Dose-dependent Increases in Ellagitannin Metabolites as Biomarkers of Intake in Humans Consuming Standardized Black Raspberry Food Products Designed for Clinical Trials.

Black raspberry (BRB) phytochemicals demonstrate anti-carcinogenic properties in experimental models, including prostate cancer. We designed and characterized two BRB foods, a confection and nectar, providing a consistent and reproducible product for human clinical studies.Men with clinically localized prostate cancer were sequentially enrolled to a control group or one of 4 intervention groups (confection or nectar, 10 or 20 gram dose; n = 8 per group) for 4-weeks prior to prostatectomy. Primary outcomes included: safety, adherence and ellagitannin (ET) metabolism. Adherence to the intervention was >96%. No significant (≥ grade II) toxicities were detected. Urinary urolithins (A, B, C, and D) and dimethyl ellagic acid (DMEA) quantified by UPLC/MS/MS indicated a dose-dependent excretion yet heterogeneous patterns among men. Men in the BRB confection groups had greater urinary excretion of the microbial urinary metabolites urolithin A and DMEA, suggesting that this food matrix provides greater colonic microflora exposure.Fully characterized BRB confections and nectar are ideal for food-based large phase III human clinical studies. BRB products provide a bioavailable source of BRB phytochemicals, however large inter individual variation in polyphenol metabolism suggests that host genetics, microflora and other factors are critical to understanding bioactivity and metabolism. This article is protected by copyright. All rights reserved.