Skip to main content
    • Aa
    • Aa

Long chain omega-3 fatty acids and cardiovascular disease: a systematic review

  • Javier Delgado-Lista (a1) (a2), Pablo Perez-Martinez (a1) (a2), Jose Lopez-Miranda (a1) (a2) and Francisco Perez-Jimenez (a1) (a2)

Introduction: Cardiovascular disease remains the commonest health problem in developed countries, and residual risk after implementing all current therapies is still high. The use of marine omega-3 fatty acids (DHA and EPA) has been recommended to reduce cardiovascular risk by multiple mechanisms. Objectives: To update the current evidence on the influence of omega-3 on the rate of cardiovascular events. Review Methods: We used the MEDLINE and EMBASE databases to identify clinical trials and randomized controlled trials of omega-3 fatty acids (with quantified quantities) either in capsules or in dietary intake, compared to placebo or usual diet, equal to or longer than 6 months, and written in English. The primary outcome was a cardiovascular event of any kind and secondary outcomes were all-cause mortality, cardiac death and coronary events. We used RevMan 5·1 (Mantel-Haenszel method). Heterogeneity was assessed by the I2 and Chi2 tests. We included 21 of the 452 pre-selected studies. Results: We found an overall decrease of risk of suffering a cardiovascular event of any kind of 10 % (OR 0·90; [0·85–0·96], p = 0·001), a 9 % decrease of risk of cardiac death (OR 0·91; [0·83–0·99]; p = 0·03), a decrease of coronary events (fatal and non-fatal) of 18 % (OR 0·82; [0·75–0·90]; p < 1 × 10− 4), and a trend to lower total mortality (5 % reduction of risk; OR 0·95; [0·89–1·02]; p = 0·15. Most of the studies analyzed included persons with high cardiovascular risk. Conclusions: marine omega-3 fatty acids are effective in preventing cardiovascular events, cardiac death and coronary events, especially in persons with high cardiovascular risk.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Long chain omega-3 fatty acids and cardiovascular disease: a systematic review
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Long chain omega-3 fatty acids and cardiovascular disease: a systematic review
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Long chain omega-3 fatty acids and cardiovascular disease: a systematic review
      Available formats
Corresponding author
*Corresponding author: F. Perez-Jimenez, fax +34 957 204763, email
Hide All
1 Kris-Etherton PM, Harris WS & Appel LJ (2002) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106, 27472757.
2 Lichtenstein AH, Appel LJ, Brands M, et al. (2006) Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 114, 8296.
3 Lavie CJ, Milani RV, Mehra MR, et al. (2009) Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol 54, 585594.
4 Mente A, de Koning L, Shannon HS, et al. (2009) A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med 169, 659669.
5 Riediger ND, Othman RA, Suh M, et al. (2009) A systemic review of the roles of n-3 fatty acids in health and disease. J Am Diet Assoc 109, 668679.
6 Filion KB, El Khoury F, Bielinski M, et al. (2010) Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of randomized controlled trials. BMC Cardiovasc Disord 10, 24.
7 Jadad AR, Moore RA, Carroll D, et al. (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17, 112.
8 Dehmer GJ, Popma JJ, van den Berg EK, et al. (1988) Reduction in the rate of early restenosis after coronary angioplasty by a diet supplemented with n-3 fatty acids. N Engl J Med 319, 733740.
9 Nye ER, Ablett MB, Robertson MC, et al. (1990) Effect of eicosapentaenoic acid on restenosis rate, clinical course and blood lipids in patients after percutaneous transluminal coronary angioplasty. Aust N Z J Med 20, 549552.
10 Bairati I, Roy L & Meyer F (1992) Double-blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary angioplasty. Circulation 85, 950956.
11 Leaf A, Jorgensen MB, Jacobs AK, et al. (1994) Do fish oils prevent restenosis after coronary angioplasty? Circulation 90, 22482257.
12 Sacks FM, Stone PH, Gibson CM, et al. (1995) Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol 25, 14921498.
13 Eritsland J, Arnesen H, Gronseth K, et al. (1996) Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am J Cardiol 77, 3136.
14 Leng GC, Lee AJ, Fowkes FG, et al. (1998) Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease. Clin Nutr 17, 265271.
15 Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. (1999) Lancet 354, 447–455.
16 Johansen O, Brekke M, Seljeflot I, et al. (1999) N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. Coronary Angioplasty Restenosis Trial. J Am Coll Cardiol 33, 16191626.
17 von Schacky C, Angerer P, Kothny W, et al. (1999) The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 130, 554562.
18 Nilsen DW, Albrektsen G, Landmark K, et al. (2001) Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Am J Clin Nutr 74, 5056.
19 Burr ML, Ashfield-Watt PA, Dunstan FD, et al. (2003) Lack of benefit of dietary advice to men with angina: results of a controlled trial. Eur J Clin Nutr 57, 193200.
20 Leaf A, Albert CM, Josephson M, et al. (2005) Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Circulation 112, 27622768.
21 Raitt MH, Connor WE, Morris C, et al. (2005) Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 293, 28842891.
22 Brouwer IA, Zock PL, Camm AJ, et al. (2006) Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 295, 26132619.
23 Yokoyama M, Origasa H, Matsuzaki M, et al. (2007) Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 369, 10901098.
24 Gissi HFI, Tavazzi L, Maggioni AP, et al. (2008) Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 372, 12231230.
25 Einvik G, Klemsdal TO, Sandvik L, et al. (2010) A randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk. Eur J Cardiovasc Prev Rehabil 17, 588592.
26 Galan P, Kesse-Guyot E, Czernichow S, et al. (2010) Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ 341, c6273.
27 Rauch B, Schiele R, Schneider S, et al. (2010) OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Circulation 122, 21522159.
28 Nodari S, Triggiani M, Campia U, et al. (2011) Effects of n-3 polyunsaturated fatty acids on left ventricular function and functional capacity in patients with dilated cardiomyopathy. J Am Coll Cardiol 57, 870879.
29 Kromhout D, Giltay EJ, Geleijnse JM, et al. (2010) n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 363, 20152026.
30 von Schacky C & Harris WS (2007) Cardiovascular benefits of omega-3 fatty acids. Cardiovasc Res 73, 310315.
31 Mozaffarian D (2008) Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death. Am J Clin Nutr 87, 1991S1996S.
32 Marik PE & Varon J (2009) Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol 32, 365372.
33 Saravanan P, Davidson NC, Schmidt EB, et al. (2010) Cardiovascular effects of marine omega-3 fatty acids. Lancet 376, 540550.
34 Singh RB, Niaz MA, Sharma JP, et al. (1997) Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival–4. Cardiovasc Drugs Ther 11, 485491.
35 Horton R (2005) Expression of concern: Indo-Mediterranean Diet Heart Study. Lancet 366, 354356.
36 White C (2005) Suspected research fraud: difficulties of getting at the truth. BMJ 331, 281288.
37 Iso H, Kobayashi M, Ishihara J, et al. (2006) Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation 113, 195202.
38 Watanabe N, Watanabe Y, Kumagai M, et al. (2009) Administration of dietary fish oil capsules in healthy middle-aged Japanese men with a high level of fish consumption. Int J Food Sci Nutr 60, Suppl. 5, 136142.
39 Origasa H, Yokoyama M, Matsuzaki M, et al. (2010) Clinical importance of adherence to treatment with eicosapentaenoic acid by patients with hypercholesterolemia. Circ J 74, 510517.
40 Mozaffarian D (2007) Fish, n-3 fatty acids, and cardiovascular haemodynamics. J Cardiovasc Med (Hagerstown) 8, Suppl. 1, S23S26.
41 Perez-Martinez P, Delgado-Lista J, Perez-Jimenez F, et al. (2010) Update on genetics of postprandial lipemia. Atheroscler Suppl 11, 3943.
42 Teslovich TM, Musunuru K, Smith AV, et al. (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707713.
43 Pishva H, Mahboob SA, Mehdipour P, et al. (2010) Fatty acid-binding protein-2 genotype influences lipid and lipoprotein response to eicosapentaenoic acid supplementation in hypertriglyceridemic subjects. Nutrition 26, 11171121.
44 Olano-Martin E, Anil E, Caslake MJ, et al. (2010) Contribution of apolipoprotein E genotype and docosahexaenoic acid to the LDL-cholesterol response to fish oil. Atherosclerosis 209, 104110.
45 Caslake MJ, Miles EA, Kofler BM, et al. (2008) Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study. Am J Clin Nutr 88, 618629.
46 Mozaffarian D & Rimm EB (2006) Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 296, 18851899.
47 Thies F, Garry JM, Yaqoob P, et al. (2003) Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet 361, 477485.
48 Harris WS, Miller M, Tighe AP, et al. (2008) Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis 197, 1224.
49 Serhan CN, Chiang N & Van Dyke TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 8, 349361.
50 Morris MC, Sacks F & Rosner B (1993) Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation 88, 523533.
51 Yamagishi K, Nettleton JA & Folsom AR (2008) Plasma fatty acid composition and incident heart failure in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J 156, 965974.
52 Mozaffarian D, Psaty BM, Rimm EB, et al. (2004) Fish intake and risk of incident atrial fibrillation. Circulation 110, 368373.
53 Gillet L, Roger S, Bougnoux P, et al. (2011) Beneficial effects of omega-3 long-chain fatty acids in breast cancer and cardiovascular diseases: voltage-gated sodium channels as a common feature? Biochimie 93, 46.
54 Saravanan P, Bridgewater B, West AL, et al. (2010) Omega-3 fatty acid supplementation does not reduce risk of atrial fibrillation after coronary artery bypass surgery: a randomized, double-blind, placebo-controlled clinical trial. Circ Arrhythm Electrophysiol 3, 4653.
55 Brouwer IA, Raitt MH, Dullemeijer C, et al. (2009) Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators. Eur Heart J 30, 820826.
56 Verkerk AO, van Ginneken AC, Berecki G, et al. (2006) Incorporated sarcolemmal fish oil fatty acids shorten pig ventricular action potentials. Cardiovasc Res 70, 509520.
57 Coronel R, Wilms-Schopman FJ, Den Ruijter HM, et al. (2007) Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts. Cardiovasc Res 73, 386394.
58 Wang C, Harris WS, Chung M, et al. (2006) n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr 84, 517.
59 Chalupka S (2009) Omega-3 polyunsaturated fatty acid in primary and secondary cardiovascular disease prevention. AAOHN J 57, 480.
60 Knapp HR, Reilly IA, Alessandrini P, et al. (1986) In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis. N Engl J Med 314, 937942.
61 Kristensen SD, Iversen AM & Schmidt EB (2001) n-3 polyunsaturated fatty acids and coronary thrombosis. Lipids 36, S79S82.
62 Eritsland J, Arnesen H, Seljeflot I, et al. (1995) Long-term effects of n-3 polyunsaturated fatty acids on haemostatic variables and bleeding episodes in patients with coronary artery disease. Blood Coagul Fibrinolysis 6, 1722.
63 Watson PD, Joy PS, Nkonde C, et al. (2009) Comparison of bleeding complications with omega-3 fatty acids+aspirin+clopidogrel–versus–aspirin+clopidogrel in patients with cardiovascular disease. Am J Cardiol 104, 10521054.
64 Park K & Mozaffarian D (2010) Omega-3 fatty acids, mercury, and selenium in fish and the risk of cardiovascular diseases. Curr Atheroscler Rep 12, 414422.
65 Fremont L, Gozzelino MT, Franchi MP, et al. (1998) Dietary flavonoids reduce lipid peroxidation in rats fed polyunsaturated or monounsaturated fat diets. J Nutr 128, 14951502.
66 Hau MF, Smelt AH, Bindels AJ, et al. (1996) Effects of fish oil on oxidation resistance of VLDL in hypertriglyceridemic patients. Arterioscler Thromb Vasc Biol 16, 11971202.
67 Sorensen NS, Marckmann P, Hoy CE, et al. (1998) Effect of fish-oil-enriched margarine on plasma lipids, low-density-lipoprotein particle composition, size, and susceptibility to oxidation. Am J Clin Nutr 68, 235241.
68 Bonanome A, Biasia F, De Luca M, et al. (1996) n-3 fatty acids do not enhance LDL susceptibility to oxidation in hypertriacylglycerolemic hemodialyzed subjects. Am J Clin Nutr 63, 261266.
69 Brude IR, Drevon CA, Hjermann I, et al. (1997) Peroxidation of LDL from combined-hyperlipidemic male smokers supplied with omega-3 fatty acids and antioxidants. Arterioscler Thromb Vasc Biol 17, 25762588.
70 Higdon JV, Du SH, Lee YS, et al. (2001) Supplementation of postmenopausal women with fish oil does not increase overall oxidation of LDL ex vivo compared to dietary oils rich in oleate and linoleate. J Lipid Res 42, 407418.
71 Petersson H, Riserus U, McMonagle J, et al. (2010) Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study. Br J Nutr 104, 13571362.
72 Leaf A, Kang JX, Xiao YF, et al. (2003) Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation 107, 26462652.
73 Leng GC, Taylor GS, Lee AJ, et al. (1999) Essential fatty acids and cardiovascular disease: the Edinburgh Artery Study. Vasc Med 4, 219226.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 58
Total number of PDF views: 546 *
Loading metrics...

Abstract views

Total abstract views: 1234 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 19th October 2017. This data will be updated every 24 hours.