title: Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans.
abstract: BACKGROUND
  Consumption of flavonoid-rich beverages, including tea and red wine, has been associated with a reduction in coronary events, but the physiological mechanism remains obscure. Cocoa can contain extraordinary concentrations of flavanols, a flavonoid subclass shown to activate nitric oxide synthase in vitro.
  
  
  OBJECTIVE
  To test the hypothesis that flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in humans.
  
  
  METHODS
  The study prospectively assessed the effects of Flavanol-rich cocoa, using both time and beverage controls. Participants were blinded to intervention; the endpoint was objective and blinded.
  
  
  METHODS
  Pulse wave amplitude was measured on the finger in 27 healthy people with a volume-sensitive validated calibrated plethysmograph, before and after 5 days of consumption of Flavanol-rich cocoa [821 mg of flavanols/day, quantitated as (-)-epicatechin, (+)-catechin, and related procyanidin oligomers]. The specific nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) was infused intravenously on day 1, before cocoa, and on day 5, after an acute ingestion of cocoa.
  
  
  RESULTS
  Four days of flavanol-rich cocoa induced consistent and striking peripheral vasodilation (P = 0.009). On day 5, pulse wave amplitude exhibited a large additional acute response to cocoa (P = 0.01). L-NAME completely reversed this vasodilation (P = 0.004). In addition, intake of flavanol-rich cocoa augmented the vasodilator response to ischemia. Flavanol-poor cocoa induced much smaller responses (P = 0.005), and none was induced in the time-control study. Flavanol-rich cocoa also amplified the systemic pressor effects of L-NAME (P = 0.005).
  
  
  CONCLUSIONS
  In healthy humans, flavanol-rich cocoa induced vasodilation via activation of the nitric oxide system, providing a plausible mechanism for the protection that flavanol-rich foods induce against coronary events.
authors.affiliation: Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. nfisher@partners.org
authors.forename: Naomi D L
authors.initials: ND
authors.lastname: Fisher
authors.forename: Meghan
authors.initials: M
authors.lastname: Hughes
authors.forename: Marie
authors.initials: M
authors.lastname: Gerhard-Herman
authors.forename: Norman K
authors.initials: NK
authors.lastname: Hollenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001132:Arm / Q000098:blood supply*; D001628:Beverages; D001794:Blood Pressure / Q000187:drug effects; D002099:Cacao; D003971:Diastole / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage*; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D006940:Hyperemia / Q000097:blood / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D011446:Prospective Studies; D011673:Pulsatile Flow / Q000187:drug effects; D011674:Pulse; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D009569:Nitric Oxide; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester