Abstract

Large interindividual variations in the biological response to citrus flavanones have been observed, and this could be associated with high variations in their bioavailability. The aim of this study was to identify the main determinants underlying interindividual differences in citrus flavanone metabolism and excretion. In a randomized cross-over study, non-obese and obese volunteers, aged 19–40 years, ingested single doses of Pera and Moro orange juices, and urine was collected for 24 h. A large difference in the recovery of the urinary flavanone phase II metabolites was observed, with hesperetin-sulfate and hesperetin-sulfo-O-glucuronide being the major metabolites. Subjects were stratified according to their total excretion of flavanone metabolites as high, medium, and low excretors, but the expected correlation with the microbiome was not observed at the genus level. A second stratification was proposed according to phase II flavanone metabolism, whereby participants were divided into two excretion groups: Profiles A and B. Profile B individuals showed greater biotransformation of hesperetin-sulfate to hesperetin-sulfo-O-glucuronide, as well as transformation of flavanone-monoglucuronide to the respective diglucuronides, suggestive of an influence of polymorphisms on UDP-glucuronosyltransferase. In conclusion, this study proposes a new stratification of volunteers based on their metabolic profiles. Gut microbiota composition and polymorphisms of phase II enzymes may be related to the interindividual variability of metabolism.

Highlights

  • IntroductionIntroduction published maps and institutional affilOrange fruit

  • Introduction published maps and institutional affilOrange fruit

  • The soluble fraction of hesperidin was higher in Moro orange orange juice (MOJ) than in Pera orange juice (POJ) (16% and 9%, respectively) (Table S4)

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Summary

Introduction

Introduction published maps and institutional affilOrange fruit Osbeck) and 100% orange juice, which are rich sources of flavanones, have been associated with health benefits leading to decreases in the occurrence of chronic non-communicable diseases such as obesity, diabetes, and hypertension [1,2,3,4]. Intake of 100% orange juice has been shown to have lipid- [9,10,11], glucose- [12], and blood-pressure-lowering activities as well as being associated with an improvement in insulin sensitivity [4,9,13,14]. Recent systematic reviews of animal studies and human clinical studies had different conclusions about citrus flavonoids and orange juice protection against cardiometabolic diseases. One of them had no definitive conclusion about the effects of orange juice intake iations

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