Modulation of Immune Response by Omega-3 in Health and Disease



During the last 3-4 decades, there has been vast information on effect of omega-3 on the immune system in health and in diseases, especially those caused by excessive inflammatory response. In this chapter, attempts have been made to elucidate the effect of omega-3 on different components of immune system, especially during child development and in aged individuals. Omega-3 is also known to reduce the pathological manifestations especially in diseases related to inflammation, allergy and autoimmunity which are the major challenges today. Earlier studies on effect of polyunsaturated fatty acids in immune system were conducted using animal systems; in this chapter, more emphasis is given on human studies. n-3 PUFAs have been shown to be very effective in controlling inflammation by affecting extravasation, phagocytic response, generation of cytokines, inflammatory mediators and adhesion molecules. They also manipulate the functions of antigen-presenting cells and lymphocytes including T and B cells, NK cells, LAK cells and also T regulatory cells. Most of the reports on effect of dietary omega-3 in human health have been conducted as clinical trials, extrapolated from experiences in animals and also using in vitro techniques, which have limitations. The chapter reports trials conducted to assess the effectiveness of omega-3 diet supplementation in healthy volunteers using in vitro and in vivo assays. It also deals with the effect of omega-3 diet supplementation on pregnancy and lactation, especially in relation to infant allergies. Cognizance has also been taken of the effects of omega-3 diet supplementation in aged population. Finally, the chapter reviews important literature on the effectiveness of n-3 PUFAs in controlling inflammatory and autoimmune diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease (IBD), psoriasis, cardiovascular disease, diabetes, multiple sclerosis and systemic lupus erythematosus (SLE).


PUFA dietary omega-3 Immune system Anti-inflammatory effect of dietary omega-3 Modulation of lymphocyte functions by dietary omega-3 Effect of dietary omega-3 on production of soluble mediators Effect dietary omega-3 on immune status of healthy individuals Effect dietary omega-3 in aged population Effect dietary omega-3 during pregnancy and lactation Effect dietary omega-3 in controlling inflammatory Autoimmune and allergic diseases 



The author wishes to thank Mr. Aniket Mali for his valuable help in the preparation of this manuscript.


  1. 1.
    Gangal S, Sontakke S. Text book of basic and clinical immunology. India: Publ. Universities Press; 2013.Google Scholar
  2. 2.
    Umasunthar T, Leonardi-Bee J, Hodes M, Turner PJ, Gore C, Habibi P, Warner JO, Boyle RJ. Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis. Clin Exp Allergy. 2013;43(12):1333–41.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Moraes ML, Ramalho DM, Delogo KN, Miranda PF, Mesquita ED, de MeloGuedes, de Oliveira HM, Netto AR, Dos Anjos MJ, Kritski AL, de Oliveira MM. Association of serum levels of iron, copper, and zinc, and inflammatory markers with bacteriological sputum conversion during tuberculosis treatment. Biol Trace Elem Res. 2014;160(2):176–84.Google Scholar
  4. 4.
    Bailey N. Immunonutrition: the role of long chain omega-3 fatty acids, the nutrition practitioner. California: Spring; 2010. p. 1–5.Google Scholar
  5. 5.
    Simopoulus AP. Omega-6/omega-3 essential fatty acids: biological effects. World Rev Nutr Diet. 2009;99:1–16.CrossRefGoogle Scholar
  6. 6.
    Calder PC. Immunomodulaion by omega-3 fatty acids. Prostaglad Leukot Essent Fatty Acids. 2007;77:327–35.CrossRefGoogle Scholar
  7. 7.
    Calder PC. Polyunsaturated fatty acids and inflammatory processes: new twist in the old tale. Biochemie. 2009;91:791–5.CrossRefGoogle Scholar
  8. 8.
    PC. The relationship between fatty acid composition of immune cells and their function. Prostaglad Leukot Essent Fatty Acids. 2008;79:101–8.Google Scholar
  9. 9.
    Lennie TA, Chung ML, Habash DL, Moser DK. Dietary fat intake and proinflammatory cytokine levels in patients with heart failure. J Card Fail. 2005;11:613–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Trebble T, Arden NK, Stroud MA, Wootton SA, Burdge GC, Miles EA, Ballinger AB, Thompson RA, Calder PC. Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish oil supplementation in healthy men and response to antioxidant co-supplementation. Br J Nutr. 2003;90:405–12.PubMedCrossRefGoogle Scholar
  11. 11.
    Mehra MR, Levis CJ, Ventura HO, Milani RV. Fish oils produce anti-inflammatory effect and improve body weight in severe heart failure. J Heart Lung Transplant. 2006;25:834–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Stenson WF, Cort D, Rodgers J, Burakoff R, DeSchryver-Kecskemeti K, Gramlich TL, Beeken W. Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med. 1992;116:609–14.PubMedCrossRefGoogle Scholar
  13. 13.
    Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of enteric coated fish-oil preparation on relapses in Crohn’s disease. N Eng J Med. 1996;334:1557–60.CrossRefGoogle Scholar
  14. 14.
    Endres S, Lorenz R, Loeschke K. Lipid treatment of inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 1999;2:117–20.PubMedCrossRefGoogle Scholar
  15. 15.
    Galarraga B, Ho M, Youssef HM, Hill A, Mcmahon H, Hall C, Ogston S, Nuki G, Belch JJ. Cod liver oil (n-3 fatty acids) as an non-steroid anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatology. 2008;47:665–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Kelley DS, Taylor PC, Nelson GI, Mackey BE. Dietary Docosahexaenoic acid and immune-competence in young healthy men. Lipids. 1998;33:359–66.Google Scholar
  17. 17.
    Furuhjelm C, Warstedt K, Fagerås M, Fälth-Magnusson K, Larsson J, Fredriksson M, Duchén K. Allergic disease in infants up to 2 years of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation in pregnancy and lactation. Pediatr Allergy Immunol. 2011;22:505–14.Google Scholar
  18. 18.
    Furuhjelm C, Jenmalm MC, Fälth-Magnusson K, Duchén K. Th1 and Th2 chemokines, vaccine-induced immunity, and allergic disease in infants after maternal omega-3 fatty acid supplementation during pregnancy and lactation. Pediatr Res. 2011;69(3):259–64.PubMedCrossRefGoogle Scholar
  19. 19.
    Pompeia C, Lopes RA, Miyasaka CK, Procopio J, Sannomiya P, Curi R. Effect of fatty acids on leukocyte function. Braz J Med Biol Res. 2000;33:1255–68.PubMedCrossRefGoogle Scholar
  20. 20.
    De Pablo MA, De Cienfuegos GA. Modulatory effect of dietary lipids on immune system functions. Immunol Cell Biol. 2000;78:31–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Clamp AG, Ladha S, Clark DC, Grimble RF, Lund EK. The influence of dietary lipids on the composition and fluidity of rat hepatocyte plasma membrane. Lipids. 1997;32:179–822.PubMedCrossRefGoogle Scholar
  22. 22.
    Kromann N, Green A. Epidemiological studies in Upernavic District, Greenland. Acta Med Scand. 1980;208:401–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Fritsche K. Fatty acids as modulators of the immune response. Annu Rev Nutr. 2006;26:45–73.PubMedCrossRefGoogle Scholar
  24. 24.
    Chavali SR, Weeks CE, Zhong WW, Forse RA. Increased production of TNF- α and decreased levels of Dienoic eicosanoids, IL-6 and IL-10 in mice fed menhaden oil and juniper oil diets in response to an intra-peritoneal lethal dose of LPS. Prostaglandins Leukot Essent Fatty Acids. 1998;59:89–93.PubMedCrossRefGoogle Scholar
  25. 25.
    Grimble RF, Tappia PS. The modulatory influence of unsaturated fatty acids on the biology of tumour necrosis factor. Biochem Soc Trans. 1995;287:282–6.CrossRefGoogle Scholar
  26. 26.
    Virella G, Kilpatrick JM, Rugeles MT, Hyman B, Russell R. Depression of humoral responses and phagocytic functions in vivo and in vitro by fish oil and eicosapentaenoic acid. Clin Immunol Immunopathol. 1989;52:257–70.PubMedCrossRefGoogle Scholar
  27. 27.
    Shapiro C, Wu D, Peydani SN. Ecosanoid derived from arachidonic and elcosapentaenoic acids inhibit T cell proliferative response. Prostaglandins. 1993;45:229–40.PubMedCrossRefGoogle Scholar
  28. 28.
    Sampath H, Ntambi JM. Polyunsaturated fatty acid regulation of genes of lipid metabolism. Ann Rev Nutr. 2005;25:317–40.CrossRefGoogle Scholar
  29. 29.
    Valledor AF, Ricote M. Nuclear receptor signalling in macrophages. Biochem Pharmacol. 2004;67:201–12.PubMedCrossRefGoogle Scholar
  30. 30.
    Calder PC. Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids. Braz J Med Biol Res. 1998;31:467–90.PubMedCrossRefGoogle Scholar
  31. 31.
    Bellinati-Pires R, Waitzberg DL, Salgado MM, Carneiro-Sampaio MM. Functional alterations of human neutrophils by medium chain triglyceroid emulsions: evaluation of phagocytosis, bacterial killing and oxidative activity. J Leuko Biol. 1993;53:404–41.PubMedGoogle Scholar
  32. 32.
    Khair-El-Din T, Sicher SC, Vazquez MA, Chung GW, Stallworth KA, Kitamura K, Miller RT, Lu CY. Transcription of murine iNOS gene is inhibited by docosahexaenoic acid, a major constituent of fetal and neonatal sera as well as fish oils. J Exp Med. 1996;183:1241–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Kumaratilake LM, Ferrante A, Robinson BS, Jaeger T, Poulos A. Enhancement of neutrophil mediated killing of Plasmodium falcipm asexual blood forms by fatty acids: importance of fatty acid structure. Infect Immun. 1997;65:4152–7.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Endress S. N-3 polyunsaturated fatty acids and human cytokine synthesis. Lipids. 1996;31:S239–42.CrossRefGoogle Scholar
  35. 35.
    DeLuca P, Rossetti RG, Alavian C, Karmin P, Zurier RB. Effect of gamma linolenic acid on interleukin-I beta and tumour Necrosis Factor-alpha secretion by stimulated human peripheral blood monocytes: Studies in vitro and in vivo. J Invest Med. 1999;47:317–24.Google Scholar
  36. 36.
    Blok WL, Katan MB, van der Meer JWM. Modulation of inflammation and cytokine production by dietary (n-3) fatty acids. J Nutr. 1996;126:1515–33.PubMedGoogle Scholar
  37. 37.
    Purasiri P, McKechnie A, Heys SD, Eremin O. Modulation in vitro of human natural cytotoxicity, lymphocyte proliferative response to mitogens and cytokine production by essential fatty acids. Immunology. 1997;92:166–72.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Young VM, Toborec M, Yang F, McClain CJ, Henning B. Effect of linoleic acid on endothelial cell inflammatory mediators. Metabilosm. 1998;47:566–72.CrossRefGoogle Scholar
  39. 39.
    Hayashi N, Tashiro T, Yamamori H, Takagi K, Morishima Y, Otsubo Y, Sugiura T, Furukawa K, Nitta H, Nakajima N, Suzuki N, Ito I. Effect of tntravenous omega-3 and omega-6 fat emulsion on cytokine production and delayed type hypersensitivity in burned rats receiving total parenteral nutrition. Parenter Enteral Nutr. 1998;22:363–7.CrossRefGoogle Scholar
  40. 40.
    Sadeghi S, Wallace FA, Calder PC. Dietary lipids modify the cytokine response to bacterial lipopolysaccharide in mice. Immunology. 1999;96:404–10.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Oh-hashi K, Takahashi T, Watanabe S, Kobayashi T, Okuyama H. Possible mechanism for the differential effect of high linoleate safflower oil and high alpha linolenateperilla oil diets on platelet activating factor production by rat polymorphonuclear leukocytes. J Lipid Mediat Cell Signal. 1997;17:207–20.PubMedCrossRefGoogle Scholar
  42. 42.
    Ishihara K, Murata M, Kaneniwa M, Saito H, Shinohara K, Maeda-Yamamoto M, Kawasaki K, Ooizumi T. Effect of tetracosahexaenoic acid on the content and release of histamine and eicosanoid production by MC/9 mouse mast cell. Lipids. 1998;33:1107–14.PubMedCrossRefGoogle Scholar
  43. 43.
    Stuling TM. Immunomodulation by polyunsaturated fatty acids: Mechanisms and effects. Int Arch Allergy Immunol. 2003;132:310–21.CrossRefGoogle Scholar
  44. 44.
    Yaqoob P. Lipids and the immune response: from molecular mechanisms to clinical applications. Curr Opin Clin Nutr Metab Care. 2003;6:133–50.PubMedCrossRefGoogle Scholar
  45. 45.
    Hughes DO, Pinder AC. Polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes and inhibits antigen presentation in vitro. Clin Exp Immunol. 1997;110:516–23.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Zapata-Gonzalez F, Rueda F, Petriz J, Domingo P, Villarroya F, Diaz-Delfin J, de Madariaga MA, Domingo JC. Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPARγ:RXR heterodimers: comparison with other polyunsaturated fatty acids. J Leuko Biol. 2008;84:1172–82.PubMedCrossRefGoogle Scholar
  47. 47.
    Khalfoun B, Thibault G, Bardos P, Lebranchu Y. Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human lymphocyte-endothelial cell adhesion. Transplantation. 1996;62:1649–57.PubMedCrossRefGoogle Scholar
  48. 48.
    Pompos LJ, Fritsche KL. Antigen driven murine CD4 T lymphocyte proliferation and interleukin 2 production are diminished by dietary (n-3) polyunsaturated fatty acids. J Nutr. 2002;132:3293–300.PubMedGoogle Scholar
  49. 49.
    Zeyda M, Stulnig TM. Lipid Rafts & Co.: an integrated model of membrane organization in T cell activation. Prog Lipid Res. 2006;45:187–202.PubMedCrossRefGoogle Scholar
  50. 50.
    Ma DW, Seo J, Switzer KC, Fan YY, McMurray DN, Lupton JR. Chapkin RS.n-3 PUFA and membrane microdomains: a new frontier in bioactive lipid research. J Nutr Biochem. 2004;15:700–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Shaikh SR, Edidin M. Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to balance immunotherapy and susceptibility to infection. Chem Phys Lipids. 2008;153:24–33.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Yaqoob P, Newsholme EA, Calder PC. Inhibition of natural killer cell activity by dietary lipids. Immunol Lett. 1994;41:241–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Yamashita N, Maruyama M, Yamazaki K, Hamazaki T, Yano S. Effect of eicosapentaenoic and docoxahexaenoic acid on natural killer cell activity in human peripheral blood lymphocytes. Clin Immunol Immunopathol. 1991;59:335–45.PubMedCrossRefGoogle Scholar
  54. 54.
    Kelly DS, Taylor PC, Nelson JH, Mackay BE. Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids. 1999;34:317–24.CrossRefGoogle Scholar
  55. 55.
    Mukaro VR, Costabile M, Murphy KJ, Hii CS, Howe PR, Ferrante A. Leukocyte numbers and function in subjects eating n-3 enriched foods: selective depression of natural killer cell levels. Arthritis Res Ther. 2008;14(10):R57.CrossRefGoogle Scholar
  56. 56.
    Gogus CA, Ginopoulos P, Zoumbos NC, Apostolidou E, Kalfarentzos F. The effect of dietary omega-3 polyunsaturated fatty acids in T lymphocyte subsets of patients with solid tumours. Cancer Detect Prev. 1995;19:415–7.Google Scholar
  57. 57.
    Monk JM, Turk HF, Yanyi Fan, Callaway E, Weeks B, Yang P, Mcmurray DN, Chapkin RS. Antagonizing arachidonic acid derived eicosanoids reduces Th17 and Th1 cell mediated inflammation and colitis severity. Mediators Inflam. 2014;917149.Google Scholar
  58. 58.
    Monk JM, Hou TY, Turk HF, Weeks B, Wu C, Mcmurray DN, Chapkins RS. Dietary N-3 polyunsaturated fatty acids (PUFA) decrease obesity associated TH17 cell mediated inflammation during colitis. PLoS ONE. 2012;7(11):e49739.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Fisher PR, Levine PH, Weiner BH, Johnson MH, Doyle EM, et al. Dietary n-3 fatty acid supplementation reduces superoxide production and chemileuminescence in a monocyte enriched preparation of leukocytes. Am J Nutr. 1990;51:804–8.Google Scholar
  60. 60.
    Dooper MM, van Riel B, Graus YM, M’Rabet L. Dihomo-gamma-linolenic acid inhibits tumour necrosis factor-alpha production by human leucocytes independently of cyclooxygenase activity. Immunology. 2003;110(3):348–57.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Blonk MC, Bilo HJ, Nauta JJ, Popp-Snijders C, Mulder C, Domker AJ. Dose-response effects of fish-oil supplementation in healthy volunteers. Am J Clin Nutr. 1990;52:120–7.PubMedGoogle Scholar
  62. 62.
    Blok WL, Deslypere JP, Demacker PN, van der Ven-JongekrijgJ Hectors MP, et al. Pro- and anti-inflammatory cytokine production by dietary (n-3) fatty acids. J Nutr. 1997;126:1515–33.Google Scholar
  63. 63.
    Kinsella LE, Broughton S, Whelan JW. Dietary unsaturated fatty acids: interactions and possible needs in relation to eicosanoid synthesis. J Nutr Biochem. 1990;1:123–41.PubMedCrossRefGoogle Scholar
  64. 64.
    Miles EA, Bannerjee T, Dooper MM, M’rabet L, Graus YM, Calsed PC. Influence of different combinations of gamma-Linolenic acids tearidonic acid and EPA on immune functions in healthy young male subjects. Br J Nutr. 2004;91:893-05.CrossRefGoogle Scholar
  65. 65.
    Jones KDJ, Berkley JA, Warner JO. Perinatal nutrition and immunity to infection. Pediatr Aller Immunol. 2010;21:564–76.CrossRefGoogle Scholar
  66. 66.
    Birch EE, Khoury JC, Berseth CL, Castañeda YS, Couch JM, Bean J, Tamer R, Harris CL, Mitmesser SH, Scalabrin DM. The impact of early nutrition on incidence of allergic manifestations and common respiratory illnesses in children. J Pediatr. 2010;156(902–906):e1.PubMedGoogle Scholar
  67. 67.
    Manley BJ, Makrides M, Collins CT, McPhee AJ, Gibson RA, Ryan P, Sullivan TR, Davis PG. High-dose docosahexaenoic acid supplementation of preterm infants: respiratory and allergy outcomes. Pediatrics. 2011;128:e71–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Kremmyda LS, Vlachava M, Noakes PS, Diaper ND, Miles EA, Calder PC. Atopy risk in infants and children in relation to early exposure to fish, oily fish, or long-chain omega-3 fatty acids: a systematic review. Clin Rev Aller Immunol. 2011;41:36–66.CrossRefGoogle Scholar
  69. 69.
    Shek LP, Foong-Fong Chong M, Lim JY, SE, Chong YS. Role of dietary long-chain polyunsaturated fatty acids in infant allergies and respiratory diseases. Clin Dev Immunol. 2012.Google Scholar
  70. 70.
    Gottrand F. Long-chain polyunsaturated fatty acids influence the immune system of infants. J Nutr. 2008;138:1807S–12S.PubMedGoogle Scholar
  71. 71.
    Sausenthaler S, Koletzko S, Schaaf B, Lehmann I, Borte M, Herbarth O, von Berg A, Wichmann HE, Heinrich J. Maternal diet during pregnancy in relation to eczema and allergic sensitization in the offspring at 2 y of age. Am J Clin Nutr. 2007;85:530–7.PubMedGoogle Scholar
  72. 72.
    Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, Holt PG, Prescott SL. Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clin Exp Allergy. 2003;33:442–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Krauss-Etschmann S, Hartl D, Rzehak P, Heinrich J, Shadid R, del Carmen Ramírez-Tortosa M, Campoy C, Pardillo S, Schendel DJ, Decsi T, Demmelmair H. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-β levels after fish oil supplementation of pregnant women. J Allergy Clin Immunol. 2008;121:464–70.PubMedCrossRefGoogle Scholar
  74. 74.
    Lauritzen L, Kjær TMR, Fruekilde MB. Michaelsena k, Frøkiær FH. Fish oil supplementation of lactating mothers affects cytokine production in 2 1/2-year-old children. Lipids. 2005;40:669–76.PubMedCrossRefGoogle Scholar
  75. 75.
    Romieu I, Torrent M, Garcia-Esteban R, Ferrer C, Ribas-Fitó N, Antó JM, Sunyer J. Maternal fish intake during pregnancy and atopy and asthma in infancy. Clin Exp Allergy. 2007;37:518–25.PubMedCrossRefGoogle Scholar
  76. 76.
    Furuhjelm C, Warstedt K, Larsson J, Fredriksson M, Böttcher MF, Fälth-Magnusson K, Duchén K. Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy. Acta Paediatr. 2009;98(9):1461–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Olsen SF, Østerdal ML, Salvig JD, Mortensen LM, Rytter D, Secher NJ, Henriksen TB. Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up from a randomized controlled trial. Am J Clin Nutr. 2008;88(1):167–75.PubMedGoogle Scholar
  78. 78.
    Palmer DJ, Sullivan T, Gold MS. Prescott SL, Heddle R, Gibson RA, Makrides M. Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants’ allergies in first year of life: randomised controlled trial. Br Med J. 2012;344:e184.CrossRefGoogle Scholar
  79. 79.
    Villani AM, Crotty M, Cleland LG, James MJ, Fraser RJ, Cobiac L, Miller MD. Fish oil administration in older adults: Is their potential for adverse events? A systematic review of literature. Genetics. 2113;13:41–49.Google Scholar
  80. 80.
    Holguin F, Tellez-Rojo MM, Lazo M, Mannino D, Schwartz J, Hernandez M, Romieu I. Cardiac autonomic changes associated with fish oil vs soy oil supplementation with elderly. Chest. 2005;127:1102–7.PubMedGoogle Scholar
  81. 81.
    Rondeneli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montoefano G, Negroni M, Berra B, Politi P, Rizzo AM. Effect of omega-3 fatty acid supplementation on depressive symptoms and on health-related quality of life in treatment of elderly women with depression: a double-blind, placebo-controlled, randomized clinical trial. J Am Coll Nutr. 2010;29:55–64.CrossRefGoogle Scholar
  82. 82.
    Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJ. Effect of glucasamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis. Adv Ther. 2009;26:858–87.PubMedCrossRefGoogle Scholar
  83. 83.
    van de Rest O, Geleijnse JM, kok FJ, vansteveren WA, OldeRikkert MGM, Beekman ATF, de Groot CPGM. Effect of fish oil supplementation on quality of life in general population of older Douch subjects: a randomized, double-blind, placebo-controlled trial. J Am Geratr Soc. 2009;57:1481–86.Google Scholar
  84. 84.
    Fakhrzadeh H, ghaderpanahi m, SharifiF,Mirarefin M, Badamchizade Z, Akbrikamrani A, Larijani B. The effects of low dose n-3 fatty acids on serum lipid profiles and insulin resistance of the elderly: a randomized controlled clinical trial. Int J Vitamin Nutr Res. 2010;80:107–16.Google Scholar
  85. 85.
    Harris WS. Expert openion:omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol. 2007;99:S44–6.CrossRefGoogle Scholar
  86. 86.
    Letter regarding dietary supplement health claim for omega-3 and coronary heart disease.
  87. 87.
    Calder PC. Omega-3 fatty acids and inflammatory process. Nutrients. 2010;2:355–74.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Simopoulos AP. Omega-3 fatty acids in Inflammation and autoimmune diseases. Am J College Nutr. 2002;21:495–505.CrossRefGoogle Scholar
  89. 89.
    Kremer J, Jubiz W, Michalek A, Rynes RI, Bartholomew LE, Bigaouette J, Tinchalk M, Beeler D, Lininger L. Fish oil fatty acid supplementation in active rheumatoid arthritis. A double blinded, controlled cross over study. Ann Intern Med. 1987;106:497–503.Google Scholar
  90. 90.
    Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer WMJ, Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaefer EJ, Wolff SM, Dinarello CA. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumour necrosis factor by mononuclear cells. N Eng J Med. 1989;320:265–71.CrossRefGoogle Scholar
  91. 91.
    Calder PC. PUFA, inflammatory process and rheumatoid arthritis. Proc Nutr Soc. 2008;67:116–22.CrossRefGoogle Scholar
  92. 92.
    Fortin PR, Lew RA, Liang MH, Wright EA, Backeet LA, Chaimers TC, Sperling RI. Validation of meta-analysis: the effect of fish oil in rheumatoid arthritis. J Clin Epidemiol. 1995;48:1379–90.PubMedCrossRefGoogle Scholar
  93. 93.
    Broughton KS, Johnson CS, Pace BK, Liebman M, Kleppinger KM. Reduced asthma symptoms with n-3 fatty acid ingestion are related to 5-series leukotreine production. Am J Clin Nutr. 1997;65:1011–7.PubMedGoogle Scholar
  94. 94.
    Okamoto M, Mitsunobu F, Ashida K, Mifune T, Hosaki Y, Tsugeno H, harada s, Tanizaki Y. Effects of dietary supplementation with n-3 fatty acids compared to n-6 fatty acids on bronchial asthma. Inter. Med. 2000;39:107–11.Google Scholar
  95. 95.
    Schachter HM,Reisman J,Tran K, Dales B, Kourad K, Barnes D, Sampson M, Morrison A, Gaboury I, Blackman J. Health effects of omega-3 fatty acids on asthma. Rockville, Agency for Healthcare Research and Quality, 2004. Evidence report/technical assessment no. 91. AHRQ publ. No. 04-E013-2.Google Scholar
  96. 96.
    Cobrin GM, Abreu MT. Defects in mucosal immunity leading to Crohn’s disease. Immunol Rev. 2005;206:277–95.PubMedCrossRefGoogle Scholar
  97. 97.
    Sharon p, Stenson WF. Enhanced synthesis of leukotreine B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology. 1984;86:453–60.Google Scholar
  98. 98.
    Shoda R, Matsueda K, Yamoto S, Umeda N. Epidemiological analysis of Crohn’s disease in Japan: increased dietary intakes of n-6 polyunsaturated fatty acids and animal protein relates to increased incidence of Crohn’s disease in Japan. Am J Clin Nutr. 1996;63:741–5.PubMedGoogle Scholar
  99. 99.
    Calder PC. Polyunsaturated fatty acids, inflammatory process and inflammatory bowel diseases. Mol Nutr Food Res. 2008;52:885–97.PubMedCrossRefGoogle Scholar
  100. 100.
    MaLean CH, Mojika, WA, Morton SC, Pencharz J. hasenfeld Garland R, Tu W, Newberry SJ, Jungvig LK, Grossman J, Khanna P, Rhodes S, Shekella P. Effect of omega-3 fatty acids on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus and osteoporosis. Rockville, Agency for Healthcare Research and Quality. 2004. Evidence report/technical assessment no. 89. AHRQ publication no.o4-E012-2.Google Scholar
  101. 101.
    Feagan BG, Sandborn WJ, Mittmann U, bar-Meir S, D’Haens G, Bradette M,, Cohen A, dallaaire AC, Ponich TP, McDonald JW, He’buterne X, Pare’ P, Klvana P, Niv Y, Ardizzone S, Alexeeva O, Rostom A, Kiudelis G, Spleiss J, GilgenD, Vandervoort MK, Wong CJ, Zou GY, Donner A, Rutgeerts P. Omega-3 free fatty acids for maintenance of remission in Crohn’s disease. The EPIC randomized controlled trials. JAMA. 2008;299:1690–97.Google Scholar
  102. 102.
    Balbás GM, Regaña MS, Millet PU. Study on the use of omega-3 fatty acids as a therapeutic supplement in treatment of psoriasis. Clin Cosmet Investig Dermatol. 2011;4:73–7.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Wolters M. Diet and psoriasis: experimental data and clinical evidence. Br J Dermatol. 2005;153:706–14.PubMedCrossRefGoogle Scholar
  104. 104.
    Wolters M. The significance of diet and associated factors in psoriasis. Hautartz. 2006;57:999–1004.CrossRefGoogle Scholar
  105. 105.
    Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep. 2004;6:461–7.PubMedCrossRefGoogle Scholar
  106. 106.
    Gogus U, Smith C. n-3 omega fatty acids: a review of current knowledge. Int J Food Sci Tech. 2010;45:417–36.CrossRefGoogle Scholar
  107. 107.
    Zyriax BC, Windlier E. Dietary fat and prevention of cardiovascular disease—a review. Eur J Lipid Sci Technol. 2000;162:355–85.CrossRefGoogle Scholar
  108. 108.
    Harris, Ws, Park Y, Isley WL. Cardiovascular disease and long chain omega-3 fatty acids. Curr Opin Lipidol. 2003;14:9–14.Google Scholar
  109. 109.
    Russo GL. Dietary n-6 and n-3 polyunsaturated fatty acids: from biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol. 2009;77:937–46.PubMedCrossRefGoogle Scholar
  110. 110.
    Ross R. Atherosclerosis—an inflammatory disease. N Eng J Med. 1999;340:115–26.CrossRefGoogle Scholar
  111. 111.
    Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. Br Med J. 1996;312:1061–5.CrossRefGoogle Scholar
  112. 112.
    Khalfoun B, Thibault F, Watier H, Bardos P, Lebranchu Y. Docosahexaenoic and eisosapentaenoic acids inhibit in vitro human endothelial cell production of interleukin-6. In: Honn KV, Nigam S, Marnett LJ, editors. Eicosanoids and other bioactive lipids in cancer, inflammation and radiation injury 2. New York: Plenum; 1997.Google Scholar
  113. 113.
    Woods A, Brull DJ, Humphries SE, Montgomery HE. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6Eur. Heart J. 2000;21:1574–83.CrossRefGoogle Scholar
  114. 114.
    Turner DN, Braby LA, Ford J, Lupton RJ. Opportunities for nutritional amelioration of radiation induced cellular damage. Nutrition. 2002;18:904–12.PubMedCrossRefGoogle Scholar
  115. 115.
    Menta A, Koning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a casual link between dietary factors and coronary heart disease. Arch Intern Med. 2009;169:659–69.CrossRefGoogle Scholar
  116. 116.
    Preiss D, Sattar N. Lipids, lipid modifying agents and cardiovascular risk: a review of the evidence. Clin Endocrinol. 2009;70:815–28.CrossRefGoogle Scholar
  117. 117.
    De Caterina R, Madonna R, Bertolotto A, Schmidt EB. n-3 Fatty acids in the treatment of diabetic patients: biological rationale and clinical data. Diabet Care. 2007;30:1012–26.CrossRefGoogle Scholar
  118. 118.
    Fonseca V, Desouza C, Asnani S, Jailal I. Non-traditional risk factors for cardiovascular disease is diabetes. Endocr Rev. 2004;25:153–75.PubMedCrossRefGoogle Scholar
  119. 119.
    Jorgensen ME, Bjeregaar DP, Borcjohnsen K. Diabetes and impaired glucose tolerance among the Inuit population of Greenland. Diabetes Care. 2002;25:1766–71.PubMedCrossRefGoogle Scholar
  120. 120.
    Raheja BS, Sadikot SM, Phatak RB, Rao MB. Significance of n -6/N-3 ratio for insulin action in diabetes. Ann N Y Acad Sci. 1993;683:258–71.PubMedCrossRefGoogle Scholar
  121. 121.
    Harris WS, Bulchandani D. Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol. 2006;17:387–93.PubMedCrossRefGoogle Scholar
  122. 122.
    Schmidt EB, Sorensen PJ, Pedersen JO, jersild C, Ditzel J, Grunnet N, Dyerberg J. The effect of n-3 unsaturated fatty acids on lipids, haemostasis, neutrophil and monocyte chemotaxis in insulin dependent diabetes mellitus. J. Intern. Med Suppl. 1989;731:201–206.Google Scholar
  123. 123.
    Hartweg J, Farmer AJ, Holman RR, Neil HA. Meta-analysis of the effects of n-3 polyunsaturated fatty acids on haematological and thrombogenic factors in type 2 diabetes. Diabetologia. 2007;50:250–8.PubMedCrossRefGoogle Scholar
  124. 124.
    Hartweg J, Farmer AJ, Holman RR, Neil A. Potential impact of omega-3 treatment on cardiovascular disease in type 2 diabetes. Curr Opin Lipidol. 2009;20:30–8.PubMedCrossRefGoogle Scholar
  125. 125.
    Djemli-Shipkolye A, Raccah D, Pieroni G, Vague P, Coste TC, Gerbi A. Differential effect of omega3 PUFA supplementations on Na, K-ATPase and Mg-ATPase activities: possible role of the membrane omega6/omega3 ratio. J Membr Biol. 2003;191:37–47.PubMedCrossRefGoogle Scholar
  126. 126.
    Hagiwara S, Makita Y, Gu L, Tanimoto M, Zhang M, Nakamura S, Kaneko S, Itoh T, Gohda T, Horikoshi S, Tomino Y. Eicosapentaenoic acid ameliorates diabetic nephropathy of type 2 diabetic KKAy/Ta mice: involvement of MCP-1 suppression and decreased ERK1/2 and p38 phosphorylation. Nephrol Dial Transplant. 2006;21:605–15.PubMedCrossRefGoogle Scholar
  127. 127.
    Klein R, Klein BE, Moss SE, Cruickshanks KJ. The wisconsin epidemiologic study of diabetic retinopathy. XV. The long-term incidence of macular edema. Ophthalmology. 1995;102:7–16.PubMedCrossRefGoogle Scholar
  128. 128.
    Mozaffarian D, Kamineni A, Carnethon M, Djousse L, Mukamal KJ, Siscovic KD. Lifestyle risk factors and new-onset diabetes mellitus in older adults: the cardiovascular health study. Arch Intern Med. 2009;169:798–807.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Kromhout D, Giltay EJ, Geleijnse JM. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010;363:2015–26.PubMedCrossRefGoogle Scholar
  130. 130.
    Meyer KA, Kushi LH, Jacobs DR Jr, Folsom AR. Dietary fat and incidence of type 2 diabetes in older Iowa women. Diabetes Care. 2001;24:1528–35.PubMedCrossRefGoogle Scholar
  131. 131.
    Kaushik M, Mozaffarian D, Spiegelman D, Manson JE, Willett WC, Hu FB. Long-chain omega-3 fatty acids, fish intake, and the risk of type 2 diabetes mellitus. Am J Clin Nutr. 2009;90:613–20.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Hodge AM, English DR, O’Dea K, Sinclair AJ, Makrides M, Gibson RA, Giles GG. Plasma phospholipid and dietary fatty acids as predictors of type 2 diabetes: interpreting the role of linoleic acid. Am J Clin Nutr. 2007;86:189–97.PubMedGoogle Scholar
  133. 133.
    Laaksonen DE, Lakka TA, Lakka HM, Nyyssönen K, Rissanen T, Niskanen LK, Salonen JT. Serum fatty acid composition predicts development of impaired fasting glycaemia and diabetes in middle-aged men. Diabet Med. 2002;19:456–64.PubMedCrossRefGoogle Scholar
  134. 134.
    Djoussé L, Biggs ML, Lemaitre RN, King IB, Song X, Ix JH, Mukamal KJ, Siscovick DS, Mozaffarian D. Plasma omega-3 fatty acids and incident diabetes in older adults. Am J Clin Nutr. 2011;94:527–533.Google Scholar
  135. 135.
    Mehta LR, Dworkin RH, Schwid SR. Polyunsaturated fatty acids and their potential therapeutic role in multiple sclerosis. Nat Clin Pract Neurol. 2009;5:82–92.PubMedCrossRefGoogle Scholar
  136. 136.
    Schwarz S, Knorr C, Geiger H, Flachenecker P. Complementary and alternative medicine for multiple sclerosis. Mult Scler. 2008;14:1113–9.PubMedCrossRefGoogle Scholar
  137. 137.
    Zhang SM, Willett WC, Hernán MA, Olek MJ, Ascherio A. Dietary fat in relation to risk of multiple sclerosis among two large cohorts of women. Am J Epidemiol. 2000;152:1056–64.PubMedCrossRefGoogle Scholar
  138. 138.
    Kampman MT, Wilsgaard T, Mellgren SI. Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle. J Neurol. 2007;254:471–7.PubMedCrossRefGoogle Scholar
  139. 139.
    Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25—hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2004;296:2832–8.CrossRefGoogle Scholar
  140. 140.
    Koch M, Ramsaransing GSM, Fokkema MR, Heersema DJ, De Keyser J. Erythrocyte membrane fatty acids in benign and progressive forms of multiple sclerosis. J Neurol Sci. 2006;244:123–6.PubMedCrossRefGoogle Scholar
  141. 141.
    Serhan CN, Chiang N, Van Dyke TE. resolving inflammation: duel anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008;8:349–61.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    SerhanCN, Gotlinger K, Hong S, Arita M.Resolvins, dicosatrines and neuroprotectins, novel omega-3 derived mediators, and their aspirin triggered epimers. Lipids. 2004;39:1125–32.Google Scholar
  143. 143.
    Ghosh S, Hayden MS. New regulators of NF-κB in inflammation. Nat Rev Immunol. 2008;8:837–48.PubMedCrossRefGoogle Scholar
  144. 144.
    Salvati S, Natali F, Attorri L, Di Benedetto R, Leonardi F, Di Biase A, Ferri F, Fortuna S, Lorenzini P, Sanchez M, Ricceri L, Vitelli L. Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain. J Neurosci Res. 2008;86:776–84.PubMedCrossRefGoogle Scholar
  145. 145.
    Heneka MT, Landreth GE, Hüll M. Drug insight: effect mediated by peroxisome proliferator-activated receptor-ɣ in CNS disorders. Nat Clin Pract Neurol. 2007;3:496–04.Google Scholar
  146. 146.
    Farinotti M, Simi S, Di Pietrantonj C, McDowell N, Brait L, Lupo D, Filippini G. Dietary interventions for multiple sclerosis. Cochrane database of systematic reviews. 2007; Issue No. 1, Art. No.:CD004192.Google Scholar
  147. 147.
    Yu SL, Kuan WP, Wong CK, Li EK, Tam LS. Immunopathological roles of cytokines, chemokines, signalling molecules and pattern recognition receptors in systemic lupus erythematosus. Clin Dev Immunol. 2012;2012:715190.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Borges MC, Santos F de Miranda M, Telles RW, Correia MITD, Lanna CCD. Polyunsaturated omega-3 fatty acids and systemic Lupus Erythematosus: what do we know? Rev Bras de Rheumatologia (Engl Ed) 2014; 54:459–66.Google Scholar
  149. 149.
    Write SA, OPrey FM, McHenry MT, Leahey WJ, Devine AB, Duffy EM, Johnston DG, Finch MB, Bell AL, McVeigh GE. A randomized intervention trial of ω-3 polyunsaturated acids on endothelial function and disease activity in systemic Lupus Erythematosus. Ann Rheum Dis. 2008; 67:841–848.Google Scholar
  150. 150.
    Elkan AC, Anania C, Gustafsson T, Jogestrand T, Hafstrom I, Frostegard J. Diet and fatty acid pattern among patients with SLE: association with disease activity, blood lipids, and atherosclerosis. Lupus. 2012;21:1405–11.PubMedCrossRefGoogle Scholar
  151. 151.
    Bello KJ, Fang H, Fazeli P, Bolad W, Corretti M, Magder LH, Petr M. Omega-3 in SLE: a double blind, placebo-controlled randomized clinical trial of endothelial dysfunction and disease activity in systemic lupus erythematosus. Rheumatol Int. 2013;33:2789–96.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Aghdassi E, Ma DWL, Morrison S, Hillyer LM, Clarke S, Gladman DD, Urowitz MB, Fortin PR. Alterations in circulating fatty acid composition in patients with systemic lupus erythematosus: a pilot study. JPEN. 2011;35:198–208.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Integrated Centre for Cancer Treatment and ResearchPuneIndia
  2. 2.Formerly, Head, Immunology DivisionCancer Research InstituteMumbaiIndia

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