(P03-054-24) Urinary Polyphenol Metabolite Signatures in a Phase I Trial of a Novel Black Raspberry Nectar and Placebo Developed for Long-Term Cancer Prevention Studies

Objectives: We developed a novel fully characterized, polyphenol rich, black raspberry nectar (BRB) for testing in human clinical cancer prevention studies. We completed a placebo controlled randomized phase I/II study to assess compliance, safety, and targeted metabolomic/polyphenol urinary signatures in smokers and non-smokers.

Methods: A 12-wk, phase I/II, randomized (BRB-nectar, 185ml/10g BRB/day vs placebo) study with 110 subjects (16 smokers, 94 non-smokers) was completed. Participants consumed a low polyphenol diet. Urine samples (24-hr) were collected at 4-time points: before (usual diet) and after a 2-wk washout (low polyphenol diet), mid-intervention (wk 5-8) and end of intervention (wk 11-13). Intervention compliance and safety/toxicities were quantitated. Urine was analyzed by HPLC-mass spectrometry (LCMS) for BRB phytochemicals and their metabolites.

Results: Adherence to BRB nectar was 86 ± 27% based on consumption records. Toxicities to BRB or placebo were limited to grade I NIH toxicity criteria, typically transient, and often not attributable to the products (24% BRB, 23% Placebo). Mild gastrointestinal symptoms were the common toxicities noted. Urinary polyphenol signatures were dramatically different between placebo and BRB intervention groups but similar at the 6 and 12-wk time point. The prominent urinary BRB polyphenols include ellagitannins, ellagic acid, quercetin glycosides, and anthocyanins with several metabolites detected (urolithins, quercetin glucuronides/sulfates, methylated anthocyanins). Significant heterogeneity in BRB metabolic profile exists between individuals consuming the BRB product.

Conclusions: A fully characterized BRB nectar product shows high compliance based on food records and urinary biomarker measurements. Toxicity was minimal. Urinary BRB polyphenol metabolic signatures are strongly related to product consumption. Individuals show diverse quantities and patterns of metabolites, likely due to a combination of host and microbial action. Polyphenol metabolic signatures may predict individuals who show different biological responses to BRB nectar. A BRB nectar is an ideal product for future cancer prevention efforts for oral cancer and other malignancies, particularly in high-risk individuals, such as smokers.

Funding Sources: NCI