excretion of 11-dehydrothromboxane B2, the latter being an indicator of platelet activation.

Platelet Hyperactivity. Several studies have confirmed an increased tendency for aggregation of platelets from diabetic subjects, linking the tendency to increased thromboxane production and showing that prior treatment with α-tocopherol can ameliorate the increased tendency for platelet aggregation (Colette et al., 1988; Gisinger et al., 1988; Jain et al., 1998; Kunisaki et al., 1990). However, no clinical intervention trials have tested directly whether antioxidants can decrease the incidence of thrombosis in vivo.

Diabetic Neuropathy. Tutuncu et al. (1998) studied 21 subjects with type II diabetes and neuropathy, who were randomly assigned to receive either 900 mg/day of α-tocopherol or a placebo for 6 months. Although fasting and postprandial glucose were unchanged, nerve conduction velocity in the median motor nerve fibers and tibial motor nerve distal latency improved significantly with vitamin E treatment. The authors concluded that further studies with a larger number of patients for longer periods of time are needed.

Summary. The available data strongly suggest that individuals with diabetes are subject to increased oxidative stress. However, no clinical intervention trials have tested directly whether vitamin E can ameliorate the complications of diabetes mellitus. A gap remains between the effects of vitamin E treatment on biochemical markers of oxidative stress, clinical efficacy, and validation of a relationship between biomarkers and clinical outcomes. Studies in humans show that lipid and lipoprotein oxidation proceed more rapidly in patients with diabetes than in nondiabetic people and that treatment with vitamin E can partially reverse this process (Reaven, 1995; Yoshida et al., 1997). In theory then, intervention with vitamin E therapy to inhibit atherogenesis might be more effective in individual diabetics than in nondiabetics. However, as of this date there are insufficient data on which to base a recommendation of supplemental vitamin E in diabetics.

Cancer

Cancer is believed to develop as the result of an accumulation of mutations that are unrepaired. DNA is constantly undergoing damage due to interaction with free radicals, and therefore one mecha-



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