Elimination of Cigarette Smoke-derived Acetaldehyde in Saliva by Slow-release L-Cysteine Lozenge Is a Potential New Method to Assist Smoking Cessation. A Randomised, Double-blind, Placebo-controlled Intervention

Anticancer Res. 2016 May;36(5):2297-306.


Background/aim: Harmans are condensation products of acetaldehyde and biogenic amines in saliva. Like other monoamine oxidase inhibitors, harmans help maintain behavioral sensitization to nicotine and mediate the addictive potential of cigarette smoke-derived acetaldehyde. The aim of this study was to test the hypothesis that effective elimination of acetaldehyde in saliva by slow-release L-cysteine (Acetium™ lozenge; Biohit Oyj, Helsinki, Finland) blocks the formation of harmans and eliminates acetaldehyde-enhanced nicotine addiction in smokers.

Study design: A double-blind, randomized, placebo-controlled trial comparing Acetium lozenges and placebo in smoking intervention was undertaken.

Materials and methods: A cohort of 423 cigarette smokers were randomly allocated to intervention (n=212) and placebo arms (n=211). Smoking-related data were recorded by questionnaires, together with nicotine dependence testing by Fagerström scale. The participants used a smoking diary to record the daily number of cigarettes, test lozenges and sensations of smoking. The data were analyzed separately for point prevalence of abstinence and prolonged abstinence endpoints.

Results: Altogether, 110 study participants completed the trial per protocol, 234 had minor violations, and the rest (n=79) were lost to follow-up. During the 6-month trial, 65 participants quit smoking; 38 (17.9%) in the intervention arm and 27 (12.8%) in the placebo arm [odds ratio (OR)=1.48; 95% confidence intervals (CI)=0.87-2.54; p=0.143]. Success in the per protocol group was better (42.9% vs. 31.1%, respectively; OR=1.65, 95% CI=0.75-3.62; p=0.205) than in the modified intention-to-treat group: 13.5% vs. 7.4% (p=0.128).

Conclusion: If the efficacy of Acetium lozenge can be confirmed in an adequately powered study, this new approach would represent a major breakthrough in smoking quit intervention because slow-release L-cysteine is non-toxic with no side-effects or limitations of use.

Keywords: L-cysteine; Smoking intervention; clinical trial; double-blind; lozenge; placebo-controlled; randomized; slow-release; smoking quit.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acetaldehyde / analysis*
  • Administration, Oral
  • Adult
  • Breath Tests
  • Carbon Monoxide / analysis
  • Cysteine / administration & dosage*
  • Delayed-Action Preparations
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Harmine / analogs & derivatives
  • Harmine / biosynthesis
  • Humans
  • Male
  • Medical Records
  • Middle Aged
  • Saliva / chemistry*
  • Smoke*
  • Smoking Cessation
  • Surveys and Questionnaires
  • Tobacco Products*
  • Tobacco Use Cessation Devices*
  • Treatment Outcome


  • Delayed-Action Preparations
  • Smoke
  • Harmine
  • Carbon Monoxide
  • harman
  • Acetaldehyde
  • Cysteine