Food-Based Approach To Cancer Prevention: A Phase I Assessment Of Amorphous Confections In Modulating Exposure And Metabolism Of Black Raspberry Compounds In The Oral Cavity

Background: Oral cancer remains a major global malignancy, largely due to persistence of tobacco use worldwide. Preventive strategies focusing upon high risk individuals due to long term tobacco use or presence of pre-malignancy are needed. Based upon strong epidemiologic and laboratory evidence we have developed a black raspberry food-based product targeting this population and have tested variations in a phase I trial. Objective: 1. To test three amorphous solids (glassy, elastic, and viscous) containing a bioactive rich black raspberry (BRB) fraction in a confectionary system for compliance. 2. To investigate the impact of amorphous structure in modulating oral exposure and metabolism of black raspberry compounds in the oral cavity as measured by differences in duration of black raspberry exposure and profile of black raspberry metabolites from saliva. Methods: A four week, phase I, randomized, parallel study design with 60 non-smoking adults was used to investigate three amorphous forms having different release rates (prolonged, intermediate, and rapid), each at two doses (4 or 8 g BRB/day). Salivary kinetics and changes in black raspberry composition among and within individuals were assessed. HPLC with Tandem MS/MS was used to quantify and characterize black raspberry compounds from the confections and profile them in the saliva. Results: All confections were well accepted having excellent adherence (94 ± 2%). Toxicities were limited to a grade I toxicity (NIH criteria). Oral residence time was 74% longer and saliva volume was 42% greater with glassy than the other two amorphous forms. Anthocyanin (cyanidin-3-glucoside) and ellagitannins were prevalent compounds in the saliva. Conclusions: Three amorphous confectionary forms of a BRB food-based delivery vehicle demonstrated excellent compliance, with the glassy form showing potential for greater oral distribution, suggesting the potential for greater bioactivity. Food science and technology provides many strategies to develop novel and fully characterized food products for cancer prevention trials. Citation Format: Jennifer H. Ahn-Jarvis, Steven K. Clinton, Elizabeth M. Grainger, Christina Simpson, Junnan Gu, Matthew D. Teegarden, Kenneth M. Riedl, Thomas J. Knobloch, Christopher M. Weghorst, Steven J. Schwartz, Yael Vodovotz. Food-based approach to cancer prevention: A phase I assessment of amorphous confections in modulating exposure and metabolism of black raspberry compounds in the oral cavity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-295.