Dietary n-3 polyunsaturated fatty acids and amelioration of cardiovascular disease: possible mechanisms

Abstract

Consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) is associated with a reduced incidence of coronary arterial diseases. Dietary n-3 PUFAs act via several mechanisms. They depress plasma lipids, especially triglycerides (TGs), by inhibiting hepatic TGs and possibly apoprotein synthesis. They replace arachidonic acid (AA) in phospholipid pools with eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA). EPA and DHA, when released, inhibit cyclooxygenase and lipoxygenase and reduce eicosanoid synthesis, particularly thromboxane (TXA2) and leukotriene B4 (LTB4), by platelets and macrophages. Reduction of the proaggregatory, vasoconstrictive TXA2 decreases the thrombotic tendency of platelets. This is augmented by the limited depression of the vasoactive antiaggregatory prostacyclin (PGI2) and the generation of antiaggregatory prostaglandin I3 (PGI3) from EPA. The n-3 PUFAs also depress eicosanoid metabolism in platelets, monocytes, and macrophages, and thereby may retard the initiation and progress of atherogenesis. n-3 PUFAs reduce blood pressure and blood viscosity and modulate membrane fluidity and associated enzyme and receptor functions. The collective effects of n-3 PUFAs may account for the reduction in coronary arterial disease in populations consuming foods containing n-3 PUFAs.

Dietary n-6- or n-3-rich vegetable fats and α-tocopheryl acetate: effects on fatty acid composition and stability of rabbit plasma, liver and meat

“…If the n-6/n-3 fatty acid (FA) ratio of diets is reduced, this generates eicosanoids with more beneficial effects in some chronic diseases than those derived from n-6 FA (Kinsella et al, 1990;Simopoulos, 1997;Siddiqui et al, 2008).…”

Administration of low doses of fish oil derived N-3 fatty acids to elderly subjects

“…A modi®ed milk formula was designed to provide low amounts of ®sh oil, which might have a bene®cial effect in cardiovascular disease and other diseases common among elderly people (Kinsella et al, 1990;Simopoulos, 1991). In addition, the formula also provided essential nutrients for elderly subjects, such as minerals and vitamins.…”

“…Since this observation was made, a number of studies have con®rmed the bene®cial effect of n-3 PUFA in the prevention of cardiovascular disease (Kromhout et al, 1985;Leaf & Weber, 1988). These fatty acids appear to modulate eicosapentaenoic metabolism and lower serum triglycerides, and thus may have potential for the amelioration of atherogenesis and thrombosis (Kinsella et al, 1990;Simopoulos, 1991). In addition, other bene®cial effects have been described for n-3 PUFA in the treatment of arthritis, psoriasis, lupus, cancer and diabetes (Simopoulos, 1991), which are common diseases in elderly people.…”

“…Many factors are implicated in the development of coronary heart disease: genetic factors, hypertension, high plasma levels of low density lipoproteins, low levels of high density lipoproteins, diabetes mellitus, stress, some adverse behaviors such as cigarette smoking and also dietary factors are among the most relevant (Kinsella et al, 1990). Epidemiological studies reported that populations with a high consumption of ®sh such as the Greenland Eskimos and the Japanese showed a low incidence of coronary heart disease, which was attributed to n-3 polyunsaturated fatty acids (PUFA) derived from ®sh and specially to eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids (Bang et al, 1971;Bang et al, 1976).…”

Increased lipid peroxidation during long-term intervention with high doses of n-3 fatty acids (PUFAs) following an acute myocardial infarction

“…As the beneficial effects of n-3 PUFAs (Kinsella et al, 1990;Schmidt & Dyerberg, 1994) may be opposed by an enhanced lipid peroxidation, the main aim of this study was to prospectively assess the impact of concentrated n-3 PUFAs vs corn oil on lipid peroxidation during 12 months of treatment in 300 acute myocardial infarction (MI) patients demonstrating improvement in lipids (Nilsen et al, 2001). As a marker of lipid peroxidation, we determined TBA-MDA measured by HPLC.…”