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Effects of modulation of inflammatory and immune parameters in patients with rheumatic and inflammatory disease receiving dietary supplementation of n-3 and n-6 fatty acids

  • Inflammation and the Immune System
  • Published:
Lipids

Abstract

To describe the rationale and status of n-3 and n-6 fatty acid dietary supplementation in patients with inflammatory disease. The most recent literature is reviewed with a focus on rheumatoid arthritis (RA) as most investigations have described the use of n-3 supplements in this disease entity. Investigations from Europe, the United States, and Australia have described consistent improvement in tender joint scores with many investigators also observing improvements in morning stiffness. A meta analysis has confirmed the predictable improvement in tender joints. Recent studies also suggest that some patients with RA are able to discontinue nonsteroidal anti-inflammatory drugs (NSAIDs) while receiving n-3 fatty acids. A large number of peer reviewed publications from around the world have established the utility of dietary supplementation with n-3 fatty acids in reducing tender joint counts and morning stiffness in patients with RA. Some patients are also able to discontinue NSAIDs while on these supplements.

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Abbreviations

DGLA:

dihomogammalinolenic acid

EPA:

eicosapentaenoic acid

GLA:

γ-linolenic acid

IL-1B:

interleukin-1B

LTB4, B5 :

leukotreine B4, B5

NSAID:

nonsteroidal antiinflammatory drug

PAF:

platelet activating factor

PGE1, E2, E3 :

prostaglandin E1, E2, E3

RA:

rheumatoid arthritis

TNF:

tumor necrosis factor

References

  1. Weber, P.C. (1988) Membrane Phospholipid Modification by Dietary n-3 Fatty Acids: Effects on Eicosanoid Formation and Cell Function, inBiological Membranes, Aberrations in Membrane Structure and Function, pp. 263–274, Alan R. Liss, New York.

    Google Scholar 

  2. Prickett, J.D., Robinson, D.R., and Steinberg, A.D. (1981) Dietary Enrichment With the Polyunsaturated Fatty Acid Eicosapentaenoic Acid Prevents Proteinuria and Prolongs Survival in (NZBxNZW) F1 Mice,J. Clin. Invest. 68, 556.

    PubMed  CAS  Google Scholar 

  3. Lee, T.H., Hoover, R.L., Williams, J.D., Sperling, R.I., Ravalese, J. III, Spur, B.W., Robinson, D.R., Corey E.J., Lewis, R.A., and Austin, K.F. (1985) Effect of Dietary Enrichment with Eicosapentaenoic and Docosahexaenoic Acids onin Vitro Neutrophil and Monocyte Leukotriene Generation and Neutrophil Function,N. Engl. Med. 312, 1217.

    Article  CAS  Google Scholar 

  4. Shekelle, R.B., Missell, L.V., Oglesby, P., MacMillan-Shryock, A., and Stamer, J. (1985) Fish Consumption and Mortality from Coronary Heart Disease,N. Engl. J. Med. 313, 820.

    Article  Google Scholar 

  5. Willis, A.L., Comai, K., Kuhn, D.C., and Paulsrud, J. (1974) Dihomogammalinolenate Suppresses Platelet Aggregation When Administeredin Vitro orin Vivo, Prostaglandins 7, 509.

    Article  Google Scholar 

  6. Zurier, R.B. (1982) Prostaglandins, Immune Responses, and Murine Lupus,Arthritis Rheum. 25, 804–809.

    Article  PubMed  CAS  Google Scholar 

  7. Tate, G.A., Mandell, B.F., Karmali, R.A., Laposata, M., Baker, D.G., Schumacher, H.R. Jr., and Zurier, R.B. (1988) Suppression of Monosodium Urate Crystal-Induced Acute Inflammation by Diets Enriched With Gammalinolenic Acid and Eicosapentaenoic Acid,Arthritis Rheum. 31, 1543.

    Article  PubMed  CAS  Google Scholar 

  8. Baker, D.G., Krakauer, K.A., Tate, G., Laposata, M., and Zurier, R.B. (1989) Suppression of Human Synovial Cell Proliferation by Dihomogammalinolenic Acid,Arthritis Rheum. 32, 1273.

    Article  PubMed  CAS  Google Scholar 

  9. Hansen, T.M., Lerche, A., Kassis, V., Lorenzen, I., and Sondergaard, J. (1983) Treatment of Rheumatoid Arthritis With Prostaglandin E1 Precursors Cis-Linoleic Acid and Gamma-Linolenic Acid,Scand. J. Rheum. 12, 85.

    PubMed  CAS  Google Scholar 

  10. Jantti, J., Nikkari, T., Solakivi, T., Vapaatalo, H., and Isomaki, H. (1989) Evening Primrose Oil in Rhematoid Arthritis: Changes in Serum Lipids and Fatty Acids,Ann. Rheum. Dis. 48, 124.

    PubMed  CAS  Google Scholar 

  11. Leventhal, L.J., Boyce, E.G., and Zurier, R.B. (1993) Treatment of Rheumatoid Arthritis with Gammalinolenic Acid,Ann. Intern. Med. 119, 867–873.

    PubMed  CAS  Google Scholar 

  12. Santoli, D., and Zurier, R.B. (1989) Prostaglandin E Precursor Fatty Acids Inhibit Human IL-2 Production by a Prostaglandin E-Independent Mechanisms,J. Immunol. 143, 1303–1309.

    PubMed  CAS  Google Scholar 

  13. Santoli, D., Philips, P.D., and Zurier, R.B. (1990) Suppression of Interleukin 2-Dependent Human T Cell Growth by Prostaglandin E (PGE) and Their Precursor Fatly Acids, Evidence for a PGE Independent Mechanism of Inhibition by the Fatty Acids.J. Clin. Invest. 85, 424–432.

    PubMed  CAS  Google Scholar 

  14. Robinson, D.R., Tateno, S., Balkrishna, P., and Hirai, A. (1988) Lipid Mediators of Inflammatory and Immune Reactions,JPEN, 12, 375.

    Google Scholar 

  15. Ferretti, A., and Flanagan, V.P. (1990) Modification of Prostaglandin Metabolismin vivo by Long-Chain n-3 Polyunsaturates,Biochem. Biophysic. Acta. 1045, 299.

    CAS  Google Scholar 

  16. Holman, R.T. (1964) Nutritional and Metabolic Interrelationships Between Fatty Acids,Fed. Proc. 23, 1062.

    PubMed  CAS  Google Scholar 

  17. Simopoulos, A.P., Kifer, R.R., and Martin, R.E. (eds.), (1986) Health Effects of Polyunsaturated Fatty Acids in Seafoods. Academic Press, New York.

    Google Scholar 

  18. Lee, T.H., Mencia-Huerta, J.M., Shih, C., Corey, E.J., Lewis, R.A., and Austin, K.F. (1984) Characterization and Biologic Properties of 5,12-Dihydroxy Derivatives of Eicosapentaenoic Acid, Including Leukotriene B5 and the Double Lipoxygenase Product,J. Biol. Chem. 259, 2383.

    PubMed  CAS  Google Scholar 

  19. Lee, T.H., Hoover, R.L., Williams, J.D., Sperling, R.I., Ravalese, J. III, Spur, B.W., Robinson, D.R., Corey, E.J., Lewis, R.A., and Austin, K.F. (1985) Effect of Dietary Enrichment with Eicosapentaenoic and Docosahexaenoic Acids onin vitro Neutrophil Function,N. Engl. J. Med. 312, 1217.

    Article  PubMed  CAS  Google Scholar 

  20. Sperling, R.I., Weinblatt, M., Robin, J.L., Ravalese, J. III, Hoover, R.L., House, F., Coblyn, J.S., Fraser, P.A., Spur, B.W., Robinson, D.R., Lewis, R.A., and Austin, K.F. (1987) Effects of Dietary Supplementation with Marine Fish Oil on Leukocyte Lipid Mediator Generation and Function in Rheumatoid Arthritis,Arthritis Rheum. 30, 988.

    Article  PubMed  CAS  Google Scholar 

  21. Dulioust, A., Salem, P., Vivier, E., Benveniste, J., and Thomas, Y. (1988) Immunoregulatory Functions of PAF-Acether (Platelet-Activating Factor) in Biological Membranes: Aberrations in Membrane Structure and Function,Prog. Clin. Biol. Res., pp. 87–96, Alan R. Liss, New York.

    Google Scholar 

  22. Humphrey, D.M., McManase, L., Satouchi, K., Hanahan, D.J., and Pinckard, R.N. (1982) Vasoactive Properties of Acelyl Glyceryl Ether Phosphorylcholine and Analogs,Lab Invest. 46, 422.

    PubMed  CAS  Google Scholar 

  23. Endres, S., Ghorbani, R., Kelley, V.E., Georgilis, K., Lonnemann, G., VanderMeer, J.W., Cannon J.G., Rogers, T.S., Klempner, M.S., Weber, D.C., Schaefer, E.J., Wolff, S.M., and Dinarello, C.A. (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, 265.

    Article  PubMed  CAS  Google Scholar 

  24. Robinson, D.R., Prickett, J.D., Makoul, G.T., Steinberg, A.D., and Colvin, R.B. (1986) Dietary Fish Oil Reduces Progression of Established Renal Disease in (NZBxNZW)F1 Mice and Delays Renal Disease, in BXSB and MRL/1 Strains,Arthritis and Rheumatism 29, 539–546.

    Article  PubMed  CAS  Google Scholar 

  25. Prickett, J.D., Trentham, D.E., and Robinson, D.R. (1984) Dietary Fish Oil Augments the Induction of Arthritis in Rats Immunized with Type II Collagen,J. Immunol. 132, 725–729.

    PubMed  CAS  Google Scholar 

  26. Robinson, D.R., Tateno, S., Knoell, C., Olesiak, W., Xu, L., Hirai, A., Guo, M., and Colvin, R.B. (1989) Dietary Marine Lipids Suppress Murine Autoimmune Disease,J. Int. Med. 225, 211.

    Google Scholar 

  27. Kremer, J.M., Bigauoette, J., and Michalek, A.U. (1985) Effects of Manipulating Dietary Fatty acids on Clinical Manifestations of Rheumatoid Arthritis,Lancet 1, 184.

    Article  PubMed  CAS  Google Scholar 

  28. Kremer, J.M., Jubiz, W., Michalek, A., Rynes, R.I., Bartholomew, L.E., Bigauette, J., Timchalk, M., and Lininger, L. (1987) Fish-Oil Fatty Acid Supplementation in Active Rheumatoid Arthritis: A Double-Blinded, Controlled Crossover Study,Ann. Int. Med. 106, 498.

    Google Scholar 

  29. Sperling, R.I., Weinblatt, M., Robin, J.L., Ravalese, J. III, Hoover, R.L., House, F., Coblyn, J.S., Fraser, P.A., Spur, B.W., Robinson, D.R., Lewis, R.A., and Austin, K.F. (1987) Effects of Dietary Supplementation with Marine Fish Oil on Leukocyte Lipid Mediator Generation and Function in Rheumatoid Arthrits,Arth. Rheum. 30, 988–997.

    Article  CAS  Google Scholar 

  30. Kremer, J.M., Lawrence, D.A., Jubiz, W., DiGiacomo, R., Rynes, R., Bartholomew, L.E., and Sherman, M. (1990) Dietary Fish Oil and Olive Oil Supplementation in Patients with Rheumatoid Arthritis: Clinical and Immunologic Effects,Arth. Rheum. 33, 810.

    Article  CAS  Google Scholar 

  31. Kremer, J.M., Lawrence, D.A., Petrillo, G.F., Litts, L.L., Mullaly, P.M., Rynes, R.I., Stocker, R.P., Parhami, N., Greenstein, N.S., Fuchs, B.R., Mathur, A., Robinson, D.R., Sperling, R.I., and 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,Arth. Rheum. 38, 1107–1114.

    Article  CAS  Google Scholar 

  32. Cleland, L.G., French, J.K., Betts, W.H., Murphy, G.A., and Elliott, M.J. (1988) Clinical and Biochemical Effects of Dietary Fish-Oil Supplements in Rheumatoid Arthritis,J. Rheum. 15, 1471.

    PubMed  CAS  Google Scholar 

  33. van der Tempel, H., Tulleken, J.E., Limburg, P.C., Muskiet F.A.J., and van Riiswijk, M.H. (1990) Detects of Fish Oil Supplementation in Rheumatoid Arthritis,Ann. Rheum. Dis. 49, 76–80.

    PubMed  Google Scholar 

  34. Skoldstam, L., Boriesson, O., Kjallman, A., Seiving, B., and Akesson, B. (1992) Effect of Six Months of Fish Oil Supplementation in Stable Rheumatoid Arthritis. A Double-Blind, Controlled Study,Scand. J. Rheum., 21, 178–185.

    PubMed  CAS  Google Scholar 

  35. Kjeldsen-Kragh, J., Lund, J.A., Riise, T., Finnanger, B., Haaland, K., Finstad, R., Mikkelsen, K., and 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 

  36. Nielsen, G.L., Faarvang, K.L., Thomsen, B.S., Teglbjaerg, K.L., Jensen, L.T., Hansen, T.M., Lervang, H.H., Schmidt, E.B., Dyerberg, J., and Ernst, E. (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, 687–691.

    PubMed  CAS  Google Scholar 

  37. Belch, J.J.F., Ansell, D., Madhok, R., Dowd, A.O., and Sturock, R.D. (1988) Effects of Altering Dietary Essential Fatty Acids on Requirements for Non-Steroidal Anti-Inflammatory Drugs in Patients with Rheumatoid Arthrits: A Double Blind Placebo Controlled Study,Ann. Rheum. Dis. 47, 96–104.

    Article  PubMed  CAS  Google Scholar 

  38. Sperson, G.T., Grunnet, N., Lervang, H.H., Nielsen, G.L., Thomsen, B.S., Faarvang, K.L., Dyerberg, J., and Ernst, E. (1992) Decreased, Interleukin-1 Beta Levels in Plasma From Rheumatoid Arthritis Patients After Dietary Supplementation with n-3 Polyunsaturated Fatty Acids,Clin. Rheum. 11, 383–395.

    Google Scholar 

  39. Geusens, P., Wouters, C., Nijs, J., Jiang, Y., and Dequeker, J. (1994) Long-Term Effect of n-3 Fatty Acid Supplementation in Active Rheumatoid Arthrits. A 12 Month Double Blind Controlled Study,Arth. Rheum. 37, 824–829.

    Article  CAS  Google Scholar 

  40. Bigaouette, J., Timchalk, M.A., and Kremer, J. (1987) Nutritional Adequacy of Diet and Supplements in Patients with Rheumatoid Arthritis Taking Medications,J. Amer. Dietetic Assn. 87, 11–12.

    Google Scholar 

  41. Fortin, P.R., Liang, M.H., Beckett, L.A., Wright, E.A., Kremer, J.M., Chalmers, T.C., and Sperling, R.I. (1992) A Meta-Analysis of the Efficacy of Fish Oil in Rheumatoid Arthrits,Arth. Rheum. 35, S201.

    Google Scholar 

  42. Kremer, J.M. (1992) Clinical Studies of n-3 Fatty Acids Supplementation in Patients with Rheumatoid Arthrits,Rheum. Dis. Clinics, 17, 391–402.

    Google Scholar 

  43. Kremer, J.M. (1993) Nutrition in the Rheumatic Disease, inTextbook of Rheumatology, 4th edn., pp. 484–495, W.B. Saunders, Philadelphia.

    Google Scholar 

  44. Lee, T.H., Hoover, R.L., Williams, J.D., Sperling, R.I., Ravalese, J. III, Spur, B.W., Robinson, D.R., Corey, E.J., Lewis, R.A., and Austin, K.F. (1985) Effect of Dietary Enrichment with Eicosapentaenoic and Docosahexaenoic Acids on thein vitro Neutrophil and Monocyte Leukotriene Generation and Neutrophil Function,N. Engl. J. Med. 312, 1217.

    Article  PubMed  CAS  Google Scholar 

  45. Robinson, D.R., Tateno, S., Balkrishna, P., and Hirai, A. (1988) Lipid Mediators of Intlammatory and Immune Reactions,JPEN 12, 375.

    Google Scholar 

  46. Lewis, R.A., Austen, K.F., and Soberman, R.J. (1990) Leukotrienes and Other Products of the 5-Lipoxygenase Pathway,N. Engl. J. Med. 323, 645–655.

    Article  PubMed  CAS  Google Scholar 

  47. Endres, S., Ghorbani, R., Kelley, V.E., Georgilis, K., Lonnemann, G., VanderMeer, J.W., Cannon, J.G., Rogers, T.S., Klempner, M.S., Weber, D.C., Schaefer, E.J., Wolff, S.M., and Dinarello, C.A. (1989) The Effects of Dietary Supplementation with n-3 Polyunsaturated Fatty Acids on the Synthesis of Inter-leukin-1 and Tumor Necrosis Factor by Mononuclear Cells,N. Engl. J. Med. 320, 265.

    Article  PubMed  CAS  Google Scholar 

  48. Lau, C.S., Morley, K.D., and Belch, J.J. (1993) Effects of Fish Oil Supplementation on Non-Steroidal Antiinflammatory Drug Requirements in Patients with Mild Rheumatoid Arthritis. A Double Blind Placebo Controlled Study,Brit. J. Rheum. 32, 982–989.

    Article  CAS  Google Scholar 

  49. Stenson, W.F., Eirt, D., Rodgers, J., Burakoff, R., DeSchryver-Keckemeti, K., Gramlich, T.L., and Beeken, W. (1992) Dietary Supplementation with Fish Oil in Ulcerative Colitis,Ann. Int. Med. 116, 609–614.

    PubMed  CAS  Google Scholar 

  50. Donadio, J.V., Bergstrath, E.J., Offord, K.P., Spenser, D.C., and Holley, K.E. (1994) A Controlled Trial of Fish Oil in IgA Nephropathy,N. Eng. J. Med. 331, 1194–1199.

    Article  Google Scholar 

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Kremer, J.M. Effects of modulation of inflammatory and immune parameters in patients with rheumatic and inflammatory disease receiving dietary supplementation of n-3 and n-6 fatty acids. Lipids 31, S243–S247 (1996). https://doi.org/10.1007/BF02637084

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