, Volume 63, Issue 9, pp 845–853 | Cite as

The Role of Fish Oils in the Treatment of Rheumatoid Arthritis

  • Leslie G. ClelandEmail author
  • Michael J. James
  • Susanna M. Proudman
Leading Article


Fish oils are a rich source of omega-3 long chain polyunsaturated fatty acids (n-3 LC PUFA). The specific fatty acids, eicosapentaenoic acid and docosahexaenoic acid, are homologues of the n-6 fatty acid, arachidonic acid (AA). This chemistry provides for antagonism by n-3 LC PUFA of AA metabolism to pro-inflammatory and pro-thrombotic n-6 eicosanoids, as well as production of less active n-3 eicosanoids. In addition, n-3 LC PUFA can suppress production of pro-inflammatory cytokines and cartilage degradative enzymes.

In accordance with the biochemical effects, beneficial anti-inflammatory effects of dietary fish oils have been demonstrated in randomised, double-blind, placebo-controlled trials in rheumatoid arthritis (RA). Also, fish oils have protective clinical effects in occlusive cardiovascular disease, for which patients with RA are at increased risk.

Implementation of the clinical use of anti-inflammatory fish oil doses has been poor. Since fish oils do not provide industry with the opportunities for substantial profit associated with patented prescription items, they have not received the marketing inputs that underpin the adoption of usual pharmacotherapies. Accordingly, many prescribers remain ignorant of their biochemistry, therapeutic effects, formulations, principles of application and complementary dietary modifications. Evidence is presented that increased uptake of this approach can be achieved using bulk fish oils. This approach has been used with good compliance in RA patients. In addition, an index of n-3 nutrition can be used to provide helpful feedback messages to patients and to monitor the attainment of target levels.

Collectively, these issues highlight the challenges in advancing the use of fish oil amid the complexities of modern management of RA, with its emphasis on combination chemotherapy applied early.


Rheumatoid Arthritis Chain Polyunsaturated Fatty Acid Plasma Phospholipid Fatty Acid Recent Onset Rheumatoid Arthritis PUFA Enrichment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Funding from NHMRC is acknowledged. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.


  1. 1.
    Goldman DW, Pickett WC, Goetzl EJ. Human neutrophil chemotactic and degranulating activities of leukotriene B5 (LTB5) derived from eicosapentaenoic acid. Biochem Biophys Res Commun 1983; 117: 282–8PubMedCrossRefGoogle Scholar
  2. 2.
    Moncada S, Vane JR. The role of prostacyclin in vascular tissue. Fed Proc 1979; 38: 66–71PubMedGoogle Scholar
  3. 3.
    Caughey GE, Pouliot M, Cleland LG, et al. Regulation of tumor necrosis factor alpha and interleukin-1 beta synthesis by thromboxane A2 in non-adherent human monocytes. J Immunol 1997; 158: 351–8PubMedGoogle Scholar
  4. 4.
    Caughey GE, Mantzioris E, Gibson RA, et al. The effect on human tumor necrosis factor a and interleukin-1β production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 1996; 63: 116–22PubMedGoogle Scholar
  5. 5.
    Westacott CI, Sharif M. Cytokines in osteoarthritis: mediators or markers of joint destruction? Semin Arthritis Rheum 1996; 25: 254–72PubMedCrossRefGoogle Scholar
  6. 6.
    Hawkes JS, James MJ, Cleland LG. Biological activity of prostaglandin E3 with regard to oedema formation in mice. Agents Actions 1992; 35: 85–7PubMedCrossRefGoogle Scholar
  7. 7.
    Dooper MM, Wassink L, M'Rabet L, et al. The modulatory effects of prostaglandin-E on cytokine production by human peripheral blood mononuclear cells are independent of the prostaglandin subtype. Immunology 2002; 107: 152–9PubMedCrossRefGoogle Scholar
  8. 8.
    Hawkes JS, James MJ, Cleland LG. Separation and quantification of PGE3 following derivatization with panacyl bromide by high pressure liquid chromatography with fluorometric detection. Prostaglandins 1991; 42: 355–68PubMedCrossRefGoogle Scholar
  9. 9.
    Knapp HR, FitzGerald GA. The antihypertensive effects of fish oil: a controlled study of polyunsaturated fatty acid supplements in essential hypertension. N Engl J Med 1989; 320: 1037–43PubMedCrossRefGoogle Scholar
  10. 10.
    Serhan CN, Clish CB, Brannon J, et al. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 2000; 192: 1197–204PubMedCrossRefGoogle Scholar
  11. 11.
    Serhan CN, Hong S, Gronert K, et al. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 2002; 196: 1025–37PubMedCrossRefGoogle Scholar
  12. 12.
    Kremer JM, Bigauoette J, Michalek AV, et al. Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. Lancet 1985; I: 184–7CrossRefGoogle Scholar
  13. 13.
    Kremer JM, Jubiz W, Michalek A, et al. Fish-oil fatty acid supplementation in active rheumatoid arthritis. Ann Intern Med 1987; 106: 497–503PubMedGoogle Scholar
  14. 14.
    Kremer JM, Lawrence DA, Jubiz W, et al. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Arthritis Rheum 1990; 33: 810–20PubMedCrossRefGoogle Scholar
  15. 15.
    Kremer JM, Lawrence DA, Petrillo GF, et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Arthritis Rheum 1995; 38: 1107–14PubMedCrossRefGoogle Scholar
  16. 16.
    Cleland LG, French JK, Betts WH, et al. Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. J Rheumatol 1988; 15: 1471–5PubMedGoogle Scholar
  17. 17.
    Tulleken JE, Limburg PC, Muskiet FAJ, et al. Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis. Arthritis Rheum 1990; 33: 1416–9PubMedCrossRefGoogle Scholar
  18. 18.
    van der Tempel H, Tulleken JE, Limburg PC, et al. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis 1990; 49: 76–80PubMedCrossRefGoogle Scholar
  19. 19.
    Skoldstam L, Borjesson O, Kjallman A, et al. Effect of six months of fish oil supplementation in stable rheumatoid arthritis: a double blind, controlled study. Scand J Rheumatol 1992; 21: 178–85PubMedCrossRefGoogle Scholar
  20. 20.
    Kjeldsen-Kragh J, Lund JA, Riise T, et al. Dietary omega-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis. J Rheumatol 1992; 19: 1531–6PubMedGoogle Scholar
  21. 21.
    Nielsen GL, Faarvang KL, Thomsen BS, et al. The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized double blind trial. Eur J Clin Invest 1992; 22: 687–91PubMedCrossRefGoogle Scholar
  22. 22.
    Lau CS, Morley KD, Belch JJF. Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis: a double blind placebo controlled study. Br J Rheumatol 1993; 32: 982–9PubMedCrossRefGoogle Scholar
  23. 23.
    Geusens P, Wouters C, Nijs J, et al. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. Arthritis Rheum 1994; 37: 824–9PubMedCrossRefGoogle Scholar
  24. 24.
    Volker D, Fitzgerald P, Major G, et al. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol 2000; 27: 2343–6PubMedGoogle Scholar
  25. 25.
    James MJ, Cleland LG. Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum 1997; 27: 85–97PubMedCrossRefGoogle Scholar
  26. 26.
    Fortin PR, Lew RA, Liang MH, et al. Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. J Clin Epidemiol 1995; 48: 1379–90PubMedCrossRefGoogle Scholar
  27. 27.
    Cleland LG, James MJ, Neumann MA, et al. Linoleate inhibits EPA incorporation from dietary fish oil supplements in human subjects. Am J Clin Nutr 1992; 55: 395–9PubMedGoogle Scholar
  28. 28.
    Mantzioris E, Cleland LG, Gibson RA, et al. Biochemical effects of a diet containing foods enriched with n-3 fatty acids. Am J Clin Nutr 2000; 72: 42–8PubMedGoogle Scholar
  29. 29.
    Mantzioris E, James MJ, Gibson RA, et al. Dietary substitution with an α-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues. Am J Clin Nutr 1994; 59: 1304–9PubMedGoogle Scholar
  30. 30.
    Cleland LG, Proudman SM, Hall C, et al. A biomarker of n-3 status in patients taking fish oil for inflammatory diseases. Lipids. In pressGoogle Scholar
  31. 31.
    Marchioli R, Barzi F, Bomba E, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Grup-po Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 2002; 105: 1897–903PubMedCrossRefGoogle Scholar
  32. 32.
    Albert CM, Campos H, Stampfer MJ, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 2002; 346: 1113–8PubMedCrossRefGoogle Scholar
  33. 33.
    Kang JX, Leaf A. Antiarrhythmic effects of polyunsaturated fatty acids: recent studies. Circulation 1996; 94: 1774–80PubMedCrossRefGoogle Scholar
  34. 34.
    Metcalf RG, James MJ, Cowie R, et al. Effect of fish oil on electrically induced ventricular tachycardia in high risk cardiac patients [abstract]. Australian Society for Medical Research (SA). Annual Scientific Meeting; 2002 May 30; AdelaideGoogle Scholar
  35. 35.
    O'Keefe Jr JH, Harris WS. From Inuit to implementation: omega-3 fatty acids come of age. Mayo Clin Proc 2000; 75: 607–14PubMedCrossRefGoogle Scholar
  36. 36.
    Bacon PA, Townend JN. Nail in the coffin: increasing evidence for the role of rheumatic disease in the cardiovascular mortality of rheumatoid arthritis. Arthritis Rheum 2001; 44: 2707–10PubMedCrossRefGoogle Scholar
  37. 37.
    Darlametsos IE, Varonos DD. Role of prostanoids and endothelins in the prevention of cyclosporine-induced nephrotoxicity. Prostaglandins Leukot Essent Fatty Acids 2001; 64: 231–9PubMedCrossRefGoogle Scholar
  38. 38.
    Cleland LG, James MJ, Stamp LK, et al. COX-2 inhibition and thrombotic tendency: a need for surveillance. Med J Aust 2001; 175: 214–7PubMedGoogle Scholar
  39. 39.
    Haagsma CJ, Blom HJ, van Riel PL, et al. Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis 1999; 58: 79–84PubMedCrossRefGoogle Scholar
  40. 40.
    Frauman AG. An overview of the adverse reactions to adrenal corticosteroids. Adverse Drug React Toxicol Rev 1996; 15: 203–6PubMedGoogle Scholar
  41. 41.
    Kruger MC, Coetzer H, de Winter R, et al. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano) 1998; 10: 385–94Google Scholar
  42. 42.
    Emery P, Breedveld FC, Dougados M, et al. Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis 2002; 61: 290–7PubMedCrossRefGoogle Scholar
  43. 43.
    Belluzzi A, Brignola C, Campieri M, et al. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med 1996; 334: 1557–60PubMedCrossRefGoogle Scholar
  44. 44.
    Donadio JV. The emerging role of omega-3 polyunsaturated fatty acids in the management of patients with IgA nephropathy. J Ren Nutr 2001; 11: 122–8PubMedCrossRefGoogle Scholar
  45. 45.
    Robinson DR, Prickett JD, Makoul GT, et al. Dietary fish oil reduces progression of established renal disease in (NZB X NZW)F1 mice and delays renal disease in BXSB and MRL/1 strains. Arthritis Rheum 1986; 29: 539–46PubMedCrossRefGoogle Scholar
  46. 46.
    Mayser P, Mrowietz U, Arenberger P, et al. Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, multicenter trial. J Am Acad Dermatol 1998; 38: 539–47PubMedCrossRefGoogle Scholar
  47. 47.
    Curtis CL, Rees SG, Little CB, et al. Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids. Arthritis Rheum 2002; 46: 1544–53PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Leslie G. Cleland
    • 1
    Email author
  • Michael J. James
    • 1
  • Susanna M. Proudman
    • 1
  1. 1.Rheumatology UnitRoyal Adelaide HospitalAdelaideAustralia

Personalised recommendations