This past week, the American College of Cardiology’s (ACC) virtual scientific sessions included several presentations that centered around the relationship between the omega 3’s, EPA and DHA and the risk of heart disease.
Before discussing the contentious omega 3 study presented, let me provide a brief historical overview that has led to the current controversy and stems from multiple studies demonstrating heart-related benefits with purified EPA but not with the combination of EPA and DHA.
On the one hand, one might have thought that EPA (eicosapentanoic acid) and DHA (docosahexanoic acid) would behave in a similar manner when it comes to heart protection. After all, eating fish containing EPA and DHA has been shown to be cardioprotective, especially when these polyunsaturated fats replace other animal based saturated fat. In addition, EPA and DHA reduce high triglyceride (fat) levels associated with elevated cardiovascular risk.
To date, however, all studies testing purified EPA have shown favorable results. The first study, entitled JELIS (click here for details) was a Japanese study that found purified EPA to be associated with an approximate 20% reduction in initial and recurrent heart attack events. At the time, many of us were surprised by these results because we did not expect such a robust benefit in a population that already consumes an EPA enriched fish on a regular basis.
Then a second study, entitled REDUCE-IT (click here for details) tested another purified EPA compound (icosapent ethyl) in men and women with high triglycerides and established heart disease or at high risk of a heart attack/stroke (due to a history of diabetes/other risk factors).
REDUCE-IT was embraced by the cardiology community because of the impressive results seen, namely a 25% reduction in heart-related events. Two additional studies known as EVAPORATE (click here for details) and CHERRY (click here for details) provided further evidence of benefit with purified EPA that included less plaque buildup in coronary arteries.
But what about studies testing purified DHA to prevent heart disease? Surprisingly, they don’t exist. Instead, studies assessing DHA have traditionally incorporated EPA and this combination has repeatedly failed to demonstrate cardiovascular benefit. Among the criticisms voiced for the consistent negative results were the relatively low doses of EPA/DHA used and the lack of testing a population with high triglycerides.
To address these limitations, the STRENGTH study was undertaken (click here for details). This was a well conducted study that tested men and women with high triglycerides and used sufficiently high doses of EPA/DHA to lower triglycerides. Unfortunately and like its EPA/DHA predecessors, results of this study were disappointingly neutral with no reduction in cardiovascular events observed.
In other words, all studies to date using purified EPA have shown benefit whereas all studies using the combination of EPA/DHA have not. In fact, pioneering research by my friend and colleague, Dr. Preston Mason has found opposing effects between EPA and DHA, with EPA exhibiting anti-inflammatory, anti-oxidant and other heart protective properties whereas DHA appears to mitigate these as effects. Dr. Mason’s groundbreaking research (summarized here) provides the basis for what has been confirmed in clinical trials, namely, that EPA benefits the heart whereas DHA blunts/attenuates these effects.
To return to last week’s ACC meetings, a sub-study from STRENGTH found no benefit in those subjects who achieved the highest blood levels of EPA in the trial. While these results might appear to directly contradict that of REDUCE IT, it turns out that EPA and DHA were significantly correlated with each other. In other words, patients with the highest levels of EPA were also more likely to exhibit high, if not the highest levels of DHA. As we have seen time and again, DHA and EPA don’t mix well when it comes to optimizing heart health because based on current evidence, DHA offsets the benefits of EPA.
Food for thought: If a bar of gold were contaminated with other metals/alloys, would it still be worth its weight in gold?
As we reel in highlights related to Omega-3’s and your heart, remember these:
- Omega-3 supplements containing EPA and DHA have not been shown to reduce the risk of a heart attack or stroke.
- The prescription form of purified EPA (Icosapent ethyl) reduced heart attacks, strokes & cardiovascular death by 25% in men and women with high triglycerides (135 mg/dL or greater) and elevated heart disease risk.
- For each gram of omega-3 fatty acids consumed, triglyceride levels are reduced 8-10%.
- Fish with a high content of omega-3s are anchovies, herring, mackerel, salmon & sardines.
- Replacement of animal based saturated fat with plant/fish based polyunsaturated fat reduces the risk of heart disease by nearly 30%!
- Excellent sources of plant-based omega-3’s include chia seeds, flaxseeds, soybeans and walnuts.
- Compared to a diet high in saturated animal fats, a diet enriched in plant and fish based omega-3s is associated with a lower risk of heart disease.
Michael Miller, MD is Professor of Cardiovascular Medicine at the University of Maryland School of Medicine in Baltimore, Maryland and author of “Heal Your Heart….”: published by Penguin Random House. He served on the International Steering Committee for the REDUCE-IT trial.