Daily use of smokeless tobacco: systemic effects

Ann Intern Med. 1989 Jul 15;111(2):112-6. doi: 10.7326/0003-4819-111-2-112.


Study objective: To compare exposure to nicotine and related cardiovascular effects as well as urinary mutagenicity (a potential marker of systemic absorption of carcinogenic compounds) during use of oral snuff, chewing tobacco, and cigarettes, as desired.

Design: Crossover sequential treatments, balanced-order experimental study.

Setting: Clinical research center.

Participants: Eight healthy men who regularly smoked cigarettes and had previous experience with the use of both oral snuff and chewing tobacco.

Interventions: Four 3- or 4-day blocks during which participants used oral snuff, chewing tobacco, and cigarettes as desired, or abstained from all tobacco. Concentrations of nicotine and cotinine (the primary metabolite of nicotine), cardiovascular effects, and urine sodium, catecholamine and mutagenicity were measured over 24 hours at the end of each treatment block.

Measurements and main results: Circadian exposure to nicotine and cardiovascular effects, including urinary catecholamine excretion, were similar for all forms of tobacco use. Urine sodium excretion was greater while using smokeless tobacco than while smoking, probably due to absorption of sodium from the smokeless tobacco. Urine mutagenicity was markedly increased while smoking cigarettes and tended to be increased (P less than 0.10) while chewing tobacco but not while using oral snuff.

Conclusions: Systemic absorption of nicotine, sodium, and carcinogenic chemicals from smokeless tobacco may cause or aggravate human illness in addition to the known adverse effects on the oral cavity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Catecholamines / urine
  • Cotinine / blood
  • Electrolytes / urine
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Mutagens / urine
  • Nicotine / administration & dosage*
  • Nicotine / pharmacokinetics
  • Plants, Toxic*
  • Smoking / metabolism
  • Smoking / physiopathology
  • Tobacco*
  • Tobacco, Smokeless*


  • Catecholamines
  • Electrolytes
  • Mutagens
  • Nicotine
  • Cotinine