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Diabetes Patients Can Benefit from n-3 Fatty Acids

Dec 15, 2011

Use of a margarine fortified with n-3 fatty acids significantly reduced post-myocardial infarction ventricular arrhythmia-related events by 84% among diabetic patients….

Daan Kromhout, MPH, PhD, from Wageningen University in Wageningen, the Netherlands, and colleagues found that when compared with placebo, patients who used the margarine experienced an 84% reduction in ventricular arrhythmia-related events.

The supplementation with n-3 fatty acids also conferred a protective effect against cardiac arrest and sudden death, according to the study. The benefit in the subset of patients with diabetes softens somewhat the disappointment with overall results from the ALPHA-OMEGA trial, which Kromhout reported at the European Society of Cardiology meeting.

The study was designed as a secondary prevention trial that tested the hypothesis that n-3 fatty acid supplementation could reduce the risk of second heart attacks in elderly males.

When Kromhout reported the results at the ESC meeting he said that after 40 months, it “had no effect on the rate of major cardiovascular events,” despite the fact that there appeared to be an early benefit with the intervention.

ALPHA-OMEGA enrolled 4,837 men, ages 60 to 80, who had survived MI. The secondary analysis was limited to a subset of 1,014 patients considered high risk due to diabetes.

Nearly three-quarters of the patients were diagnosed with diabetes from the combination of elevated blood glucose levels, physician-diagnosed self-report, and drug treatment. About 14% were diagnosed with diabetes on elevated glucose levels only, 9.9% on self-report only, and 3.4% on drug treatment only.

The margarine contained eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA). They randomized patients to four groups: placebo, ALA, EPA-DHA, and EPA-DHA plus ALA.

Baseline characteristics between these four groups did not differ significantly, including factors such as use of antithrombotic drugs, blood pressure medication, lipid-lowering drugs, and antidiabetic drugs.

Researchers recorded a mean intake of margarine of 18.6 g/day and had an 86% compliance rate to the full protocol.

The median follow-up was 40.7 months, equating to 3,195 person-years of follow-up. In that time, 29 patients developed a ventricular arrhythmia-related event, two died suddenly, one had a nonfatal cardiac arrest, 11 had a fatal cardiac arrest, and 15 had a cardioverter defibrillator implanted.

After Kromhout and colleagues adjusted for age, sex, and current smoking, they found that the consumption of n-3 fatty acids significantly reduced ventricular arrhythmia-related events: 0.9% versus 5.6% for placebo, P=0.03 (HR 0.16, 95% CI 0.04 to 0.69).

The fatty acids also helped reduce other cardiovascular events. The hazard ratio for the combined endpoint of cardiac arrest and sudden death was 0.13 (95% CI 0.02 to 1.09) and for placement of a cardioverter defibrillator, it was 0.19 (95% CI 0.02 to 1.55).

The n-3 fatty acid supplementation did not make a significant difference for fatal MI, but in the adjusted model, the combination of all three fatty acids was the closest to reaching significance for this endpoint with a hazard ratio of 0.53.

They concluded, “These mechanistic findings support an important role for n-3 fatty acids in the etiology of diabetes, a major risk factor of fatal MI.”

Practice Pearls:
  • Results of this secondary analysis of data from a prospective, placebo controlled trial suggest that low-dose supplementation of n-3 fatty acids has a protective effect.
  • Some observational studies have suggested that supplementation with fatty acids eicosapentaenoic acid and docosahexaenoic acid may have beneficial effects upon outcomes of coronary heart disease and vulnerability to cardiac arrhythmias, but failed to confirm a benefit in elderly men with a history of MI.

Kromhout, D et al “N-3 fatty acids, ventricular arrhythmia-related events, and fatal myocardial infarction in postmyocardial infarction patients with diabetes” Diabetes Care 2011; 34: 2515-2520, 2011