Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis

British Journal of Nutrition

Volumn 107, Issue SUPPL. 2, 2012, Pages

  Miles, Elizabeth A ^a   Calder, Philip C ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

Arachidonic acid; Cytokine; Docosahexaenoic acid; Eicosapentaenoic acid; Fish oil; Lipid mediator

Indexed keywords

ARACHIDONIC ACID; CYTOKINE; DOCOSAHEXAENOIC ACID; FISH OIL; ICOSANOID; ICOSAPENTAENOIC ACID; INTERLEUKIN 1; INTERLEUKIN 6; NATURAL PRODUCT; NONSTEROID ANTIINFLAMMATORY AGENT; OMEGA 3 FATTY ACID; REACTIVE OXYGEN METABOLITE; RESOLVIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANTIGEN PRESENTATION; ANTIINFLAMMATORY ACTIVITY; ARTHRALGIA; CELL FUNCTION; CYTOKINE PRODUCTION; DENDRITIC CELL; DISEASE ACTIVITY; DISEASE SEVERITY; EVIDENCE BASED MEDICINE; HUMAN; IMMUNE RESPONSE; INFLAMMATION; JOINT SWELLING; LIPID COMPOSITION; MORNING STIFFNESS; OUTCOME ASSESSMENT; PAIN ASSESSMENT; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RHEUMATOID ARTHRITIS; RISK REDUCTION; SYSTEMATIC REVIEW; T LYMPHOCYTE;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTIOXIDANTS; ARACHIDONIC ACID; ARTHRITIS, RHEUMATOID; DIET; FATTY ACIDS, OMEGA-3; FISHES; HUMANS; IMMUNITY; IMMUNOLOGIC FACTORS; INFLAMMATION; INFLAMMATION MEDIATORS;

ANIMALIA;

EID: 84861170926     PISSN: 00071145     EISSN: 14752662     Source Type: Journal    
DOI: 10.1017/S0007114512001560     Document Type: Review

References (95)

1. Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423, 356-361. (Pubitemid 40852711)
2. Feldmann M & Maini RN (1999) The role of cytokines in the pathogenesis of rheumatoid arthritis. Rheumatol 38, Suppl. 2, 3-7. (Pubitemid 29533264)
3. Calder PC (2008) PUFA, inflammatory processes and rheumatoid arthritis. Proc Nutr Soc 67, 409-418.
4. Sweeney SE & Firestein GS (2004) Rheumatoid arthritis: regulation of synovial inflammation. Int J Biochem Cell Biol 36, 372-378. (Pubitemid 37542434)
5. Bowes J & Barton A (2008) Recent advances in the genetics of RA susceptibility. Rheumatol 47, 399-402.
6. Panayi GS (1999) Targetting of cells involved in the pathogenesis of rheumatoid arthritis. Rheumatol 38, Suppl. 2, 8-10. (Pubitemid 29533265)
7. Tilley SL, Coffman TM & Koller BH (2001) Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 108, 15-23. (Pubitemid 32634916)
8. Calder PC (2006) N-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83, 1505S-1519S. (Pubitemid 44713092)
9. Sano H, Hla T, Maier JAM, et al. (1992) 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 89, 97-108.
10. Sperling RI (1995) Eicosanoids in rheumatoid arthritis. Rheum Dis Clin N Am 21, 741-758.
11. Lee TH, Hoover RL, Williams JD, et al. (1985) 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 312, 1217-1224. (Pubitemid 15009155)
12. Endres S, Ghorbani R, Kelley VE, et al. (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 Eng J Med 320, 265-271. (Pubitemid 19045549)
13. Sperling RI, Benincaso AI, Knoell CT, et al. (1993) Dietary v-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Invest 91, 651-660. (Pubitemid 23064151)
14. Gibney MJ & Hunter B (1993) The effects of short-and longterm 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 47, 255-259. (Pubitemid 23111664)
15. Caughey GE, Mantzioris E, Gibson RA, Cleland LG & James MJ (1996) The effect on human tumor necrosis factor a and interleukin 1b production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 63, 116-122. (Pubitemid 26005735)
16. Yaqoob P, Pala HS, Cortina-Borja M, Newsholme EA & Calder PC (2000) Encapsulated fish oil enriched in a-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. Eur J Clin Invest 30, 260-274. (Pubitemid 30153668)
17. Healy DA, Wallace FA, Miles EA, Calder PC & Newsholme P (2000) The effect of low to moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids 35, 763-768. (Pubitemid 30624541)
18. Thies F, Nebe-von-Caron G, Powell JR, et al. (2001) Dietary supplementation with g-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. J Nutr 131, 1918-1927. (Pubitemid 32661059)
19. Kew S, Banerjee T, Minihane AM, et al. (2003) 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 77, 1278-1286. (Pubitemid 44858447)
20. Kew S, Mesa MD, Tricon S, et al. (2004) Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans. Am J Clin Nutr 79, 674-681. (Pubitemid 41103914)
21. Rees D, Miles EA, Banerjee T, et al. (2006) Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr 83, 331-342. (Pubitemid 44713195)
22. Faber J, Berkhout M, Vos AP, et al. (2011) Supplementation with a fish oil-enriched, high-protein medical food leads to rapid incorporation of EPA into white blood cells and modulates immune responses within one week in healthy men and women. J Nutr 141, 964-970.
23. Calder PC (2008) The relationship between the fatty acid composition of immune cells and their function. Prostagland Leukotr Essent Fatty Acids 79, 101-108.
24. Meydani SN, Endres S, Woods MM, et al. (1991) Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 121, 547-555.
25. Von Schacky C, Kiefl R, Jendraschak E & Kaminski WE (1993) N-3 fatty acids and cysteinyl-leukotriene formation in humans in vitro, ex vivo and in vivo. J Lab Clin Med 121, 302-309. (Pubitemid 23073137)
26. Kremer JM, Bigauoette J, Michalek AV, et al. (1985) Effects of manipulation of dietary fatty acids on manifestations of rheumatoid arthritis. Lancet i, 184-187. (Pubitemid 15151457)
27. Kremer JM, Jubiz W, Michalek A, et al. (1987) Fish-oil supplementation in active rheumatoid arthritis. Ann Int Med 106, 497-503.
28. Kremer JM, Lawrence DA, Jubiz W, et al. (1990) Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Arth Rheum 33, 810-820. (Pubitemid 20205760)
29. Sperling RI, Weinblatt M, Robin JL, et al. (1987) Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator generation and function in rheumatoid arthritis. Arth Rheum 30, 988-997. (Pubitemid 17149908)
30. 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. (Pubitemid 18263092)
31. van der Tempel H, Tullekan JE, Limburg PC, Muskiet FAJ & van Rijswijk MH (1990) Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis 49, 76-80. (Pubitemid 20041007)
32. Cleland LG, Caughey GE, James MJ & Proudman SM (2006) Reduction of cardiovascular risk factors with long term fish oil treatment in early rheumatoid arthritis. J Rheumatol 33, 1973-1979. (Pubitemid 44571869)
33. Goldman DW, Pickett WC & Goetzl EJ (1983) Human neutrophil chemotactic and degranulating activities of leukotriene B5 (LTB5) derived from eicosapentaenoic acid. Biochem Biophys Res Commun 117, 282-288. (Pubitemid 14216878)
34. Lee TH, Mencia-Huerta JM, Shih C, et al. (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, 2383-2389. (Pubitemid 14190356)
35. Bagga D, Wang L, Farias-Eisner R, Glaspy JA & Reddy ST (2003) Differential effects of prostaglandin derived from v-6 and v-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci USA 100, 1751-1756. (Pubitemid 36254520)
36. Tull SP, Yates CM, Maskrey BH, et al. (2009) Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment. PLoS Biol 7, e1000177.
37. Serhan CN, Clish CB, Brannon J, et al. (2000) 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 4, 643-654. (Pubitemid 32049518)
38. Serhan CN, Clish CB, Brannon J, et al. (2000) 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 192, 1197-1204.
39. Serhan CN, Hong S, Gronert K, et al. (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, 1025-1037. (Pubitemid 35231761)
40. Hong S, Gronert K, Devchand P, Moussignac R-L & Serhan CN (2003) Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood and glial cells: autocoids in anti-inflammation. J Biol Chem 278, 14677-14687. (Pubitemid 36799790)
41. Marcheselli VL, Hong S, Lukiw WJ & Hua Tian X (2003) Novel docosanoids inhibit brain ischemia reperfusionmediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 278, 43807-43817. (Pubitemid 37346009)
42. De Caterina R, Cybulsky MI, Clinton SK, Gimbrone MA & Libby P (1994) The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscler Thromb 14, 1829-1836.
43. Khalfoun B, Thibault F, Watier H, et al. (1997) Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human endothelial cell production of interleukin-6. Adv Exp Biol Med 400, 589-597.
44. Lo CJ, Chiu KC, Fu M, Lo R & Helton S (1999) Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity. J Surg Res 82, 216-221. (Pubitemid 29394126)
45. Babcock TA, Novak T, Ong E, et al. (2002) Modulation of lipopolysaccharide-stimulated macrophage tumor necrosis factor-a production by v-3 fatty acid is associated with differential cyclooxygenase-2 protein expression and is independent of interleukin-10. J Surg Res 107, 135-139. (Pubitemid 35191824)
46. Novak TE, Babcock TA, Jho DH, Helton WS & Espat NJ (2003) NF-k kappa B inhibition by omega-3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol 284, L84-L89. (Pubitemid 35471261)
47. Zhao Y, Joshi-Barve S, Barve S, Chen LH, Barve S & Chen LH (2004) Eicosapentaenoic acid prevents LPS-induced TNFalpha expression by preventing NF-kappaB activation. J Am Coll Nutr 23, 71-78. (Pubitemid 38200837)
48. Trebble T, Arden NK, Stroud MA, et al. (2003) Inhibition of tumour necrosis factor-a and interleukin-6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation. Brit J Nutr 90, 405-412. (Pubitemid 36992542)
49. Wallace FA, Miles EA & Calder PC (2003) Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects. Brit J Nutr 89, 679-689. (Pubitemid 36592094)
50. Cooper AL, Gibbons L, Horan MA, Little RA & Rothwell NJ (1993) Effect of dietary fish oil supplementation on fever and cytokine production in human volunteers. Clin Nutr 12, 321-328. (Pubitemid 24006127)
51. Abbate R, Gori AM, Martini F, et al. (1996) n-3 PUFA supplementation, monocyte PCA expression and interleukin-6 production. Prostagland Leukotr Essent Fatty Acids 54, 439-444. (Pubitemid 26313463)
52. Gallai V, Sarchielli P, Trequattrini A, et al. (1995) Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol 56, 143-153.
53. Thies F, Miles EA, Nebe-von-Caron G, et al. (2001) Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. Lipids 36, 1183-1193. (Pubitemid 34007971)
54. Kew S, Banerjee T, Minihane AM, et al. (2003) Lack of effect of foods enriched with plant-or marine-derived n-3 fatty acids on human immune function. Am J Clin Nutr 77, 1287-1295. (Pubitemid 44858448)
55. Miles EA, Banerjee T, Dooper MM, M'Rabet L, Graus YM & Calder PC (2004) The influence of different combinations of gamma-linolenic acid, stearidonic acid and EPA on immune function in healthy young male subjects. Brit J Nutr 91, 893-903. (Pubitemid 38931453)
56. Blok WL, Deslypere JP, Demacker PN, et al. (1997) Proand anti-inflammatory cytokines in healthy volunteers fed various doses of fish oil for 1 year. Eur J Clin Invest 27, 1003-1008. (Pubitemid 28012622)
57. Molvig J, Pociot F, Worsaae H, et al. (1991) Dietary supplementation with omega-3-polyunsaturated fatty acids decreases mononuclear cell proliferation and interleukin-1 beta content but not monokine secretion in healthy and insulin-dependent diabetic individuals. Scand J Immunol 34, 399-410.
58. Cannon JG, Fiatarone MA, Meydani M, et al. (1995) Aging and dietary modulation of elastase and interleukin-1 beta secretion. Am J Physiol 268, R208-R213.
59. Esperson GT, Grunnet N, Lervang HH, et al. (1992) Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids. Clin Rheumatol 11, 393-395.
60. Kremer JM, Lawrence DA, Petrillo GF, et al. (1995) Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal anti-inflammatory drugs: clinical and immune correlates. Arth Rheum 38, 1107-1114.
61. Adam O, Beringer C, Kless T, et al. (2003) Antiinflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int 23, 27-36. (Pubitemid 36207854)
62. Kolahi S, Ghorbanihaghjo A, Alizadeh S, et al. (2010) Fish oil supplementation decreases serum soluble receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio in female patients with rheumatoid arthritis. Clin Biochem 43, 576-580.
63. Varming K, Schmidt EB, Svaneborg N, et al. (1995) The effect of n-3 fatty acids on neutrophil chemiluminescence. Scand J Clin Lab Invest 55, 47-52.
64. Thompson PJ, Misso NLA, Passarelli M & Phillips MJ (1991) The effect of eicosapentaenoic acid consumption on human neutrophil chemiluminescence. Lipids 26, 1223-1226.
65. Luostarinen R & Saldeen T (1996) Dietary fish oil decreases superoxide generation by human neutrophils: relation to cyclooxygenase pathway and lysosomal enzyme release. Prostagland Leukotr Essent Fatty Acids 55, 167-172. (Pubitemid 26366834)
66. Fisher M, Levine PH, Weiner BH, et al. (1990) Dietary n-3 fatty acid supplementation reduces superoxide production and chemiluminescence in monocyte enriched preparation of leukocytes. Am J Clin Nutr 51, 804-808.
67. Schmidt EB, Varming K, Moller JM, Bulow Pederson I, Madsen P & Dyerberg J (1996) No effect of a very low dose of n-3 fatty acids on monocyte function in healthy humans. Scand J Clin Invest 56, 87-92. (Pubitemid 26063570)
68. Magaro M, Altomonte L, Zoli A, et al. (1988) Influence of diet with different lipid composition on neutrophil chemiluminescence and disease activity in patients with rheumatoid arthritis. Ann Rheum Dis 47, 793-796.
69. Calder PC & Newsholme EA (1992) Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2 production. Clin Sci 82, 695-700.
70. Miles EA, Banerjee T, Wells SJ & Calder PC (2006) Limited effect of eicosapentaenoic acid on T-lymphocyte and natural killer cell numbers and functions in healthy young males. Nutrition 22, 512-519.
71. Khair-El-Din TA, Sicher SC, Vazquez MA, Wright WJ & Lu CY (1995) Docosahexaenoic acid, a major constituent of fetal serum and fish oil diets, inhibits IFNg-induced Ia-expression by murine macrophages in vitro. J Immunol 154, 1296-1306.
72. Hughes DA, Southon S & Pinder AC (1996) (n-3) Polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes in vitro. J Nutr 126, 603-610. (Pubitemid 26081168)
73. Calder PC (2007) Polyunsaturated fatty acids alter the rules of engagement. Future Lipidol 2, 27-30. (Pubitemid 46805487)
74. Hughes DA, Pinder AC, Piper Z, Johnson IT & Lund EK (1996) Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes. Am J Clin Nutr 63, 267-272. (Pubitemid 26036250)
75. Leslie CA, Gonnerman WA, Ullman MD, et al. (1985) Dietary fish oil modulates macrophage fatty acids and decreases arthritis susceptibility in mice. J Exp Med 162, 1336-1339.
76. Volker DH, FitzGerald PEB & Garg ML (2000) The eicosapentaenoic to docosahexaenoic acid ratio of diets affects the pathogenesis of arthritis in Lew/SSN rats. J Nutr 130, 559-565. (Pubitemid 30118071)
77. Ierna M, Kerr A, Scales H, Berge K & Griinari M (2010) Supplementation of diet with krill oil protects against experimental rheumatoid arthritis. BMC Musculoskel Disord 11, 136.
78. Fortin PR, Lew RA, Liang MH, et al. (1995) Validation of a metaanalysis: The effects of fish oil in rheumatoid arthritis. J Clin Epidemiol 48, 1379-1390.
79. MacLean CH, Mojica WA & Morton SC, et al. (2004) 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; available at http://www.ahrq.gov/clinic/tp/ o3lipidtp.htm
80. Goldberg RJ & Katz J (2007) A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain 129, 210-233.
81. Jadad AR, Moore RA, Carroll D, et al. (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Contr Clin Trials 17, 1-12. (Pubitemid 26120810)
82. Belch JJF, Ansell D, Madhok R, O'Dowd A & Sturrock RD (1988) Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. Ann Rheum Dis 47, 96-104. (Pubitemid 18046613)
83. Tullekan JE, Limburg PC, Muskiet FAJ & van Rijswijk MH (1990) Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis. Arthr Rheum 33, 1416-1419. (Pubitemid 20365573)
84. Skoldstam L, Borjesson O, Kjallman A, Seiving B & Akesson B (1992) Effect of six months of fish oil supplementation in stable rheumatoid arthritis: a double blind, controlled study. Scand J Rheumatol 21, 178-185.
85. Nielsen GL, Faarvang KL, Thomsen BS, et al. (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.
86. Kjeldsen-Kragh J, Lund JA, Riise T, et al. (1992) Dietary omega-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis. J Rheumatol 19, 1531-1536.
87. 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. Brit J Rheumatol 32, 982-989. (Pubitemid 23334899)
88. Geusens P, Wouters C, Nijs J, Jiang Y & Dequeker J (1994) Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. Arth Rheum 37, 824-829.
89. Volker D, Fitzgerald P, Major G & Garg M (2000) Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol 27, 2343-2346.
90. Remans PH, Sont JK, Wagenaar LW, et al. (2004) Nutrient supplementation with polyunsaturated fatty acids and micronutrients in rheumatoid arthritis: clinical and biochemical effects. Eur J Clin Nutr 58, 839-845. (Pubitemid 38923181)
91. Sundrarjun T, Komindr S, Archararit N, et al. (2004) 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 32, 443-454. (Pubitemid 39255589)
92. Berbert AA, Kondo CR, Almendra CL, Matsuo T & Dichi I (2005) Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition 21, 131-136. (Pubitemid 40255720)
93. Galarraga B, Ho M, Youssef HM, et al. (2008) Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatol 47, 665-669. (Pubitemid 351619210)
94. Dawczynski C, Schubert R, Hein G, et al. (2009) Long-term moderate intervention with n-3 long-chain PUFAsupplemented dairy products: effects on pathophysiological biomarkers in patients with rheumatoid arthritis. Brit J Nutr 101, 1517-1526.
95. Das Gupta AB, Hossain AKMM, Islam MH, Dey SR & Khan MAL (2009) Role of omega-3 fatty acid supplementation with indomethacin in suppression of disease activity in rheumatoid arthritis. Bangladesh Med Res Counc Bull 35, 63-68.