P. Ferber et al., High dose supplementation of RRR-alpha-tocopherol decreases cellular hemostasis but accelerates plasmatic coagulation in type 2 diabetes mellitus, HORMONE MET, 31(12), 1999, pp. 665-671
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.