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Fish oil and rheumatoid arthritis: past, present and future

  • Michael James (a1), Susanna Proudman (a1) and Les Cleland (a1)
  • DOI:
  • Published online: 28 May 2010

Meta- and mega-analysis of randomised controlled trials indicate reduction in tender joint counts and decreased use of non-steroidal anti-inflammatory drugs with fish-oil supplementation in long-standing rheumatoid arthritis (RA). Since non-steroidal anti-inflammatory drugs confer cardiovascular risk and there is increased cardiovascular mortality in RA, an additional benefit of fish oil in RA may be reduced cardiovascular risk via direct mechanisms and decreased non-steroidal anti-inflammatory drug use. Potential mechanisms for anti-inflammatory effects of fish oil include inhibition of inflammatory mediators (eicosanoids and cytokines), and provision of substrates for synthesis of lipid suppressors of inflammation (resolvins). Future studies need progress in clinical trial design and need to shift from long-standing disease to examination of recent-onset RA. We are addressing these issues in a current randomised controlled trial of fish oil in recent-onset RA, where the aim is to intervene before joint damage has occurred. Unlike previous studies, the trial occurs on a background of drug regimens determined by an algorithm that is responsive to disease activity and drug intolerance. This allows drug use to be an outcome measure whereas in previous trial designs, clinical need to alter drug use was a ‘problem’. Despite evidence for efficacy and plausible biological mechanisms, the limited clinical use of fish oil indicates there are barriers to its use. These probably include the pharmaceutical dominance of RA therapies and the perception that fish oil has relatively modest effects. However, when collateral benefits of fish oil are included within efficacy, the argument for its adjunctive use in RA is strong.

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*Corresponding author: Dr Michael James, fax 61-8-82224139, email
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1.PR Fortin , RA Lew , MH Liang (1995) Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. J Clin Epidemiol 48, 13791390.

2.MJ James & LG Cleland (1997) Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum 27, 8597.

3.JM Kremer , DA Lawrence , GF Petrillo (1995) Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Arthritis Rheum 38, 11071114.

4.RJ Goldberg & J Katz (2007) A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain 129, 210223.

6.L Skoldstam , O Borjesson , A Kjallman (1992) Effect of six months of fish oil supplementation in stable rheumatoid arthritis. A double blind, controlled study. Scand J Rheumatol 21, 178185.

7.JJF Belch , D Ansell , R Madhok (1988) Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind controlled study. Ann Rheum Dis 47, 96–104.

8.CS Lau , KD Morley & JJ Belch (1993) 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 32, 982989.

9.JM Kremer , DA Lawrence , W Jubiz (1990) Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Arthritis Rheum 33, 810820.

11.DC Nordstrom , VE Honkanen , Y Nasu (1995) Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed. Rheumatol Int 14, 231234.

12.GL Nielsen , KL Faarvang , BS Thomsen (1992) 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 22, 687691.

13.S Van Doornum , G McColl & IP Wicks (2002) Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum 46, 862873.

14.H Maradit-Kremers , CS Crowson , PJ Nicola (2005) Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 52, 402411.

15.H John , G Kitas , T Toms (2009) Cardiovascular co-morbidity in early rheumatoid arthritis. Best Pract Res Clin Rheumatol 23, 7182.

16.ME Farkouh & BP Greenberg (2009) An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs. Am J Cardiol 103, 12271237.

18.CM Albert , H Campos , MJ Stampfer (2002) Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 346, 11131118.

19.GISSI Prevenzione Investigators (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 354, 447455.

20.PL McLennan , TM Bridle , MY Abeywardena (1992) Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey. Am Heart J 123, 15551561.

21.PL McLennan (2001) Myocardial membrane fatty acids and the antiarrhythmic actions of dietary fish oil in animal models. Lipids 36, S111S114.

22.GE Billman , JX Kang & A Leaf (1999) Prevention of sudden cardiac death by dietary pure ν-3 polyunsaturated fatty acids in dogs. Circulation 99, 24522457.

23.RG Metcalf , P Sanders , MJ James (2008) Effect of dietary n-3 polyunsaturated fatty acids on the inducibility of ventricular tachycardia in patients with ischemic cardiomyopathy. Am J Cardiol 101, 758761.

24.R Schrepf , T Limmert , P Claus Weber (2004) Immediate effects of n-3 fatty acid infusion on the induction of sustained ventricular tachycardia. Lancet 363, 14411442.

26.JF Fries , KN Murtagh , M Bennett (2004) The rise and decline of nonsteroidal antiinflammatory drug-associated gastropathy in rheumatoid arthritis. Arthritis Rheum 50, 24332440.

27.CJ Smith , Y Zhang , CM Koboldt (1998) Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci USA 95, 1331313318.

28.T Hori , T Oka , M Hosoi (1998) Pain modulatory actions of cytokines and prostaglandin E2 in the brain. Ann NY Acad Sci 840, 269281.

29.D Engblom , M Ek , S Saha (2002) Prostaglandins as inflammatory messengers across the blood-brain barrier. J Mol Med 80, 5–15.

30.J Guay , K Bateman , R Gordon (2004) Carrageenan-induced paw edema in rat elicits a predominant prostaglandin E2 (PGE2) response in the central nervous system associated with the induction of microsomal PGE2 synthase-1. J Biol Chem 279, 2486624872.

31.M Chen , BK Lam , Y Kanaoka (2006) Neutrophil-derived leukotriene B4 is required for inflammatory arthritis. J Exp Med 203, 837842.

32.WE Lands (1991) Biosynthesis of prostaglandins. Annu Rev Nutr 11, 4160.

33.JS Hawkes , MJ James & LG Cleland (1991) Separation and quantification of PGE3 following derivatization with panacyl bromide by high pressure liquid chromatography with fluorometric detection. Prostaglandins 42, 355368.

34.LG Cleland , MJ James , RA Gibson (1990) Effect of dietary oils on the production of n-3 and n-6 metabolites of leukocyte 5-lipoxygenase in five rat strains. Biochim Biophys Acta 1043, 253258.

35.DW Goldman , WC Pickett & EJ Goetzl (1983) Human neutrophil chemotactic and degranulating activities of leukotriene B5 (LTB5) derived from eicosapentaenoic acid. Biochem Biophys Res Commun 117, 282288.

37.S Endres , R Ghorbani , VE Kelley (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 320, 265271.

42.CN Serhan , N Chiang & TE Van Dyke (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8, 349361.

43.Y-P Sun , SF Oh , J Uddin (2007) Resolvin D1 and Its Aspirin-triggered 17R Epimer: Stereochemical assignments, anti-inflamamatory properties, and enzymic inactivation. J Biol Chem 282, 93239334.

44.CN Serhan , S Hong , K Gronert (2002) Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 196, 10251037.

45.M Arita , F Bianchini , J Aliberti (2005) Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med 201, 713722.

48.JE Tulleken , PC Limburg , FAJ Muskiet (1990) Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis. Arthritis Rheum 33, 14161419.

49.H van der Tempel , JE Tulleken , PC Limburg (1990) Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis 49, 7680.

51.JM Kremer , W Jubiz , A Michalek (1987) Fish-oil fatty acid supplementation in active rheumatoid arthritis. Ann Intern Med 106, 497503.

54.P Geusens , C Wouters , J Nijs (1994) Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. Arthritis Rheum 37, 824829.

56.JR O'Dell , R Leff , G Paulsen (2002) Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46, 11641170.

59.RN Maini , FC Breedveld , JR Kalden (2004) Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum 50, 10511065.

60.LW Moreland , MH Schiff , SW Baumgartner (1999) Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med 130, 478486.

61.ME Weinblatt , EC Keystone , DE Furst (2003) Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 48, 3545.

62.M James & L Cleland (2008) COMET results are not stellar. Lancet 372, 18071808.

63.SM Proudman , HI Keen , LK Stamp (2007) Response-driven combination therapy with conventional disease-modifying antirheumatic drugs can achieve high response rates in early rheumatoid arthritis with minimal glucocorticoid and nonsteroidal anti-inflammatory drug use. Semin Arthritis Rheum 37, 99–111.

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