Salivary Areca and tobacco alkaloids for bioverification in the Betel Nut Intervention Trial

The Betel Nut Intervention Trial (BENIT) is the first known randomized controlled intervention trial designed to help minority Pacific Islanders in Guam and Saipan quit chewing the carcinogenic Areca catechu nut (AN). We report the BENIT's saliva bioverification results against the self-reported chewing status ("quitter" or "chewer") at day 22 follow-up.

AN-specific (arecoline, arecaidine, guvacoline, and guvacine) and tobacco-specific (nicotine, cotinine, and hydroxycotinine) alkaloids were analyzed in saliva from 176 BENIT participants by an established and sensitive liquid chromatography mass spectrometry-based assay.

The combined four AN alkaloid levels decreased from baseline in quitters (n = 50) and chewers (n = 108) by 32% and 9%, respectively. In quitters, decreases were significant for arecoline (p = 0.044)-the most prominent AN alkaloid, along with arecaidine (p = 0.042) and nicotine (p = 0.011). In chewers, decreases were significant only for hydroxycotinine (p = 0.004). Similar results were obtained when quitters and chewers were stratified by treatment arm.

Salivary AN alkaloid levels generally agreed with self-reported chewing status, which suggests the former can be used to verify the latter.

Our results can help to objectively evaluate compliance and program effectiveness in AN cessation programs.