Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation

OBJECTIVE: The beneficial effect of dietary fish oil, rich in omega-3 polyunsaturated fatty acids (PUFAs), on cardiovascular disease is multifactorial and may partly rely on their anticoagulant action. We studied how fish oil intake influenced thrombin generation in plasma and which factors were involved herein. METHODS AND RESULTS: Twenty-five healthy males with borderline overweight received 3.0 g omega-3 PUFAs daily for 4 weeks. Fish oil intake reduced plasma triglycerides and lowered platelet integrin activation, as well as plasma levels of fibrinogen and factor V, but had no effect on vitamin K-dependent coagulation factors. Before fish oil intake, thrombin generation (reflecting the coagulant potential) considerably varied between plasmas from individual subjects, which were partly explained by variation in prothrombin, antithrombin, fibrinogen, and factor V levels. Fish oil intake reduced thrombin generation in the presence and absence of platelets. This reduction correlated with the fish oil effect on fibrinogen and factor V levels. Interestingly, the lowering effect of fish oil on thrombin generation and fibrinogen clustered around subjects with high fibrinogen carrying a structural fibrinogen alpha-chain polymorphism. CONCLUSIONS: Dietary omega-3 PUFAs provoke a hypocoagulant, vitamin K-independent effect in humans, the degree of which may depend on fibrinogen level. Intake of fish oil reduced fibrinogen and factor V levels as well as thrombin generation in plasma. The effects on thrombin generation and fibrinogen clustered around subjects with high fibrinogen carrying alpha-chain fibrinogen polymorphism. Thus, dietary fish oil can provoke a hypocoagulant effect depending on the fibrinogen level