RESUMEN
SCOPE: An understanding of the pharmacokinetics of structurally related (-)-epicatechin metabolites (SREM) is a prerequisite for considering cocoa flavanols (CF) in the context of dietary recommendations. The objective of this study was to compare the absorption, metabolism, and excretion of SREM in healthy young and elderly Caucasian men. METHODS AND RESULTS: Intraindividual variability of SREM was assessed in seven young subjects, after consuming 10.7 mg CF/kg body weight (BW) on two occasions separated by 1 week. The effect of age on flavanols ADME was assessed in 20 young (18-35 years) and 20 elderly (65-80 years) healthy male subjects receiving 5.3 and 10.7 mg total CF/kg BW or 1 g of acetaminophen as a control to compare differences in Phase II metabolism on three days separated by 1 week of wash-out. Blood and urine samples were collected for 24-h post consumption. The intraindividual variation, measured as CV(%) with respect to the area-under-the-curve of the concentration over time (AUC(0-6h) ) of SREM, was 16%, while the interindividual variation in AUC(0-6h) , was 38%, comparable to acetaminophen (39%). The AUC(0-6h) and the 24-h excretion of total SREM was not significantly different between young and elderly subjects. At the high intake amount, the AUC(0-6h) of (-)-epicatechin-3'-ß-D-glucuronide was greater in elderly subjects, whereas the AUC(0-6h) of 3'-O-methyl-(-)-epicatechin-5-sulfate and 3'-O-methyl-(-)-epicatechin-7-sulfate as well as the 24-h urinary excretion of γ-valerolactone metabolites were lower in the elderly. CONCLUSION: Cocoa flavanols are absorbed, metabolized, and excreted in healthy young and elderly subjects with relatively small differences between the two groups.
Asunto(s)
Envejecimiento , Bebidas/análisis , Cacao/química , Flavonoides/metabolismo , Absorción Intestinal , Lactonas/orina , Eliminación Renal , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Catequina/análogos & derivados , Catequina/sangre , Catequina/química , Catequina/metabolismo , Estudios Cruzados , Flavonoides/administración & dosificación , Flavonoides/sangre , Flavonoides/orina , Glucurónidos/sangre , Glucurónidos/química , Glucurónidos/metabolismo , Semivida , Humanos , Cinética , Lactonas/química , Lactonas/metabolismo , Masculino , Metilación , Pacientes Desistentes del Tratamiento , Estereoisomerismo , Ésteres del Ácido Sulfúrico/sangre , Ésteres del Ácido Sulfúrico/química , Ésteres del Ácido Sulfúrico/metabolismo , Adulto JovenRESUMEN
The antiproliferative effects of a purified white grape pomace extract (PWGPE), as well as of some phenolic standards on colon cancer cells were examined. The phenolic composition of the PWGPE was determined by rapid resolution liquid chromatography/mass spectrometry (RRLC/MS). The PWGPE had 92.6, 43.3 and 6.01mg/g of flavanols, flavonols and phenolic acids, respectively and, along with pure catechin, epicatechin, quercetin and gallic acid, they were all found capable of inhibiting cellular proliferation. PWGPE (100µg/ml) inhibited the proliferation of cells by 52.1% at 48h, whilst catechin, epicatechin, quercetin and gallic acid (60µg/ml) inhibited growth by 65.2%, 62.2%, 81.0% and 71.0%, respectively, at 72h. The PWGPE is an interesting source of phenolic compounds with antiproliferative properties, that could be of interest in the food and pharmaceutical industries.
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Cromatografía Líquida de Alta Presión/métodos , Neoplasias Colorrectales/prevención & control , Flavonoides/análisis , Hidroxibenzoatos/química , Espectrometría de Masas/métodos , Extractos Vegetales/química , Vitis/química , Catequina/análisis , Flavonoles/análisis , Humanos , Quercetina/análisisRESUMEN
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.
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Cacao/metabolismo , Flavonoides/metabolismo , Digestión , Femenino , Absorción Gastrointestinal , Humanos , MasculinoRESUMEN
Accumulating evidence suggest that diets rich in cocoa flavanols may have beneficial effects on cardiovascular health. The major cocoa flavanol monomer, (-)-epicatechin (EC), is readily absorbed and circulates primarily as glucuronidated, sulfated, and O-methylated metabolites in human plasma. However, cellular metabolism, for example in endothelial cells, is less well defined. In the present study we detail the uptake and cellular metabolism of EC and its major in vivo metabolites, (-)-epicatechin-3'-ß-D-glucuronide (E3G), (-)-epicatechin-3'-sulfate (E3S), 3'-O-methyl-(-)-epicatechin-5-sulfate (3ME5S), and 3'-O-methyl-(-)-epicatechin-7-sulfate (3ME7S) in human endothelial (HUVEC), liver (HepG2) and intestinal epithelial cells (Caco-2 monolayer). Our results indicate that EC associates with HUVECs, leading to its intracellular metabolism to 3ME7G and 3ME7S. In contrast, none of the metabolites were taken up by the cells. The metabolic rate and pattern of metabolism in HUVECs was similar to that observed in HepG2 cells, whilst in Caco-2 cells EC was metabolized to E3G, 3ME5G, 3ME7G, 4ME5G, 4ME7G and 3ME7S. Our data support the notion that endothelial cells may contribute significantly to EC metabolism. However, major human circulating metabolites are not accounted for in these model systems underscoring that caution should be taken when drawing conclusions on in vivo flavanol metabolism from in vitro experiments.
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Catequina/metabolismo , Células Endoteliales/metabolismo , Absorción , Transporte Biológico , Células CACO-2 , Células Hep G2 , HumanosRESUMEN
Accumulating evidence suggests that diets rich in (poly)phenols may have positive effects on human health. Currently there is limited information regarding the effects of processing on the (poly)phenolic content of berries, in particular in processes related to the baking industry. This study investigated the impact of cooking, proving, and baking on the anthocyanin, procyanidin, flavonol, and phenolic acid contents of wild blueberry using HPLC with UV and fluorescence detection. Anthocyanin levels decreased during cooking, proving, and baking, whereas no significant changes were observed for total procyanidins. However, lower molecular weight procyanidins increased and high molecular weight oligomers decreased during the process. Quercetin and ferulic and caffeic acid levels remained constant, whereas increases were found for chlorogenic acid. Due to their possible health benefits, a better understanding of the impact of processing is important to maximize the retention of these phytochemicals in berry-containing products.
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Arándanos Azules (Planta)/química , Manipulación de Alimentos/métodos , Frutas/química , Polifenoles/química , Culinaria/métodos , Calor , Estructura MolecularRESUMEN
The health benefits of blueberry consumption on the vascular system and brain are mediated in part by their flavonoid content. In light of this, six cultivated highbush blueberry varieties ( Vaccinium corymbosum L.) and one lowbush or wild blueberry ( Vaccinium angustifolium L.) were analyzed for their anthocyanin, flavanol oligomer, and chlorogenic acid contents. The highbush varieties Bluecrop, O'Neal, Bluejay, and Brigitta had significantly greater levels of anthocyanidins compared to the other varieties, whereas Bluejay and Brigitta organic had the highest amount of flavanol oligomers. The organically grown highbush blueberry had the highest flavanol oligomer and chlorogenic acid contents but a lower anthocyanidin content than its conventionally grown counterpart. The lowbush variety contained the highest chlorogenic acid concentration. Delphinidin and malvidin were the predominant anthocyanidins in the varieties tested, with concentrations ranging between 45.0 and 74.9 mg/100 g FW for delphinidin and between 37.1 and 62.2 mg/100 g FW for malvidin. Flavanol dimers were the most abundant flavanols, with a mean percentage of 24 ± 1.5% of the total, with flavanol monomers representing 11 ± 0.7%.