Formulation and in-vivo evaluation of l-cysteine chewing gums for binding carcinogenic acetaldehyde in the saliva during smoking

Abstract Cigarette smoke contains toxic amounts of acetaldehyde that dissolves in saliva, posing a significant risk of developing oral, laryngeal and pharyngeal carcinomas. l-Cysteine, a non-essential amino acid, can react covalently with carcinogenic acetaldehyde to form a stable, non-toxic 2-methylthiazolidine-4-carboxylic acid. The main aim of this study was to find out whether it is possible to develop a chewing gum formulation that would contain cysteine in amounts sufficient to bind all the acetaldehyde dissolved in saliva during the smoking of one cigarette. The main variables in the development process were: (1) chemical form of cysteine (l-cysteine or l-cysteine hydrochloride), (2) the amount of the active ingredient in a gum and (3) manufacturing procedure (traditional or novel compression method). Saliva samples were taken over 2.5 minutes before smoking and since smoking was started for 2.5 minutes periods for 10 minutes. During a five minutes smoking period with a placebo chewing gum, acetaldehyde levels increased from 0 to 150–185 μm. Once smoking was stopped, the acetaldehyde levels quickly fell to levels clearly below the in-vitro mutagenic level of 50 μm. All chewing gums containing cysteine could bind almost the whole of the acetaldehyde in the saliva during smoking. However, elimination of saliva acetaldehyde during smoking does not make smoking completely harmless. Cysteine as a free base would be somewhat better than cysteine hydrochloride due to its slower dissolution rate. Both traditional and direct compression methods to prepare chewing gums can be utilized and the dose of l-cysteine required is very low (5 mg).