Cocoa Flavonoids Research Articles

Cocoa Consumption Decreases Oxidative Stress, Proinflammatory Mediators and Lipid Peroxidation in Healthy Subjects: A Randomized Placebo-Controlled Dose-Response Clinical Trial.

Cocoa flavonoids have been described to reduce the cardiovascular risk. Nevertheless, the involved mechanisms should be clarified and the dose-effect relation has never been evaluated. To investigate the dose-dependent effects of cocoa flavonoids on markers of endothelial and platelet activation and oxidative stress. According to a randomized, double-blind, controlled, cross-over design, 20 healthy nonsmokers were assigned to receive either five treatments with daily intake of 10g cocoa (0, 80, 200, 500 and 800mg cocoa flavonoids/day) in five periods lasting 1 week each. Compared with flavonoid-free cocoa control, cocoa reduced sICAM-1 mean values [from 1190.2 to 1123.0; 906.3; 741.7 and 625.6 pg/mL (p = 0.0198 and p = 0.0016, for 500 and 800mg respectively], sCD40L mean values [from 218.8 to 210.2; 165.5; 134.5 and 128.4 pg/mL (p = 0.023 and p = 0.013, for 500 and 800mg respectively] and 8-isoprostanes F2 mean values [from 4703.9 to 4670.7; 2000.1; 2098.4 and 2052.3 pg/mL (p = 0.025; p = 0.034 and p = 0.029, for 200, 500 and 800mg respectively)]. In our study we observed that short-term cocoa consumption improved proinflammatory mediators, lipid peroxidation and oxidative stress with a significant effect for higher dosages of flavonoids. Our findings suggest cocoa might be a valid tool for dietary intervention in prevention of atherosclerosis.

Abstract P158: Intake of Chocolate by Subtypes and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies

Backgrounds: Cocoa and cocoa flavonoids may exert health benefits including improving insulin sensitivity and lowering type 2 diabetes (T2D) risk. Previous studies have reported inverse associations between chocolate consumption and T2D risk, although it is largely unknown regarding whether the associations differ between dark chocolate and milk chocolate. The objective of this study is to prospectively examine the associations between the consumption of dark chocolate, milk chocolate, and total chocolate, and the risk of T2D, in three large cohort studies with repeat dietary measurements over 10 years of follow-up. Methods: Data from three prospective cohorts in the United States were used, including Nurses’ Health Study (2006-2020), Nurses’ Health Study II (2007-2019), and Health Professionals Follow-Up Study (2006-2020). Dark and milk chocolate consumption information was assessed at baseline and updated every 4 years through a validated food frequency questionnaire. Chocolate consumption was categorized into 4 groups: never or <1 serving/month, 1 serving/month to 1 serving/week, 1-4 servings/week, and ≥5 servings/week. Self-reported T2D cases were confirmed using a supplementary questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between total, dark, and milk chocolate intake, and the risk of T2D. Results: After adjusting for lifestyle and dietary risk factors for diabetes, compared to participants who never or rarely eat chocolate, those who consumed any chocolate ≥5 servings/week had a 22% (95% CI: 10% to 32%; p for trend = 0.0003) lower rate of T2D. For dark chocolate, those who consumed ≥5 servings/week had a non-significant 16% (95% CI: -2% to 31%; p for trend = 0.005) lower rate of T2D than those who never or rarely eat dark chocolate. The associations between milk chocolate intake and T2D risk are largely null. Spline regression shows an L-shaped non-linear dose-response relationship between total chocolate intake and the risk of T2D (p=0.02 for curvature). The risk reduction plateaus when the total chocolate intake is higher than 5 servings/week. There is a linear dose-response association between dark chocolate intake with the risk of T2D (p=0.006 for linearity). Conclusion: Higher consumption of total chocolate and especially dark chocolate was significantly associated with a lower risk of type 2 diabetes. These findings support the potential cardiometabolic benefits of consuming chocolates that are rich in flavonoids.

Preventive Effect of Cocoa Flavonoids via Suppression of Oxidative Stress-Induced Apoptosis in Auditory Senescent Cells.

Presbycusis or Age-related hearing loss (ARHL) is a sensorineural hearing loss that affects communication, leading to depression and social isolation. Currently, there are no effective treatments against ARHL. It is known that cocoa products have high levels of polyphenol content (mainly flavonoids), that are potent anti-inflammatory and antioxidant agents with proven benefits for health. The objective is to determine the protective effect of cocoa at the cellular and molecular levels in Presbycusis. For in vitro study, we used House Ear Institute-Organ of Corti 1 (HEI-OC1), stria vascularis (SV-k1), and organ of Corti (OC-k3) cells (derived from the auditory organ of a transgenic mouse). Each cell line was divided into a control group (CTR) and an H2O2 group (induction of senescence by an oxygen radical). Additionally, every group of every cell line was treated with the cocoa polyphenolic extract (CPE), measuring different markers of apoptosis, viability, the activity of antioxidant enzymes, and oxidative/nitrosative stress. The data show an increase of reactive oxidative and nitrogen species (ROS and RNS, respectively) in senescent cells compared to control ones. CPE treatment effectively reduced these high levels and correlated with a significant reduction in apoptosis cells by inhibiting the mitochondrial-apoptotic pathway. Furthermore, in senescence cells, the activity of antioxidant enzymes (Superoxide dismutase, SOD; Catalase, CAT; and Glutathione peroxidase, GPx) was recovered after CPE treatment. Administration of CPE also decreased oxidative DNA damage in the auditory senescent cells. In conclusion, CPE inhibits the activation of senescence-related apoptotic signaling by decreasing oxidative stress in auditory senescent cells.

Cocoa flavonoids: a promising ingredient that potentiates vitamin d action in skeletal muscle cells

Rationale: Vitamin D (VitD) effects take place by binding to its receptor (VDR) which is a classical nuclear receptor responsible for genomic effects, but there is also a fraction of the VDR located in the muscle plasma membrane that is responsible for its non-genomic effects. In addition to the established effect of VitD in bone and mineral homeostasis, VitD insufficiency/deficiency is linked to a range of muscle disorders including frailty and muscle loss/dysfunction. Flavonoids decrease insulin resistance and have antioxidant and anti-inflammatory properties by activating Akt signaling pathways. Our study has aimed to evaluate, in VitD deficient conditions, if cocoa flavonoids (CF) are able to mediate the interacction between VitD and skeletal muscle glucose uptake by triggerring the modulation of its genomic and non-genomic signaling pathways. This could be useful in pathological deficient VitD situations, such as diabetes or sarcopenia where muscle function is compromised due to the onset of insulin resistance.

Physical Activity and Fatigue in Multiple Sclerosis: Secondary Outcomes from a Double-blinded Randomized Controlled Trial of Cocoa Flavonoid Drinks

Physical Activity and Fatigue in Multiple Sclerosis: Secondary Outcomes from a Double-blinded Randomized Controlled Trial of Cocoa Flavonoid Drinks Maedeh Mansoubi()1,2, Shelly Coe1,2,3, Jo Cossington1, Johnny Collet1,2, Miriam Clegg4, Jacqueline Palace5, Ana Cavey5, Gabriele C DeLuca5, Martin Ovington1 and Helen Dawes1,2,6 1Center for Movement, Occupational and Rehabilitation Sciences, Oxford Institute of Nursing, Midwifery and Allied Health Research, Oxford Brookes University, Oxford, United Kingdom 2Oxford Clinical Allied Technology and Trial Services Unit (OxCATTS), Oxford, United Kingdom 3Oxford Brookes Center for Nutrition and Health, Oxford Brookes University, Oxford, United Kingdom 4Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom 5Department of Neurology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom 6Oxford Health NHS Foundation Trust, United Kingdom © The Authors Abstract Fatigue is a common and pervasive symptom reducing physical activity in people with multiple sclerosis (pwMS). Exercise may reduce fatigue, although evidence to guide optimal prescription is limited. Specifically, supportive evidence for the timing of exercise for fatigue management or the impact of dietary supplements is unavailable. We performed intensive phenotyping of the interrelation of time of day, physical activity levels, and fatigue to evidence exercise prescription in 40 pwMS participating in a six week randomized controlled trial of morning flavonoid intake (n=19) or a control (n=21). Physical activity was measured over seven days by using an accelerometer at baseline, week three and week six. Participants self-reported their fatigue on a 1–10 rating scale at 10 am, 3 pm, and 8 pm daily. Physical activity levels were calculated for 2.5 h before and after fatigue was reported. Generalized estimating equations were used to explore the time of day fatigue profiles, the relationship of physical activity to fatigue, and the effect of morning flavonoids on this relationship. Participants experienced higher fatigue at 8 pm (4.64±2.29) than at 3 pm (4.39±2.28) and 10 am (3.90±2.10) (P<0.001). Higher fatigue was shown to predict subsequent lower physical activity behavior (P=0.015), but physical activity did not predict higher subsequent fatigue (P>0.05). Morning flavonoid cocoa consumption reduced the relationship of fatigue to physical activity (P=0.049) and fatigue to time of the day (P<0.001). Fatigue levels increased during the day and higher fatigue reduced physical activity in pwMS, but physical activity did not increase fatigue. In addition, morning cocoa reduced daytime fatigue and the relationship of fatigue to subsequent physical activity levels. Therefore morning exercise prescription is indicated; in combination with dietary flavonoids, it may optimize exercise and physical activity potential in pwMS. Trial registration: ISRCTN69897291, https://doi.org/10.1186/ISRCTN69897291 Registration name: A study to determine whether the daily consumption of flavonoid-rich pure cocoa has the potential to reduce fatigue in people with relapsing-remitting multiple sclerosis (RRMS). Consort Statement: In this study, we adhered to CONSORT guidelines. As this paper is a secondary analysis, we therefore did not repeat some parts in the methods, results, diagrams, or tables that have been published in the first paper authored by Coe et al. 2019.

Translational Medicine and Exercise Prescription (TMEP): Advancing the Era of Exercise Medicine

Translational Medicine and Exercise Prescription (TMEP): Advancing the Era of Exercise Medicine

Effect of a High Flavonoid Supplement on Intestinal Inflammation, Short Chain Fatty Acids, and the Gut Microbiome

Abstract Objectives Endurance exercise is a known cause of intestinal inflammation. Recent studies suggest that dietary flavonoids may protect the gut from chronic low-grade inflammation and have other effects at the gastrointestinal barrier. As a result, the purpose of this study was to determine the effects of a high flavonoid supplement containing blueberry, green tea, and cocoa on gut health. We investigated changes in intestinal inflammation, fecal short chain fatty acids (SCFA), and the gut microbiome in a randomized clinical trial. Methods In a double-blind, crossover design, 12 recreationally-active cyclists (VO2 max: 43.2 + 5.9 ml/kg/min) completed two 15-day supplementation periods with either a high flavonoid supplement or placebo. The high flavonoid beverage (HFB, 490 mg total flavonoids) and macronutrient-matched low flavonoid control (LFB, 5 mg flavonoids) were consumed once daily, two hours prior to training. Stool samples were collected once during days 9–11 of each intervention to determine microbiome composition and SCFA (acetic, propionic, butyric, isobutyric, valeric, isovaleric, and caproic acid). Fecal calprotectin was used as a marker of intestinal inflammation. Results Food frequency questionnaires estimated that the participants’ average weekly consumption of total flavonoids was 634.7 ± 194.6 mg, with the highest subgroups being flavan-3-ols, flavonols, and anthocyanidins (296.3 ± 169.3, 136.5 ± 21.9, 109.6 ± 35.4 mg, respectively). There was no significant difference in fecal calprotectin on the HFB versus LFB (P > 0.05). Average fecal calprotectin were low (HFB: 12.9 ± 1.2, LFB: 12.9 ± 0.9 ug/g stool), suggesting that subjects had low overall gut inflammation. There were no significant differences in individual and total SCFA (P > 0.05). The total SCFA on the HFB treatment was 115.1 ± 11.3 mM/g vs. 107.9 ± 9.7 mM/g on the LFB. Furthermore, there were no differences in any measures alpha or beta diversity as a result of the dietary intervention (P > 0.05). Conclusions Fifteen-day consumption of a blend of blueberry, cocoa, and green tea flavonoids did not significantly affect gut inflammation, SCFA content, and alpha or beta diversity of the gut microbiome. Funding Sources Build Dairy.

An Assessment of the Impact of Cocoa Flavonoid on Health

An Assessment of the Impact of Cocoa Flavonoid on Health

Beneficial Effects of Dark Chocolate for Episodic Memory in Healthy Young Adults: A Parallel-Groups Acute Intervention with a White Chocolate Control

There is good evidence that cocoa flavonoids can acutely improve cognitive function in humans, possibly via mechanisms such as increased cerebral blood flow. To date, much of the evidence is based on measures of executive function with extracts and cocoa-based interventions with a high flavonoid content. The aim of the present study was to explore whether benefits to episodic verbal memory and mood are observed two hours post consumption of a commercially available dark chocolate (DC) bar relative to a 35 g white chocolate bar (WC). Ninety-eight healthy young adults (n = 57 females) aged 18–24 years consumed either a 35 g DC bar or a calorie-matched low flavonoid WC bar. Verbal episodic memory and mood were assessed pre consumption and 2 h post consumption. An ANOVA analysis showed that the DC was associated with better verbal memory performance for several outcome measures of the Rey Auditory Verbal Learning Test relative to the WC, however, there were no effects on mood. These findings lend support to the notion that everyday available portions of dark chocolate can confer benefits to the brain in healthy consumers.

Health benefits of bioactive compounds from cocoa (Theobroma cacao)

Cocoa is regarded as a super food due to its high nutrient content and proven health benefits. Cocoa beans are rich in carbohydrate (31%), protein (11%), fat (54%), fibre (16%) and minerals. Cocoa is a good source of bioactive compounds too. The major bioactive components are polyphenols constituted of flavanoids and non flavanoids. The bioactive components with rich antioxidants and anti-inflammatory activities contribute to various health benefits. The flavonoid rich chocolates improve peripheral vascular function. The consumption of cocoa or chocolate are beneficial in inhibiting the complex molecular process leading to cancer. Flavanoids in cocoa increases insulin sensitivity by improving endothelial function and reducing oxidative stress. The cocoa flavonoids also penetrate and accumulate in the brain regions involved in learning and memory. The knowledge on bioactive compounds in cocoa and cocoa products suggests that they could be consumed as a part of wholesome, health promoting nutritional food.

The Efficacy of Cocoa Polyphenols in the Treatment of Mild Cognitive Impairment: A Retrospective Study.

Background: Mild cognitive impairment (MCI) is characterized by cognition impairment that does not interfere with the usual activities of daily living. It is considered to be a transitional stage between normal aging and dementia. No treatment is available for MCI. Methods: This retrospective cohort study included 55 patients (29 males and 26 females, aged 56–75 years) with a diagnosis of amnestic MCI who attended the Center for Cognitive Disorder and Dementia of the IRCCS Centro Neurolesi Bonino Pulejo (Messina, Italy) between January and December of 2017. As we aimed to evaluate the effect of cocoa polyphenols on cognition, the study population was separated into two groups depending on the change in their Mini-Mental State Examination (MMSE) score at a one-year follow-up. Results: Compared to G2 (i.e., patients with a worsening in cognitive functions), the rate of polyphenol intake was significantly higher in patients without a worsening in cognition (i.e., G1) (χ2 = 13.79, df = 1, p-value < 0.001). By subdividing G1 patients based on whether they improved or were stable at follow-up, we found that 46.2% of those who had improved were treated with polyphenols. Conclusions: Dietary supplementation of cocoa flavonoids seems to reduce the progression of MCI to dementia. Further prospective studies with larger sample volumes are required to confirm these promising findings.

Development and Characterization of a Pilot-Scale Model Cocoa Fermentation System Suitable for Studying the Impact of Fermentation on Putative Bioactive Compounds and Bioactivity of Cocoa.

Cocoa is a concentrated source of dietary flavanols—putative bioactive compounds associated with health benefits. It is known that fermentation and roasting reduce levels of native flavonoids in cocoa, and it is generally thought that this loss translates to reduced bioactivity. However, the mechanisms of these losses are poorly understood, and little data exist to support this paradigm that flavonoid loss results in reduced health benefits. To further facilitate large-scale studies of the impact of fermentation on cocoa flavanols, a controlled laboratory fermentation model system was increased in scale to a large (pilot) scale system. Raw cocoa beans (15 kg) were fermented in 16 L of a simulated pulp media in duplicate for 168 h. The temperature of the fermentation was increased from 25–55 °C at a rate of 5 °C/24 h. As expected, total polyphenols and flavanol levels decreased as fermentation progressed (a loss of 18.3% total polyphenols and 14.4% loss of total flavanols during fermentation) but some increases were observed in the final timepoints (120–168 h). Fermentation substrates, metabolites and putative cocoa bioactive compounds were monitored and found to follow typical trends for on-farm cocoa heap fermentations. For example, sucrose levels in pulp declined from >40 mg/mL to undetectable at 96 h. This model system provides a controlled environment for further investigation into the potential for optimizing fermentation parameters to enhance the flavanol composition and the potential health benefits of the resultant cocoa beans.

Effects of Cocoa Antioxidants in Type 2 Diabetes Mellitus.

Type 2 Diabetes mellitus (T2D) is the most common form of diabetes and one of the most common chronic diseases. Control of hyperglycaemia by hypoglycaemic drugs is insufficient in for patients and nutritional approaches are currently being explored. Natural dietary compounds such as flavonoids, abundant in fruits and vegetables, have received broad attention because of their potential capacity to act as anti-diabetic agents. Especially cocoa flavonoids have been proved to ameliorate important hallmarks of T2D. In this review, an update of the most relevant reports published during the last decade in cell culture, animal models and human studies is presented. Most results support an anti-diabetic effect of cocoa flavonoids by enhancing insulin secretion, improving insulin sensitivity in peripheral tissues, exerting a lipid-lowering effect and preventing the oxidative and inflammatory damages associated to the disease. While it could be suggested that daily consumption of flavanols from cocoa or dark chocolate would constitute a potential preventive tool useful for the nutritional management of T2D, this recommendation should be cautious since most of commercially available soluble cocoa products or chocolates contain low amount of flavanols and are rich in sugar and calories that may aggravate glycaemic control in T2D patients.

Dark Chocolate: Opportunity for an Alliance between Medical Science and the Food Industry?

Dark chocolate (DC) was originally introduced in human nutrition as a medicinal product consumable in a liquid form. Century-long efforts of food industry transformed this hardly appealing product into a valuable modern culinary delight with clear predominance of confectionery brands of DC on the market. However, current epidemiological data as well as multiple experimental and clinical observations reveal that DC consumption may have a profound effect on cardiovascular, central nervous systems, hemostasis, and lipid metabolism. However, despite of growing body of modern scientific evidence revealing medicinal properties of cocoa-based products, DC remains more gourmet culinary item than medicinal food product. Even today there are no clear dietary recommendations on consumption of cocoa flavonoids (flavanols) for health purpose. Clinical trials with DC rarely include monitoring of plasma flavanol concentration in volunteers. Moreover, there is no standardized assay or any quantitative requirements for flavanol content in the commercial brands of DC. High flavanol content is often sacrificed during manufacturing for a better taste of DC due to bitterness of cocoa flavonoids. All these problems including subsequently arising ethical issues need to be addressed by joint efforts of food industry and medical science. Moreover, application of microencapsulation technology in DC manufacturing, as well as molecular selection of best flavanol producers may drastically change bioavailability of DC bioactive ingredients and DC production technology. Nevertheless, only strict causative approach, linking possible health effect of DC to its bioactive ingredients considered as nutraceuticals, may change the current landscape in nutritional research related to cocoa-based products and create a trustworthy path for their medicinal use.

Enhancing Human Cognition with Cocoa Flavonoids.

Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects.

Green and Efficient Extraction Method to Determine Polyphenols in Cocoa and Cocoa Products

Cocoa and cocoa products have broad and well-proven health benefits, most of which are associated with the high antioxidant capacity of cocoa flavonoids. Most extraction methods for flavonoids in cocoa products use several steps including a defatting step and large amount of organic solvents. Moreover, they are labor-intensive and time-consuming. In this work, a pressurized hot water extraction (PHWE) method has been compared to conventional sonication extraction (CSE) method. The contribution of individual compounds to the total antioxidant capacity of the extracts was evaluated by developing an analytical technique consisting of high-performance liquid chromatography (HPLC) with photodiode array coupled to electrochemical and to charged aerosol detectors and HPLC-mass spectrometry for the confirmation of the identity of compounds present. Additionally, procyanidins were analyzed by fluorescence detection. PHWE turned out to be more efficient in extracting phenolics and methylxanthines, as compared to the conventional method, in addition to being more “green” in terms of using less organic solvents.

Effect of Flavonoids on Oxidative Stress and Inflammation in Adults at Risk of Cardiovascular Disease: A Systematic Review.

Oxidative stress (OS) and inflammatory processes initiate the first stage of cardiovascular disease (CVD). Flavonoid consumption has been related to significantly improved flow-mediated dilation and blood pressure. Antioxidant and anti-inflammatory mechanisms are thought to be involved. The effect of flavonoids on markers of oxidative stress and inflammation, in at risk individuals is yet to be reviewed. Systematic literature searches were conducted in MEDLINE, Cochrane Library, CINAHL and SCOPUS databases. Randomised controlled trials in a Western country providing a food-based flavonoid intervention to participants with one or two modifiable risk factors for CVD measuring a marker of OS and/or inflammation, were included. Reference lists were hand-searched. The Cochrane Collaboration Risk of Bias Tool was used to assess study quality. The search strategy retrieved 1248 articles. Nineteen articles meeting the inclusion criteria were reviewed. Eight studies were considered at low risk of bias. Cocoa flavonoids provided to Type 2 diabetics and olive oil flavonoids to mildly-hypertensive women reduced OS and inflammation. Other food sources had weaker effects. No consistent effect on OS and inflammation across patients with varied CVD risk factors was observed. Study heterogeneity posed a challenge for inter-study comparisons. Rigorously designed studies will assist in determining the effectiveness of flavonoid interventions for reducing OS and inflammation in patients at risk of CVD.

Flavanol-rich chocolate acutely improves arterial function and working memory performance counteracting the effects of sleep deprivation in healthy individuals.

Sleep deprivation is a risk factor for cardiovascular disease. Cocoa flavonoids exert cardiovascular benefits and neuroprotection. Whether chocolate consumption may mitigate detrimental effects of sleep loss on cognitive performance and cardiovascular parameters has never been studied. We investigated the effects of flavanol-rich chocolate consumption on cognitive skills and cardiovascular parameters after sleep deprivation. Thirty-two healthy participants underwent two baseline sessions after one night of undisturbed sleep and two experimental sessions after one night of total sleep deprivation. Two hours before each testing session, participants were randomly assigned to consume high or poor flavanol chocolate bars. During the tests were evaluated, the Psychomotor Vigilance Task and a working memory task, office SBP and DBP, flow-mediated dilation and pulse-wave velocity. Sleep deprivation increased SBP/DBP. SBP/DBP and pulse pressure were lower after flavanol-rich treatment respect to flavanol-poor treatment (SBP: 116.9 ± 1.6 vs. 120.8 ± 1.9 mmHg, respectively, P = 0.00005; DBP: 70.5 ± 1.2 vs. 72.3 ± 1.2 mmHg, respectively, P = 0.01; pulse pressure: 46.4 ± 1.3 vs. 48.4 ± 1.5 mmHg, P = 0.004). Sleep deprivation impaired flow-mediated dilation (5.5 ± 0.5 vs. 6.5 ± 0.6%, P = 0.02), flavanol-rich, but not flavanol-poor chocolate counteracted this alteration (flavanol-rich/flavanol-poor chocolate: 7.0 ± 0.6 vs. 5.0 ± 0.4%, P = 0.000001). Flavanol-rich chocolate mitigated the pulse-wave velocity increase (P = 0.001). Flavanol-rich chocolate preserved working memory accuracy in women after sleep deprivation. Flow-mediated dilation correlated with working memory performance accuracy in the sleep condition (P = 0.04). Flavanol-rich chocolate counteracted vascular impairment after sleep deprivation and restored working memory performance. Improvement in cognitive performance could be because of the effects of cocoa flavonoids on blood pressure and peripheral and central blood flow.

Nutraceuticals with a clinically detectable blood pressure-lowering effect: a review of available randomized clinical trials and their meta-analyses.

The aim of the present study was to review and comment on the available evidence on nutraceuticals with a clinically demonstrable blood pressure (BP)-lowering effect. We reviewed studies published in the English language from 1990 to 2015 on dietary supplements or nutraceuticals claiming to show an effect on human BP. An initial list of possibly effective agents and studies was obtained from the online reference, the Natural Medicine Comprehensive Database. Using PubMed, we searched agents identified from this list using the MeSH terms 'hypertension', 'blood pressure', 'dietary supplement' and 'nutraceuticals', alone and in combination. We then focused our attention on meta-analyses and randomized clinical trials. Beyond the well-known effects on BP of the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet, a large number of studies have investigated the possible BP-lowering effect of different dietary supplements and nutraceuticals, most of which are antioxidant agents with a high tolerability and safety profile. In particular, a relatively large body of evidence supports the use of potassium, magnesium, L-arginine, vitamin C, cocoa flavonoids, beetroot juice, coenzyme Q10, controlled-release melatonin and aged garlic extract. The antihypertensive effect of all these nutraceuticals seems to be dose related and the overall tolerability is good. Some nutraceuticals might have a positive impact on BP in humans. Further clinical research is needed, to identify from the available active nutraceuticals those with the best cost-effectiveness and risk-benefit ratio for widespread and long-term use in the general population with a low-added cardiovascular risk related to uncomplicated hypertension.

Cocobiota: Implications for Human Health

Manufacturing of dark chocolate and other cocoa-based products is a complex multistage process beginning with spontaneous cocoa bean fermentation driven in the postharvest period by different microorganisms derived from the environment. Cocobiota defined as the association of microbial species involved in cocoa bean fermentation may have considerable impact on the medicinal properties of cocoa products via various primary and secondary metabolites, whose presence in dark chocolate and other cocoa-derived products has to be taken into consideration when analyzing medicinal effects of cocoa. Metabolites of acetic acid and lactic acid bacteria, two major cocobiota members, are recently shown to have considerable antifungal and cholesterol-lowering activities and promote the formation of short chain fatty acids and mannitol, an important prebiotic capable of modifying gut microbiota. Penicillium citrinum, a major type of fungi identifiable in fermented cocoa beans, produces a thermostable alkaloid, Penicitrinine A, as well as lovastatin, compounds with antineoplastic and cholesterol-lowering abilities, respectively. Moreover, recent results suggest that bacterial and fungal metabolites produced by cocobiota have a significant anti-infective potential. Therefore, various metabolites produced by cocobiota can mimic some medicinal effects of dark chocolate and other cocoa-derived products previously attributed to cocoa flavonoids and methylxanthines and need to be thoroughly investigated in in vitro and in vivo systems.