Understanding the bioactivity of pomegranate ellagitannins in humans: results of a literature review

Objectives. There is strong evidence in animal models suggesting that pomegranate fruit exerts health benefits relating to their antioxidant and anti-inflammatory properties [1]. Beneficial effects are certainly the consequence of the presence of the pomegranate polyphenols, mostly consisting of ellagitannins (ETs). However, studies in humans often failed to show clear associations between pomegranate intake and health outcomes, possibly due to inter-individual variation in absorption, distribution, metabolism, and excretion (ADME) of ETs. Methods. A literature review was conducted using the PubMed and Scopus databases including all original research articles on the relationship between inter-individual variability and ADME of ETs in humans. Data were summarized in a tabulated summary containing: study design, population, description of the intervention, duration, outcomes relevant to inter-individual variability in bioavailability and metabolism of ETs. Results. From 2004 to date, most of the research studies are mainly related to cardiometabolic risk biomarkers. Intervention studies are carried out using pomegranate juice or phenolic extracts at different doses of ETs. Additionally, the study designs used differ for each trial. Data on the four criteria ADME were not available in all publications. Results showed that urolithins are the predominant metabolites following pomegranate consumption. Anyhow, few works are still focused on the bioconversion of pomegranate ETs to their active metabolites. Conclusions. Urolithins are colonic microbiota metabolites of ETs and are considered responsible for in vivo health effects. The recently discovered existence of human metabolic phenotypes or metabotypes [2] could explain the variability seen in diet intervention studies. An understanding of the ADME of ETs in relation to the inter-individual variability is crucial for the elucidation of the mechanisms responsible for the health benefits of pomegranate and other ET-rich foods. Acknowledgments. This study was supported by the SIR programme (no. RBSI14LHMB) granted by the Italian Ministry of Education, University and Research. References. [1] Danesi & Ferguson. Could pomegranate juice help in the control of inflammatory diseases? Nutrients 2017; 9(9):E958. [2] Tomás-Barberán et al. Ellagic acid metabolism by human gut microbiota: consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age, and health status. J. Agric. Food Chem. 2014; 62(28):6535–8.