Current Atherosclerosis Reports

, Volume 6, Issue 6, pp 461–467 | Cite as

Omega-3 fatty acids and inflammation

  • Trevor A. Mori
  • Lawrence J. Beilin


Dietary omega-3 (n-3) fatty acids have a variety of anti-inflammatory and immune-modulating effects that may be of relevance to atherosclerosis and its clinical manifestations of myocardial infarction, sudden death, and stroke. The n-3 fatty acids that appear to be most potent in this respect are the long-chain polyunsaturates derived from marine oils, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and this review is restricted to these substances. A variety of biologic effects of EPA and DHA have been demonstrated from feeding studies with fish or fish oil supplements in humans and animals. These include effects on triglycerides, high-density lipoprotein cholesterol, platelet function, endothelial and vascular function, blood pressure, cardiac excitability, measures of oxidative stress, pro- and anti-inflammatory cytokines, and immune function. Epidemiologic studies provide evidence for a beneficial effect of n-3 fatty acids on manifestations of coronary heart disease and ischemic stroke, whereas randomized, controlled, clinical feeding trials support this, particularly with respect to sudden cardiac death in patients with established disease. Clinically important anti-inflammatory effects in man are further suggested by trials demonstrating benefits of n-3 fatty acids in rheumatoid arthritis, psoriasis, asthma, and inflammatory bowel disorders. Given the evidence relating progression of atherosclerosis to chronic inflammation, the n-3 fatty acids may play an important role via modulation of the inflammatory processes.


Atorvastatin Arterioscler Thromb Vasc Biol G338 Tumor Necrosis Factor Alpha Production Vascular Smooth Muscle Cell Apoptosis 
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References and Recommended Reading

  1. 1.
    Mori TA, Beilin LJ: n-3 Fatty acids, blood lipids and cardiovascular risk reduction. Curr Opin Lipidol 2001, 12:1211–1217.CrossRefGoogle Scholar
  2. 2.
    Calder PC: Polyunsaturated fatty acids, inflammation, and immunity. Lipids 2001, 36:1007–1024.PubMedCrossRefGoogle Scholar
  3. 3.
    Ross R: Atherosclerosis—an inflammatory disease. N Engl J Med 1999, 340:115–126.PubMedCrossRefGoogle Scholar
  4. 4.
    Browning LM: n-3 Polyunsaturated fatty acids, inflammation and obesity-related disease. Proc Nutrition Soc 2003, 62:447–453.CrossRefGoogle Scholar
  5. 5.
    Simopoulos AP: Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002, 21:495–505.PubMedGoogle Scholar
  6. 6.
    Gil A: Polyunsaturated fatty acids and inflammatory diseases. Biomed Pharmacother 2002, 56:388–396.PubMedCrossRefGoogle Scholar
  7. 7.
    Sakr HM, Dunham EW: Mechanism of arachidonic acid-induced vasoconstriction in the intact rat kidney: possible involvement of thromboxane A2. J Pharmacol Exp Ther 1982, 221:614–622.PubMedGoogle Scholar
  8. 8.
    De Caterina R, Endres S, Kristensen SD, Schmidt EB: n-3 fatty acids and renal diseases. Am J Kidney Dis 1994, 24:397–415.PubMedGoogle Scholar
  9. 9.
    Mori TA, Beilin LJ, Burke V, et al.: Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 1997, 17:279–286.PubMedGoogle Scholar
  10. 10.
    Harbige LS: Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3. Lipids 2003, 38:323–341.PubMedCrossRefGoogle Scholar
  11. 11.
    McCarty MF: Interleukin-6 as a central mediator of cardiovascular risk associated with chronic inflammation, smoking, diabetes, and visceral obesity: down-regulation with essential fatty acids, ethanol and pentoxifylline. Med Hypotheses 1999, 52:465–477.PubMedCrossRefGoogle Scholar
  12. 12.
    Madsen T, Skou HA, Hansen VE, et al.: C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease. Am J Cardiol 2001, 88:1139–1142.PubMedCrossRefGoogle Scholar
  13. 13.
    Ridker PM, Cushman M, Stampfer MJ, et al.: Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997, 336:973–979.PubMedCrossRefGoogle Scholar
  14. 14.
    Dunstan JA, Mori TA, Barden A, et al.: The effects of omega-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition. Eur J Clin Nutr 2004, 58:429–437.PubMedCrossRefGoogle Scholar
  15. 15.
    Dunstan JA, Mori TA, Barden A, et al.: Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clin Exper Allergy 2003, 33:442–448.CrossRefGoogle Scholar
  16. 16.
    Dunstan JA, Mori TA, Barden A, et al.: Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomised controlled trial. J Allergy Clin Immunol 2003, 112:1178–1184.PubMedCrossRefGoogle Scholar
  17. 17.
    Fox PL, DiCorleto PE: Fish oils inhibit endothelial cell production of platelet-derived growth factor-like protein. Science 1988, 241:453–456.PubMedCrossRefGoogle Scholar
  18. 18.
    Chandrasekar B, Troyer DA, Venkatraman JT, Fernandes G: Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor beta mRNA and protein expression. J Autoimmunity 1995, 8:381–393.CrossRefGoogle Scholar
  19. 19.
    Nakayama M, Fukuda N, Watanabe Y, et al.: Low dose of eicosapentaenoic acid inhibits the exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats through suppression of transforming growth factor-beta. J Hypertens 1999, 17:1421–1430.PubMedCrossRefGoogle Scholar
  20. 20.
    Grande JP, Walker HJ, Holub BJ, et al.: Suppressive effects of fish oil on mesangial cell proliferation in vitro and in vivo. Kidney Int 2000, 57:1027–1040.PubMedCrossRefGoogle Scholar
  21. 21.
    Grimble RF, Howell WM, O’Reilly G, et al.: The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production. Am J Clin Nutr 2002, 76:454–459.PubMedGoogle Scholar
  22. 22.
    Chan DC, Watts GF, Barrett PH, et al.: Effect of atorvastatin and fish oil on plasma high sensitive C-reactive protein concentrations in individuals with visceral obesity. Clin Chem 2002, 48:877–883.PubMedGoogle Scholar
  23. 23.
    Nenseter MS, Drevon CA: Dietary polyunsaturates and peroxidation of low density lipoprotein. Curr Opin Lipidol 1996, 7:8–13.PubMedCrossRefGoogle Scholar
  24. 24.
    Steinberg D, Parthasarathy S, Carew TE, et al.: Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989, 320:915–924.PubMedCrossRefGoogle Scholar
  25. 25.
    Liu J, Yeo HC, Doniger SJ, Ames BN: Assay of aldehydes from lipid peroxidation: gas chromatography-mass spectrometry compared to thiobarbituric acid. Anal Biochem 1997, 245:161–166.PubMedCrossRefGoogle Scholar
  26. 26.
    Lawson JA, Rokach J, Fitzgerland GA: Isoprostanes: formation, analysis and use as indices of lipid peroxidation in vivo. J Biol Chem 1999, 274:24441–24444.PubMedCrossRefGoogle Scholar
  27. 27.
    Leitinger N, Huber J, Rizza C, et al.: The isoprostane 8-iso-PGF2a stimulates endothelial cells to bind monocytes: differences from thromboxane-mediated endothelial activation. FASEB J 2001, 15:1254–1256.PubMedGoogle Scholar
  28. 28.
    Mori TA, Dunstan DW, Burke V, et al.: Effects of dietary fish and exercise training on urinary F2-isoprostane excretion in non-insulin dependent diabetic patients. Metabolism 1999, 48:1402–1408.PubMedCrossRefGoogle Scholar
  29. 29.
    Barden AE, Mori TA, Dunstan JA, et al.: Fish oil supplementation in pregnancy lowers F2-isoprostanes in neonates at high risk of atopy. Free Rad Res 2004, 38:233–239.CrossRefGoogle Scholar
  30. 30.
    Quaggiotto P, Leitch JW, Falconer J, et al.: Plasma F2alpha isoprostane levels are lowered in pigs fed an (n-3) polyunsaturated fatty acid supplemented diet following occlusion of the left anterior descending coronary artery. Nutr Res 2000, 20(5):675–684.CrossRefGoogle Scholar
  31. 31.
    Higdon JV, Liu JK, Du SH, et al.: Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F2-isoprostanes. Am J Clin Nutr 2000, 72:714–722.PubMedGoogle Scholar
  32. 32.
    Mori TA, Puddey IB, Burke V, et al.: Effect of n-3 fatty acids on oxidative stress in humans: GCMS measurement of urinary F2-isoprostane excretion. Redox Rep 2000, 5:45–46.PubMedGoogle Scholar
  33. 33.
    Mori TA, Woodman RJ, Burke V, Puddey IB, Croft KD, Beilin LJ: Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers, in treated-hypertensive Type 2 diabetic subjects. Free Rad Biol Med 2003, 35:772–781.PubMedCrossRefGoogle Scholar
  34. 34.
    Fisher M, Levine PH, Weiner BH, et al.: Dietary n-3 fatty acid supplementation reduces superoxide production and chemiluminescence in a monocyte-enriched preparation of leukocytes. Am J Clin Nutr 1990, 51:804–808.PubMedGoogle Scholar
  35. 35.
    Takahashi M, Tsuboyama-Kasaoka N, Nakatani T, et al.: Fish oil feeding alters liver gene expressions to defend against PPAR alpha activation and ROS production. Am J Physiol Gastrointest Liver Physiol 2002, 282:G338-G348.PubMedGoogle Scholar
  36. 36.
    Hansen JB, Olsen JO, Wilsgard L, Osterud B: Effects of dietary supplementation with cod liver oil on monocyte thromboplastin synthesis, coagulation and fibrinolysis. J Intern Med Suppl 1989, 225:133–139.Google Scholar
  37. 37.
    Baumann KH, Hessel F, Larass I, et al.: Dietary omega-3, omega-6, and omega-9 unsaturated fatty acids and growth factor and cytokine gene expression in unstimulated and stimulated monocytes. A randomized volunteer study. Arterioscler Thromb Vasc Biol 1999, 19:59–66.PubMedGoogle Scholar
  38. 38.
    Shimokawa H, Vanhoutte PM: Dietary omega 3 fatty acids and endothelium-dependent relaxations in porcine coronary arteries. Am J Physiol 1989, 256(4 Pt 2):H968-H973.PubMedGoogle Scholar
  39. 39.
    De Caterina R, Zampolli A: n-3 Fatty acids: antiatherosclerotic effects. Lipids 2001, 36(Suppl):S69-S78.PubMedCrossRefGoogle Scholar
  40. 40.
    Beilin LJ, Mori TA: Dietary n-3 fatty acids. In Lifestyle Modification for the Prevention and Treatment of Hypertension. Edited by PK Whelton, He J, Louis GT. New York: Marcel Dekker; 2003:275–300.Google Scholar
  41. 41.
    Mori TA, Watts GF, Burke V, et al.: Differential effects of eicosapentaenoic acid and docosahexaenoic acid on forearm vascular reactivity of the microcirculation in hyperlipidaemic, overweight men. Circulation 2000, 102:1264–1269.PubMedGoogle Scholar
  42. 42.
    Suzuki T, Fukuo K, Suhara T, et al.: Eicosapentaenoic acid protects endothelial cells against anoikis through restoration of cFLIP. Hypertension 2003, 42:342–348.PubMedCrossRefGoogle Scholar
  43. 43.
    Diep QN, Touyz RM, Schiffrin EL: Docosahexaenoic acid, a peroxisome proliferator-activated receptor-alpha ligand, induces apoptosis in vascular smooth muscle cells by stimulation of p38 mitogen-activated protein kinase. Hypertension 2000, 36:851–855.PubMedGoogle Scholar
  44. 44.
    Meydani SN, Lichtenstein AH, Cornwall S, et al.: Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment. J Clin Invest 1993, 92:105–113.PubMedCrossRefGoogle Scholar
  45. 45.
    Calder PC, Zurier RB: Polyunsaturated fatty acids and rheumatoid arthritis. Curr Opin Clin Nutr Metab Care 2001, 4:115–121.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Trevor A. Mori
    • 1
  • Lawrence J. Beilin
    • 1
  1. 1.School of Medicine and Pharmacology - Royal Perth Hospital UnitThe University of Western AustraliaPerthAustralia

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