title: Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week.
abstract: A single-dose ingestion of flavanol-rich cocoa acutely reverses endothelial dysfunction. To investigate the time course of endothelial function during daily consumption of high-flavanol cocoa, we determined flow-mediated dilation (FMD) acutely (for up to 6 hours after single-dose ingestion) and chronically (administration for 7 days). The study population represented individuals with smoking-related endothelial dysfunction; in addition to FMD, plasma nitrite and nitrate were measured. The daily consumption of a flavanol-rich cocoa drink (3 x 306 mg flavanols/d) over 7 days (n=6) resulted in continual FMD increases at baseline (after overnight fast and before flavanol ingestion) and in sustained FMD augmentation at 2 hours after ingestion. Fasted FMD responses increased from 3.7 +/- 0.4% on day 1 to 5.2 +/- 0.6%, 6.1 +/- 0.6%, and 6.6 +/- 0.5% (each P < 0.05) on days 3, 5, and 8, respectively. FMD returned to 3.3 +/- 0.3% after a washout week of cocoa-free diet (day 15). Increases observed in circulating nitrite, but not in circulating nitrate, paralleled the observed FMD augmentations. The acute, single-dose consumption of cocoa drinks with 28 to 918 mg of flavanols led to dose-dependent increases in FMD and nitrite, with a maximal FMD at 2 hours after consumption. The dose to achieve a half-maximal FMD response was 616 mg (n=6). Generally applied biomarkers for oxidative stress (plasma, MDA, TEAC) and antioxidant status (plasma ascorbate, urate) remained unaffected by cocoa flavanol ingestion. The daily consumption of flavanol-rich cocoa has the potential to reverse endothelial dysfunction in a sustained and dose-dependent manner.
authors.affiliation: Institute for Biochemistry and Molecular Biology I, Aachen, Germany. heissc@medicine.ucsf.edu
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: David
authors.initials: D
authors.lastname: Finis
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: Arne
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000097:blood; D002099:Cacao / Q000737:chemistry*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D044948:Flavonols / Q000494:pharmacology*; D006801:Humans; D049449:Luminescence; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D014527:Uric Acid / Q000097:blood; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D000975:Antioxidants; D044948:Flavonols; D009566:Nitrates; D009573:Nitrites; D014527:Uric Acid; D008315:Malondialdehyde; D001205:Ascorbic Acid