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

• Absolute Change From Baseline in Plasma Gamma-tocopherol (Vitamin E) at Day 7 From Day 0. [ Time Frame: Day 0 and 7 of intervention ] [ Designated as safety issue: No ]
  Plasma measurements of gamma-tocopherol was assessed in response to smoking cessation and in combination with gamma-tocopherol (vitamin E) supplementation.
• Absolute Change From Baseline in Plasma Malondialdehyde at Day 7 From Day 0. [ Time Frame: Day 0 and 7 of intervention ] [ Designated as safety issue: No ]
  Plasma measurements of malondialdehyde, a marker of lipid peroxidation was assessed in response to smoking cessation and in combination with gamma-tocopherol (vitamin E) supplementation

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.

• Other: Nicotine Replacement Therapy (NRT)
  Participants will quit smoking with nicotine patches
  Other Names:

  • Nicotine patches
  • NicoDerm
• Dietary Supplement: Gamma-Tocopherol
  Participants will take gamma-tocopherol (500 mg/d) supplements for 7 days
  Other Name: Vitamin E
• Other: Placebo
  Participants will take placebo for 7 days
  Other Name: Corn oil
• Behavioral: Smoking cessation
  Participants will quit smoking without any pharmacological aids

• Experimental: Placebo + Smoking Cessation
  Individuals will quit smoking without use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days
  Interventions:

  • Other: Placebo
  • Behavioral: Smoking cessation
• Experimental: Supplement + Smoking Cessation
  Individuals will quit smoking without the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days
  Interventions:

  • Dietary Supplement: Gamma-Tocopherol
  • Behavioral: Smoking cessation
• Experimental: Placebo + Nicotine Replacement Therapy
  Individuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a placebo for 7 days
  Interventions:

  • Other: Nicotine Replacement Therapy (NRT)
  • Other: Placebo
  • Behavioral: Smoking cessation
• Experimental: Supplement + Nicotine Replacement Therapy
  Individuals will quit smoking with the use of nicotine replacement therapy (NRT) and ingest a gamma-tocopherol supplement for 7 days
  Interventions:

  • Other: Nicotine Replacement Therapy (NRT)
  • Dietary Supplement: Gamma-Tocopherol
  • Behavioral: Smoking cessation

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.