Polyphenol metabolome in human urine and its association with intake of polyphenol-rich foods across European countries.
BACKGROUND
An improved understanding of the contribution of the diet to health and disease risks requires accurate assessments of dietary exposure in nutritional epidemiologic studies. The use of dietary biomarkers may improve the accuracy of estimates.


OBJECTIVE
We applied a metabolomic approach in a large cohort study to identify novel biomarkers of intake for a selection of polyphenol-containing foods. The large chemical diversity of polyphenols and their wide distribution over many foods make them ideal biomarker candidates for such foods.


METHODS
Metabolic profiles were measured with the use of high-resolution mass spectrometry in 24-h urine samples from 481 subjects from the large European Prospective Investigation on Cancer and Nutrition cohort. Peak intensities were correlated to acute and habitual dietary intakes of 6 polyphenol-rich foods (coffee, tea, red wine, citrus fruit, apples and pears, and chocolate products) measured with the use of 24-h dietary recalls and food-frequency questionnaires, respectively.


RESULTS
Correlation (r > 0.3, P < 0.01 after correction for multiple testing) and discriminant [pcorr (1) > 0.3, VIP > 1.5] analyses showed that >2000 mass spectral features from urine metabolic profiles were significantly associated with the consumption of the 6 selected foods. More than 80 polyphenol metabolites associated with the consumption of the selected foods could be identified, and large differences in their concentrations reflecting individual food intakes were observed within and between 4 European countries. Receiver operating characteristic curves showed that 5 polyphenol metabolites, which are characteristic of 5 of the 6 selected foods, had a high predicting ability of food intake.


CONCLUSIONS
Highly diverse food-derived metabolites (the so-called food metabolome) can be characterized in human biospecimens through this powerful metabolomic approach and screened to identify novel biomarkers for dietary exposures, which are ultimately essential to better understand the role of the diet in the cause of chronic diseases.
International Agency for Research on Cancer, Lyon, France;
William Mb
WM
Edmands
International Agency for Research on Cancer, Lyon, France;
Pietro
P
Ferrari
International Agency for Research on Cancer, Lyon, France;
Joseph A
JA
Rothwell
International Agency for Research on Cancer, Lyon, France;
Sabina
S
Rinaldi
International Agency for Research on Cancer, Lyon, France;
Nadia
N
Slimani
International Agency for Research on Cancer, Lyon, France;
Dinesh K
DK
Barupal
International Agency for Research on Cancer, Lyon, France;
Carine
C
Biessy
International Agency for Research on Cancer, Lyon, France;
Mazda
M
Jenab
French Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France; Université Paris Sud, UMRS 1018, Villejuif, France; Institut Gustave Roussy, Villejuif, France;
Françoise
F
Clavel-Chapelon
French Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France; Université Paris Sud, UMRS 1018, Villejuif, France; Institut Gustave Roussy, Villejuif, France;
Guy
G
Fagherazzi
French Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France; Université Paris Sud, UMRS 1018, Villejuif, France; Institut Gustave Roussy, Villejuif, France;
Marie-Christine
MC
Boutron-Ruault
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany;
Verena A
VA
Katzke
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany;
Tilman
T
Kühn
German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany;
Heiner
H
Boeing
Hellenic Health Foundation, Athens, Greece; Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece;
Antonia
A
Trichopoulou
Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, MA;
Pagona
P
Lagiou
Hellenic Health Foundation, Athens, Greece; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, MA;
Dimitrios
D
Trichopoulos
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy;
Domenico
D
Palli
Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy;
Sara
S
Grioni
Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, Provincial Health Unit Ragusa, Italy;
Rosario
R
Tumino
Medical Research Council, Public Health England Center for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom; HuGeF Foundation, Turin, Italy; and.
Paolo
P
Vineis
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
Amalia
A
Mattiello
International Agency for Research on Cancer, Lyon, France;
Isabelle
I
Romieu
International Agency for Research on Cancer, Lyon, France; scalberta@iarc.fr.
Augustin
A
Scalbert
D015415:Biomarkers / Q000652:urine*; D002099:Cacao; D002957:Citrus; D003069:Coffee; D004032:Diet; D005060:Europe; D005260:Female; D005638:Fruit; D006801:Humans; D008297:Male; D027845:Malus; D011939:Mental Recall; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D059808:Polyphenols / Q000008:administration & dosage* / Q000652:urine*; D011446:Prospective Studies; D031989:Pyrus; D011795:Surveys and Questionnaires; D013662:Tea; D014920:Wine
D015415:Biomarkers; D003069:Coffee; D059808:Polyphenols; D013662:Tea
EPIC; citrus fruits; coffee; dietary biomarkers; flavonoids; food metabolome; phenolic acids; polyphenols; red wine; tea