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Ecuador has excellent agroclimatic conditions for cocoa production, but there are also problems in: the production, harvest, and post-harvest links; the lack of investment by financial entities; and high costs throughout the cocoa value chain. This reality causes the impoverishment of cacotera families. Faced with this, through this project we will work to increase the income of cocoa families and contribute to reducing poverty in rural areas, through the generation of genetic material in certified cocoa nurseries, which guarantee its quality for the planting and renewal of aging cocoa plantations; complementing economic resources between various local actors, government, and cooperation for the implementation of the nurseries. For this, it is proposed to carry out the activities of: identifying local actors for the management of nurseries, identifying international cooperation and government actors, implementing the nurseries accompanying and monitoring the entire production process of plant material to be planted in the cocoa farms in the intervention areas of the project. El Ecuador reúne excelentes condiciones agroclimáticas para la producción de cacao, pero además se dan problemas en: los eslabones de producción, cosecha y postcosecha; la falta de inversión de las entidades financieras; y altos costos en toda la cadena de valor de cacao. Esta realidad, provoca el empobrecimiento de las familias cacoteras. Frente a ello, a través del presente proyecto se trabajará para incrementar los ingresos en las familias cacaoteras y contribuir a la disminución de la pobreza en las zonas rurales, mediante la generación de material genético en viveros de cacao certificados, que garanticen su calidad para la siembra y renovación de las plantaciones envejecidas de cacao; complementando recursos económicos entre varios actores locales, gobierno, y cooperación para la implementación de los viveros. Para ello, se propone realizar las actividades de: identificar actores locales para la gestión de viveros, identificar actores de cooperación internacional y de gobierno, implementar de los viveros, acompañamiento y seguimiento de todo el proceso de producción de material vegetal para ser sembrado en las fincas cacaoteras en las zonas de intervención del proyecto.

Aging, a critical risk factor of several diseases, including neurodegenerative disorders, affects an ever-growing number of people. Cacao supplementation has been suggested to improve age-related neuronal deficits. Therefore, this study investigated the protective effects of raw cacao powder on oxidative stress-induced aging. Male Sprague–Dawley rats were divided into 4 groups: Control (C), d-galactose-induced aging (G), d-galactose injection with 10% (LC), and 16% (HC) cacao powder mixed diet. d-galactose (300 mg/3 mL/kg) was intraperitoneally injected into all but the control group for 12 weeks. Cacao supplemented diets were provided for 8 weeks. The levels of serum Malondialdehyde (MDA), Advanced Glycation End-products (AGEs), brain and liver MDA, the indicators of the d-galactose induced oxidative stress were significantly decreased in LC and HC but increased in G. The Acetylcholinesterase (AChE) activity of brain showed that the cholinergic impairment was significantly lower in LC, and HC than G. Furthermore, the expression levels of catalase (CAT), phospho-Akt/Akt, and procaspase-3 were significantly increased in LC and HC. In conclusion, cacao consumption attenuated the effects of oxidative stress, cholinergic impairment and apoptosis, indicating its potential in future clinical studies.

Few studies with mixed results have examined the association between chocolate consumption and mortality. We aimed to examine this association in a US population. A population-based cohort of 91891 participants aged 55 to 74 years was identified. Chocolate consumption was assessed via a food frequency questionnaire. Cox regression was used to estimate risk estimates. After an average follow-up of 13.5 years, 19586 all-cause deaths were documented. Compared with no regular chocolate consumption, the maximally adjusted hazard ratios of all-cause mortality were 0.89 [95% confidence interval (CI) 0.84-0.94], 0.84 (95% CI 0.79-0.90), 0.86 (95% CI 0.81-0.93), and 0.87 (95% CI 0.82-0.93) for >0-0.5 servings/week, >0.5-1 serving/week, >1-2 servings/week, and >2 servings/week, respectively (Ptrend = 0.009). A somewhat stronger inverse association was observed for mortality from cardiovascular disease and Alzheimer's disease. A nonlinear dose-response pattern was found for all-cause and cardiovascular mortality (all Pnonlinearity < 0.01), with the lowest risk observed at chocolate consumption of 0.7 servings/week and 0.6 servings/week, respectively. The favorable associations with all-cause and cardiovascular mortality were found to be more pronounced in never smokers than in current or former smokers (all Pinteraction < 0.05). In conclusion, chocolate consumption confers reduced risks of mortality from all causes, cardiovascular disease, and Alzheimer's disease in this US population.

This work was supported by Abbott and a grant from the Spanish Ministerio de Ciencia, Innovacion y Universidades cofinanced by Fondo Europeo de Desarrollo Regional (RTI2018-099278-B-I00 to JC and JE) ., Besides skeletal muscle wasting, sarcopenia entails morphological and molecular changes in distinct components of the neuromuscular system, including spinal cord motoneurons (MNs) and neuromuscular junctions (NMJs); moreover, noticeable microgliosis has also been observed around aged MNs. Here we examined the impact of two flavonoid-enriched diets containing either green tea extract (GTE) catechins or cocoa flavanols on age-associated regressive changes in the neuromuscular system of C57BL/6J mice. Compared to control mice, GTE- and cocoa-supplementation significantly improved the survival rate of mice, reduced the proportion of fibers with lipofuscin aggregates and central nuclei, and increased the density of satellite cells in skeletal muscles. Additionally, both supplements significantly augmented the number of innervated NMJs and their degree of maturity compared to controls. GTE, but not cocoa, prominently increased the density of VAChT and VGluT2 afferent synapses on MNs, which were lost in control aged spinal cords; conversely, cocoa, but not GTE, significantly augmented the proportion of VGluT1 afferent synapses on aged MNs. Moreover, GTE, but not cocoa, reduced aging-associated microgliosis and increased the proportion of neuroprotective microglial phenotypes. Our data indicate that certain plant flavonoids may be beneficial in the nutritional management of age-related deterioration of the neuromuscular system., Abbott Laboratories, Spanish Ministerio de Ciencia, Innovacion y Universidades, European Commission RTI2018-099278-B-I00

Cardiovascular disease (CVD) remains the leading cause of death today. Many of the biochemical alterations associated with the pathophysiology of CVD can be modified by adequate intakes of bioactive nutrients through a correct diet or supplementation. Recently, there has been growing public and clinical interest in cocoa polyphenols (CPs) and omega-3 (ω-3) fatty acids. A plethora of nutritional intervention trials and experimental studies demonstrates that consumption of these bioactive food compounds is beneficial to promote cardiovascular health. The purpose of this review is to summarize the major cardioprotective effects of CPs and ω-3 fatty acids, providing a scientific rationale for incorporating the combination of these molecules as a nutritional intervention in the prevention of CVD. Although several studies have shown the individual cardioprotective nature of these compounds, a combination treatment with CPs and ω-3 fatty acids may be a promising approach to enhance the preventive value of these molecules and reduce cardiovascular risk factors associated with aging. Therefore, this article also reviews some of the key studies on the interaction between CPs and the metabolism of ω-3 fatty acids.

To determine if ingestion of lycosome-formulated dark chocolate (DC) containing astaxanthin (ASTX) improves bioavailability of ASTX and affects markers of hypoxia and oxidative stress in aging individuals. Randomized, blinded, four-arm, prospective study. Lycotec Ltd, Cambridge, United Kingdom and Institute of Cardiology, Saratov, Russian Federation. 32 healthy individuals aged 60–70 years with confirmed signs of oxidative stress (increased serum levels of oxidized LDL and malonic dialdehyde) randomized into four study groups (8 volunteers each). Volunteers of first group were given orally 10 gr of dark chocolate (DC). Individuals from the second group received 7 mg of astaxanthin (ASTX). Third group of volunteers was supplemented with 10 gr of DC and 7 mg of ASTX ingested simultaneously as two separate formulations. Last group of the individuals was given 10 gr of a lycosomal formulation of DC containing 7 mg of co-crystalized ASTX (L-DC-ASTX), a newly developed highly bioavailable nutraceutical composition of DC containing 2 groups of antioxidants (cocoa flavanols and ASTX). All formulations were given orally, once daily for a month. Serum ASTX was measured by high-performance liquid chromatography. Nitric oxide, malonic dialdehyde and oxidized LDL were quantified spectrophotometrically. Oxygenation parameters were evaluated by near-infrared spectroscopy. One month ingestion of singular formulation of ASTX lead to a 20 fold buildup in serum ASTX level whereas the 4 week ingestion of L-DC-ASTX formulation was accompanied by more prominent accumulation of ASTX in serum (a 40 fold increase over the basal values) at the same daily dose of ASTX. Both antioxidants taken separately decreased serum levels of oxidized LDL and malonic dialdehyde. However effect of L-DC-ASTX formulation was more prominent. ASTX ingested alone caused a borderline increase (p=0.054) in serum nitric oxide (NO) levels, whereas DC ingestion lead to small but statistically significant increase in serum NO concentration. Higher values of NO level were seen after co-ingestion of DC and ASTX, especially in case of L-DC-ASTX formulation suggesting additive/synergistic effects of DC and ASTX on nitric oxide production. These changes were in agreement with the increase in plasma oxygen transport and tissue oxygen saturation seen in the volunteers supplemented with L-DC-ASTX formulation. The nutraceutical formulation of DC and ASTX with an enhanced bioavailability of ASTX can be efficiently used for the correction of oxidative status in aging individuals.

The mechanisms of action of the dietary components of the Mediterranean diet are reviewed in prevention of cardiovascular disease, stroke, age-associated cognitive decline and Alzheimer disease. A companion article provides a comprehensive review of extra-virgin olive oil. The benefits of consumption of long-chain ω-3 fatty acids are described. Fresh fish provides eicosapentaenoic acid while α-linolenic acid is found in canola and soybean oils, purslane and nuts. These ω-3 fatty acids interact metabolically with ω-6 fatty acids mainly linoleic acid from corn oil, sunflower oil and peanut oil. Diets rich in ω-6 fatty acids inhibit the formation of healthier ω-3 fatty acids. The deleterious effects on lipid metabolism of excessive intake of carbohydrates, in particular high-fructose corn syrup and artificial sweeteners, are explained. The critical role of the ω-3 fatty acid docosahexaenoic acid in the developing and aging brain and in Alzheimer disease is addressed. Nutritional epidemiology studies, prospective population-based surveys, and clinical trials confirm the salutary effects of fish consumption on prevention of coronary artery disease, stroke and dementia. Recent recommendations on fish consumption by pregnant women and potential mercury toxicity are reviewed. The polyphenols and flavonoids of plant origin play a critical role in the Mediterranean diet, because of their antioxidant and anti-inflammatory properties of benefit in type-2 diabetes mellitus, cardiovascular disease, stroke and cancer prevention. Polyphenols from fruits and vegetables modulate tau hyperphosphorylation and beta amyloid aggregation in animal models of Alzheimer disease. From the public health viewpoint worldwide the daily consumption of fruits and vegetables has become the main tool for prevention of cardiovascular disease and stroke. We review the important dietary role of cereal grains in prevention of coronary disease and stroke. Polyphenols from grapes, wine and alcoholic beverages are discussed, in particular their effects on coagulation. The mechanisms of action of probiotics and vitamins are also included.

Cocoa is a source of flavanols, and these phenolic compounds exert beneficial effects on health and aging, and reduce the risk of suffering chronic diseases (cardiovascular diseases, metabolic disorders, cancer). An increasing body of evidence has emerged to suggest that cocoa flavanols potentially are important chemopreventive natural agents. This review summarizes human studies from the past two decades, providing data related to the effects derived from cocoa intake on health and disease. Most human studies have reported beneficial effects of cocoa consumption on health and chronic diseases; however, outcomes are not unequivocal. Review of human studies enable to identify different mechanisms of action for cocoa, although they are not fully understood at present. In addition, it remains unclear whether cocoa consumption should be recommended to healthy subjects or to patients and what is the appropriate dosage or duration of cocoa consumption. Elucidation of information regarding these crucial issues could lead to cocoa use as an approach for decreasing the risk of certain chronic diseases, as well as improving health and quality of life., This work was supported by the RTI2018-095059-B-I00 (MCIU/AEI/FEDER, UE) grant.

The consumption of dietary antioxidants is considered to be a good strategy against photo-aging. However, the results of previous clinical trials that investigated the effects of oral consumption of high-flavanol cocoa products on skin photo-aging have been contradictory.The aim of this study was to investigate whether high-flavanol cocoa supplementation would improve the moderately photo-aged facial skin of female participants, by assessing skin wrinkles and elasticity.We performed a 24-wk, randomized, double-blind, placebo-controlled study to evaluate the effects of oral supplementation of cocoa flavanols on cutaneous photo-aging. All participants were moderately photo-aged Korean women with visible facial wrinkles (age range: 43-86 y). Participants were randomly assigned to receive a placebo beverage or cocoa beverage that contained 320 mg total cocoa flavanols/d. We measured wrinkles, skin elasticity, and hydration at baseline and at 12 and 24 wk. The primary endpoint was the mean percentage change in the average roughness value (Rz) at 24 wk.At 24 wk, the mean percentage change in Rz (primary endpoint) was significantly lower in the cocoa group than in the placebo group (-8.7 percentage points; 95% CI: -16.1, -1.3 percentage points; P = 0.023). The mean percentage changes in gross elasticity, as determined by a cutometer, also differed between the groups at 12 wk (9.1 percentage points; 95% CI: 1.5, 16.7 percentage points; P = 0.020) and 24 wk (8.6 percentage points; 95% CI: 1.0, 16.2 percentage points; P = 0.027). However, there were no significant differences in skin hydration and barrier integrity between the 2 groups.In moderately photo-aged women, regular cocoa flavanol consumption had positive effects on facial wrinkles and elasticity. Cocoa flavanol supplementation may contribute to the prevention of the progression of photo-aging. This trial was registered at clinicaltrials.gov as NCT02060097.

Lung cancer is a common malignancy in men and the second leading cause of cancer-related mortality in men in the western world. Phenolic cocoa ingredients have a strong antioxidative activity and the potential to have a protective effect against cancer. In the present study, we have evaluated the influence of cocoa beans subjected to different processing conditions on cell viability and apoptosis of human lung cancer cells (A549). We measured the viability of lung cells treated with cocoa beans, unroasted slates (US), roasted slates (RS), unroasted well fermented (UWF) cocoa, and roasted well fermented (RWF) cocoa for 24 h. Using an MTT assay, we observed a decrease in the viability of A549 cells after treatment with cocoa bean extracts. Flow cytometer analysis revealed that cocoa beans increased the percentage of cells in sub-G1phase and promoted up to twofold increase of apoptotic cells when compared to the control group. Taken together, the present study suggests that cocoa beans may have a protective effect against lung cancer.

Background Cocoa flavanols in the diet have had positive effects on cognition, blood lipid levels, and glucose metabolism. Methods Cognitively healthy older adults aged 65–75 years were recruited for an eight-week randomized, double-blind controlled trial to investigate the effectiveness of cocoa flavanols on cognitive functions. At baseline, nutrient and polyphenol intakes from diet were assessed with three-day food diaries. The intervention group received 50 g dark chocolate containing 410 mg of flavanols per day, and the control group 50 g dark chocolate containing 86 mg of flavanols per day, for eight weeks. Cognition was assessed with Verbal Fluency (VF) and the Trail Making Test (TMT) A and B as the main outcome measures. Changes in blood lipids and glucose were also measured. Results The older adults participating numbered 100 (63% women), mean 69 y (range 65 to 74). They were highly educated with a mean 14.9 years of education (SD 3.6). No differences in changes in cognition were seen between groups. The mean change (± SEs) in the time to complete the TMT A and B in the intervention group was −4.6 s (−7.1 to −2.1) and −16.1 s (−29.1 to −3.1), and in the controls −4.4 s (−7.0 to −1.9) and −12.5 s (−22.8 to −2.1)(TMT A p = 0.93; TMT B p = 0.66). No difference was apparent in the changes in blood lipids, glucose levels, or body weight between the groups. Conclusions The healthy older adults showed no effect from the eight-week intake of dark chocolate flavanols on cognition.

Scope An understanding of the pharmacokinetics of structurally related (−)‐epicatechin metabolites (SREM) is a prerequisite for considering cocoa flavanols (CF) in the context of dietary recommendations. The objective of this study was to compare the absorption, metabolism, and excretion of SREM in healthy young and elderly Caucasian men. Methods and results Intraindividual variability of SREM was assessed in seven young subjects, after consuming 10.7 mg CF/kg body weight (BW) on two occasions separated by 1 week. The effect of age on flavanols ADME was assessed in 20 young (18–35 years) and 20 elderly (65–80 years) healthy male subjects receiving 5.3 and 10.7 mg total CF/kg BW or 1 g of acetaminophen as a control to compare differences in Phase II metabolism on three days separated by 1 week of wash‐out. Blood and urine samples were collected for 24‐h post consumption. The intraindividual variation, measured as CV(%) with respect to the area‐under‐the‐curve of the concentration over time (AUC(0‐6h)) of SREM, was 16%, while the interindividual variation in AUC(0‐6h), was 38%, comparable to acetaminophen (39%). The AUC(0‐6h) and the 24‐h excretion of total SREM was not significantly different between young and elderly subjects. At the high intake amount, the AUC(0‐6h) of (−)‐epicatechin‐3′‐β‐D‐glucuronide was greater in elderly subjects, whereas the AUC(0‐6h) of 3′‐O‐methyl‐(−)‐epicatechin‐5‐sulfate and 3′‐O‐methyl‐(−)‐epicatechin‐7‐sulfate as well as the 24‐h urinary excretion of γ‐valerolactone metabolites were lower in the elderly. Conclusion Cocoa flavanols are absorbed, metabolized, and excreted in healthy young and elderly subjects with relatively small differences between the two groups.

Oxidative stress (OS) can induce cell apoptosis and thus plays an important role in aging. Antioxidant foods protect tissues from OS and contribute to a healthier lifestyle. In this study, we described the used of medaka embryos (Oryzias latipes) to study the putative antioxidant capacity of dietary cocoa extract in vertebrates. A polyphenol-enriched cocoa extract regulated the expression of several genes implicated in OS, thereby protecting fish embryos from induced OS. The cocoa extract activated superoxide dismutase enzyme activity in embryos and adult fish tissues, suggesting a common mechanism for protection during embryonic development and adulthood. Furthermore, long-term feeding of the cocoa extract increased fish life span. Our study demonstrates that the polyphenol-enriched cocoa extract decreases OS and extends life span in medaka fish, validating the use of medaka embryos as an economical platform to screen the antioxidant capacity of food compounds.

Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells. Chemical composition, total phenolic content, and antioxidant capacity of cocoa polyphenols extracted from roasted cocoa beans were determined. THP-1 cells were activated with both lipopolysaccharides and interferon-γfor M1 or with IL-4 for M2 switch, and specific cytokines were quantified. Cellular metabolism, through mitochondrial oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage response as demonstrated by a significantly lowered secretion of proinflammatory cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols influences macrophage metabolism by promoting oxidative pathways, thus leading to a significant increase in O2consumption by mitochondrial complexes as well as a higher production of ATP through oxidative phosphorylation. In conclusion, cocoa polyphenolic extract suppresses inflammation mediated by M1 phenotype and influences macrophage metabolism by promoting oxidative pathways and M2 polarization of active macrophages.

The aim of this study was to estimate the dietary intake and major food sources of polyphenols in the Mediterranean healthy Eating, Aging and Lifestyles (MEAL) study cohort. A total of 1937 individuals (18 + y) of urban population of Catania, Italy, completed a validated 110-item food frequency questionnaire; Phenol-Explorer database was used to estimate polyphenol intake. Mean intake of polyphenols was 663.7 mg/d; the most abundant classes were phenolic acids (362.7 mg/d) and flavonoids (258.7 mg/d). The main dietary sources of total polyphenols were nuts, followed by tea and coffee as source of flavanols and hydroxycinnamic acids, respectively, fruits (i.e. cherries were sources of anthocyanins and citrus fruits of flavanones) and vegetables (i.e. artichokes and olives were sources of flavones and spinach and beans of flavonols); chocolate, red wine and pasta contributed to flavanols and tyrosols, respectively. These findings will be useful to assess the potential benefits of foods with high polyphenol content.

Polyphenols in general are compounds that are known to promote health and have a preventive effect against various chronic diseases. The influence of cocoa polyphenols on skin, however, has scarcely been studied from a histological point of view. The aim of this study is to assess the influence of cocoa polyphenols on several indicators of skin elasticity and skin tonus, namely, glycosaminoglycans and collagen I, III and IV. This was carried out by using a model of ex vivo human skin explants maintained in survival, on which a cocoa polyphenol extract was applied. After processing by standard histological techniques (fixation, paraffin embedding, sectioning, staining, immunostaining and microscopical observation), the influence of cocoa polyphenols on the evaluated parameters was quantified by image analysis. The results obtained show that cocoa polyphenols exhibit a positive action on the parameters assessed, and the dose at which they improve the most parameters associated with skin tonus and elasticity was determined. Their activity was compared with a commercially available product, and the results obtained show that their efficacy is equivalent. Moreover, an enhancing effect of cocoa butter on activity of cocoa polyphenol was highlighted. Now that the properties of cocoa polyphenols on ex vivo skin restructuring parameters have been assessed, the next step could include their evaluation in vivo.

Numerous studies have indicated that increased vulnerability to oxidative stress may be the main factor involved in functional declines during normal and pathological ageing, and that antioxidant agents, such as polyphenols, may improve or prevent these deficits. We examined whether 1-year administration of a cocoa polyphenolic extract (Acticoa powder), orally delivered at the dose of 24 mg/kg per d between 15 and 27 months of age, affects the onset of age-related cognitive deficits, urinary free dopamine levels and lifespan in old Wistar-Unilever rats. Acticoa powder improved cognitive performances in light extinction and water maze paradigms, increased lifespan and preserved high urinary free dopamine levels. These results suggest that Acticoa powder may be beneficial in retarding age-related brain impairments, including cognitive deficits in normal ageing and perhaps neurodegenerative diseases. Further studies are required to elucidate the mechanisms of cocoa polyphenols in neuroprotection and to explore their effects in man.

Laura Fernández-Fernández et al., © 2015 The Royal Society of Chemistry. The possible modulatory effect of the functional LMN diet, rich in theobromine, polyphenols and polyunsaturated fatty acids, on the catecholaminergic and cholinergic neurotransmission, affecting cognition decline during aging has been studied. 129S1/SvlmJ mice were fed for 10, 20, 30 and 40 days with either LMN or control diets. The enzymes involved in catecholaminergic and cholinergic metabolism were determined by both immunohistological and western blot analyses. Noradrenalin, dopamine and other metabolites were quantified by HPLC analysis. Theobromine, present in cocoa, the main LMN diet component, was analysed in parallel using SH-SY5Y and PC12 cell lines. An enhanced modulatory effect on both cholinergic and catecholaminergic transmissions was observed on 20 day fed mice. Similar effect was observed with theobromine, besides its antioxidant capacity inducing SOD-1 and GPx expression. The enhancing effect of the LMN diet and theobromine on the levels of acetylcholine-related enzymes, dopamine and specially noradrenalin confirms the beneficial role of this diet on the >cognitive reserve> and hence a possible reducing effect on cognitive decline underlying aging and Alzheimer's disease., The present study was supported by the Spanish Ministry of Industry (CDTI) through the following projects: Project CENIT (MET-DEV-FUN); Programa Ingenio 2010, Programa INCOMES and a grant from the Chinese Scholarship Council (P. S.)

Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging. In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 22 young (

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.

Foods and beverages rich in flavonoids are being heralded as potential preventive agents for a range of pathologic conditions, ranging from hypertension to coronary heart disease to stroke and dementia. We and others have demonstrated that short-term ingestion of cocoa, particularly rich in the subclass of flavonoids known as flavanols, induced a consistent and striking peripheral vasodilation in healthy people, improving endothelial function in a nitric oxide-dependent manner. The vasodilator response was reversed by N-nitro-L-arginine methyl ester, an arginine analog that blocks nitric oxide synthesis. Flavanol-poor cocoa induced much smaller responses. Because impairment of endothelial function is a nearly universal accompaniment of the aging process, we examined the peripheral vasodilator response to flavanol-rich cocoa in healthy older subjects. Observations point to a favorable response among the older. Together with peripheral vascular disease, cerebrovascular disease is responsible for significant mortality with advancing age. An association of decreased cerebral perfusion with dementia has been recently highlighted. The prospect of increasing cerebral perfusion with cocoa flavanols is extremely promising. Our still preliminary data hold out the promise that the cerebral blood supply in the elderly participates in the vasodilator response. With the modalities of transcranial Doppler and MRI, we have the capabilities of analyzing the potential benefits of flavanols on brain perfusion and, subsequently, on cognition.

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.

Sarcopenia is a notable and debilitating age-associated condition. Flavonoids are known for their healthy effects and limited toxicity. The flavanol (−)-epicatechin (Epi) enhances exercise capacity in mice, and Epi-rich cocoa improves skeletal muscle structure in heart failure patients. (−)-Epicatechin may thus hold promise as treatment for sarcopenia. We examined changes in protein levels of molecular modulators of growth and differentiation in young vs. old, human and mouse skeletal muscle. We report the effects of Epi in mice and the results of an initial proof-of-concept trial in humans, where muscle strength and levels of modulators of muscle growth were measured. In mice, myostatin and senescence-associated β-galactosidase levels increase with aging, while those of follistatin and Myf5 decrease. (−)-Epicatechin decreases myostatin and β-galactosidase and increases levels of markers of muscle growth. In humans, myostatin and β-galactosidase increase with aging while follistatin, MyoD and myogenin decrease. Treatment for 7 days with (−)-epicatechin increases hand grip strength and the ratio of plasma follistatin/myostatin. In conclusion, aging has deleterious effects on modulators of muscle growth/differentiation, and the consumption of modest amounts of the flavanol (−)-epicatechin can partially reverse these changes. This flavanol warrants its comprehensive evaluation for the treatment of sarcopenia.

This paper compiles the beneficial effects of cocoa polyphenols on human health, especially with regard to cardiovascular and inflammatory diseases, metabolic disorders, and cancer prevention. Their antioxidant properties may be responsible for many of their pharmacological effects, including the inhibition of lipid peroxidation and the protection of LDL-cholesterol against oxidation, and increase resistance to oxidative stress. The phenolics from cocoa also modify the glycemic response and the lipid profile, decreasing platelet function and inflammation along with diastolic and systolic arterial pressures, which, taken together, may reduce the risk of cardiovascular mortality. Cocoa polyphenols can also modulate intestinal inflammation through the reduction of neutrophil infiltration and expression of different transcription factors, which leads to decreases in the production of proinflammatory enzymes and cytokines. The phenolics from cocoa may thus protect against diseases in which oxidative stress is implicated as a causal or contributing factor, such as cancer. They also have antiproliferative, antimutagenic, and chemoprotective effects, in addition to their anticariogenic effects.

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 ≈990 mg (high flavanols), ≈520 mg (intermediate flavanols), or ≈45 mg (low flavanols) of cocoa flavanols per day. Cognitive function was assessed by Mini Mental State Examination, Trail Making Test A and B, and verbal fluency test. At the end of the follow-up period, Mini Mental State Examination was similar in the 3 treatment groups ( P =0.13). The time required to complete Trail Making Test A and Trail Making Test B was significantly ( P P z score variability through the study period (partial r 2 =0.4013; P

Cocoa powder and chocolate contain numerous substances among which there is a quite large percentage of antioxidant molecules, mainly flavonoids, most abundantly found in the form of epicatechin. These substances display several beneficial actions on the brain. They enter the brain and induce widespread stimulation of brain perfusion. They also provoke angiogenesis, neurogenesis and changes in neuron morphology, mainly in regions involved in learning and memory. Epicatechin improves various aspects of cognition in animals and humans. Chocolate also induces positive effects on mood and is often consumed under emotional stress. In addition, flavonoids preserve cognitive abilities during ageing in rats, lower the risk for developing Alzheimer's disease and decrease the risk of stroke in humans. In addition to their beneficial effects on the vascular system and on cerebral blood flow, flavonoids interact with signalization cascades involving protein and lipid kinases that lead to the inhibition of neuronal death by apoptosis induced by neurotoxicants such as oxygen radicals, and promote neuronal survival and synaptic plasticity. The present review intends to review the data available on the effects of cocoa and chocolate on brain health and cognitive abilities.

The purpose was to test the hypothesis that a multifaceted 11 weeks randomized controlled intervention would have a significant influence of functional abilities in old nursing home residents. Participants were 121 old (>65 years) residents in seven Danish nursing homes. The intervention consisted of nutrition (chocolate, homemade oral supplements), group exercise (moderate intensity) and oral care. Measurements taken were weight, body mass index (BMI), energy and protein intake, and functional abilities (activities of daily living = ADL, cognitive performance, and social engagement). The results showed that the nutrition and exercise were well accepted. After 11 weeks the change in % weight (1.3 vs. 0.6%, p = 0.005), % BMI (0.4 vs.0.2%, p = 0.003), energy intake (0.7 vs.0.3 MJ/day, p = 0.084) and protein intake (5 vs. 2 g/day, p = 0.012) was higher in the intervention group than in the control group. Also, after 11 weeks, social and physical function had decreased in the control group but was unchanged in the intervention group. The difference between groups was significant in relation to social engagement (p = 0.009). After the end of the intervention both groups had lost weight and physical function. Cognitive performance did not change, at any time. In conclusion, it seems possible to maintain social (and physical) functional abilities in old nursing home residents by means of a multifaceted intervention.

This report presents a 93-year-old woman with prolonged angioedema associated with diabetic chocolate and chronic angiotensin-converting enzyme inhibitor use.

Nutrition is important for the development and maintenance of bone structure and for the prevention of osteoporosis and fracture. The relation of chocolate intake with bone has yet to be investigated.We investigated the relation of chocolate consumption with measurements of whole-body and regional bone density and strength.Randomly selected women aged 70-85 y (n=1460) were recruited from the general population to a randomized controlled trial of calcium supplementation and fracture risk. We present here a cross-sectional analysis of 1001 of these women. Bone density and strength were measured with the use of dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and quantitative ultrasonography. Frequency of chocolate intake was assessed with the use of a questionnaire and condensed into 3 categories:1 time/wk, 1-6 times/wk,or=1 time/d.Higher frequency of chocolate consumption was linearly related to lower bone density and strength (P0.05). Daily (or=1 times/d) consumption of chocolate, in comparison to1 time/wk, was associated with a 3.1% lower whole-body bone density; with similarly lower bone density of the total hip, femoral neck, tibia, and heel; and with lower bone strength in the tibia and the heel (P0.05, for all). Adjustment for covariates did not influence interpretation of the results.Older women who consume chocolate daily had lower bone density and strength. Additional cross-sectional and longitudinal studies are needed to confirm these observations. Confirmation of these findings could have important implications for prevention of osteoporotic fracture.

Previous studies indicate that, in adulthood, neonatally handled rats consume more sweet food than nonhandled rats. The aim of the present study was to assess the effects of the chronic exposure to a palatable diet (chocolate) in adult neonatally handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, abdominal fat deposition, and levels of plasma lipids, glucose, insulin, and corticosterone in adult neonatally handled (10 min/d, first 10 d of life) and nonhandled rats. We found an increased intake of chocolate in handled rats, but this consumption decreased over time. Handled male animals exhibited higher body weight, higher caloric efficiency, and lower triglyceride levels. Nonhandled females that were exposed long-term to the highly caloric diet had increased abdominal fat deposition compared with handled females. Overall female rats had increased abdominal fat deposition, higher total cholesterol and glucose levels, and lower insulin in comparison with males. Interestingly, chocolate consumption diminished the weight of the adrenal glands in both handled and nonhandled animals. These findings suggest that neonatal handling induces a particular metabolic pattern that is sex specific.

We hypothesized that chocolate preference would be related to health and psychological well-being in old men. We have followed up a socio-economically homogenous group of men, born in 1919–1934, since the 1960s. In 2002–2003, a mailed questionnaire was used to assess the health and well-being (including questions related to positive life orientation, visual analogue scales and the Zung depression score) of survivors. In addition, candy preference was inquired. Those men who reported no candy consumption (n=108) were excluded from the analyses. Psychological well-being in old age. The response rate was 69% (1367 of 1991). Of the respondents, 860 and 399 preferred chocolate and other type of candy, respectively. The average age in both candy groups was 76 years. Of the respondents, 99% were home-dwelling, 96% were retired and 87% were presently married, without differences between the candy groups. Men preferring chocolate had lower body mass index and waist circumference, and they also reported more exercise and better subjective health (P=0.008) than other candy consumers. Variables related to psychological well-being were consistently better in those preferring chocolate. The differences were statistically significant in feeling of loneliness (P=0.01), feeling of happiness (P=0.01), having plans for the future (P=0.0002) and the Zung depression score (P=0.02). In this socioeconomically homogenous male cohort, chocolate preference in old age was associated with better health, optimism and better psychological well-being. The Academy of Finland, the Paivikki and Sakari Sohlberg Foundation, the Helsinki University Central Hospital and the Finnish Foundation for Cardiovascular Research.

Objective Effective approaches should be established to prevent the onset of type 2 diabetes mellitus, which has been increasing in developed countries. The present study examined whether dietary supplementation with cacao liquor proanthocyanidins (CLPr) could prevent elevation of blood glucose levels in mice with diabetes mellitus and obesity. Methods C57BL/KsJ-db/db (db/db) diabetic obese mice and C57BL/KsJ-db/+m (db/+m) control mice were fed a diet containing 0% w/w CLPr (0% CLPr), 0.5% w/w CLPr (0.5% CLPr), or 1.0% w/w CLPr (1.0% CLPr) from age 3 wk to age 6 wk. Levels of blood glucose were measured at 4 and 5 wk of age. The animals were sacrificed and the levels of blood glucose and fructosamine were measured at 6 wk of age. Results The levels of blood glucose and fructosamine were higher in the db/db mice than in the db/+m mice fed a diet containing 0%, 0.5%, or 1.0% CLPr. In the db/+m mice, the levels of blood glucose or fructosamine were not significantly different across animals fed 0% CLPr, 0.5% CLPr, and 1.0% CLPr. In the db/db mice, however, a diet containing 0.5% or 1.0% CLPr decreased the levels of blood glucose and fructosamine compared with that containing 0% CLPr without significant effects on body weights or food consumption. Conclusion Dietary supplementation with CLPr can dose-dependently prevent the development of hyperglycemia in diabetic obese mice. The dietary intake of food or drinks produced from cacao beans might be beneficial in preventing the onset of type 2 diabetes mellitus.

Strong evidence has secured aging as a powerful predictor of both cardiovascular risk and endothelial dysfunction, yet specific treatment is not available. We tested the hypothesis that vascular responsiveness to flavanol-rich cocoa increases with advancing age. We have previously shown that flavanol-rich cocoa induced peripheral vasodilation, improving endothelial function via a nitric oxide (NO)-dependent mechanism.We studied blood pressure and peripheral arterial responses to several days of cocoa in 15 young (50 years) and 19 older (50) healthy subjects.The nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine-methyl-ester (L-NAME) induced significant pressor responses following cocoa administration only among the older subjects: systolic blood pressure (SBP) rose 13 +/- 4 mmHg, diastolic blood pressure (DBP) 6 +/- 2 mmHg (P = 0.008 and 0.047, respectively); SBP was significantly higher in the older subjects (P0.05). Flow-mediated vasodilation, measured by tonometry in the finger, was enhanced with flavanol-rich cocoa in both groups, but significantly more so among the old (P = 0.01). Finally, basal pulse wave amplitude (PWA) followed a similar pattern. Four to six days of flavanol-rich cocoa caused a rise in PWA in both groups. At peak vasodilation following acute cocoa intake on the final day, both groups showed a further, significant rise in PWA. The response in the older subjects was more robust; P0.05. L-NAME significantly reversed dilation in both groups.Flavanol-rich cocoa enhanced several measures of endothelial function to a greater degree among older than younger healthy subjects. Our data suggest that the NO-dependent vascular effects of flavanol-rich cocoa may be greater among older people, in whom endothelial function is more disturbed.

In the current issue of the journal, Fisher and Hollenberg [1] elegantly demonstrate a significant increase in flowmediated dilation, as measured by finger tonometry, in 15 healthy individuals aged < 50 years and 19 healthy individuals aged ! 50 years, after 4–6 days of cocoa supplementation. Of note, cocoa-related changes in flowmediated dilation were age-dependent, being evident in both groups but more striking among older individuals. Similar findings were found for pulse wave velocity, an index of arterial stiffness rather than of endothelial function [2], that remained unchanged after cocoa supplementation in both groups, but increased after an additional cocoa drink on the final study day. Because the vascular effects of cocoa weremarkedly attenuated by N-nitro-L-arginine-methyl-ester, the intriguing findings provided by Fisher and Hollenberg [1] suggest that cocoa can significantly improve nitric oxide bioavailability in healthy individuals, particularly after 50 years of age. More generally, because the risk for developing atherosclerosis in industrialized countries has been suggested to be linked to the endothelial dysfunction, their study also suggests that changes in dietary habitudes could be of help in preserving nitric oxide bioavailability, thereby blunting the onset of age-related atherosclerotic lesions.

The articles in the issue provide important evidence for the acute effects of cocoa flavanols on the peripheral vascular response in humans. As Hollenberg and Luscher point out, ‘‘not only does flavanol-rich cocoa-induced nitric oxide production show a dramatic influence on blood vessels in healthy individuals, preliminary information available indicates that the influence on nitric oxide synthesis is evident in patients with advanced atherosclerosis, hypertension, or diabetes mellitus.’’ 1 Blood flow, of course, also has a fundamental role in brain function. Neuroimaging techniques designed to measure aspects of cerebral blood flow (CBF)—such as functional magnetic resonance imaging (fMRI), which is based on the increase in blood flow accompanying neural activity in the brain—have amply demonstrated the critical relationships of cerebrovascular responses and cerebrovascular health to human cognitive 2 and emotional 3 functions. The article by Francis et al 4 in this issue provides some of the first evidence that flavanol-rich cocoa can affect CBF in humans. Using blood oxygenation level-dependent (BOLD) fMRI they observed an increase in relative blood flow in brain areas subserving a cognitive switching task in 16 healthy young adults. Equally interesting are their findings from a pilot study on 4 healthy young adults in which arterial spin-labeling sequence (ASL) magnetic resonance imaging (MRI) was used to assess the time course of a single serving of flavanol-rich cocoa on brain blood flow. This study showed that flavanol-rich cocoa could acutely increase CBF in gray matter, suggesting it may have potential for the treatment of cerebrovascular deficits. The reason these data are important for documenting the effects of flavanol-rich cocoa on CBF is because unlike BOLD fMRI, arterial spin-labeling perfusion MRI technique provides a direct quantitative measure of CBF using arterial blood water as an endogenous contrast agent. With excellent reproducibility over long-term time periods 5,6 and minimal sensitivity to magnetic-field inhomogeneity effects, 7 perfusion fMRI is ideal for imaging the time course of flavanol-rich cocoa effects, and permitting comparisons of CBF before and after consumption of flavanol-rich cocoa. Perfusion fMRI also has reduced scanner noise level and reduced sensitivity to subject motion. 8 Figure 3 in Francis et al 4 illustrates the usefulness of arterial spin labeling MRI for tracking the temporal effects on CBF of an acute dose of high flavanols cocoa drink relative to the effects of a low flavanols cocoa drink. These data leave little doubt that quantitative neuroimaging methods (eg, arterial spin-labeling perfusion fMRI, positron-emission tomography, transcranial Doppler ultrasound) should be the techniques of choice for future studies of flavanol-rich cocoa effects on CBF. Evidence that flavanols increase CBF is a key step in demonstrating their action in the cerebrovasculature, but ideally 1 would also hope to see changes in the functional status of brain, especially because increases in blood flow to neuronal vasculature accompany increases in neural activity in the brain. 2 This is the reason that functional MRI is such a popular and useful tool in the burgeoning area of cognitive neuroscience. Why then, were Francis et al 4 able to measure greater changes from the high flavanols cocoa drink (relative to the low flavanols cocoa