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.
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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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