Skip to main content
SpringerLink
Log in

n-3 Fatty acids in the treatment of rheumatoid arthritis

  • Chapter
Medicinal Fatty Acids in Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

Summary

The pathophysiology of rheumatoid arthritis (RA) is complex and still not fully understood. Currently the main hypothesis is that chronic inflammation occurs after stimulation by T cell-macrophage interaction, induced by unknown antigen(s). This is accompanied by a complex sequence of highly integrated actions between macrophages, synoviocytes, polymorphonuclear cells and endothelial cells. The chronic inflammation is a major cause of pain and functional impairment, ultimately resulting in joint destruction. The production of eicosanoids (prostaglandins and leukotrienes) by macrophages/synoviocytes is only one of the many pathways of the inflammatory reaction, but the well-established efficacy of NSAIDs in patients with RA underscores the importance of the pro-inflammatory cyclo-oxygenase-pathway products in the pathophysiology of the symptoms. A positive clinical effect of n-3 fatty acids has been shown in some but not all animal experiments of arthritis. In patients with RA, n-3 fatty acid supplementation decreased clinical symptoms. Differences from patients treated with placebo (but still on NSAIDs or disease modifying drugs) were significant in some studies. A significant difference from placebo in the tender joint score and morning stiffness was found in a meta-and mega-analysis of 10 studies. In long-term studies, treatment with n-3 fatty acids resulted in a substantial decrease of the use of NSAIDs and/or disease modifying drugs as compared to placebo. No effects have been documented on the progression of joint destruction. No major side effects were reported compared to placebo. Therefore, as part of the total treatment program of RA, patients should be advised about the potential moderate effects on their symptoms of diet supplements with n-3 fatty acids.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Panayi GS, Lanchbury JS, Kingsley GH (1992) The importance of the T cell in initiating and maintaining the chronic synovitis of RA. Arthritis Rheum 35: 729–735

    Article  PubMed  CAS  Google Scholar 

  2. Harris ED (1989) Pathogenesis of RA. In: WN Kelley, ED Harris, S Ruddy, CB Sledge (eds): Textbook of Rheumatology. WB Saunders Company, 929–932

    Google Scholar 

  3. Pincus T, Callahan LF (1993) What is the natural history of rheumatoid Arthritis? Rheumat Dis Clin N Amer 19: 123–151

    CAS  Google Scholar 

  4. Flower RJ, Rothwell NJ (1994) Lipocortin-1: cellular mechanisms and clinical relevance. Trends Pharmacol Sci 15: 71–76

    Article  PubMed  CAS  Google Scholar 

  5. Crofford LJ, Wilder RL, Ristimaki SAP, Remmers EF, Epps HR, Hla T (1994) Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues: effect of interleukin-113, phorbol ester, and corticosteroids. J Clin Invest 93: 1095–1101

    Article  PubMed  CAS  Google Scholar 

  6. Pincus T, Callahan LF (1993) Variability in individual responses of 532 patients with rheumatoid arthritis to first-line and second-line drugs. Agents Actions Suppl 44: 67–75

    PubMed  CAS  Google Scholar 

  7. Vane J, Botting J, Botting R (eds) (1996) Improved non-steroidal anti-inflammatory drugs: COX-2 enzyme inhibitors. Kluwer Academic Publishers and William Harvey Press, Hingham, MA, USA

    Book  Google Scholar 

  8. Pincus T (1992) The paradox of effective therapies but poor long-term outcome in rheumatoid arthritis. Semin Arthritis Rheum 21: 2–15

    Article  PubMed  CAS  Google Scholar 

  9. Kremer JM, Bigaouette J, Michalek AV, Timchalk MA, Lininger L, Rynes RI, Huyck C, Zieminski J, Bartholomew LE (1985) Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. Lancet 1: 184–187

    Article  PubMed  CAS  Google Scholar 

  10. Kremer JM, Jubiz W, Michalek A, Rynes RI, Bartholomew LE, Bigaouette J, Timchalk MA, Beeler D, Lininger L (1987) Fish-oil fatty acid supplementation in active rheumatoid arthritis. A double-blinded, controlled cross-over study. Ann of Intern Med 106: 497–502

    CAS  Google Scholar 

  11. Cleland LG, French JK, Betts WH, Murphy GA, Elliot MJ (1988) Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. J Rheumatol 15: 1471–1475

    PubMed  CAS  Google Scholar 

  12. Kremer JM, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE, Sherman M (1990) Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum 33: 810–820

    Article  PubMed  CAS  Google Scholar 

  13. Tulleken JE, Limburg PC, Muskiet FAJ, van Rijswijk MH (1990) Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis. Arthritis Rheum 33: 1416–1419

    Article  PubMed  CAS  Google Scholar 

  14. Van der Tempel H, Tulleken JE, Limburg PC, Muskiet FAJ, van Rijswijk MH (1990) Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis 49: 76–80

    Article  PubMed  Google Scholar 

  15. Skoldstam L, Borjesson O, Kjallman A, Seiving B, Akesson B (1992) Effect of six month of fish oil supplementation in stable rheumatoid arthritis: a double-blind, controlled study. Scand J Rheumatol 21: 178–185

    Article  PubMed  CAS  Google Scholar 

  16. Kjeldsen-Kragh J, Lund JA, Ruse T, Finnanger B, Haaland K, Finstad R, Mikkelsen K, Forre O (1992) Dietary n-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis. J Rheum 19: 1531–1536

    PubMed  CAS  Google Scholar 

  17. Nielsen GL, Faarvang KL, Thomsen BS, Teglbjaerg KL, Jensen LT, Hansen TM, Lervang HH, Schmidt EB, Dyerberg J, Ernst E (1992) The effect of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomised, double blind trial. Eur J Clin Invest 22: 687–691

    Article  PubMed  CAS  Google Scholar 

  18. Lau CS, Morley KD, Belch JJF (1993) Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis. Br J Rheumatol 32: 982–989

    Article  PubMed  CAS  Google Scholar 

  19. Geusens P, Wouters C, Nijs J, Jiang Y, Dequeker J (1994) Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. Arthritis Rheum 37 (6), 824–829

    Article  PubMed  CAS  Google Scholar 

  20. Kremer JM, Lawrence DA, Petrillo GF, Litts LL, Mullaly PM, Rynes RL, Stocker RP, Parhami N, Greenstein NS, Fuchs BR, Mathur A, Robinson DR, Sperling RI, Bigaouette J (1995) The effect of high dose fish oil on rheumatoid arthritis after stopping NSAIDs: clinical and immune correlates in patients with rheumatoid arthritis. Arthr Rheumat 38: 1107–1114

    Article  CAS  Google Scholar 

  21. Sano H, Hla T, Maier JAM et al (1992) In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthosis and rats with adjuvant and streptococcal cell wall arthritis. J Clin Invest 89: 97–108

    Article  PubMed  CAS  Google Scholar 

  22. Masferrer JL, Zweifel BS, Manning PT et al (1994) Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc Natl Acad Sci USA 91: 3228–3232

    Article  PubMed  CAS  Google Scholar 

  23. Vane JR, Mitchell JA, Appleton I et al (1994) Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation. Proc Natl Acad Sci USA 91: 2046–2050

    Article  PubMed  CAS  Google Scholar 

  24. Robinson DR, Prickett JD, Makoul GT, Steinber AD, Colvin RB (1986) Dietary fish oil reduces progression of established renal disease in (NZB x NZW) mice and delays renal disease in BXSB and MRL/1 strains. Arthritis Rheum 29: 539–546

    Article  PubMed  CAS  Google Scholar 

  25. Prickett JD, Trentham DE, Robinson DR (1984) Dietary fish oil augments the induction of arthritis in rats immunised with type II collagen. J Immunol 132: 725–729

    PubMed  CAS  Google Scholar 

  26. Prickett JD, Robinson DR, Steinberg AD {1981) Dietary enrichment with the polyunsaturated fatty acid eicosapentaenoic acid prevents proteinuria and prolongs survival in NZB x NZW mice. J Clin Invest 68: 556–559

    Article  PubMed  CAS  Google Scholar 

  27. Kelley VE, Ferretti A, Izui S, Strom TB (1985) A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites and suppresses lupus in MRL/lpr mice. J Immunol 134: 1914–1919

    PubMed  CAS  Google Scholar 

  28. Leslie CA, Gonnerman WA, Ullman MD, Hayes KC, Franzblau C, Cathcart ES (1985) Dietary fish oil modulates macrophage fatty acids and decreases arthritis susceptibility in mice. J Exp Med 162: 1336–1349

    Article  PubMed  CAS  Google Scholar 

  29. Sperling RI (1995) Eicosanoids in rheumatoid arthritis. Rheumat Dis Clin N Amer 21: 741–758

    CAS  Google Scholar 

  30. De Luca P, Rothman D, Zurier RB (1995) Marine and botanic lipids as immunomodulatiry and therapeutic agents in the treatment of rheumatoid arthritis. Rheumat Dis Clin N Amer 21: 759–777

    Google Scholar 

  31. Cleland LG, Hill CL, James MJ (1995) Diet and arthritis. Baillière’s Clin Rheumatol 9: 771–785

    Article  CAS  Google Scholar 

  32. Kremer JM (1996) Effects of modulation of inflammatory and immune parameters with rheumatic and inflammatory disease receiving dietary supplementation of n-3 and n-6 fatty acids. Lipids 31: S243–S247

    Article  PubMed  CAS  Google Scholar 

  33. James MJ, Cleland LG (1997) Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Semin Arthritis Rheum 27: 85–97

    Article  PubMed  CAS  Google Scholar 

  34. Gürsel T, Firat S, Ercan ZS (1997) Increased serum leukotriene B4 level in the active stage of rheumatoid arthritis in children. Prostaglandins, Leukotrienes and Essential Fatty Acids 56: 205–207

    Article  Google Scholar 

  35. Robinson DR, Tashjian AH, Levine L (1975) Prostaglandin E2 induced bone resorption by rheumatoid synovia. A model of bone destruction in RA. J Clin Invest 56: 1181–1187

    Article  PubMed  CAS  Google Scholar 

  36. Rïstimaki A, Garfinkel S, Wessendorf J, Masiag T, Hla T (1994) Induction of cyclooxygenase-2 by interleukin-1a. Evidence for post-transcriptional regulation. J Biol Chem 269: 11769–11775

    PubMed  Google Scholar 

  37. Mehindate K, Al-Daccak R, Dayer JM (1995) Superantigen-induced collagenase gene expression in human IFN-y-treated fibroblast-like synoviocytes involves prostaglandin E2. J Immunol 155: 3570–3577

    PubMed  CAS  Google Scholar 

  38. Sperling RI, Weinblatt M, Robin JL, Ravalese J, Hoover RL, House F, Coblyn JS, Fraser PA, Spur BW, Robinson DR, Lewis RA, Austin KF (1987) Effect of dietary supplementation with marine fish oil on leucocyte mediator generation and function in rheumatoid arthritis. Arthritis Rheum 30: 988

    Article  PubMed  CAS  Google Scholar 

  39. Espersen GT, Grunnet N, Lervang HH et al (1992) Decreased interleukin-1ß levels in plasma from rheumatoid arthritis after dietary supplementation with n-3 polyunsaturated fatty acids. Clin Rheum 11: 393–395

    Article  CAS  Google Scholar 

  40. Endres S (1996) n-3 polyunsaturated fatty acids and human cytokine synthesis. Lipids 31: S239–242

    Article  PubMed  CAS  Google Scholar 

  41. Forest C, Franckhauser S, Glorian M, Antras-Ferry J, Robin D, Robin D (1997) Regulation of gene transcription by fatty acids, fibrates and prostaglandins: the phosphoenolpyruvate carboxykinase gene as a modal. Prostaglandins, Leukotrienes and Essential Fatty Acids 57: 47–56

    Article  CAS  Google Scholar 

  42. Nunez EA (1997) Fatty acids involved in signal cross-talk between cell membrane and nucleus. Prostaglandins, Leukotrienes and Essential Fatty Acids 57: 429–434

    Article  CAS  Google Scholar 

  43. Shapiro JA, Koepsell TD, Voigt LF, Dugowson CE, Kestin M, Nelson JL (1996) Diet and rheumatoid arthritis: a possible protective effect of fish consumption. Epidemiology 7: 256–263

    Article  PubMed  CAS  Google Scholar 

  44. Kremer JM, Bigaouette J (1996) Nutritient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper and magnesium. J Rheumatol 23: 990–994

    PubMed  CAS  Google Scholar 

  45. Fortin PR, Lew RA, Liang MH, Wright EA, Beckett LA, Chalmers TC, Sperling RI (1995) Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. J Clin Epidemiol 48: 1379–1390

    Article  PubMed  CAS  Google Scholar 

  46. Belch JJ, Ansel D, Madhok et al (1988) Effects of altering dietary essential fatty acids on requirements for non-steroidal antiinflammarory drugs in patients with rheumatoid arthritis: a double-blind placebo controlled study. Ann Rheumat Dis 47: 96–104

    Article  PubMed  CAS  Google Scholar 

  47. Tulleken JE (1991) Long chain omega-3 polyunsaturated fatty acids in rheumatoid arthritis. Rijksuniversiteit Groningen, Thesis

    Google Scholar 

  48. Belluzzi A, Brignola C, Campieri M, Pera A, Bosch S, Miglioli M (1996) Effect of enteric-coated fish-oil preparation on relapses in Crohn’s disease. N Engl J Med 334: 1557–1560

    Article  PubMed  CAS  Google Scholar 

  49. Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ (1996) The effect on human tumor necrosis factor α and interleukin-1ß production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 63: 116–122

    CAS  Google Scholar 

  50. Nettleton JA (1991) Omega-3 Fatty acids: comparison of plant and seafood sources in human nutrition. J Am Diet Assoc 91: 331–337

    PubMed  CAS  Google Scholar 

  51. Cleland LG, James MJ (1997) Rheumatoid arthritis and balance of dietary n-6 and n-3 essential fatty acids. Brit J Rheumatol 36: 513–515

    Article  CAS  Google Scholar 

  52. Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, van Zeben D, Dijkmans BA, Peeters AJ, Jacobs P, van den Brink HR, Schouten HJ, van der Heijde DM, Boonen A, van der Linden S (1997) Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 2: 309–318

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Research Center for Bone and Joint Diseases, Dr. L. Willems-lnstituut, Limburgs Universitair Centrum, B-3590, Diepenbeek, Belgium

    Piet P. Geusens

Authors
  1. Piet P. Geusens
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Rheumatology, Albany Medical College, Albany, NY, 12208, USA

    Joel M. Kremer (Professor of Medicine, Head) (Professor of Medicine, Head)

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Basel AG

About this chapter

Cite this chapter

Geusens, P.P. (1998). n-3 Fatty acids in the treatment of rheumatoid arthritis. In: Kremer, J.M. (eds) Medicinal Fatty Acids in Inflammation. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8825-7_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-8825-7_9

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9788-4

  • Online ISBN: 978-3-0348-8825-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation