Researchers published a new study “Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials” in Mayo Clinic Proceedings that they claim provides the most comprehensive analysis of the role of omega-3 dosage on cardiovascular prevention to date. The team says its meta-analysis, which is an in-depth review of 40 clinical trials, provides authoritative evidence for consuming more EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) omega-3 fats.

The research concludes that EPA and DHA omega-3 intake is associated with reduced risk of coronary heart disease (CHD) events, the cause of 7.4 million deaths globally each year, and reduced risk of myocardial infarction, including fatal heart attack.

Specifically, the study found that EPA+DHA supplementation is associated with a statistically significant reduced risk of:

  • Fatal myocardial infarction (35 percent)
  • Myocardial infarction (13 percent)
  • CHD events (10 percent)
  • CHD mortality (9 percent)

The objectives of the study were “To quantify the effect of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on cardiovascular disease (CVD) prevention and the effect of dosage,” write the investigators.

“This study is designed as a random effects meta-analysis and meta-regression of randomized control trials with EPA/DHA supplementation. This is an update and expanded analysis of a previously published meta-analysis which covers all randomized control trials with EPA/DHA interventions and cardiovascular outcomes published before August 2019.

“The outcomes included are myocardial infarction (MI), coronary heart disease (CHD) events, CVD events (a composite of MI, angina, stroke, heart failure, peripheral arterial disease, sudden death, and non-scheduled cardiovascular surgical interventions), CHD mortality and fatal MI. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.

“A total of 40 studies with a combined 135,267 participants were included. Supplementation was associated with reduced risk of MI (relative risk [RR], 0.87; 95% CI, 0.80 to 0.96), high certainty number needed to treat (NNT) of 272; CHD events (RR, 0.90; 95% CI, 0.84 to 0.97), high certainty NNT of 192; fatal MI (RR, 0.65; 95% CI, 0.46 to 0.91]), moderate certainty NNT = 128; and CHD mortality (RR, 0.91; 95% CI, 0.85 to 0.98), low certainty NNT = 431, but not CVD events (RR, 0.95; 95% CI, 0.90 to 1.00). The effect is dose dependent for CVD events and MI.

Cardiovascular disease remains the leading cause of death worldwide. Supplementation with EPA and DHA is an effective lifestyle strategy for CVD prevention, and the protective effect probably increases with dosage.”

“The study supports the notion that EPA and DHA intake contributes to cardioprotection, and that whatever patients are getting through the diet, they likely need more,” said Carl “Chip” Lavie, MD, a cardiologist at Ochsner Health in New Orleans, and one of the study authors.

Cardiovascular benefits appear to increase with dosage. The researchers found that adding an extra 1000 mg of EPA and DHA per day decreased the risk of cardiovascular disease and heart attack even more: risk of cardiovascular disease events decreased by 5.8 percent and risk for heart attack decreased by 9.0 percent. The study looked at dosages of up to 5500 mg/day.

This research corroborates the results of an earlier meta-analysis from Harvard School of Public Health, published in fall 2019, that looked at EPA and DHA dosage using the 13 largest clinical studies. This new paper encompasses more than triple the number of studies, which represents the totality of the evidence to date and includes more than 135,000 study participants.

“When separate analyses arrive at similar results, that’s not only validating; it also underscores the science base needed to inform future intake recommendations,” said co-author Aldo Bernasconi, PhD, vice president of data science for the Global Organization for EPA and DHA Omega-3s (GOED), Salt Lake City, UT, which commissioned this study. “Because this paper included more studies and all dosages, the estimates for a dose-response are more precise and the conclusions stronger.”

EPA and DHA omega-3s are long-chain, marine-based fatty acids. Eating fish, particularly fatty fish such as salmon, anchovies, and sardines, is the optimal way to get EPA and DHA omega-3s, since fish also provides other beneficial nutrients. However, most people around the world eat much less than the amount of fish recommended, so supplementing with omega-3s helps close the gap.

“People should consider the benefits of omega-3 supplements, at doses of 1000 to 2000 mg per day—far higher than what is typical, even among people who regularly eat fish,” added Lavie. “Given the safety and diminished potential for interaction with other medications, the positive results of this study strongly suggest omega-3 supplements are a relatively low-cost, high impact way to improve heart health with few associated risks and should be considered as part of a standard preventive treatment for most patients with cardiovascular diseases and those recovering from myocardial infarction.”

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