Inclusion of a study of questionable scientific integrity. The British Medical Journal has published a long article shedding serious     doubt on  the credibility of the work of RB Singh 7 . Nevertheless, a study from this author was included. 

 Inclusion of studies not designed to detect effects on mortality, cardiovascular disease, and cancer.

Contradiction in search criteria. A search of the literature was conducted up to February 2002. Nevertheless, some trials published later were included (most notably the DART-2 study). Accordingly, how the studies were selected is not clear.

Combining outcomes from studies conducted in different populations. In two endpoint studies, EPA and DHA reduced total mortality mainly by reducing sudden cardiac death, but not non-fatal myocardial infarctions 4,8 . These trials were conducted in Europe , an area with a high incidence of sudden cardiac death. However, in populations with a high background intake of marine omega-3 fatty acids, like the Japanese, sudden cardiac death rarely occurs, and increasing intake of EPA reduced the occurrence of other major cardiovascular events, like fatal and non-fatal myocardial infarctions. Therefore, uncritically combining endpoints across vastly different cultures is not scientifically sound.

 Inconsistencies in logic. It is stated with respect to DART-2, that “this RCT had the longest follow-up of all RCTs and the harmful effects of methylmercury could be cumulative.” This is a puzzling statement for two reasons: 1) there is no conclusive evidence that the amount of methylmercury obtained from 2 oily fish meals per week increases risk for cardiovascular disease, and 2) the excess mortality was seen, not in the fish advice group where methylmercury might conceivably have played a role, but in the group taking fish oil capsules which are free of methylmercury.  The authors then go on to state “This advice [i.e. to eat more oily fish especially after myocardial infarction] should continue at present.” If methylmercury was the problem, then advice to eat fish should not continue at present.  

Attempting to treat diets/supplements as drugs. Truswell has recently published a critique of the Cochrane approach to meta-analysis, noting that their approach, which works reasonably well for drug studies, is not appropriate for dietary interventions 9 . He notes that no expert committees or international bodies have embraced past Cochrane conclusions regarding the role of nutritional interventions in CHD.

         A number of studies using different scientific methodologies have appeared since the cut-off date of the Cochrane analysis (2002 or 2003). They continue to show a protective effect of EPA and DHA for cardiovascular endpoints 10,11 . One example is the randomized open-label Japan EPA Lipid Intervention Study (JELIS), conducted in Japan in 18,645 hyperlipidemic persons being treated with statins who were followed for 4.6 years 12 . This study (reported at the AHA meeting in 2005) found a 19% reduction in major adverse cardiovascular events in the EPA group (p=0.01).  

        The weight of the evidence in favour of omega-3 fatty acids does not rest solely on the publications chosen for the Cochrane analysis as alluded to above. Each type of scientific evidence has its inherent limitations, and therefore, conclusions must be drawn based upon the magnitude of the effect and consistency of the results seen using all types of research paradigms – clinical trials, observational studies, and mechanistic experimental investigations 13,14 . Taking the weight of the scientific evidence together, the cardiovascular benefit of fish and fish oils has clearly been demonstrated.  

        In our view, the weight of the evidence available in May of 2006 is sufficient to conclude, even in light of the Cochrane analysis, that EPA and DHA reduce risk for cardiovascular diseases. Not only do we feel so, but also the American Heart Association/American College of Cardiology 15 , the European Society for Cardiology 16 , a systematic review conducted for the Agency for Healthcare Research and Quality at the NIH 17 , the Harvard Center for Risk Analysis 18 , and a number of other national and international bodies 19-22 .