Effect of high-dose α-tocopherol supplementation on biomarkers of oxidative stress and inflammation and carotid atherosclerosis in patients with coronary artery disease

Background: Oxidative stress and inflammation are crucial in atherogenesis. α-Tocopherol is both an antioxidant and an antiinflammatory agent. Objective: We evaluated the effect of RRR-α-tocopherol supplementation on carotid atherosclerosis in patients with stable coronary artery disease (CAD) on drug therapy. Design: Randomized, controlled, double-blind trial compared RRR-α-tocopherol (1200 IU/d for 2 y) with placebo in 90 patients with CAD. Intimal medial thickness (IMT) of both carotid arteries was measured by high-resolution B-mode ultrasonography at 0, 1, 1.5, and 2 y. At 6-mo intervals, plasma α-tocopherol concentrations, C-reactive protein (CRP), LDL oxidation, monocyte function (superoxide anion release, cytokine release, and adhesion to endothelium), and urinary F₂-isoprostanes were measured. Results: α-Tocopherol concentrations were significantly higher in the α-tocopherol group but not in the placebo group. High-sensitivity CRP concentrations were significantly lowered with α-tocopherol supplementation than with placebo (32%; P < 0.001). α-Tocopherol supplementation significantly reduced urinary F₂-isoprostanes (P < 0.001) and monocyte superoxide anion and tumor necrosis factor release compared with baseline and placebo (P < 0.001). No significant difference was observed in the mean change in total carotid IMT in the placebo and α-tocopherol groups. In addition, no significant difference in cardiovascular events was observed (P = 0.21). Conclusions: High-dose RRR-α-tocopherol supplementation in patients with CAD was safe and significantly reduced plasma biomarkers of oxidative stress and inflammation but had no significant effect on carotid IMT during 2 y.