title: Absorption, Metabolism and Excretion of Cranberry (Poly)phenols in Humans: A Dose Response Study and Assessment of Inter-Individual Variability.
abstract: The beneficial health effects of cranberries have been attributed to their (poly)phenol content. Recent studies have investigated the absorption, metabolism and excretion of cranberry (poly)phenols; however, little is known about whether they follow a dose response in vivo at different levels of intake. An acute double-blind randomized controlled trial in 10 healthy men with cranberry juices containing 409, 787, 1238, 1534 and 1910 mg total (poly)phenols was performed. Blood and urine were analyzed by UPLC-Q-TOF-MS. Sixty metabolites were identified in plasma and urine including cinnamic acids, dihydrocinnamic, flavonols, benzoic acids, phenylacetic acids, benzaldehydes, valerolactones, hippuric acids, catechols, and pyrogallols. Total plasma, but not excreted urinary (poly)phenol metabolites, exhibited a linear dose response (r² = 0.74,p <0.05), driven by caffeic acid 4-O-ß-d-glucuronide, quercetin-3-O-ß-d-glucuronide, ferulic acid 4-O-ß-d-glucuronide, 2,5-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid, ferulic acid, caffeic acid 3-O-ß-d-glucuronide, sinapic acid, ferulic acid 4-O-sulfate, 3-hydroxybenzoic acid, syringic acid, vanillic acid-4-O-sulfate, (4R)-5-(3'-hydroxyphenyl)-γ-valerolactone-4'-O-sulfate, 4-methylgallic acid-3-O-sulfate, and isoferulic acid 3-O-sulfate (allr² ≥ 0.89,p <0.05). Inter-individual variability of the plasma metabolite concentration was broad and dependent on the metabolite. Herein, we show that specific plasma (poly)phenol metabolites are linearly related to the amount of (poly)phenols consumed in cranberry juice. The large inter-individual variation in metabolite profile may be due to variations in the gut microbiome.
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany. rodrigopedrofeliciano@gmail.com.
authors.forename: Rodrigo P
authors.initials: RP
authors.lastname: Feliciano
authors.affiliation: Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. charlotte.1.mills@kcl.ac.uk.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Mills
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany. geoffrey.istas@kcl.ac.uk.|Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. geoffrey.istas@kcl.ac.uk.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Istas
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany. Christian.Heiss@med.uni-duesseldorf.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, Moorenstrasse 5, Düsseldorf 40225, Germany. ana.rodriguez-mateos@kcl.ac.uk.|Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. ana.rodriguez-mateos@kcl.ac.uk.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez-Mateos
mesh_terms: D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D002934:Cinnamates / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000652:urine; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000652:urine; D005638:Fruit / Q000737:chemistry*; D000067030:Fruit and Vegetable Juices; D020719:Glucuronides / Q000378:metabolism / Q000652:urine; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D010636:Phenols / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000652:urine; D059808:Polyphenols / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000652:urine; D065667:Renal Elimination; D015203:Reproducibility of Results; D029799:Vaccinium macrocarpon / Q000737:chemistry*; D055815:Young Adult
chemical_list: D002934:Cinnamates; D005419:Flavonoids; D020719:Glucuronides; D010636:Phenols; D059808:Polyphenols
keywords: bioavailability; cranberry; dose-response; inter-individual variability; kinetics