title: Mediation of coffee-induced improvements in human vascular function by chlorogenic acids and its metabolites: Two randomized, controlled, crossover intervention trials.
abstract: Polyphenol intake has been linked to improvements in human vascular function, although data on hydroxycinnamates, such as chlorogenic acid (CGA) have not yet been studied. We aimed to investigate the impact of coffee intake rich in chlorogenic acid on human vascular function and whether CGAs are involved in potential effects.
  
  
  
  Two acute randomized, controlled, cross-over human intervention trials were conducted. The impact of coffee intake, matched for caffeine but differing in CGA content (89, and 310 mg) on flow-mediated dilatation (FMD) was assessed in 15 healthy male subjects. In a second intervention trial conducted with 24 healthy male subjects, the impact of pure 5-caffeoylquinic acid (5-CQA), the main CGA in coffee (5-CQA; 450 mg and 900 mg) on FMD was also investigated.
  
  
  
  We observed a bi-phasic FMD response after low and high polyphenol, (89 mg and 310 mg CGA) intake, with increases at 1 (1.10 ± 0.43% and 1.34 ± 0.62%, respectively) and 5 (0.79% ± 0.32 and 1.52% ± 0.40, respectively) hours post coffee consumption. FMD responses to coffee intake was closely paralleled by the appearance of CGA metabolites in plasma, notably 3-, 4- and 5-feruloylquinic acid and ferulic-4'-O-sulfate at 1 h and isoferulic-3'-O-glucuronide and ferulic-4'-O-sulfate at 5 h. Intervention with purified 5-CQA (450 mg) also led to an improvement in FMD response relative to control (0.75 ± 1.31% at 1 h post intervention, p = 0.06) and concomitant appearance of plasma metabolites.
  
  
  
  Coffee intake acutely improves human vascular function, an effect, in part, mediated by 5-CQA and its physiological metabolites.
  
  
  
  The National Institutes of Health (NIH) on ClinicalTrials.govNCT01813981 and NCT01772784.
authors.affiliation: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, RG2 6AP, Reading, UK.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Mills
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital Bern, CH-3010, Bern, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Flury
authors.affiliation: Nestlé Research Centre, Route du Jorat 94, Lausanne, 1000, Switzerland.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Marmet
authors.affiliation: Nestlé Research Centre, Route du Jorat 94, Lausanne, 1000, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Poquet
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital Bern, CH-3010, Bern, Switzerland.
authors.forename: Stefano F
authors.initials: SF
authors.lastname: Rimoldi
authors.affiliation: Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Sartori
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital Bern, CH-3010, Bern, Switzerland.
authors.forename: Emrush
authors.initials: E
authors.lastname: Rexhaj
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital Bern, CH-3010, Bern, Switzerland.
authors.forename: Roman
authors.initials: R
authors.lastname: Brenner
authors.affiliation: Department of Cardiology and Clinical Research, Inselspital, University Hospital Bern, CH-3010, Bern, Switzerland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allemann
authors.affiliation: Nestlé Research Centre, Route du Jorat 94, Lausanne, 1000, Switzerland.
authors.forename: Diane
authors.initials: D
authors.lastname: Zimmermann
authors.affiliation: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, RG2 6AP, Reading, UK.
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gibson
authors.affiliation: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, RG2 6AP, Reading, UK.
authors.forename: Don S
authors.initials: DS
authors.lastname: Mottram
authors.affiliation: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, RG2 6AP, Reading, UK.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Oruna-Concha
authors.affiliation: Nestlé Research Centre, Route du Jorat 94, Lausanne, 1000, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Actis-Goretta
authors.affiliation: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, RG2 6AP, Reading, UK. Electronic address: j.p.e.spencer@reading.ac.uk.
authors.forename: Jeremy P E
authors.initials: JPE
authors.lastname: Spencer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D002726:Chlorogenic Acid / Q000008:administration & dosage* / Q000097:blood; D003069:Coffee; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D059808:Polyphenols / Q000008:administration & dosage* / Q000097:blood; D011801:Quinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D003069:Coffee; D059808:Polyphenols; C472707:caffeoylquinic acid; D011801:Quinic Acid; D002726:Chlorogenic Acid
keywords: Chlorogenic acid; Coffee; Flow mediated dilatation (FMD); Phenolics; Vascular