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Mayo Clinic Report Affirms Omega-3s’ Heart Benefits
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Review affirms key benefits, details omega-3s’ known impact on specific risk factors and cardiac conditions, and addresses dose questions

by Craig Weatherby

What’s tone got do with it?

The term “autonomic tone” refers to the effect of the autonomic nervous system on the heart rate via the vagus nerve and the release of salt and other chemicals, among other avenues.

Chronic imbalance of the autonomic nervous system is a prevalent and potent risk factor for adverse cardiovascular events and sudden cardiac death. 

Although not widely recognized by doctors, this risk factor is easily assessed with treadmill-type stress tests.

Anything that provides a proverbial shock to the system – such as emotional or physical stress – can exert an adverse effect on heart tone, while any factor that balances tone (e.g., omega-3s) tends to improve outcomes. 

Insulin resistance and blood pressure drugs can also trigger an arrhythmia – and resulting sudden death – when autonomic tone is in an unfavorable condition (Curtis BM, O'Keefe JH Jr 2002).

What does it means to say that fish oil is good for the heart? We’re overdue for an updated answer to this basic question, and the publication of a new evidence review is a welcome coincidence.

The paper’s authors include James O'Keefe, M.D. and William Harris, Ph.D.… names well known to folks who follow the subject of omega-3s and heart health.

(Dr. O’Keefe works at Kansas City’s Mid America Heart Institute and University of Missouri, while Dr. Harris conducts research at the University of South Dakota’s School of Medicine.)

Last month, the journal “Mayo Clinic Proceedings” published a new review of the best clinical (human) evidence concerning the effects of omega-3s on cardiac health risks, authored by Drs. O’Keefe and Harris and scientific colleagues from New Orleans and Italy (Lee JH et al. 2008).

The authors considered the epidemiological evidence but focused on the best available clinical evidence, which comes from three large, placebo-controlled trials that involved a total of 32,000 volunteers.

The participants in all three trials were randomly assigned to take either omega-3 fish oil capsules or placebo oil capsules.

In these three key clinical trials, the risk of “adverse cardiac events” – heart attack, stroke, arrhythmia, sudden death – dropped by 19 percent to 45 percent among the participants who took fish oil, compared with those who took placebo capsules.

Findings summarize heart-related omega-3 research

The results of the new evidence review affirm several key theories about omega-3s, and summarize what we know about how they work, at what doses, and in which forms (Lee JH et al. 2008):

Cardiovascular health benefits

  • Omega-3s reduce the risk of a second heart attack.

  • Omega-3s reduce the risk of ischemic strokes, which account for 85 percent of all strokes.

  • Omega-3s reduce the risk of sudden cardiac death (SCD), which causes half of all heart-related fatalities and usually results from an unexpected heart rhythm problem (arrhythmia).

  • Eating one fish meal per week reduces the risk of developing heart disease by 15 percent. Eating five or more fish meals per week reduces the risk by 40 percent

Dose and form

  • Americans’ average intake of omega-3s, whether from fish or fish oil, should be increased, especially in those with or at risk for coronary artery disease.

  • The long-chain “marine” omega-3s in fish oil (DHA and EPA) enjoy far more evidence of benefit, versus the omega-3 found in plant foods (ALA).

  • People without diagnosed heart disease or risk factors for heart disease should consume about 500 mg of omega-3s – the approximate amount in two meals of oily fish – per day.

  • People with diagnosed coronary artery disease should take about 1 gram of omega-3s per day. Fish oil supplements are usually needed to reach this daily dose.

  • Patients with elevated triglycerides who take 3 to 4 grams of omega-3s per day usually lower their triglyceride levels by 20-50 percent. Fish oil supplements are usually needed to reach this daily dose.

  • Combining a statin with an omega-3 fish oil supplement is a safe and effective way to improve lipid levels and cardiovascular prognosis beyond the benefits provided by statin therapy alone.

  • Reduced cardiac risk is linked more clearly to having high DHA blood levels than to high EPA levels. However, it’s difficult to separate the effects of these two omega-3s, which have overlapping effects and occur together in all fish oils. (Some prescription fish oils contain mostly EPA, without good evidence that this is better than the approximate 45/55 blend of DHA and EPA found in most fish and fish oil supplements.)

Diagnostic markers and prospects

  • Blood levels of DHA and EPA could help identify patients with deficient levels and to individualize dosage recommendations.

  • The quantity of DHA in our blood and cell membranes correlates closely with the quantity of DHA in our heart muscles.

  • Higher DHA blood/cell/heart levels correlates with a reduced risk of adverse cardiac events.
Mechanism of action
  • Omega-3s appear to confer cardiovascular benefits largely through enrichment of our cell membranes. Via this mechanism, omega-3s help reduce the likelihood of erratic heart rhythms, lower blood pressure, improve the functioning of our arteries and their linings, reduce platelet aggregation (blood stickiness), and favorably affect “autonomic tone” (see sidebar above).
  • It is important to note, as the authors do, that to date no randomized controlled trial has shown that omega-3s can definitely reduce the risk of a first heart attack or stroke.
  • But in one of the large clinical trials reviewed in the Mayo Clinic paper, the Japanese participants who were free of heart disease and took fish oil were 18 percent less likely to suffer an adverse cardiac event before the study ended.
  • While the new paper uncovers nothing new, this clear, concise evidence review presents the most pertinent research in one place, and adds many details of interest to physicians, patients, and all health-conscious folks.
To read the entire Mayo Clinic paper – titled “Omega-3 Fatty Acids for Cardioprotection” –  click here.


  • Lee JH, O’Keefe JH Jr, Lavie CJ, Marchioli R, Harris WS. Omega-3 Fatty Acids for Cardioprotection. Mayo Clin Proc. 2008;83(3):324-332.
  • Curtis BM, O'Keefe JH Jr. Autonomic tone as a cardiovascular risk factor: the dangers of chronic fight or flight. Mayo Clin Proc. 2002 Jan;77(1):45-54. Review.
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