The ongoing debate about the health benefits of omega-3 fatty acids is contentious to say the least. Several studies in recent years have shown that fish oil supplements commonly taken to reduce the risk of cardiovascular disease may not be effective. A new meta-analysis of 38 randomized controlled trials now suggests that the key to beneficial cardiovascular outcomes from omega-3 supplements may lie in the specific type of fatty acid consumed.
Three types of omega-3 fatty acids are known to play a role in human health. Alpha-linolenic acid (ALA) is perhaps the most common, found mainly in plant foods. The other two, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are the classic “fish oil” omega-3 fatty acids that are regularly found in food supplements.
Many over-the-counter fish oil supplements contain a combination of EPA and DHA. It is traditionally believed to provide the best health benefits, especially in terms of cardiovascular disease prevention.
Last year, a large phase 3 clinical trial was canceled after initial data indicated that a purified, concentrated combination of EPA and DHA did not reduce the risk of adverse cardiovascular events. The trial’s failure was contrasted with another FDA-approved drug called Vascepa, which reported increasingly positive cardiovascular effects.
Vascepa is a purified and concentrated form of EPA, and a growing hypothesis suggests that the cardiovascular benefits of omega-3 fish oil are solely due to EPA. And these benefits can be offset when EPA is given along with DHA.
The new research adds weight to this idea by comparing the results of studies testing EPA + DHA supplements with studies looking solely at EPA monotherapy. The results certainly showed reduced mortality and improved cardiovascular health when EPA was administered alone.
The researchers think it plausible to point out that the cardiovascular benefits of omega-3 fish oil are limited to EPA. The two fatty acids have significantly different properties and interact with human cells in a unique way.
A compelling recent study, which has yet to be peer-reviewed and published, provides evidence to support the EPA hypothesis. The study followed nearly 1,000 patients at high risk for adverse cardiovascular events for 10 years. Circulating levels of EPA and DHA were measured in their blood, and research found that those with the highest EPA levels had the lowest risk of adverse cardiac events. But high DHA levels mitigated the benefits seen in patients with high EPA levels.
“Our results show that not all omega-3 fatty acids are created equal and that the combination of EPA and DHA, which are often found in dietary supplements, negates the benefits that patients and their doctors are hoping for,” says Viet T. Le , senior researcher on the study.
Of course, to continue the trend of confusingly inconsistent omega-3 research, another recent study looked at the differences in EPA and DHA blood levels in subjects in a large omega-3 clinical trial. There was no difference in cardiovascular events between those with high EPA blood levels who took EPA supplements and those in the placebo group. Even the subjects with high DHA levels in the study showed no difference to the placebo group.
“To be thorough, we looked at the data in several ways – absolute EPA and DHA levels, changes in the levels of these omega-3 fatty acids, the level of red blood cells and by subgroups of primary and secondary prevention,” explains Lead author Steven Nissen. “All of these analyzes showed no benefit or harm.”
Deepak Bhatt, co-author of the new meta-analysis, is confident that EPA is the source of omega-3 fish oil’s cardiovascular benefits. Bhatt was also the lead researcher in a large study called REDUCE-IT that focused solely on the cardiovascular effects of high doses of a purified ethyl ester from EPA.
“REDUCE-IT was the largest and most rigorous study on EPA to date, but there were others,” says Bhatt. “Now we can see that all of the evidence supports robust and consistent benefits from EPA. This meta-analysis sheds light on the role of omega-3 fatty acids, especially prescription EPAs. It should encourage researchers to further study the cardiovascular effects of EPA in various clinical settings. “
The new study was published in the Lancet journal EclinicalMedicine.
Source: Brigham and Women’s Hospital