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Effect of cocoa in diabetes: The potential of the pancreas and liver as key target organs, more than an antioxidant effect?
International Journal of Food Science & Technology
Abstract
Increasingly, type 2 diabetes mellitus is being linked to metabolic abnormalities within the liver and pancreas, associated with fat deposition and oxidative stress. Cocoa and chocolate have been seen to improve oxidative stress and enhance insulin sensitivity. Recent in vitro and animal model studies have begun to investigate the potential of cocoa and cocoa extracts in modulating fatty liver and pancreatic function. Evidence from these studies has highlighted a number of mechanisms, which facilitate insulin secretion and enhanced survival in pancreatic beta cells. Whilst in liver, improved effect of insulin was observed with some improvements in fatty infiltration. However, what was seen as a common effect was an increase in endogenous antioxidant capability. The potential of cocoa products in the management of fatty liver and supporting pancreatic function in humans is likely to be limited by their macronutrient and energy profile or palatability, unless taken as cocoa extract supplements.
... The favourable effect of chocolate and cocoa consumption with respect to CVD risk factors could be explained by several mechanisms that have been linked to its antioxidantlike and anti-inflammatory properties [5]. The proposed mechanism varies, from induction of endothelial nitric oxide synthase as a mechanism for the improvement in endothelial function, to induction of endogenous antioxidant systems including superoxide dismutase to explain the antioxidant-like effects seen [53]. With the previously held view that the antioxidant effects observed in vitro simply could be translated to in vivo being widely dismissed due to low circulating levels of these compounds due to poor absorption and bioavailability. ...
... With the previously held view that the antioxidant effects observed in vitro simply could be translated to in vivo being widely dismissed due to low circulating levels of these compounds due to poor absorption and bioavailability. Further mechanisms have been explored to explain the blood pressure-lowering effects possibly being linked to inhibition of ACE and insulin resistance via modulation of AMP-kinase pathway in skeletal muscle and liver [53][54][55]. However, critics have suggested that the same amount of flavanols and epicatechin could be met through the consumption of other foods and food products (e.g. via tea) [11]. ...
Randomized controlled trials and meta-analyses have demonstrated the potential protective effect of cocoa and chocolate consumption with respect to cardiovascular disease (CVD) risk markers. Findings from experimental studies are in concordance with observational data, which include reduction in clinical disease (especially stroke) being associated with chocolate consumption. However, the effect size of any benefit, and the exact mechanism of action due to variability in reporting of dose and type potential bioactive compounds remains unclear. Thus, the present review aimed to analyse the published work where cocoa and chocolate have been assessed for their potential to protect against CVD and highlight the role of study design and type of product used in the variances of outcomes and how that might be used in formulating health advice.
... This is supported by underlying biological and mechanistic data, which suggest a diet rich in vegetable and fruit matter, including extra virgin olive oil rich in bioactive compounds including polyphenols, is cardioprotective. Both in vitro and in vivo laboratory studies have demonstrated potential mechanisms by which these compounds can moderate the inflammatory effects of fatty liver [44,45]. A systematic review of randomised controlled trials highlighted the importance of polyphenol-rich food products and cardiovascular outcomes [45]. ...
Background:
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease, affecting ~30% of the population and increasing CVD. This study aimed to explore the direct, indirect and combined effects of Mediterranean diet, NAFLD and inflammation on the 10-year CVD risk in a healthy adult population.
Methods:
Using baseline and 10-year follow-up data from the ATTICA study, adherence to Mediterranean diet was measured using MedDietScore, and presence of NAFLD at baseline was assessed using the fatty liver index (FLI). Participants' 10-year CVD outcomes were recorded and C-reactive protein (CRP) was used as a surrogate marker for inflammation. The direct and indirect roles of these factors were explored using logistic regression models and the pathways between them were analysed using a structural equation model (SEM).
Results:
NAFLD prevalence was 22.9% and its presence was 17% less likely for every unit increase in MedDietScore. NAFLD presence at baseline was associated with increased 10-year CVD incidence (39.4% vs. 14.5%, p = 0.002), but when adjusted for MedDietScore, NAFLD was not an independent predictor of 10-year CVD risk. MedDietScore was an independent protective factor of 10-year CVD risk (OR = 0.989, 95% CI: 0.847, 0.935), when adjusted for NAFLD at baseline, age, gender, sedentary lifestyle and other confounders. Further exploration using SEM showed that MedDietScore was associated with CVD risk directly even when inflammation as CRP was introduced as a potential mediator.
Conclusion:
FLI as a proxy measure of NAFLD is a strong predictor of 10-year CVD risk, and this prognostic relationship seems to be moderated by the level of adherence to Mediterranean diet. Adherence to Mediterranean diet remained an independent and direct CVD risk factor irrespective of NAFLD status and CRP.
... In the human diet, many different plant-based products are consumed throughout the day, even within the same meal. Fruit and vegetables are associated with various health benefits, due to their variety of bioactive compounds, i.e., vitamins, minerals, and secondary plant metabolites [1]. In comparison to vitamins and minerals, secondary plant metabolites, such as phenolics, are not regarded as essential for human health by today's knowledge [2]. ...
Bioactive compounds in fruit and vegetables influence each other’s antioxidant activity. Pure standards, and mixtures of the common plant compounds, namely ascorbic acid, 5-caffeoylquinic acid, and quercetin-3-rutinoside (sum 0.3 mM), in the presence and absence of iron, were analyzed pre- and post-thermal processing in an aqueous solution. Antioxidant activity was measured by total phenolic content (TPC), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (TEAC) radical-scavenging assays. Ionic ferrous iron (Fe²⁺) and ferric iron (Fe³⁺) were measured photometrically. For qualification and quantification of reaction products, HPLC was used. Results showed that thermal processing does not necessarily lead to a decreased antioxidant activity, even if the compound concentrations decreased, as then degradation products themselves have an antioxidant activity. In all used antioxidant assays the 2:1 ratio of ascorbic acid and 5-caffeoylquinic acid in the presence of iron had strong synergistic effects, while the 1:2 ratio had strong antagonistic effects. The pro-oxidant iron positively influenced the antioxidant activity in combination with the used antioxidants, while ferrous iron itself interacted with common in vitro assays for total antioxidant activity. These results indicate that the antioxidant activity of compounds is influenced by factors such as interaction with other molecules, temperature, and the minerals present.
... Unlike other superfoods, cocoa-related research attracted much attention in many perspectives, including research reviewing cocoa/chocolate consumption and cardiovascular health (Fernández-Murga et al., 2011;Kerimi and Williamson, 2015), diabetes (Mellor and Naumovski, 2016), and colon cancer . ...
During the last decade, gluten-free food consumption has become a widespread diet trend due to the awareness of gluten intolerances/allergies, as better diagnostic tools are becoming available, and because of the increased number of consumers following this diet regardless of medical needs. However, production of gluten-free foods comprises technological challenges that have to be addressed. The chapter is initially introducing the concept of gluten-free food production in accordance to current gluten-free product markets and labeling regulations worldwide. The need to improve the quality of gluten-free products highlighting both nutritional and formulations aspects is also examined. In this context, it provides a comprehensive overview of various techniques applied in the production of gluten-free foods for combating the commonly encountered problems related to the elimination of gluten. These techniques include compositional approaches, such as the addition of different ingredients and additives in gluten-free formulations. Additionally, bioprocessing fermentations, novel optimal processing technologies, and transgenic methodologies are discussed as the main emerging technological approaches for affecting physico-chemical, sensory, and nutritional characteristics of gluten-free foods.
... Unlike other superfoods, cocoa-related research attracted much attention in many perspectives, including research reviewing cocoa/chocolate consumption and cardiovascular health (Fernández-Murga et al., 2011;Kerimi and Williamson, 2015), diabetes (Mellor and Naumovski, 2016), and colon cancer . ...
... This information will be useful for the formulation of new food products or for the design of new food processes.KEYWORDS antioxidant activity, flavonoid, heat processing, modelling, thermal stability1 | INTRODUCTIONOver the last few decades, epidemiological studies have shown that consuming fruit and vegetables rich in phenolic compounds leads to a general well-being of consumers (Tom as-Barber an, Ferreres, & Gil, 2000). These benefits have been attributed to phenolic compound properties, particularly antioxidant activity which plays a role in this health-promoting capacity(Mellor & Naumovski, 2016). Among phenolic compounds, flavonoids are the most studied class and much interest is focused on them. ...
Les objectifs de cette thèse sont d’une part d'étudier les effets d’un traitement thermique et de l’environnement physico-chimique sur la stabilité de 6 flavonoïdes de structure différente et sur l'évolution de leur activité anti-oxydante. Les conditions du traitement thermique ont été les suivantes : (i) chauffage dans des conditions isothermes durant 2h pour des températures allant de 30 à 130°C et (ii) chauffage dans des conditions non isothermes par microcalorimétrie (de 30 à 130°C, 4°C/ heure). Les flavonoïdes ont été solubilisés dans de l’eau. Nous avons constaté que les flavonoïdes glycosylés sont plus résistants que les flavonoïdes aglycones. Les énergies d'activation de dégradation calculées dépendent aussi de la structure du flavonoïde. Pour se dégrader, les flavonoïdes glycosylés ont besoin d’une énergie élevée par rapport à la forme aglycone. L’exposition à la lumière a été réalisée durant 15 jours avec et sans oxygène, le témoin de l’expérience étant un stockage à l’obscurité avec et sans oxygène. La dégradation des flavonoïdes est influencée par la présence de lumière et par la quantité d'oxygène. Les molécules ont une sensibilité différente en fonction de leur structure, le classement suivant est obtenu d’après : naringine, ériodictyol puis rutine, lutéoline, lutéoline 7-O-glucoside et enfin le mesquitol. En effet, la présence d'un groupe hydroxyle en position 3 et une double liaison C2-C3 diminue la stabilité des flavonoïdes. En outre, il a été observé que, malgré la dégradation totale de certains flavonoïdes par le traitement thermique et l’environnement physico-chimique, les solutions traitées conservent une activité anti-oxydante
... When assessing antioxidant activity, the system in which antioxidants function must be considered, meaning that no one assay is able to fully assess the complexity of antioxidant interactions and synergy in foods and organisms. If the antioxidant is considered in vivo, there is evidence to suggest it may work (due to the relatively low concentrations) as pro-oxidants inducing pathways linked to endogenous antioxidant capacity, especially in the liver (Mellor & Naumovski, 2016). This mechanism might be via activation of intracellular signalling pathways or regulation of gene expression. ...
The use of the word ‘antioxidant’ has become widespread in food science, nutrition and consumer language, having become associated with potential health benefits linked to consuming sources of antioxidants in our food supply. However, there is significant doubt about direct antioxidant effects on human health. This may partly relate to methodology used for assessing functionality and activity (both in food matrices and in human health) as well as how data is extrapolated with respect to health based on laboratory analyses. In this review, the purpose and impact of antioxidants in food systems and on human health will be discussed, along with highlighting the best current methodology for analysing antioxidant effects. Consideration will also be made with respect to recommendations of how antioxidant activity should be reported, with a focus on being both scientifically accurate as well as minimising the risk of unwarranted extrapolations of benefits which might mislead end consumers.
... There can be little argument that the relationship between food and human health has featured very highly in the attention of both the consumer and the food industry in recent years. The manipulation of diabetes and obesity is one of the current challenges food researchers are engaged with, and this is demonstrated by articles investigating the potential beneficial effects of cocoa (Mellor & Naumovski, 2016), legumes (Reynolds et al., 2016), combinations of soy milk and probiotics together with prebiotics Xie et al., 2017) and collagen from fish material (Zhang et al., 2016). The role of dietary fibres and plant bioactive ingredients has been recognised as vital components of a healthy diet as evidenced by the article by Grundy et al. (2016) on the potential use of almonds in improving digestive health, as well as the manuscript illustrating the role of whole grains and resistant starch in terms of insulin control (Aggarwal et al., 2017). ...
... This has a deep routed history, with cocoa having cultural along with a role in traditional medicine dating back to the Aztecs and Mayans in Central America. Historical benefits include an association with increased endurance, with the Codex of the time recording that Emperor Montezuma II claimed that a soldier could march for a whole day on a single cup of cocoa (Dillinger et al., 2000;Ellam & Williamson, 2013;Mellor & Naumovski, 2016). ...
The potential health effects of cocoa flavanols are well described. Ranging from reducing risk of developing type 2 diabetes and cardiovascular disease at population levels, moderating disease risk factors including endothelial function and lipid metabolism in clinical trials and mechanistic studies in laboratory studies highlighting target tissues and pathways. However, translating these benefits into public health messages is problematic, due to the high energy and sugar content of many cocoa products, including chocolate. This review considered the role of sugar in cocoa products, what are its physiological effects on bioavailability and bioactivity? Considering, then how cocoa products can be reformulated to reduce sugar intake, and the likely effects on beneficial effects of cocoa flavanols and consumer preferences. Ultimately, although interesting physiological effects are seen with cocoa flavanols, their use as a disease-modifying commodities may be limited the effect such products may have within an individual's and populations overall dietary patterns.
... Some epidemiological studies have shown that consuming fruits and vegetables rich in phenolic compounds leads to a general well-being of consumers (Gil et al. 2000). The antioxidant capacity of phenolic compounds plays a role in healthpromoting capacity (Mellor and Naumovski 2016). In fact, during periods of stress such as drought or sun exposure, many polyphenols produced by plants contribute to stress tolerance for animals that consume them. ...
Phytochemicals extracted from flowers, roots and bark, leaves, and other plant sources have been used extensively throughout human history with varying levels of efficacy in prevention and treatment of disease. Recently, advanced methods for characterization and clinical use of these materials have allowed modern understanding of their properties to be used as immunomodulatory agents that act by enhancement of endogenous cytoprotective mechanisms, avoiding interference with normal physiologic signaling and highly effective medical treatment with minimal adverse side effects. Simple methods have been identified for improving their biological effects, such as thermal conditioning by heating or freezing-prominent example being heat treatment of lycopene and tetrahydrocannabinol. The present investigation shows improvement of the ability of heat to augment splenocyte proliferation, natural killer (NK) cell activities, and antioxidant capacity of the flavonoid luteolin-7-O-β-glucoside (L7G) in comparison with the native (non heat-treated) molecule, while further demonstrating that both the native and the heat-treated variants exhibit comparable antioxidant properties, as evidenced by their effects in macrophages by inhibition of nitric oxide production and lysosomal enzyme activity in experiments that strengthen lysosomal membrane integrity. Outcomes of these studies suggest that heat-treated L7G shows promise for use in immunotherapy, including anti-cancer regimens, as shown by its improvement of NK cell cytotoxicity.
... antioxidant activity, flavonoid, heat processing, modelling, thermal stability 1 | I N T R O D U C T I O N Over the last few decades, epidemiological studies have shown that consuming fruit and vegetables rich in phenolic compounds leads to a general well-being of consumers (Tom as-Barber an, Ferreres, & Gil, 2000). These benefits have been attributed to phenolic compound properties, particularly antioxidant activity which plays a role in this health-promoting capacity (Mellor & Naumovski, 2016 ). Among phenolic compounds, flavonoids are the most studied class and much interest is focused on them. ...
The objective of this paper is on the one hand to study the effect of heat processing (30 to 130°C for 2 h) on the stability and antioxidant activity of six flavonoids (rutin, naringin, eriodictyol, mesquitol, luteolin, and luteolin 7-O glucoside), and on the other hand to establish the relation structure–activity–stability of these compounds. The dependency on temperature of the six kinetics was well described by the Arrhenius law and the main parameters provided by this model are determined and compared in this paper. Activation energies found were 107.3 kJ/mol for rutin, 100.6 for naringin, 33.3 for mesquitol, 68.2 for eriodictyol, 51.4 for luteolin, and 120 for luteolin 7-O-glucoside. The data collected showed that glycosylated flavonoids are more resistant than aglycon flavonoids to heat treatment. Moreover, it was also observed that despite the total degradation of some flavonoids, the treated solutions still have an antioxidant activity. Flavonoids are mainly consumed in processed foods. Thus, flavonoids often undergo heat processing. Knowing the thermal stability and the evolution of their antioxidant activity are particularly relevant in the field of food processing. The results of this study allow information to be collected on the relationship between heat stability-flavonoid structure and antioxidant activity. This information will be useful for the formulation of new food products or for the design of new food processes.
... antioxidant activity, flavonoid, heat processing, modelling, thermal stability 1 | I N T R O D U C T I O N Over the last few decades, epidemiological studies have shown that consuming fruit and vegetables rich in phenolic compounds leads to a general well-being of consumers (Tom as-Barber an, Ferreres, & Gil, 2000). These benefits have been attributed to phenolic compound properties, particularly antioxidant activity which plays a role in this health-promoting capacity (Mellor & Naumovski, 2016 ). Among phenolic compounds, flavonoids are the most studied class and much interest is focused on them. ...
The objective of this paper is to study the effect the light on the stability of 6 flavonoids with different structures under different oxygen amounts. The evolution of their antioxidant activity and the identification of degradation products were also investigated. The results obtained indicated that the kinetics of flavonoid degradation are not only influenced by the light intensity and the oxygen amount but also by the flavonoid structure. The 6 flavonoids can be ranked below according to their stability: naringin, eriodictyol then rutin, luteolin, luteolin-7-O-glucoside and mesquitol. The presence of a hydroxyl group in position 3 and a double bond C2-C3 decrease flavonoid stability. Moreover, it was also observed that despite the total degradation of some flavonoids, the treated solutions still have an antioxidant activity. The identification of the degraded products by LC–MS showed that the degradation pathways are different according to the flavonoid studied.
This study was conducted in order to optimize the extraction process of phenolic antioxidants in cocoa pods and to evaluate the effect of optimized extract and storage time on the oxidative stability of palm olein heated at 180 °C using response surface methodology (RSM). The optimization of the extraction process of cocoa pods antioxidants was done and the results showed that the total polyphenols of 153.51 mg GAE/g and scavenging activity of 100% were obtained under optimal conditions. Vanillic acid was the phenolic antioxidant detected in the optimized extract using HPLC‐DAD (diode array detector). Rancimat test showed this extract was efficient in delaying palm olein oxidation. To preserve quality of palm olein during heating at 180 °C, RSM concerning iodine value and thiobarbituric acid value proposes to supplement the oil with 2,000 ppm of cocoa pods extract during 1–7 days (03 hr heating cycle per day) of treatments.
Practical applications
To improve the oxidative stability and shelf‐life of vegetable oils, only few natural sources who are supposed to be safer than synthetic antioxidants have been authorized for industrial purpose (case of rosemary). Therefore, there is a strong rational to continue the search of new natural sources of antioxidants by screening plant materials. This study can be useful for the development of industrial extraction process of cocoa pods and its application as an ingredient to delay lipid oxidation in oils.
Non-alcoholic fatty liver disease (NAFLD) is a growing health problem around the world, especially in developed countries. NAFLD includes all cases of fatty liver disease from simple steatosis to cirrhosis, without excessive alcohol intake, use of steatogenic medication or hereditary disorders. Pathogenesis is associated with dietary high fat intake, decreased free fatty acid (FFA) oxidation, increased hepatic lipogenesis and lipolysis from the adipose tissue. These metabolic alterations contribute to the hepatic fat accumulation. Consequently, stimulated oxidative stress and inflammation play a major role in hepatocellular damage. Therefore, antioxidant and anti-inflammatory agents may have a role in the prevention of this disease. Carotenoids are potent antioxidant and anti-inflammatory micronutrients, which have been investigated in the prevention and treatment of NAFLD. The main sources of the carotenoids are fruits and vegetables. In this article we review the potential role and possible molecular mechanism of carotenoids in NAFLD.
Prospective cohort studies showed inverse associations between the intake of flavonoid-rich foods (cocoa and tea) and cardiovascular disease (CVD). Intervention studies showed protective effects on intermediate markers of CVD. This may be due to the protective effects of the flavonoids epicatechin (in cocoa and tea) and quercetin (in tea).
We investigated the effects of supplementation of pure epicatechin and quercetin on vascular function and cardiometabolic health.
Thirty-seven apparently healthy men and women aged 40-80 y with a systolic blood pressure (BP) between 125 and 160 mm Hg at screening were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. CVD risk factors were measured before and after 4 wk of daily flavonoid supplementation. Participants received (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 wk in random order. The primary outcome was the change in flow-mediated dilation from pre- to postintervention. Secondary outcomes included other markers of CVD risk and vascular function.
Epicatechin supplementation did not change flow-mediated dilation significantly (1.1% absolute; 95% CI: -0.1%, 2.3%; P = 0.07). Epicatechin supplementation improved fasting plasma insulin (Δ insulin: -1.46 mU/L; 95% CI: -2.74, -0.18 mU/L; P = 0.03) and insulin resistance (Δ homeostasis model assessment of insulin resistance: -0.38; 95% CI: -0.74, -0.01; P = 0.04) and had no effect on fasting plasma glucose. Epicatechin did not change BP (office BP and 24-h ambulatory BP), arterial stiffness, nitric oxide, endothelin 1, or blood lipid profile. Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors.
Our results suggest that epicatechin may in part contribute to the cardioprotective effects of cocoa and tea by improving insulin resistance. It is unlikely that quercetin plays an important role in the cardioprotective effects of tea. This study was registered at clinicaltrials.gov as NCT01691404.
© 2015 American Society for Nutrition.
The increasing incidence of diabetic cardiovascular disease in Africa calls for the search for proper pharmacologic elementsfor its management. This research therefore, focused on the modifying effect of aqueous cocoa powder extract on predictors of cardiovascular disease. Forty female Albino rats weighing 200-250g were divided into five groups made up of three aqueous cocoa powder (200mg/kg, 300mg/kg, 500mg/kg),diabetic untreated and normoglycemicgroups, each consisting of 8 rats. Diabetes was induced using 120mg/kg alloxan administered intraperitoneally into all the rats except the normoglycemiccontrol. Freshly prepared doses of aqueous cocoa powder were administered orally to the respective groups of diabetic rats once daily for 40 days in a constant volume. Fasting blood collected by cardiac puncture under diethyl ether anaesthesia was analysed for lipid profile, lipid peroxidation and cardiovascular biomarkers determined. The result showed a significant (p<0.05) low plasma malondialdehyde level, hypertriglyceridemia, low plasma level of LDLC; and non-significant (p>0.05) hypocholesterolemia and high plasma level of HDLC in all the rats given different doses of aqueous cocoa powder extract and glibenclamidein comparison to the diabetic untreated control. Also, there was a reduction in both the atherogenic and coronary risk indices following ingestion of the aqueous extract. These results suggest that aqueous cocoa powder extract ingestion modifies diabetic dyslipidemia, prevents lipid peroxidationand prevents cardiovascular disease in rat.
Recent evidence has indicated that flavanol consumption may have many health benefits in humans, including improved cognitive activities.
The aim was to evaluate the effect of flavanol consumption on cognitive performance in cognitively intact elderly subjects.
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).
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 r(2) = 0.1703, P < 0.0001).
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.
© 2015 American Society for Nutrition.
Adherence to the Mediterranean diet is associated with lower mortality in a general population but limited evidence exists on the effect of a Mediterranean diet on mortality in subjects with diabetes. We aim to examine the association between the Mediterranean diet and mortality in diabetic individuals.
Prospective cohort study on 1995 type 2 diabetic subjects recruited within the MOLI-SANI study. Methods: Food intake was recorded by the European Project Investigation into Cancer and Nutrition food frequency questionnaire. Adherence to the Mediterranean diet was appraised by the Greek Mediterranean diet score. Hazard ratios were calculated using multivariable Cox-proportional hazard models.
During follow-up (median 4.0 years), 109 all-cause including 51 cardiovascular deaths occurred. A 2-unit increase in Mediterranean diet score was associated with 37% (19%-51%) lower overall mortality. Data remained unchanged when restricted to those being on a hypoglycaemic diet or on antidiabetic drug treatment. A similar reduction was observed when cardiovascular mortality only was considered (hazard ratio = 0.66; 0.46-0.95). A Mediterranean diet-like pattern, originated from principal factor analysis, indicated a reduced risk of overall death (hazard ratio = 0.81; 0.62-1.07). The effect of Mediterranean diet score was mainly contributed by moderate alcohol drinking (14.7% in the reduction of the effect), high intake of cereals (12.2%), vegetables (5.8%) and reduced consumption of dairy and meat products (13.4% and 3.4% respectively).
The traditional Mediterranean diet was associated with reduced risk of both total and cardiovascular mortality in diabetic subjects, independently of the severity of the disease. Major contributions were offered by moderate alcohol intake, high consumption of cereals, fruits and nuts and reduced intake of dairy and meat products.
© The European Society of Cardiology 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
In recent years, there is growing evidence that polyphenols-rich natural products, like nutraceuticals and food supplements, may offer unique treatment modalities for various aspects of type 2 diabetes mellitus (T2DM), due to their biological properties. Therefore, research is now focused on potential efficacy of different types of polyphenols, including phenolic acids, flavonoids, stilbenes, lignans and anthocyans. Animal and human studies showed that polyphenols modulate carbohydrate and lipid metabolism, decrease glycemia, atherogenic dyslipidemia and insulin resistance, improve adipose tissue metabolism, and modulate oxidative stress and inflammatory processes. It is relevant to understand the proper dose and duration of supplementation with polyphenols-rich extracts in order to guide effective therapeutic interventions in diabetic patients.
During the last years, the list of resveratrol effects has grown in parallel with the number of other members of the polyphenol family described to modulate glucose or lipid handling. In the same time, more than ten human studies on the influence of resveratrol supplementation on two related metabolic diseases, obesity and diabetes, have indicated that impressive beneficial effects co-exist with lack of demonstration of clinical relevance, irrespective of the daily dose ingested (0.075 to 1.5 g per capita) or the number of studied patients. Such contrasting observations have been proposed to depend on the degree of insulin resistance of the patients incorporated in the study. To date, no definitive conclusion can be drawn on the antidiabetic or antiobesity benefits of resveratrol. On the opposite, studies on animal models of diabesity consistently indicated that resveratrol impairs diverse insulin actions in adipocytes, blunting glucose transport, lipogenesis and adipogenesis. Since resveratrol also favours lipolysis and limits the production of proinflammatory adipokines, its administration in rodents results in limitation of fat deposition, activation of hexose uptake into muscle, improvement of insulin sensitivity, and facilitation of glucose disposal. Facing to a somewhat disappointing extrapolation to man of these promising antidiabetic and antiobesity properties, attention must be paid to re-examine resveratrol targets, especially those attainable after polyphenol ingestion and to re-define the responses to low doses. In this context, human adipocytes are proposed as a convenient model for the screening of "novel" polyphenols that can reproduce, outclass, or reinforce resveratrol metabolic actions, Moreover, the use of combination of polyphenols is proposed to treat diabesity complications in view of recently reported synergisms. Lastly, multidisciplinar approaches are recommended for future investigations, considering the wide range of polyphenol actions that induce body fat reduction, liver disease mitigation, muscle function improvement, cardiovascular and renal protection.
In the past couple of decades, evidence from prospective observational studies and clinical trials has converged to support the importance of individual nutrients, foods, and dietary patterns in the prevention and management of type 2 diabetes. The quality of dietary fats and carbohydrates consumed is more crucial than is the quantity of these macronutrients. Diets rich in wholegrains, fruits, vegetables, legumes, and nuts; moderate in alcohol consumption; and lower in refined grains, red or processed meats, and sugar-sweetened beverages have been shown to reduce the risk of diabetes and improve glycaemic control and blood lipids in patients with diabetes. With an emphasis on overall diet quality, several dietary patterns such as Mediterranean, low glycaemic index, moderately low carbohydrate, and vegetarian diets can be tailored to personal and cultural food preferences and appropriate calorie needs for weight control and diabetes prevention and management. Although much progress has been made in development and implementation of evidence-based nutrition recommendations in developed countries, concerted worldwide efforts and policies are warranted to alleviate regional disparities.
Background and aim: Altered glucose metabolism, oxidative stress, lipid levels and inflammatory markers are important risk factors in diabetes, cardiovascular, and many other diseases. Cocoa has been shown to exert antioxidant and anti-inflammatory effects. The aim of this study is twofold: to assess the effect of Cocoa on the lipid profile and peroxidation in addition to the inflammatory markers in type 2 diabetic patients, and to represent a virtual model of probable action mechanism of observed clinical effects of Cocoa consumption using in silico analysis and bioinformatics data.Materials and methods: One hundred subjects with type 2 diabetes were included in a randomized clinical control trial. Fifty treatment subjects received 10 grams cocoa powder and 10 grams milk powder dissolved in 250 ml of boiling water, and the other fifty control subjects received only 10 grams milk powder dissolved in 250 ml boiling water. Both groups were on the mentioned regimen twice daily for 6 weeks. Blood samples were obtained prior to Cocoa consumption and 6 weeks after intervention. Serum lipids and lipoproteins profile, malondialdehyde and inflammatory markers including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and high sensitive C-reactive protein (hs-CRP) were measured. For statistical analysis two independent and paired samples t-test and linear regression were used. Bioinformatics and virtual analysis were performed using string data base and Molegro virtual software.
Cocoa consumption lowered blood cholesterol,triglyceride, LDL-cholesterol, and TNF-alpha, hs-CRP, IL-6 significantly (P < 0.01). The results showed that the levels of HDL-cholesterol decreased significantly (P < 0.05) but Cocoa inhibited lipid peroxidation in treatment group than control group (P < 0.0001). Virtual analysis showed that the most frequent Cocoa ingredients, (+)-Catechin and (-)-Epicatechin, can dock to the enzyme COX-2.
These data support the beneficial effect of Cocoa on the lipid peroxidation prevention and inflammatory markers in type 2 diabetic patients. Cocoa ingredients block the Cox-2 activation and reduce inflammatory prostanoids synthesis according to virtual analysis.
The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship. Less is known about the effects of cocoa/chocolate on the augmentation index (AI), a measure of vascular stiffness and vascular tone in the peripheral arterioles. We enrolled thirty middle-aged, overweight adults in a randomised, placebo-controlled, 4-week, cross-over study. During the active treatment (cocoa) period, the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage (total cocoa = 22 g/d, total flavanols (TF) = 814 mg/d). Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar (TF = 3 mg/d). Treatments were matched for total fat, saturated fat, carbohydrates and protein. The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6 % (+2 mm) and basal blood flow volume by 22 %. Substantial decreases in the AI, a measure of arterial stiffness, were observed in only women. Flow-mediated dilation and the reactive hyperaemia index remained unchanged. The consumption of cocoa had no effect on fasting blood measures, while the control treatment increased fasting insulin concentration and insulin resistance (P= 0·01). Fasting blood pressure (BP) remained unchanged, although the acute consumption of cocoa increased resting BP by 4 mmHg. In summary, the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women.
There is no standard meal plan or eating pattern that works universally for all people with diabetes (1). In order to be effective, nutrition therapy should be individualized for each patient/client based on his or her individual health goals; personal and cultural preferences (241,242); health literacy and numeracy (243,244); access to healthful choices (245,246); and readiness, willingness, and ability to change. Nutrition interventions should emphasize a variety of minimally processed nutrientdense foods in appropriate portion sizes as part of a healthful eating pattern and provide the individual with diabetes with practical tools for day-to-day food plan and behavior change that can be maintained over the long term.
Diabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress-induced degenerative and age-related diseases. Flavonoids constitute an important part of the human diet; they can be found in most plant foods, including green tea, grapes or cocoa and possess multiple biological activities. This study investigates the chemo-protective effect of a cocoa phenolic extract (CPE) containing mainly flavonoids against oxidative stress induced by tert-butylhydroperoxide (t-BOOH) on Ins-1E pancreatic beta cells. Cell viability and oxidative status were evaluated. Ins-1E cells treatment with 5-20 μg/mL CPE for 20 h evoked no cell damage and did not alter ROS production. Addition of 50 μM t-BOOH for 2 h increased ROS and carbonyl groups content and decreased reduced glutathione level. Pre-treatment of cells with CPE significantly prevented the t-BOOH-induced ROS and carbonyl groups and returned antioxidant defences to adequate levels. Thus, Ins-1E cells treated with CPE showed a remarkable recovery of cell viability damaged by t-BOOH, indicating that integrity of surviving machineries in the CPE-treated cells was notably protected against the oxidative insult.
Cocoa products present great health potential due to their high content of polyphenols, mainly of flavanols. However, the antioxidant, anti-inflammatory and other health effects of regularly consuming cocoa products seem to depend on the intake and health status of the consumer, etc. and need to be further clarified. A randomised, controlled, cross-over, free-living study was carried out in healthy (n 24) and moderately hypercholesterolaemic (>2000 mg/l, n 20) subjects to assess the influence of regularly consuming (4 weeks) two servings (15 g each) of a cocoa product rich in fibre (containing 33·9 % of total dietary fibre (TDF) and 13·9 mg/g of soluble polyphenols) in milk v. consuming only milk (control) on (1) serum lipid and lipoprotein profile, (2) serum malondialdehyde levels, carbonyl groups, ferric reducing/antioxidant power, oxygen radical absorbance capacity and free radical-scavenging capacity, (3) IL-1β, IL-6, TNF-α, IL-10, IL-8, monocyte chemoattractant protein-1, and vascular and intracellular cell adhesion molecule levels, and (4) systolic and diastolic blood pressure and heart rate. Throughout the study, the diet and physical activity of the volunteers, as well as any possible changes in weight or other anthropometric parameters, were also evaluated. The intake of TDF increased (P< 0·001) to the recommended levels. Serum HDL-cholesterol (HDL-C) levels were increased (P< 0·001), whereas glucose (P= 0·029), IL-1β (P= 0·001) and IL-10 (P= 0·001) levels were decreased. The rest of the studied cardiovascular parameters, as well as the anthropometric ones, remained similar. In conclusion, regularly consuming a cocoa product with milk improves cardiovascular health by increasing HDL-C levels and inducing hypoglycaemic and anti-inflammatory effects in healthy and hypercholesterolaemic individuals without causing weight gain.
Treatment with diet alone, insulin, sulfonylurea, or metformin is known to improve glycemia in patients with type 2 diabetes mellitus, but which treatment most frequently attains target fasting plasma glucose (FPG) concentration of less than 7.8 mmol/L (140 mg/dL) or glycosylated hemoglobin A1c (HbA1c) below 7% is unknown.
To assess how often each therapy can achieve the glycemic control target levels set by the American Diabetes Association.
Randomized controlled trial conducted between 1977 and 1997. Patients were recruited between 1977 and 1991 and were followed up every 3 months for 3, 6, and 9 years after enrollment.
Outpatient diabetes clinics in 15 UK hospitals.
A total of 4075 patients newly diagnosed as having type 2 diabetes ranged in age between 25 and 65 years and had a median (interquartile range) FPG concentration of 11.5 (9.0-14.4) mmol/L [207 (162-259) mg/dL], HbA1c levels of 9.1% (7.5%-10.7%), and a mean (SD) body mass index of 29 (6) kg/m2.
After 3 months on a low-fat, high-carbohydrate, high-fiber diet, patients were randomized to therapy with diet alone, insulin, sulfonylurea, or metformin.
Fasting plasma glucose and HbA1c levels, and the proportion of patients who achieved target levels below 7% HbA1c or less than 7.8 mmol/L (140 mg/dL) FPG at 3, 6, or 9 years following diagnosis.
The proportion of patients who maintained target glycemic levels declined markedly over 9 years of follow-up. After 9 years of monotherapy with diet, insulin, or sulfonylurea, 8%, 42%, and 24%, respectively, achieved FPG levels of less than 7.8 mmol/L (140 mg/dL) and 9%, 28%, and 24% achieved HbA1c levels below 7%. In obese patients randomized to metformin, 18% attained FPG levels of less than 7.8 mmol/L (140 mg/dL) and 13% attained HbA1c levels below 7%. Patients less likely to achieve target levels were younger, more obese, or more hyperglycemic than other patients.
Each therapeutic agent, as monotherapy, increased 2- to 3-fold the proportion of patients who attained HbA1c below 7% compared with diet alone. However, the progressive deterioration of diabetes control was such that after 3 years approximately 50% of patients could attain this goal with monotherapy, and by 9 years this declined to approximately 25%. The majority of patients need multiple therapies to attain these glycemic target levels in the longer term.
Background:
In healthy participants, short-term flavan-3-ol and isoflavone intakes improve vascular function; however, the potential combined benefit of these compounds on atherosclerosis progression remains unclear for those at elevated risk of cardiovascular disease.
Objective:
The objective was to examine whether combined isoflavone and flavan-3-ol intake alters vascular function in postmenopausal women with type 2 diabetes mellitus (T2DM).
Design:
A double-blind, parallel-design, placebo-controlled 1-y trial was conducted in postmenopausal T2DM patients randomly assigned to a split dose of 27 g flavonoid-enriched chocolate/d [850 mg flavan-3-ols (90 mg epicatechin) + 100 mg isoflavones (aglycone equivalents)/d] or matched placebo. Intima-media thickness of the common carotid artery (CCA-IMT), pulse wave velocity (PWV), augmentation index, blood pressure (BP), and vascular biomarkers were assessed.
Results:
A total of 93 patients completed the trial. Overall, the flavonoid intervention did not significantly change CCA-IMT, augmentation index, or BP, but pulse pressure variability improved (flavonoid: -0.11 ± 0.07 mm Hg/min; placebo: 0.10 ± 0.11 mm Hg/min; P = 0.04). In a subgroup with PWV data, net improvements were observed [flavonoid (n = 18): -0.07 ± 0.38 m/s; placebo (n = 17): 0.68 ± 0.25 m/s; P = 0.01], which equated to a 10% CV risk reduction. Equol producers (n = 17) had larger reductions in diastolic BP, mean arterial pressure, and PWV (-2.24 ± 1.31 mm Hg, -1.24 ± 1.30 mm Hg, and -0.68 ± 0.40 m/s, respectively; P < 0.01) compared with non-equol producers (n = 30).
Conclusions:
Although the 1-y intervention did not change CCA-IMT or BP, clinically relevant improvements in arterial stiffness were observed; equol producers were particularly responsive. Flavonoids may augment existing therapeutic strategies to reduce cardiovascular disease risk in postmenopausal T2DM patients, and longer studies are needed to examine the effects on atherosclerosis progression. This trial was registered at clinicaltrials.gov as NCT00677599.
Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD.
Recent epidemiological studies show that high intakes of carotenoids might be useful to maintain bone health, but little is known about the association of serum carotenoids with change of bone mineral density (BMD). The objective of this study was to investigate longitudinally whether serum carotenoids are associated with bone loss.
We conducted a follow-up on 146 male and 99 pre- and 212 post-menopausal female subjects from the Mikkabi study. Those who participated in previous BMD surveys and completed four years of follow-up were examined longitudinally.
During a 4-year follow-up, 15 of the post-menopausal female subjects developed new-onset osteoporosis. In contrast, none of the male and pre-menopausal female subjects did. In male and pre-menopausal female subjects, the six serum carotenoids at the baseline were not associated with bone loss. On the other hand, in post-menopausal female subjects, the 4-year bone loss of radius was inversely associated with the serum carotenoid concentrations, especially in β-carotene. After adjustments for confounders, the odds ratios (OR) for osteoporosis in the highest tertiles of serum β-carotene and β-cryptoxanthin against the lowest tertiles were 0.24 (95% confidence interval 0.05-1.21) and 0.07 (CI: 0.01-0.88), respectively. Serum β-cryptoxanthin was also inversely associated with the risk for osteopenia and/or osteoporosis (P for trend, 0.037). In addition, our retrospective analysis revealed that subjects who developed osteoporosis and/or osteopenia during the survey period had significantly lower serum concentrations of β-cryptoxanthin and β-carotene at the baseline than those in the normal group.
Antioxidant carotenoids, especially β-cryptoxanthin and β-carotene, are inversely associated with the change of radial BMD in post-menopausal female subjects.
Diabetes alters lipid metabolism that could lead to hepatic steatosis. The present study aimed to investigate the effect of a cocoa-enriched diet in type 2 diabetic Zucker diabetic fatty (ZDF) rats and that of cocoa-flavanol epicatechin (EC) in high-glucose-exposed HepG2 cells on hepatic lipid metabolism. Male ZDF cocoa-fed-rats had decreased body weight gain and improved circulating and hepatic lipid levels. Similarly, EC alleviated the altered lipid values induced in high-glucose-challenged HepG2 cells. The lipid-lowering effect was related to diminished fatty acid synthesis (sterol-regulatory-element-binding protein-1-c and fatty-acid synthase down-regulation), and increased fatty-acid oxidation (proliferator-activated-receptor α up-regulation). These effects depended on 5′-AMP-activated-protein-kinase (AMPK), protein kinase B (AKT) and protein kinase C (PKC)-ζ, which phosphorylated levels returned to control values upon cocoa or EC administration. Moreover, PKCζ played a role on AKT and AMPK regulation. These findings suggest that cocoa and EC protect hepatocytes in vivo and in vitro by improving lipid metabolism through multiple-signalling pathways.
The biological effects of antioxidant nutrients are mediated in part by activation of antioxidant response elements (AREs) on genes for enzymes involved in endogenous pathways that prevent free radical damage. Traditional approaches for identifying antioxidant molecules in foods, such as total phenolic compound (TP) content or oxygen radical absorption capacity (ORAC), do not measure capacity to activate AREs.
The goal of this study was to develop an assay to assess the ARE activation capacity of fruit and vegetable extracts and determine whether such capacity was predicted by TP content and/or ORAC activity.
Fruits and vegetables were homogenized, extracted with acidified ethanol, lyophilized, and resuspended in growth medium. Human IMR-32 neuroblastoma cells, transfected with an ARE-firefly luciferase reporter, were exposed to extracts for 5 h. Firefly luciferase was normalized to constitutively expressed Renilla luciferase with tertiary butylhydroquinone (tBHQ) as a positive control. TP content and ORAC activity were measured for each extract. Relations between TPs and ORAC and ARE activity were determined.
A total of 107 of 134 extracts tested significantly activated the ARE-luciferase reporter from 1.2- to 58-fold above that of the solvent control (P < 0.05) in human IMR-32 cells. ARE activity, TP content, and ORAC ranked higher in peels than in associated flesh. Despite this relation, ARE activity did not correlate with TP content (Spearman ρ = 0.05, P = 0.57) and only modestly but negatively correlated with ORAC (Spearman ρ = -0.24, P < 0.01). Many extracts activated the ARE more than predicted by the TP content or ORAC.
The ARE reporter assay identified many active fruit and vegetable extracts in human IMR-32 cells. There are components of fruits and vegetables that activate the ARE but are not phenolic compounds and are low in ORAC. The ARE-luciferase reporter assay is likely a better predictor of the antioxidant benefits of fruits and vegetables than TP or ORAC.
© 2015 American Society for Nutrition.
Insulin resistance is the primary characteristic of type 2 diabetes and results from insulin signaling defects. Cocoa has been shown to exert anti-diabetic effects by lowering glucose levels. However, the molecular mechanisms responsible for this preventive activity and whether cocoa exerts potential beneficial effects on the insulin signaling pathway in the liver remain largely unknown. Thus, in this study, the potential anti-diabetic properties of cocoa on glucose homeostasis and insulin signaling were evaluated in type 2 diabetic Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed a control or cocoa-rich diet (10%), and Zucker lean animals received the control diet. ZDF rats supplemented with cocoa (ZDF-Co) showed a significant decrease in body weight gain, glucose and insulin levels, as well as an improved glucose tolerance and insulin resistance. Cocoa-rich diet further ameliorated the hepatic insulin resistance by abolishing the increased serine-phosphorylated levels of the insulin receptor substrate 1 and preventing the inactivation of the glycogen synthase kinase 3/glycogen synthase pathway in the liver of cocoa-fed ZDF rats. The anti-hyperglycemic effect of cocoa appeared to be at least mediated through the decreased levels of hepatic phosphoenolpyruvate carboxykinase and increased values of glucokinase and glucose transporter 2 in the liver of ZDF-Co rats. Moreover, cocoa-rich diet suppressed c-Jun N-terminal kinase and p38 activation caused by insulin resistance. These findings suggest that cocoa has the potential to alleviate both hyperglycemia and hepatic insulin resistance in type 2 diabetic ZDF rats.
Copyright © 2015. Published by Elsevier Inc.
Polyphenols and other compounds found in cocoa and chocolate have therapeutic potential in the management of diabetes in humans. Polyphenols benefits have been proposed supported by in vitro studies, animal work and clinical trials, which have been conducted mostly in healthy volunteers. The energy dense formulations of many cocoa and chocolate products which can be up to 50% sugar by weight have given the perception that chocolate may be harmful through its contribution to obesity. A review of both clinical trial databases and published literature yielded 15 registered trials and seven published studies. The published data interventions reported are diverse vary widely in quality, including poor selection of control products or inadequate blinding procedures. There are also inconsistencies in reporting of data with limited information on the effect of cocoa and chocolate supplementation on weight and glycemic control despite the potential benefits reported with respect to the cardiovascular risk factors of endothelial function and lipids. More studies are required powered for primary clinical outcomes together with the development of standardized product formulations that optimize the dose of polyphenols within a palatable and energy restricted product.
The objective of this study was to examine the relationship between diet and inflammation, and adiposity in minority youth.
The study was designed as a cross-sectional analysis of 142 overweight (≥85th body mass index percentile) Hispanic and African-American adolescents (14-18 years) with the following measures: anthropometrics, adiposity via magnetic resonance imaging, dietary intake via 24-h dietary recalls, and inflammation markers from fasting blood draws utilizing a multiplex panel. Partial correlations were estimated and analysis of covariance (ancova) models fit to examine the relationship among dietary variables, inflammation markers and adiposity measures with the following a priori covariates: Tanner stage, ethnicity, sex, total energy intake, total body fat and total lean mass.
Inference based on ancova models showed that the highest tertile of fibre intake (mean intake of 21.3 ± 6.1 g d(-1) ) vs. the lowest tertile of fibre intake (mean intake of 7.4 ± 1.8 g d(-1) ) was associated with 36% lower plasminogen activator inhibitor-1 (P = 0.02) and 43% lower resistin (P = 0.02), independent of covariates. Similar results were seen for insoluble fibre. No other dietary variables included in this study were associated with inflammation markers.
These results suggest that increases in dietary fibre could play an important role in lowering inflammation and therefore metabolic disease risk in high-risk minority youth.
© 2015 World Obesity.
To test the widespread idea that chocolate is harmful in instances of acne vulgaris, 65 subjects with moderate acne ate either a bar containing ten times the amount of chocolate in a typical bar, or an identical-appearing bar which contained no chocolate. Counting of all the lesions on one side of the face before and after each ingestion period indicated no difference between the bars. Five normal subjects ingested two enriched chocolate bars daily for one month; this represented a daily addition of the diet of 1,200 calories, of which about half was vegetable fat. This excessive intake of chocolate and fat did not alter the composition or output of sebum. A review of studies purporting to show that diets high in carbohydrate or fat stimulate sebaceous secretion and adversely affect acne vulgaris indicates that these claims are unproved.
Cocoa (Theobroma cacao) is appreciated by its flavor and high content of bioactive compounds. A Brazilian Amazon Rainforest fruit, cupuassu (Theobroma grandiflorum), emerges as another Theobromaceae fruit with health potential. Here, we investigated the role of phenolic-rich extracts from cocoa and cupuassu liquors upon oxidative stress and metabolic changes associated with a high fat diet (HFD). The main flavonoids in cupuassu liquor extract were Hypolaetin-8-O-β-D-glucuronide and Hypolaetin − 3′ − methyl ether − 8 − O-β-D − glucuronide − 3”-O-sulfate, absent in cocoa liquor. Male Wistar rats received control diet or HFD for 16 weeks, and for the last 28 days some rats received by gavage cocoa or cupuassu liquor phenolic-rich extracts, at two doses. At the end of 16th week were evaluated the adiposity, liver function, lipid peroxidation, antioxidant capacity and enzyme activities. Both liquor extracts attenuated the liver damage associated to HFD by decreasing lipid peroxidation and increasing plasma and tissue antioxidant capacities. Notably, only cupuassu liquor phenolics were capable to improve glucose tolerance by increase insulin sensitivity.
Oxidative stress plays a main role in the pathogenesis of type 2 diabetes mellitus (T2DM). Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in T2DM because of their protective effects against oxidative stress and insulin-like properties. In this study, the protective effect of EC and a cocoa phenolic extract (CPE) against oxidative stress induced by a high glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells.
Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs), nuclear factor E2-related factor 2 (Nrf2) and p-(Ser)-IRS-1 expression, and glucose uptake were evaluated. EC and CPE regulated antioxidant enzymes and activated ERK and Nrf2. EC and CPE pre-treatment prevented high glucose-induced antioxidant defences and p-MAPKs, and maintained Nrf2 stimulation. The presence of selective MAPK inhibitors induced changes in redox status, glucose uptake, p-(Ser)- and total IRS-1 levels that were observed in CPE-mediated protection.
EC and CPE recovered redox status of insulin-resistant HepG2 cells, suggesting that the functionality in EC- and CPE-treated cells was protected against high glucose-induced oxidative insult. CPE beneficial effects on redox balance and insulin resistance were mediated by targeting MAPKs. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Diabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress-induced degenerative and age-related diseases. Flavonoids constitute an important part of the human diet; they can be found in most plant foods, including green tea, grapes or cocoa and possess multiple biological activities. This article summarizes the latest results obtained with a cocoa phenolic extract (CPE) and its main flavonoid component epicatechin (EC) in cell culture models of beta cells and hepatocytes. The effect of CPE and EC on cell integrity and redox status and their chemo-protective capacity against an oxidative stress induced by tert-butylhydroperoxide (t-BOOH) were tested on pancreatic beta cells as well as cell viability and first elements of the insulin signaling pathway were evaluated in hepatocytes. Doses of 1-20 mu g/mL CPE and 1-20 mu M EC, considered realistic, evoked no damage and preserved the redox status of cultured beta cells and hepatocytes. Treatment of beta cells with CPE/EC significantly prevented the t-BOOH-induced oxidative damage. Besides, treatment of hepatocytes with CPE/EC increased responsiveness to insulin and decreased glucose production. Thus, CPE and EC show favorable effects against a diabetic condition both in pancreatic and hepatic cells.
We have recently shown that cocoa flavanols may have anti-diabetic potential by promoting survival and function of pancreatic beta-cells in vitro. In this work, we investigated if a cocoa-rich diet is able to preserve beta-cell mass and function in an animal model of type 2 diabetes and the mechanisms involved. Our results showed that cocoa feeding during the pre-diabetic state attenuates hyperglycaemia, reduces insulin resistant and increases beta cell mass and function in obese Zucker diabetic (ZDF) rats. At the molecular level, cocoa-rich diet prevented beta-cell apoptosis by increasing the levels of Bcl-xL and decreasing Bax levels and caspase-3 activity. Cocoa diet enhanced the activity of endogenous antioxidant defenses, mainly glutathione peroxidase, preventing thus oxidative injury induced by the pre-diabetic condition and leading to apoptosis prevention. These findings provide the first in vivo evidence that a cocoa-rich diet may delay the loss of functional beta-cell mass and delay the progression of diabetes by preventing oxidative stress and beta-cell apoptosis. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Chronic hyperglycemia in diabetes is associated with oxidative stress-mediated tissue damage. The present study is aimed to explore the role of a cocoa-enriched diet in ameliorating the oxidative stress-induced damage in the liver of young type 2 diabetic Zucker Diabetic fatty (ZDF) rats. Male ZDF rats were fed a control or cocoa-rich diet (10%), and Zucker Lean (ZL) animals received the control diet. ZDF rats fed with cocoa (ZDF-Ca) decreased body weight gain, glucose and insulin levels, and improved glucose tolerance and insulin resistance. Cocoa diet further reduced reactive oxygen species (ROS) levels and carbonyl content in the liver of ZDF animals. The diminished activity of superoxide dismutase (SOD) and the enhanced activity of heme oxygenase (HO-1) in ZDF-C were returned to ZL values upon cocoa administration. Cocoa did not restore the decreased glutathione-S-transferase (GST) activity in both ZDF groups in comparison to ZL rats. Glutathione (GSH) content and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) remained unaltered among all animal groups. Moreover, cocoa-rich diet suppressed total and phosphorylated nuclear factor erythroid-derived 2-like 2 (Nrf2), as well as p65-nuclear factor-kappaB (NF-ĸB) enhanced levels observed in ZDF rats. The results indicate that cocoa protects the hepatocytes by improving the antioxidant competence in the liver of young type 2 diabetic ZDF rats.
Carotenoids may reduce diabetes risk, due to their antioxidant properties. However, the association between dietary carotenoids intake and type 2 diabetes risk is still unclear. Therefore, the objective of this study was to examine whether higher dietary carotenoid intakes associate with reduced type 2 diabetes risk.
Data from 37,846 participants of the European Prospective Investigation into Cancer and Nutrition- Netherlands study were analyzed. Dietary intakes of β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein & zeaxanthin and the sum of these carotenoids were assessed using a validated food frequency questionnaire. Incident type 2 diabetes was mainly self-reported, and verified against general practitioner information. Mean ±SD total carotenoid intake was 10 ± 4 mg/day. During a mean ±SD follow-up of 10 ± 2years, 915 incident cases of type 2 diabetes were ascertained. After adjustment for age, sex, diabetes risk factors, dietary intake, waist circumference and BMI, higher β-carotene intakes associated inversely with diabetes risk [Hazard Ratio quartile 4 versus quartile 1 (HRQ4): 0.78 (95%CI:0.64,0.95), P-linear trend 0.01]. For α-carotene, a borderline significant reduced risk was observed, with a HRQ4 of 0.85 (95%CI:0.70,1.03), and P-linear trend 0.05. β-cryptoxanthin, lycopene, lutein & zeaxanthin, and the sum of all carotenoids did not associate with diabetes risk.
This study shows that diets high in β-carotene and α-carotene are associated with reduced type 2 diabetes in generally healthy men and women.
Copyright © 2015 Elsevier B.V. All rights reserved.
Although there is growing interest surrounding the potential health benefits of cocoa and chocolate, the relative contribution of bioactive constituents for these effects remains unclear. This review summarizes the recent research on the cardiometabolic effects of cocoa and chocolate with a focus on two key constituents: flavan-3-ols and theobromine.
Recent meta-analyses suggest beneficial cardiometabolic effects of chocolate following short-term intake, including improvements in flow-mediated dilatation, blood pressure, lipoprotein levels and biomarkers of insulin resistance. Flavan-3-ols may play a role, but it is currently unclear which specific compounds or metabolites are key. Theobromine has also been shown to improve lipoprotein levels in trials, although these findings need verification at habitual intake levels. Longer term dose-response randomized controlled trials are required to determine the sustainability of the short-term effects and the optimal dose. Quantifying levels of bioactives in intervention products and their metabolites in biological samples will facilitate the assessment of their relative impact and the underlying mechanisms of action.
Promising data support the beneficial cardiometabolic effects of cocoa and chocolate intake, with significant interest in the flavan-3-ol and theobromine content. Validated biomarkers of intake together with more relevant mechanistic insights from experimental models using physiologically relevant concentrations and metabolites will continue to inform this research field.
Background:
Stroke risk is modifiable through many risk factors, one being healthy dietary habits. Fibre intake was associated with a reduced stroke risk in recent meta-analyses; however, data were contributed by relatively few studies, and few examined different stroke types.
Methods:
A total of 27,373 disease-free women were followed up for 14.4 years. Diet was assessed with a 217-item food frequency questionnaire and stroke cases were identified using English Hospital Episode Statistics and mortality records. Survival analysis was applied to assess the risk of total, ischaemic or haemorrhagic stroke in relation to fibre intake.
Results:
A total of 135 haemorrhagic and 184 ischaemic stroke cases were identified in addition to 138 cases where the stroke type was unknown or not recorded. Greater intake of total fibre, higher fibre density and greater soluble fibre, insoluble fibre and fibre from cereals were associated with a significantly lower risk for total stroke. For total stroke, the hazard ratio per 6 g/day total fibre intake was 0.89 (95% confidence intervals: 0.81-0.99). Different findings were observed for haemorrhagic and ischaemic stroke in healthy-weight or overweight women. Total fibre, insoluble fibre and cereal fibre were inversely associated with haemorrhagic stroke risk in overweight/obese participants, and in healthy-weight women greater cereal fibre was associated with a lower ischaemic stroke risk. In non-hypertensive women, higher fibre density was associated with lower ischaemic stroke risk.
Conclusions:
Greater total fibre and fibre from cereals are associated with a lower stroke risk, and associations were more consistent with ischaemic stroke. The different observations by stroke type, body mass index group or hypertensive status indicates potentially different mechanisms.
There is interest in the potential of cocoa flavanols, including monomers and procyanidins, to prevent obesity and type-2 diabetes. Fermentation and processing of cocoa beans influence the qualitative and quantitative profiles of individual cocoa constituents. Little is known regarding how different cocoa flavanols contribute to inhibition of obesity and type-2 diabetes. The objective of this study was to compare the impacts of long-term dietary exposure to cocoa flavanol monomers, oligomers and polymers on the effects of high-fat feeding. Mice were fed a high-fat diet supplemented with either a cocoa flavanol extract, or a flavanol fraction enriched with monomeric, oligomeric, or polymeric procyanidins for 12 weeks. The oligomer-rich fraction proved to be most effective in preventing weight gain, fat mass, impaired glucose tolerance, and insulin resistance in this model. This is the first long-term feeding study to examine the relative activities of cocoa constituents on diet-induced obesity and insulin resistance.
Metabolic syndrome is a condition of at least three of the cardiovascular risk factors: obesity, excessive visceral fat storage, dyslipidemia, hypertension and hyperglycaemia or Type 2 diabetes. It is a state of insulin resistance, oxidative stress and chronic inflammation. Cardiovascular disease is the highest cause of death globally. Certain dietary components and over 800 plants help prevent or moderate metabolic syndrome by assisting the body homeostasis mechanisms. This review compiles the most current studies on foods that help fight metabolic syndrome and the scientific evidences to support their use. This includes functional fats, digestive enzymes inhibitors, various beverages, different fruits, specific vegetables, grains, legumes, herbs and spices that can reduce cardiovascular disease risk, through several cellular mechanisms.
Diabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress-induced degenerative and age-related diseases. Flavonoids such as epicatechin (EC) constitute an important part of the human diet; they can be found in green tea, grapes, and cocoa and possess multiple biological activities. This study investigates the chemo-protective effect of EC against oxidative stress induced by tert-butylhydroperoxide (t-BOOH) on Ins-1E pancreatic beta cells.
Cell viability, oxidative status, phosphorylated Jun kinase (p-JNK) expression, and insulin secretion were evaluated. Ins-1E cells treatment with 5-20 μM EC for 20 h evoked no cell damage and enhanced antioxidant enzymes and insulin secretion. Addition of 50 μM t-BOOH for 2 h induced reactive oxygen species, p-JNK, and carbonyl groups and decreased GSH and insulin secretion. Pretreatment of cells with EC prevented the t-BOOH-induced reactive oxygen species, carbonyl groups, p-JNK expression and cell death, and recovered insulin secretion.
Ins-1E cells treated with EC showed a remarkable recovery of cell viability and insulin secretion damaged by t-BOOH, indicating that integrity of secreting and surviving machineries in the EC-treated cells was notably protected against the oxidative insult.
Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective destruction of pancreatic beta-cells. Although successful islet transplantation provides a promising treatment, high cost, lack of donor organs, immune-mediated destruction of transplanted islets, and side effects from immunosuppressive drugs greatly limit its uses. Therefore, the search for novel and cost-effective agents that can prevent or ameliorate T1D is extremely important to decrease the burden of T1D. In this study, we discovered that epicatechin (EC, 0.5% in drinking water), a flavonol primarily in cocoa, effectively prevented T1D in non-obese diabetic (NOD) mice. At 32 weeks of age, 66.7% control mice had overt diabetes, whereas only 16.6% EC-treated mice became diabetic. Consistently, EC mice had significantly higher plasma insulin levels but lower glycosylated hemoglobin concentrations compared to control mice. EC had no significant effects on food or water intake and body weight gain in NOD mice, suggesting that EC's effect was not due to alterations in these variables. Treatment with EC elevates circulating anti-inflammatory cytokine interleukin-10 levels, ameliorates pancreatic insulitis, and improved pancreatic islet mass. These findings demonstrate that EC may be a novel, plant-derived compound capable of preventing T1D by modulating immune function and thereby preserving islet mass.
Purpose:
To investigate the effect of cocoa powder supplementation on obesity-related inflammation in high fat (HF)-fed obese mice.
Methods:
Male C57BL/6J (n = 126) were fed with either low-fat (LF, 10 % kcal from fat) or HF (60 % kcal from fat) diet for 18 weeks. After 8 weeks, mice from HF group were randomized to HF diet or HF diet supplemented with 8 % cocoa powder (HF-HFC group) for 10 weeks. Blood and tissue samples were collected for biochemical analyses.
Results:
Cocoa powder supplementation significantly reduced the rate of body weight gain (15.8 %) and increased fecal lipid content (55.2 %) compared to HF-fed control mice. Further, cocoa supplementation attenuated insulin resistance, as indicated by improved HOMA-IR, and reduced the severity of obesity-related fatty liver disease (decreased plasma alanine aminotransferase and liver triglyceride) compared to HF group. Cocoa supplementation also significantly decreased plasma levels of the pro-inflammatory mediators interleukin-6 (IL-6, 30.4 %), monocyte chemoattractant protein-1 (MCP-1, 25.2 %), and increased adiponectin (33.7 %) compared to HF-fed mice. Expression of pro-inflammatory genes (Il6, Il12b, Nos2, and Emr1) in the stromal vascular fraction (SVF) of the epididymal white adipose tissue (WAT) was significantly reduced (37-56 %) in the cocoa-supplemented mice.
Conclusions:
Dietary supplementation with cocoa ameliorates obesity-related inflammation, insulin resistance, and fatty liver disease in HF-fed obese mice, principally through the down-regulation of pro-inflammatory gene expression in WAT. These effects appear to be mediated in part by a modulation of dietary fat absorption and inhibition of macrophage infiltration in WAT.
Background & aims:
Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of the Mediterranean diet (MD), a diet high in monounsaturated fatty acids, on steatosis and insulin sensitivity, using gold standard techniques.
Methods:
Twelve non-diabetic subjects (6 Females/6 Males) with biopsy-proven NAFLD were recruited for a randomised, cross-over 6-week dietary intervention study. All subjects undertook both the MD and a control diet, a low fat-high carbohydrate diet (LF/HCD), in random order with a 6-week wash-out period in- between. Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ((1)H-MRS).
Results:
At baseline, subjects were abdominally obese with elevated fasting concentrations of glucose, insulin, triglycerides, ALT, and GGT. Insulin sensitivity at baseline was low (M=2.7 ± 1.0 mg/kg/min(-1)). Mean weight loss was not different between the two diets (p=0.22). There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD: 39 ± 4% versus 7 ± 3%, as measured by (1)H-MRS (p=0.012). Insulin sensitivity improved with the MD, whereas after the LF/HCD there was no change (p=0.03 between diets).
Conclusions:
Even without weight loss, MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD, compared to current dietary advice. This diet should be further investigated in subjects with NAFLD.
Scope:
Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in diabetes, but the mechanism for their insulin-like effects remains unknown. In this study, the modulation of insulin signalling by EC and a cocoa phenolic extract (CPE) on hepatic HepG2 cells was investigated by analysing key proteins of the insulin pathways, namely insulin receptor, insulin receptor substrate (IRS) 1 and 2, PI3K/AKT and 5'-AMP-activated protein kinase (AMPK), as well as the levels of the glucose transporter GLUT-2 and the hepatic glucose production.
Methods and results:
EC and CPE enhanced the tyrosine phosphorylation and total insulin receptor, IRS-1 and IRS-2 levels and activated the PI3K/AKT pathway and AMPK in HepG2 cells. CPE also enhanced the levels of GLUT-2. Interestingly, EC and CPE modulated the expression of phosphoenolpyruvate carboxykinase, a key protein involved in the gluconeogenesis, leading to a diminished glucose production. In addition, EC- and CPE-regulated hepatic gluconeogenesis was prevented by the blockage of AKT and AMPK.
Conclusion:
Our data suggest that EC and CPE strengthen the insulin signalling by activating key proteins of that pathway and regulating glucose production through AKT and AMPK modulation in HepG2 cells.
Flavanol compounds in wine, cocoa products and tea can exert a cardioprotective effect, for example by influencing endothelial-cell function1, antithrombic mechanisms2 and blood pressure3, 4. Serafini et al.5 claim that consuming dark chocolate, but not milk chocolate or dark chocolate together with milk, increases the antioxidant capacity of human plasma, and suggest that interaction between milk proteins and chocolate flavonoids inhibits the in vivo antioxidant activity of chocolate and the absorption of epicatechin into the bloodstream. This inference could have implications beyond chocolate consumption if dairy products do indeed counteract the putative health benefits of dietary flavanols.
