New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study

The intake of hesperidin-rich sources, mostly found in orange juice, can decrease cardiometabolic risk, potentially linked to the gut microbial phase-II hesperetin derivatives. However, the low hesperidin solubility hampers its bioavailability and microbial metabolism, yielding a high inter-individu...

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Autores: Ávila-Gálvez, María Ángeles, Giménez-Bastida, J. A., González-Sarrías, Antonio, Espín de Gea, Juan Carlos
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/411930
Acceso en línea:http://hdl.handle.net/10261/411930
Access Level:acceso abierto
Palabra clave:Flavanones
Gut microbiota
Citrus
Orange
Hesperidin
Lemon
Eriocitrin
Pharmacokinetics
Hesperetin metabolites
Eriodictyol metabolites
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spelling New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic studyÁvila-Gálvez, María ÁngelesGiménez-Bastida, J. A.González-Sarrías, AntonioEspín de Gea, Juan CarlosFlavanonesGut microbiotaCitrusOrangeHesperidinLemonEriocitrinPharmacokineticsHesperetin metabolitesEriodictyol metabolitesThe intake of hesperidin-rich sources, mostly found in orange juice, can decrease cardiometabolic risk, potentially linked to the gut microbial phase-II hesperetin derivatives. However, the low hesperidin solubility hampers its bioavailability and microbial metabolism, yielding a high inter-individual variability (high vs. low-producers) that prevents consistent health-related evidence. Contrarily, the human metabolism of (lemon) eriocitrin is hardly known. We hypothesize that the higher solubility of (lemon) eriocitrin vs. (orange) hesperidin might yield more bioavailable metabolites than hesperidin. A randomized-crossover human pharmacokinetic study (n = 16) compared the bioavailability and metabolism of flavanones from lemon and orange extracts and postprandial changes in oxidative, inflammatory, and metabolic markers after a high-fat-high-sugars meal. A total of 17 phase-II flavanone-derived metabolites were identified. No significant biomarker changes were observed. Plasma and urinary concentrations of all metabolites, including hesperetin metabolites, were higher after lemon extract intake. Total plasma metabolites showed significantly mean lower Tmax (6.0 ± 0.4 vs. 8.0 ± 0.5 h) and higher Cmax and AUC values after lemon extract intake. We provide new insights on hesperetin-eriodictyol interconversion and naringenin formation from hesperidin in humans. Our results suggest that regular consumption of a soluble and eco-friendly eriocitrin-rich lemon extract could provide a circulating concentration metabolites threshold to exert health benefits, even in the so-called low-producers.This research was funded by Euromed S.A. (Mollet del Vallès, Barcelona, Spain).Peer reviewedMultidisciplinary Digital Publishing InstituteConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/411930reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésÁvila-Gálvez, María Ángeles; Giménez-Bastida, J. A.; González-Sarrías, Antonio; Espín de Gea, Juan Carlos; 2021; Supplementary Materials: New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study [Dataset]; Multidisciplinary Digital Publishing Institute; https://doi.org/10.3390/antiox10030435https://doi.org/10.3390/antiox10030435Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4119302026-05-22T06:33:51Z
dc.title.none.fl_str_mv New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study
title New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study
spellingShingle New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study
Ávila-Gálvez, María Ángeles
Flavanones
Gut microbiota
Citrus
Orange
Hesperidin
Lemon
Eriocitrin
Pharmacokinetics
Hesperetin metabolites
Eriodictyol metabolites
title_short New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study
title_full New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study
title_fullStr New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study
title_full_unstemmed New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study
title_sort New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study
dc.creator.none.fl_str_mv Ávila-Gálvez, María Ángeles
Giménez-Bastida, J. A.
González-Sarrías, Antonio
Espín de Gea, Juan Carlos
author Ávila-Gálvez, María Ángeles
author_facet Ávila-Gálvez, María Ángeles
Giménez-Bastida, J. A.
González-Sarrías, Antonio
Espín de Gea, Juan Carlos
author_role author
author2 Giménez-Bastida, J. A.
González-Sarrías, Antonio
Espín de Gea, Juan Carlos
author2_role author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Flavanones
Gut microbiota
Citrus
Orange
Hesperidin
Lemon
Eriocitrin
Pharmacokinetics
Hesperetin metabolites
Eriodictyol metabolites
topic Flavanones
Gut microbiota
Citrus
Orange
Hesperidin
Lemon
Eriocitrin
Pharmacokinetics
Hesperetin metabolites
Eriodictyol metabolites
description The intake of hesperidin-rich sources, mostly found in orange juice, can decrease cardiometabolic risk, potentially linked to the gut microbial phase-II hesperetin derivatives. However, the low hesperidin solubility hampers its bioavailability and microbial metabolism, yielding a high inter-individual variability (high vs. low-producers) that prevents consistent health-related evidence. Contrarily, the human metabolism of (lemon) eriocitrin is hardly known. We hypothesize that the higher solubility of (lemon) eriocitrin vs. (orange) hesperidin might yield more bioavailable metabolites than hesperidin. A randomized-crossover human pharmacokinetic study (n = 16) compared the bioavailability and metabolism of flavanones from lemon and orange extracts and postprandial changes in oxidative, inflammatory, and metabolic markers after a high-fat-high-sugars meal. A total of 17 phase-II flavanone-derived metabolites were identified. No significant biomarker changes were observed. Plasma and urinary concentrations of all metabolites, including hesperetin metabolites, were higher after lemon extract intake. Total plasma metabolites showed significantly mean lower Tmax (6.0 ± 0.4 vs. 8.0 ± 0.5 h) and higher Cmax and AUC values after lemon extract intake. We provide new insights on hesperetin-eriodictyol interconversion and naringenin formation from hesperidin in humans. Our results suggest that regular consumption of a soluble and eco-friendly eriocitrin-rich lemon extract could provide a circulating concentration metabolites threshold to exert health benefits, even in the so-called low-producers.
publishDate 2021
dc.date.none.fl_str_mv 2021
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/411930
url http://hdl.handle.net/10261/411930
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Ávila-Gálvez, María Ángeles; Giménez-Bastida, J. A.; González-Sarrías, Antonio; Espín de Gea, Juan Carlos; 2021; Supplementary Materials: New insights into the metabolism of the flavanones eriocitrin and hesperidin: A comparative human pharmacokinetic study [Dataset]; Multidisciplinary Digital Publishing Institute; https://doi.org/10.3390/antiox10030435
https://doi.org/10.3390/antiox10030435

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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repository.mail.fl_str_mv
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