ABSTRACT
Much evidence has accumulated from various lines of inquiry that indicates that the dietary fatty acid intake and lipid acyl composition of tissues is a determinant of many of the chronic diseases prominent in the Western World, notably cardiovascular disease. It has been appreciated since the 1950s that when dietary polyunsaturated fat intake is increased, a decrease in the total serum and lipoprotein cholesterol levels results [1]. Bang and Dyerberg, in their study of the Greenland Eskimos, a group in which CVD had an extremely low incidence, made the ground breaking inference that the high dietary intake of the long chain polyunsaturated fatty acids, eicosapentanoate and docosahexaenoate was responsible for this protection from disease [2]. More recently, several epidemiological studies have reported a relationship between dietary n-3 polyunsaturates and the risk of CVD [3-8]. For example, Dolechek et al. found an inverse relationship between alpha-linolenate and mortality from CVD, all CVD and on all cause mortality, however no relationships were found for linoleate [3]. They also observed an inverse relationship of fish oil fats with coronary heart disease, CVD, and all cause mortality. In agreement with these findings was the study by Siscovick et al. who observed that a level of fish fats equivalent to about one meal a week was associated with a 50% reduction in the risk of primary cardiac arrest [4]. The n-3 fatty acids have also been the subject of large secondary prevention trials. In the LYON Heart Study, deLorgeril et al. found that a diet enriched with alpha-linoleate was more effective than other diets in use for this purpose for the secondary prevention of coronary events and death [9]. Burr et al. in the DART trial, found a 29% reduction in overall mortality after 2 years when a large group of men advised to consume fish twice a week after surviving a heart attack [10]. Singh et al. reported a decline in coronary heart disease events in patients with suspected myocardial infarctions after one year of consuming either 2 g of long chain n-3 fatty acids or 2.9g of alpha-linolenic acid per day [11]. A very large trial (GISSI-Prevenzionne) of 11,324 patients demonstrated that 850 mg of eicosapentaenoate/docosahexanoate per day led to a 20% reduction in total mortality over a 3.5 year follow-up period in patients with a history of CVD [12]. McLennan et al. found that fish oil fed marmoset monkeys were resistant to cardiac arrhythmias [13]. Billman et al. subsequently showed that dogs infused with a fish oil emulsion had a remarkable resistance to cardiac arrhythmias induced by compression of the left circumflex artery [14]. Kang and Leaf, in a series of publications (for
effects of long chain polyunsaturates against arrhythmias. Lands et al. proposed the unifying concept that dietary supplementation with n-3 fatty acids leads to loss of cellular arachidonate and increases in eicosapentanoate and docosahexaenoate [16]. This then leads to a diminished eicosanoid response upon cellular stimulation due to the decreased efficacy of the n-3 eicosanoid analogues to the arachidonate-derived eicosanoids. Lands et al. suggested that the percentage of plasma phospholipid arachidonate is related to thromboxane generation and platelet activation and thus to the risk of cardiovascular deaths [16]. Harris, in his review, suggested that increased long chain n-3 fatty acid intake leads to decreases in plasma triglyceride levels due to decreased hepatic synthesis and secretion [17]. A recent meta-analysis of 17 studies involving over 46,000 men and 10,000 women suggested that the plasma triglycerides level is a risk factor for CVD that is independent of HDL-cholesterol [18]. In addition to the aforementioned studies, Knapp et al. found an anti-hypertensive effect of fish oil [19] and Christensen et al. a beneficial effect on heart rate variability [20]. It should be clear then that the balance of dietary fatty acids and the resulting tissue fatty acid composition are critical determinants of cardiovascular function and the predisposition to disease.
