The ongoing debate over the health benefits of omega-3 fatty acids is divisive to say the least. Several studies over the past few years have suggested fish oil supplements, commonly taken to reduce a person’s risk of cardiovascular disease, may not be effective. A new meta-analysis of 38 randomized controlled trials is now suggesting the key to beneficial cardiovascular outcomes from omega-3 supplements could come down to the specific kind of fatty acid being consumed.
Three kinds of omega-3 fatty acids are known to play a role in human health. Alpha-linolenic acid (ALA) is perhaps the most common, primarily found in plant foods. The other two, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are the classic “fish oil” omega-3 fatty acids regularly found in health supplements.
Many over-the-counter fish oil supplements contain a combination of EPA and DHA. This has traditionally been thought to offer the best health benefits, particularly from the standpoint of preventing cardiovascular disease.
Last year a large Phase 3 clinical trial was discontinued after early data indicated a purified concentrated combination of EPA and DHA did not reduce the risk of adverse cardiovascular events. The trial failure was contrasted against another already FDA-approved drug called Vascepa, which was reporting increasingly positive cardiovascular effects.
Vascepa is a purified and concentrated form of EPA, and a growing hypothesis is suggesting the cardiovascular benefits of omega-3 fish oil could be solely due to EPA. And those benefits may be offset when EPA is administered alongside DHA.
The new research adds weight to that idea comparing the results of trials testing EPA + DHA supplements against trials looking solely at EPA monotherapy. The results confidently showed reduced mortality and improved cardiovascular health when EPA was administered alone.
The researchers note it is plausible to suggest the cardiovascular benefits of omega-3 fish oil are limited to EPA. The two fatty acids have distinctly different properties and interact with human cells in unique ways.
A compelling recent study, yet to be peer-reviewed and published, offers evidence backing up the EPA hypothesis. The research followed nearly 1,000 patients at a high risk of adverse cardiovascular events for 10 years. Circulating levels of both EPA and DHA were measured in their blood and the research found those with the highest levels of EPA showed the lowest risk for adverse cardiac events. But high DHA levels blunted the benefits seen in patients with high EPA levels.
"Our findings show that not all Omega-3s are alike, and that EPA and DHA combined together, as they often are in supplements, may void the benefits that patients and their doctors hope to achieve,” says Viet T. Le, principal investigator on the study.
Of course, continuing the trend of confusingly inconsistent omega-3 research, another recent study looked at the differences in EPA and DHA blood levels in subjects from a large omega-3 clinical trial. It reported no difference in cardiovascular events between those with high EPA blood levels taking EPA supplements and those in the placebo group. Even those subjects with high DHA levels in the trial showed no difference to the placebo group.
"To be thorough, we looked at the data multiple ways--absolute EPA and DHA levels, change in levels of these omega-3 fatty acids, red blood cell levels, and by primary and secondary prevention subgroups," explains lead author Steven Nissen. "All of these analyses showed no benefits or harms."
Deepak Bhatt, a co-author on the new meta-analysis, is confident in suggesting EPA is the source of omega-3 fish oil’s cardiovascular benefits. Bhatt was also lead investigator on a large trial called REDUCE-IT, focusing solely on the cardiovascular effects of high doses from a purified ethyl ester of EPA.
"REDUCE-IT was the largest and most rigorous contemporary trial of EPA, but there have been other ones as well,” Bhatt says. "Now, we can see that the totality of evidence supports a robust and consistent benefit of EPA. This meta-analysis provides reassurance about the role of omega-3 fatty acids, specifically prescription EPA. It should encourage investigators to explore further the cardiovascular effects of EPA across different clinical settings."
The new study was published in the Lancet journal, EClinicalMedicine.
Source: Brigham and Women’s Hospital
