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.

Background: Recent evidence has indicated that flavanol consumption may have many health benefits in humans, including improved cognitive activities.Objective: The aim was to evaluate the effect of flavanol consumption on cognitive performance in cognitively intact elderly subjects.Design: This was a double-blind, controlled, parallel-arm study conducted in 90 elderly individuals without clinical evidence of cognitive dysfunction who were randomly assigned to consume daily for 8 wk a drink containing 993 mg [high flavanol (HF)], 520 mg [intermediate flavanol (IF)], or 48 mg [low flavanol (LF)] cocoa flavanols (CFs). Cognitive function was assessed at baseline and after 8 wk by using the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT) A and B, and the Verbal Fluency Test (VFT).Results: The changes in MMSE score in response to the 3 different treatments were not different. In contrast, there was a positive impact of the intervention on specific aspects of cognitive function. Mean changes (±SEs) in the time required to complete the TMT A and B after consumption of the HF (−8.6 ± 0.4 and −16.5 ± 0.8 s, respectively) and IF (−6.7 ± 0.5 and −14.2 ± 0.5 s, respectively) drinks significantly (P < 0.0001) differed from that after consumption of the LF drinks (−0.8 ± 1.6 and −1.1 ± 0.7 s, respectively). Similarly, VFT scores significantly improved among all treatment groups, but the magnitude of improvement in the VFT score was significantly (P < 0.0001) greater in the HF group (7.7 ± 1.1 words/60 s) than in the IF (3.6 ± 1.2 words/60 s) and LF (1.3 ± 0.5 words/60 s) groups. Significantly different improvements in insulin resistance (P < 0.0001), blood pressure (P < 0.0001), and lipid peroxidation (P = 0.001) were also observed for the HF and IF groups in comparison with the LF group. Changes in insulin resistance explained ∼17% of changes in composite z score (partial r2 = 0.1703, P < 0.0001).Conclusions: This dietary intervention study provides evidence that regular CF consumption can reduce some measures of age-related cognitive dysfunction, possibly through an improvement in insulin sensitivity. These data suggest that the habitual intake of flavanols can support healthy cognitive function with age. This trial was registered at www.controlled-trials.com as ISRCTN68970511.

Abstract-Flavanol consumption is favorably associated with cognitive function. We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment. We conducted a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing Ϸ990 mg (high flavanols), Ϸ520 .02 seconds, respectively). Similarly, verbal fluency test score was significantly (PϽ0.05) better in subjects assigned to high flavanols in comparison with those assigned to low flavanols (27.50Ϯ6.75 versus 22.30Ϯ8.09 words per 60 seconds). Insulin resistance, blood pressure, and lipid peroxidation also decreased among subjects in the high-flavanol and intermediate-flavanol groups. Changes of insulin resistance explained Ϸ40% of composite z score variability through the study period (partial r 2 ϭ0.4013; PϽ0.0001). To the best of our knowledge, this is the first dietary intervention study demonstrating that the regular consumption of cocoa flavanols might be effective in improving cognitive function in elderly subjects with mild cognitive impairment. This effect appears mediated in part by an improvement in insulin sensitivity. 1,2 MCI represents an interesting field of research, because MCI increases the risk of later developing dementia, and, in this phase, an interventional therapy could have the greatest potential to improve cognitive performance and to slow down disease progression.3 A growing body of evidence suggests that specific dietary components may impact brain function through the regulation of neurotransmitter pathways, signal-transduction pathways, and synaptic transmission. 4 Several dietary components, including omega-3 fatty acids, B vitamins, vitamins D and E, and choline, have been identified as having favorable effects on cognitive abilities. 4 More recently, evidence suggests that the consumption of flavonoids, a diverse group of polyphenolic compounds widely present in plant-based foods, may be associated with a decreased risk of incident dementia 5 and with a lower prevalence of cognitive impairment, 6 a better cognitive evolution over a 10-year period, 7 and better dose-dependent performance of several cognitive abilities in elderly subjects. 8 Among the flavonoids, flavanols, a subclass abundant in tea, grapes, red wine, apples, and cocoa products, including chocolate, have been proposed to be highly effective in Received February 11, 2012; first decision March 6, 2012; revision accepted July 11, 2012. Correspondence to Giovambattista Desideri, University of L'Aquila, Department of Life, Health, and Environmental Sciences, Viale S Salvatore, Delta 6 Medicina, 67100 Coppito, L'Aquila, Italy. E-mail giovambattista.desideri@cc.univaq.it © 2012 American Heart Association, Inc. reversing age-related declines in neurocognitive performance by increasing the number of and strength of connections between neurons, reducing neuronal loss attributed to neurodegenerative processes, and throu...