Meanwhile, the STRENGTH trial used a therapy containing both EPA and docosahexaenoic acid (DHA), an omega-3 fatty acid used for high cholesterol and heart disease.
For the STRENGTH trial, investigators enrolled over 13,000 patients in 22 countries beginning in 2014. It was halted in January 2020 when results showed it was unlikely to show any benefit for carboxylic acid, which can include amino acids and fatty acids. The study used a corn oil placebo because it would have a neutral effect, lead author of STRENGTH, Dr. A. Michael Lincoff, professor of medicine and vice chairman for research, Cardiovascular Medicine, Cleveland Clinic, said according to a press release. He noted that mineral oil would create a “negative control.”
“We believe the questions surrounding the benefit versus risk of fish oil will remain unanswered unless another trial using a neutral placebo such as corn oil is able to definitively show cardiovascular benefits for an omega-3 fatty acid medication," he said.
Lincoff said that unlike the mineral oil used in the REDUCE-IT trial, corn oil did not elevate low-density lipoprotein cholesterol — LDL, which is considered the “bad” cholesterol — or two key biomarkers. He said that suggests “that it was a truly neutral comparator.”
The ONEMI trail resulted in similar findings.
“The fact that no indication of any impact from the omega-3 fatty acids were found in this group, along with the results of other recent neutral trials, suggests that omega-3 supplements are ineffective for cardiovascular prevention,” said the ONEMI trial’s lead investigator. Dr. Are A. Kalstad of the Center for Clinical Research at Oslo University Hospital in Oslo, Norway.
Discussing the REDUCE-IT trail and the STRENGTH trial, Alberico Catapano, Ph.D., said it wasn’t clear whether the effect of the mineral oil or placebo would completely explain the difference between the two studies.
“Given the current uncertain state of knowledge, neither patients nor physicians can be confident that omega-3 fatty acids have any health benefits, yet in 2019 the global market for omega-3 fatty acids reached $4.1 billion and is expected to double by 2025,” wrote deputy editor Dr. Gregory Curfman.