Aachen, Germany - The benefits of cocoa, known recently for its ability to reduce blood pressure and improve endothelial function, also extends to diabetic patients, a new study has shown [1]. In a small, randomized study, investigators showed that the consumption of a big mug of hot cocoa can reverse vascular dysfunction in patients with diabetes, suggesting a therapeutic potential of cocoa in this patient population.

"Our study clearly established improvements of endothelial function after regular consumption of flavanol-containing cocoa in patients with type 2 diabetes, highlighting the potential of flavanol-containing diets and underscoring the potential health benefit for reducing the risk of cardiovascular events in diabetic patients," write lead investigator Dr Jan Balzer (University Hospital RWTH, Aachen, Germany) and colleagues in the June 3, 2008 issue of the Journal of the American College of Cardiology.

The findings are just the latest in a string of studies showing the cardiovascular promise of foods like cocoa that contain flavanols. Flavanols are a subgroup of plant-derived phytochemicals known as flavonoids, and several studies have shown that flavanol-containing foods, including cocoa, certain fruits and vegetables, tea, and red wine, have beneficial effects on LDL oxidation, platelet aggregation, insulin sensitivity, endothelial function, and blood pressure.

Despite the existing data, however, studies on the effects of flavanols on the vasculature in diabetic patients were missing. Patients with type 2 diabetes, writes Balzer and colleagues, might receive particular benefit from flavanol-containing cocoa, because various observational studies have shown that lifestyle modifications are particularly important in the prevention of diabetes and its complications.

The investigators performed two studies: a 10-patient feasibility study to determine the appropriate dosing, to assess safety and tolerability, and to measure the effect size of the intervention to calculate sample size of the efficacy study. In total, 44 patients with treated type 2 diabetes were enrolled in the randomized, double-blind, parallel-group efficacy study, with half allocated to the treatment arm of 321 mg of flavanols per dose three times daily. The control patients also received some flavanols, albeit a much smaller amount, about 25 mg per dose three times daily.

Baseline flow-mediated dilation (FMD) values were 3.3% in both the treatment and control arms at the start of the intervention. The daily consumption of flavanol-containing cocoa by patients in the treatment arm resulted in continual increases in FMD, increasing from 3.3% at baseline to 4.1% on day 8 and to 4.3% by study completion on day 30. The investigators note that the acute effects of drinking cocoa in the treatment arm, those recorded two hours after ingestion, were of a similar effect size at study entry, day 8, and day 30, suggesting that patients did not become desensitized or immune to the effects of drinking cocoa.

On day 30, the investigators report that the composite maximum increase in FMD—a combination of the chronic and acute effects of cocoa ingestion—was 5.8%, suggesting "a reversal of endothelial dysfunction." This reversal in endothelial dysfunction with cocoa is comparable to intermediate- and long-term interventions using exercise and various medications, including insulin, pioglitazone, ACE inhibitors, and statins, write Balzer and colleagues.

The high-flavanol cocoa used in this study—which provides much more flavanol than the typical US dietary intake of 20 to 100 mg daily—is not sold in the supermarket.

The present study was not designed to determine the precise molecular mechanism by which flavanols improve endothelial function. However, the investigators point out that FMD of the brachial artery is almost entirely dependent on nitric oxide (NO) and that endothelial function measured by FMD is commonly used as a marker of endothelial NO synthesis.

This proposed mechanism, they note, would make sense considering that recurrent and prolonged hyperglycemia in diabetic patients reduces NO bioavailability, which leads to endothelial dysfunction. In support of this hypothesis, Balzer and colleagues report no improvement in endothelium-independent vasodilation after the administration of nitroglycerin, which suggests that improvements in vascular function are secondary to the effects of treatment on endothelial function and NO bioavailability.

In an editorial accompanying the study, Drs Umberto Campia and Julio A Panza (Washington Hospital Center, Washington, DC) note that interest in the cardiovascular benefits of cocoa started with observations of the Kuna Indians [2]. This indigenous population in Panama consumes a large amount of cocoa rich in flavanols and, despite a diet that also has a large amount of salt, they have a very low prevalence of heart disease, stroke, diabetes, and cancer compared with Kuna Indians living in Panama City.

Campia and Panza write that because the endothelium plays a significant role in hypertension and atherosclerosis, research efforts have focused on the acute and chronic effects of cocoa, as well as other drinks and food, in the hope that their consumption could improve vascular function.

One important question, the editorialists note, that this study answers pertains to previous concerns that nutrients in the diet of diabetic patients might not reach needed physiological levels due to secondary impairments in gastrointestinal function. That absorption concern is apparently unwarranted, as these data suggest flavanol intake in diabetics results in plasma levels consistent with those observed in nondiabetic patients. Second, this study also shows that FMD increased steadily and was maintained over time, "suggesting a lack of significant desensitization or tolerance."

The study, according to Campia and Pana, extends the understanding of the vascular effects of flavanols to diabetic patients, but more work is still needed. "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," they write.