differences among study populations and the type, amount, or preparation method of seafood consumed. For example, among studies reviewed, it has been hypothesized that the benefit of greater amounts of seafood may be more apparent in populations that have low seafood intakes and are at higher risk for cardiovascular disease (Marckmann and Gronbaek, 1999). Although initial studies suggested an optimal level of seafood consumption, more recent analyses have brought this observation into question and have suggested a more continuous association between seafood consumption and prevention of cardiovascular disease (p for trend = 0.03) (He et al., 2004b).

The possible mechanisms by which seafood or EPA/DHA supplements are cardioprotective include demonstrated antiarrhythmic, antithrombotic, antiatherosclerotic, and anti-inflammatory effects. Ismail (2005) and Calder (2004) linked the consumption of EPA/DHA to improved endothelial function, lower blood pressure, and lower fasting and postprandial triglyceride concentrations. Furthermore, populations and individuals who consume large amounts of seafood also tend to consume smaller amounts of alternative protein sources, such as beef, that are rich in saturated fats that are known to increase blood cholesterol levels and to elicit a proinflammatory state (Weisberger, 1997; Baer et al., 2004; Miller, 2005). Any one or a combination of these effects may explain the association between seafood intake and cardiovascular protection observed in some studies.

It is important to note that supplementation trials have been mostly conducted in individuals with existing cardiovascular disease for secondary prevention. Therefore, these findings are relevant to the progression of existing cardiovascular disease, but may not be relevant to the development of new cardiovascular disease in the general population, as these two processes may have different biological determinants. On the other hand, many observational studies of seafood consumption have been conducted in the general population and are relevant to primary prevention and the development of cardiovascular disease in the first place. Again, as determinants of cardiovascular disease development may be different from those of disease progression, the pertinence of these observational studies to secondary prevention is limited. These studies are, however, more informative than supplementation studies to assess the role of seafood in a healthy diet. The committee has tried to clearly differentiate these two types of studies and the conclusions that can be derived from them in the discussions that follow.

Seafood or Omega-3 Fatty Acid Consumption and Coronary Heart Disease

Randomized Controlled Trials in High Risk Populations

No randomized controlled trials have been carried out on subjects representative of the general population, as the small expected number of



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