Salivary arecoline levels during areca nut chewing in human volunteers

Arecoline stimulates cultured cells above 0.1 microg/ml and is cytotoxic above 10 microg/ml. Although this alkaloid seems important for areca nut induced oral carcinogenesis, little is known of the levels achieved during chewing.

Saliva was collected in 3- to 5-min intervals over 50 min in 32 habitual chewers: before, for 25 min during, and for 20 min after chewing areca nut (0.5 g) without any other additives. Salivary arecoline was quantitated by HPLC-MS. Controls comprised six subjects who denied areca nut use, and who were given rubber-base material to chew during experiments instead.

Arecoline was detected before chewing in 22 subjects, exceeding the 0.1 microg/ml threshold in 20 cases. Salivary arecoline exceeded either the 0.1 or 10 microg/ml thresholds in all participants during chewing (P < 0.001). Maximum concentrations ranged from 5.66 to 97.39 microg/ml. All subjects reached 0.1 microg/ml salivary arecoline in at least 85% of time points studied (P < 0.0001), whereas 10 microg/ml was reached in 11 participants in at least 30% of the time points (P < 0.003). Arecoline concentrations varied greatly over time between individuals, and levels were much lower when peak concentrations were reached before 3 min, than in cases where arecoline peaked later (P < 0.02). No salivary arecoline was found in control saliva.

Areca nut users have persistent background salivary arecoline levels long after chewing, whereas concentrations achieved are highly variable and consistent with a role in oral pre-malignancy and malignancy.