A new study published in Mayo Clinic Proceedings, “Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials,” showed a connection between an increase in omega-3 intake and a variety of cardiovascular risk reductions. The paper, which was commissioned by GOED, the Global Organization for EPA and DHA Omega-3s, is the most comprehensive meta-analysis to date, looking at 40 clinical trials with more than 135,000 subjects. Specifically, the meta-analysis found that EPA and DHA supplementation was associated with statistically significant reductions in several cardiovascular outcomes:

• 35% reduced risk of fatal myocardial infarction (MI)
• 13% reduced risk of MI
• 10% reduced risk of coronary heart disease (CHD) events
• 9% reduced risk of CHD mortality.

This paper is important because over the years there have been seemingly contradictory results in the clinical research on EPA and DHA omega-3 intake and cardiovascular health. This has not only puzzled academics who study the topic, it has also led healthcare practitioners and consumers to question the value of omega-3 supplementation.

Research Then and Now
As background, research on omega-3s and heart health accelerated after the 1970s, during which time seminal research by Dyerberg and Bang found that native Greenlanders who ate traditional diets high in marine fats tended to have more EPA and DHA in their blood and experience less cardiovascular disease. From 1980 to 2011, scientists published more than 21,000 papers on EPA and DHA—2,554 of which were clinical trials—mostly showing a positive correlation between EPA+DHA consumption and heart health.

In 2012, a large-scale clinical trial, ORIGIN, studying heart health outcomes in 12,536 diabetics and prediabetics interrupted the trend established in previous decades of research, finding no significant heart health benefit of EPA and DHA consumption. Furthermore, Dr. Evangelos Rizos (one of the co-authors of the ORIGIN trial) published one of the first meta-analyses on the topic during the same year, arguing that the previous body of research had not proved a cardioprotective effect for omega-3s.

After 2012, clinical trials and other meta-analyses continued to demonstrate contradictory findings and mainstream consumer media reporting on the studies increasingly used “click bait” negative headlines, even when writing about neutral studies. This in turn affected consumer attitudes toward omega-3s, resulting in lower omega-3 sales, particularly in the U.S. For several years, few randomized controlled trials (RCTs) on omega-3s and cardiovascular outcomes were published.

Omega-3 research took a huge leap forward in 2018 when three large scale clinical trials on omega-3s were published. The three studies—ASCEND, VITAL, and REDUCE-IT—more than doubled the number of subjects who had been studied for the impact of omega-3s on cardiovascular outcomes. This introduced the possibility of analyzing the impact of omega-3 dosage on cardiovascular outcomes and led to the current meta-analysis.

The Dosage Connection
The Mayo Clinic Proceedings paper was co-authored by Aldo Bernasconi, PhD, vice president of data science at GOED, along with cardiologist Carl “Chip” Lavie of the John Ochsner Heart and Vascular Institute and Ochsner Clinical School, and biostatistician Michelle Wiest of the University of Idaho. The study demonstrated that omega-3 dosage could be correlated with improved cardiovascular outcomes.

Incorporating data from ASCEND, VITAL, and REDUCE-IT along with the prior body of evidence, Bernasconi and co-authors found that an additional 1 g/day of EPA+DHA resulted in additional statistically significant risk reductions:

• 5.8% reduction in the risk of cardiovascular disease (CVD) events
• 9.0% reduction in the risk of MI.

(The study looked at dosages up to 5.5 grams per day. See Figure 1.)


Figure 1. Impact of Omega-3 Dosage on CVD and MI Risk Reduction

Importantly, the study also looked at other factors—in addition to dosage—that could have impacted the contradictory results over the years, namely, the year the study was published (which could indicate differences in study design or the addition of modern cardiovascular prevention such as statins), the baseline omega-3 levels of the participants, and whether the treatment included EPA+DHA or EPA only. The meta-analysis found that of all these, only dosage mattered.

“Each new study contributes a little bit to our understanding of any scientific question,” said Bernasconi in discussing the results. “I think this article in particular is the most comprehensive exploration to date of what factors affect the effect of omega-3 supplementation. It found that, unsurprisingly, dosage is the most important factor. Simply put, studies with higher dosages are more likely to find a positive effect. I think that this may help design future studies to have sufficient dosage in order to see a measurable effect.”

There are also implications for public health. As co-author Lavie pointed out, “Considering the relatively low costs and side effect profiles of omega-3 supplementation and the low drug-drug interactions with other standard therapies used in cardiovascular prevention, consumers and physicians should consider the potential benefits of omega-3 (EPA+DHA) supplementation, especially using dosages of 1,000-2,000 mg/day, which are rarely obtained in most Westernized diets, even those including some routine fish consumption.” 

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Chris Gearheart (chris@goedomega3.com) is Director – Member Communications & Engagement at GOED, the Global Organization for EPA and DHA Omega-3s. GOED is a trade organization with more than 170 members throughout the omega-3 supply chain. GOED’s mission is to increase consumption of EPA and DHA omega-3s around the world and to ensure that its members produce quality products that consumers can trust.