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Carl L. Keen - One of the best experts on this subject based on the ideXlab platform.

  • dietary Flavanols a review of select effects on vascular function blood pressure and exercise performance
    Journal of The American College of Nutrition, 2018
    Co-Authors: Yousef A Aldashti, Roberta R Holt, Carl L. Keen, Charles L Stebbins, Robert M. Hackman
    Abstract:

    ABSTRACTAn individual's diet affects numerous physiological functions and can play an important role in reducing the risk of cardiovascular disease. Epidemiological and clinical studies suggest that dietary Flavanols can be an important modulator of vascular risk. Diets and plant extracts rich in Flavanols have been reported to lower blood pressure, especially in prehypertensive and hypertensive individuals. Flavanols may act in part through signaling pathways that affect vascular function, nitric oxide availability, and the release of endothelial-derived relaxing and constricting factors. During exercise, Flavanols have been reported to modulate metabolism and respiration (e.g., maximal oxygen uptake, O2 cost of exercise, and energy expenditure), and reduce oxidative stress and inflammation, resulting in increased skeletal muscle efficiency and endurance capacity. Flavanol-induced reductions in blood pressure during exercise may decrease the work of the heart. Collectively, these effects suggest that fla...

  • intake of dietary procyanidins does not contribute to the pool of circulating Flavanols in humans
    The American Journal of Clinical Nutrition, 2012
    Co-Authors: Javier I Ottaviani, Carl L. Keen, Catherine Kwikuribe, Hagen Schroeter
    Abstract:

    Background: Accumulating data show a causal role for Flavanols in the mediation of cardiovascular benefits associated with the consumption of flavanol- and procyanidin-containing foods. Evidence for a direct causal role for procyanidins in this context is far less profound due to the poor absorption of procyanidins. However, it has been proposed that procyanidins may break down in the gastrointestinal tract, resulting in monomeric Flavanols, which contribute to the systemic flavanol pool. Verification or rejection of this supposition could significantly affect the interpretation of epidemiologic and dietary intervention data and the design of food-content databases. Objective: We assessed the respective contribution of Flavanols and procyanidins to the systemic pool of Flavanols and 5-(3,4-dihydroxyphenyl)c-valerolactone (c-VL) in humans. Design: Test drinks that contained only Flavanols (D1), procyanidins with a degree of polymerization that ranged from 2 to 10 (D2‐10), or Flavanols and procyanidins with a degree of polymerization that ranged from 2 to 10 (D1‐10) were consumed by humans (n =1 2) according to a randomized, double-masked, crossover design. Plasma and urine samples were collected postprandially and analyzed. Results: The ingestion of D1‐10 resulted in the systemic presence of Flavanols (plasma concentration: 863 6 77 nmol/L), c-VLs (24-h urine: 93 6 18 lmol), and minute concentrations of procyanidin B2. With correction for small residual amounts of Flavanols present in D2‐10, only negligible concentrations of circulating Flavanols were detected after ingestion of the drink, whereas the intake of D1 resulted in circulating flavanol concentrations similar to those detected after D1‐10 consumption. Conclusions: These outcomes show that dietary procyanidins do not contribute to the systemic pool of Flavanols in humans. Thus, these data reject the notion that procyanidins, through their breakdown into Flavanols and subsequent absorption, causally modulate vascular function. This trial was registered at clinicaltrials.gov as NCT01483508. Am J Clin Nutr doi: 10.3945/ajcn.111.028340.

  • the stereochemical configuration of Flavanols influences the level and metabolism of Flavanols in humans and their biological activity in vivo
    Free Radical Biology and Medicine, 2011
    Co-Authors: Javier I Ottaviani, Tony Y. Momma, Hagen Schroeter, Christian Heiss, Catherine Kwikuribe, Carl L. Keen
    Abstract:

    Abstract Extensive epidemiological and clinical evidence associates diets high in flavanol-containing foods with cardiovascular health benefits in humans. Catechin and epicatechin, the most common Flavanols in foods, are present in the diet in different enantiomeric forms. This study investigated the influence of the stereochemical configuration of Flavanols on their absorption, metabolism, and biological activity. Healthy adult males were asked to consume equal amounts of the stereochemically pure Flavanols (−)­epicatechin, (−)­catechin, (+)­catechin, and (+)­epicatechin (1.5 mg/kg bw) in a well-defined cocoa-based, dairy-containing drink matrix, and flavanol levels were subsequently determined in plasma and 24-h urine. The results obtained show that the stereochemical configuration of Flavanols has a profound influence on their uptake and metabolism in humans. In addition, we assessed the vasodilatory activity of each flavanol stereoisomer in vivo and found (−)-epicatechin to be the single stereoisomer capable of mediating a significant arterial dilation response. Importantly, this effect was independent of the classic antioxidant properties of Flavanols. Overall, these results indicate that the proposed beneficial health effects associated with the consumption of flavanol-containing foods will significantly depend on the stereochemical configuration of the Flavanols ingested.

  • recommending Flavanols and procyanidins for cardiovascular health current knowledge and future needs
    Molecular Aspects of Medicine, 2010
    Co-Authors: Hagen Schroeter, Carl L. Keen, Jeremy P. E. Spencer, Christian Heiss, Joanne R Lupton, Harold H Schmitz
    Abstract:

    Data on the potential health benefits of dietary Flavanols and procyanidins, especially in the context of cardiovascular health, are considerable and continue to accumulate. Significant progress has been made in flavanol analytics and the creation of phytonutrient-content food databases, and novel data emanated from epidemiological investigations as well as dietary intervention studies. However, a comprehensive understanding of the pharmacological properties of Flavanols and procyanidins, including their precise mechanisms of action in vivo, and a conclusive, consensus-based accreditation of a causal relationship between intake and health benefits in the context of primary and secondary cardiovascular disease prevention is still outstanding. Thus, the objective of this review is to identify and discuss key questions and gaps that will need to be addressed in order to conclusively demonstrate whether or not dietary Flavanols and procyanidins have a role in preventing, delaying the onset of, or treating cardiovascular diseases, and thus improving human life expectancy and quality of life.

  • Flavanols and cardiovascular disease prevention
    European Heart Journal, 2010
    Co-Authors: Christian Heiss, Carl L. Keen, Malte Kelm
    Abstract:

    Diet is a major lifestyle factor in the primary and secondary prevention of numerous chronic diseases, including myocardial infarction, stroke, and diabetes. Epidemiological studies suggest that the beneficial cardiovascular health effects of diets rich in fruits and vegetables are in part mediated by their flavonoid content, with particular benefits provided by one member of this family, the Flavanols. This concept is supported by findings from small-scale intervention studies with surrogate endpoints including endothelium-dependent vasodilation, blood pressure, platelet function, and glucose tolerance. Mechanistically, short-term effects on endothelium-dependent vasodilation following the consumption of flavanol-rich foods, as well as purified Flavanols, have been linked to an increased nitric oxide bioactivity in healthy humans, and those with increased cardiovascular risk. The critical biological target(s) for Flavanols have yet to be identified and the extent to which these acute results are important in the context of long-term human health is unknown. While Flavanols represent a promising class of food components with respect to their ability to lower cardiovascular risk the flavanol-rich foods used in many trials have been poorly defined with respect to their flavanol content and flavanol-isomer profile; several studies have lacked appropriate controls, and the long-term randomized controlled intervention trials with flavanol-rich foods are missing. Thus, while the literature regarding Flavanols and vascular health is encouraging, more in-depth and well-controlled clinical and experimental studies are needed to better define the potential protective vascular effects of these nutrients and their therapeutic value in cardiovascular medicine.

Andrew P. Neilson - One of the best experts on this subject based on the ideXlab platform.

  • mechanisms by which cocoa Flavanols improve metabolic syndrome and related disorders
    Journal of Nutritional Biochemistry, 2016
    Co-Authors: Karen M Strat, Matthew W. Hulver, Thomas J Rowley, Andrew T Smithson, Jeffery S Tessem, Brenda M Davy, Kevin P Davy, Andrew P. Neilson
    Abstract:

    Dietary administration of cocoa Flavanols may be an effective complementary strategy for alleviation or prevention of metabolic syndrome, particularly glucose intolerance. The complex flavanol composition of cocoa provides the ability to interact with a variety of molecules, thus allowing numerous opportunities to ameliorate metabolic diseases. These interactions likely occur primarily in the gastrointestinal tract, where native cocoa flavanol concentration is high. Flavanols may antagonize digestive enzymes and glucose transporters, causing a reduction in glucose excursion, which helps patients with metabolic disorders maintain glucose homeostasis. Unabsorbed Flavanols, and ones that undergo enterohepatic recycling, will proceed to the colon where they can exert prebiotic effects on the gut microbiota. Interactions with the gut microbiota may improve gut barrier function, resulting in attenuated endotoxin absorption. Cocoa may also positively influence insulin signaling, possibly by relieving insulin-signaling pathways from oxidative stress and inflammation and/or via a heightened incretin response. The purpose of this review is to explore the mechanisms that underlie these outcomes, critically review the current body of literature related to those mechanisms, explore the implications of these mechanisms for therapeutic utility, and identify emerging or needed areas of research that could advance our understanding of the mechanisms of action and therapeutic potential of cocoa Flavanols.

  • loss of native Flavanols during fermentation and roasting does not necessarily reduce digestive enzyme inhibiting bioactivities of cocoa
    Journal of Agricultural and Food Chemistry, 2016
    Co-Authors: Caroline Ryan, Liyun Ye, Sean F Okeefe, Weslie Khoo, Joshua D Lambert, Andrew P. Neilson
    Abstract:

    Polyphenol profiles and in vitro digestive enzyme inhibitory activities were compared between cocoa extracts from unfermented beans (UB), fermented beans (FB), unfermented liquor (UL), and fermented liquor (FL). Total polyphenols, total Flavanols, and individual Flavanols were significantly different between UB/FB and UL/FL. All extracts effectively inhibited α-glucosidase (lowest IC50 = 90.0 μg/mL, UL) and moderately inhibited α-amylase (lowest IC50 = 183 μg/mL, FL) and lipase (lowest IC25 = 65.5 μg/mL, FB). Our data suggest that fermentation does not reduce α-glucosidase inhibition, while roasting may enhance inhibition. For α-amylase, both fermentation and roasting improved inhibition. Finally, for lipase, both fermentation and roasting attenuated inhibition. Conclusive correlations between inhibition and mDP, total polyphenol, and flavanol contents were not found. Our data suggest that enzyme inhibition activities of cocoa are not uniformly reduced by polyphenol/flavanol losses during fermentation and...

  • Dietary Supplementation with Cocoa Flavanols Does Not Alter Colon Tissue Profiles of Native Flavanols and Their Microbial Metabolites Established during Habitual Dietary Exposure in C57BL/6J Mice
    Journal of Agricultural and Food Chemistry, 2014
    Co-Authors: Katheryn M. Goodrich, Melanie R. Dorenkott, Liyun Ye, Sean F. O'keefe, Matthew W. Hulver, Andrew P. Neilson
    Abstract:

    Metabolism of Flavanols (catechins, procyanidins) by gut microbiota has been extensively characterized. Comparatively little is known about accumulation of Flavanols and their metabolites in the colon tissues, particularly during chronic exposure to low doses. Mice were fed low doses of cocoa Flavanols for 12 weeks. Supplementation of the control diet with Flavanols did not increase colonic tissue accumulation of Flavanols nor microbial metabolites versus control. The type of cocoa Flavanols did not affect colonic tissue accumulation of native Flavanols or metabolites. Total phenolic content of the diets indicated that these results are not explained by background levels of undetected phenolics in the control diet. This is the longest known chronic flavanol feeding study to examine colonic tissue accumulation. Vast differences appear to exist between acute high doses and chronic low doses, to which gut microbiota and epithelium adapt. These results indicate that the fate of Flavanols in the colon during c...

  • oligomeric cocoa procyanidins possess enhanced bioactivity compared to monomeric and polymeric cocoa procyanidins for preventing the development of obesity insulin resistance and impaired glucose tolerance during high fat feeding
    Journal of Agricultural and Food Chemistry, 2014
    Co-Authors: Melanie R. Dorenkott, Katheryn M. Goodrich, Liyun Ye, Matthew W. Hulver, Laura E Griffin, Katherine A Thompsonwitrick, Gabrielle Fundaro, Joseph R Stevens, Sean F Okeefe, Andrew P. Neilson
    Abstract:

    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 ...

Javier I Ottaviani - One of the best experts on this subject based on the ideXlab platform.

  • reliable accessible and transferable method for the quantification of Flavanols and procyanidins in foodstuffs and dietary supplements
    Food & Function, 2020
    Co-Authors: Ugo Bussy, Javier I Ottaviani, Alan Crozier, Yusuf Olanrewaju, Gregory Hewitt, Nicholas Anderson, Catherine Kwikuribe
    Abstract:

    Flavanols and procyanidins are plant-derived bioactives that are receiving increasing attention because of their potential health benefits. Analytical tools that can accurately identify and reproducibly quantify these bioactives are critical to researchers for test material characterization, as well as to the food industry and regulators, notably for product labeling. However, the chemical complexity of procyanidins, and the absence of analytical standards have prevented the development of methods that could serve the needs of these different sectors. This report describes the development and validation of a reliable, accessible and transferable method for the quantification of flavanol monomers and procyanidins in cocoa-derived dietary supplements and foodstuffs. To accomplish this, Flavanols and procyandins from cocoa, one of the most studied dietary sources of these compounds, were used as a model system. To overcome limitations related to the absence of analytical standards, a cocoa extract was thoroughly characterized for use as a calibrant. It was then used in the development and validation of a method based on reliable and accessible instrumentation, namely HPLC coupled with fluorescence detection. The resulting method permitted the quantification of Flavanols and procyanidins in amounts ranging from 2 to 500 mg g−1, with high precision (%RSD 0.2 to 1.9%) and accuracy (100.7 to 102.9%). The method was successfully applied to assess the flavanol and procyanidin content of different cocoa-based commercial products. Furthermore, the high precision of the methods showed the feasibility of using principal component analysis of flavanol and procyanidin profiles to discriminate cocoa-derived products by origin and manufacturing processes. A feature that offers advantages in monitoring product authenticity/adulteration. Overall, these findings support the application of this method for the routine analysis of cocoa Flavanols and procyandins.

  • methylxanthines enhance the effects of cocoa Flavanols on cardiovascular function randomized double masked controlled studies
    The American Journal of Clinical Nutrition, 2017
    Co-Authors: Roberto Sansone, Jeremy P. E. Spencer, Javier I Ottaviani, Ana Rodriguezmateos, Yvonne Heinen, Dorina Noske, Alan Crozier, Marc W Merx, Malte Kelm
    Abstract:

    Background: Cocoa flavanol intake, especially that of (−)-epicatechin, has been linked to beneficial effects on human cardiovascular function. However, cocoa also contains the methylxanthines theobromine and caffeine, which may also affect vascular function. Objective: We sought to determine whether an interaction between cocoa Flavanols and methylxanthines exists that influences cocoa flavanol–dependent vascular effects. Design: Test drinks that contained various amounts of cocoa Flavanols (0–820 mg) and methylxanthines (0–220 mg), either together or individually, were consumed by healthy volunteers (n = 47) in 4 different clinical studies—3 with a randomized, double-masked crossover design and 1 with 4 parallel crossover studies. Vascular status was assessed by measuring flow-mediated vasodilation (FMD), brachial pulse wave velocity (bPWV), circulating angiogenic cells (CACs), and blood pressure before and 2 h after the ingestion of test drinks. Results: Although cocoa flavanol intake increased FMD 2 h after intake, the consumption of cocoa Flavanols with methylxanthines resulted in a greater enhancement of FMD. Methylxanthine intake alone did not result in statistically significant changes in FMD. Cocoa flavanol ingestion alone decreased bPWV and diastolic blood pressure and increased CACs. Each of these changes was more pronounced when cocoa Flavanols and methylxanthines were ingested together. It is important to note that the area under the curve of the plasma concentration of (−)-epicatechin metabolites over time was higher after the co-ingestion of cocoa Flavanols and methylxanthines than after the intake of cocoa Flavanols alone. Similar results were obtained when pure (−)-epicatechin and the methylxanthines theobromine and caffeine were consumed together. Conclusion: A substantial interaction between cocoa Flavanols and methylxanthines exists at the level of absorption, in which the methylxanthines mediate an increased plasma concentration of (−)-epicatechin metabolites that coincides with enhanced vascular effects commonly ascribed to cocoa flavanol intake. This trial was registered at clinicaltrials.gov as NCT02149238.

  • intake of dietary procyanidins does not contribute to the pool of circulating Flavanols in humans
    The American Journal of Clinical Nutrition, 2012
    Co-Authors: Javier I Ottaviani, Carl L. Keen, Catherine Kwikuribe, Hagen Schroeter
    Abstract:

    Background: Accumulating data show a causal role for Flavanols in the mediation of cardiovascular benefits associated with the consumption of flavanol- and procyanidin-containing foods. Evidence for a direct causal role for procyanidins in this context is far less profound due to the poor absorption of procyanidins. However, it has been proposed that procyanidins may break down in the gastrointestinal tract, resulting in monomeric Flavanols, which contribute to the systemic flavanol pool. Verification or rejection of this supposition could significantly affect the interpretation of epidemiologic and dietary intervention data and the design of food-content databases. Objective: We assessed the respective contribution of Flavanols and procyanidins to the systemic pool of Flavanols and 5-(3,4-dihydroxyphenyl)c-valerolactone (c-VL) in humans. Design: Test drinks that contained only Flavanols (D1), procyanidins with a degree of polymerization that ranged from 2 to 10 (D2‐10), or Flavanols and procyanidins with a degree of polymerization that ranged from 2 to 10 (D1‐10) were consumed by humans (n =1 2) according to a randomized, double-masked, crossover design. Plasma and urine samples were collected postprandially and analyzed. Results: The ingestion of D1‐10 resulted in the systemic presence of Flavanols (plasma concentration: 863 6 77 nmol/L), c-VLs (24-h urine: 93 6 18 lmol), and minute concentrations of procyanidin B2. With correction for small residual amounts of Flavanols present in D2‐10, only negligible concentrations of circulating Flavanols were detected after ingestion of the drink, whereas the intake of D1 resulted in circulating flavanol concentrations similar to those detected after D1‐10 consumption. Conclusions: These outcomes show that dietary procyanidins do not contribute to the systemic pool of Flavanols in humans. Thus, these data reject the notion that procyanidins, through their breakdown into Flavanols and subsequent absorption, causally modulate vascular function. This trial was registered at clinicaltrials.gov as NCT01483508. Am J Clin Nutr doi: 10.3945/ajcn.111.028340.

  • the stereochemical configuration of Flavanols influences the level and metabolism of Flavanols in humans and their biological activity in vivo
    Free Radical Biology and Medicine, 2011
    Co-Authors: Javier I Ottaviani, Tony Y. Momma, Hagen Schroeter, Christian Heiss, Catherine Kwikuribe, Carl L. Keen
    Abstract:

    Abstract Extensive epidemiological and clinical evidence associates diets high in flavanol-containing foods with cardiovascular health benefits in humans. Catechin and epicatechin, the most common Flavanols in foods, are present in the diet in different enantiomeric forms. This study investigated the influence of the stereochemical configuration of Flavanols on their absorption, metabolism, and biological activity. Healthy adult males were asked to consume equal amounts of the stereochemically pure Flavanols (−)­epicatechin, (−)­catechin, (+)­catechin, and (+)­epicatechin (1.5 mg/kg bw) in a well-defined cocoa-based, dairy-containing drink matrix, and flavanol levels were subsequently determined in plasma and 24-h urine. The results obtained show that the stereochemical configuration of Flavanols has a profound influence on their uptake and metabolism in humans. In addition, we assessed the vasodilatory activity of each flavanol stereoisomer in vivo and found (−)-epicatechin to be the single stereoisomer capable of mediating a significant arterial dilation response. Importantly, this effect was independent of the classic antioxidant properties of Flavanols. Overall, these results indicate that the proposed beneficial health effects associated with the consumption of flavanol-containing foods will significantly depend on the stereochemical configuration of the Flavanols ingested.

  • improvement of endothelial function with dietary Flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease
    Journal of the American College of Cardiology, 2010
    Co-Authors: Christian Heiss, Sarah Jahn, Melanie Taylor, Wendy May Real, Franca S Angeli, Maelene L Wong, Nicolas Amabile, Megha Prasad, Tienush Rassaf, Javier I Ottaviani
    Abstract:

    Objectives In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs). Background Dietary Flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function. Methods In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64 ± 3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days. Results Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: −4.2 ± 2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74 ± 32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs. Conclusions Sustained improvements in endothelial dysfunction by regular dietary intake of Flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; [NCT00553774][1]). [1]: http://www.clinicaltrials.gov/ct2/show/NCT00553774%3Fterm%3DNCT00553774%26rank%3D1

Jeremy P. E. Spencer - One of the best experts on this subject based on the ideXlab platform.

  • methylxanthines enhance the effects of cocoa Flavanols on cardiovascular function randomized double masked controlled studies
    The American Journal of Clinical Nutrition, 2017
    Co-Authors: Roberto Sansone, Jeremy P. E. Spencer, Javier I Ottaviani, Ana Rodriguezmateos, Yvonne Heinen, Dorina Noske, Alan Crozier, Marc W Merx, Malte Kelm
    Abstract:

    Background: Cocoa flavanol intake, especially that of (−)-epicatechin, has been linked to beneficial effects on human cardiovascular function. However, cocoa also contains the methylxanthines theobromine and caffeine, which may also affect vascular function. Objective: We sought to determine whether an interaction between cocoa Flavanols and methylxanthines exists that influences cocoa flavanol–dependent vascular effects. Design: Test drinks that contained various amounts of cocoa Flavanols (0–820 mg) and methylxanthines (0–220 mg), either together or individually, were consumed by healthy volunteers (n = 47) in 4 different clinical studies—3 with a randomized, double-masked crossover design and 1 with 4 parallel crossover studies. Vascular status was assessed by measuring flow-mediated vasodilation (FMD), brachial pulse wave velocity (bPWV), circulating angiogenic cells (CACs), and blood pressure before and 2 h after the ingestion of test drinks. Results: Although cocoa flavanol intake increased FMD 2 h after intake, the consumption of cocoa Flavanols with methylxanthines resulted in a greater enhancement of FMD. Methylxanthine intake alone did not result in statistically significant changes in FMD. Cocoa flavanol ingestion alone decreased bPWV and diastolic blood pressure and increased CACs. Each of these changes was more pronounced when cocoa Flavanols and methylxanthines were ingested together. It is important to note that the area under the curve of the plasma concentration of (−)-epicatechin metabolites over time was higher after the co-ingestion of cocoa Flavanols and methylxanthines than after the intake of cocoa Flavanols alone. Similar results were obtained when pure (−)-epicatechin and the methylxanthines theobromine and caffeine were consumed together. Conclusion: A substantial interaction between cocoa Flavanols and methylxanthines exists at the level of absorption, in which the methylxanthines mediate an increased plasma concentration of (−)-epicatechin metabolites that coincides with enhanced vascular effects commonly ascribed to cocoa flavanol intake. This trial was registered at clinicaltrials.gov as NCT02149238.

  • Assessment of flavanol stereoisomers and caffeine and theobromine content in commercial chocolates.
    Food Chemistry, 2016
    Co-Authors: M.e. Alañón, Sophie M. Castle, P.j. Siswanto, Tania Cifuentes-gomez, Jeremy P. E. Spencer
    Abstract:

    Abstract Assessment of the flavanol composition of 41 commercial chocolates was by HPLC-DAD. Among individual flavonols ranged from 0.095 to 3.264 mg g −1 , epicatechin was the predominant flavanol accounting for 32.9%. Contrary to catechin, epicatechin was a reliable predictive value of the polyphenol content. Conversely the percentage of theobromine used as a proxy measure for nonfat cocoa solids (NFCS) was not a good predictor of epicatechin or flavanol content. In a further chiral analysis, the naturally occurring forms of cocoa Flavanols, (−)-epicatechin and (+)-catechin, was determined joint the occurrence of (+)-epicatechin and (−)-catechin due to the epimerization reactions produced in chocolate manufacture. (−)-Epicatechin, the most bioactive compound and predominant form accounted of 93%. However, no positive correlation was found with% cocoa solids, the most significant quality parameter.

  • The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial
    Psychopharmacology, 2015
    Co-Authors: Daniel J. Lamport, Jeremy P. E. Spencer, Christina Moutsiana, David T. Field, Claire M. Williams, Laurie T. Butler
    Abstract:

    Rationale There has recently been increasing interest in the potential of Flavanols, plant-derived compounds found in foods such as fruit and vegetables, to ameliorate age-related cognitive decline. Research suggests that cocoa Flavanols improve memory and learning, possibly as a result of their anti-inflammatory and neuroprotective effects. These effects may be mediated by increased cerebral blood flow (CBF), thus, stimulating neuronal function. Objectives The present study employed arterial spin labelling functional magnetic resonance imaging to explore the effect of a single acute dose of cocoa Flavanols on regional CBF. Methods CBF was measured pre- and post-consumption of low (23 mg) or high (494 mg) 330 ml equicaloric flavanol drinks matched for caffeine, theobromine, taste and appearance according to a randomized counterbalanced crossover double-blind design in eight males and ten females, aged 50–65 years. Changes in perfusion from pre- to post-consumption were calculated as a function of each drink. Results Significant increases in regional perfusion across the brain were observed following consumption of the high flavanol drink relative to the low flavanol drink, particularly in the anterior cingulate cortex and the central opercular cortex of the parietal lobe. Conclusions Consumption of cocoa flavanol improves regional cerebral perfusion in older adults. This provides evidence for a possible acute mechanism by which cocoa Flavanols are associated with benefits for cognitive performance.

  • factors affecting the absorption metabolism and excretion of cocoa Flavanols in humans
    Journal of Agricultural and Food Chemistry, 2015
    Co-Authors: Tania Cifuentesgomez, M.e. Alañón, Ana Rodriguezmateos, Isidro Gonzalezsalvador, Jeremy P. E. Spencer
    Abstract:

    Cocoa is rich in a subclass of flavonoids known as Flavanols, the cardiovascular health benefits of which have been extensively reported. The appearance of flavanol metabolites in the systemic circulation after flavanol-rich food consumption is likely to mediate the physiological effects on the vascular system, and these levels are influenced by numerous factors, including food matrix, processing, intake, age, gender, or genetic polymorphisms, among others. This review will focus on our current understanding of factors affecting the absorption, metabolism, and excretion of cocoa Flavanols in humans. Second, it will identify gaps in these contributing factors that need to be addressed to conclusively translate our collective knowledge into the context of public health, dietary guidelines, and evidence-based dietary recommendations.

  • influence of sugar type on the bioavailability of cocoa Flavanols
    British Journal of Nutrition, 2012
    Co-Authors: Ana Rodriguezmateos, M J Orunaconcha, Catherine L Kwikuribe, Alberto Vidal, Jeremy P. E. Spencer
    Abstract:

    The beneficial effects of cocoa on vascular function are mediated by the absorption of monomeric Flavanols into the circulation from the small intestine. As such, an understanding of the impact of the food matrix on the delivery of Flavanols to the circulation is critical in assessing the potential vascular impact of a food. In the present study, we investigated the impact of carbohydrate type on flavanol absorption and metabolism from chocolate. A randomised, double-blind, three-arm cross-over study was conducted, where fifteen volunteers were randomly assigned to either a high-flavanol (266 mg) chocolate containing maltitol, a high-flavanol (251 mg) chocolate with sucrose or a low-flavanol (48 mg) chocolate with sucrose. Test chocolates were matched for micro- and macronutrients, including the alkaloids theobromine and caffeine, and were similar in taste and appearance. Total flavanol absorption was lower after consumption of the maltitolcontaining test chocolate compared with following consumption of its sucrose-containing equivalent (P¼0·002). Although the O-methylation pattern observed for absorbed Flavanols was unaffected by sugar type, individual levels of unmethylated (2)-epicatechin metabolites, 3 0 -O-methyl-epicatechin and 4 0 -O-methyl-epicatechin metabolites were lower for the maltitol-containing test chocolate compared with the sucrose-containing equivalent. Despite a reduction in the total plasma pool of Flavanols, the maximum time (Tmax) was unaffected. The present data indicate that full assessment of intervention treatments is vital in future intervention trials with Flavanols and that carbohydrate content is an important determinant for the optimal delivery of Flavanols to the circulation.

Christian Heiss - One of the best experts on this subject based on the ideXlab platform.

  • the stereochemical configuration of Flavanols influences the level and metabolism of Flavanols in humans and their biological activity in vivo
    Free Radical Biology and Medicine, 2011
    Co-Authors: Javier I Ottaviani, Tony Y. Momma, Hagen Schroeter, Christian Heiss, Catherine Kwikuribe, Carl L. Keen
    Abstract:

    Abstract Extensive epidemiological and clinical evidence associates diets high in flavanol-containing foods with cardiovascular health benefits in humans. Catechin and epicatechin, the most common Flavanols in foods, are present in the diet in different enantiomeric forms. This study investigated the influence of the stereochemical configuration of Flavanols on their absorption, metabolism, and biological activity. Healthy adult males were asked to consume equal amounts of the stereochemically pure Flavanols (−)­epicatechin, (−)­catechin, (+)­catechin, and (+)­epicatechin (1.5 mg/kg bw) in a well-defined cocoa-based, dairy-containing drink matrix, and flavanol levels were subsequently determined in plasma and 24-h urine. The results obtained show that the stereochemical configuration of Flavanols has a profound influence on their uptake and metabolism in humans. In addition, we assessed the vasodilatory activity of each flavanol stereoisomer in vivo and found (−)-epicatechin to be the single stereoisomer capable of mediating a significant arterial dilation response. Importantly, this effect was independent of the classic antioxidant properties of Flavanols. Overall, these results indicate that the proposed beneficial health effects associated with the consumption of flavanol-containing foods will significantly depend on the stereochemical configuration of the Flavanols ingested.

  • recommending Flavanols and procyanidins for cardiovascular health current knowledge and future needs
    Molecular Aspects of Medicine, 2010
    Co-Authors: Hagen Schroeter, Carl L. Keen, Jeremy P. E. Spencer, Christian Heiss, Joanne R Lupton, Harold H Schmitz
    Abstract:

    Data on the potential health benefits of dietary Flavanols and procyanidins, especially in the context of cardiovascular health, are considerable and continue to accumulate. Significant progress has been made in flavanol analytics and the creation of phytonutrient-content food databases, and novel data emanated from epidemiological investigations as well as dietary intervention studies. However, a comprehensive understanding of the pharmacological properties of Flavanols and procyanidins, including their precise mechanisms of action in vivo, and a conclusive, consensus-based accreditation of a causal relationship between intake and health benefits in the context of primary and secondary cardiovascular disease prevention is still outstanding. Thus, the objective of this review is to identify and discuss key questions and gaps that will need to be addressed in order to conclusively demonstrate whether or not dietary Flavanols and procyanidins have a role in preventing, delaying the onset of, or treating cardiovascular diseases, and thus improving human life expectancy and quality of life.

  • Flavanols and cardiovascular disease prevention
    European Heart Journal, 2010
    Co-Authors: Christian Heiss, Carl L. Keen, Malte Kelm
    Abstract:

    Diet is a major lifestyle factor in the primary and secondary prevention of numerous chronic diseases, including myocardial infarction, stroke, and diabetes. Epidemiological studies suggest that the beneficial cardiovascular health effects of diets rich in fruits and vegetables are in part mediated by their flavonoid content, with particular benefits provided by one member of this family, the Flavanols. This concept is supported by findings from small-scale intervention studies with surrogate endpoints including endothelium-dependent vasodilation, blood pressure, platelet function, and glucose tolerance. Mechanistically, short-term effects on endothelium-dependent vasodilation following the consumption of flavanol-rich foods, as well as purified Flavanols, have been linked to an increased nitric oxide bioactivity in healthy humans, and those with increased cardiovascular risk. The critical biological target(s) for Flavanols have yet to be identified and the extent to which these acute results are important in the context of long-term human health is unknown. While Flavanols represent a promising class of food components with respect to their ability to lower cardiovascular risk the flavanol-rich foods used in many trials have been poorly defined with respect to their flavanol content and flavanol-isomer profile; several studies have lacked appropriate controls, and the long-term randomized controlled intervention trials with flavanol-rich foods are missing. Thus, while the literature regarding Flavanols and vascular health is encouraging, more in-depth and well-controlled clinical and experimental studies are needed to better define the potential protective vascular effects of these nutrients and their therapeutic value in cardiovascular medicine.

  • improvement of endothelial function with dietary Flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease
    Journal of the American College of Cardiology, 2010
    Co-Authors: Christian Heiss, Sarah Jahn, Melanie Taylor, Wendy May Real, Franca S Angeli, Maelene L Wong, Nicolas Amabile, Megha Prasad, Tienush Rassaf, Javier I Ottaviani
    Abstract:

    Objectives In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs). Background Dietary Flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function. Methods In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64 ± 3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days. Results Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: −4.2 ± 2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74 ± 32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs. Conclusions Sustained improvements in endothelial dysfunction by regular dietary intake of Flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; [NCT00553774][1]). [1]: http://www.clinicaltrials.gov/ct2/show/NCT00553774%3Fterm%3DNCT00553774%26rank%3D1

  • epicatechin mediates beneficial effects of flavanol rich cocoa on vascular function in humans
    Proceedings of the National Academy of Sciences of the United States of America, 2006
    Co-Authors: Hagen Schroeter, Petra Kleinbongard, Carl L. Keen, Helmut Sies, Christian Heiss, Catherine Kwikuribe, Norman K Hollenberg, Jan Balzer, Harold H Schmitz
    Abstract:

    Epidemiological and medical anthropological investigations suggest that flavanol-rich foods exert cardiovascular health benefits. Endothelial dysfunction, a prognostically relevant key event in atherosclerosis, is characterized by a decreased bioactivity of nitric oxide (NO) and impaired flow-mediated vasodilation (FMD). We show in healthy male adults that the ingestion of flavanol-rich cocoa was associated with acute elevations in levels of circulating NO species, an enhanced FMD response of conduit arteries, and an augmented microcirculation. In addition, the concentrations and the chemical profiles of circulating flavanol metabolites were determined, and multivariate regression analyses identified (–)-epicatechin and its metabolite, epicatechin-7-O-glucuronide, as independent predictors of the vascular effects after flavanol-rich cocoa ingestion. A mixture of Flavanols/metabolites, resembling the profile and concentration of circulating flavanol compounds in plasma after cocoa ingestion, induced a relaxation in preconstricted rabbit aortic rings ex vivo, thus mimicking acetylcholine-induced relaxations. Ex vivo flavanol-induced relaxation, as well as the in vivo increases in FMD, were abolished by inhibition of NO synthase. Oral administration of chemically pure (–)-epicatechin to humans closely emulated acute vascular effects of flavanol-rich cocoa. Finally, the concept that a chronic intake of high-flavanol diets is associated with prolonged, augmented NO synthesis is supported by data that indicate a correlation between the chronic consumption of a cocoa flavanol-rich diet and the augmented urinary excretion of NO metabolites. Collectively, our data demonstrate that the human ingestion of the flavanol (–)-epicatechin is, at least in part, causally linked to the reported vascular effects observed after the consumption of flavanol-rich cocoa.