Effects of omega-3 fatty acids on cardiovascular disease.

Screening All abstracts identified through the literature search were screened using eligibility criteria developed in conjunction with the TEP. These criteria were designed to minimize incorrect exclusion of relevant studies. We included all English language original, experimental, or observational studies that evaluated any potential source of omega-3 fatty acids in at least 5 human subjects, regardless of the study outcomes reported in the abstract. In addition, we excluded abstracts that clearly included only subjects who had a non-CVD-related condition (e.g., cancer, schizophrenia, or organ transplant). Reports published only as letters or as abstracts in proceedings were also excluded. All abstracts were categorized to 1 or more of the key questions or as rejects. Full Article Inclusion Criteria Articles that passed the abstract screening process were retrieved, and the full articles were screened for eligibility. The following types of articles were rejected during this round: review articles, inappropriate human population, pediatric studies and studies conducted on subjects less than 19 years old, no mention of omega-3 fatty acid intake, dietary supplements, or fish consumption, daily dose of omega-3 fatty acid greater than 6 g, fewer than 5 subjects in omega-3 fatty acid arm(s), prospective interventional studies of less than 4 weeks duration, and no appropriate outcome of interest reported. Stud ies that reported only the tissue level of omega-3 fatty acid without explicitly reporting the amount of omega-3 fatty acid consumed were also excluded. However, we included studies of Mediterranean diets and studies that reported fish servings. Specific sources of omega-3 fatty acid considered acceptable included fish oils, dietary fish, canola (rapeseed) oil, soybean oil, flaxseed or linseed oil, walnuts or walnut oil, and mustard seed oil. Other sources were eligible if omega-3 fatty acid levels were reported to be greater than control. For each study that was rejected, the reason(s) for rejection was noted. For analyses of adverse events and drug interactions, all studies were included regardless of omega-3 fatty acid dose or study duration (including washout period). Inclusion and exclusion criteria for maximal omega-3 fatty acid intake were based on discussions with the TEP, in which it was agreed that omega-3 fatty acid intake above 6 g per day is impractical and has little relevance for health care recommendations. Therefore, with the exception of studies of adverse events, the inclusion criterion for maximum daily intake was set at 6 g per day and studies of higher daily intake were excluded. The definition of omega-3 fatty acid dose varied greatly across studies. Thus, the maximal allowable dose may have applied to total daily omega-3 fatty acid, total EPA+DHA, or a total of other combinations of omega-3 fatty acids. The total did not refer to total fish oil. In this report, we accepted randomized controlled trials (RCTs) or prospective cohort studies with a minimum of 1-year follow-up to address CVD outcome questions. We also accepted casecontrol studies and cross-sectional studies that assessed the prevalence of CVD in populations with varying leve ls of omega-3 fatty acid consumption. In some cases, a study was reported in multiple publications (e.g., interim results might have been reported in 1 publication and various outcomes in others). For these studies, we identified and grouped articles belonging to the same