Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension

Abstract

Background: Essential hypertension is characterized by reciprocal relations between endothelial dysfunction and insulin resistance. Cocoa flavanols stimulate production of the vasodilator nitric oxide from vascular endothelium.

Objective: The objective was to test the hypothesis that consumption of cocoa may simultaneously lower blood pressure, improve endothelial dysfunction, and ameliorate insulin resistance in subjects with essential hypertension.

Design: We conducted a randomized, placebo-controlled, double-blind, crossover trial of a flavanol-rich cocoa drink (150 mL twice a day, approximately 900 mg flavanols/d) in individuals with essential hypertension (n = 20). Antihypertensive medications were discontinued before study enrollment. After a 7-d cocoa-free run-in period, cocoa or flavanol-poor placebo (approximately 28 mg flavanols/d) treatment for 2 wk was followed by a 1-wk washout and then crossover to the other treatment arm. Blood pressure was measured thrice weekly. At baseline and after each treatment period, we assessed insulin sensitivity (hyperinsulinemic-isoglycemic glucose clamp) and insulin-stimulated changes in brachial artery diameter and forearm skeletal muscle capillary recruitment (Doppler ultrasound with or without microbubble contrast).

Results: Cocoa treatment for 2 wk increased insulin-stimulated changes in brachial artery diameter when compared with placebo [median percentage increase from baseline (25th-75th percentile): 8.3 (4.2-11.3) compared with 5.9 (-0.3 to 9.6); P < 0.04]. Nevertheless, cocoa treatment did not significantly reduce blood pressure or improve insulin resistance and had no significant effects on skeletal muscle capillary recruitment, circulating plasma concentrations of adipocytokines, or endothelial adhesion molecules.

Conclusions: Daily consumption of flavanol-rich cocoa for 2 wk is not sufficient to reduce blood pressure or improve insulin resistance in human subjects with essential hypertension. This trial was registered at clinicaltrials.gov as NCT00099476.

FIGURE 1

Participant flow throughout the trial.

FIGURE 2

Mean (± SEM) circulating plasma flavanols and their metabolites after oral ingestion of a placebo drink (≈14 mg total flavanols; ○) or cocoa drink (≈450 mg total flavanols; ●) in subjects (n = 20) with essential hypertension. A comparison of the 2 curves with repeated-measures 2-factor ANOVA showed that the interaction term between treatment (placebo or cocoa drink) and sampling time was significant (P < 0.0001). Therefore, pairwise comparison with the Bonferroni post hoc test was used to assess differences between treatments at each time interval. ^*Significantly different from placebo, P < 0.001.