The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 13 No. 6 • December 2010

Low Dose Omega-3 Fatty Acids “Fails” to Reduce
Cardiovascular Events in Heart Attack Patients

The Unfortunate Result of Poorly Designed Clinical
Trials without Adequate Explanation of Findings

The cardiovascular benefits of omega-3 fatty acids have been well established in several hundred peer reviewed scientific papers, but as some conflicting data continue to be published (unavoidable when study designs and populations studied can greatly differ), there is still some confusion among doctors and the public concerning the use of omega-3 fatty acid supplements. One particularly unfortunate study was published in the Nov. 18, 2010 the New England Journal of Medicine showing that a “low dose” of omega-3 fatty acids “did not significantly reduce the rate of major cardiovascular events among patients who had had a myocardial infarction …”

The core of the problem with this study was the way the dose of the omega-3 fatty acids was chosen and why it was so low (too low to provide the intended benefits). In fact, how the dose was selected wasn’t even discussed in the paper, but it became all too apparent to us after identifying the source of the omega-3 enriched margarine used in the study. The supplier of the trial margarines was Unilever R&D, as identified at the very end of the paper. Clearly, then, the purpose of the study from Unilever’s point of view was to evaluate the benefits in a clinical trial of an omega-3 fortified margarine they were developing. Nothing wrong with that, of course, but it appears likely that the dose of omega-3 fatty acids added to the margarine had to be restricted to a low dose due to the problem of preventing off-tastes if the dose were higher. As a result, the study tested the effects of a low dose chosen to avoid off-tastes rather than a higher dose more likely to provide the desired benefits to the heart attack patients.

The subjects were 4837 patients who had had a prior heart attack and who were 60–80 years of age, with 78% being men. These patients, who were receiving “state-of-the-art” antihypertensive, antithrombotic, and lipid lowering therapy then received one of four trial margarines: a margarine supplemented with EPA and DHA (with a targeted additional daily intake of 400 mg of EPA-DHA), a margarine supplemented with ALA (alpha linolenic acid (an omega-3 fatty acid which has a shorter carbon chain than DHA and EPA) targeted to deliver 2 grams of ALA a day, a margarine supplemented with EPA-DHA and ALA, and a placebo margarine.

In fact, the subjects ate on average 18.8 grams of margarine a day, which resulted in additional intakes of 226 mg of EPA combined with 150 mg of DHA, 1.9 grams of ALA, or both, in the active treatment groups.

Lower Than the Omega-3 Dose Recommended By the American Heart Association

In the AHA Scientific Statement,2 the authors concluded that “[e]vidence from prospective secondary prevention studies suggests that EPA + DHA supplementation ranging from 0.5 to 1.8 g/d (either as fatty fish or supplements) significantly reduces subsequent cardiac and all-cause mortality.” Hence, the low-dose margarine did not supply even as much of EPA + DHA as the lowest dose in the AHA recommended range. We personally recommend 2 grams of EPA + DHA for most people, and suggest that those at risk for heart attacks ask their doctor if he or she would see a problem with an intake of 4 grams a day of EPA + DHA.

Unfortunately, the media reported this study as a failure of omega-3 fatty acids to provide protection. Despite the negative conclusion, in fact in the subgroup of women receiving the ALA supplemented margarine, there was a reduction in the rate of major cardiovascular events that approached significance (p = 0.07). Moreover, a post hoc exploratory analysis carried out by the authors found that in diabetic patients, “we found reductions in cardiovascular end points with EPA-DHA, as compared with placebo, that were in line with those shown in the GISSI-Prevenzione trial. The strongest effects — reductions of approximately 50% — were the effects on the rates of fatal coronary heart disease and arrhythmia-related events. The rate of arrhythmia-related events was also reduced with ALA as compared with placebo or EPA-DHA only.”

We hope that Unilever and other companies developing omega-3 supplemented margarines do not lose interest as a result of this study but look into the possibility that better stabilized omega-3 fatty acids (such as the purified and deodorized omega-3 fatty acids we offer in our omega-3 formulation) would allow an increased amount of omega-3 to be added to the margarine. We certainly hope that the negative media reports on this study do not discourage doctors from recommending and consumers from taking DHA-EPA supplements.


  1. Kromhout et al. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 363:2015-26 (2010).
  2. Kris-Etherton et al and for the Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation [an American Heart Association journal] 106:2747-57 (2002).

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