Cardiologist follows the science to a new conclusion on fish oil supplements l Expert Opinion

I have been a long-term proponent of fish oil supplements to prevent heart disease. I did a radio show every Sunday night for several years talking about the importance of lifestyle changes combined with taking high dose omega-3 fatty acids to help prevent coronary problems. There was good science behind it at the time, as fish oil had been shown to be anti-inflammatory, several studies had demonstrated a lower risk of heart attacks, and there seemed to be no downside risk. There were few side effects other than burping up an occasional taste of fish.

In 2019 the global market for omega-3 fatty acids reached $4.1 billion.

Over the last couple of years, there have been several studies that have questioned the benefit of fish oil supplements. The exception has been a trial called REDUCE-IT, in which a highly purified fish oil called Vascepa (icosapent ethyl) was used. This study examined people with high triglycerides and high cholesterol who were already on a statin to lower their cholesterol, and who had heart disease. It showed a 25% decrease in cardiac risk compared to half the participants in the study who took a placebo, which was mineral oil. The results were so impressive that Vascepa has become a hugely successful prescription product, with sales of $614 million in 2020, up 40% from 2019.

Another trial called STRENGTH looked at a similar group of people, and it used a slightly different fish oil preparation. It showed no difference between the fish oil and a placebo, which was corn oil.

No one has been able to reconcile the different results of these two trials.

Fish oil contains two omega-3 fatty acids called docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

In a study released this month at the American College of Cardiology (ACC) meeting and simultaneously published in JAMA Cardiology, authors noted that while Vascepa is pure EPA, the STRENGTH oil was a mixture of DHA and EPA.

But the STRENGTH investigators looked at EPA and DHA blood levels in their participants. If EPA is good for you and DHA bad, then the group that had the highest blood levels of EPA, which was similar to the levels found in REDUCE-IT, would have been expected to do better. They did not.

Another reason has been suggested. It is possible that the placebo in REDUCE-IT was not a placebo at all. It was mineral oil, which can be inflammatory. In other words, the group that did well taking fish oil might have only done well because the placebo group was harmed, magnifying the difference.

Until a new trial is done comparing Vascepa to a different, inert placebo, we will not know if it is effective or it was compared to the wrong placebo.

One of the main reasons that I have recommended fish oil to patients for years has been the idea that it did no harm. In a recent meta-analysis (a review and analysis of multiple trials) published in the European Society of Cardiology, the authors found that people treated for high triglycerides with high dose (4 grams per /day) fish oil had more atrial fibrillation, an irregular heart rhythm. This analysis included everyone who participated in the STRENGTH and REDUCE-IT trials. The conclusion: People receiving fish oil had a significantly greater risk of atrial fibrillation, which can lead to a higher risk of stroke. The Vital Rhythm Study, published in JAMA in March, randomized 12,542 participants to receive a smaller dose of omega-3 fatty acids (847 mg of mixed DHA/EPA), and 12,577 people to receive a placebo containing olive oil. This trial did not show a significant incidence of atrial fibrillation, suggesting lower doses may be safer, but do not potentially help with prevention.

Fish oil can no longer be considered harmless. In high doses, it can increase the risk of developing atrial fibrillation.

It has been shown to be effective in just one major trial, and its results are now controversial. It was tested only in people with known coronary disease who already are taking a statin, and at high doses of 4 grams per day. Other groups of people either do not benefit or have never been tested.

In the future, based on these new studies, I will not be recommending fish oil to my patients to help prevent cardiac issues. Following the science can lead to unexpected places.

Of note: Every study done to date affirms the importance of diet, exercise, and weight loss to prevent cardiac problems, albeit without the use of fish oil supplements.

David Becker is a board-certified cardiologist with Chestnut Hill Temple Cardiology in Flourtown. He has been in practice for more than 30 years.