Fatty acid facts, Part III: Cardiovascular disease, or, a fish diet is not fishy

Preclinical and clinical studies have demonstrated that omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a significant role in the prevention of cardiovascular disease. These fatty acids are called essential fatty acids as they fulfil essential functions and the mammalian cell cannot synthesize them de novo. Dietary sources of n-3 PUFAs include fish oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The clinical relevance of these molecules is derived from the incorporation of EPA and DHA into cell membranes. The presence of EPA/DHA alters the physical characteristics of the membrane. Both these altered physicochemical membrane properties and the presence of n-3 PUFAs released by the action of phospholipid lipases (resulting in antiinflammatory eicosanoids) improve biological functions such as signal transduction, ion channelling and ligand binding to nuclear receptors. EPA/DHA also reduce or quench gene expression of cyclooxygenase-2 and other enzymes, thereby diminishing the formation of proinflammatory molecules. Increased EPA/DHA concentration also gives rise to antiinflammatory lipid mediators, called lipoxins, resolvins and protectins. Another important function of n-3 PUFAs is scavenging of free radicals, which diminishes inflammatory response and oxidation of lipoprotein particles, notably low density lipoproteins. The interplay of these molecular processes has distinct cardioprotective effects, which involve actions on lipid metabolism, lipoprotein particle size, blood pressure, vascular function, coagulation potential, inflammatory response, atheroma formation and antiarrhythmic. In view of these actions, fish oil preparations and/or intake of oily fish are recommended as primary and secondary prevention of cardiovascular disease and sudden cardiac death. Large, ongoing trials will further elucidate the presumed favorable effects of EPA/DHA in heart failure and diabetes. This review provides a summary of the physiological mechanisms of the action of EPA and DHA and highlights the epidemiological evidence for a reduction in cardiac events and mortality.