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

Fisher, Naomi DL; Hughes, Meghan; Gerhard-Herman, Marie; Hollenberg, Norman K

Original papers: Endothelium

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.

Departments of Medicine and Radiology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.

Note: Previously presented in poster format at the American Society of Hypertension 2003 (Fisher NDL, Hughes M, Hollenberg NK. Cocoa induces nitric oxide-dependent vasodilation in healthy humans. Am J Hypertens 2003;16:72A).

Sponsorship: This study was supported in part by the National Institutes of Health grants (T32 HL-07609, NCRR GCRC M01RR026376, P01AC00059916, 1P50ML53000-01, and 1 R01 DK5468-01), and Mars, Incorporated.

Potential conflicts of interest or disclaimers: None.

Correspondence and requests for reprints to Naomi D.L. Fisher MD, Brigham and Women's Hospital, Endocrine-Hypertension Division, 221 Longwood Avenue, Boston, MA 02115, USA. Tel: +1 617 732 5654; fax: +1 617 732 5764; e-mail:

Received 23 June 2003 Revised 11 August 2003 Accepted 13 August 2003

See editorial commentary on page 2231

© 2003 Lippincott Williams & Wilkins, Inc.