Background: Vitamin E isomers may protect against atherosclerosis. The aim of this study was to compare the effects of supplementation with either alpha-tocopherol (alpha T) or mixed tocopherols rich in gamma-tocopherol (gamma T) on markers of oxidative stress and inflammation in patients with type 2 diabetes.Methods: In a double-blind, placebo-controlled trial, 55 patients with type 2 diabetes were randomly assigned to receive (500 mg/day) (a) alpha T, (b) mixed tocopherols, or (0 placebo for 6 weeks. Cellular tocopherols, plasma and urine F-2-isoprostanes, erythrocyte antioxidant enzyme activities, plasma inflammatory markers, and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation.Results: Neutrophil alpha T and gamma T increased (both P < 0.001) with mixed tocopherol supplementation, whereas alpha T (P < 0.001) increased and gamma T decreased (P < 0.005) after alpha T supplementation. Both alpha T and mixed tocopherol supplementation resulted in reduced plasma F-2-isoprostanes (P < 0.001 and P = 0.001, respectively) but did not affect 24-h urinary F-2-isoprostanes or erythrocyte antioxidant enzyme activities. Neither aT nor mixed tocopherol supplementation affected plasma C-reactive protein, interleukin 6, tumor necrosis factor-alpha, or monocyte chemoattractant protein-1. Stimulated neutrophil leukotriene B-4 production decreased significantly in the mixed tocopherol group (P = 0.02) but not in the alpha T group (P = 0.15).Conclusions: The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes. In populations with well-controlled type 2 diabetes, supplementation with either alpha T or mixed tocopherols rich in gamma T is unlikely to confer further benefits in reducing inflammation. (c) 2007 American Association for Clinical Chemistry.