Applying drug-like endpoints to omega-3s reviews bound to end in failure, experts say

By Hank Schultz

- Last updated on GMT

Applying drug-like endpoints to omega-3s reviews bound to end in failure, experts say

Related tags omega-3 Cardiovascular disease

Reaction continues to roll in on the recent Cochrane review that found little evidence supporting the cardiovascular benefits of omega-3s. Experts questioned the underlying assumptions in how the review was put together.

Last week, Cochrane published a review titled “Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.”​ The publication combed through the results of 79 randomized trials involving 112,059 subjects.

These studies assessed effects of consuming more omega-3s or using omega-3s supplements on the incidence of diseases of the heart and circulation. Of the 79 trials, 25 studies were assessed as highly trustworthy because the authors judged them to be well-designed and conducted.

Little support found for omega-3s CVD benefits

The Cochrane researchers found that increasing long-chain omega 3 provides little if any benefit on most outcomes that they looked at. Those were: All-cause mortality, cardiovascular deaths, cardiovascular events, coronary heart disease deaths, coronary heart disease events, stroke or arrhythmias (moderate and high-quality evidence). 

They found high certainty evidence that long-chain omega 3 fats had little or no meaningful effect on the risk of death from any cause. The risk of death from any cause was 8.8% in subjects who had increased their intake of omega-3s, compared with 9% in participants in the control groups.

Experts questioned some of the underlying assumptions that the authors seemed to have made in choosing which studies to include in the review and the methodology used to assess the results of those studies.

Nutrients operate differently than do drugs

One of the world’s foremost omega-3s researchers, William Harris, PhD, of the Sanford School of Medicine at the University of South Dakota, said if you use drug-like protocols in assessing nutrition studies, you are liable to be disappointed.

We agree that short-term trials with low doses of omega-3 supplements might not be able to replicate the beneficial effects of long-term fish or omega-3 intake. You can’t treat nutrients like they are drugs,”​ Harris told NutraIngredient-USA.

Andrea Wong, PhD, vice president of scientific and regulatory affairs for the Council for Responsible Nutrition agreed that the Cochrane authors seemed to have been looking at the studies with drug-tinted lenses.

CVD is a complex, multifactorial disease, and expectations about the role dietary supplements can play in reducing risk must be managed responsibly. The road to good health is not a one-way street and no single action—or supplement—can clear all detours and roadblocks on this lifelong journey. Omega-3s can contribute to CVD risk reduction, but only when used in combination with other healthy choices such as diet and exercise,”​ she said.

Conclusions were over broad

Harris said any study on nutrition needs to look at the status of the population, and this was all over the map with the studies the authors chose to review.

“We need to understand what the studies included in these meta-analyses were testing. Typically, the people in these studies were older, already had some chronic disease, and were taking several other medications. What’s more, low doses of omega-3s were typically given, and the studies ran for only two or three years on average. We agree that omega-3s may not significantly reduce risk for heart disease in this scenario, but the conclusion that ‘omega-3s don’t improve heart health’ is far too broad,”​ he said.

Wong agreed that the authors painted with far too broad a brush.

The review’s authors make a broad conclusion that both sidesteps the existing literature supporting the benefits of omega-3 fatty acids for heart health and misconstrues the role of dietary supplements as part of a healthy lifestyle. This review does not represent the totality of evidence, nor does it recognize how consumers incorporate omega-3s into their lifestyles to maintain a healthy heart in the first place,”​ she said.

Baseline values lacking

Harris is the co-founder of the Omega 3 Index, a method of assessing omega-3 status via a blood test. He is also president of OmegaQuant LLC, a company in Sioux City, IA that markets a mail-in blood spot version of the test. 

The index is expressed as a percentage, with 8% being the baseline where the best cardioprotective benefits are to be had. Not having this baseline information in many of the studies the authors looked at greatly complicates the task of deriving an overall signal from them, he said.

“The doses of EPA and DHA typically used in these studies is unlikely to produce a cardio-protective omega-3 blood level, which would be 8% based on the Omega-3 Index. Most likely, the people in these studies reached an Omega-3 Index of about 6%, which is still 2 percentage points away from significantly reducing your risk of CHD. If you are going to treat this nutrient like a drug, a high enough dose must be used and the blood levels achieved must be confirmed,”​ he said.

Redundant meta-analyses

Harris said the appreciation of the need for this kind of baseline data is informing current and future omega-3s research. He questioned the value of doing repeated meta-analyses that don’t add much to the overall discussion.

“Why do we keep doing meta-analyses on the same studies? There is no new information here. We’ve seen these high profile ‘no effect’ meta-analyses every year for the last five years, while at the same time, there have been other meta-analyses that found overall benefits for EPA and DHA that have not been widely reported on.

"This new meta-analysis is just a re-hash of old data and certainly does not provide the final answer on the omega-3 question. New data is needed and will be forthcoming,”​ he said.

Source: Cochrane Database of Systematic Reviews
DOI: 10.1002/14651858.CD003177.pub3.
“Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease”
Authors: Abdelhamid AS, Brown TJ, Brainard JS, et al.

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