Is this the final end of all hopes for the preventive effects of omega-3 fatty acids on cardiovascular disease? Once again, fish oil capsules have been shown in a large Italian study on cardiovascular-risk patients to be ineffective. Prof. Dr. Clemens von Schacky, director of preventive cardiology at the Ludwig Maximilian University of Munich and CEO of Omegametrix GmbH, talked with EJCPR in order to offer a possible explanation.
According to Prof. Dr. Clemens von Schacky, “The problem with the ethyl ester capsules is the poor bio-availability of the omega-3 fatty acids. Without food intake they have virtually no effect.”
The new study was randomized, double-blind, placebo-controlled, and included more than 12,000 patients in primary prevention who exhibited several cardiovascular risk factors. The study was conducted in Italy where the famous GISSI data was collected, where the original basis for the positive benefits of Omega-3 fatty acids was formed.
However, the Italian authors of the Risk and Prevention study by Maria Carla Roncaglioni of the Instituto di Ricerche Farmacologiche in Milan, now report in the New England Journal of Medicine that in their rather large study the daily intake of omega-3 fatty acids over the course of 5 years did not reduce cardiovascular mortality and morbidity . “Our results provide no evidence for a benefit of n-3 fatty acids in the prevention of cardiovascular disease or cardiovascular death,” writes the research group.
For years, cardiologists and nutrition experts have discussed the preventive effects of fish oil for cardiovascular disease. In some studies, especially the known GISSI-Prevention trial in post-infarction patients, supplementation with omega-3 fatty acids had demonstrated success in patients who had already suffered a heart attack, and in patients with heart failure. In other recently published studies, such as in ORIGIN in patients with early diabetes or impaired glucose tolerance, and in OPERA for the prevention of postoperative atrial fibrillation, supplementation with omega-3 fatty acids had, however, no effect.
Some of the researchers involved in the study group also took part in the GISSI study, and had hoped for an equally positive effect of fish oil capsules in cardiovascular risk patients. Almost 10 years ago when Roncaglioni and colleagues had begun, there were a total of 12,513 patients with multiple cardiovascular risk factors who were randomize so that they were given either omega-3 fatty acids (1 g daily) or placebo (olive oil). The patients were cared for by 860 physicians practicing in Italy.
But the result after an average of 5 years of follow-up were disappointing: The curves of the primary endpoint – the time until death or hospitalization, both due to cardiovascular causes, – were absolutely identical in the two groups. Also with respect to all secondary endpoints (combination of time until death as a result of myocardial infarction or stroke as well as the combination of time to death due to cardiovascular causes or hospitalization for cardiovascular causes), there were no differences between the fish oil and placebo group.
The authors lack a plausible explanation for the discrepancy between their results and those of the GISSI study. They merely express a guess: “It is possible that the n-3 fatty acids act especially in patients who are particularly susceptible to ventricular arrhythmic events, such as patients with an infarct scar or left ventricular dysfunction,” they write. Their study, the authors said, had only a very limited capacity to detect sudden deaths or cardiac-induced arrhythmic events.
Schacky thinks there may be one possible explanation for the null result of the study. “The problem with the ethyl ester capsules is the poor bioavailability of the omega-3 fatty acids. Without food intake they have virtually no effect,” he told EJCPR.
“The result is disappointing indeed – a study with more neutral results. When I asked when patients should take the capsules, I was told by the Study Group, ‘for breakfast ‘. Since the Italian breakfast is made up almost exclusively of espresso, I’m not surprised by the results.” When taken with food, declared Schacky, digestive enzymes secreted by the pancreas break down omega-3 fatty acids, so they can be absorbed. In the GISSI study, he says, the capsules were taken at a different time of day.
The second problem Schacky considers is the different omega-3 levels of patients at baseline. Together with Prof. Dr. W. S. Harris of the non-profit research organization Sanford Research in Sioux Falls, South Dakota, USA, Schacky has launched the 2002 Omega-3 Index to Life. The index measures the proportion of the fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in the erythrocytes and is expressed as a percentage of the total n-3 fatty acids. The values that are influenced, among others, are fish consumption, age, sex, weight and medical history, and are ideally between 8-11%. For many people in Italy the index often would only be around 4%, explained Schacky. In patients with optimal values, he says, the effect of supplementation equals to zero. Therefore, he suggests a further study be conducted exclusively with patients who have a low omega-3 index.
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