Continuing evidence for association between omega-3 supplementation and lower cardiovascular disease risk

November 19, 2019

The October 2019 issue of the Journal of the American Heart Association reported the results of an updated meta-analysis that revealed lower risks of myocardial infarction (MI, or heart attack), coronary heart disease deaths, total coronary heart disease events, cardiovascular disease deaths and total cardiovascular disease events in association with marine omega-3 fatty acid supplementation.

The current meta-analysis updates an earlier analysis of ten randomized, controlled trials that included 77,917 participants, published in JAMA Cardiology in 2018. For the new meta-analysis, JoAnn E. Manson and her colleagues added three recent randomized controlled trials: the ASCEND (A Study of Cardiovascular Events in Diabetes) trial, which included 15,480 diabetics, VITAL (Vitamin D and Omega-3 Trial), which included 25,871 participants at risk of cardiovascular disease, and REDUCE-IT (Reduction of Cardiovascular Events of Icosapent Ethyl-Intervention Trial), which found benefits for a high dose (4,000 milligrams per day) of a purified form of the omega-3 fatty acid EPA in an investigation that included 8,179 men and women.

Pooled analysis of the trials’ results (not including the results of REDUCE-IT) revealed an 8% reduction in the risk of fatal and/or nonfatal heart attack, an 8% reduction in the risk of coronary heart disease death, a 5% reduction in the risk of total coronary heart disease events (defined as MI, death from coronary heart disease, or coronary revascularization), a 7% reduction in the risk of death from cardiovascular disease and a 3% reduction in the risk of total cardiovascular disease events (nonfatal MI, nonfatal stroke, death from cardiovascular disease, or hospitalization because of a cardiovascular cause) in association with omega-3 fatty acid supplementation in comparison with the control subjects. Adding the findings of the exceptional REDUCE-IT investigation to the analysis further reduced the risk of these outcomes in association with omega-3 supplementation. Risk for heart attack was lowered to 12% and total coronary heart disease to 7% among omega-3 treated subjects compared to the controls. An association was observed between increasing doses of omega-3 and declining total cardiovascular disease event risk levels both with and without the inclusion of REDUCE-IT.

“The current updated meta-analysis incorporating data from 13 RCTs, including 3 recent large trials, suggests that marine omega-3 supplementation is associated with lower risk of MI, total coronary heart disease, total cardiovascular disease, and death from coronary heart disease or cardiovascular disease causes,” the authors conclude. “Such inverse associations may be particularly evident at higher doses of marine omega-3 supplementation.”

Their conclusion is reflected in a new review titled “Sea Change for Marine Omega-3s: Randomized Trials Show Fish Oil Reduces Cardiovascular Events,” that appeared on October 15, 2019 in Mayo Clinic Proceedings. Noting the recent publication of the findings of the trials that were added to the updated meta-analysis described above, authors Evan L. O’Keefe, MS, and colleagues observe, “In recent years, many people ceased omega-3 supplementation after a run of publicity suggested no benefit for fish oil. It now appears that these studies were either too small or studied populations already consuming high levels of omega-3 in their diets or did not provide a high-enough dose of EPA/DHA to achieve cardioprotective omega-3 levels. With REDUCE-IT, ASCEND and VITAL, we now have a clearer picture of the potential long-term benefits that can accrue from taking EPA alone or combined EPA/DHA.”

“Taking an omega-3 product that supplies between 500 to 4000 mg per day of EPA plus DHA appears to be an effective, safe and affordable strategy for improving long-term cardiovascular health, particularly for high-risk persons who have elevated triglyceride levels and for people who do not consume fish regularly,” they conclude.

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Apply What You’ve Learned: Cardiovascular Disease

  • Ischemic heart disease is the leading cause of death, but it doesn’t have to be.1 The American Heart Association estimates that 80% of cardiovascular disease is preventable.2
  • Know your risk. Regular blood pressure monitoring and blood testing can help. In addition to standard blood tests that measure cholesterol and triglycerides, knowing one’s level of homocysteine, C-reactive protein (CRP), omega-3 and other factors is helpful. Age, smoking status, whether one has diabetes and the presence of obesity also play a role in determining cardiovascular disease risk.
  • You’ve heard it all before, but it bears repeating—consuming a healthy diet that contains plenty of fruits and vegetables, engaging in regular physical activity, maintaining a healthy body weight and managing stress can go a long way toward preventing cardiovascular disease, as well as many other diseases.
  • In addition to consuming an optimal amount of fruit and vegetables, supplementing the diet with the amino acid L-arginine, coenzyme Q10 (CoQ10), selenium, vitamins C and E, garlic and more may help further support cardiovascular health.3-5


  1. “The Top 10 Causes of Death,” World Health Organization, 24 May 2018,
  2. “CDC Prevention Programs,” American Heart Association, 18 May 2018,
  3. Yin WH et al. Clin Nutr. 2005 Dec;24(6):988-97.
  4. Shargorodsky M et al. Nutr Metab (Lond). 2010 Jul 6;7:55.
  5. Koscielny J et al. Atherosclerosis. 1999 May;144(1):237-49.

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