Experts say Cochrane review that finds little support for CVD benefits of omega-3s fails to properly weigh 'totality of evidence'
Published yesterday, the review, titled “Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease,” combines 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. These trials were, as the authors said, “At low risk of selection bias, performance bias and detection bias, plus low risk of performance bias in supplemental trials.”
Two-thirds of RCTs eliminated
The winnowing of what was considered to be relevant research was an important aspect of the review and had a strong effect on the outcome. The authors acknowledged as much, saying that, “We assessed the validity of evidence in meta-analyses by running sensitivity analyses that removed trials not at low summary risk of bias. When sensitivity analyses removed LCn3 trials at moderate to high summary risk of bias, effect sizes moved closer to no effect (RR 1.0) for all primary outcomes except arrhythmias, where the RR rose to 1.10.”
“This lack of effect in the studies at lowest risk of bias (with suggestions of effect in studies at moderate to high risk of bias) was an important finding from this review and supported our interpretation of lack of effect of long-chain omega-3 fats on our primary outcomes,” they added.
Studies on healthy subjects as well as those who were already ill
The studies the authors looked at were done on both men and women, and on healthy subjects as well as those with existing illnesses, such as subjects who had already had a heart attack. The studies came from North America, Europe, Australia and Asia. Participants were randomly assigned to increase their intake of omega-3s or to maintain their usual intake of fat for at least a year.
Most studies investigated the impact of giving a long-chain omega-3s via capsules or softgels and compared that to a placebo. Only a few studies assessed the effects of increasing the intake of whole fish.
The authors also included studies on ALA, which is usually consumed in a whole food form via flax, walnuts or other sources. Most ALA trials added omega 3 fats to foods such as margarine and gave these enriched foods, or naturally ALA-rich foods such as walnuts, to people in the intervention groups, and usual (non-enriched) foods to other participants.
Little to no benefit found on CVD measures, all-cause mortality
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: Totality of evidence supports omega-3s
Scientific experts said the Cochrane results needed to be taken seriously. But they questioned some of the ways in which the reviewers chose what they considered to be the relevant research.
In a comment posted on the Cochrane site, Tom Sanders, PhD, professor emeritus of Nutrition and Dietetics, King's College London, had this to say: “The major limitation of this review of randomised controlled trials is that it has been unable to allow for the increased intakes of omega-3 fatty acids over the past 20 years.”
“Most of the trials in this review were in patients with pre-existing cardiovascular disease (CVD), which is a further limitation when extrapolating to the prevention of heart attacks in the general population. This is important as a substantial proportion of first heart attacks are fatal (it is worth noting that this proportion has fallen greatly in the past twenty years). Previous observational cohort studies, not looked at here, suggest that omega-3 fatty acids may reduce the risk of sudden cardiac death,” he added.
Harry Rice, PhD, the vice president of scientific and regulatory affairs for the Global Organization for EPA and DHA Omega-3s (GOED), had this to say:
“While the authors should be applauded for the breadth of their review, their overall interpretation of the data demonstrated a lack of appreciation for and understanding of the decades of research demonstrating the heart health benefits of omega-3s. Such research includes not just meta-analyses, but RCTs, observational studies, as well as animal and in vitro studies. It's about the totality of the scientific evidence.”
“Despite being downplayed by the authors, the present review revealed a protective effect for CHD and CHD mortality—benefits that have been reported previously in GOED-commissioned meta-analyses,” Rice added.
Conclusion is far too broad
"We need to understand the 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 2-3 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," said William Harris, PhD, a noted omega-3s researcher at the Sanford School of Medicine at the University of South Dakota.
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.
