Absorption, Metabolism, and Excretion of Cider Dihydrochalcones in Healthy Humans and Subjects with an Ileostomy

The phloretin-O-glycosides, phloretin-2'-O-glucoside and phloretin-2'-O-(2 ''-O-xylosyl)glucoside, are thought to be unique to apples and apple products. To investigate the metabolism and bioavailability of these compounds, nine healthy and five ileostomy human subjects consumed 500 mL of Thatchers Redstreak apple cider containing 46,mu mol of phloretin-O-glycosides. Over the ensuing 24 h period, plasma, urine, and ileal fluid were collected prior to analysis by high-performance liquid chromatography-mass spectrometry (HPLC-MS). The sole metabolite present in quantifiable amounts in plasma was phloretin-2'-O-glucuronide, which reached a peak concentration (C-max,) of 73 nmol/L and 0.6 h after ingestion (T-max) with the healthy subjects, and statistically similar values were obtained with the ileostomy volunteers. Phloretin-2'-O-glucuronide was also detected in urine along with two additional phloretin-O-glucuronides and a phloretin-O-glucuronide-O-sulfate. The quantity of phloretin metabolites excreted in urine represented 5.0 +/- 0.9% of intake in healthy volunteers and 5.5 +/- 0.6% in ileostomy volunteers. The similarity in the excretion levels of the two groups and the rapid plasma Tmax indicate absorption of the dihydrochalcones in the small intestine. Of the two major phloretin-O-glycosides in cider, only phloretin-2'-O-(2-O-xylosyl)glucoside was recovered in ileal fluid in quantities corresponding to 22% of intake. The absence of phloretin-2'-O-glucoside in ileal fluid suggests that it is more readily absorbed than phloretin-2'-O-(2-O-xylosyl)glucoside. Phloretin-2'O-glucuronide, two other phloretin-O-glucuronides, one phloretin-O-glucuronide-O-sulfate, two phloretin-O-sulfates, and the aglycone phloretin were also detected in the ileal fluid. This implies that the wall of the small intestine contains beta-glycosidase, sulfuryltransferase, and UDP-glucuronosyltransferase activities and that, as well as being absorbed, sizable amounts of the phloretin metabolites that are formed efflux back into the lumen of the gastrointestinal tract. The overall recovery of the dihydrochalcones and their metabolites in the ileal fluid was equivalent to 38.6% of intake.