γ-Tocopherol-rich supplementation additively improves vascular endothelial function during smoking cessation

Oxidative stress and inflammation persist years after smoking cessation thereby limiting the restoration of vascular endothelial function (VEF). Although short-terrn smoking cessation improves VEF, no studies have examined co-therapy of antioxidants in combination with smoking cessation to improve VEF. We hypothesized that improvements in gamma-tocopherol (gamma-T) status during smoking cessation would improve VEF beyond that from smoking cessation alone by decreasing oxidative stress and proinflammatory responses. A randomized, double-blind, placebo-controlled study was conducted in otherwise healthy smokers (22 +/- 1 years; mean +/- SEM) who quit smoking for 7 days with placebo (n=14) or gamma-T-rich supplementation (n=16; 500 mg gamma-T/day). Brachial artery flow-mediated dilation (FMD), cotinine, and biomarkers of antioxidant status, oxidative stress, and inflammation were measured before and after 7 days of smoking cessation. Smoking cessation regardless of supplementation similarly decreased plasma cotinine, whereas gamma-T-rich supplementation increased plasma gamma-T by seven times and its urinary metabolite gamma-carboxyethyl hydroxychroman by nine times (P < 0.05). Smoking cessation with gamma-T-rich supplementation increased FM!) responses by 1.3% (P <0.05) beyond smoking cessation alone (4.1 +/- 0.6% vs 18 +/- 0.3%; mean +/- SEM). Although plasma malondialdehyde decreased similarly in both groups (P < 0.05), plasma oxidized LDL and urinary F-2-isoprostanes were unaffected by smoking cessation or gamma-Trich supplementation. Plasma TNF-a and myeloperoxidase decreased (P < 0.05) only in those receiving gamma-T-rich supplements and these were inversely related to FM!) (P < 0.05; R= -0.46 and -0.37, respectively). These findings demonstrate that short-term gamma-T-rich supplementation in combination with smoking cessation improved VEF beyond that from smoking cessation alone in young smokers, probably by decreasing the proinflammatory mediators TNF-alpha and myeloperoxidase. (C) 2013 Elsevier Inc. All rights reserved.