Omega-3 fatty acids in cardiovascular disease--an uphill battle

In cardiology, results of recent large intervention trials with eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplements were neutral. In contrast, in epidemiologic studies, an inverse relation between clinical events and intake of EPA+DHA was found which was steeper for higher levels of EPA+DHA. A standardized way of determining levels is the Omega-3 Index, which is the percentage of EPA+DHA of a total of 26 fatty acids measured in erythrocytes. According to current criteria, a low Omega-3 Index is a cardiovascular risk factor. What can explain this contradiction? Trial participants were recruited irrespective of their baseline status in EPA+DHA - an important predictor of events. Levels of EPA+DHA have a statistically normal distribution; together with the large inter-individual variability of levels' responding to increased intake, this created a large overlap of EPA+DHA levels between intervention and control groups. Moreover, trial participants were advised to take EPA+DHA supplements with breakfast, frequently a low fat meal, resulting in poor bioavailability. As a result, there is an urgent need for new intervention trials in cardiology, for which participants with a low baseline omega-3 index are recruited, and then treated with individually tailored doses of EPA+DHA to a prespecified target range.