title: Orange juice (poly)phenols are highly bioavailable in humans.
abstract: BACKGROUND
  We assessed the bioavailability of orange juice (poly)phenols by monitoring urinary flavanone metabolites and ring fission catabolites produced by the action of the colonic microbiota.
  
  
  OBJECTIVE
  Our objective was to identify and quantify metabolites and catabolites excreted in urine 0-24 h after the acute ingestion of a (poly)phenol-rich orange juice by 12 volunteers.
  
  
  METHODS
  Twelve volunteers [6 men and 6 women; body mass index (in kg/m(2)): 23.9-37.2] consumed a low (poly)phenol diet for 2 d before first drinking 250 mL pulp-enriched orange juice, which contained 584 μmol (poly)phenols of which 537 μmol were flavanones, and after a 2-wk washout, the procedure was repeated, and a placebo drink was consumed. Urine collected for a 24-h period was analyzed qualitatively and quantitatively by using high-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography-mass spectrometry (GC-MS).
  
  
  RESULTS
  A total of 14 metabolites were identified and quantified in urine by using HPLC-MS after orange juice intake. Hesperetin-O-glucuronides, naringenin-O-glucuronides, and hesperetin-3'-O-sulfate were the main metabolites. The overall urinary excretion of flavanone metabolites corresponded to 16% of the intake of 584 μmol (poly)phenols. The GC-MS analysis revealed that 8 urinary catabolites were also excreted in significantly higher quantities after orange juice consumption. These catabolites were 3-(3'-methoxy-4'-hydroxyphenyl)propionic acid, 3-(3'-hydroxy-4'-methoxyphenyl)propionic acid, 3-(3'-hydroxy-4'-methoxyphenyl)hydracrylic acid, 3-(3'-hydroxyphenyl)hydracrylic acid, 3'-methoxy-4'-hydroxyphenylacetic acid, hippuric acid, 3'-hydroxyhippuric acid, and 4'-hydroxyhippuric acid. These aromatic acids originated from the colonic microbiota-mediated breakdown of orange juice (poly)phenols and were excreted in amounts equivalent to 88% of (poly)phenol intake. When combined with the 16% excretion of metabolites, this percentage raised the overall urinary excretion to ∼ 100% of intake.
  
  
  CONCLUSIONS
  When colon-derived phenolic catabolites are included with flavanone glucuronide and sulfate metabolites, orange juice (poly)phenols are much-more bioavailable than previously envisaged. In vitro and ex vivo studies on mechanisms underlying the potential protective effects of orange juice consumption should use in vivo metabolites and catabolites detected in this investigation at physiologic concentrations. The trial was registered at BioMed Central Ltd (www.controlledtrials.com) as ISRCTN04271658.
authors.affiliation: From the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (GP-C, GB, JvdH, and AC); the School of Biosciences and Medicine, Faculty of Health and Medical Sciences, The Dorothy Hodgkins Building, University of Surrey, Guildford, Surrey, United Kingdom (MNC); the Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, Parma, Italy (DDR); the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom (MEJL); the Global Scientific and Regulatory Affairs, The Coca-Cola Company, Atlanta, GA (SAR); and Research and Development, Coca-Cola Services nv, Brussels, Belgium (MBK).
authors.forename: Gema
authors.initials: G
authors.lastname: Pereira-Caro
authors.affiliation: From the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (GP-C, GB, JvdH, and AC); the School of Biosciences and Medicine, Faculty of Health and Medical Sciences, The Dorothy Hodgkins Building, University of Surrey, Guildford, Surrey, United Kingdom (MNC); the Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, Parma, Italy (DDR); the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom (MEJL); the Global Scientific and Regulatory Affairs, The Coca-Cola Company, Atlanta, GA (SAR); and Research and Development, Coca-Cola Services nv, Brussels, Belgium (MBK).
authors.forename: Gina
authors.initials: G
authors.lastname: Borges
authors.affiliation: From the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (GP-C, GB, JvdH, and AC); the School of Biosciences and Medicine, Faculty of Health and Medical Sciences, The Dorothy Hodgkins Building, University of Surrey, Guildford, Surrey, United Kingdom (MNC); the Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, Parma, Italy (DDR); the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom (MEJL); the Global Scientific and Regulatory Affairs, The Coca-Cola Company, Atlanta, GA (SAR); and Research and Development, Coca-Cola Services nv, Brussels, Belgium (MBK).
authors.forename: Justin
authors.initials: J
authors.lastname: van der Hooft
authors.affiliation: From the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (GP-C, GB, JvdH, and AC); the School of Biosciences and Medicine, Faculty of Health and Medical Sciences, The Dorothy Hodgkins Building, University of Surrey, Guildford, Surrey, United Kingdom (MNC); the Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, Parma, Italy (DDR); the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom (MEJL); the Global Scientific and Regulatory Affairs, The Coca-Cola Company, Atlanta, GA (SAR); and Research and Development, Coca-Cola Services nv, Brussels, Belgium (MBK).
authors.forename: Michael N
authors.initials: MN
authors.lastname: Clifford
authors.affiliation: From the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (GP-C, GB, JvdH, and AC); the School of Biosciences and Medicine, Faculty of Health and Medical Sciences, The Dorothy Hodgkins Building, University of Surrey, Guildford, Surrey, United Kingdom (MNC); the Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, Parma, Italy (DDR); the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom (MEJL); the Global Scientific and Regulatory Affairs, The Coca-Cola Company, Atlanta, GA (SAR); and Research and Development, Coca-Cola Services nv, Brussels, Belgium (MBK).
authors.forename: Daniele
authors.initials: D
authors.lastname: Del Rio
authors.affiliation: From the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (GP-C, GB, JvdH, and AC); the School of Biosciences and Medicine, Faculty of Health and Medical Sciences, The Dorothy Hodgkins Building, University of Surrey, Guildford, Surrey, United Kingdom (MNC); the Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, Parma, Italy (DDR); the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom (MEJL); the Global Scientific and Regulatory Affairs, The Coca-Cola Company, Atlanta, GA (SAR); and Research and Development, Coca-Cola Services nv, Brussels, Belgium (MBK).
authors.forename: Michael E J
authors.initials: ME
authors.lastname: Lean
authors.affiliation: From the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (GP-C, GB, JvdH, and AC); the School of Biosciences and Medicine, Faculty of Health and Medical Sciences, The Dorothy Hodgkins Building, University of Surrey, Guildford, Surrey, United Kingdom (MNC); the Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, Parma, Italy (DDR); the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom (MEJL); the Global Scientific and Regulatory Affairs, The Coca-Cola Company, Atlanta, GA (SAR); and Research and Development, Coca-Cola Services nv, Brussels, Belgium (MBK).
authors.forename: Susan A
authors.initials: SA
authors.lastname: Roberts
authors.affiliation: From the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (GP-C, GB, JvdH, and AC); the School of Biosciences and Medicine, Faculty of Health and Medical Sciences, The Dorothy Hodgkins Building, University of Surrey, Guildford, Surrey, United Kingdom (MNC); the Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, Parma, Italy (DDR); the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom (MEJL); the Global Scientific and Regulatory Affairs, The Coca-Cola Company, Atlanta, GA (SAR); and Research and Development, Coca-Cola Services nv, Brussels, Belgium (MBK).
authors.forename: Michele B
authors.initials: MB
authors.lastname: Kellerhals
authors.affiliation: From the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (GP-C, GB, JvdH, and AC); the School of Biosciences and Medicine, Faculty of Health and Medical Sciences, The Dorothy Hodgkins Building, University of Surrey, Guildford, Surrey, United Kingdom (MNC); the Laboratory of Phytochemicals in Physiology, Human Nutrition Unit, Department of Food Science, University of Parma, Parma, Italy (DDR); the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom (MEJL); the Global Scientific and Regulatory Affairs, The Coca-Cola Company, Atlanta, GA (SAR); and Research and Development, Coca-Cola Services nv, Brussels, Belgium (MBK).
authors.forename: Alan
authors.initials: A
authors.lastname: Crozier
mesh_terms: D000328:Adult; D001628:Beverages / Q000032:analysis*; D001682:Biological Availability; D015992:Body Mass Index; D002851:Chromatography, High Pressure Liquid; D032084:Citrus sinensis / Q000737:chemistry*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D044950:Flavanones / Q000493:pharmacokinetics / Q000652:urine; D005638:Fruit / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D020719:Glucuronides / Q000493:pharmacokinetics / Q000652:urine; D064368:Healthy Volunteers; D006569:Hesperidin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000652:urine; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D059808:Polyphenols / Q000493:pharmacokinetics* / Q000652:urine; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D044950:Flavanones; D020719:Glucuronides; D059808:Polyphenols; C587870:hesperetin-7-O-glucuronide; D006569:Hesperidin; C005273:naringenin; C028610:flavanone