Impact of Smoking Cessation and γ-Tocopherol to Restore Vascular Endothelial Function

Cigarette smoking is a significant risk factor for cardiovascular disease (CVD) and is the
leading cause of premature mortality in the US. The detrimental effects of smoking on
vascular dysfunction are attributed to the effects of smoke itself and the inflammatory
responses it induces. Smoking cessation restores vascular function by alleviating these
stress responses. However, smoking cessation with nicotine replacement therapy (NRT), the
prevailing approach to mitigate tobacco dependence, fails to allow full restoration of
vascular function. Thus, a critical public health problem exists to understand how NRT
prevents restoration of vascular function and how these NRT-mediated impairments can be
overcome by using gamma-tocopherol (g-T) as an innovative co-therapy. The objective of this
study is to conduct a clinical intervention trial that aims to reduce CVD risk by defining
how smoking cessation and g-T restore vascular function. The hypothesis is that smoking
cessation and dietary g-T supplementation will synergistically restore smoking-induced
impairments in vascular function by ameliorating oxidative/nitrosative stress responses, and
that g-T will facilitate full restoration of vascular function otherwise precluded by NRT. A
placebo-controlled, g-T intervention study will be conducted in cigarette smokers undergoing
nicotine-free or NRT smoking cessation. Prior to and after 24 h and 7 days of placebo or g-T
administration, vascular function will be evaluated using a non-invasive ultrasound
technique and an array of antioxidants and biomarkers for vascular inflammation and
oxidative/nitrosative stress responses will be assessed. Collectively, these studies will
help identify how vascular function is regulated in individuals undergoing smoking
cessation, and whether g-T can be used as a strategy to better improve vascular function
during smoking cessation.