in high-risk cardiovascular patients supplemented with 300 mg/day of all rac-α-tocopherol (GISSI-Prevenzione Investigators, 1999) and 400 IU (268 mg)/day of RRR-α-tocopherol (HOPE Study Investigators, 2000), were neutral. As of this date there are insufficient data on which to base a recommendation of supplemental vitamin E as a heart disease preventative for the general population.
Since cardiovascular complications account for the major causes of death in diabetes mellitus, it has been suggested that similar oxidative processes associated with cardiovascular disease may play a role in this chronic disease.
Oxidative Stress. It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be amenable to treatment with anti-oxidants (Baynes, 1991; Mullarkey et al., 1990; Semenkovich and Heinecke, 1997). Supplementation of either diabetic or nondiabetic subjects with α-tocopherol decreases the susceptibility of their LDL to ex vivo oxidation (Fuller et al., 1996; Reaven et al., 1995), but this treatment does not change blood glucose levels. Ceriello et al. (1991), using 600 and 1,200 mg/day of α-tocopherol, also observed decreases in labile hemoglobin Al (HbAl) and plasma glycosylated proteins. While Jain et al. (1996a) found a decrease in glycosylated hemoglobin with α-tocopherol supplementation at a relatively low dose (100 IU/day), Reaven et al. (1995) using a much larger dose (1,600 IU/day of α-tocopherol) found no effects on glycosylated hemoglobin or other glycosylated plasma proteins. Paolisso et al. (1993), using 900 mg/day of α-tocopherol, reported minimal, but statistically significant, improvements in control of blood glucose. The reason for the above discordance in results is not apparent.
Vitamin E treatment has been reported to decrease TBARS reactivity in plasma of patients with diabetes, but this reaction is not highly specific to vitamin E (Jain et al., 1996b). Davi et al. (1999) did a comprehensive study using the urinary excretion of F2-isoprostanes (8-iso-prostaglandin F2) as an indicator of oxidative stress. They found a highly significant increase in F2-isoprostane excretion in diabetic subjects, and the level of excretion correlated inversely with the degree of control of blood glucose. When the subjects were supplemented with α-tocopherol acetate (600 mg/day for 14 days), they reported a statistically significant reduction (37 percent) in F2-isoprostane excretion and also in the urinary