Phytochemicals known as flavanols, which are found in chocolate, fruits and vegetables, can boost the levels of nitric oxide in the blood of smokers and reverse some of their smoking-related impairment in blood vessel function, according to a new study in the Oct. 4, 2005, issue of the Journal of the American College of Cardiology.

"While the long-term benefits of such improvements remain to be established, we believe that one exciting outcome of this study is the demonstration that flavanol-rich cocoa can significantly improve an important marker of cardiovascular health in a population with an established cardiovascular risk factor. This raises the possibility that a potential new agent for the prevention and/or treatment of cardiovascular disease may emerge from additional research," said Malte Kelm, M.D. from the Heinrich-Heine-University in Duesseldorf, Germany.

The researchers studied smokers because their blood vessels tend to respond poorly to changes in blood flow, possibly related to impairments in how nitric oxide sends signals to the inner lining, the endothelium, of blood vessels. This impaired endothelial function is a marker for increased risk of cardiovascular disease.

A dozen smokers (six men and six women) in their early 30s, who did not have any known health problems, were enrolled in the double-blind crossover study to compare the effects of a cocoa drink rich in flavanols to a cocoa drink that tasted the same, but contained very low levels of flavanols. One woman was excluded from the analysis because she had high cholesterol levels. Circulating nitric oxide levels and blood vessel responses (flow-mediated dilation) were measured before drinking the cocoa and again two hours later. Each participant drank flavanol-rich and flavanol-poor cocoa drinks during different testing sessions.

There were significant increases in circulating nitric oxide and flow-mediated dilation after ingestion of drinks containing 176 to 185 milligrams of flavanols, a dose potentially exerting maximal effects. These changes correlated with increases in flavanol metabolites. In addition, the improvements were reversed when the participants were given a drug (L-NMMA) that interferes with nitric oxide signaling, thus supporting the idea that the flavanol-rich cocoa drink produced its effects by influencing the nitric oxide system.

"Taken together, these findings support the notion that flavanol-rich foods, including cocoa products, may help to promote cardiovascular health," Dr. Kelm said.

However, he said the main point of the study was to identify the active ingredients so that they can be studied further. The researchers pointed out that the cocoa drink they used was specially processed to retain much higher levels of flavanols than are typically found in commercially-available cocoa drinks; so it is unlikely that drinking more hot chocolate would produce a similar effect.

Even though this study involved only 11 participants, lead author Christian Heiss, M.D., Ph.D., pointed out that the results were in agreement with other studies indicating potential benefits from flavanol-rich foods, including cocoa and chocolate.

"Therefore, we feel that there exists an increasing body of evidence for an acute effect of flavanol-rich foods on vascular reactivity. Nevertheless, the conclusion drawn from these results have to be interpreted with caution, because it is not known whether or not the chronic consumption of flavanol-rich foods leads to sustained increases in endothelial function, and the prevention of future cardiovascular events. In particular in smokers, it is unlikely that cocoa can completely attenuate the deleterious effects of continued smoking," Dr. Heiss said.

Dr. Heiss is currently affiliated with the Division of Cardiology, University of California in San Francisco, California.

The researchers emphasized that this study was not designed to investigate whether flavanols could protect smokers; smokers were enrolled because they tend to have abnormal blood vessel responses.

Mary B. Engler, Ph.D., who is also at the University of California in San Francisco, but was not connected with this study, noted that it is the first such study in smokers to demonstrate that endothelial function improved after drinking cocoa with high levels of flavonoids.

"The study has helped to identify the optimal concentrations, potential mechanisms and the role of biologically active metabolites of the cocoa flavonoids in the improvement in vascular function in smokers. Although, it is a small study with 11 subjects, it has important implications and further supports the current evidence on the heart-healthy benefits of dark chocolate and drinks rich in cocoa flavonoids. Larger, long-term studies are definitely needed in follow-up," Dr. Engler said.

Dr. Engler emphasized that quitting smoking is the best way to reduce heart disease risk. She also pointed out that many foods and beverages contain a substantial amount of the same flavonoids (flavanols-epicatechin, catechin) found in cocoa and dark chocolate. These foods include green and black tea (especially Ceylon tea), red wine, sweet cherries, apples, apricots, purple grapes, blackberries, raspberries and broad beans.

Professor Gerd Heusch, M.D., at the Universitätsklinikum Essen in Essen, Germany, who also was not connected to this research effort, said the study indicates that flavonoids have an effect on the same nitric oxide system that is damaged by smoking.

"A flavanol- rich drink is capable of increasing nitric oxide levels in the blood and reversing the detrimental effect of smoking on vascular adaptation. It remains to be seen whether the acute beneficial effect of a flavanol-rich drink translates into a long-term benefit, in terms of attenuating or preventing the development of atherosclerosis," Dr. Heusch said.

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