The Mechanism of Action of Omega-3 Fatty Acids in Secondary Prevention Post-Myocardial Infarction

Nigel Harrison; Brihad Abhyankar

Disclosures

Curr Med Res Opin. 2005;21(1):95-100. 

In This Article

Other Effects of Omega-3 Fatty Acids

Blood Pressure

Omega-3 fatty acids appear to have a small, dosedependent, hypotensive effect, the extent of which seems to be dependent on the degree of hypertension.[33] In a meta-analysis, Morris et al .[34] found a significant reduction in blood pressure of 3.4/2.0 mmHg in studies with hypertensive subjects who consumed 5.6 g/day of omega-3 fatty acids. However this may happen at the cost of adverse reactions in such a high dose.[35] Omega-3 fatty acids in such high doses are not recommended for treatment of hypertension.

Thrombosis and Haemostasis

Omega-3 fatty acids decrease platelet aggregation[36,37] resulting in a modest prolongation of the bleeding time.[38] Although it seems clear that omega-3 fatty acids beneficially influence collagen-induced platelet aggregation thereby affecting haemostasis, their clinically relevant effects on thrombosis remain unclear. There is little evidence to suggest that an intake < 3 g/day of omega-3 fatty acids would cause clinically significant bleeding and in the GISSI-Prevenzione[1] study, there were no reported adverse events related to bleeding, although more than 80% patients were on aspirin.

Anti-Atherogenic and Anti-Inflammatory Effects

Mechanisms to explain the antiatherogenic (inhibition of new plaque formation) effect of omega-3 fatty acids have been proposed.[39] EPA and DHA appear to alter the metabolism of such molecules as vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intercellular adhesion molecule-1 (ICAM-1). In addition, they interfere with the arachidonic acid cascade that generates a wide variety of eicosanoids. EPA can not only replace arachidonic acid in phospholipid bilayers, but it also acts as a competitive inhibitor of cyclo-oxygenase. This results in a reduction in the production of the 2-series prostaglandins (thromboxanes and prostacyclins) and the 4-series leukotrienes. The 3- and 5-series prostaglandins produced from EPA are biologically less active.

Thies et al.[40] recently showed that atherosclerotic plaques readily incorporate n-3 fatty acids from fish-oil supplementation, inducing changes that can enhance the stability of atherosclerotic plaques.

Triglyceride Lowering

Omega-3 fatty acids reduce triglyceride concentrations in a dose dependent manner, with intakes of about 4 g per day lowering serum triglycerides by 25-30%. The hypo-triglyceridaemic effects of omega-3 fatty acids from fish oils are well established. In a comprehensive review of human studies, Harris[41] reported that 4 g/day of omega-3 fatty acids from fish oil decreased serum triglyceride concentrations by 25-30%. There were accompanying increases in low density lipoprotein (LDL) cholesterol of 5-10%, in high density lipoprotein (HDL) cholesterol of 1-3% and a dose-response relationship between omega-3 fatty acid intake and triglyceride lowering. Postprandial triglyceridaemia is especially sensitive to chronic omega-3 fatty acid consumption, with quite small intakes (2 g/day) producing significant reductions.[42]

Omacor is licensed in the dose of 2-4 g/day for the treatment of endogenous hypertriglyceridaemia as a supplement to diet when dietary measures alone are insufficient to produce an adequate response: - type IV in monotherapy, - type IIb/III in combination with statins, when control of triglyceride levels is insufficient.[43]

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