Polyunsaturated fatty acids and inflammation: Therapeutic potential in rheumatoid arthritis

Current Rheumatology Reviews

Volumn 5, Issue 4, 2009, Pages 214-225

  Calder, Philip C ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

Cytokine; Eicosanoid; Fatty acid; Fish oil; Inflammation

Indexed keywords

ARACHIDONIC ACID; DOCOSAHEXAENOIC ACID; ICOSAPENTAENOIC ACID; LEUKOTRIENE B4; NONSTEROID ANTIINFLAMMATORY AGENT; OMEGA 3 FATTY ACID; OMEGA 6 FATTY ACID; POLYUNSATURATED FATTY ACID; PROSTAGLANDIN E2;

ANTIGEN PRESENTATION; CHEMICAL COMPOSITION; CYTOKINE PRODUCTION; HUMAN; INFLAMMATION; NONHUMAN; NUTRITIONAL ASSESSMENT; PATHOPHYSIOLOGY; PHOSPHOLIPID MEMBRANE; PRIORITY JOURNAL; REVIEW; RHEUMATOID ARTHRITIS; T LYMPHOCYTE;

EID: 74249109544     PISSN: 15733971     EISSN: None     Source Type: Journal    
DOI: 10.2174/157339709790192558     Document Type: Review

References (132)

1. Calder PC, Burdge GC. Fatty acids. In: Nicolaou A, Kokotos G, Eds., Bioactive Lipids, Bridgewater, USA: The Oily Press 2004: pp. 1-36.
2. Calder PC, Bond JA, Harvey DJ, Gordon S, Newsholme EA. Uptake and incorporation of saturated and unsaturated fatty acids into macrophage lipids and their effect upon macrophage adhesion and phagocytosis. Biochem J 1990; 269: 807-14.
3. Calder PC, Yaqoob P, Harvey DJ, Watts A, Newsholme EA. The incorporation of fatty acids by lymphocytes and the effect on fatty acid composition and membrane fluidity. Biochem J 1994; 300: 509-18.
4. Yaqoob P, Newsholme EA, Calder PC. Influence of cell culture conditions on diet-induced changes in lymphocyte fatty acid composition. Biochim Biophys Acta 1995; 1255: 333-40.
5. Peterson LD, Jeffery NM, Thies F, Sanderson P, Newsholme EA, Calder PC. Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity. Lipids 1998; 33: 171-80.
6. Wallace FA, Neely SJ, Miles EA, Calder PC. Dietary fats affect macrophage-mediated cytotoxicity towards tumour cells. Immunol Cell Biol 2000; 78: 40-8.
7. Wallace FA, Miles EA, Evans C, Stock TE, Yaqoob P, Calder PC. Dietary fatty acids influence the production of Th1- but not Th2-type cytokines. J Leuk Biol 2001; 69: 449-57.
8. Kew S, Wells S, Thies F, et al. The effect of eicosapentaenoic acid on rat lymphocyte proliferation depends upon its position in dietary triacylglycerols. J Nutr 2003; 133: 4230-8.
9. Fritsche K. Important differences exist in the dose-response relationship between diet and immune cell fatty acids in humans and rodents. Lipids 2007; 42: 961-79.
10. Lee TH, Hoover RL, Williams JD, et al. Effects of dietary enrichment with eicosapentaenoic acid and docosahexaenoic acid on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Eng J Med 1985; 312: 1217-24.
11. Endres S, Ghorbani R, Kelley VE, et al. 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 Eng J Med 1989; 320: 265-71.
12. Sperling RI, Benincaso AI, Knoell CT, Larkin JK, Austen KF, Robinson DR. Dietary ω-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Invest 1993; 91: 651-60.
13. Gibney MJ, Hunter B. The effects of short- and long-term supplementation with fish oil on the incorporation of n-3 polyunsaturated fatty acids into cells of the immune system in healthy volunteers. Eur J Clin Nutr 1993; 47: 255-9.
14. Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ. The effect on human tumor necrosis factor α and interleukin 1β production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 1996; 63: 116-22.
15. Yaqoob P, Pala HS, Cortina-Borja M, Newsholme EA, Calder PC. Encapsulated fish oil enriched in α-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. Eur J Clin Invest 2000; 30: 260-74.
16. Healy DA, Wallace FA, Miles EA, Calder PC, Newsholme P. The effect of low to moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids 2000; 35: 763-8.
17. Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC. Dietary supplementation with γ-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. J Nutr 20001; 131: 1918-27.
18. Kew S, Banerjee T, Minihane AM, Finnegan YE, Williams CM, Calder PC. Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in healthy, free-living subjects aged 25-72 y. Am J Clin Nutr 2003; 77: 1278-86.
19. Miles EA, Banerjee T, Calder PC. The influence of different combinations of gamma-linolenic, stearidonic and eicosapentaenoic acids on the fatty acid composition of blood lipids and mononuclear cells in human volunteers. Prost Leuk Essent Fatty Acids 2004; 70: 529-38.
20. Kew S, Mesa MD, Tricon S, Buckley R, Minihane AM, Yaqoob P. Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans. Am J Clin Nutr 2004; 79: 674-81.
21. Rees D, Miles EA, Banerjee T, et al. Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 2006; 83: 331-42.
22. Kelley DS, Nelson GJ, Love JE, et al. Dietary alpha-linolenic acid alters tissue fatty acid composition, but not blood lipids, lipoproteins or coagulation status in humans. Lipids 1993; 28: 533-7.
23. Kew S, Banerjee T, Minihane AM, et al. Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function. Am J Clin Nutr 2003; 77: 1287-95.
24. Mantzioris E, James MJ, Gibson RA, Cleland LG. Dietary substitution with an alpha-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues. Am J Clin Nutr 1994; 59: 1304-9.
25. Calder PC. The relationship between the fatty acid composition of immune cells and their function. Prost Leukot Essent Fatty Acids 2008; 79: 101-8.
26. Pike LJ. Lipid rafts: bringing order to chaos. J Lipid Res 2003; 44: 655-67.
27. Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 2000; 1: 31-41.
28. Miles EA, Calder PC. Modulation of immune function by dietary fatty acids. Proc Nutr Soc 1998; 57: 277-92.
29. Lo CJ, Chiu KC, Fu M, Lo R, Helton S. Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity. J Surg Res 1999; 82: 216-21.
30. Novak TE, Babcock TA, Jho DH, Helton WS, Espat NJ. NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol 2003; 284: L84-9.
31. Zhao Y, Joshi-Barve S, Barve S, Chen LH. Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF-kappaB activation. J Am Coll Nutr 2004; 23: 71-8.
32. Grimaldi PA. Peroxisome proliferator-activated receptors as sensors of fatty acids and derivatives. Cell Mol Life Sci 2007; 64: 2459-64.
33. Bensinger SJ, Tontonoz P. Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 2008; 454: 470-7.
34. Marion-Letellier R, Déchelotte P, Iacucci M, Ghosh S. Dietary modulation of peroxisome proliferator-activated receptor gamma. Gut 2009; 58: 586-93.
35. Sampath H, Ntambi JM. Polyunsaturated fatty acid regulation of genes of lipid metabolism. Ann Rev Nutr 2005; 25: 317-40.
36. Jump DB. N-3 polyunsaturated fatty acid regulation of hepatic gene transcription. Curr Opin Lipidol 2008; 19: 242-7.
37. Jump DB, Botolin D, Wang Y, Xu J, Demeure O, Christian B. Docosahexaenoic acid (DHA) and hepatic gene transcription. Chem Phys Lipids 2008; 153: 3-13.
38. Lewis RA, Austen KF, Soberman RJ. Leukotrienes and other products of the 5-lipoxygenase pathway: biochemistry and relation to pathobiology in human diseases. N Eng J Med 1990; 323: 645-55.
39. Tilley SL, Coffman TM, Koller BH. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 2001; 108: 15-23.
40. Feldmann M, Maini RN. The role of cytokines in the pathogenesis of rheumatoid arthritis. Rheumatology 1999; 38(Suppl 2): 3-7.
41. Sano H, Hla T, Maier JAM, et al. In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis. J Clin Invest 1992; 89: 97-108.
42. Sperling RI. Eicosanoids in rheumatoid arthritis. Rheum Dis Clin North Am 1995; 21: 741-58.
43. Yaqoob P, Calder PC. Effects of dietary lipid manipulation upon inflammatory mediator production by murine macrophages. Cell Immunol 1995; 163: 120-8.
44. Chapkin RS, Akoh CC, Miller CC. Influence of dietary n-3 fatty acids on macrophage glycerophospholipid molecular species and peptidoleukotriene synthesis. J Lipid Res 1991; 32: 1205-13.
45. Kelley DS, Taylor PC, Nelson GJ, Mackey BE. Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men. Lipids 1998; 33: 125-30.
46. Meydani SN, Endres S, Woods MM, et al. Gorbach. Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 1991; 121: 547-55.
47. Von Schacky C, Kiefl R, Jendraschak E, Kaminski WE. N-3 fatty acids and cysteinyl-leukotriene formation in humans in vitro, ex vivo and in vivo. J Lab Clin Med 1993; 121: 302-9.
48. Kelley DS, Taylor PC, Nelson GJ, et al. Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 1999; 34: 317-24.
49. Wachtler P, Konig W, Senkal M, Kemen M, Koller M. Influence of a total parenteral nutrition enriched with ω-3 fatty acids on leukotriene synthesis of peripheral leukocytes and systemic cytokine levels in patients with major surgery. J Trauma 1997; 42: 191-8.
50. Mayer K, Fegbeutel C, Hattar K, et al. Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation. Intensive Care Med 2003; 29: 1472-81.
51. Grimm H, Mertes N, Goeters C, et al. Improved fatty acid and leukotriene pattern with a novel lipid emulsion in surgical patients. Eur J Nutr 2006; 45: 55-60.
52. Hudert CA, Weylandt KH, Lu Y, et al. Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis. Proc Natl Acad Sci USA 2006; 103: 11276-81.
53. 5 (LTB5) derived from eicosapentaenoic acid. Biochem Biophys Res Commun 1983; 117: 282-8.
54. Lee TH, Mencia-Huerta JM, Shih C, et al. Characterization and biologic properties of 5,12-dihydroxy derivatives of eicosapentaenoic acid, including leukotriene-B5 and the double lipoxygenase product. J Biol Chem 1984; 259: 2383-9.
55. Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST. Differential effects of prostaglandin derived from ω-6 and ω-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci USA 2003; 100: 1751-6.
56. Dooper MMBW, Wassink L, M'Rabet L, Graus YMF. The modulatory effects of prostaglandin-E on cytokine production by human peripheral blood mononuclear cells are independent of the prostaglandin subtype. Immunology 2002; 107: 152-9.
57. Miles EA, Allen E, Calder PC. In vitro effects of eicosanoids derived from different 20-carbon fatty acids on production of monocyte-derived cytokines in human whole blood cultures. Cytokine 2002; 20: 215-23.
58. Miles EA, Aston L, Calder PC. In vitro effects of eicosanoids derived from different 20-carbon fatty acids on T helper type 1 and T helper type 2 cytokine production in human whole-blood cultures. Clin Exp Allergy 2003; 33: 624-32.
59. Serhan CN, Clish CB, Brannon J, et al. Anti-inflammatory lipid signals generated from dietary n-3 fatty acids via cyclooxygenase-2 and transcellular processing: a novel mechanism for NSAID and n-3 PUFA therapeutic actions J Physiol Pharmacol 2000; 4: 643-54.
60. Serhan CN, Clish CB, Brannon J, et al. Novel functional sets of lipid-derived mediators with antinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 2000; 192: 1197-204.
61. 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 pro-inflammation signals. J Exp Med 2002; 196: 1025-37.
62. Hong S, Gronert K, Devchand P, Moussignac R-L, Serhan CN. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood and glial cells: autocoids in anti-inflammation. J Biol Chem 2003; 278: 14677-87.
63. Marcheselli VL, Hong S, Lukiw WJ, Hua Tian X. Novel docosanoids inhibit brain ischemia reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278: 43807-17.
64. Arita M, Yoshida M, Hong S, et al. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci USA 2005; 102: 7621-6.
65. Schmidt EB, Pedersen JO, Ekelund S, Grunnet N, Jersild C, Dyerberg J. Cod liver oil inhibits neutrophil and monocyte chemotaxis in healthy males. Atherosclerosis 1989; 77: 53-7.
66. Schmidt EB, Varming K, Perdersen JO, et al. Long term supplementation with n-3 fatty acids. ii. Effect on neutrophil and monocyte chemotaxis. Scand J Clin Lab Invest 1992; 52: 229-36.
67. Luostarinen R, Siegbahn A, Saldeen T. Effect of dietary fish oil supplemented with different doses of vitamin E on neutrophil chemotaxis in healthy volunteers. Nutr Res 1992; 12: 1419-30.
68. Schmidt EB, Pedersen JO, Varming K, et al. N-3 fatty acids and leukocyte chemotaxis: effects in hyperlipidemia, and dodseresponse studies in healthy males. Arterioscler Thromb 1991; 11: 429-35.
69. Kumar A, Takada Y, Boriek AM, Aggarwal BB. Nuclear factorkappaB: its role in health and disease. J Mol Med 2004; 82: 434-48.
70. Sigal LH. Basic science for the clinician 39: NF-kappaB-function, activation, control, and consequences. J Clin Rheumatol 2006; 12: 207-11.
71. Perkins ND. Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 2007; 8: 49-62.
72. Szanto A, Nagy L. The many faces of PPARgamma: anti-inflammatory by any means? Immunobiology 2008; 213: 789-803.
73. Van den Berghe W, Vermeulen L, Delerive P, De Bosscher K, Staels B, Haegeman G. A paradigm for gene regulation: inflammation, NF-kappaB and PPAR. Adv Exp Med Biol 2003; 544: 181-96.
74. De Caterina R, Cybulsky MI, Clinton SK, Gimbrone MA, Libby P. The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscler Thromb 1994; 14: 1829-36.
75. Khalfoun B, Thibault F, Watier H, Bardos P, Lebranchu Y. Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human endothelial cell production of interleukin-6. Adv Exp Biol Med 1997; 400: 589-97.
76. Babcock TA, Novak T, Ong E, Jho DH, Helton WS, Espat NJ. Modulation of lipopolysaccharide-stimulated macrophage tumor necrosis factor-α production by ω-3 fatty acid is associated with differential cyclooxygenase-2 protein expression and is independent of interleukin-10. J Surg Res 2002; 107: 135-9.
77. Lo CJ, Chiu KC, Fu MJ, Chu A, Helton S. Fish oil modulates macrophage P44/42 mitogen-activated protein kinase activity induced by lipopolysaccharide. JPEN J Parenter Enteral Nutr 2000; 24: 159-163.
78. Xi S, Cohen D, Barve S, Chen LH. Fish oil suppressed cytokines and nuclear factor kappaB induced by murine AIDS virus infection. Nutr Res 2001; 21: 865-78.
79. Billiar T, Bankey P, Svingen B, et al. Fatty acid uptake and Kupffer Cell function: fish oil alters eicosanoid and monokine production to endotoxin stimulation. Surgery 1988; 104: 343-9.
80. Renier G, Skamene E, de Sanctis J, Radzioch D. Dietary n-3 polyunsaturated fatty acids prevent the development of atherosclerotic lesions in mice: modulation of macrophage secretory activities. Arterioscler Thromb 1993; 13: 1515-24.
81. Sadeghi S, Wallace FA, Calder PC. Dietary lipids modify the cytokine response to bacterial lipopolysaccharide in mice. Immunology 1999; 96: 404-10.
82. Trebble T, Arden NK, Stroud MA, et al. Inhibition of tumour necrosis factor-α and interleukin-6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation. Brit J Nutr 2003; 90: 405-12.
83. Wallace FA, Miles EA, Calder PC. Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects. Brit J Nutr 20003; 89: 679-89.
84. Calder PC. N-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006; 83: 1505S-19S.
85. Calder PC, Bond JA, Bevan SJ, Hunt SV, Newsholme EA. Effect of fatty acids on the proliferation of concanavalin A-stimulated rat lymph node lymphocytes. Int J Biochem 1991; 23: 579-88.
86. Calder PC, Newsholme EA. Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2 production. Clin Sci 1992; 82: 695-700.
87. Calder PC, Newsholme EA. Unsaturated fatty acids suppress interleukin-2 production and transferrin receptor expression by concanavalin A-stimulated rat lymphocytes. Mediat Inflamm 1992; 1: 107-15.
88. Yaqoob P, Newsholme EA, Calder PC. The effect of dietary lipid manipulation on rat lymphocyte subsets and proliferation. Immunology 1994; 82: 603-10.
89. Jolly CA, Jiang YH, Chapkin RS, McMurray DN. Dietary (n-3) polyunsaturated fatty acids suppress murine lymphoproliferation, interleukin-2 secretion, and the formation of diacylglycerol and ceramide. J Nutr 1997; 127: 37-43.
90. Peterson LD, Thies F, Sanderson P, Newsholme EA, Calder PC. Low levels of eicosapentaenoic and docosahexaenoic acids mimic the effects of fish oil upon rat lymphocytes. Life Sci 1998; 62: 2209-17.
91. Calder PC, Bevan SJ, Newsholme EA. The inhibition of T-lymphocyte proliferation by fatty acids is via an eicosanoid-independent mechanism. Immunology 1992; 75: 108-15.
92. Stulnig TM, Zeyda M. Immunomodulation by polyunsaturated fatty acids: impact on T-cell signaling. Lipids 2004; 39: 1171-5.
93. Zeyda M, Stulnig TM. Lipid Rafts & Co., An integrated model of membrane organization in T cell activation. Prog Lipid Res 2006; 45: 187-202.
94. Katagiri YU, Kiyokawa N, Fujimoto J. A role for lipid rafts in immune cell signaling. Microbiol Immunol 2001; 45: 1-8.
95. Razzaq TM, Ozegbe P, Jury EC, Sembi P, Blackwell NM, Kabouridis PS. Regulation of T-cell receptor signaling by membrane microdomains. Immunology 2004; 113: 413-26.
96. Harder T. Lipid raft domains and protein networks in T-cell receptor signal transduction. Curr Opin Immunol 2004; 16: 353-9.
97. Stulnig T, Berger M, Sigmund T, Raderstorff D, Stockinger H, Waldhausl W. Polyunsaturated fatty acids inhibit T cell signal transduction by modification of detergent-soluble membrane domains. J Cell Biol 1998; 143: 637-44.
98. Stulnig TM, Huber J, Leitinger N, et al. Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition. J Biol Chem 2001; 276: 37335-40.
99. Fan YY, McMurray DN, Ly LH, Chapkin RS. Dietary n-3 polyunsaturated fatty acids remodel mouse T-cell lipid rafts. J Nutr 2003; 133: 1913-20.
100. Zeyda M, Szekeres AB, Saemann MD, et al. Suppression of T cell signaling by polyunsaturated fatty acids: selectivity in inhibition of mitogen-activated protein kinase and nuclear factor activation. J Immunol 2003; 170: 6033-9.
101. Zeyda M, Staffler G, Horejsi V, Waldhausl W. LAT displacement from lipid rafts as a molecular mechanism for the inhibition of T cell signalling by polyunsaturated fatty acids. J Biol Chem 2002; 277: 28418-23.
102. Sanderson P, Calder PC. Dietary fish oil appears to prevent the activation of phospholipase C-γ in lymphocytes. Biochim Biophys Acta 1998; 1392: 300-8.
103. Fan YY, Ly LH, Barhoumi R, McMurray DN, Chapkin RS. Dietary docosahexaenoic acid suppresses T cell protein kinase Cθ lipid raft recruitment and IL-2 production. J Immunol 2004; 173: 6151-60.
104. Calder PC. Polyunsaturated fatty acids alter the rules of engagement. Future Lipidol 2007; 2: 27-30.
105. Sanderson P, MacPherson GG, Jenkins CH, Calder PC. Dietary fish oil diminishes the antigen presentation activity of rat dendritic cells. J Leuk Biol 1997; 62: 771-7.
106. Leslie CA, Gonnerman WA, Ullman MD, Hayes KC, Franzblau C, Cathcart ES. Dietary fish oil modulates macrophage fatty acids and decreases arthritis susceptibility in mice. J Exp Med 1985; 162: 1336-9.
107. Volker DH, FitzGerald PEB, Garg ML. The eicosapentaenoic to docosahexaenoic acid ratio of diets affects the pathogenesis of arthritis in Lew/SSN rats. J Nutr 2000; 130: 559-65.
108. Kremer JM, Bigauoette J, Michalek AV, et al. Effects of manipulation of dietary fatty acids on manifestations of rheumatoid arthritis. Lancet 1985; i: 184-7.
109. Kremer JM, Jubiz W, Michalek A, et al. Fish-oil supplementation in active rheumatoid arthritis. Ann Intern Med 1987; 106: 497-503.
110. Cleland LG, French JK, Betts WH, Murphy GA, Elliot MJ. Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. J Rheumatol 1988; 15: 1471-5.
111. van der Tempel H, Tullekan JE, Limburg PC, Muskiet FAJ, van Rijswijk MH. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis 1990; 49; 76-80.
112. Tullekan JE, Limburg PC, Muskiet FAJ, van Rijswijk MH. Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis. Arthritis Rheum 1990; 33: 1416-9.
113. Cleland LG, Caughey GE, James MJ, Proudman SM. Reduction of cardiovascular risk factors with longterm fish oil treatment in early rheumatoid arthritis. J Rheumatol 2006; 33: 1973-9.
114. Kremer JM, Lawrence DA, Jubiz W, et al. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Arthritis Rheumatol 1990; 33: 810-20.
115. Esperson GT, Grunnet N, Lervang HH, et al. Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids. Clin Rheumatol 1992; 11: 393-5.
116. Sundrarjun T, Komindr S, Archararit N, et al. Effects of n-3 fatty acids on serum interleukin-6, tumour necrosis factor-alpha and soluble tumour necrosis factor receptor p55 in active rheumatoid arthritis. J Int Med Res 2004; 32: 443-54.
117. Sperling RI, Weinblatt M, Robin JL, et al. Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator generation and function in rheumatoid arthritis. Arthritis Rheum 1987; 30: 988-97.
118. Skoldstam L, Borjesson O, Kjallman A, Seiving B, Akesson B. Effect of six months of fish oil supplementation in stable rheumatoid arthritis: a double blind, controlled study. Scand J Rheumatol 1992; 21: 178-85.
119. 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: 687-91.
120. 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: 1531-6.
121. Lau CS, Morley KD, Belch JJF. Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis. Br J Rheumatol 1993; 32: 982-9.
122. Geusens P, Wouters C, Nijs J, Jiang Y, Dequeker J. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. Arthritis Rheum 1994; 37: 824-9.
123. Kremer JM, Lawrence DA, Petrillo GF, et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal anti-inflammatory drugs: clinical and immune correlates. Arthritis Rheum 1995; 38: 1107-14.
124. Volker D, Fitzgerald P, Major G, Garg M. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol 2000; 27: 2343-6.
125. Adam O, Beringer C, Kless T, et al. Antiinflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int 2003; 23: 27-36.
126. Remans PH, Sont JK, Wagenaar LW, et al. Nutrient supplementation with polyunsaturated fatty acids and micronutrients in rheumatoid arthritis: clinical and biochemical effects. Eur J Clin Nutr 2004; 58: 839-45.
127. Berbert AA, Kondo CR, Almendra CL, Matsuo T, Dichi I. Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition 2005; 21: 131-6.
128. Galarraga B, Ho M, Youssef HM, et al. Cod liver oil (n-3 fatty acids) as a non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatol 2008; 47: 665-9.
129. Calder PC. PUFA, inflammatory processes and rheumatoid arthritis. Proc Nutr Soc 2008; 67: 409-18.
130. Fortin PR, Lew RA, Liang MH, et al. Validation of a metaanalysis: The effects of fish oil in rheumatoid arthritis. J Clin Epidemiol 1995; 48: 1379-90.
131. MacLean CH, Mojica WA, Morton SC, et al. Effects of Omega-3 Fatty Acids on Inflammatory Bowel Disease, Rheumatoid Arthritis, Renal Disease, Systemic Lupus Erythematosus, and Osteoporosis, Evidence Report/Technical Assessment no. 89. AHRQ Publication no. 04-E012-2. Rockville, MD: Agency for Healthcare Research and Quality; 2004; available at http://www.ahrq.gov/clinic/ tp/o3lipidtp.htm.
132. Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain 2007; 129: 210-33.