title: Cranberry (poly)phenol metabolites correlate with improvements in vascular function: A double-blind, randomized, controlled, dose-response, crossover study.
abstract: Cranberries are rich in potentially bioactive (poly)phenols. The aim of this paper was to investigate whether cranberry juice intake can improve vascular function in healthy men in a dose- and time-dependent manner, and to understand which of the circulating (poly)phenol metabolites correlate with vascular effects.
  
  
  
  A double-blind randomized controlled crossover trial was conducted in ten healthy males. Flow-mediated dilation (FMD), blood pressure, pulse wave velocity and augmentation index were investigated at baseline, 1, 2, 4, 6, and 8 h post-consumption of cranberry juices containing 409, 787, 1238, 1534, and 1910 mg of total cranberry (poly)phenols (TP), and a control drink. Plasma (poly)phenol metabolites were analyzed by UPLC-Q-TOF MS using authentic standards. We observed dose-dependent increases in FMD at 1, 2, 4, 6, and 8 h with a peak at 4 h and maximal effects with juice containing 1238 mg TP. A total of 60 metabolites were quantified in plasma after cranberry consumption. Twelve (poly)phenol metabolites significantly correlated with the increases in FMD, including ferulic and caffeic acid sulfates, quercetin-3-O-ß-D-glucuronide and a γ-valerolactone sulfate.
  
  
  
  (Poly)phenols in cranberry juice can improve vascular function in healthy males and this is linked to the presence of specific newly identified plasma metabolites.
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany. ana.rodriguez-mateos@med.uni-duesseldorf.de.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez-Mateos
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Rodrigo P
authors.initials: RP
authors.lastname: Feliciano
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Boeres
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Timon
authors.initials: T
authors.lastname: Weber
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, Oeiras, Portugal.|Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.
authors.forename: Claudia Nunes
authors.initials: CN
authors.lastname: Dos Santos
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Avenida da República, Oeiras, Portugal.
authors.forename: M Rita
authors.initials: MR
authors.lastname: Ventura
authors.affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D000067030:Fruit and Vegetable Juices / Q000032:analysis; D006801:Humans; D008297:Male; D059808:Polyphenols / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D063177:Pulse Wave Analysis; D029799:Vaccinium macrocarpon / Q000737:chemistry*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D059808:Polyphenols
keywords: (Poly)phenols; Cranberry; Endothelial function; Metabolites; Primary prevention