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Clinical Trial
. 2020 May;64(10):e1900800.
doi: 10.1002/mnfr.201900800. Epub 2020 Mar 17.

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

Kristen M Roberts  1 , Elizabeth M Grainger  2 , Jennifer M Thomas-Ahner  2 , Alice Hinton  3 , Junnan Gu  1 , Ken Riedl  2   4   5 , Yael Vodovotz  2   4 , Ronney Abaza  6   7 , Steven J Schwartz  2   4   5 , Steven K Clinton  2   5   8
Affiliations
Clinical Trial

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

Kristen M Roberts et al. Mol Nutr Food Res. 2020 May.

Abstract

Scope: Black raspberry (BRB) phytochemicals demonstrate anti-carcinogenic properties in experimental models, including prostate cancer. Two BRB foods, a confection and nectar, providing a consistent and reproducible product for human clinical studies are designed and characterized.

Methods and results: Men with clinically localized prostate cancer are sequentially enrolled to a control group or one of four intervention groups (confection or nectar, 10 or 20 g dose; n = 8 per group) for 4 weeks prior to prostatectomy. Primary outcomes include: safety, adherence, and ellagitannin metabolism. Adherence to the intervention is >96%. No significant (≥grade II) toxicities are detected. Urinary urolithins (A, B, C, and D) and dimethyl ellagic acid (DMEA) quantified by Ultra high performance liquid chromatography tandem mass spectroscopy (UPLC/MS/MS) indicate a dose-dependent excretion yet heterogeneous patterns among men. Men in the BRB confection groups have greater urinary excretion of the microbial urinary metabolites urolithin A and DMEA, suggesting that this food matrix provides greater colonic microflora exposure.

Conclusion: 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.

Keywords: black raspberries; ellagitannins; polyphenol explorer database; polyphenols; urolithins.

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Conflict of interest statement

Conflict of Interest:

The authors declare no conflict of interest.

Figures

Figure 1:
Figure 1:
Hypothesized metabolism of Ellagitannins
Figure 2:
Figure 2:
The phase I/II study design evaluating the two black raspberry food products on safety, compliance, and polyphenol metabolism in men with clinically localized prostate cancer and undergoing prostatectomy.
Figure 3:
Figure 3:
Urinary urolithin A and DMEA in the 24-hour urine for men on the phase I/II trial of two BRB food product prior to prostatecomy.1 Medians are represented by bars and means are represented by triangles. P-values are calculated using Dunn’s test following the non-parametric Kruskal-Wallis test and represent differences between the control and BRB-intervention groups.
See this image and copyright information in PMC

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