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.

While it is well known that smoking cessation reduces the risk of cardiovascular disease (CVD), the rate in which CVD risk is normalized is relatively slow. This suggests a need to better define co-therapies that target oxidative stress and inflammatory responses that otherwise impair vascular function. In this randomized placebo-controlled clinical study, smokers undergoing smoking cessation with or without nicotine replacement therapy will receive dietary supplementation of gamma-tocopherol (500 mg/day) or placebo for 7 days. Their vascular function and biomarkers of CVD risk (inflammatory proteins, antioxidants, oxidized lipids) will be assessed prior to, and at 1 day and 7 days during smoking cessation with and without gamma-tocopherol supplementation to define potential mechanisms by which gamma-tocopherol may accelerate the restoration of vascular function and assist in reducing CVD risk.

Eligibility Criteria:
Inclusion Criteria:

* male or female between 18-60 y,
* premenopausal status for women
* healthy, verified by serum clinical chemistry
* stable body weight (±5 lbs) for 2-mo and BMI 19-30 kg/m2
* non-nutritional supplement user for \>2-mo
* free of known diseases including diabetes, CVD, cancer, infections, HIV/AIDS, hepatitis, and bleeding disorders
* resting blood pressure \<140/90 mm Hg;
* smokers (≥10 cigarettes/d, ≥1 year)
* maintaining normal exercise patterns (\<7 h/week) and willingness to avoid exercise 24 h prior to blood sampling and vascular testing
* willingness to ingest a dietary vitamin E supplement (gamma-tocopherol; 500 mg/d) or a placebo (composed of tocopherol-free corn oil) daily for 1 week.

Exclusion Criteria:

* serum chemistry outside normal limits
* alcohol consumption \>3 drinks/d or \>10 drinks per week
* nutritional supplement user with past 2 months
* \>7 hours/week of exercise
* use of any pharmacological therapy to treat high cholesterol or high blood pressure
* pregnancy, lactation, or initiation or change in hormonal birth control within the previous 3 mo
* use of vasoactive compounds (e.g. erectile dysfunction medication, omega 3-fatty acids, niacin)
* suffering from major psychiatric illnesses
* currently using non-nicotine aids or drugs to quit smoking; or 10) allergy to adhesive tape.