Many people take fish oil supplements to try to improve various aspects of their health, but new work from the Cleveland Clinic has suggested that high doses of an omega-3 fatty acid supplement don't help people at high risk of cardiovascular events reduce their risk of those events. The conclusions are from the STRENGTH Trial: Cardiovascular Outcomes With Omega-3 Carboxylic Acids (Epanova) In Patients With High Vascular Risk And Atherogenic Dyslipidemia, which were reported in the Journal of the American Medical Association (JAMA) and at the virtual Scientific Sessions of the American Heart Association.
The STRENGTH trial involved 13,078 volunteers that took either high dose omega-3 fatty acids or a corn oil placebo. Compared to people taking corn oil, there was no reduction in major adverse cardiovascular events for people taking the omega-3 drug, and the trial was halted early because no difference between the groups was identified.
These results are contrary to another study done in 2018, which suggested that compared to a mineral oil placebo, a highly pure form of omega-3 fatty acid called icosapent ethyl could significantly reduce adverse cardiovascular events and cardiovascular death among patients at high-risk. The mineral oil placebo was a potential study problem, however, that may have promoted the benefit of mineral oil.
"These results have prompted the question of why the STRENGTH trial was neutral while a previous trial was favorable," said senior study author Steven Nissen, M.D., Chief Academic Officer of the Heart, Vascular and Thoracic Institute at Cleveland Clinic. "Compared with mineral oil used in the previous trial, corn oil did not raise levels of bad cholesterol or markers of inflammation, suggesting that it was a truly neutral placebo."
"The question of whether administration of omega-3 fatty acids plays a role in the prevention of cardiovascular disease has been investigated with varying results," said study co-author Michael Lincoff, M.D., vice chair in the department of cardiovascular medicine and director of C5Research at Cleveland Clinic.
"The STRENGTH trial showed a 67 percent increase in atrial fibrillation in the omega-3 CA treatment group, indicating that there is some uncertainty whether there is net benefit or harm with administration of any omega-3 fatty acid formulation. Given that two large clinical trials have now demonstrated a greater incident rate of atrial fibrillation with high dose omega-3 fatty acid administration, this observation requires further study," Lincoff said.
"These results suggest that a review of the entire class of fish oil products is warranted to determine what labeling changes might be appropriate for these products, including whether high-dose fish oil supplements truly provide benefits given the risk of atrial fibrillation," Nissen added. "These results also have implications for over-the-counter fish oil since many patients take large doses to avoid the expense of prescription drugs."