title: Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double-Blind, Randomized, Placebo-Controlled Trial.
abstract: OBJECTIVE
  Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics.
  
  
  RESULTS
  CF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.2±0.6% to 4.8±0.9% versus placebo, 3.2±0.7% to 3.3±0.8%; P<0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.4±0.9% to 3.9±0.8% versus placebo, 3.5±0.7% to 3.5±0.7%; P<0.001), with reduced diastolic BP (73±12 to 69±11 mmHg versus placebo, 70±11 to 73±13 mmHg; P=0.03) and increased heart rate (70±12 to 74±13 bpm versus placebo, 75±15 to 74±13 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.4±0.9% to 2.7±0.6% versus placebo, 3.5±0.7% to 2.0±0.6%; P<0.001). This effect was sustained throughout the study (acute on chronic, 3.9±0.9% to 3.0±0.7% versus placebo, 3.5±0.7% to 2.2±0.6; P=0.01).
  
  
  CONCLUSIONS
  Dietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD.
authors.affiliation: Department of Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany; Tienush.Rassaf@uk-essen.de.
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
authors.affiliation: Department of Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany;
authors.forename: Christos
authors.initials: C
authors.lastname: Rammos
authors.affiliation: Department of Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany;
authors.forename: Ulrike B
authors.initials: UB
authors.lastname: Hendgen-Cotta
authors.affiliation: Department of Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: DaVita Renal Center Düsseldorf, Düsseldorf, Germany;
authors.forename: Werner
authors.initials: W
authors.lastname: Kleophas
authors.affiliation: DaVita Renal Center Düsseldorf, Düsseldorf, Germany;
authors.forename: Frank
authors.initials: F
authors.lastname: Dellanna
authors.affiliation: Department of Nephrology, Rheinish-Westphalian Technical High School, University of Aachen, Aachen, Germany; and.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: DaVita Renal Center Düsseldorf, Düsseldorf, Germany;
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Hetzel
authors.affiliation: Department of Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany; Medical Faculty, Cardiovascular Research Institute Düsseldorf (CARID), University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
mesh_terms: D000328:Adult; D000368:Aged; D002099:Cacao / Q000737:chemistry*; D002392:Catechin / Q000494:pharmacology; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D059808:Polyphenols / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D006435:Renal Dialysis / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D059808:Polyphenols; D020011:Protective Agents; D002392:Catechin
keywords: blood pressure; cocoa-flavanols; double-blind method; endothelial function; heart rate; hemodialysis; hemodynamics; humans; kidney failure, chronic; nutrition; vascular functions