Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans

J Hypertens. 2003 Dec;21(12):2281-6. doi: 10.1097/00004872-200312000-00016.


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.

Design: 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).

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arm / blood supply*
  • Beverages*
  • Blood Pressure / drug effects
  • Cacao*
  • Diastole / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage
  • Female
  • Flavonoids / administration & dosage*
  • Glucose / administration & dosage
  • Humans
  • Hyperemia / blood
  • Hyperemia / physiopathology
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • Nitric Oxide / metabolism*
  • Prospective Studies
  • Pulsatile Flow / drug effects
  • Pulse
  • Reference Values
  • Regional Blood Flow / drug effects
  • Systole / drug effects
  • Vasodilation / drug effects*


  • Enzyme Inhibitors
  • Flavonoids
  • Nitric Oxide
  • Glucose
  • NG-Nitroarginine Methyl Ester