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All Publications
Dec
2016
The American Journal of Clinical Nutrition
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...Jul
2016
Nature Scientific Reports
Diet is a major life style factor affecting human health, emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack...Dec
2015
Clinical Journal of the American Society of Nephrology
Background and objectives Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow–mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)–rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol–rich bioactive food ingredients on acute and chronic HD–induced...Nov
2015
The American Journal of Clinical Nutrition®
Background: Evidence from dietary intervention studies shows that the intake of flavanols and procyanidins can be beneficial for cardiovascular health. Nevertheless, there is a clear need for advancing our understanding with regard to safe amounts of intake for these bioactive. Objective: The aim was to investigate in healthy adults the effects of cocoa flavanol (CF) intake amount and intake duration on blood pressure, platelet function,...Jun
2015
British Journal of Nutrition
Cocoa flavanol (CF) intake improves endothelial function in patients with cardiovascular risk factors and disease. We investigated the effects of CF on surrogate markers of cardiovascular health in low risk, healthy, middle-aged individuals without history, signs or symptoms of CVD. In a 1-month, open-label, one-armed pilot study, bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function (measured as flow-...May
2015
AGE, the official journal of the American Aging Association
Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or...Apr
2015
Organic Letters
The first novel stereoselective synthesis of naturally occurring A1 (1) and A2 proanthocyanidins (2) has been achieved. The key synthetic steps involved (a) the formation of a coupled product (13 or 14) between an open chain C-ring C-4 hydroxyethoxy analogue of either (+)-catechin or (−)-epicatechin with 5,7,3′,3′-tetra-O-benzyl-(+)-catechin/-(−)-epicatechin in the presence of bentonite clay K-10, (b) removal of benzyl protecting groups under...Jan
2015
The American Journal of Clinical Nutrition
Background Recent evidence has indicated that flavanol consumption may have many health benefits in humans, including improved cognitive activities. Objective The aim was to evaluate the effect of flavanol consumption on cognitive performance in cognitively intact elderly subjects. Design This was a double-blind, controlled, parallel-arm study conducted in 90 elderly individuals without clinical evidence of cognitive dysfunction who...Oct
2014
Nature Neuroscience 17, 1798–1803 (2014)
The dentate gyrus (DG) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline. Causal evidence is needed, however, to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function. We addressed this issue by first using a high-resolution variant of functional...May
2013
J AOAC Int 2013, In press.
05/16/2013 - An AOAC expert review panel (ERP), chaired by James Harnly of the U.S. Department of Agriculture, granted First Action status to two methods for flavanols in foods. Methods were evaluated against standard method performance requirements (SMPRs) developed and approved through volunteer stakeholder consensus. On March 14, 2013, during the AOAC Mid-Year Meeting, the ERP agreed that the method, “Modification to OMA 2012.24 Analysis...Apr
2013
Tetrahedron: Asymmetry 2013, 24 (7), 362-373.
Ten orthogonally protected (−)-epicatechin and 3′- or 4′-O-methyl-(−)-epicatechin derivatives were prepared in a regiospecific and enantioselective manner. For each orthogonally protected (−)-epicatechin derivative, one specific phenolic hydroxyl was protected with a methoxymethyl (MOM) or p-methoxybenyzl (PMB) group and the remainder were protected as benzyl ethers. These uniquely protected (−)-epicatechin derivatives were designed to...Feb
2013
J Nat Prod 2013, 76 (2), 157-69.
The monoglucuronides and sulfates of epicatechin, 3′-O-methylepicatechin, and 4′-O-methylepicatechin, respectively, were synthesized as authentic bioanalytical standards. Reversed-phase HPLC methods capable of baseline separation of the glucuronides and sulfates have been developed. Both the epicatechin glucuronides and sulfates were stable in the solid state when stored under ambient conditions and in aqueous solution when stored refrigerated....Dec
2012
Br J Nutr 2012, 1-8. Br J Nutr. 2012 Dec 28;108(12):2243-50. doi: 10.1017/S0007114512000475. Epub 2012 Mar 7.
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...Sep
2012
Hypertension 2012, 60 (3), 794-801. 2012 Sep;60(3):794-801. doi: 10.1161/HYPERTENSIONAHA.112.193060. Epub 2012 Aug 14.
Flavanol consumption is favorably associated with cognitive function. We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment. We conducted a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing ≈990 mg (high flavanols), ≈520 mg (intermediate flavanols), or ≈45 mg (low flavanols...Mar
2012
Tetrahedron Letters 2012, 53 (12), 1501-1503.
A versatile new approach is reported for the total synthesis of five glucuronide metabolites of epicatechin, using selective protection/deprotection techniques. Graphical abstractMar
2012
J AOAC Int 2012, 95 (2), 500-7. J AOAC Int. 2012 Mar-Apr;95(2):500-7.
A single-laboratory validation study was performed for an HPLC method to identify and quantify the flavanol enantiomers (+)- and (-)-epicatechin and (+)- and (-)-catechin in cocoa-based ingredients and products. These compounds were eluted isocratically with an ammonium acetate-methanol mobile phase applied to a modified beta-cyclodextrin chiral stationary phase and detected using fluorescence. Spike recovery experiments using appropriate matrix...Feb
2012
American Journal of Clinical Nutrition 2012, 95 (4), 851-858. Am J Clin Nutr. 2012 Apr;95(4):851-8. doi: 10.3945/ajcn.111.028340. Epub 2012 Feb 29.
OBJECTIVE: We assessed the respective contribution of flavanols and procyanidins to the systemic pool of flavanols and 5-(3,4-dihydroxyphenyl)-γ-valerolactone (γ-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 subjects (n = 12)...Dec
2011
Free Radic Biol Med 2012, 52 (8), 1403-12. Free Radic Biol Med. 2012 Apr 15;52(8):1403-12. doi: 10.1016/j.freeradbiomed.2011.12.010. Epub 2011 Dec 23.
Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. Although recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn are largely...Sep
2011
J Food Sci 2011, 76 (7), C1010-7. J Food Sci. 2011 Sep;76(7):C1010-7. doi: 10.1111/j.1750-3841.2011.02322.x.
Cacao (Theobroma cacao L.) is rich in procyanidins, a large portion of which degrades during the natural fermentation process of producing cocoa powder. Recent advances in technology have enabled scientists to produce unfermented cocoa powder, preserving the original profile of procyanidins present in cocoa and allowing for the development of highly concentrated procyanidin-rich extracts. During this process, the anthocyanins naturally present...Jun
2011
J Agric Food Chem 2011, 59 (12), 6740-7. J Agric Food Chem. 2011 Jun 22;59(12):6740-7. doi: 10.1021/jf200993f. Epub 2011 May 23.
The physicochemical properties of acidified milk gels after the addition of cocoa flavanols were studied. As the flavanol level increased (from 0 to 2.5 mg/g), syneresis and gel elasticity (tan δ) were found to significantly increase and decrease, respectively. Flavanol addition reduced the stress at fracture, with no changes in fracture strain, suggesting that the bond type (i.e., covalent vs noncovalent) was the underlying factor explaining...Pages
Cardiovascular Publications
Dec
2016
The American Journal of Clinical Nutrition
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...Jul
2016
Nature Scientific Reports
Diet is a major life style factor affecting human health, emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack...Dec
2015
Clinical Journal of the American Society of Nephrology
Background and objectives Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow–mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)–rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol–rich bioactive food ingredients on acute and chronic HD–induced...Jun
2015
British Journal of Nutrition
Cocoa flavanol (CF) intake improves endothelial function in patients with cardiovascular risk factors and disease. We investigated the effects of CF on surrogate markers of cardiovascular health in low risk, healthy, middle-aged individuals without history, signs or symptoms of CVD. In a 1-month, open-label, one-armed pilot study, bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function (measured as flow-...May
2015
AGE, the official journal of the American Aging Association
Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or...Sep
2012
Hypertension 2012, 60 (3), 794-801. 2012 Sep;60(3):794-801. doi: 10.1161/HYPERTENSIONAHA.112.193060. Epub 2012 Aug 14.
Flavanol consumption is favorably associated with cognitive function. We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment. We conducted a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing ≈990 mg (high flavanols), ≈520 mg (intermediate flavanols), or ≈45 mg (low flavanols...Feb
2012
American Journal of Clinical Nutrition 2012, 95 (4), 851-858. Am J Clin Nutr. 2012 Apr;95(4):851-8. doi: 10.3945/ajcn.111.028340. Epub 2012 Feb 29.
OBJECTIVE: We assessed the respective contribution of flavanols and procyanidins to the systemic pool of flavanols and 5-(3,4-dihydroxyphenyl)-γ-valerolactone (γ-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 subjects (n = 12)...Dec
2010
Journal of Cerebral Blood Flow and Metabolism 2010, 30 (12), 1951-1961.
Epidemiologic studies have shown that foods rich in polyphenols, such as flavanols, can lower the risk of ischemic heart disease; however, the mechanism of protection has not been clearly established. In this study, we investigated whether epicatechin (EC), a flavanol in cocoa and tea, is protective against brain ischemic damage in mice. Wild-type mice pretreated orally with 5, 15, or 30 mg/kg EC before middle cerebral artery occlusion (MCAO)...Dec
2010
Mol Aspects Med 2010, 31 (6), 546-57
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...Sep
2010
J Hum Hypertens 2010, 24 (9), 568-76.
Consumption of flavanol-containing cocoa products has been shown to lower blood pressure (BP), but the minimum dose required to reduce BP is not known. This study aimed to examine the effect of three different doses of cocoa flavanols (CF) on 24-h mean arterial BP. Twenty four hour ambulatory BP (24-ABP) monitoring was performed in 32 men and 20 postmenopausal women with untreated mild hypertension (seated clinic BP >130/85 andJul
2010
J Am Coll Cardiol 2010, 56 (3), 218-24.
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...May
2010
Br J Nutr 2010, 103 (10), 1480-4.
Impaired endothelial vasodilatation may contribute to the exaggerated blood pressure (BP) responses to exercise in individuals who are overweight/obese. The present study investigated whether consumption of cocoa flavanols, which improve endothelium-dependent flow-mediated dilatation (FMD), can modify BP responsiveness to exercise. Twenty-one volunteers (eight females and thirteen males, 54.9 (se 2.2) years, BMI 31.6 (se 0.8) kg/m2, systolic BP...Feb
2009
J Med Food 2009, 12 (1), 1-7.
Flavanols and procyanidins isolated from cocoa have been reported to possess multiple activities potentially relevant to oxidant defenses, vascular function, and immune function. In a combination of in vivo and in vitro studies, we and others have observed that cocoa can be an anti-inflammatory modulator and that compounds in cocoa are capable of modulating eicosanoid production, platelet aggregation, and the pool size of nitric oxide. The...Aug
2008
Arch Biochem Biophys 2008, 476 (2), 211-5.
The availability of l-arginine can be a rate-limiting factor for cellular NO production by nitric oxide synthases (NOS). Arginase competes with NOS for l-arginine as the common substrate. Increasedarginase activity has been linked to low NO levels, and an inhibition of arginase activity has been reported to improve endothelium-dependent vasorelaxation. Based on the above, we hypothesized that an increase in the circulating NO pool following...Aug
2008
Int J Obes (Lond) 2008, 32 (8), 1289-96.
OBJECTIVE: Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals. DESIGN: Overweight and obese adults were randomly assigned to high-flavanol cocoa...Jun
2008
J Am Coll Cardiol 2008, 51 (22), 2141-9.
OBJECTIVES: Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients. BACKGROUND: Even in fully medicated diabetic patients, overall prognosis is unfavorable due to deteriorated cardiovascular function. Based on epidemiological data, diets rich in flavanols are associated with a reduced cardiovascular risk....Jan
2008
Asia Pac J Clin Nutr 2008, 17 Suppl 1, 284-7.
Epidemiologic investigations support the hypothesis that regular consumption of flavonoid-containing foods can reduce the risk of cardiovascular diseases (CVD). While flavonoids are ubiquitous in plants,cocoa can be particularly rich in a sub-class of flavonoids known as flavanols. A number of human dietary intervention trials with flavanol-containing cocoa products have demonstrated improvements in endothelial and platelet function, as well as...Feb
2007
J Cardiovasc Pharmacol 2007, 49 (2), 74-80.
A single-dose ingestion of flavanol-rich cocoa acutely reverses endothelial dysfunction. To investigate the time course of endothelial function during daily consumption of high-flavanol cocoa, we determined flow-mediated dilation (FMD) acutely (for up to 6 hours after single-dose ingestion) and chronically (administration for 7 days). The study population represented individuals with smoking-related endothelial dysfunction; in addition to FMD,...Jan
2007
Int J Med Sci 2007, 4 (1), 53-8.
Substantial data suggest that flavonoid-rich food could help prevent cardiovascular disease andcancer. Cocoa is the richest source of flavonoids, but current processing reduces the content substantially. The Kuna living in the San Blas drink a flavanol-rich cocoa as their main beverage, contributing more than 900 mg/day and thus probably have the most flavonoid-rich diet of any population. We used diagnosis on death certificates to compare cause...Oct
2006
Free Radic Biol Med 2006, 41 (8), 1247-56.
Procyanidins can exert cytoprotective, anti-inflammatory, and anticarcinogenic actions in the gastrointestinal tract. Previous evidence has shown that procyanidins can interact with synthetic membranes and protect them from oxidation and disruption. Thus, in this study we investigated the capacity of a hexameric procyanidin fraction (Hex) isolated from cocoa to protect Caco-2 cells from deoxycholic (DOC)-induced cytotoxicity, cell oxidant...Pages
Brain Health Publications
Jan
2015
The American Journal of Clinical Nutrition
Background Recent evidence has indicated that flavanol consumption may have many health benefits in humans, including improved cognitive activities. Objective The aim was to evaluate the effect of flavanol consumption on cognitive performance in cognitively intact elderly subjects. Design This was a double-blind, controlled, parallel-arm study conducted in 90 elderly individuals without clinical evidence of cognitive dysfunction who...Oct
2014
Nature Neuroscience 17, 1798–1803 (2014)
The dentate gyrus (DG) is a region in the hippocampal formation whose function declines in association with human aging and is therefore considered to be a possible source of age-related memory decline. Causal evidence is needed, however, to show that DG-associated memory decline in otherwise healthy elders can be improved by interventions that enhance DG function. We addressed this issue by first using a high-resolution variant of functional...Sep
2012
Hypertension 2012, 60 (3), 794-801. 2012 Sep;60(3):794-801. doi: 10.1161/HYPERTENSIONAHA.112.193060. Epub 2012 Aug 14.
Flavanol consumption is favorably associated with cognitive function. We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment. We conducted a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing ≈990 mg (high flavanols), ≈520 mg (intermediate flavanols), or ≈45 mg (low flavanols...Dec
2010
Journal of Cerebral Blood Flow and Metabolism 2010, 30 (12), 1951-1961.
Epidemiologic studies have shown that foods rich in polyphenols, such as flavanols, can lower the risk of ischemic heart disease; however, the mechanism of protection has not been clearly established. In this study, we investigated whether epicatechin (EC), a flavanol in cocoa and tea, is protective against brain ischemic damage in mice. Wild-type mice pretreated orally with 5, 15, or 30 mg/kg EC before middle cerebral artery occlusion (MCAO)...Oct
2010
J Psychopharmacol 2010, 24 (10), 1505-14.
Cocoa flavanols (CF) positively influence physiological processes in ways that suggest theirconsumption may improve aspects of cognitive function. This study investigated the acute cognitiveand subjective effects of CF consumption during sustained mental demand. In this randomized, controlled, double-blinded, balanced, three period crossover trial 30 healthy adults consumed drinks containing 520 mg, 994 mg CF and a matched control, with a three-...Apr
2008
Neuropsychiatr Dis Treat 2008, 4 (2), 433-40.
BACKGROUND AND PURPOSE: Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-richcocoa (FRC) consumption on cerebral blood flow in older healthy volunteers. METHODS: We used transcranial Doppler (TCD)...May
2007
J Neurosci 2007, 27 (22), 5869-78.
Diet and exercise have a profound impact on brain function. In particular, natural nutrients found in plants may influence neuronal survival and plasticity. Here, we tested whether consumption of aplant-derived flavanol, (-)epicatechin, enhances cognition in sedentary or wheel-running female C57BL/6 mice. Retention of spatial memory in the water maze was enhanced by ingestion of (-)epicatechin, especially in combination with exercise. Improved...Jan
2006
J Cardiovasc Pharmacol 2006, 47 Suppl 2, S210-4.
Foods and beverages rich in flavonoids are being heralded as potential preventive agents for a range of pathologic conditions, ranging from hypertension to coronary heart disease to stroke and dementia. We and others have demonstrated that short-term ingestion of cocoa, particularly rich in the subclass of flavonoids known as flavanols, induced a consistent and striking peripheral vasodilation in healthy people, improving endothelial function in...Jan
2006
J Cardiovasc Pharmacol 2006, 47 Suppl 2, S215-20.
Flavanols are the main flavonoids found in cocoa and chocolate, and can be especially abundant in certain cocoas. Research over the past decade has identified flavanols as showing diverse beneficial physiologic and antioxidant effects, particularly in context of vascular function. The present study employed functional magnetic resonance imaging based on blood oxygenation level-dependent (BOLD) contrast to explore the effect of flavanols on the...Oct
2002
Am J Clin Nutr 2002, 76 (4), 798-804.
BACKGROUND: Epidemiologic studies have linked flavonoid-rich foods with a reduced risk of cardiovascular mortality. Some cocoas are flavonoid-rich and contain the monomeric flavanols (-)-epicatechin and (+)-catechinand oligomeric procyanidins formed from these monomeric units. Both the monomers and the oligomers have shown potential in favorably influencing cardiovascular health in in vitro and preliminary clinical studies. Although previous...Biological Effects Publications
Dec
2016
The American Journal of Clinical Nutrition
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...Jul
2016
Nature Scientific Reports
Diet is a major life style factor affecting human health, emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack...Dec
2015
Clinical Journal of the American Society of Nephrology
Background and objectives Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow–mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)–rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol–rich bioactive food ingredients on acute and chronic HD–induced...Nov
2015
The American Journal of Clinical Nutrition®
Background: Evidence from dietary intervention studies shows that the intake of flavanols and procyanidins can be beneficial for cardiovascular health. Nevertheless, there is a clear need for advancing our understanding with regard to safe amounts of intake for these bioactive. Objective: The aim was to investigate in healthy adults the effects of cocoa flavanol (CF) intake amount and intake duration on blood pressure, platelet function,...May
2015
AGE, the official journal of the American Aging Association
Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or...Sep
2012
Hypertension 2012, 60 (3), 794-801. 2012 Sep;60(3):794-801. doi: 10.1161/HYPERTENSIONAHA.112.193060. Epub 2012 Aug 14.
Flavanol consumption is favorably associated with cognitive function. We tested the hypothesis that dietary flavanols might improve cognitive function in subjects with mild cognitive impairment. We conducted a double-blind, parallel arm study in 90 elderly individuals with mild cognitive impairment randomized to consume once daily for 8 weeks a drink containing ≈990 mg (high flavanols), ≈520 mg (intermediate flavanols), or ≈45 mg (low flavanols...Sep
2011
J Food Sci 2011, 76 (7), C1010-7. J Food Sci. 2011 Sep;76(7):C1010-7. doi: 10.1111/j.1750-3841.2011.02322.x.
Cacao (Theobroma cacao L.) is rich in procyanidins, a large portion of which degrades during the natural fermentation process of producing cocoa powder. Recent advances in technology have enabled scientists to produce unfermented cocoa powder, preserving the original profile of procyanidins present in cocoa and allowing for the development of highly concentrated procyanidin-rich extracts. During this process, the anthocyanins naturally present...Jan
2010
Exp Biol Med (Maywood) 2010, 235 (1), 77-89.
There is cumulative strong evidence that diets rich in flavanols can provide certain positive health benefits, particularly with respect to the cardiovascular system. Consequently, it has been suggested that increasing one's dietary intake of flavanols may be of benefit. Complicating this idea, there are reports that high intakes of certain flavonoids during pregnancy are associated with an increased riskfor acute infant leukemia due to a poison...Nov
2009
Biochem Pharmacol 2009, 78 (9), 1252-62
Given the central role of the transcription factor NF-kappaB in inflammation, molecules that can inhibit NF-kappaB are being actively investigated. The present work characterize potential interactions between dimeric procyanidins [B-type (B1 and B2) and A-type (A1 and A2)] and NF-kappaB proteins. B1 and B2, inhibited tumor necrosis factor alpha (TNFalpha)- and phorbol 12-myristate 13-acetate (PMA)-induced transactivation of NF-kappaB-driven...Dec
2008
J Nutr Biochem 2008, 19 (12), 797-808.
Flavanols, a class of polyphenols present in certain plant-based foods, have received increasing attention for their putative anticancer activity. In vitro and in vivo studies, which have compared the effectiveness of various monomer flavanols, indicate that the presence of a galloyl residue on the 3 position on the C-ring enhances the cytotoxicity of these compounds. Procyanidins, oligomerized flavanols, have been reported to be more cytotoxic...Aug
2008
Int J Obes (Lond) 2008, 32 (8), 1289-96.
OBJECTIVE: Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals. DESIGN: Overweight and obese adults were randomly assigned to high-flavanol cocoa...Jun
2008
J Am Coll Cardiol 2008, 51 (22), 2141-9.
OBJECTIVES: Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients. BACKGROUND: Even in fully medicated diabetic patients, overall prognosis is unfavorable due to deteriorated cardiovascular function. Based on epidemiological data, diets rich in flavanols are associated with a reduced cardiovascular risk....Jun
2008
Cell Cycle 2008, 7 (11), 1648-57.
Cocoa-derived flavanols and procyanidins have been previously reported to exhibit anti-oxidant and anti-tumor properties. In this study, we have investigated the cellular growth inhibitory effect of chemically-synthesized procyanidin [3-O-galloyl]-(-)-epicatechin-(4beta,8)-(+)-catechin-3-O-gallate (GECGC) on a variety of human cancer cell lines. Among 16 human cancer cell lines tested, GECGC selectively inhibited proliferation of a subset of...Apr
2008
Neuropsychiatr Dis Treat 2008, 4 (2), 433-40.
BACKGROUND AND PURPOSE: Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-richcocoa (FRC) consumption on cerebral blood flow in older healthy volunteers. METHODS: We used transcranial Doppler (TCD)...Apr
2008
J Nutr 2008, 138 (4), 725-31.
Previous studies with plant sterols (PS) and cocoa flavanols (CF) provide support for their dietary use in maintaining cardiovascular health. This double-blind, placebo-controlled, cross-over study evaluated the efficacy of daily consumption of a cocoa flavanol-containing dark chocolate bar with added PS on serum lipids, blood pressure, and other circulating cardiovascular health markers in a population with elevated serum cholesterol. We...Apr
2008
Apr 1 2008
Due to long-term toxicity of current Hodgkin's lymphoma (HL) treatment, the present challenge is to find new therapies that specifically target deregulated signaling cascades, including NF-kappaB, which are involved in Hodgkin (H) and Reed-Sternberg (RS) cell proliferation and resistance to apoptosis. We previously presented evidence that dimeric procyanidin B2 (B2) can interact with NF-kappaB proteins inhibiting the binding of NF-kappaB to DNA...Feb
2007
Eur J Nutr 2007, 46 (1), 53-6.
BACKGROUND: Long term cocoa ingestion leads to an increased resistance against UV-induced erythema and a lowered transepidermal water loss. AIM OF THE STUDY: To investigate the acute effects of a single dose of cocoa rich in flavanols on dermal microcirculation. METHODS: In a crossover design study, 10 healthy women ingested a cocoa drink (100 ml) with high (329 mg) or low (27 mg) content of flavanols. The major flavanol monomer in both...Nov
2006
J Am Diet Assoc 2006, 106 (11), 1804-13.
BACKGROUND: Dietary intervention studies incorporating phytosterol-enriched margarine spreads have reported significant decreases in total and low-density lipoprotein (LDL) cholesterol in populations with both normal lipid levels and those with hypercholesterolemia. There is emerging support for more diverse and lower-fat phytosterol-enriched matrixes. Controversy exists, however, over whether phytosterol-enriched foods affect serum fat-soluble...Aug
2006
Eur J Oral Sci 2006, 114 (4), 343-8.
The aim of this study was to determine if cocoa polyphenols could interfere with biofilm formation byStreptococcus mutans or Streptococcus sanguinis, and reduce acid production from sucrose by S.mutans. The antimicrobial activity of cocoa polyphenols was assessed against cariogenic (S. mutans) and health-associated (S. sanguinis) species by minimum inhibitory concentration assays. Cocoapolyphenol dimer, tetramer, and pentamer inhibited the...Aug
2006
J Hypertens 2006, 24 (8), 1575-80.
OBJECTIVES: Strong evidence has secured aging as a powerful predictor of both cardiovascular risk and endothelial dysfunction, yet specific treatment is not available. We tested the hypothesis thatvascular responsiveness to flavanol-rich cocoa increases with advancing age. We have previously shown that flavanol-rich cocoa induced peripheral vasodilation, improving endothelial function via a nitric oxide (NO)-dependent mechanism. METHODS: We...Pages
Chemistry Publications
Apr
2015
Organic Letters
The first novel stereoselective synthesis of naturally occurring A1 (1) and A2 proanthocyanidins (2) has been achieved. The key synthetic steps involved (a) the formation of a coupled product (13 or 14) between an open chain C-ring C-4 hydroxyethoxy analogue of either (+)-catechin or (−)-epicatechin with 5,7,3′,3′-tetra-O-benzyl-(+)-catechin/-(−)-epicatechin in the presence of bentonite clay K-10, (b) removal of benzyl protecting groups under...Apr
2013
Tetrahedron: Asymmetry 2013, 24 (7), 362-373.
Ten orthogonally protected (−)-epicatechin and 3′- or 4′-O-methyl-(−)-epicatechin derivatives were prepared in a regiospecific and enantioselective manner. For each orthogonally protected (−)-epicatechin derivative, one specific phenolic hydroxyl was protected with a methoxymethyl (MOM) or p-methoxybenyzl (PMB) group and the remainder were protected as benzyl ethers. These uniquely protected (−)-epicatechin derivatives were designed to...Feb
2013
J Nat Prod 2013, 76 (2), 157-69.
The monoglucuronides and sulfates of epicatechin, 3′-O-methylepicatechin, and 4′-O-methylepicatechin, respectively, were synthesized as authentic bioanalytical standards. Reversed-phase HPLC methods capable of baseline separation of the glucuronides and sulfates have been developed. Both the epicatechin glucuronides and sulfates were stable in the solid state when stored under ambient conditions and in aqueous solution when stored refrigerated....Mar
2012
Tetrahedron Letters 2012, 53 (12), 1501-1503.
A versatile new approach is reported for the total synthesis of five glucuronide metabolites of epicatechin, using selective protection/deprotection techniques. Graphical abstractFeb
2012
American Journal of Clinical Nutrition 2012, 95 (4), 851-858. Am J Clin Nutr. 2012 Apr;95(4):851-8. doi: 10.3945/ajcn.111.028340. Epub 2012 Feb 29.
OBJECTIVE: We assessed the respective contribution of flavanols and procyanidins to the systemic pool of flavanols and 5-(3,4-dihydroxyphenyl)-γ-valerolactone (γ-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 subjects (n = 12)...Dec
2011
Free Radic Biol Med 2012, 52 (8), 1403-12. Free Radic Biol Med. 2012 Apr 15;52(8):1403-12. doi: 10.1016/j.freeradbiomed.2011.12.010. Epub 2011 Dec 23.
Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. Although recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn are largely...Jun
2011
J Agric Food Chem 2011, 59 (12), 6740-7. J Agric Food Chem. 2011 Jun 22;59(12):6740-7. doi: 10.1021/jf200993f. Epub 2011 May 23.
The physicochemical properties of acidified milk gels after the addition of cocoa flavanols were studied. As the flavanol level increased (from 0 to 2.5 mg/g), syneresis and gel elasticity (tan δ) were found to significantly increase and decrease, respectively. Flavanol addition reduced the stress at fracture, with no changes in fracture strain, suggesting that the bond type (i.e., covalent vs noncovalent) was the underlying factor explaining...Jan
2011
Free Radic Biol Med 2011, 50 (2), 237-44.
Extensive epidemiological and clinical evidence associates diets high in flavanol-containing foods with cardiovascular health benefits in humans. Catechin and epicatechin, the most common flavanolsin 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 biologicalactivity. Healthy adult males were asked to consume...Aug
2010
Molecules 2010, 15 (8), 5595-619.
The first enantioselective syntheses of sulfur flavan-3-ol analogues 1-8 have been accomplished, whereby the oxygen atom of the pyran ring has been replaced by a sulfur atom. The key steps were: (a) Pd(0) catalyzed introduction of -S t-butyl group, (b) Sharpless enantioselective dihydroxylation of the alkene, (c) acid catalyzed ring closure to produce the thiopyran ring, and (d) removal of benzyl groups using N,N-dimethylaniline and AlCl(3). The...Jul
2010
Journal of Labelled Compounds & Radiopharmaceuticals 2010, 53 (10), 605-612.
The first synthesis of doubly labeled, [2-13C, 4-13C]-(2R,3S)-catechin 15 and [2-13C, 4-13C]-(2R,3R)-epicatechin 18 starting from labeled 2-hydroxy-4, 6-bis(benzyloxy)acetophenone 3 and labeled 3, 4-bis(benzyloxy)-benzaldehyde 7 are described.Aug
2008
Aug 15 2008
Hexameric procyanidins inhibit TNFalpha-induced NF-kappaB activation in Caco-2 cells. Most of the physiological actions of high molecular weight procyanidins could be limited to the gut lumen. Transcription factor NF-kappaB plays a central role in inflammation including human intestinal bowel disease. We investigated the capacity of a hexameric procyanidin fraction (Hex) to prevent tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB...Jan
2008
Asia Pac J Clin Nutr 2008, 17 Suppl 1, 280-3.
There has been growing interest in the potential cardiovascular benefits associated with cocoaconsumption. As a result of accurate analytical methodologies, there is evidence to support that theflavanols in cocoa can be absorbed, are bioactive, and may be responsible for the cardiovascular benefits associated with regular cocoa consumption. The flavanols in cocoa exist in a multitude of different stereochemical configurations, thus giving rise...Aug
2006
J Cardiovasc Pharmacol 2006, 48 (2), 54-70.
A proteomic analysis of procyanidin B(2) isolated from cocoa against oxidized low-density lipoprotein-induced lipid-laden macrophage formation was performed. Of approximately 400 detected proteins, 12 were differentially expressed as a result of B(2) treatment. They were subsequently identified by liquid chromatography-electrospray ionization-tandem mass spectrometry and the SWISS-PROT database. Further reverse transcriptase-polymerase chain...Jan
2006
Proc Natl Acad Sci U S A 2006, 103 (4), 1024-9.
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 cocoawas associated with acute elevations in levels of...Jun
2005
J Agric Food Chem 2005, 53 (12), 5041-8.
The antioxidant and membrane effects of dimer (Dim) and trimer (Trim) procyanidins isolated fromcocoa (Theobroma cacao) (B- and C-bonded) and peanut (Arachis hypogea L.) skin (A-bonded) were evaluated in phosphatidyl choline liposomes. When liposomes were oxidized with a steady source of oxidants, the above dimers and trimers inhibited to a similar extent lipid oxidation in a concentration (0.33-5 microM)-dependent manner. With respect to...Dec
2003
FEBS Lett 2003, 555 (3), 597-600.
It was determined that flavan-3-ols and procyanidins have an inhibitory effect on angiotensin Iconverting enzyme (ACE) activity, and the effect was dependent on the number of epicatechin units forming the procyanidin. The inhibition by flavan-3-ols and procyanidins was competitive with the two substrates assayed: N-hippuryl-L-histidyl-L-leucine (HHL) and N-[3-(2-furyl)acryloyl]-L-phenylalanylglycylglycine (FAPGG). Tetramer and hexamer fractions...Dec
2003
Nature 2003, 426 (6968), 787-8; discussion 788.
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...Apr
2003
Am J Clin Nutr 2003, 77 (4), 912-8.
BACKGROUND: Proanthocyanidins, the most abundant polyphenols in chocolate, are not depolymerized in the stomach and reach the small intestine intact, where they are hardly absorbed because of their high molecular weight. In vitro and in vivo studies using pure compounds as substrates suggest that proanthocyanidins and the related catechin monomers may be degraded into more bioavailable low-molecular-weight phenolic acids by the microflora in...Mar
2003
Biochem Pharmacol 2003, 65 (5), 773-81.
We have recently reported that flavonoids of cocoa inhibit the mammalian 15-lipoxygenase-1-a catalyst of enzymatic lipid peroxidation. To elucidate the structure-activity relationship of the inhibitory effect, we investigated the effects of 18 selected flavonoids of variable structure on pure rabbit reticulocyte and soybean 15-lipoxygenases using linoleic acid as substrate. Moreover, the inhibitionby quercetin was studied in detail to gain...Jan
2003
J Agric Food Chem 2003, 51 (3), 828-33.
Cocoa flavanols and procyanidins have numerous biological activities. It is known that (-)-epicatechin, (+)-catechin, epicatechin-(4beta-8)-epicatechin (dimer B2), and epicatechin-(4beta-6)-epicatechin (dimer B5) are unstable at physiologic pH, degrading almost completely within several hours, whereas they are relatively stable at pH 5.0. The present study investigated the effects of ascorbic and citricacid on the stability of monomers and...Pages
Analytical Methods Publications
May
2013
J AOAC Int 2013, In press.
05/16/2013 - An AOAC expert review panel (ERP), chaired by James Harnly of the U.S. Department of Agriculture, granted First Action status to two methods for flavanols in foods. Methods were evaluated against standard method performance requirements (SMPRs) developed and approved through volunteer stakeholder consensus. On March 14, 2013, during the AOAC Mid-Year Meeting, the ERP agreed that the method, “Modification to OMA 2012.24 Analysis...Feb
2013
J Nat Prod 2013, 76 (2), 157-69.
The monoglucuronides and sulfates of epicatechin, 3′-O-methylepicatechin, and 4′-O-methylepicatechin, respectively, were synthesized as authentic bioanalytical standards. Reversed-phase HPLC methods capable of baseline separation of the glucuronides and sulfates have been developed. Both the epicatechin glucuronides and sulfates were stable in the solid state when stored under ambient conditions and in aqueous solution when stored refrigerated....Mar
2012
J AOAC Int 2012, 95 (2), 500-7. J AOAC Int. 2012 Mar-Apr;95(2):500-7.
A single-laboratory validation study was performed for an HPLC method to identify and quantify the flavanol enantiomers (+)- and (-)-epicatechin and (+)- and (-)-catechin in cocoa-based ingredients and products. These compounds were eluted isocratically with an ammonium acetate-methanol mobile phase applied to a modified beta-cyclodextrin chiral stationary phase and detected using fluorescence. Spike recovery experiments using appropriate matrix...Dec
2011
Free Radic Biol Med 2012, 52 (8), 1403-12. Free Radic Biol Med. 2012 Apr 15;52(8):1403-12. doi: 10.1016/j.freeradbiomed.2011.12.010. Epub 2011 Dec 23.
Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. Although recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn are largely...Jun
2011
J Agric Food Chem 2011, 59 (12), 6740-7. J Agric Food Chem. 2011 Jun 22;59(12):6740-7. doi: 10.1021/jf200993f. Epub 2011 May 23.
The physicochemical properties of acidified milk gels after the addition of cocoa flavanols were studied. As the flavanol level increased (from 0 to 2.5 mg/g), syneresis and gel elasticity (tan δ) were found to significantly increase and decrease, respectively. Flavanol addition reduced the stress at fracture, with no changes in fracture strain, suggesting that the bond type (i.e., covalent vs noncovalent) was the underlying factor explaining...Jun
2009
J Chromatogr A 2009, 1216 (24), 4831-40.
The quantitative parameters and method performance for a normal-phase HPLC separation offlavanols and procyanidins in chocolate and cocoa-containing food products were optimized and assessed. Single laboratory method performance was examined over three months using three separate secondary standards. RSD(r) ranged from 1.9%, 4.5% to 9.0% for cocoa powder, liquor andchocolate samples containing 74.39, 15.47 and 1.87 mg/g flavanols and...Jan
2008
Asia Pac J Clin Nutr 2008, 17 Suppl 1, 280-3.
There has been growing interest in the potential cardiovascular benefits associated with cocoaconsumption. As a result of accurate analytical methodologies, there is evidence to support that theflavanols in cocoa can be absorbed, are bioactive, and may be responsible for the cardiovascular benefits associated with regular cocoa consumption. The flavanols in cocoa exist in a multitude of different stereochemical configurations, thus giving rise...Jul
2006
Journal of Food Science 2003, 68 (9), 2618-2622.
A near-infrared reflectance (NIR) spectroscopy technique for the prediction of procyanidins in cocoa beans (Theobroma cacao) has been developed. A select group of cocoa liquors from different origins used for the manufacture of chocolate were analyzed to determine quantitative levels of procyanidin oligomers (monomer to decamer) using normal-phase high-performance liquid chromatography. The calibration set included seasonal, environmental, and...Jan
2006
J Agric Food Chem 2006, 54 (5), 1571-6.
A new chromatographic approach for separating cacao procyanidins according to their degree ofpolymerization has been developed. It utilizes diol stationary phase columns operating in normal phase mode with a binary gradient of acidified acetonitrile and methanol-water. Performance of thediol stationary phase was evaluated on an analytical scale utilizing classical chromatographic conditions for the normal phase separation of procyanidins...Jan
2006
J Cardiovasc Pharmacol 2006, 47 Suppl 2, S110-8; discussion S119-21.
Flavanols and their related oligomeric compounds, the procyanidins, have received increased attention during the past decade due to their reported health benefits. On the basis of compelling data published during the past decade demonstrating that the consumption of certain flavanol-richfoods can improve markers of cardiovascular health, additional clinical, and epidemiological research is clearly warranted to establish appropriate public health...Aug
2005
J Hypertens 2005, 23 (8), 1453-9.
PURPOSE OF REVIEW: Cardiovascular benefits for cocoa are being claimed in the scientific literature with growing intensity. To date, excitement over the potential health benefits of flavonoids has been driven mostly by epidemiological studies of tea and red wine, but raw cocoa contains specific flavonoids in concentrations far exceeding those from most other sources. Early evidence supports cocoa's enhancement of endothelial function via...Mar
2005
Clin Dev Immunol 2005, 12 (1), 35-41.
Evidence suggesting that dietary polyphenols, flavanols, and proanthocyanidins in particular offer significant cardiovascular health benefits is rapidly increasing. Accordingly, reliable and accurate methods are needed to provide qualitative and quantitative food composition data necessary for high quality epidemiological and clinical research. Measurements for flavonoids and proanthocyanidinshave employed a range of analytical techniques, with...Mar
2004
J Nutr 2004, 134 (3), 613-7.
Proanthocyanidins (PAs) have been shown to have potential health benefits. However, no data exist concerning their dietary intake. Therefore, PAs in common and infant foods from the U.S. were analyzed. On the bases of our data and those from the USDA's Continuing Survey of Food Intakes by Individuals (CSFII) of 1994-1996, the mean daily intake of PAs in the U.S. population (>2 y old) was estimated to be 57.7 mg/person. Monomers, dimers, trimers...Dec
2003
J Agric Food Chem 2003, 51 (25), 7513-21.
A normal-phase HPLC-MS/MS method was applied to screen for proanthocyanidins in 88 different kinds of foods. Thirty-nine foods were found to contain proanthocyanidins. These foods include 19 kinds of fruits, eight cereals/beans, seven nuts, two beverages, two spices, and one vegetable. Twenty-five kinds of foods were found to contain both oligomeric (DP 10), and the other 14 foods contained only oligomers. Procyanidins with B-type linkages were...Dec
2003
J Mass Spectrom 2003, 38 (12), 1272-80.
The proanthocyanidins in three foods (pinto beans, plums and cinnamon) were studied with electrospray ionization (ESI) mass spectrometry (MS) in the negative mode following separation by normal-phase high-performance liquid chromatography. The MS/MS analysis demonstrated that the major ions derived from heterocyclic ring fission and retro-Diels-Alder reaction of flavan-3-ol provided information about the hydroxylation pattern and type of...Aug
2002
J Agric Food Chem 2002, 50 (17), 4852-60.
The polymeric procyanidins were fractionated from lowbush blueberry on a Sephadex LH-20 column. The degree of polymerization (DP) for the polymers was determined by thiolysis to be in a range of 19.9 to 114.1. Normal-phase HPLC analysis indicated that the polymeric procyanidins did not contain oligomeric procyanidins with DP...Mar
2001
J Agric Food Chem 2001, 49 (3), 1270-6.
Blueberries and cranberries were analyzed for procyanidins using normal-phase HPLC/MS. Monomers, identified as (+)-catechin and (-)-epicatechin, and a series of oligomers were detected inblueberries, and MS data confirmed that the oligomers consisted of (epi)catechin units that were exclusively singly linked (B-type). The procyanidin "fingerprints" were similar for Tifblue and Rubel but higher than that for lowbush blueberries. In whole...Jan
2001
J Food Comp Anal 2001, 14 (6), 553-563.
The Kuna Amerinds reside chiefly in the San Blas islands (Kuna Yala) on the Caribbean coast of Panama. The diet of this population has not previously been described in detail and composition data for certain foods consumed by this population does not exist or is lacking for certain important nutrients. The protein, fat, moisture, fiber, sugar, mineral and procyanidin content was determined in foods selected because of the frequency with which...Aug
2000
J Nutr 2000, 130 (8S Suppl), 2086S-92S.
Procyanidins are a subclass of flavonoids found in commonly consumed foods that have attracted increasing attention due to their potential health benefits. However, little is known regarding their dietary intake levels because detailed quantitative information on the procyanidin profiles present in many food products is lacking. Therefore, the procyanidin content of red wine, chocolate, cranberry juice and four varieties of apples has been...Nov
1999
FEBS Lett 1999, 462 (1-2), 167-70.
Flavonoids, natural plant constituents, protect against peroxynitrite and can thereby play a role in defense against this mediator of inflammation. Procyanidin oligomers of different size (monomer through nonamer), isolated from the seeds of Theobroma cacao, were examined for their ability to protect against peroxynitrite-dependent oxidation of dihydrorhodamine 123 and nitration of tyrosine. By molarity, oligomers were more effective than the...Pages
Absorption and Metabolism Publications
Dec
2016
The American Journal of Clinical Nutrition
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...Jul
2016
Nature Scientific Reports
Diet is a major life style factor affecting human health, emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack...Nov
2015
The American Journal of Clinical Nutrition®
Background: Evidence from dietary intervention studies shows that the intake of flavanols and procyanidins can be beneficial for cardiovascular health. Nevertheless, there is a clear need for advancing our understanding with regard to safe amounts of intake for these bioactive. Objective: The aim was to investigate in healthy adults the effects of cocoa flavanol (CF) intake amount and intake duration on blood pressure, platelet function,...Jun
2015
British Journal of Nutrition
Cocoa flavanol (CF) intake improves endothelial function in patients with cardiovascular risk factors and disease. We investigated the effects of CF on surrogate markers of cardiovascular health in low risk, healthy, middle-aged individuals without history, signs or symptoms of CVD. In a 1-month, open-label, one-armed pilot study, bi-daily ingestion of 450 mg of CF led to a time-dependent increase in endothelial function (measured as flow-...Apr
2015
Organic Letters
The first novel stereoselective synthesis of naturally occurring A1 (1) and A2 proanthocyanidins (2) has been achieved. The key synthetic steps involved (a) the formation of a coupled product (13 or 14) between an open chain C-ring C-4 hydroxyethoxy analogue of either (+)-catechin or (−)-epicatechin with 5,7,3′,3′-tetra-O-benzyl-(+)-catechin/-(−)-epicatechin in the presence of bentonite clay K-10, (b) removal of benzyl protecting groups under...Dec
2012
Br J Nutr 2012, 1-8. Br J Nutr. 2012 Dec 28;108(12):2243-50. doi: 10.1017/S0007114512000475. Epub 2012 Mar 7.
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...Feb
2012
American Journal of Clinical Nutrition 2012, 95 (4), 851-858. Am J Clin Nutr. 2012 Apr;95(4):851-8. doi: 10.3945/ajcn.111.028340. Epub 2012 Feb 29.
OBJECTIVE: We assessed the respective contribution of flavanols and procyanidins to the systemic pool of flavanols and 5-(3,4-dihydroxyphenyl)-γ-valerolactone (γ-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 subjects (n = 12)...Dec
2011
Free Radic Biol Med 2012, 52 (8), 1403-12. Free Radic Biol Med. 2012 Apr 15;52(8):1403-12. doi: 10.1016/j.freeradbiomed.2011.12.010. Epub 2011 Dec 23.
Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. Although recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn are largely...Jan
2011
Free Radic Biol Med 2011, 50 (2), 237-44.
Extensive epidemiological and clinical evidence associates diets high in flavanol-containing foods with cardiovascular health benefits in humans. Catechin and epicatechin, the most common flavanolsin 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 biologicalactivity. Healthy adult males were asked to consume...Aug
2008
Aug 15 2008
Hexameric procyanidins inhibit TNFalpha-induced NF-kappaB activation in Caco-2 cells. Most of the physiological actions of high molecular weight procyanidins could be limited to the gut lumen. Transcription factor NF-kappaB plays a central role in inflammation including human intestinal bowel disease. We investigated the capacity of a hexameric procyanidin fraction (Hex) to prevent tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB...Oct
2006
Free Radic Biol Med 2006, 41 (8), 1247-56.
Procyanidins can exert cytoprotective, anti-inflammatory, and anticarcinogenic actions in the gastrointestinal tract. Previous evidence has shown that procyanidins can interact with synthetic membranes and protect them from oxidation and disruption. Thus, in this study we investigated the capacity of a hexameric procyanidin fraction (Hex) isolated from cocoa to protect Caco-2 cells from deoxycholic (DOC)-induced cytotoxicity, cell oxidant...Jan
2004
Biol Res 2004, 37 (2), 293-300.
We investigated the effects of the interaction between flavanols and related procyanidins (dimer to hexamer) with both cell and synthetic membranes, on bilayer fluidity and susceptibility to oxidation.Cocoa derived dimers (0.05 to 1 microg/ml) protected Jurkat T cells from AMVN-mediated oxidation and increased plasma membrane fluidity. These effects occurred in a concentration- and chain length-dependent manner. In liposomes, procyanidins...Dec
2003
FEBS Lett 2003, 555 (3), 597-600.
It was determined that flavan-3-ols and procyanidins have an inhibitory effect on angiotensin Iconverting enzyme (ACE) activity, and the effect was dependent on the number of epicatechin units forming the procyanidin. The inhibition by flavan-3-ols and procyanidins was competitive with the two substrates assayed: N-hippuryl-L-histidyl-L-leucine (HHL) and N-[3-(2-furyl)acryloyl]-L-phenylalanylglycylglycine (FAPGG). Tetramer and hexamer fractions...Dec
2003
Nature 2003, 426 (6968), 787-8; discussion 788.
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...Jul
2003
Life Sci 2003, 73 (7), 857-69.
Macronutrients in food and gastric acid are known to have a pronounced effect on the metabolism of many xenobiotics, an effect that impacts their efficacy as bioactive agents. In this investigation we assessed the impact of select food treatments and the histamine H(2)-receptor antagonist Famotidine (Pepcid-AC) on flavanol absorption and metabolism. Four crossover intervention studies were conducted with 6 subjects each. Volunteers consumed...Apr
2003
Am J Clin Nutr 2003, 77 (4), 912-8.
BACKGROUND: Proanthocyanidins, the most abundant polyphenols in chocolate, are not depolymerized in the stomach and reach the small intestine intact, where they are hardly absorbed because of their high molecular weight. In vitro and in vivo studies using pure compounds as substrates suggest that proanthocyanidins and the related catechin monomers may be degraded into more bioavailable low-molecular-weight phenolic acids by the microflora in...Jan
2003
J Agric Food Chem 2003, 51 (3), 828-33.
Cocoa flavanols and procyanidins have numerous biological activities. It is known that (-)-epicatechin, (+)-catechin, epicatechin-(4beta-8)-epicatechin (dimer B2), and epicatechin-(4beta-6)-epicatechin (dimer B5) are unstable at physiologic pH, degrading almost completely within several hours, whereas they are relatively stable at pH 5.0. The present study investigated the effects of ascorbic and citricacid on the stability of monomers and...Nov
2002
J Nutr Biochem 2002, 13 (11), 645-652.
Cocoa flavan-3-ols (catechin, epicatechin and oligomeric procyanidins) were tested for their ability to decrease LDL oxidative susceptibility and spare alpha-tocopherol (alpha-toc) in vitro. Physiologic concentration (0.10-0.50 &mgr;M) of flavanols were used. The flavanols increased LDL conjugated diene lag times dose-dependently from 23-207% and 15-143% in response to copper and AAPH oxidation, respectively, and delayed alpha-toc consumption....Nov
2002
Am J Clin Nutr 2002, 76 (5), 1106-10.
BACKGROUND: Polyphenolic procyanidins are abundant flavonoid polymers in Western diets. In vitro biological activity has been reported for these compounds, but activity in vivo depends on the amount and chemical nature of the flavonoids reaching the gastrointestinal tract. Degradation of procyanidinsunder simulated gastric conditions at pH 2.0 has been reported in vitro. OBJECTIVE: The objective was to examine whether depolymerization of...May
2002
Exp Biol Med (Maywood) 2002, 227 (5), 321-9.
Excessive peroxidation of biomembranes is thought to contribute to the initiation and progression of numerous degenerative diseases. The present study examined the inhibitory effects of a cocoaextract, individual cocoa flavanols (-)-epicatechin and (+)-catechin, and procyanidin oligomers (dimer to decamer) isolated from cocoa on rat erythrocyte hemolysis. In vitro, the flavanols and theprocyanidin oligomers exhibited dose-dependent protection...Pages
Microbiome Publications
Jan
2011
Am J Clin Nutr 2011, 93 (1), 62-72. Am J Clin Nutr. 2011 Jan;93(1):62-72. doi: 10.3945/ajcn.110.000075. Epub 2010 Nov 10.
BACKGROUND: The absorption of cocoa flavanols in the small intestine is limited, and the majority of the flavanols reach the large intestine where they may be metabolized by resident microbiota. OBJECTIVE: We assessed the prebiotic potential of cocoa flavanols in a randomized, double-blind, crossover, controlled intervention study. DESIGN: Twenty-two healthy human volunteers were randomly assigned to either a high-cocoa flavanol (HCF)...Feb
2009
J Med Food 2009, 12 (1), 1-7.
Flavanols and procyanidins isolated from cocoa have been reported to possess multiple activities potentially relevant to oxidant defenses, vascular function, and immune function. In a combination of in vivo and in vitro studies, we and others have observed that cocoa can be an anti-inflammatory modulator and that compounds in cocoa are capable of modulating eicosanoid production, platelet aggregation, and the pool size of nitric oxide. The...Apr
2008
Br J Nutr 2008, 99 (4), 782-92.
We have investigated the bacterial-dependent metabolism of ( - )-epicatechin and (+)-catechin using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal region of the humanlarge intestine. Incubation of ( - )-epicatechin or (+)-catechin (150 mg/l or 1000 mg/l) with faecalbacteria, led to the generation of 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone, 5-phenyl-gamma-valerolactone and phenylpropionic acid. However...Feb
2007
Exp Biol Med (Maywood) 2007, 232 (2), 293-300.
There has been considerable work on the relationships between nutrition and the immune response, particularly on studies that have focused on adaptive responses. There is increasing recognition of the importance of innate immunity in host protection and initiation of cytokine networks. In this study, we examined the effect of select cocoa flavanols and procyanidins on innate responses in vitro.Peripheral blood mono-nuclear cells (PBMCs), as well...History of Cocoa Flavanols Publications
Jan
2006
J Cardiovasc Pharmacol 2006, 47 Suppl 2, S103-9; discussion 119-21.
A low sodium diet has often been implicated in the protection of low blood pressure populations fromhypertension, but several other dietary factors, including those as yet unidentified, may also be involved. The Kuna Indians of Panama are free of hypertension and cardiovascular disease, but this is changing with migration to urban areas. We compared the indigenous diet of Kuna Indians living on remote islands in Panama (Ailigandi), whose...Aug
2000
J Nutr 2000, 130 (8S Suppl), 2057S-72S.
The medicinal use of cacao, or chocolate, both as a primary remedy and as a vehicle to deliver other medicines, originated in the New World and diffused to Europe in the mid 1500s. These practices originated among the Olmec, Maya and Mexica (Aztec). The word cacao is derived from Olmec and the subsequent Mayan languages (kakaw); the chocolate-related term cacahuatl is Nahuatl (Aztec language), derived from Olmec/Mayan etymology. Early colonial...Aug
2000
J Med Food 2000, 3 (2), 77-105.
Chocolate and cocoa are extensively used in many cultures. Although their composition has been studied, the functional significance of the components has not been as well defined. There are indications that cocoa constituents exert beneficial effects on human health, and therefore cocoa and chocolate may be considered functional foods. The use of functional foods to modulate human health has gained greater significance in recent years, and...Nov
1999
Lancet 1999, 354 (9192), 1825.
Ilya Arts and colleagues (Aug 7, p 488) report that chocolate and tea may contribute significantly to total dietary catechin intake (20% and 55%, respectively). However, their methods only took into account the monomeric catechins and neglected the more abundant oligomers found in chocolate,Anchor which are present in only minor concentrations in tea. Indeed, Arts and colleagues' method to determine catechin content illustrates a commonly...Reviews Publications
Dec
2010
Mol Aspects Med 2010, 31 (6), 546-57
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...Jan
2008
Asia Pac J Clin Nutr 2008, 17 Suppl 1, 284-7.
Epidemiologic investigations support the hypothesis that regular consumption of flavonoid-containing foods can reduce the risk of cardiovascular diseases (CVD). While flavonoids are ubiquitous in plants,cocoa can be particularly rich in a sub-class of flavonoids known as flavanols. A number of human dietary intervention trials with flavanol-containing cocoa products have demonstrated improvements in endothelial and platelet function, as well as...Jan
2006
J Cardiovasc Pharmacol 2006, 47 Suppl 2, S187-96; discussion S206-9.
Epidemiology studies suggest that the consumption of diets rich in flavonoids is associated with reduced risk of cardiovascular disease. Plant-derived foods and beverages, such as red wine, tea, grape and grape juice, cocoa and chocolate, can be rich in 1 particular class of flavonoid, the flavan-3-ols. There is now an increasing body of research that suggests that consuming flavanol-rich foods can positively affect hemostasis, through...Jan
2006
J Cardiovasc Pharmacol 2006, 47 Suppl 2, S128-35; discussion S172-6.
Endothelial dysfunction is the pathophysiologic principle involved in the initiation and progression of arteriosclerosis, thus endothelial function serves as a "barometer" for cardiovascular health that can be used for the evaluation of new therapeutic strategies. This review provides an introduction to the concept of endothelial dysfunction, and it explores the importance of this prognostic marker in the context of clinical, dietary...Jan
2006
Journal of Cardiovascular Pharmacology 2006, 47, S99-S102.
Diet patterns are widely recognized as contributors to hypertension. Widely studied potential contributors include intake of sodium, potassium, magnesium, calcium, soluble fiber, omega-3 fatty acids, alcohol, protein, and calories. We add to that list the effect of dietary flavanols present in certain cocoas, which have sufficient activity on vascular nitric oxide to influence blood pressure control. Kuna Indians who live on islands near Panama...Jan
2006
J Cardiovasc Pharmacol 2006, 47 Suppl 2, S110-8; discussion S119-21.
Flavanols and their related oligomeric compounds, the procyanidins, have received increased attention during the past decade due to their reported health benefits. On the basis of compelling data published during the past decade demonstrating that the consumption of certain flavanol-richfoods can improve markers of cardiovascular health, additional clinical, and epidemiological research is clearly warranted to establish appropriate public health...Aug
2005
J Hypertens 2005, 23 (8), 1453-9.
PURPOSE OF REVIEW: Cardiovascular benefits for cocoa are being claimed in the scientific literature with growing intensity. To date, excitement over the potential health benefits of flavonoids has been driven mostly by epidemiological studies of tea and red wine, but raw cocoa contains specific flavonoids in concentrations far exceeding those from most other sources. Early evidence supports cocoa's enhancement of endothelial function via...Jan
2005
Am J Clin Nutr 2005, 81 (1 Suppl), 298S-303S.
An increasing body of epidemiologic evidence supports the concept that diets rich in fruits and vegetables can promote health and attenuate, or delay, the onset of various diseases. Epidemiologic data support the idea that these health benefits are causally linked to the consumption of certain flavonoids present in fruit and vegetables. In the context of cardiovascular health, a particular group of flavonoids, namely, the flavan-3-ols (flavanols...Sep
2004
Br J Cardiol 2004, 11 (5), 379-386.
There has been a long-standing interest in the relation between what we eat and cardiovascular risk. Over the years, attention has been given to calories, total fat, saturated fat, cholesterol, omega-3 polyunsaturated fatty acids, trans fatty acids, folic acid, antioxidants and, most recently, flavanols. Flavanol concentrations can be moderately high in a number of foods that have been associated with a reduction in cardiovascular risk including...Feb
2003
J Am Diet Assoc 2003, 103 (2), 215-23.
This paper offers a review of current scientific research regarding the potential cardiovascular health benefits of flavonoids found in cocoa and chocolate. Recent reports indicate that the main flavonoids found in cocoa, flavan-3-ols and their oligomeric derivatives, procyanidins, have a variety of beneficial actions, including antioxidant protection and modulation of vascular homeostasis. These findings are supported by similar research on...May
2002
Phytochemical Reviews 2002, 1 (231-240).
Fruits and vegetables have historically been considered rich sources of essential dietary micronutrients, soluble fiber, and antioxidants. More recently they are have been recognized as important sources for a wide array of phytochemicals that individually, or in combination, may benefit vascular health. Flavonoids are the largest, and most widely distributed class of phytochemicals, and can be further subdivided into several different sub-...May
2002
Nutr Today 2002, 37 (3), 103-109
Cocoa and chocolate foods produced by appropriate methods can contribute significant amounts ofheart-healthy flavanols to the diet. These flavanols may enhance cardiovascular health by delaying blood clotting, improving vascular endothelial function, and helping to moderate inflammation. The benefits of chocolate can be enjoyed without guilt as part of a healthful balanced diet.Aug
2000
J Med Food 2000, 3 (2), 77-105.
Chocolate and cocoa are extensively used in many cultures. Although their composition has been studied, the functional significance of the components has not been as well defined. There are indications that cocoa constituents exert beneficial effects on human health, and therefore cocoa and chocolate may be considered functional foods. The use of functional foods to modulate human health has gained greater significance in recent years, and...