OBJECTIVE: Markers of oxidative stress and plasma alanine transferase (ALT) levels are increased and circulating antioxidant concentrations are reduced in individuals with insulin resistance. Vitamin E improves glycemic control in people with diabetes. We tested the hypothesis that vitamin E would decrease markers of oxidative stress and plasma ALT levels and improve insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS: Eighty overweight individuals (BMI >27 kg/m(2)) were randomly allocated to receive either 800 IU vitamin E per day or a matching placebo for 3 months. The dose of vitamin E was increased to 1,200 IU per day for a further 3 months. RESULTS: Plasma peroxides decreased by 27% at 3 months and by 29% at 6 months in the group that received vitamin E and were positively correlated with plasma vitamin E concentrations at the 6-month time point. At 3 months, fasting plasma glucose and insulin concentrations were significantly reduced and homeostasis model assessment increased. These changes were not apparent at 6 months. Plasma ALT concentrations declined significantly throughout the study period. CONCLUSIONS: In conclusion, these findings indicate that vitamin E improves oxidative stress and hepatocellular function. Although insulin resistance also improves, this effect appears transient.