High dose supplementation of RRR-alpha-tocopherol decreases cellular hemostasis but accelerates plasmatic coagulation in type 2 diabetes mellitus

Background: Diabetes mellitus is associated with increased generation of fr ee oxygen radicals and depleted scavenging potential (oxidative stress), le ading to increased LDL oxidation and platelet hyperreactivity, the major co mponents of atherothrombotic vascular lesions. A main goal of antioxidant t herapy is to protect the LDL particle from atherogenic oxidation and to red uce the activated cellular hemostasis. Methods: We evaluated the influence of a high dose supplementation with 800 IU of the natural antioxidant RRR-alpha-tocopherol (vitamin E) per day for six months on serum levels, vitamin E load of LDL particles (HPLC), lag ph ase of LDL oxidation (Esterbauer's assay), platelet adhesion molecules, leu kocyte-platelet coaggregation (flow cytometry, D-III protocol) and coagulat ion (INR/PTT) in a group of 36 patients with type 2 diabetes (f/m 22/14; ag e 58 +/- 8.0: HbA(1) at baseline 10.25 +/- 1.7). Results: Average vitamin E levels Increased 2.65-fold accompanied by a 1.83 -fold increase of LDL-associated vitamin E and a 12.3 min prolongation of t he lag-phase of LDL oxidation (p < 0.001 for all parameters at six months). Platelet expression of PECAM-1 (CD31) (-30.2% positive cells, p < 0.001: a ntigen density -25%, p < 0.001), ICAM-2 (CD102) (-2.9 % positive cells, p < 0.01; antigen density -10.6%, p < 0.001) and fibrinogen (-1.6% positive ce lls, p < 0.001; antigen density -16.1%, p < 0.001) decreased. Concomitantly , platelet-leukocyte-coaggregation increased by 44% (p < 0.001), correlatin g to an INR reduction of 10.4% (1.06 +/- 0.09 to 0.95 +/- 0.09, p < 0.001, r = - 0.34). The PTT remained constant. Conclusion: The antioxidant protection from the increased vitamin E was acc ompanied by a decreased expression of constitutive and function-dependent p latelet adhesion molecules. However, increases in platelet-leukocyte coaggr egates and a shortened INR time suggest extrinsic coagulation activation, p ossibly by induction of a leukocyte tissue factor dependent mechanism. High dose supplements of alpha-tocopherol may override the available redox bala nce in well controlled type 2 diabetes. However, intrinsic effects of alpha -tocopherol must be discussed.