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Fish Oil May Not Reduce Cardiac Events, Study Finds

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Key Takeaways

  • A study comparing fish oil components EPA and DHA found they didn't reduce cardiac events in high-risk patients.
  • The fatty acids can lower triglycerides, according to research.
  • Other studies that use only EPA indicate there are cardiovascular benefits to the supplements.

Fish oil may not be a cardiovascular event cure-all, according to a new report.

The science has gone back and forth over the years as to whether or not taking a fish oil supplement or a prescription fish oil supplement can lower the risk of cardiac events. Some have found that fish oil can lower triglycerides—the fats most commonly found in the body.

In 2017, the American Heart Association (AHA) issued an advisory saying that prescription omega-3 fish oil supplements may be able to prevent death from heart disease in patients who recently had a heart attack. They also said it could prevent death and hospitalizations in patients with heart failure.

The latest study shows that a combination of eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA) doesn't lower major cardiac events in high-risk patients. The fatty acids are both omega-3 fatty acids found in certain fish.

The study, published in JAMA and recently presented at the American Heart Association’s Scientific Sessions 2020, detail the results of the STRENGTH trial. In the trial, researchers assessed omega-3 carboxylic acids or omega-3 CA (brand name Enova), a medication derived from fish oil.

“Many people continue to take fish oil supplements to prevent heart disease. However, the fish oil medication we tested in the STRENGTH trial was not effective for that purpose,” A. Michael Lincoff, MD, lead author and an interventional cardiologist at the Cleveland Clinic, said in a statement.

The STRENGTH trial, which began in 2014, encompassed data from 13,078 adults at 675 centers in 22 countries. All of the patients were being treated with statins and had known heart, brain, or leg artery blockages. They were at a higher risk for heart disease due to factors such as smoking and diabetes.

People either took the omega-3 CA medication or a placebo. The placebo used was corn oil.

The team compared the rates of cardiovascular death, heart attack, stroke, need for stenting or bypass surgery, and hospitalization for unstable angina in all of the study participants.

They found that 1,580 patients experienced at least one cardiac event. There weren’t any significant differences in cardiac event risk between participants in one group versus the other. But researchers did find that people taking the omega-3 CA medication developed atrial fibrillation (irregular heartbeat) more frequently than those who took corn oil.

The trial was stopped in January 2020 after researchers concluded it likely wouldn’t prove the benefit of the omega-3 CA medication.

Evaluating Fish Oil and Heart Health

Other studies have looked at fish oil and cardiovascular health. Evidence has been mixed, as researchers have used different types and quantities of fish oils and different placebos.

  • The 2007 JELIS trial also evaluated the use of EPA and statins, and found a reduction in non-fatal coronary events. Major coronary events were reduced slightly in those with a history of coronary artery disease. No placebo was used.
  • The 2019 VITAL study used supplements including vitamin D3 and omega-3 fatty acids. It showed fish oil didn’t lower the risk for major cardiac events.
  • The 2019 REDUCE-IT trial evaluated icosapent ethyl (brand name Vascepa), a high-dose pure EPA (form of omega-3). The study included people with heart disease or people who were taking a statin medication with raised triglyceride levels. People on the omega-3 supplement had a 25% lower incidence of heart disease and stroke, and a 20% reduction in death from heart disease.

STRENGTH used a supplement with DHA and EPA (Epanova), while REDUCE-IT only used EPA (Vascepa). Both trials showed different results.

Interpreting Results

Steven E. Nissen, MD, a doctor at the Cleveland Clinic Heart and Vascular Institute and one of the STRENGTH trial researchers, tells Verywell that multiple studies have shown fish oil doesn’t protect from cardiac events. Using prescription fish oil does have some benefits, though. It lowers triglycerides, he says.

Omega-3 fatty acids do lower triglycerides, but not all of them reduce cardiovascular risk, notes Deepak L. Bhatt, MD, executive director of interventional cardiovascular programs and a professor at Harvard Medical School. "So, the triglyceride reduction per se may not be the mechanism that is actually providing cardiovascular benefit." Bhatt was a researcher in the REDUCE-IT trial.

The REDUCE-IT trial did show heart benefits, but Nissen thinks it’s “all about the placebo” that they used.  

In STRENGTH, researchers used corn oil. REDUCE-IT used mineral oil.

“We postulate that REDUCE-IT is a false positive,” Nissen says.

Michael Miller, MD, a professor of cardiovascular medicine, epidemiology and public health at the University of Maryland School of Medicine, says he believes using corn oil was a shortcoming on the STRENGTH trial. He was one of the researchers in the REDUCE-IT trial.

“Corn oil consists of polyunsaturated fatty acids (PUFA) well known to be cardioprotective,” he tells Verywell.

“Even if we exclude mineral oil and corn oil placebo groups, basic science studies show EPA to have antioxidant and other cardioprotective properties whereas DHA has pro-oxidant and other properties that oppose EPA,” Miller says.

While the two primary omega-3 fatty acids found in fish oil, DHA and EPA, can both lower triglycerides, only EPA has been shown to reduce the risk of cardiovascular events, Miller adds.

“The bottom line is that two large independent studies have shown EPA only to be cardioprotective whereas at least a dozen EPA/DHA studies have all been negative,” Miller says.


Who Should Take Fish Oil?

"I understand fish oil supplements are very popular, but I do not recommend them [for healthy people], as the clinical trials have not shown any significant reductions in cardiovascular risk," Bhatt says. For people looking to stay healthy, a diet high in omega-3 fatty acids can be a good part of a balanced diet.

For patients with appropriate indications, Bhatt recommends Vascepa (EPA) because it is shown to reduce heart attacks and strokes in patients with cardiovascular disease, in patients with diabetes, and in patients with other risk factors for heart disease.

Nathan Wong, MD, director of the University of California Irvine Heart Disease Prevention Program (who was not affiliated with the research), says people should know that not all fish oil products are the same.

"Many dietary supplement products have impurities such as saturated fats, and other prescription products have mixtures of different fish oils and we are not sure, for example, whether DHA might counteract the benefits of EPA," Wong tells Verywell.

Only Vascepa has been shown to reduce cardiovascular events in persons with known cardiovascular disease or diabetes, Wong says.

What This Means For You

The STRENGTH trial demonstrates two things about fish oil, Satjit Bhusri, MD, a cardiovascular disease specialist at Upper East Side Cardiology in New York, tells Verywell. He was not affiliated with any of the studies.

"First, it reinforces the power of EPA in cardiac protection, and second, it lowers the efficacy and need of DHA," he says. "Fish oil, as an over the counter supplement, is a relatively harmless pill. Minimal side effects and possible benefits from added EPA, in whatever quantity, will be helpful."

 

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  1. Nicholls SJ, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: The STRENGTH randomized clinical trialJAMA. Nov. 15, 2020. doi:10.1001/jama.2020.22258

  2. Yokoyama M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. The Lancet. March 31, 2007. doi:10.1016/S0140-6736(07)60527-3

  3. Manson JE, Cook NR, Lee I-M, Christen W, Bassuk SS, Mora S, et al. Marine n−3 fatty acids and prevention of cardiovascular disease and cancer. New Eng J Med. Jan. 3, 2019. doi:10.1056/NEJMoa1811403

  4. Bhatt D, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. New Eng J Med. Jan. 3, 2019. doi:10.1056/NEJMoa1812792

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