Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in male cigarette smokers

Objective The effects of omega-3 fatty acids on endothelial function, fibrinolysis and platelet function are uncertain. We investigated the effects of omega-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis, and platelet and monocyte activation in healthy cigarette smokers; a group at increased risk of myocardial infarction. Design, setting, participants Twenty cigarette smokers were recruited into a randomised, double-blind, placebo-controlled, crossover trial of omega-3 fatty acid supplementation. Intervention omega-3 fatty acid supplements (2 g/day) or placebo for a 6-week period. Main outcome measures Peripheral blood was taken for analysis of platelet and monocyte activation, and forearm blood flow (FBF) was assessed in a subset of 12 smokers during intrabrachial infusions of acetylcholine, substance P and sodium nitroprusside. Stimulated plasma tissue plasminogen activator (t-PA) concentrations were measured during substance P infusion. Results All vasodilators caused dose-dependent increases in FBF (p<0.0001). Compared with placebo, omega-3 fatty acid supplementation led to greater endothelium-dependent vasodilatation with acetylcholine and substance P (p=0.0032 and p=0.056). Substance P caused a dose-dependent increase in plasma t-PA concentrations (p<0.0001) that was greater after omega-3 fatty acid supplementation compared with placebo (8.8 +/- 2.3 IU ml(-1) vs 3.6 +/- 1.1 IU ml(-1); p=0.029). omega-3 fatty acids did not affect platelet-monocyte aggregation, platelet P-selectin or CD40L, or monocyte CD40. Conclusions We have demonstrated for the first time that omega-3 fatty acids augment acute endothelial t-PA release and improve endothelial vasomotor function in cigarette smokers. Improved endogenous fibrinolysis and endothelial function may represent important mechanisms through which omega-3 fatty acids confer potential cardiovascular benefits.