTX for at least 3 consecutive months and drink tea daily were included in this study. RA Disease activity was assessed in all patients by clinical disease activity index (CDAI). A direct interview with all patient were done, each patient was asked about their tea intake and the size of cup used. This study showed that the average consumption of tea per day for each patient was approximated to 8 small cups, this high level of consumption was associated with a high value of RA disease activity as measured by CDAI in greater than the half of patient who participated in this study. There is a direct positive correlation between evaluator global assessment and swelling joint count with tea consumption. In conclusion tea consumption decreases the effectiveness of MTX in Iraqi patients with rheumatoid arthritis.


rheumatoid arthritis, methotrexate, adenosine, disease activity, tea
[1]  Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD, Tanasescu R. Extra-articular manifestations in rheumatoid arthritis. Maedica (Buchar), 5:286-91. Dec. 2010.
[2]  Brauna J, Rau R. An update on methotrexate. Curr Opin Rheumatol, 21(3):216-23. May. 2009.
[3]  3. Cronstein BN. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev. 57(2):163-72. Jun. 2005.View Article  PubMed
[4]  Cutolo M, Sulli A, Pizzorni C, Seriolo B, Straub RH. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis, 60:729- 735. Aug. 2001.View Article  PubMed
[5]  Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate: increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest. 92(6):2675-82. Dec.1993.View Article  PubMed
[6]  Morabito L, Montesinos MC, Schreibman DM, Balter L, Thompson LF, Resta R, Carlin G, Huie MA, Cronstein BN. Methotrexate and sulfasalazine promote adenosine release by a mechanism that requires ecto-5'-nucleotidase-mediated conversion of adenine nucleotides. J Clin Invest, 101(2):295-300. Jan. 1998.View Article  PubMed
[7]  Biaggioni I, Paul S, Puckett A, Arzubiaga C. Caffeine and theophylline as adenosine receptor antagonists in humans. J Pharmacol Exp Ther. 258(2):588-93. Aug. 1991. PubMed
[8]  Montesinos C, Yap JS, Desai A, Posadas I, McCrary CT, Cronstein BN. Reversal of the antiinflammatory effects of methotrexate by the nonselective adenosine receptor antagonists theophylline and caffeine. Evidence that the antiinflammatory effects of methotrexate are mediated via multiple adenosine receptors in rat adjuvant arthritis. Arthritis Rheum. 43(3):656-63. Mar. 2000.View Article
[9]  Nesher G, Mates M, Zevin S. Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis. Arthritis Rheum. 48(2):571-2. Feb. 2003.View Article  PubMed
[10]  Matthews CM. Steep your genes in health: drink tea. Proc (Bayl Univ Med Cent). 23(2):142-4. Apr. 2010.
[11]  Mahamood HY. Estimation of Lead in some of foods and drinks common popular in Basrah city – Iraq. Diyala Agricultural Sciences, 3 (1); 101-106. 2011.
[12]  Hamad MN, Abdul-Hussain DA. Gravimetric Estimation of Caffeine in Different Commercial Kinds of Tea Found in the Iraqi Market. Iraqi J Pharm Sci, 19(2); 48-53. 2010.
[13]  Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH,Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 31(3):315-24. Mar. 1988.View Article  PubMed
[14]  14. Gorial FI. Validity and reliability of CDAI in comparison to DAS28 in Iraqi patients with active rheumatoid arthritis. J Fac Med Baghdad. 54 (3); 231-33. 2012.
[15]  Alastair Hicks. Current Status and Future Development of Global Tea Production and Tea Products. AU J.T. 12(4): 251-264. Apr. 2009.
[16]  Evripidis Kaltsonoudis, Charalampos Papagoras, Alexandros A Drosos. Current and Future Role of Methotrexate in the Therapeutic Armamentarium for Rheumatoid Arthritis. Int J Clin Rheumatol. 7(2):179-189. 2012.View Article
[17]  Silke C, Murphy MS, Buckley T, Busteed S, Molloy MG, Phelan M. The effect of caffeine ingestion on the efficacy of methotrexate [abstract]. Rheumatology Oxford, 40 Suppl:34. 2001.
[18]  Benito-Garcia E, Heller JE, Chibnik LB, Maher NE, Matthews HM, Bilics JA, Weinblatt ME, Shadick NA. Dietary caffeine intake does not affect methotrexate efficacy in patients with rheumatoid arthritis. J Rheumatol. 33(7):1275-81. Jul. 2006. PubMed
[19]  Saevarsdottir S, Wallin H, Seddighzadeh M et al. SWEFOT Trial Investigators Group. Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial. Ann. Rheum. Dis.70,469-475. 2011.View Article  PubMed
[20]  Weinblatt ME, Kaplan H, Germain BF, Block S, Solomon SD, Merriman RC, Wolfe F, Wall B, Anderson L,Gall E, et al. “Methotrexate in rheumatoid arthritis: a five-year prospective multicenter study. Arthritis Rheum. 37(10):1492-8. Oct. 1994.View Article  PubMed
[21]  Rohekar G, Pope J. Test-retest reliability of patient global assessment and physician global assessment in rheumatoid arthritis. J Rheumatol. 36(10):2178-82. Oct. 2009.View Article  PubMed
[22]  Soubrier M, Zerkak D, Gossec L, et al. Which variables best predict change in rheumatoid arthritis therapy in daily clinical practice?. J Rheumatol. 33(7):1243-6. Jul. 2006. PubMed