Long‐term Effects of Dietary Marine ω‐3 Fatty Acids upon Plasma and Cellular Lipids, Platelet Function, and Eicosanoid Formation in Humans

Abstract

We studied the incorporation and metabolism of eicosapentaenoic (EPA) and docosahexaenoic acid in six human volunteers who supplemented their normal Western diet for 5 mo daily with 10-40 ml of cod liver oil, rich in w-3 polyunsaturated fatty acids. EPA and docosahexaenoic acid were incorporated into the total phospholipids of plasma, platelets, and erythrocytes in a doseand time-dependent manner. During w-3 fatty acid ingestion serum triacylglycerols were lowered and platelet aggregation upon low doses of collagen was reduced. Concomitantly, formation and excretion of prostanoids showed a characteristic change. As measured in serum from whole clotted blood, thromboxane A3 was formed in small amounts, whereas thromboxane A2 formation was reduced to 50% of control values. Excretion of the main urinary thromboxane A metabolites was unaltered in subjects with low basal excretion rates, but decreased markedly in two subjects with high control values. As determined from the main urinary metabolite, prostaglandin I3 was formed from EPA at rates up to 50% of unaltered prostaglandin l2 formation. The biochemical and functional changes observed lasted for the entire supplementation period of 5 mo and were reversible within 12 wk after cessation of cod liver oil intake. Favorable changes induced by long-chain w-3 fatty acids include a dose-related and sustained shift of the prostaglandin I/thromboxane A balance to a more antiaggregatory and vasodilatory state.

Insulin Resistance, Inflammation, and Serum Fatty Acid Composition

“…These relations were most likely to have a dietary explanation because food is the major source of these FAs. EPA, in part converted from DHA, is transformed into a nonaggregatory agent that increases the synthesis of a vasodilator, prostaglandin I 3 , leading to further reduction in platelet aggregation and to increased vasodilation (24).…”

Aspirin-induced decline in prostacyclin production in patients with coronary artery disease is due to decreased endoperoxide shift. Analysis of the effects of a combination of aspirin and n-3 fatty acids on the eicosanoid profile.

“…In this study, we used eicosapentaenoic acid (EPA) from fish oil as a "probe" to help clarify in vivo the role of endoperoxide shift in the ASAinduced decrease in PGI2 production in patients with atherosclerotic disease (Figure 1 27,35,37,38 Thus, any shift of three series (EPAderived) endoperoxides from the platelet to the endothelial cell should be minimal. Therefore, if the ASA-induced decline in endothelial cell prostacyclin production is due largely to the loss of the supply of endoperoxides from platelets, then PGI2 production should decline far more than PGI1 production.…”

Effects of eicosapentaenoic and docosahexaenoic acids on apoprotein B mRNA and secretion of very low density lipoprotein in HepG2 cells.

“…21 EPA competes with arachidonic acid for cyclooxygenation and thus inhibits the production of protaglandins of the 2-series. 22 It also inhibits the synthesis of leukotrienes and lipooxygenase products in monocytes and neutrophils. 23 By contrast, DHA is incorporated and conserved in phospholipids of tissues like the brain and retina.…”