title: Reducing nicotine exposure results in weight gain in smokers randomised to very low nicotine content cigarettes.
abstract: The Food and Drug Administration can reduce the nicotine content in cigarettes to very low levels. This potential regulatory action is hypothesised to improve public health by reducing smoking, but may have unintended consequences related to weight gain.
  
  
  
  Weight gain was evaluated from a double-blind, parallel, randomised clinical trial of 839 participants assigned to smoke 1 of 6 investigational cigarettes with nicotine content ranging from 0.4 to 15.8 mg/g or their own usual brand for 6 weeks. Additional analyses evaluated weight gain in the lowest nicotine content cigarette groups (0.4 and 0.4 mg/g, high tar) to examine the effect of study product in compliant participants as assessed by urinary biomarkers. Differences in outcomes due to gender were also explored.
  
  
  
  There were no significant differences in weight gain when comparing the reduced nicotine conditions with the 15.8 mg/g control group across all treatment groups and weeks. However, weight gain at week 6 was negatively correlated with nicotine exposure in the 2 lowest nicotine content cigarette conditions. Within the 2 lowest nicotine content cigarette conditions, male and female smokers biochemically verified to be compliant on study product gained significantly more weight than non-compliant smokers and control groups.
  
  
  
  The effect of random assignment to investigational cigarettes with reduced nicotine on weight gain was likely obscured by non-compliance with study product. Men and women who were compliant in the lowest nicotine content cigarette conditions gained 1.2 kg over 6 weeks, indicating weight gain is a likely consequence of reduced exposure to nicotine.
  
  
  
  NCT01681875, Post-results.
authors.affiliation: Center for Neuroscience at the University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Rupprecht
authors.affiliation: Division of Biostatistics, School of Public Health at the University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Koopmeiners
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Dermody
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Oliver
authors.affiliation: Department of Family Medicine, University of Minnesota Medical School, Duluth, Minnesota, USA.
authors.forename: Mustafa
authors.initials: M
authors.lastname: al'Absi
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, California, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, USA.
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
authors.affiliation: Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Denlinger-Apte
authors.affiliation: Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Drobes
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hatsukami
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: F Joseph
authors.initials: FJ
authors.lastname: McClernon
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Pacek
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Smith
authors.affiliation: Center for Neuroscience at the University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Sved
authors.affiliation: Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tidey
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Vandrey
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage*; D000074285:Smokers; D012907:Smoking / Q000378:metabolism*; D062789:Tobacco Products / Q000032:analysis*; D015430:Weight Gain
chemical_list: D009538:Nicotine
keywords: Harm Reduction; Nicotine; Public policy