Does taking fish oil pills actually protect your heart?

"With heart healthy Omega-3s,” says the label of Nature Made Fish Oil Gummies.

Fish oil is big business.

Do supplements or drugs that supply EPA, DHA, or both omega-3 fats cut the risk of a heart attack, stroke, or other cardiovascular event? In 2020, scientists reported surprising new findings.

The STRENGTH trial

In the STRENGTH trial, researchers randomly assigned roughly 13,000 people to take 4,000 milligrams a day of either fish oil (which contains EPA and DHA) or corn oil (which contains neither) for about three years.

“The trial was focused on patients who had high triglycerides, low HDL, and either established cardiovascular disease or a high risk for development of cardiovascular disease,” noted Michael Lincoff, professor of medicine at the Cleveland Clinic Lerner College of Medicine, at the American Heart Association’s Scientific Sessions 2020. All of the participants were also taking statins.

The trial used Epanova, a drug that contains EPA and DHA made by AstraZeneca, which funded the research.

“We specifically used a corn oil placebo because it’s a neutral placebo, unlike mineral oil, which does have some adverse effects on cardiovascular markers,” explained Lincoff.

The REDUCE-IT trial

Mineral oil was the placebo in the 2018 REDUCE-IT trial, which reported a 25 percent lower risk of cardiovascular events in high-risk people who were given a highly purified version of EPA (a drug called Vascepa) instead of mineral oil. (The study was funded by Amarin Pharma, which makes Vascepa.)

Some scientists worried that the mineral oil might have raised risks in REDUCE-IT’s control group, which would have made Vascepa appear effective.

But an expert panel advising the FDA concluded that mineral oil could have explained only a small fraction of the difference between groups.

Unlike REDUCE-IT, the STRENGTH trial—with its neutral placebo—came up empty.

Epanova “did not reduce major adverse cardiac events,” said Lincoff.

And the drug had a downside.

“The risk of atrial fibrillation—a potentially dangerous arrhythmia—was increased by as much as 70 percent,” Lincoff noted.

That wasn’t common, though. Epanova caused the irregular heartbeat—which can increase the risk of stroke—in about 1 of every 100 users.

The REDUCE-IT trial also reported more atrial fibrillation in EPA takers than in placebo takers.

What about people who aren’t at high risk?

As it happens, scientists released the results of the VITAL Rhythm Study at the same Heart Association meeting.

VITAL Rhythm tested whether daily EPA (460 mg) plus DHA (380 mg) could prevent atrial fibrillation in roughly 25,000 people at ordinary risk.

While those taking fish oil had no lower risk, “the good news is that there wasn’t an increase in risk,” reported Christine Albert, who chairs the cardiology department at Cedars-Sinai in Los Angeles.

(The full study hadn’t been published at the time.)

The bottom line

Aim for one to two servings of seafood a week, as the American Heart Association advises. The jury is still out on fish oil supplements.