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CLINICAL RESEARCH: VASCULAR FUNCTION

Sustained Benefits in Vascular Function Through Flavanol-Containing Cocoa in Medicated Diabetic Patients

A Double-Masked, Randomized, Controlled Trial

Jan Balzer, MD^_*, Tienush Rassaf, MD^_*, Christian Heiss, MD^_*, Petra Kleinbongard, PhD^_*, Thomas Lauer, MD^_*, Marc Merx, MD^_*, Nicole Heussen, PhD, Heidrun B. Gross, PhD, Carl L. Keen, PhD, Hagen Schroeter, PhD and Malte Kelm, MD^_*,_*

^_* Department for Cardiology, Pulmonology, and Vascular Medicine, University Hospital RWTH Aachen, Aachen, Germany
Department of Medical Statistics, University Hospital RWTH Aachen, Aachen, Germany
Department of Nutrition, University of California, Davis, California
Mars Symbioscience, Rockville, Maryland.

Manuscript received November 14, 2007; revised manuscript received January 7, 2008, accepted January 21, 2008.

^_* Reprint requests and correspondence: Dr. Malte Kelm, Department for Cardiology, Pulmonology, and Vascular Medicine, University Hospital RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany. (Email: mkelm{at}ukaachen.de).

Objectives: Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients.

Background: Even in fully medicated diabetic patients, overall prognosis is unfavorable due to deteriorated cardiovascular function. Based on epidemiological data, diets rich in flavanols are associated with a reduced cardiovascular risk.

Methods: In a feasibility study with 10 diabetic patients, we assessed vascular function as flow-mediated dilation (FMD) of the brachial artery, plasma levels of flavanol metabolites, and tolerability after an acute, single-dose ingestion of cocoa, containing increasing concentrations of flavanols (75, 371, and 963 mg). In a subsequent efficacy study, changes in vascular function in 41 medicated diabetic patients were assessed after a 30-day, thrice-daily dietary intervention with either flavanol-rich cocoa (321 mg flavanols per dose) or a nutrient-matched control (25 mg flavanols per dose). Both studies were undertaken in a randomized, double-masked fashion. Primary and secondary outcome measures included changes in FMD and plasma flavanol metabolites, respectively.

Results: A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols and FMD (at 2 h: from 3.7 ± 0.2% to 5.5 ± 0.4%, p < 0.001). A 30-day, thrice-daily consumption of flavanol-containing cocoa increased baseline FMD by 30% (p < 0.0001), while acute increases of FMD upon ingestion of flavanol-containing cocoa continued to be manifest throughout the study. Treatment was well tolerated without evidence of tachyphylaxia. Endothelium-independent responses, blood pressure, heart rate, and glycemic control were unaffected.

Conclusions: Diets rich in flavanols reverse vascular dysfunction in diabetes, highlighting therapeutic potentials in cardiovascular disease.

Abbreviations and Acronyms   FMD = flow-mediated dilation   GTN = glycerol trinitrate   NO = nitric oxide

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