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

Abstract

Oxidative stress and inflammation persist years after smoking cessation thereby limiting the restoration of vascular endothelial function (VEF). Although short-term 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 γ-tocopherol (γ-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 γ-T-rich supplementation (n=16; 500 mg γ-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 γ-T-rich supplementation increased plasma γ-T by seven times and its urinary metabolite γ-carboxyethyl hydroxychroman by nine times (P<0.05). Smoking cessation with γ-T-rich supplementation increased FMD responses by 1.3% (P<0.05) beyond smoking cessation alone (4.1 ± 0.6% vs 2.8 ± 0.3%; mean ± SEM). Although plasma malondialdehyde decreased similarly in both groups (P<0.05), plasma oxidized LDL and urinary F2-isoprostanes were unaffected by smoking cessation or γ-T-rich supplementation. Plasma TNF-α and myeloperoxidase decreased (P<0.05) only in those receiving γ-T-rich supplements and these were inversely related to FMD (P<0.05; R=-0.46 and -0.37, respectively). These findings demonstrate that short-term γ-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-α and myeloperoxidase.

Keywords: 2,3 dinor-8-iso-PGF(2α); 2,3-dinor-5,6-dihydro-8-iso-PGF(2α); 2,3-dinor-F1; 2,3-dinor-F2; C-reactive protein; CRP; CVD; FMD; Flow-mediated dilation; Free radicals; IFN-γ; Inflammation; MCP-1; MPO; Oxidative stress; RNS; ROS; Smoking cessation; VEF; Vascular function; Vitamin E; cIMT; cardiovascular disease; carotid intima media thickness; flow-mediated dilation; interferon-γ; monocyte chemoattractant protein-1; myeloperoxidase; reactive nitrogen species; reactive oxygen species; sICAM-1; soluble intracellular adhesion molecule-1; vascular endothelial function; γ-CEHC; γ-T; γ-T-rich mixture of tocopherols; γ-TmT; γ-carboxyethyl hydroxychroman; γ-tocopherol.