Omega-3s for heart health? Exploring potential benefits and risks

Despite popularity of fish oil omega-3 supplements, big knowledge gaps remain

Chances are, you or someone you know takes fish oil capsules with hopes of preventing heart disease - the leading cause of death. Made from omega-3 fatty acids, which the body cannot make on its own, they are among the most common type of dietary supplement used by U.S. adults, particularly those 60 and over, according to the Centers for Disease Control and Prevention.

But do these supplements really live up to their heart-healthy reputation? The results from clinical trials have been mixed, and a few recent studies even suggest they might cause some harm. That has led scientists to conclude that the supplement's usefulness in heart disease prevention is nuanced, at best. And ongoing research - on everything from the particular omega-3 fatty acids that drive its effectiveness to who benefits most and why - is bearing that out.

Take the Vitamin D and Omega-3 trial called VITAL, the largest randomized, placebo-controlled clinical trial investigating the cardiovascular effects of marine omega-3s in primary prevention. The NIH-funded study enrolled nearly 26,000 U.S. adults aged 50 and older without a history of heart disease, stroke, or cancer and followed them for five years. 

The primary findings, published in the New England Journal of Medicine in 2018, showed that taking 1 gram of omega-3 supplements daily did not significantly lower the overall risk of major cardiovascular disease (CVD) events - a combined measure of heart attacks, stroke, and CVD death. Yet, when researchers analyzed the data further and looked at those who consumed higher amounts of fish versus lower amounts of fish before taking supplements, they found that higher omega-3s were linked to a statistically significant 19% reduction in major CVD events.

Also, when they focused on heart attacks, they found a statistically significant 28% reduction for adults taking omega-3s vs placebo in the overall study population and a 40% reduction in those with low fish intake at baseline. They showed that three groups seemed to get the greatest benefit from omega-3s in reducing heart attack risk: people with low fish intake, those with two or more risk factors for heart disease, and African Americans.

"We think that omega-3s have coronary or heart benefits and some people seem to benefit more than others," said JoAnn E. Manson M.D., Dr.P.H., chief of the division of preventive medicine at Brigham and Women's Hospital and Harvard Medical School and the VITAL trial's principal investigator.

In addition to the reduction in heart attacks found with omega-3s among people who didn't eat much fish, the researchers saw a 44% reduction in heart attacks in people with two or more heart disease risk factors (such as smoking or high blood pressure), and they saw an astounding 77% reduction in African American participants. Researchers suspect that genetic variants related to the synthesis and metabolism of omega-3 fats may play a role in the benefits to the latter group, but further studies are needed.

For reasons the study authors don't yet understand, omega-3s did not affect the risk of stroke compared to placebo. Still, "People who fit into one of these subgroups may want to talk to their clinician about whether either prescription omega-3s or fish oil supplements might be helpful for them," Manson said.

Lawrence J. Fine, M.D., a senior advisor in the clinical applications and prevention branch in the Division of Cardiovascular Sciences at NHLBI, agreed. "All this research is valuable and helping in our understanding of this important nutrient," he said. "But anybody considering taking the supplement should talk to their health care provider about whether it's appropriate for them and remember that a heart-healthy diet is the best way to get an adequate level of omega 3s for most individuals."

Another notable clinical trial, also published in 2018, explored the use of icosapent ethyl - a high-dose, prescription form of an omega-3 fatty acids known as eicosapentaenoic acid (EPA). The researchers tested 4 grams daily in 8,000 people taking statin medication who also had high blood triglycerides, a prior history of CVD, or diabetes and other CVD risk factors. Called the REDUCE-IT trial, the researchers found that daily use of the drug over the five-year study period significantly reduced the risk of major CVD events, including both heart attack and stroke, by 25% in this high-risk population. The trial led to FDA approval for icosapent ethyl for a select group of high-risk patients.

Closing the knowledge gap

And therein lies the big challenge in omega-3 CVD research: there's just a lot that researchers still don't know. Not only are they still uncertain which omega-3 prescription or fish oil supplement forms actually fight heart disease and other CVDs; they also are not sure about the exact fatty acids in fish oil that are responsible for its purported cardioprotective effect - or the mechanisms by which those components might work.

Some studies suggest that there are potential risks associated with fish oil supplements. Those risks include heavy metal contamination, such as from mercury; or oxidation of the oil found in fish oil capsules, which can increase the risk of clogged arteries. Also, in high doses, both prescription omega-3s and fish oil supplements can increase the risk of atrial fibrillation or A-fib, which causes the heart to beat rapidly; and also lead to an increased risk of bleeding. 

"The story of the effects of omega-3 fatty acids on heart disease is still a work in progress," said Manson, who hopes to extend the VITAL trial results to a large trial of EPA. She would like to see if the REDUCE-IT trial results can be replicated using an inert or nonreactive placebo. Also, given that VITAL is the only omega-3 trial with a highly diverse study population, she would like to see if the large benefits among African American participants in VITAL can be replicated, which holds promise for reducing health disparities.

As researchers continue sorting out the effects of prescription omega-3s and fish oil dietary supplements sold in stores and online, Manson said there's no need to panic about using them. However, she strongly cautions against taking high doses of fish oil unless under the supervision of a physician.

"Try to get your omega 3s from a heart-healthy diet that includes fish, rather than relying on fish oil supplements," Manson said.