Abstract-Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7Ϯ7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. O bservational studies suggest dietary flavonoids decrease the risk of death from coronary heart disease, 1 cancer, 1 and stroke. 2 Flavonoid-rich foods include fruits and vegetables as well as tea, red wine, and chocolate. 3 The high flavonoid content, particularly in flavanols (ie, catechins) and their procyanidin oligomers, of these foods may contribute to some of their putative cardiovascular benefits. 4,5 The antioxidant protection afforded by flavonoids in the vascular endothelium may reduce the risk for atherosclerosis, including their action of inhibiting the oxidative conversion of NO to peroxynitrite. 6 Accordingly, cocoa flavonoids decreased oxidant-induced peroxynitrite production in vitro 7 and increased NO synthase (NOS) expression and NO-dependent vasorelaxation in rabbit aortic rings. 8 In healthy adults, drinking flavanol-rich cocoa increased NO-dependent vasorelaxation in finger arteries, 9 and eating flavanol-rich dark chocolate (DC) improved flow-mediated dilation (FMD) in brachial arteries in association with an increase in plasma epicatechin. 10 Impaired NO-dependent vasorelaxation also contributes to a dysregulation of blood pressure (BP) 11 and a decrement of insulin-mediated glucose uptake. 12 In contrast, increased endothelial NOS expression and NO bioavailability ameliorate endothelial dysfunction, and thereby have the potential to decrease BP, increase insulin sensitivity, and slow down atherogenetic processes. In this regard, the anthocyanin cyanidin-3-glucoside was able to increase NOS expression and NO bioavailability in vascular endothelial cells. 13 We recently demonstrated decrements in BP and increments in insulin sensitivity in healthy volunteers after 15 days of DC intake. 14 Thus, we studied patients with essential hypertension (EH) to evaluate the effects of flavanol-rich DC on 24-hour ambulatory BP monitoring (ABPM), endotheliumdependent vasorelaxation via FMD of the brachial artery, insulin sensitivity via oral glucose tolerance tests (OGTTs), and 2 serum biomarkers of vascular inflammation: highsensitive C-reactive protein (hsCRP) and intercellular adhesion molecule-1 (ICAM-1).

Flavanols from chocolate appear to increase nitric oxide bioavailability, protect vascular endothelium, and decrease cardiovascular disease (CVD) risk factors. We sought to test the effect of flavanol-rich dark chocolate (FRDC) on endothelial function, insulin sensitivity, beta-cell function, and blood pressure (BP) in hypertensive patients with impaired glucose tolerance (IGT). After a run-in phase, 19 hypertensives with IGT (11 males, 8 females; 44.8 +/- 8.0 y) were randomized to receive isocalorically either FRDC or flavanol-free white chocolate (FFWC) at 100 g/d for 15 d. After a wash-out period, patients were switched to the other treatment. Clinical and 24-h ambulatory BP was determined by sphygmometry and oscillometry, respectively, flow-mediated dilation (FMD), oral glucose tolerance test, serum cholesterol and C-reactive protein, and plasma homocysteine were evaluated after each treatment phase. FRDC but not FFWC ingestion decreased insulin resistance (homeostasis model assessment of insulin resistance; P < 0.0001) and increased insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity index (ISI), ISI(0); P < 0.05) and beta-cell function (corrected insulin response CIR(120); P = 0.035). Systolic (S) and diastolic (D) BP decreased (P < 0.0001) after FRDC (SBP, -3.82 +/- 2.40 mm Hg; DBP, -3.92 +/- 1.98 mm Hg; 24-h SBP, -4.52 +/- 3.94 mm Hg; 24-h DBP, -4.17 +/- 3.29 mm Hg) but not after FFWC. Further, FRDC increased FMD (P < 0.0001) and decreased total cholesterol (-6.5%; P < 0.0001), and LDL cholesterol (-7.5%; P < 0.0001). Changes in insulin sensitivity (Delta ISI - Delta FMD: r = 0.510, P = 0.001; Delta QUICKI - Delta FMD: r = 0.502, P = 0.001) and beta-cell function (Delta CIR(120) - Delta FMD: r = 0.400, P = 0.012) were directly correlated with increases in FMD and inversely correlated with decreases in BP (Delta ISI - Delta 24-h SBP: r = -0.368, P = 0.022; Delta ISI - Delta 24-h DBP r = -0.384, P = 0.017). Thus, FRDC ameliorated insulin sensitivity and beta-cell function, decreased BP, and increased FMD in IGT hypertensive patients. These findings suggest flavanol-rich, low-energy cocoa food products may have a positive impact on CVD risk factors.

Dark, but not white, chocolate decreases blood pressure and improves insulin sensitivity in healthy persons.

Nondippers have enhanced plasma sCD40L levels, which may contribute to their increased susceptibility to develop vascular damage.