Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study

Ann Intern Med. 2017 Mar 21;166(6):390-400. doi: 10.7326/M16-1107. Epub 2017 Feb 7.


Background: Given the rapid increase in the popularity of e-cigarettes and the paucity of associated longitudinal health-related data, the need to assess the potential risks of long-term use is essential.

Objective: To compare exposure to nicotine, tobacco-related carcinogens, and toxins among smokers of combustible cigarettes only, former smokers with long-term e-cigarette use only, former smokers with long-term nicotine replacement therapy (NRT) use only, long-term dual users of both combustible cigarettes and e-cigarettes, and long-term users of both combustible cigarettes and NRT.

Design: Cross-sectional study.

Setting: United Kingdom.

Participants: The following 5 groups were purposively recruited: combustible cigarette-only users, former smokers with long-term (≥6 months) e-cigarette-only or NRT-only use, and long-term dual combustible cigarette-e-cigarette or combustible cigarette-NRT users (n = 36 to 37 per group; total n = 181).

Measurements: Sociodemographic and smoking characteristics were assessed. Participants provided urine and saliva samples and were analyzed for biomarkers of nicotine, tobacco-specific N-nitrosamines (TSNAs), and volatile organic compounds (VOCs).

Results: After confounders were controlled for, no clear between-group differences in salivary or urinary biomarkers of nicotine intake were found. The e-cigarette-only and NRT-only users had significantly lower metabolite levels for TSNAs (including the carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]) and VOCs (including metabolites of the toxins acrolein; acrylamide; acrylonitrile; 1,3-butadiene; and ethylene oxide) than combustible cigarette-only, dual combustible cigarette-e-cigarette, or dual combustible cigarette-NRT users. The e-cigarette-only users had significantly lower NNAL levels than all other groups. Combustible cigarette-only, dual combustible cigarette-NRT, and dual combustible cigarette-e-cigarette users had largely similar levels of TSNA and VOC metabolites.

Limitation: Cross-sectional design with self-selected sample.

Conclusion: Former smokers with long-term e-cigarette-only or NRT-only use may obtain roughly similar levels of nicotine compared with smokers of combustible cigarettes only, but results varied. Long-term NRT-only and e-cigarette-only use, but not dual use of NRTs or e-cigarettes with combustible cigarettes, is associated with substantially reduced levels of measured carcinogens and toxins relative to smoking only combustible cigarettes.

Primary funding source: Cancer Research UK.

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Biomarkers / urine
  • Carcinogens / analysis*
  • Cross-Sectional Studies
  • Electronic Nicotine Delivery Systems / adverse effects*
  • Female
  • Humans
  • Male
  • Nicotine / analysis*
  • Nicotine / urine
  • Nitrosamines / analysis
  • Nitrosamines / urine
  • Salvia / chemistry
  • Smoking Cessation / methods
  • Time Factors
  • Tobacco Use Cessation Devices / adverse effects*
  • Volatile Organic Compounds / analysis
  • Volatile Organic Compounds / urine


  • Biomarkers
  • Carcinogens
  • Nitrosamines
  • Volatile Organic Compounds
  • Nicotine