ABSTRACT
For most of the 20th century, epidemiologists consistently told of the link between the dietary intake of fat and cholesterol and the increased risk for cardiovascular events in Western countries, which was followed by decades of guidelines to consume a low-fat/low-cholesterol diet to prevent cardiovascular disease. Today, there is a much more nuanced understanding of the complex relationship between fats and CVD risk, including their types (e.g., saturated, unsaturated, omega-3, omega-6, omega-9), molecular structures (e.g., trans vs cis bonds, triglycerides, phospholipids, free fatty acids, ethyl esters), sources (e.g., plant, animal, marine), and the doses and ratios of each. A significant shift in our understanding of the association between fatty acid intake and cardiovascular disease occurred 50 years ago when Hans Olaf Bang and Jørn Dyerberg discovered that the Inuit populations of Greenland, eating a traditional diet with an extremely high intake of dietary fat, had a lower risk for cardiovascular events than Western populations consuming much less fat. This discovery, and the subsequent publication of these findings by Bang and Dyerberg, initiated a revolution in both nutritional research and cardiovascular intervention. Since then, the long-chain marine omega-3 fatty acids discovered in the Inuit diet and blood samples have been investigated for nearly every disease outcome and biomarker, including hundreds of clinical trials in healthy and at-risk populations. In that time, omega-3 fatty acid supplementation (primarily EPA and/or DHA from fish) has become increasingly popular as a means for reducing CVD risk, as illustrated by the inclusion of omega-3 fatty acids in the American Heart Association dietary recommendations for the prevention of heart disease and the FDA approval of several omega-3 pharmaceutical products for CVD-related biomarkers.
However, the increased popularity of omega-3 fatty acid supplementation is not without controversy or confusion. A recent re-evaluation of clinical trials performed years ago, through meta-analytical methodology, has led to several publications suggesting that there is limited cardiovascular risk reduction associated with EPA and DHA supplementation; however, epidemiological studies on the effect of a high fish intake continue to show a positive association with reduced CVD risk. These controversies are further mixed with numerous other debates surrounding the design of clinical trials testing omega-3 fatty acids for CVD outcomes, including how CVD risk should be measured (i.e., biomarker vs endpoints), whether primary or secondary prevention studies are more appropriate to measure risk, bioavailability issues of omega-3 fatty acid supplements, the baseline omega-3 status of trial participants and the concomitant use of other risk-reducing agents (i.e., statin drugs) in these trials. At nearly the same time, the results of large and well-designed intervention trials have been recently published demonstrating significant CVD risk reduction after consuming n-3 fatty acid supplements in some cases and limited benefits in others. It is not surprising, then, that there is still much confusion as to the utility of supplementing omega-3 fatty acids for cardiovascular event risk reduction.
In this chapter, we will review these recent studies, as well as several seminal clinical trials from the recent past. In addition, we will discuss the mechanisms underlying the association between omega-3 fatty acid intake and the pathophysiology and biomarkers known to influence the risk for cardiovascular disease. Included in this chapter is a discussion of various products (e.g., dietary supplements, pharmaceuticals) designed to deliver omega-3 fatty acids for therapeutic use and important distinctions between these products.University of Copenhagen
