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Major study shows Omega-3 fish oil supplements reduce sudden cardiac death

The outcome of the GISSI-Prevenzione trial, conducted by researchers in Italy on 11,323 patients, showed that one gram daily of fish oil derived omega-3 fatty acid supplement taken for three months reduced the risk of sudden cardiac death from arrhythmia by one half compared to those who received a placebo. The research was published online in April 2002 in Circulation: Journal of the American Heart Association.

Lead author Roberto Marchioli MD, of Consorzio Mario Negri Sud in Santa Maria Imbaro, Italy, stated, "That was a surprise. The risk of death, and sudden death, is higher in the first months after a heart attack. It is exactly in this period that the reduced effect on sudden death was noted.”

In an attempt to determine the timing of the benefits of omega-3 polyunsaturated fatty acid supplements, recent heart attack survivors were randomized to receive the fatty acids, vitamin E supplements, both supplements or a placebo. Total mortality was significantly lowered in the group receiving the fatty acids at three months, and the risk of sudden death was significantly lowered at four months. These trends continued to reveal a similar reduction in the risk of heart related deaths at six and eight months. The risk reductions were not associated with changes in cholesterol levels or by decreases in blood coagulation.

In an accompanying editorial, Alexander Leaf MD, of Harvard Medical School, discussed the ability of fatty acids to regulate the electrical activity of heart muscle cells, and stated that the findings of this study support the theory that an imbalance of omega-3 and omega-6 fatty acids promote arrhythmias. He commented, "This study is important because there is no really effective therapy for arrhythmias."

The Italian researchers note that study participants ate a Mediterranean-style diet – high in fruits, vegetables, olive oil and fish. Yet, despite the same healthy diet, those who received the n-3 PUFA supplements had fewer sudden deaths than those who did not. N-3 PUFA are essential fatty acids – the body needs them to function properly but does not make them. Humans must obtain them through food, which in the case of n-3 PUFA means eating fish, such as salmon, tuna or mackerel.

In the GISSI-Prevenzione study, researchers enrolled 11,323 patients throughout Italy who had suffered recent heart attacks and randomized them into four groups.

In addition to standard medical treatment and lifestyle counseling for their condition, 2,835 participants received 1 gram of n-3 PUFA daily (equal to one fatty fish meal); 2,830 took 300 milligrams of vitamin E daily; another 2,830 took both; and 2,828 took a placebo.

In the new analysis, Dr. Marchioli and his colleagues found that at three months, patients treated with n-3 PUFA had significantly lower mortality than those not taking the supplements (1.1 percent vs. 1.6 percent). By the end of the trial at 42 months follow-up, mortality was 8.4 percent for those on n-3 PUFA and 9.8 percent for those not taking it.

The reduction of sudden cardiac death risk from n-3 PUFA treatment was nearly significant at 3 months (0.5 percent vs. 0.7 percent for those not on the supplement). By the study’s end at 42 months, the risk of sudden death was 2.0 percent for people taking n-3 PUFA, vs. 2.7 percent for those who did not.

“The mortality benefit was mainly due to a reduction in sudden death,” Dr. Marchioli says.

How n-3 PUFA protects the heart is unknown. However, Dr. Leaf and his colleagues have shown that the fatty acids play an important role in regulating the electrical activity of heart muscle cells. “They stabilize these cells so they are very resistant to arrhythmias,” he says.

Dr. Leaf also notes that these findings support a theory that an imbalance of n-3 PUFA and fatty acids called n-6 PUFA promote arrhythmias. He suggests that adding n-3 PUFA to an already healthy diet, while reducing n-6 PUFA (which are abundant in plant seed cooking oils and margarine – i.e. corn, safflower, sunflower seed oils), improved the ratios of the two types of fatty acids, therefore, decreasing the risk of sudden death.


GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 1999;354:447-55. [MEDLINE]

Circulation: Journal of the American Heart Association; April 2002

Key concepts: Omega-3 fatty acids, arrhythmia, sudden cardiac death