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A recent study unearths a nuance in the role of omega-3s in heart health. Photo editing by Stephen Kelly; Yulia Reznikov/Getty Images
  • Omega-3 supplements often contain a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
  • Several clinical trials have shown that only high dose EPA supplements appear to reduce major adverse cardiovascular events.
  • A new study that measured omega-3s in people’s blood found that high levels of EPA were associated with a lower risk of cardiovascular events, whereas DHA appeared to counter the beneficial effects of EPA.
  • The findings suggest that combining EPA and DHA in a supplement may void any potential benefits for heart health.

Seafood — particularly oily fish, such as salmon, mackerel, and tuna — is a rich natural source of omega-3 fatty acids. A wealth of evidence suggests that individuals who eat seafood between one and four times a week are less likely to die of heart disease than those who do not.

Many people take supplements that contain omega-3 fatty acids in the belief that these will also help protect them against cardiovascular disease. However, evidence from clinical trials investigating the benefits of these supplements for heart health has been mixed.

Some research suggests that only high doses of EPA appear to reduce the risk of major adverse cardiovascular events, including heart attack, stroke, and heart failure. However, a recently published clinical trial found no reduction in risk for people with high cardiovascular risk who took a supplement that contained a combination of EPA and DHA.

The results of a new study, which the researchers presented at the virtual 2021 conference of the American College of Cardiology, suggest a possible explanation.

The researchers, from Intermountain Healthcare’s Heart Institute in Salt Lake City, UT, found that although high levels of EPA in the blood were associated with a reduced risk of major cardiac events and death, rising levels of DHA appeared to negate these benefits.

“The advice to take omega-3s for the good of your heart is pervasive, but previous studies have shown that science doesn’t really back this up for every single omega-3,” says principal investigator Viet T. Le, a cardiovascular physician assistant at the institute.

“Our findings show that not all omega-3s are alike and that EPA and DHA combined together, as they often are in supplements, may void the benefits that patients and their doctors hope to achieve,” he added.

The team has submitted the study for publication.

For their study, the researchers drew on Intermountain Healthcare’s INSPIRE registry, which includes about 35,000 blood samples from nearly 25,000 patients and their medical records.

They randomly selected 987 individuals who had received a first heart scan at Intermountain Healthcare between 1994 and 2012 and quantified their plasma levels of EPA and DHA.

The average age of those included was 61.5 years. At the time of their scan, 41% had obesity, and 42% had severe coronary artery disease.

Over the next 10 years, 31.5% of all the patients had a major adverse cardiovascular event, which the team defined as all-cause death, heart attack, stroke, or heart failure.

The researchers discovered that people with the highest levels of EPA in their blood at the time of their first scan were less likely to experience a major cardiovascular event.

However, rising levels of DHA appeared to blunt the beneficial effects of EPA.

Those with more DHA than EPA in their blood had an increased risk of heart problems compared with those with higher levels of EPA.

These associations remained after accounting for preexisting illnesses, namely severe coronary artery disease, chronic obstructive pulmonary disease (COPD), and heart failure.

“Based on these and other findings, we can still tell our patients to eat omega-3 rich foods, but we should not be recommending them in pill form as supplements or even as combined (EPA + DHA) prescription products,” concludes Le.

Le told Medical News Today that the available data from the INSPIRE registry did not allow the researchers to determine whether people were getting their omega-3s from their diet, supplements, or a combination of both.

However, he pointed out that two randomized clinical trials have found heart benefits for EPA-only supplements, whereas four have shown no benefits from combinations of EPA and DHA.

He noted that these trials involved pharmacy-grade supplements, whereas “off-the-shelf” omega-3 products are unlikely to meet such high standards of purity. In addition, commercial supplements do not give consumers the option of taking EPA without DHA.

Le conceded that the relative levels of omega-3s that his team found in the participants’ blood could reflect some other dietary or physiological factor (a “confounder”) that also influenced their heart health risks.

“Yes, that is always possible,” Le said. “This is a prospective analysis of retrospective data and, thus, confounding can occur.”

Andrea Wong, Ph.D., a senior vice president for scientific and regulatory affairs at the Council for Responsible Nutrition (CRN) — a trade association that represents the supplement industry — said that “a large body of evidence” supports the benefits of both EPA and DHA for heart health.

She cited a recent analysis that pooled data from 17 studies and found that higher circulating levels of EPA and DHA, both separately and together, were associated with a lower risk of premature death and death from cardiovascular disease.

Dr. Wong told Medical News Today:

“Supplementing with EPA and DHA omega-3 fatty acids can contribute to heart health, but as one of many healthy habits to maintain a healthy heart. CRN recommends consumers at high risk or those with a history of cardiovascular disease talk with their cardiologist about what supplements are right for them.”