Five-Day Changes in Biomarkers of Exposure Among Adult Smokers After Completely Switching From Combustible Cigarettes to a Nicotine-Salt Pod System

Nicotine Tob Res. 2020 Jul 16;22(8):1285-1293. doi: 10.1093/ntr/ntz206.


Introduction: This study examined changes in biomarkers of exposure (BoE) after 5 days of nicotine-salt pod system (NSPS) use, compared with continuation of usual-cigarette smoking and cigarette abstinence, among adult combustible cigarette smokers.

Aims and methods: A randomized, open-label, parallel-cohort, confinement study of healthy adult smokers, naive to NSPS use, was conducted. Participants (N = 90) were randomized to six cohorts (n = 15 each): exclusive ad libitum use of NSPS (four flavors: Virginia Tobacco, Mint, Mango, Creme), continuation of usual-brand cigarette smoking, or cigarette abstinence. Total nicotine equivalents and BoE (NNN, NNAL, 3-HPMA, MHBMA, S-PMA, HMPMA, CEMA, 1-OHP, and COHb) were measured.

Results: Eight non-nicotine BoEs, measured in urine, were reduced by an aggregate of 85.0% in the pooled NSPS cohort; increased by 14.4% in the cigarette cohort (p < .001 for pooled NSPS vs. cigarette); and reduced by 85.3% in the abstinence cohort (p > .05; 99.6% relative reduction between pooled NSPS vs. abstinence). Similar changes in individual BoEs were also observed (p < .001 for each BoE between pooled NSPS vs. cigarettes; and abstinence vs. pooled NSPS; p > .05 for each BoE between pooled NSPS vs. abstinence). Blood COHb decreased by 71.8% in the pooled NSPS cohort and 69.1% in the abstinence cohort (p > .05) and increased by 13.3% in the cigarette cohort (p < .001). Mean total urine nicotine equivalents increased in the pooled NSPS and cigarette cohorts by 9% and 26%, respectively, and did not significantly differ (p > .05).

Conclusion: Complete switching from cigarettes to NSPS produced significant reductions in key non-nicotine BoEs associated with cigarette smoking.

Implications: The results of this study concorded with evidence that complete switching from combustible cigarettes to tobacco and nontobacco-flavored vapor products may reduce exposure to key carcinogens and other toxicants known to be associated with tobacco-related diseases. Future research is needed to assess the long-term health effects of NSPS use. These results should not be interpreted to mean that the use of NSPS is without any risk, particularly for nonusers of tobacco products.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinogens / analysis*
  • Cigarette Smoking / epidemiology*
  • Cigarette Smoking / psychology
  • Cigarette Smoking / urine
  • Electronic Nicotine Delivery Systems / statistics & numerical data*
  • Female
  • Humans
  • Inhalation Exposure / analysis*
  • Male
  • Middle Aged
  • Nicotine / administration & dosage
  • Nicotine / urine
  • Salts / administration & dosage
  • San Francisco / epidemiology
  • Smoke / analysis*
  • Smokers / psychology*
  • Tobacco Products / statistics & numerical data*
  • Young Adult


  • Carcinogens
  • Salts
  • Smoke
  • Nicotine