Limited AREDS2 Finds No Significant Omega-3 CVD Benefit

WASHINGTON—Omega-3 supplementation did not reduce cardiovascular disease (CVD) risk in elderly patients participating in the Age-Related Eye Disease Study 2 (AREDS2) clinical trial (JAMA Intern Med. doi:10.1001/jamainternmed.2014.328). In the ancillary Cardiovascular Outcomes Study (COS) published in JAMA Internal Medicine, AREDS2 researchers found no risk reduction in CVD or secondary CVD outcomes among the omega-3 supplemented eye disease age-related macular degeneration patients.

For the study, more than 4,200 subjects took either omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (n=1,068); the macular xanthophylls lutein and zeaxanthin (n=1,044); a combination of the two (n=1,079); or placebo (1,012). Researchers studied age-related eye disease and cardiovascular outcomes.

The study authors wrote, “We found no significant benefit among older individuals treated with either omega-3 supplements or with a combination of lutein plus zeaxanthin. Our results are consistent with a growing body of evidence from clinical trials that have found little CVD benefit from moderate levels of dietary supplementation."

But with a median age of 74 years, the participants may have been too old to reap omega-3s' heart health benefits—a limitation the authors acknowledged, noting, "…the timing of the administration of the supplements may have been too late to affect outcomes. The AREDS2 participants were older, and many had existing CVD or elevated risk for CVD." They later added, "We cannot exclude a beneficial effect from starting supplementation earlier in life."

The study did record omega-3s' heart benefits for specific populations. "For example, the researchers found a significant protective effect against cardiovascular disease for those taking omega-3 supplements who had no previous history of hypertension," explained Duffy MacKay, N.D., senior vice president, scientific and regulatory affairs, the Council for Responsible Nutrition (CRN). Similarly, the authors noted a numerical trend toward supplementation's benefits in subjects with no history of CVD or no elevated cholesterol levels. MacKay added, "These benefits underscore the value of omega-3s in combination with other healthy habits to help avoid cardiovascular disease among otherwise healthy populations."

In a statement, the Global Organization for EPA and DHA Omega-3 (GOED) noted the study would likely garner significant negative mainstream media attention—though unwarranted.

The trade organization stated the study was "grossly underpowered," noting "There was a failure to detect an effect, not a lack of effect(s)." A February 2014 meta-analysis found omega-3 supplementation reduced cardiac death by 9 percent with a population size of nearly 69,000 subjects. "GOED has calculated that in order to see a 10-percent risk reduction for cardiac death in a study like AREDS2, the study would have needed to include 36,000 patients, not the 2,000 patients actually studied," the organization said.

MacKay clarified that the study's primary outcome had drug-like criteria. "In other words, the researchers acknowledged that given the sample size they started with, they would have had to see a 25-percent risk reduction to identify the results as beneficial. This kind of statistical outcome, while realistic for pharmaceutical interventions that provide powerful and immediate results—potentially accompanied by powerful risks—may not be appropriate for studying nutrients."

Regardless, he reminded consumer and industry alike to not hinge beliefs or doubts on one study: "For those who choose to call each study the final word, or a reason to close the door on vitamins, consider this: we all wish science produced black-and-white answers, so we could have a non-negotiable roadmap to good health; the fact is science doesn’t work that way—there are always detours."