The meta-analysis excluded four large ongoing trials, due for completion next year, that will nearly double the number of subjects whose data could be included in such a study, according to Dr. Harry Rice, vice president of regulatory and scientific affairs at the Global Organization for EPA and DHA Omega-3s (GOED).
Meanwhile, Dr. Daniel Fabricant, president and CEO of the Natural Products Association (NPA), commented that the meta-analysis lacked a sensitivity analysis to determine the robustness of the results—such as analyzing data using various methods and then presenting results when some studies are removed from the analysis.
The meta-analysis of 10 clinical trials involving 77,917 participants was penned by an international group of researchers. It included only studies that had at least 500 participants, a scheduled treatment duration of at least one year, and used omega-3 supplements as an intervention.
No minimum daily dose of EPA or DHA was specified, which was a problematic flaw in the meta-analysis according to Dr. Bruce Holub of the University of Guelph.
“The doses were quite variable, and when you mix low doses…it certainly complicates meta-analysis,” he told NutraIngredients-USA. Dr. Holub is professor emeritus at the university’s Department of Human Health & Nutritional Sciences who specializes in DHA and EPA omega-3s.
“They had some doses that were as low as 400 mg per day,” Dr. Holub added. In fact, our anlaysis of the report found that four of the 10 studies analyzed used EPA/DHA doses that fall short of the 500 mg/day recommended by GOED.
GOED: ‘Meta-analysis does not really add to the body of evidence’
Dr. Rice pointed out that the current results are in fact in line with prior meta-analyses with similar foci.
“The main conclusions of the paper just confirm what we already know: EPA- and DHA-omega-3 consumption may have a modest impact on coronary heart disease,” he told NutraIngredients-USA.
He added that the the four large ongoing trials will more than double the number of subjects that have been studied to date in large trials of this sort, greatly adding to the statistical power.
“More data is needed to confirm the benefit and to that end, four large clinical trials (VITAL, ASCEND, STRENGTH, and REDUCE-IT) will be completed in the next two years and will provide that data,” he said.
“It’s important to point out that the study did not say there is NO risk reduction, just that there were no statistically significant associations and that it does not support current guidelines,” the statement continued, adding that “There was no call from the authors to change guidelines as a result of their analysis.”
Omega-3 lowered risk of major vascular events by 7%
In the paper’s discussion section, the authors acknowledged that there was a “7% lower risk of major vascular events and a 10% lower risk of coronary heart disease associated with omega-3 fatty acid supplements.”
This closely mirrors a meta-analysis from the Mayo Clinic Proceedings published last year, which associated EPA and DHA with a non-statistically significant 6% risk reduction in coronary heart disease among all population, as well as a meta-analysis published last fall in the Journal of Clinical Lipidology, which found that omega-3 may slash cardiac death risk by 8%. GOED contributed funding to both studies.
‘A compelling story’: Meta-analysis supports omega-3s for heart disease risk reduction
A meta-analysis published last January in the Mayo Clinic Proceedings looked at data from 18 randomized clinical trials, and concluded that EPA and DHA were associated with a non statistically significant 6% risk reduction in coronary heart disease.
Another meta-analysis, published last fall, reported that omega-3 supplements were associated with a risk reduction of cardiac death in people by 8%, and for those who had elevated triglycerides or LDL cholestrol, the risk reduction was 17%.
“Unfortunately, results in the JAMA Cardiology publication just missed statistical significance. What we need is more data that can be meta-analyzed,” Dr. Rice said. “As mentioned before, four large clinical trials will be completed in the next two years and those studies will nearly double the number of subjects whose data can be meta-analyzed.”
Dr. Holub had similar sentiments. “As far as overall results are concerned, I think it would be unfair to conclude from this paper that there was no apparent benefit of EPA/DHA omega-3 supplementation in regards to cardiovascular health,”
“Historically, equal to or less than 0.05 is considered to be significant, so I don’t think one can dismiss and disregard a 7% reduction in the risk of coronary heart disease,” he added. “We know that many of the conventional prescription medications for coronary disease often don’t provide any more benefit than 7% even though they’re very important and do offer a significant impact.”
What will the media say?
One major concern for the industry is what will happen when the paper reaches the popular press.
“Once the media gets a hold of the study, and the public, and the cardiologists who read those reports and are influenced by them, I think this could have an offsetting effect,” Dr. Holub added.
“It could potentially not be a good thing for the care of those with cardiovascular disease, or even prevention—in terms of prevention, you want to go aggressively as well against risk factors, which was really not focused on in the present study.”
GOED said in its statement to its members that it is monitoring media coverage and working with a public relations agency in case any action is necessary. However, Dr. Rice believes that the study’s impact on consumer perception will only be short-term.
“Consumer short-term perception of omega-3s based on this study will likely be dependent upon how the popular press spins the results,” he said.
“If the reporting is balanced, nothing should change. In the likely event the results are reported out of context, consumers may question, at least temporarily, the heart health benefits of omega-3s. This is an unfortunate situation given the overwhelming benefits of EPA/DHA associated with fatty fish and supplement intake.”
CRN, NPA highlight low seafood intake of Americans
Other dietary supplement trade groups quickly sent out statements defending the association between EPA and DHA omega-3s with a lowered risk of cardiovascular diseases.
“The U.S. Food and Drug Administration (FDA) would seem to disagree with the conclusion of this study, as it has already approved at least one prescription medication for fish oil that provides benefits for people with cardiovascular issues,” said NPA’s Dr. Fabricant.
“Moreover, there is a qualified health claim on Omega 3 fatty acids for cardiovascular diseases, which has also been approved by the FDA. We encourage people to consult with their medical professional as always, but continue to believe in the strong body of evidence that omega-3 fatty acids provide a positive nutritional supplement for millions of Americans who do not consume the recommended daily allowance of seafood.”
Duffy MacKay, ND, senior vice president, scientific and regulatory affairs with the Council for Responsible Nutrition (CRN), said: “The meta-analysis did not demonstrate the dramatic results that one would expect from a drug intervention. The meta-analysis did, however, identify the potential for a seven percent lower risk of major vascular events and a ten percent lower risk of coronary heart disease associated with omega-3 fatty acid supplements.”
“Even though these results are not statistically significant, they come close, thereby validating nutritional interventions, such as omega-3 fatty acids, as having subtle, but important, effects.”
Source: JAMA Cardiology
Published online January 31, 2018. doi:10.1001/jamacardio.2017.5205
"Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks"
Authors: Theingi Aung, Jim Halsey, Daam Kromhout, et al.