Smoking behavior and exposure to tobacco toxicants during 6 months of smoking progressively reduced nicotine content cigarettes

Cancer Epidemiol Biomarkers Prev. 2012 May;21(5):761-9. doi: 10.1158/1055-9965.EPI-11-0644. Epub 2012 Feb 21.


Background: Recent federal legislation gives the U.S. Food and Drug Administration authority to regulate the nicotine content of cigarettes. A nationwide strategy for progressive reduction of the nicotine content of cigarettes is a potential way to reduce the addictiveness of cigarettes, to prevent new smokers from becoming addicted, and to facilitate quitting in established smokers. We conducted a trial of progressive nicotine content tapering over 6 months to determine the effects on smoking behaviors and biomarkers of tobacco smoke exposure and cardiovascular effects.

Methods: One hundred and thirty-five healthy smokers were randomly assigned to one of two groups. A research group smoked their usual brand of cigarettes followed by five types of research cigarettes with progressively lower nicotine content, each smoked for one month. A control group smoked their own brand of cigarettes for the same period of time.

Results: Nicotine intake, as indicated by plasma cotinine concentration, declined progressively as the nicotine content of cigarettes was reduced. Cigarette consumption and markers of exposure to carbon monoxide and polycyclic aromatic hydrocarbons, as well as cardiovascular biomarkers remained stable, whereas urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) excretion decreased. No significant changes in biomarkers of exposure or cardiovascular effects were observed in controls.

Conclusions: Our data support the proposition that the intake of nicotine from cigarettes of smokers can be substantially lowered without increasing exposure to other tobacco smoke toxins.

Impact: These findings support the feasibility and safety of gradual reduction of the nicotine content in cigarettes.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Female
  • Humans
  • Male
  • Nicotine / administration & dosage
  • Nicotine / blood*
  • Nicotine / metabolism
  • Smoking / blood*
  • Smoking / metabolism
  • Tobacco*


  • Nicotine