Randomized study examines the effects on type 2 diabetics of topping off standard medications by drinking flavanol-rich cocoa three times a day.

by Todd Neale, Staff Writer, MedPage Today

AACHEN, Germany, May 27 — For type 2 diabetics, topping off standard medications by drinking flavanol-rich cocoa three times a day may improve endothelial function and reduce cardiovascular risk, according to a small randomized study here.

Those who had cocoa three times daily for 30 days had a 30% improvement in flow-mediated dilation of the brachial artery (P<0.0001), Malte Kelm, M.D., of University Hospital Aachen, and colleagues reported in the June 3 issue of the Journal of the American College of Cardiology. The cocoa was made from an instant cocoa beverage powder.

“Our study clearly establishes improvements of endothelial function after regular consumption of flavanol-containing cocoa in patients with type 2 diabetes,” the researchers said, “highlighting the potential of flavanol-containing diets, and underscoring the potential healthcare benefit for reducing the risk of cardiovascular events in diabetic patients.”

Action Points 
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Explain to interested patients that this study found that cocoa containing high doses of flavanols improved endothelial function in diabetics.

Point out that the concentrations of flavanols evaluated in this study were substantially higher than the average daily intake in the U.S.
These results should not, Dr. Kelm said in a statement, be used to encourage diabetics to eat more chocolate.

“Patients with type 2 diabetes can certainly find ways to fit chocolate into a healthy lifestyle, but this study is not about chocolate, and it’s not about urging those with diabetes to eat more chocolate,” he said. “While more research is needed, our results demonstrate that dietary flavanols might have an important impact as part of a healthy diet in the prevention of cardiovascular complications in diabetic patients.”

Previous studies have linked foods that have high concentrations of flavanoids, a group of plant-derived chemicals that includes flavanols, with a reduced cardiovascular disease and mortality risk. Fruits, vegetables, tea, red wine, and cocoa contain flavanols.

But controlled trials evaluating the benefits of long-term consumption of flavanol-rich cocoa in patients with diabetes has been lacking, the researchers said.

So they assessed the safety and tolerability of flavanol-rich cocoa in a feasibility study with 10 nonsmoking diabetics (mean age 64.7). Three doses of flavanols were tested — 75, 371, and 963 mg.

A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols indicating that flavanols present in cocoa are absorbed in diabetic patients.

The mean flow-mediated dilation at baseline was 3.8% and the lowest dose did not significantly change the measurement.

The highest dose, however, significantly increased the flow-mediated dilation to 5.5% at two hours after consumption (P<0.001).

All 10 participants exhibited significant increases in flow-mediated dilation and plasma flavanol concentrations.

Next, the researchers conducted a 30-day efficacy study in which they randomized 21 patients to cocoa containing 321 mg of flavanols three times daily or 20 to a control drink containing 25 mg of flavanols.

Baseline flow-mediated dilation was 3.3% in both the treatment and control groups.

Pre-consumption flow-mediated dilation increased significantly from 3.3% at the start of the study to 4.1% at eight days (P<0.001) and 4.3% at 30 days (P<0.0001).

The acute effects of flavanol consumption were similar at the start of the study (3.3% to 4.8%), at eight days (4.1% to 5.7%), and at 30 days (4.3% to 5.8%) (P<0.0001 for all), indicating that desensitization and tachyphylaxia did not occur.

A reference group of healthy participants had a mean flow-mediated dilation of 5.2%.

In both the feasibility and efficacy study, nitroglycerin-mediated dilation was not affected by any of the flavanol doses, “indicating the involvement of endothelium dependent processes,” the researchers said.

The researchers noted that the degree of the reversal of endothelial dysfunction was similar to that found in other studies of diabetics with exercise, statins, ACE inhibitors, pioglitazone, and insulin.

The mechanism by which flavanols influenced flow-mediated dilation was not identified in this study but it may be related to the production of nitric oxide, according to the researchers.

“Flow-mediated dilation of the brachial artery is almost entirely [nitric oxide] synthase dependent, correlates with endothelial function of most conduit arteries, and can, therefore, be used as a surrogate for systemic [nitric oxide] synthesis,” they said.

Nitroglycerin-mediated dilation was similar between the two groups and was not affected by the dietary interventions.

A previous study estimated that the average daily intake of flavanols in the United States was 20 to 100 mg, far below the levels used in the current study.

In an accompanying editorial, Umberto Campia, M.D., and Julio Panza, M.D., of MedStar Research Institute in Washington, D.C., wrote that these findings extend previous findings of the cardiovascular benefits of flavanols to diabetics.

“However,” they said, “although endothelial function has been shown to predict future cardiovascular events, randomized, large-scale clinical trials assessing relevant clinical outcomes are necessary before any recommendations are made regarding dietary supplementation with flavanol-rich cocoa.”


The study was supported by an unrestricted grant from Mars Inc., which provided the instant cocoa beverage powder used. Support for the study was also provided by the Deutsche Forschungsgemeinschaft, the University Hospital RWTH Aachen, the Hans und Gertie Fischer-Stiftung, and the American Heart Association.

One of Dr. Kelm’s co-authors is an employee of Mars Symbioscience, a division of Mars Inc.

Drs. Campia and Panza made no disclosures.


Primary source: Journal of the American College of Cardiology
Source reference: Balzer J, et al “Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients” J Am Coll Cardiol 2008; 51: 2141-2149.

Additional source: Journal of the American College of Cardiology
Source reference: Campia U, Panza J “Flavanol-rich cocoa: a promising new dietary intervention to reduce cardiovascular risk in type 2 diabetes?” J Am Coll Cardiol 2008; 51: 2150-2152. 

Reviewed by Zalman S. Agus, MD; Emeritus Professor, University of Pennsylvania School of Medicine.

Published: May 27, 2008

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