Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms

Background: Epidemiologic studies have shown an inverse correlation between acute coronary events and high intake of dietary vitamin E. Recent clinical studies, however, failed to show any beneficial effects of α-tocopherol on cardiovascular events. Absence of tocopherols other than α-tocopherol in the clinical studies may account for the conflicting results. Objective: This study compared the effect of a mixed tocopherol preparation rich in γ-tocopherol with that of α-tocopherol on platelet aggregation in humans and addressed the potential mechanisms of the effect. Design: Forty-six subjects were randomly divided into 3 groups: α-tocopherol, mixed tocopherols, and control. ADP and phorbol 12-myristate 13-acetate¡induced platelet aggregation, nitric oxide (NO) release, activation of endothelial constitutive nitric-oxide synthase (ecNOS; EC 1.14.13.39) and of protein kinase C (PKC), and ecNOS, superoxide dismutase (SOD; EC 1.15.1.1), and PKC protein content in platelets were measured before and after 8 wk of administration of tocopherols. Results: ADP-induced platelet aggregation decreased significantly in the mixed tocopherol group but not in the α-tocopherol and control groups. NO release, ecNOS activation, and SOD protein content in platelets increased in the tocopherol-treated groups. PKC activation in platelets was markedly decreased in the tocopherol-treated groups. Mixed tocopherols were more potent than α-tocopherol alone in modulating NO release and ecNOS activation but not SOD protein content or PKC activation. Conclusions: Mixed tocopherols were more potent in preventing platelet aggregation than was α-tocopherol alone. Effects of mixed tocopherols were associated with increased NO release, ecNOS activation, and SOD protein content in platelets, which may contribute to the effect on platelet aggregation.