Epidemiologic studies and clinical trials have reported beneficial effects of fish consumption on several cardiovascular disease (CVD) outcomes, such as all cause mortally, CVD death, cardiac death, sudden death, myocardial infarction and stroke. However, the mechanisms of this benefit are unclear.

As the first of a 3-part report on this topic, we analyzed relevant nutrition databases to describe the intake levels of various omega-3 fatty acids in the US population. We also performed a systematic review of the literature to assess the benefits of omega-3 fatty acid supplements or fish consumption on various CVD outcomes and to assess adverse events associated with intake of omega-3 fatty acid supplements.

Data Sources:
The Continuing Survey of Food Intakes by Individuals (CSFII) was reviewed and the third National Health and Nutrition Examination Survey (NHANES III) was analyzed for dietary intake. Medline, Embase, Cochrane Central Register of Controlled Trials, Biological Abstracts, and Commonwealth Agricultural Bureau databases were searched for potentially relevant studies to address the questions on the effects of omega-3 fatty acids.

Study Selection:
We screened over 7,464 abstracts and retrieved 768 full text articles. Thirty-nine studies met our inclusion criteria and provided data to address the key questions in this report. We used randomized controlled trials (RCTs) and observational studies that quantified the amount of fish or omega-3 fatty acid intake and that were at least 1 year in duration to assess the effects of omega-3 fatty acid consumption on CVD outcomes on risk of CVD in the general population (those without known CVD) and in populations at high risk due to pre-existing CVD or multiple CVD risk factors.

Data Extraction:
From each study that qualified, we extracted information about the study design, population demographics, the prescribed or estimated amount of omega-3 fatty acid supplements or fish consumed, and outcomes. For RCTs, we extracted information about the randomization and blinding techniques to assess methodological quality. For prospective cohort studies, we extracted estimated quantities of fish or fish oil consumed and their associated effect.

Data Synthesis:
The intake of omega-3 fatty acids in the population varies. Corrected for energy intake, men consume significantly less alpha-linolenic acid (ALA, 18:3 n-3) than women, adults more than youths, and subjects with a history of CVD less than those without CVD. Based on analyses of a single 24-hour dietary recall in NHANES III, only 25% of the US population reported any amount of daily eicosapentaenoic acid (EPA, 20:5 n-3) or docosahexaenoic acid (DHA, 22:6 n-3) intake.

Eleven RCTs and 1 prospective cohort study reported outcomes on CVD populations. The largest trial reported that fish oil (EPA + DHA) reduces all cause mortality and CVD events, although fish oil has no effect on stroke. Most other studies evaluating either fish oil or ALA supplements reported similar findings. There were few trials of ALA. In the only RCT that directly compared ALA and fish oil, both treatments were efficacious in reducing CVD outcome. No significant difference was found between the 2 supplements.

Twenty-two prospective cohort studies and 1 RCT reported data on general populations. Among the cohort studies there were considerable differences among the populations studied, as well as in the estimates of fish or omega-3 fatty acids consumed. Most of the large cohort studies found fish consumption was associated with lower rates of all cause mortality and CVD outcomes, but several studies reported no significant or negative results for the CVD outcomes. A significant benefit for stroke was reported in 1 study. The single RCT which evaluated ALA in a large general population lasted only 1 year yielding no significant results. Gastrointestinal symptoms associated with fish oil or ALA supplements are the most commonly reported adverse event and may require dose reduction or discontinuation in some individuals. Clinical bleeding is a theoretical concern but this was not borne out by the evidence.

Overall, consumption of omega-3 fatty acids from fish or from supplements of fish oil reduces all cause mortality and various CVD outcomes. The evidence for ALA supplements is sparse and inconclusive. The adverse events due to consumption of fish oil or ALA supplements appear to be minor. Many questions remain. The studies were heterogeneous with regard to the methods of estimating fish or omega-3 fatty acid intake, background diets, settings, and the methods of reporting results. Due to these reasons, the validity of applying the results of studies conducted in countries outside of the US to the US population is uncertain. The optimal quantity and type of omega-3 fatty acid, and the optimal ratio of omega-3 to omega-6 fatty acid (if such an optimal ratio exists), remain undefined. Not much data exists concerning the needs of different subpopulations. Different types of fish and the method of food preparation may have different effects. Future research needs to address these issues.

For full report see web address below: