Author + information
- Received December 1, 2004
- Revision received June 3, 2005
- Accepted June 6, 2005
- Published online October 4, 2005.
- 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†,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Malte Kelm, Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich-Heine-University, Moorenstr. 5, 40225 Duesseldorf, Germany.
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.
Dr. Heiss is currently affiliated with the Division of Cardiology, University of California, San Francisco, California. Mars Inc. supported this study by an unrestricted grant and through provision of the cocoa drinks. Drs. Kleinbongard and Kelm (SFB 612) and Dr. Sies (SFB 575) are supported by the Deutsche Forschungsgemeinschaft. Dr. Sies is a Fellow of the National Foundation for Cancer Research (Bethesda, Maryland).
- Received December 1, 2004.
- Revision received June 3, 2005.
- Accepted June 6, 2005.
- American College of Cardiology Foundation