Efficacy of Methotrexate in Combination with Antioxidant Vitamins (A, C & E) versus Methotrexate alone in the Treatment of Rheumatoid Arthritis

Mizanur Rahman, Kamrul Hasan Lohani, Ratan Kumar Nath, Mahtab Uddin Hasan, Sujat Paul, Mohammed Habibur Rahman, Golam Faruk, Mohammad Nezam Uddin, Rajat Sanker Roy Biswas, Mohammed Rezaul Karim


Background: There is evidence that oxidative stress plays an important role in autoimmune diseases, such as rheumatoid arthritis (RA). Despite the supporting evidence for a beneficial effect of antioxidants on clinical characteristics of RA, the right balance for optimal effectiveness of antioxidants is largely unknown. A study was designed to determine the potential beneficial effects of antioxidant intervention on clinical parameters of RA.

Methods: Randomized clinical trial of 152 patients with positive rheumatoid factor (RF) and a Disease Activity Score (DAS 28) higher than 3.2 were enrolled in the study. Patients were divided into two groups (Group A and Group B) randomly and group A received methotrexate and antioxidant vitamins (A, C and E in a fixed dose) and group B methotrexate only. They were followed up for three visits (baseline, 10th week and 14th week). The intervention was stopped after 10 weeks and was followed by a ‘wash-out’ period of 4 weeks. At baseline, 10th week and 14th week patient’s condition were assessed by means of DAS-28 score. P- Value less than <0.05 was considered significant.

Results: The numbers of swollen and tender joints were significantly reduced and general health was improved reflected by improved DAS-28 score at 10th week.

The antioxidant effect was considered beneficial as compared to the scores of 1st visit at baseline; the DAS-28 score was significantly reduced at 2nd visit at 10th week. Increment of the DAS-28 score among the group A patients who were on antioxidant up to10 weeks, after the “wash-out period” of four weeks i.e. at 14th week confirmed a significant relation between changes in clinical condition and antioxidants.

Conclusion: This study was designed to assess the potential beneficial effect of antioxidants (Vitamin A, C and E) in combination with methotrexate in the treatment of RA.


Rheumatoid arthritis, Disease Activity Score (DAS), Methotrexate, Antioxidants

Full Text:



Arnett FC, Edworthy SM, Bloch DA. 2006. The American Rheumatism association. 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31: 315-24.

Doherty M, Lanyon P, Ralston SH. 2004. Rheumatoid arthritis. In: Boon NA, Colledge NR, Walker BR, Hunter JAA, editors. Davidson’s principle and practice of medicine. 20th ed. London: Churchill Livingstone, 1101 – 6.

Firestein GS. 2005. Etiology and pathogenesis of rheumatoid arthritis. In: Kelley WN,

Melton L. 2006. The antioxidant myth: a medical fairy tale. New Scientist 2006 August

Mahajan A, Tandon VR. 2004. Antioxidants and rheumatoid arthritis. J Indian Rheumatol Assoc 12:139-42.

Hitchon CA, El-Gabalawy HS. 2006. Oxidation in rheumatoid arthritis. Arthritis Res Ther 6:265-78.

Fauci MA. 2011. Approach to articular and musculoskeletal disorder. Harison’s Internal Medicine; 18th edi: The Mcgraw- Hill Companies. 325: pp 2000-2020

Remans PH, van Oosterhout M, Smeets TJ, Sanders M, Frederiks WM, Reedquist KA et al 2005. Intracellular free radical production in synovial T lymphocytes from patients with rheumatoid arthritis. Arthritis Rheum. 52(7):2003–2009 July.

Oliver JE, Silman AJ. 2006. Risk factors for the development of rheumatoid arthritis. Scand J Rheumatol. 35(3):169174

Jaswal S, Metha HC, Sood AK, Kaur J. 2003. Antioxidant status in rheumatoid arthritis and role of antioxidant therapy. Clin Chim Acta. 338(1–2):123–129.

Richard M, van Vugt, Philip J, Ben A. C. 2008. Antioxidant intervention in rheumatoid arthritis: results of an open pilot study. Clin Rheumatol. 27(6): 771–775.

Hagfors L, Leanderson P, Skoldstam L, Anderson J, Johanson G. 2003. Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Nutr J. 2005; 30:3-9

DOI: https://doi.org/10.23954/osj.v3i1.1359


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Open Science Journal (OSJ) is multidisciplinary Open Access journal. We accept scientifically rigorous research, regardless of novelty. OSJ broad scope provides a platform to publish original research in all areas of sciences, including interdisciplinary and replication studies as well as negative results.