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Omega-3 Supplements: To Use or Not to Use?

November 09, 2018

Omega−3 fatty acids are polyunsaturated fatty acids (PUFAs).  Omega−3 fatty acids are important for normal metabolism.  There are three types of omega−3 fatty acids involved in human physiology α-linolenic acid, found in plant oils, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both commonly found in marine oils.1 Marine algae and phytoplankton are also primary sources of omega−3 fatty acids. Common plant and oil sources of omega-3 fatty acids are walnuts, clary sage seed oil, algal oil, flaxseed oil, and hemp oil.  Animal sources of omega−3 fatty acids EPA and DHA include fish, fish oils, eggs from chickens fed EPA and DHA, squid oils, and krill oil.2-3 Observation studies suggest that fish consumption once or twice a week is associated with a reduced risk of heart disease.4-8  Omega-3 fatty acid supplementation however, does not appear to affect the risk of death, cancer or heart disease.2-3, 9-10

The American Heart Association Guidelines currently recommend omega-3 fatty acids supplements for secondary prevention of cardiovascular events.  Controversy has continued from randomized fish oil supplement studies and meta-analyses which have reported failure to prevent cardiovascular events. Should the Guidelines be reconsidered?  Possibly, but a recent study, announced only by the sponsor, and not presented in abstract or in a manuscript may offer limited support for the AHA. 

REDUCE-IT is a randomized, placebo-controlled study of 8,179 statin-treated adults with elevated CV risk. REDUCE-IT demonstrated an approximately 25% relative risk reduction (p<0.001) in major adverse CV events (MACE) in an intent-to-treat patient population with use of icosapent ethyl 4 grams/day versus placebo.11 Median follow-up time in REDUCE-IT was 4.9 years.  REDUCE-IT patients inclusion criteria was an LDL-C between 41-100 mg/dL controlled by statin therapy with persistent elevated triglycerides (TGs) between 150-499 mg/dL and either established cardiovascular disease (secondary prevention cohort) or diabetes mellitus and at least one other CV risk factor (primary prevention cohort).  Icosopent ethyl was well tolerated.  Patients experienced adverse events and serious adverse events similar between the active and placebo treatment groups.

So what is the difference between earlier studies and REDUCE-IT?  Icosopent ethyl at 4 grams/day may provide additional cardiovascular risk reduction benefit on top of LDL-C control with standard of care statin therapy. REDUCE-IT results should not be generalized to fenofibrate, fish oil or omega-3 mixture products that contain DHA. A cautionary note is that the results of this study have not been presented in a form that allow scientific rigor to be assessed.  However, this agent may have benefit in patients with hyperlipidemia, controlled on a statin  and various cardiovascular risk factors including persistent elevated triglycerides (TGs) between 150-499 mg/dL (median baseline 216 mg/dL) and either established cardiovascular disease (secondary prevention cohort) or diabetes mellitus and at least one other CV risk factor (primary prevention cohort).

Mark A. Munger, PharmD, FCCP, FACC, is a professor of pharmacotherapy and adjunct professor of internal medicine, at the University of Utah, where he also serves as the associate dean of Academic Affairs for the College of Pharmacy.

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  1. Scorletti E, Byrne CD. Omega−3 fatty acids, hepatic lipid metabolism, and nonalcoholic fatty liver disease. Annual Review of Nutrition. 2013 33(1): 231–48.
  2. 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 systematic review and meta-analysis. JAMA. 2012 308(10): 1024–33.
  3. MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim YW, Traina SB, Hilton L, Garland R, Morton SC. Effects of omega−3 fatty acids on cancer risk: a systematic review. JAMA: The Journal of the American Medical Association. 2006 295(4): 403–15.
  4. Burr ML, Gilbert F, Holliday RM, Elwood PC, Fehily PC, Rogers S, Sweeknam PM, Dead man NM. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet  1939 334(8866);757-61.
  5. Burr ML, Ashjfield-Watt PA, Dunstan FD, et al. Lack of benefit of dietary advice to men with angina: results of a controlled trial. Eur J Clin Nutr 1003;57:193-200.
  6. Tvazzi L, Maggioni A{P. Marchioli R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. Lancet 2008;372:1223-30.
  7. Kromhout D, Giltay EJ, Geleijnse JM. N-3 Fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 2012;363:2015-26.
  8. The ORIGIN Trial Investigators. n-3 Fatty acids and cardiovascular outcomes in patients with dysflycemia. N Engl J Med 2012;367:309-18.
  9. Kwak SM, Myung SK, Lee YJ, Seo HG. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docusahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med 2012;172:686-94.
  10. Ag T, Halsey J, Kromhout D, et al. Association of omega-3 fatty acid supplement use with cardiovascular diseaes risks: meta-analysis of 10 trials involving 77 917 individuals. JAMA Cardiol 2018;3:225-34.
  11. Vascepa REDUCE-IT Results.  Accessed 10/2018.
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