Acute exercise-induced improvements in cognitive function are accompanied by increased (cerebral) blood flow and increased brain-derived neurotrophic factor (BDNF) levels. Acute cocoa flavanol (CF) intake may improve cognitive function, cerebral blood flow (in humans), and BNDF levels (in animals). This study investigated (i) the effect of CF intake in combination with exercise on cognitive function and (ii) cerebral hemodynamics and BDNF in response to CF intake and exercise. Twelve healthy men participated in this randomized, double-blind, crossover study. Participants performed a cognitive task (CT) at 100 min after acute 903-mg CF or placebo (PL) intake, followed by a 30-min time-trial. Immediately after this exercise, the same CT was performed. Prefrontal near-infrared spectroscopy was applied during CT and exercise to measure changes in oxygenated (ΔHbO2), deoxygenated (ΔHHb), and total haemoglobin (ΔHbtot) and blood samples were drawn and analyzed for BDNF. Reaction time was faster postexercise, but was not influenced by CF. ΔHbO2 during the resting CT was increased by CF, compared with PL. ΔHbO2, ΔHHb, and ΔHbtot increased in responseto exercise without any effect of CF. During the postexercise cognitive task, there were no hemodynamic differences between CF or PL. Serum BDNF was increased by exercise, but was not influenced by CF. In conclusion, at rest, CF intake increased cerebral oxygenation, but not BDNF concentrations, and no impact on executive function was detected. This beneficial effect of CF on cerebral oxygenation at rest was overruled by the strong exercise-induced increases in cerebral perfusion and oxygenation.

Endothelial dysfunction characterizes many disease states including subclinical atherosclerosis. The consumption of flavanol-rich cocoa and cocoa-based products has been shown to improve endothelial function in both compromised and otherwise normal, healthy individuals when administered either acutely or over a period of several days, or weeks. Women experience increased risk for cardiovascular disease after menopause, which can be associated with endothelial dysfunction. Whether a flavanol-rich cocoa-based product can improve endothelial function in hypercholesterolemic postmenopausal women is not known. The purpose of the present study was to determine whether chronic dietary administration of flavanol-rich cocoa improves endothelial function and markers of cardiovascular health in hypercholesterolemic postmenopausal women. Thirty-two postmenopausal hypercholesterolemic women were randomly assigned to consume a high-flavanol cocoa beverage (high cocoa flavanols (CF)--446 mg of total flavanols), or a low-flavanol cocoa beverage (low CF--43 mg of total flavanols) for 6 weeks in a double-blind study (n=16 per group). Endothelial function was determined by brachial artery-reactive hyperemia. Plasma was analyzed for lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), hormones (follicle-stimulating hormone), total nitrate/nitrite, activation of cellular adhesion markers (vascular cell adhesion molecule 1, intercellular adhesion molecule 1, E-Selectin, P-Selectin), and platelet function and reactivity. Changes in these plasma markers were then correlated to brachial reactivity. Brachial artery hyperemic blood flow increased significantly by 76% (P<0.05 vs. baseline) after the 6-week cocoa intervention in the high CF group, compared with 32% in the low CF cocoa group (P=ns vs. baseline). The 2.4-fold increase in hyperemic blood flow with high CF cocoa closely correlated (r2=0.8) with a significant decrease (11%) in plasma levels of soluble vascular cell adhesion molecule-1. Similar responses were not observed after chronic use of low CF. There were no significant differences between high and low CF in other biochemical markers and parameters measured. This study is the first to identify beneficial vascular effects of flavanol-rich cocoa consumption in hypercholesterolemic postmenopausal women. In addition, our results suggest that reductions in plasma soluble vascular cell adhesion molecule-1 after chronic consumption of a flavanol-rich cocoa may be mechanistically linked to improved vascular reactivity.

Cocoa and its major flavanol component, epicatechin, have therapeutic properties that may improve limb perfusion and increase calf muscle mitochondrial activity in people with lower extremity peripheral artery disease (PAD).In a phase II randomized clinical trial, to assess whether six months of cocoa improved walking performance in people with PAD, compared to placebo.Six-month double blind randomized clinical trial in which participants with PAD were randomized to either cocoa beverage vs. placebo beverage. The cocoa beverage contained 15 grams of cocoa and 75 mgs of epicatechin daily. The identical appearing placebo contained neither cocoa nor epicatechin. The two primary outcomes were six-month change in six-minute walk distance measured 2.5 hours after a study beverage at 6-month follow-up and 24 hours after a study beverage at 6-month follow-up, respectively. A one-sided P value<0.10 was considered statistically significant. Of 44 PAD participants randomized (mean age: 72.3 years (+7.1), mean ankle brachial index 0.66 (+0.15)), 40 (91%) completed follow-up. Adjusting for smoking, race, and body mass index, cocoa improved six-minute walk distance at 6-month follow-up by 42.6 meters (90% Confidence Interval (CI): +22.2,+∞, P=0.005) at 2.5 hours after a final study beverage and by 18.0 meters (90% CI:-1.7, +∞, P=0.12) at 24 hours after a study beverage, compared to placebo. In calf muscle biopsies, cocoa improved mitochondrial cytochrome c oxidase activity (P=0.013), increased capillary density (P=0.014), improved calf muscle perfusion (P=0.098), and reduced central nuclei (P=0.024), compared to placebo.These preliminary results suggest a therapeutic effect of cocoa on walking performance in people with PAD. Further study is needed to definitively determine whether cocoa significantly improves walking performance in people with PAD. Clinical Trial Registration: NCT02876887.

Beyond the well-known effects on blood pressure (BP) of the dietary approaches to stop hypertension (DASH) and the Mediterranean diets, a large number of studies has investigated the possible BP lowering effect of different dietary supplements and nutraceuticals, the most part of them being antioxidant agents with a high tolerability and safety profile. In particular relatively large body of evidence support the use of potassium, L-arginine, vitamin C, cocoa flavonoids, beetroot juice, coenzyme Q10, controlled-release melatonin, and aged garlic extract. However there is a need for data about the long-term safety of a large part of the above discussed products. Moreover further clinical research is advisable to identify between the available active nutraceuticals those with the best cost-effectiveness and risk-benefit ratio for a large use in general population with low-added cardiovascular risk related to uncomplicated hypertension.

OBJECTIVES: Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients. BACKGROUND: Even in fully medicated diabetic patients, overall prognosis is unfavorable due to deteriorated cardiovascular function. Based on epidemiological data, diets rich in flavanols are associated with a reduced cardiovascular risk. METHODS: In a feasibility study with 10 diabetic patients, we assessed vascular function as flow-mediated dilation (FMD) of the brachial artery, plasma levels of flavanol metabolites, and tolerability after an acute, single-dose ingestion of cocoa, containing increasing concentrations of flavanols (75, 371, and 963 mg). In a subsequent efficacy study, changes in vascular function in 41 medicated diabetic patients were assessed after a 30-day, thrice-daily dietary intervention with either flavanol-rich cocoa (321 mg flavanols per dose) or a nutrient-matched control (25 mg flavanols per dose). Both studies were undertaken in a randomized, double-masked fashion. Primary and secondary outcome measures included changes in FMD and plasma flavanol metabolites, respectively. RESULTS: A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols and FMD (at 2 h: from 3.7 +/- 0.2% to 5.5 +/- 0.4%, p < 0.001). A 30-day, thrice-daily consumption of flavanol-containing cocoa increased baseline FMD by 30% (p < 0.0001), while acute increases of FMD upon ingestion of flavanol-containing cocoa continued to be manifest throughout the study. Treatment was well tolerated without evidence of tachyphylaxia. Endothelium-independent responses, blood pressure, heart rate, and glycemic control were unaffected. CONCLUSIONS: Diets rich in flavanols reverse vascular dysfunction in diabetes, highlighting therapeutic potentials in cardiovascular disease.