Urinary Hippuric Acid as a Sex-Dependent Biomarker for Fruit and Nut Intake Raised from the EAT-Lancet Index and Nuclear Magnetic Resonance Analysis

<b>Background/Objectives</b>: Assessing nutrient intake is essential for understanding body homeostasis and diet–health interactions. Traditional methods, such as dietary questionnaires and quality indices, are limited by subjectivity and variability in food composition tables. Metabolom...

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Main Authors: Edwin Fernández-Cruz, Víctor de la O, Cristina M. Fernández-Diaz, Pilar Matía-Martín, M. Ángel Rubio-Herrera, Nuria Amigó, Alfonso L. Calle-Pascual, J. Alfredo Martínez
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Language:English
Published: MDPI AG 2025-05-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/6/348
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author Edwin Fernández-Cruz
Víctor de la O
Cristina M. Fernández-Diaz
Pilar Matía-Martín
M. Ángel Rubio-Herrera
Nuria Amigó
Alfonso L. Calle-Pascual
J. Alfredo Martínez
author_facet Edwin Fernández-Cruz
Víctor de la O
Cristina M. Fernández-Diaz
Pilar Matía-Martín
M. Ángel Rubio-Herrera
Nuria Amigó
Alfonso L. Calle-Pascual
J. Alfredo Martínez
author_sort Edwin Fernández-Cruz
collection DOAJ
description <b>Background/Objectives</b>: Assessing nutrient intake is essential for understanding body homeostasis and diet–health interactions. Traditional methods, such as dietary questionnaires and quality indices, are limited by subjectivity and variability in food composition tables. Metabolomic markers, like urinary hippuric acid, provide an objective means to estimate food and nutrient intake, helping to link dietary patterns with metabolic outputs and health outcomes. This study uniquely evaluates urinary hippuric acid as a putative biomarker of nut intake, expanding the previously known role as a fruit intake marker, and investigates sex-related differences in the excretion. <b>Methods</b>: Using Nuclear Magnetic Resonance (NMR) spectroscopy, 34 urinary metabolites from 138 participants (69.7% women) in the Dietary Deal project were analyzed. Metabolite concentrations were categorized by median adherence to the EAT-Lancet score (≤p50 or >p50). A validated Food Frequency Questionnaire (FFQ) assessed dietary and energy intake. Correlation analyses linked metabolites to the 14 EAT-Lancet food groups, and a linear regression adjusted model examined associations between urinary hippuric acid and fruit/nut consumption, with sensitivity analysis for sex. <b>Results</b>: The EAT-Lancet index, stratified by median adherence, effectively distinguished between high and low dietary intake of fruits (<i>p</i> = 0.012) and nuts (<i>p</i> < 0.001). Urinary hippuric acid concentrations were found to be influenced by sex (<i>p</i> = 0.020), with females showing a 44.7% higher mean concentration. Overall, urinary hippuric acid levels were positively associated with FFQ-estimated nut consumption (<i>p</i> = 0.049), providing the first evidence of potential suitability as a nut intake biomarker. <b>Conclusions</b>: Hippuric acid emerges as a promising dietary biomarker for assessing nut intake in healthy populations. This study provides novel insights that extend the application of hippuric acid to dietary nut assessment and emphasizes the importance of a sex-specific interpretation for precision nutrition purposes using NMR technology.
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spelling doaj-art-d350d093b4ce43cea8cd51a17826dce92025-08-20T02:21:04ZengMDPI AGMetabolites2218-19892025-05-0115634810.3390/metabo15060348Urinary Hippuric Acid as a Sex-Dependent Biomarker for Fruit and Nut Intake Raised from the EAT-Lancet Index and Nuclear Magnetic Resonance AnalysisEdwin Fernández-Cruz0Víctor de la O1Cristina M. Fernández-Diaz2Pilar Matía-Martín3M. Ángel Rubio-Herrera4Nuria Amigó5Alfonso L. Calle-Pascual6J. Alfredo Martínez7IMDEA Food, CEI UAM + CSIC, Carretera de Cantoblanco 8, 28049 Madrid, SpainIMDEA Food, CEI UAM + CSIC, Carretera de Cantoblanco 8, 28049 Madrid, SpainIMDEA Food, CEI UAM + CSIC, Carretera de Cantoblanco 8, 28049 Madrid, SpainEndocrinology and Nutrition Department, San Carlos Clinical Hospital and Instituto de Investigación Sanitaria San Carlos (IdISSC), 28040 Madrid, SpainEndocrinology and Nutrition Department, San Carlos Clinical Hospital and Instituto de Investigación Sanitaria San Carlos (IdISSC), 28040 Madrid, SpainDepartament de Ciències Mèdiques Bàsiques, Universitat Rovira i Virgili, 43201 Tarragona, SpainCentro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, SpainIMDEA Food, CEI UAM + CSIC, Carretera de Cantoblanco 8, 28049 Madrid, Spain<b>Background/Objectives</b>: Assessing nutrient intake is essential for understanding body homeostasis and diet–health interactions. Traditional methods, such as dietary questionnaires and quality indices, are limited by subjectivity and variability in food composition tables. Metabolomic markers, like urinary hippuric acid, provide an objective means to estimate food and nutrient intake, helping to link dietary patterns with metabolic outputs and health outcomes. This study uniquely evaluates urinary hippuric acid as a putative biomarker of nut intake, expanding the previously known role as a fruit intake marker, and investigates sex-related differences in the excretion. <b>Methods</b>: Using Nuclear Magnetic Resonance (NMR) spectroscopy, 34 urinary metabolites from 138 participants (69.7% women) in the Dietary Deal project were analyzed. Metabolite concentrations were categorized by median adherence to the EAT-Lancet score (≤p50 or >p50). A validated Food Frequency Questionnaire (FFQ) assessed dietary and energy intake. Correlation analyses linked metabolites to the 14 EAT-Lancet food groups, and a linear regression adjusted model examined associations between urinary hippuric acid and fruit/nut consumption, with sensitivity analysis for sex. <b>Results</b>: The EAT-Lancet index, stratified by median adherence, effectively distinguished between high and low dietary intake of fruits (<i>p</i> = 0.012) and nuts (<i>p</i> < 0.001). Urinary hippuric acid concentrations were found to be influenced by sex (<i>p</i> = 0.020), with females showing a 44.7% higher mean concentration. Overall, urinary hippuric acid levels were positively associated with FFQ-estimated nut consumption (<i>p</i> = 0.049), providing the first evidence of potential suitability as a nut intake biomarker. <b>Conclusions</b>: Hippuric acid emerges as a promising dietary biomarker for assessing nut intake in healthy populations. This study provides novel insights that extend the application of hippuric acid to dietary nut assessment and emphasizes the importance of a sex-specific interpretation for precision nutrition purposes using NMR technology.https://www.mdpi.com/2218-1989/15/6/348biomarker of food intakedietary assessmentEAT-Lancet indexhippuric acidprecision nutrition
spellingShingle Edwin Fernández-Cruz
Víctor de la O
Cristina M. Fernández-Diaz
Pilar Matía-Martín
M. Ángel Rubio-Herrera
Nuria Amigó
Alfonso L. Calle-Pascual
J. Alfredo Martínez
Urinary Hippuric Acid as a Sex-Dependent Biomarker for Fruit and Nut Intake Raised from the EAT-Lancet Index and Nuclear Magnetic Resonance Analysis
Metabolites
biomarker of food intake
dietary assessment
EAT-Lancet index
hippuric acid
precision nutrition
title Urinary Hippuric Acid as a Sex-Dependent Biomarker for Fruit and Nut Intake Raised from the EAT-Lancet Index and Nuclear Magnetic Resonance Analysis
title_full Urinary Hippuric Acid as a Sex-Dependent Biomarker for Fruit and Nut Intake Raised from the EAT-Lancet Index and Nuclear Magnetic Resonance Analysis
title_fullStr Urinary Hippuric Acid as a Sex-Dependent Biomarker for Fruit and Nut Intake Raised from the EAT-Lancet Index and Nuclear Magnetic Resonance Analysis
title_full_unstemmed Urinary Hippuric Acid as a Sex-Dependent Biomarker for Fruit and Nut Intake Raised from the EAT-Lancet Index and Nuclear Magnetic Resonance Analysis
title_short Urinary Hippuric Acid as a Sex-Dependent Biomarker for Fruit and Nut Intake Raised from the EAT-Lancet Index and Nuclear Magnetic Resonance Analysis
title_sort urinary hippuric acid as a sex dependent biomarker for fruit and nut intake raised from the eat lancet index and nuclear magnetic resonance analysis
topic biomarker of food intake
dietary assessment
EAT-Lancet index
hippuric acid
precision nutrition
url https://www.mdpi.com/2218-1989/15/6/348
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