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CLINICAL RESEARCH: ENDOTHELIAL DYSFUNCTION

Acute Consumption of Flavanol-Rich Cocoa and the Reversal of Endothelial Dysfunction in Smokers

Christian Heiss, MD, PhD^_*,, Petra Kleinbongard, PhD, Andrè Dejam, MD, PhD, Sandra Perré, MS, Hagen Schroeter, PhD, Helmut Sies, MD, PhD^_* and Malte Kelm, MD^,_*

^_* Institute for Biochemistry and Molecular Biology I
Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich-Heine-University, Duesseldorf, Germany
Department of Nutrition, University of California, Davis, California

Manuscript received December 1, 2004; revised manuscript received June 3, 2005, accepted June 6, 2005.

^_* Reprint requests and correspondence: Dr. Malte Kelm, Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich-Heine-University, Moorenstr. 5, 40225 Duesseldorf, Germany. (Email: kelm{at}uni-duesseldorf.de).

OBJECTIVES: This study was designed to assess the effect of flavanol-rich food on the circulating pool of bioactive nitric oxide (NO) and endothelial dysfunction in smokers.

BACKGROUND: Studies suggest that smoking-related vascular disease is caused by impaired NO synthesis and that diets rich in flavanols can increase bioactive NO in plasma.

METHODS: In smokers (n = 11), the effects of flavanol-rich cocoa on circulating NO species in plasma (RXNO) measured by reductive gas-phase chemiluminescence and endothelial function as assessed by flow-mediated dilation (FMD) were characterized in a dose-finding study orally administering cocoa containing 88 to 370 mg flavanols and in a randomized double-blind crossover study using 100 ml cocoa drink with high (176 to 185 mg) or low (<11 mg) flavanol content on two separate days. In addition to cocoa drink, ascorbic acid and NO-synthase inhibitor L-NMMA (n = 4) were applied.

RESULTS: There were significant increases in RXNO (21 ± 3 nmol/l to 29 ± 5 nmol/l) and FMD (4.5 ± 0.8% to 6.9 ± 0.9%, each p < 0.05) at 2 h after ingestion of 176 to 185 mg flavanols, a dose potentially exerting maximal effects. These changes correlated with increases in flavanol metabolites. Cocoa-associated increases in RXNO and FMD were reversed by L-NMMA. Ascorbic acid had no effect.

CONCLUSIONS: The circulating pool of bioactive NO and endothelium-dependent vasodilation is acutely increased in smokers following the oral ingestion of a flavanol-rich cocoa drink. The increase in circulating NO pool may contribute to beneficial vascular health effects of flavanol-rich food.

Abbreviations and Acronyms   FMD = flow-mediated dilation   GTN = glycerol trinitrate   HFCD = high-flavanol cocoa drink   LFCD = low-flavanol cocoa drink   NOS = nitric oxide synthase   RXNO = sum of circulating NO species

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