Skip to main content
SpringerLink
Log in

Review of Cardiometabolic Effects of Prescription Omega-3 Fatty Acids

  • Nonstatin Drugs (E. deGoma, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Populations with significant dietary fish intake tend to have lower cardiovascular (CV) risk and demonstrable physiologic differences including lower lipid/lipoprotein levels and other direct and indirect effects on the arterial wall and inhibiting factors that promote atherosclerosis. Treatment with high doses of pharmacologic-grade omega-3 fatty acid (n-3FA) supplements achieves significant reductions in triglycerides (TG), non-high-density lipoprotein- (non-HDL-) and TG-rich lipoprotein- (TRL-) cholesterol levels. n-3FA supplements have significant effects on markers of atherosclerosis risk including endothelial function, low-density lipoprotein (LDL) oxidation, cellular and humoral markers of inflammation, hemodynamic factors, and plaque stabilization. This review summarizes the lipid and cardiometabolic effects of prescription-grade n-3FAs and will discuss clinical trials, national/organizational guidelines, and expert opinion on the impact of supplemental n-3FAs on CV health and disease.

Recent Findings

Clinical trial evidence supports use of n-3FAs in individuals with established atherosclerotic cardiovascular disease (ASCVD), but the data either does not support or is lacking for other types of cardiometabolic risk including prevention of stroke, treatment in patients with heart failure, diabetes mellitus and prediabetes, and for primary prevention in the general population.

Summary

Despite inconsistent findings to support widespread benefit, there is persistent population-wide enthusiasm for n-3FA as a dietary supplement for its cardiometabolic benefits. Fortunately, there are ongoing clinical trials to assess whether the lipid/lipoprotein benefits may be extended to other at-risk populations and whether lower-dose therapy may provide background benefit for primary prevention of ASCVD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58(20):2047–67. https://doi.org/10.1016/j.jacc.2011.06.063.

    Article  CAS  PubMed  Google Scholar 

  2. Harris WS, Dayspring TD, Moran TJ. Omega-3 fatty acids and cardiovascular disease: new developments and applications. Postgrad Med. 2013;125(6):100–13. https://doi.org/10.3810/pgm.2013.11.2717.

    Article  PubMed  Google Scholar 

  3. U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 dietary guidelines for Americans. 8th Edition. December 2015. Available at http://health.gov/dietaryguidelines/2015/guidelines/. Accessed August 7, 2017.

  4. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's Strategic Impact Goal through 2020 and beyond. Circulation. 2010;121:586–613. https://doi.org/10.1161/CIRCULATIONAHA.109.192703.

    Article  PubMed  Google Scholar 

  5. Clark TC, Black LI, Stussman BJ, Barnes PM, Nahin RL. Trends in the use of complementary health approaches among adults: United States, 2002–2012. National Health Statistics reports; no 79. Hyattsville, MD: National Center for Health Statistics. 2015. Available at https://nccih.nih.gov/research/statistics/NHIS/2012/natural-products/omega3. Accessed August 5, 2017.

  6. Backes J, Anzalone D, Hilleman D, Catini J. The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia. Lipids Health Dis. 2016;15:118–29. https://doi.org/10.1186/s12944-016-0286-4.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sperling LS, Nelson JR. History and future of omega-3 fatty acids in cardiovascular disease. Curr Med Res Opin. 2016;32:301–11. https://doi.org/10.1185/03007995.2015.1120190.

    Article  CAS  PubMed  Google Scholar 

  8. •• Siscovick DS, Barringer TA, Fretts AM, JHY W, Lichtenstein AH, Costello RB, et al. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease: a science advisory from the American Heart Association. Circulation. 2017;135:e876–84. https://doi.org/10.1161/CIR.0000000000000482. Recent and comprehensive review on use of n-3FA supplementation for CVD prevention.

    Article  Google Scholar 

  9. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM. n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr. 2006;83(suppl):1526S–35S.

    CAS  PubMed  Google Scholar 

  10. Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: dietary fatty acids for healthy adults. J Acad Nutr Diet. 2014;114:136–53. https://doi.org/10.1016/j.jand.2013.11001.

    Article  Google Scholar 

  11. Bowen KJ, Harris WS, Kris-Etherton PM. Omega-3 fatty acids and cardiovascular disease: are there benefits? Curr Treat Options Cardiovasc Med. 2016;18:69. https://doi.org/10.1007/s11936-016-0487-1.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Kris-Etherton PM, Fleming JA. Emerging nutrition science on fatty acids and cardiovascular disease: nutritionists’ perspectives. Adv Nutr. 2015;6:326S–37S. https://doi.org/10.3945/an.114.006981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. • Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos. Lancet. 1971;1:1143–5. Landmark observational trial of the impact of n-3FA on reducing CV risk.

    Article  CAS  PubMed  Google Scholar 

  14. Dyerberg J, Bang HO. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet. 1979;2:433–5.

    Article  CAS  PubMed  Google Scholar 

  15. Schuchardt JP, Hahn A. Bioavailability of long-chain omega-3 fatty acids. Prostaglandins, Leukot, Essent Fatty Acids. 2013;89(1):1–8. https://doi.org/10.1016/j.plefa.2013.03.010.

    Article  CAS  Google Scholar 

  16. •• Calder PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta. 2015;1851:469–84. https://doi.org/10.1016/j.bbalip.2014.08.010. Excellent review of the ant-inflammatory effects of n-3FAs.

    Article  CAS  PubMed  Google Scholar 

  17. Fialkow J. Omega-3 fatty acid formulations in cardiovascular disease: dietary supplements are not substitutes for prescription products. Am J Cardiovasc Drugs. 2016;16:229–39. https://doi.org/10.1007/s40256-016-0170-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Prescribing information for Lovaza. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021654s023lbl.pdf. Accessed July 21, 2017.

  19. Prescribing information for Vascepa. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/202057s012lbl.pdf. Accessed July 21, 2017.

  20. Prescribing information for Omytrg. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204977s000lbl.pdf. Accessed July 21, 2017.

  21. Prescribing information for Epanova. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205060s000lbl.pdf. Accessed July 21, 2017.

  22. Weintraub HS. Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014;126:7–18. https://doi.org/10.3810/pgm.2014.11.2828.

    Article  PubMed  Google Scholar 

  23. Ito MK. A comparative overview of prescription omega-3 fatty acid products. Pharmacy and Therapeutics. 2015;40:826–57.

    PubMed  PubMed Central  Google Scholar 

  24. Davidson MH, Johnson J, Rooney MW, Kyle ML, Kling DF. A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3 acid ethyl esters: the ECLIPSE (Epanova® compared to Lovaza® in a pharmacokinetic single-dose evaluation) study. J Clin Lipidol. 2012;6(6):573–84. https://doi.org/10.1016/j.jacl.2012.01.002.

    Article  PubMed  Google Scholar 

  25. Raposo HF, Patricio PR, Simoes MC, Oliveira HC. Fibrates and fish oil, but not corn oil, up-regulate the expression of the cholesterol ester transfer protein (CETP) gene. J Nutr Biochem. 2014;25(6):669–74. https://doi.org/10.1016/j.jnutbio.2014.02.008.

    Article  CAS  PubMed  Google Scholar 

  26. Graversen CB, Lundbye-Christensen S, Thomsen B, Christensen JH, Schmidt EB. Marine n-3 polyunsaturated fatty acids lower plasma proprotein convertase subtilisin kexin type 9 in pre- and postmenopausal women: a randomised study. Vasc Pharmacol. 2016;76:37–41. https://doi.org/10.1016/j.vph.2015.07.001.

    Article  CAS  Google Scholar 

  27. • Karalis DG. A review of clinical practice guidelines for the management of hypertriglyceridemia: a focus on high dose omega-3 fatty acids. Adv Ther. 2017;34:300–23. https://doi.org/10.1007/s12325-016-0462-y. Excellent review on the management of hypertriglyceridemia.

    Article  CAS  PubMed  Google Scholar 

  28. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997;4:385–91.

    Article  CAS  PubMed  Google Scholar 

  29. Pownall HJ, Brauchi D, Kilinc C, Osmundsen K, Pao Q, Payton-Ross C, et al. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins. Atherosclerosis. 1999;143(2):285–97. https://doi.org/10.1016/S0021-9150(98)00301-3.

    Article  CAS  PubMed  Google Scholar 

  30. Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, et al. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29(7):1354–67. https://doi.org/10.1016/j.clinthera.2007.07.018.

    Article  CAS  PubMed  Google Scholar 

  31. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the multi-center, placebo-controlled, randomized, double-blind, 12-week study with an open-label extension [MARINE] trial). Am J Cardiol. 2011;108:682–90. https://doi.org/10.1016/j.amjcard.2011.04.015.

    Article  CAS  PubMed  Google Scholar 

  32. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984–92. https://doi.org/10.1016/j.amjcard.2012.05.031.

    Article  CAS  PubMed  Google Scholar 

  33. Kastelein JJ, Maki KC, Susekov A, Ezhov M, Nordestgaard BG, Machielse BN, et al. Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial. J Clin Lipidol. 2014;8:94–106. https://doi.org/10.1016/j.jacl.2013.10.003.

    Article  PubMed  Google Scholar 

  34. Maki KC, Orloff DG, Nicholls SJ, Dunbar RL, Roth EM, Curcio D, et al. A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT trial). Clin Ther. 2013;35:1400–11. https://doi.org/10.1016/j.clinthera.2013.07.420.

    Article  CAS  PubMed  Google Scholar 

  35. Jacobson TA, Glickstein SB, Rowe JD, Soni PN. Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review. J Clin Lipidol. 2012;6(1):5–18. https://doi.org/10.1016/j.jacl.2011.10.018.

    Article  PubMed  Google Scholar 

  36. Robinson JG, Stone NJ. Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids. Am J Cardiol. 2006;98(suppl):39i–49i. https://doi.org/10.1016/j.amjcard.2005.12.026.

    Article  CAS  PubMed  Google Scholar 

  37. Nestel PJ, Shige H, Pomeroy SE, Cehun M, Abbey M, Raederstorff D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am J Clin Nutr. 2002;76:326–30.

    CAS  PubMed  Google Scholar 

  38. Nestel PJ, Pomeroy SE, Sasahara T, Yamashita T, Liang YL, Dart AM, et al. Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability. Arterioscler Thromb Vasc Biol. 1997;17:1163–70.

    Article  CAS  PubMed  Google Scholar 

  39. Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis. Atherosclerosis. 2015;242:357–66. https://doi.org/10.1016/j.atherosclerosis.2015.07.035.

    Article  CAS  PubMed  Google Scholar 

  40. Bays HE, Ballantyne CM, Braeckman RA, Stirtan WG, Soni PN. Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies. Am J Cardiovasc Drugs. 2013;13(1):37–46. https://doi.org/10.1007/s40256-012-0002-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mason RP, Jacob RF. Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism. Biochim Biophys Acta. 2015;1848:502–9. https://doi.org/10.1016/j.bbamem.2014.10.016.

    Article  CAS  PubMed  Google Scholar 

  42. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systemic review. Atherosclerosis. 2006;189:19–30. https://doi.org/10.1016/j.atherosclerosis.2006.02.012.

    Article  CAS  PubMed  Google Scholar 

  43. Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willet WC, Rimm EB. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation. 2003;108:155–60. https://doi.org/10.1161/01.CIR.0000079224.46084.C2.

    Article  CAS  PubMed  Google Scholar 

  44. Geelen A, Brouwer IA, Schouten EG, Kluft C, Katan MB, Zock PL. Intake of n-3 fatty acids from fish does not lower serum concentrations of C-reactive protein in healthy subjects. Eur J Clin Nutr. 2004;58:1440–2. https://doi.org/10.1038/sj.ejcn.1601986.

    Article  CAS  PubMed  Google Scholar 

  45. Madsen T, Christensen JH, Blom M, Schmidt EB. The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a dose-response study. Br J Nutr. 2003;89:517–22. https://doi.org/10.1079/BJN2002815.

    Article  CAS  PubMed  Google Scholar 

  46. Micallef MA, Munro IA, Garg ML. An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. Eur J Clin Nutr. 2009;63:1154–6. https://doi.org/10.1038/ejcn.2009.20.

    Article  CAS  PubMed  Google Scholar 

  47. Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, 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 Engl J Med. 1989;320:265–71.

    Article  CAS  PubMed  Google Scholar 

  48. 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 Engl J Med. 1985;312:1217–24.

    Article  CAS  PubMed  Google Scholar 

  49. Sperling RI, Benincaso AI, Knoell CT, Larkin JK, Austen KF, Robinson DR, et al. Dietary n-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Investig. 1993;91:651–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ. The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable or fish oil. Am J Clin Nutr. 1996;63:116–22.

    CAS  PubMed  Google Scholar 

  51. Bannenberg G, Serhan CN. Specialized pro-resolving lipid mediators in the inflammatory response: an update. Biochim Biophys Acta. 2010;1801:1260–73. https://doi.org/10.1016/j.bbalip.2010.08.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Poreba M, Mostowik M, Siniarski A, Golebiowska-Wiatrak R, Malinowski KP, Haberka M, et al. Treatment with high-dose n-3 PUFAS has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes. Cardiovasc Diabetol. 2017;16:50. https://doi.org/10.1186/s12933-017-0523-9.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Yamakawa K, Shimabukuro M, Higa N, Asahi T, Ohba K, Arasaki O, et al. Eicosapentaenoic acid supplementation changes fatty acid composition and corrects endothelial dysfunction in hyperlipidemic patients. Cardiol Res Pract. 2012;2012:754181. https://doi.org/10.1155/2012/754181.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet. 2003;361(9356):477–85. https://doi.org/10.1016/S0140-6736(03)12468-3.

    Article  CAS  PubMed  Google Scholar 

  55. Nishio R, Shinke T, Otake H, Nakagawa M, Nagoshi R, Inoue T, et al. Stabilizing effect of combined eicosapentaenoic acid and statin therapy on coronary thin-cap fibroatheroma. Atherosclerosis. 2014;234(1):114–9. https://doi.org/10.1016/j.atherosclerosis.2014.02.025.

    Article  CAS  PubMed  Google Scholar 

  56. Yamano T, Kubo T, Shiono Y, Shimamura K, Orii M, Tanimoto T, et al. Impact of eicosapentaenoic acid treatment on the fibrous cap thickness in patients with coronary atherosclerotic plaque: an optical coherence tomography study. J Atheroscler Thromb. 2015;22(1):52–61. https://doi.org/10.5551/jat.25593.

    Article  PubMed  Google Scholar 

  57. Doi H, Kugiyama K, Oka H, Sugiyama S, Ogata N, Koide SI, et al. Remnant lipoproteins induce proatherothrombogenic molecules in endothelial cells through a redox-sensitive mechanism. Circulation. 2000;102(6):670–6. https://doi.org/10.1161/01.CIR.102.6.670.

    Article  CAS  PubMed  Google Scholar 

  58. Vanschoonbeek K, Feijge MA, Paquay M, Rosing J, Saris W, Kluft C, et al. Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation. Arterioscler Thromb Vasc Biol. 2004;24:1734–40. https://doi.org/10.1161/01.ATV.0000137119.28893.0b.

    Article  CAS  PubMed  Google Scholar 

  59. McEwen BJ, Morel-Kopp MC, Tofler GH, Ward CM. The effect of omega-3 polyunsaturated fatty acids on fibrin and thrombin generation in healthy subjects and subjects with cardiovascular disease. Semin Thromb Hemost. 2015;41(3):315–22. https://doi.org/10.1055/s-0034-1395352.

    Article  CAS  PubMed  Google Scholar 

  60. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090–8. https://doi.org/10.1016/s0140-6736(07)60527-3.

    Article  CAS  PubMed  Google Scholar 

  61. Begtrup KM, Krag AE, Hvas AM. No impact of fish oil supplements on bleeding risk: a systematic review. Dan Med J. 2017;64(5):A5366.

    PubMed  Google Scholar 

  62. Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circulation. 2005;112(13):1945–52. https://doi.org/10.1161/CIRCULATIONAHA.105.556886.

    Article  CAS  PubMed  Google Scholar 

  63. Wang Q, Liang X, Wang L, Lu X, Huang J, Cao J, et al. Effect of omega-3 fatty acids supplementation on endothelial function: a meta-analysis of randomized controlled trials. Atherosclerosis. 2012;221(2):536–43. https://doi.org/10.1016/j.atherosclerosis.2012.01.006.

    Article  CAS  PubMed  Google Scholar 

  64. Weisman D, Beinart R, Erez A, Koren-Morag N, Goldenberg I, Eldar M, et al. Effect of supplemented intake of omega-3 fatty acids on arrhythmias in patients with ICD: fish oil therapy may reduce ventricular arrhythmia. J Interv Card Electrophysiol. 2017;49(3):255–61. https://doi.org/10.1007/s10840-017-0267-1.

    Article  PubMed  Google Scholar 

  65. Jenkins DJ, Josse AR, Dorian P, Burr ML, LaBelle TR, Kendall CW, et al. Heterogeneity in randomized controlled trials of long chain (fish) omega-3 fatty acids in restenosis, secondary prevention and ventricular arrhythmias. J Am Coll Nutr. 2008;27(3):367–78.

    Article  CAS  PubMed  Google Scholar 

  66. Khoueiry G, Abi Rafeh N, Sullivan E, Saiful F, Jaffery Z, Kenigsberg DN, et al. Do omega-3 polyunsaturated fatty acids reduce risk of sudden cardiac death and ventricular arrhythmias? A meta-analysis of randomized trials. Heart Lung. 2013;42(4):251–6. https://doi.org/10.1016/j.hrtlng.2103.03.006.

    Article  PubMed  Google Scholar 

  67. Mozaffarian D, Marchioli R, Macchia A, Silletta MG, Ferrazzi P, Gardner TJ, et al. Fish oil and post-operative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial. JAMA. 2012;308:2001–11. https://doi.org/10.1001/jama2012.28733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pressure response to fish oil supplementation: meta-regression analysis of randomized trials. J Hypertens. 2002;20(8):1493–9.

    Article  CAS  PubMed  Google Scholar 

  69. Miller PE, Van Elswyk M, Alexander DD. Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials. Am J Hypertens. 2014;27(7):885–96. https://doi.org/10.1093/ajh/hpu024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Minihane AM, Armah CK, Miles EA, et al. Consumption of fish oil providing amounts of eicosapentaenoic acid and docosahexaenoic acid that can be obtained from the diet reduces blood pressure in adults with systolic hypertension: a retrospective analysis. J Nutr. 2016;146(3):516–23. https://doi.org/10.3945/jn.115.220475.

    Article  CAS  PubMed  Google Scholar 

  71. Friedberg C, Janssen M, Heine R, Grobbee D. Fish oil and glycemic control in diabetes: a meta-analysis. Diabetes Care. 1998;21:494–500.

    Article  CAS  PubMed  Google Scholar 

  72. Mori T, Burke V, Puddey IB, Shaw JE, Berlin L. Effect of fish diets and weight loss on serum leptin concentration in overweight, treated hypertensive subjects. J Hypertens. 2004;22:1983–90.

    Article  CAS  PubMed  Google Scholar 

  73. Helland A, Bratlie M, Hagen IV, Mjos SA, Sornes S, Ingvar Halstensen A, et al. High intake of fatty fish, but not lean fish, improved postprandial glucose regulation and increased the n-PUFA content in the leucocyte membrane in healthy overweight adults: a randomised trial. Br J Nutr. 2017;117(10):1368–78. https://doi.org/10.1017/S0007114517001234.

    Article  CAS  PubMed  Google Scholar 

  74. Methodology manual and policies. From the ACCF/AHA Task Force on Practice Guidelines. June 2010. Available at http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/documents/downloadable/ucm_319826.pdf. Accessed August 3, 2017.

  75. Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, et al. The VITamin D and OmegA-3 Trial (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials. 2012;33(1):159–71. https://doi.org/10.1016/j.cct.2011.09.009.

    Article  CAS  PubMed  Google Scholar 

  76. ORIGIN Trial Investigators, Bosch J, Gerstein HC, Dagenais GR, Diaz R, Dyal L, et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367:309–18. https://doi.org/10.1056/NEJMoa1203859.

    Article  Google Scholar 

  77. Risk and Prevention Study Collaborative Group, Roncaglioni MC, Tombesi M, Avanzini F, Barlera S, Caimi V, et al. n-3 fatty acids in patients with multiple cardiovascular risk factors [published correction appears in N Engl J Med. 2013;368:2146]. N Engl J Med. 2013;368:1800–8. https://doi.org/10.1056/NEJMoa1205409.

    Article  Google Scholar 

  78. Writing Group for the AREDS2 Research Group, Bonds DE, Harrington M, Worrall BB, Bertoni AG, Eaton CB, et al. Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular disease outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med. 2014;174:763–71. https://doi.org/10.1001/jamainternmed.2014.328.

    Article  Google Scholar 

  79. GISSI-Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999;354(9177):447–55.

    Article  Google Scholar 

  80. Kromhout D, Giltay EJ, Geleijnse JM, for the Alpha Omega Trial Group. N-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010;363(21):2015–26. https://doi.org/10.1056/NEJMoa1003603.

    Article  CAS  PubMed  Google Scholar 

  81. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and Reinfarction Trial (DART). Lancet. 1989;2:757–61.

    Article  CAS  PubMed  Google Scholar 

  82. Rauch B, Schiele R, Schneider S, Diller F, Victor N, Gohlke H, et al. 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. 2010;122:2152–9. https://doi.org/10.1161/CIRCULATIONAHA.110.948562.

    Article  CAS  PubMed  Google Scholar 

  83. Galan P, Kesse-Guyot E, Czemichow S, Briancon S, Blacher J, Hercberg S, et al. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ. 2010;341:c6273. https://doi.org/10.1136/bmj.c6273.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systemic review and meta-analysis. JAMA. 2012;308:1024–33. https://doi.org/10.1001/2012.jama.11374.

    Article  CAS  PubMed  Google Scholar 

  85. ASCEND: A Study of Cardiovascular Events iN Diabetes. Available at https://clinicaltrial.gov/ct2/show/NCT00135226. Accessed August 1, 2017.

  86. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, et al. 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. 2008;372(9645):1223–30. https://doi.org/10.1016/S0140-6736(08)61239-8.

    Article  PubMed  Google Scholar 

  87. Alexander DD, Miller PE, Van Elswyk ME, Kuratko CN, Bylsma LC. A meta-analysis of randomized controlled trials and prospective cohort studies of eicosapentaenoic and docosahexaenoic long-chain omega-3 fatty acids and coronary heart disease risk. Mayo Clin Proc. 2017;92(1):15–29. https://doi.org/10.1016/j.mayocp.2016.10.018.

    Article  CAS  PubMed  Google Scholar 

  88. Casula M, Soranna D, Catapano AL, Corrao G. Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: a meta-analysis of randomized, placebo controlled trials [corrected]. Atheroscler Suppl. 2013;14(2):243–51.

    Article  PubMed  Google Scholar 

  89. Bhatt DL, Steg PG, Brinton EA, Jacobson TA, Miller M, Tardif JC, et al. Rationale and design of REDUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial. Clin Cardiology. 2017;40:138–48. https://doi.org/10.1002/clc.22692.

    Article  Google Scholar 

  90. ClinicalTrials.gov. A study of AMR101 to evaluate its ability to reduce cardiovascular events in high risk patients with hypertriglyceridemia and on statin. The primary objective is to evaluate the effect of 4 g/day AMR101 for preventing the occurrence of a first major cardiovascular event (REDUCE-IT). Available at https://clinicaltrials.gov/ct2/show/NCT01492361. Accessed July 7, 2017.

  91. ClinicalTrials.gov. Outcomes study to assess statin residual risk reduction with Epanova in high CV risk patients with hypertriglyceridemia (STRENGTH). Available at https://clinicaltrials.gov/ct2/show/NCT02104817. Accessed July 7, 2017.

  92. Kris-Etherton PM, Harris WS, Appel LJ, for the American Heart Association, Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106(21):2747–57. https://doi.org/10.1161/01.CIR.0000038493.65177.94.

    Article  PubMed  Google Scholar 

  93. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123:2292–333. https://doi.org/10.1161/CIR.0b013e3182160726.

    Article  PubMed  Google Scholar 

  94. Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1—full report. J Clin Lipidol. 2015;9(2):129–69. https://doi.org/10.1016/j.jacl.2015.02.003.

    Article  PubMed  Google Scholar 

  95. Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton PM, Sikand G, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015;9(6 Suppl):S1–122.e1. https://doi.org/10.1016/j.jacl.2015.09.002.

    Article  PubMed  Google Scholar 

  96. Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(9):2969–89. https://doi.org/10.1210/jc.2011-3213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999–3058. https://doi.org/10.1093/eurheartj/ehw272.

    Article  Google Scholar 

  98. National Institutes of Health, National Center for Complementary and Integrative Health. Using dietary supplements wisely. Available at https://www.cdc.gov/nchs/databriefs/db61.htm. Accessed August 4, 2017.

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Pennsylvania Health System, 3400 Spruce Street, Philadelphia, PA, 19104, USA

    Megan F. Burke

  2. Department of Medicine, Division of Cardiology, University of Pennsylvania Health System, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA

    Frances M. Burke

  3. Department of Medicine, Divisions of Internal Medicine and Cardiology, Perelman Center for Advanced Medicine, University of Pennsylvania Health System, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA

    Daniel E. Soffer

Authors
  1. Megan F. Burke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frances M. Burke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel E. Soffer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel E. Soffer.

Ethics declarations

Conflict of Interest

Megan F. Burke and Frances M. Burke declare no conflict of interest.

Dr. Soffer reports that he has participated as a local investigator in pharmaceutical company-sponsored clinical trials that provide program support. He has been an investigator with Akcea, Ionis, Novartis, Pfizer, Regeneron, Sanofi, Amgen, Omthera/Astra Zeneca, Regenex/NIH, and Kowa pharmaceuticals, outside the submitted work. He has also received faculty payment for services as a course director for the National Lipid Association.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Nonstatin Drugs

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Burke, M.F., Burke, F.M. & Soffer, D.E. Review of Cardiometabolic Effects of Prescription Omega-3 Fatty Acids. Curr Atheroscler Rep 19, 60 (2017). https://doi.org/10.1007/s11883-017-0700-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11883-017-0700-z

Keywords

Search

Navigation