Interpretation of plasma pharmacokinetics and urinary excretion of phenolic metabolites and catabolites derived from (poly)phenols following ingestion of mango by ileostomists and subjects with a full gastrointestinal tract: complications associated with endogenous and ingested phenylalanine and tyrosine

Consumption of mango has been associated with a number of beneficial effects on health which have been attributed to phenolic catabolites originating from (poly)phenols following ingestion. To investigate the origins of potentially bioactive phenolic catabolites, ileostomists and subjects with a full gastrointestinal tract on a low(poly)phenol diet ingested a mango pulp purée containing 426 μmol of (poly)phenols consisting mainly of gallotannins and cinnamic acids, along with 231 μmol of the aromatic amino acids phenylalanine and tyrosine. Over a 24 h period post-mango intake plasma and urine were collected and analysed by UHPLC-HRMS. Phenylalanine and tyrosine, and 89 phenolic catabolites were detected in urine following mango intake, with 26 appearing in plasma characterised by a diversity of pharmacokinetic profiles. This indicated (i) metabolism and absorption in the upper gastrointestinal tract (benzoic acid derivatives), (ii) microbiota-mediated catabolism in the lower bowel (benzene catabolites), (iii) origins independent of mango intake, or a colon, via the potential breakdown of endogenous proteins releasing phenylalanine and tyrosine into the circulatory systems with subsequent conversion to phenolics (phenylhydracrylic acids and mandelic acids) and (iv) catabolites produced by more than one of these routes (hippuric acids). It is concluded that phenolic catabolites are produced by a variety of pathways, some of them independent of dietary (poly)phenol intake and the involvement of colonic microbiota. As a consequence, it is evident that elevated hippuric acid levels are not an appropriate biomarker of (poly)phenol intake. Insights into these complexities, especially the involvement of phenylalanine and tyrosine, are likely to await feeding studies with isotopically labelled substrates. Without such information, limited knowledge of their origins, complicates attempts to link individual phenolic catabolites with specific protective effects in randomised controlled feeding trials with (poly)phenol-rich dietary products. This study was registered at ClinicalTrials.gov (NCT06182540).