Regular Consumption of a Flavanol-rich Chocolate can Improve Oxidant Stress in Young Soccer Players

The consumption of a diet rich in certain flavonoids, including the flavanol sub-class, has been associated with a reduced risk for vascular disease. We evaluated the effects of the regular consumption (14 d) of a flavanol-containing milk chocolate (FCMC) or cocoa butter chocolate (CBC) on variables related to vascular disease risk, oxidative stress and physical activity. Twenty-eight free-living, young (18–20 years old) male soccer players consumed daily 105 g of FCMC (168 mg of flavanols) or CBC (<5 mg of flavanols), as part of their normal diet. The consumption of FCMC was significantly associated with a decrease in diastolic blood pressure (-5 mm Hg), mean blood pressure (-5 mm Hg), plasma cholesterol (-11%), LDL-cholesterol (-15%), malondialdehyde (-12%), urate (-11%) and lactate dehydrogenase (LDH) activity (-11%), and an increase in vitamin E/cholesterol (+12%). No relevant changes in these variables were associated with CBC consumption. No changes in the plasma levels of (-)-epicatechin were observed following analysis of fasting blood samples. In conclusion, FCMC consumption was associated with changes in several variables often associated with cardiovascular health and oxidant stress. The presence of significant quantities of flavanols in FCMC is likely to have been one of the contributing factors to these results

Identification of epicatechin as one of the key bioactive constituents of polyphenol-enriched extracts that demonstrate an anti-allergic effect in a murine model of food allergy

Polyphenols are naturally derived bioactive compounds with numerous reported health benefits. We have previously reported on the beneficial effect of a polyphenol-enriched apple extract in a murine model of food allergy. The objectives of the present study were to elucidate the class of bioactive polyphenols that exhibit a beneficial anti-allergic effect and to assess whether the protective effect matches the in vivo bioavailable metabolite concentrations. Female BALB/c mice were sensitised to ovalbumin (OVA) following the protocol of a well-established murine model of food allergy. They were fed diets containing polyphenol-enriched extracts or purified epicatechin for 8d after the last sensitisation. The sensitised mice were orally challenged with OVA after the intervention. The allergy symptoms, in addition to allergen-specific serum Ig concentrations and gene expression profiles in the intestine, of the control and treated mice were compared. Plasma samples were collected to compare the concentrations of bioavailable epicatechin metabolites in the treatment groups. Polyphenol-enriched fruit extracts containing epicatechin exhibited a significant anti-allergic effect in vivo. This effect was unambiguously attributed to epicatechin, as oral administration of this purified polyphenol to sensitised mice by inclusion in their diet modulated allergy symptoms in a dose-dependent manner. Immune parameters were also affected by the administration of epicatechin. Bioavailability measurements in plasma indicated that the attenuation of allergy symptoms could be due to the higher concentrations of bioavailable epicatechin metabolites. In conclusion, epicatechin is a key bioactive polyphenol that has the ability to modulate allergy outcomes in sensitised mic

Modulation of (-)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

ABSTRACT Widely consumed beverages such as red wine, tea, and cocoaderived products are a great source of flavanols. Epidemiologic and interventional studies suggest that cocoa flavanols such as (-)-epicatechin may reduce the risk of cardiovascular diseases. The interaction of (-)-epicatechin with food components including other polyphenols could modify its absorption, metabolism, and finally its bioactivity. In the present study we investigate (-)-epicatechin absorption and metabolism when coexposed with other polyphenols in the intestinal absorptive Caco-2 cell model. Depending on the type of polyphenols coadministered, the total amount of 39-O-methyl-epicatechin and 39-O-sulfate-epicatechin conjugates found both in apical and basal compartments ranged from 19 to 801 nM and from 6 to 432 nM, respectively. The coincubation of (-)-epicatechin with flavanols, chlorogenic acid, and umbelliferone resulted in similar amounts of 39-O-methyl-epicatechin effluxed into the apical compartment relative to control. Coincubation with isorhamnetin, kaempferol, diosmetin, nevadensin, chrysin, equol, genistein, and hesperitin promoted the transport of 39-Omethyl-epicatechin toward the basolateral side and decreased the apical efflux. Quercetin and luteolin considerably inhibited the appearance of this (-)-epicatechin conjugate both in the apical and basolateral compartments. In conclusion, we could demonstrate that the efflux of (-)-epicatechin conjugates to the apical or basal compartments of Caco-2 cells is modulated by certain classes of polyphenols and their amount. Ingesting (-)-epicatechin with specific polyphenols could be a strategy to increase the bioavailability of (-)-epicatechin and to modulate its metabolic profile

Mediation of coffee-induced improvements in human vascular function by chlorogenic acids and its metabolites: two randomized, controlled, crossover intervention trials

Background & aims Polyphenol intake has been linked to improvements in human vascular function, although data on hydroxycinnamates, such as chlorogenic acid (CGA) have not yet been studied. We aimed to investigate the impact of coffee intake rich in chlorogenic acid on human vascular function and whether CGAs are involved in potential effects. Methods Two acute randomized, controlled, cross-over human intervention trials were conducted. The impact of coffee intake, matched for caffeine but differing in CGA content (89, and 310 mg) on flow-mediated dilation (FMD) was assessed in 15 healthy male subjects. In a second intervention trial conducted with 24 healthy male subjects, the impact of pure 5-caffeoylquinic acid (5-CQA), the main CGA in coffee (5-CQA; 450 mg and 900 mg) on FMD was also investigated. Results We observed a bi-phasic FMD response after low and high polyphenol, (89 mg and 310 mg CGA) intake, with increases at 1 (1.10 ± 0.43% and 1.34 ± 0.62%, respectively) and 5 (0.79% ± 0.32 and 1.52% ± 0.40, respectively) hours post coffee consumption. FMD responses to coffee intake was closely paralleled by the appearance of CGA metabolites in plasma, notably 3-, 4- and 5-CQA and ferulic-4′-O-sulfate at 1 h and isoferulic-4′-O-glucuronide and ferulic-4′-O-sulfate at 5 h. Intervention with purified 5-CQA (450 mg) also led to an improvement in FMD response relative to control (0.75 ± 1.31% at 1 h post intervention, p = 0.06) and concomitant appearance of plasma metabolites. Conclusions Coffee intake acutely improves human vascular function, an effect, in part, mediated by 5-CQA and its physiological metabolites

The Impact of Epicatechin on Human Cognition: The Role of Cerebral Blood Flow

Epicatechin is a monomeric flavanol found in food sources such as tea, apples, berries and cocoa. A number of large-scale epidemiological studies have demonstrated an association between the consumption of these foods and cognitive function, as well as improved blood flow. The aim of this review is to summarise the evidence from intervention studies to clarify the effect of epicatechin on cognition and to consider the role of increased cerebral blood flow as a mechanism for any effects. The effects of epicatechin as consumed in cocoa are, therefore, reviewed here as this represents the only dietary source where it is purported to be the major active component. Our main findings are that a) the positive modulation of tasks that involve memory, executive function and processing speed in older adults; b) the cognitive benefits are more often shown in studies containing more than 50 mg epicatechin/day; and c) all studies with a duration of 28 days or longer in populations >50 years old demonstrate a cognitive improvement. However, as highlighted by this review, it is not currently possible to attribute effects solely to epicatechin without consideration of synergies. In order to overcome this issue, further studies examining the cognitive effects of epicatechin in isolation are required. The role of cerebral blood flow also requires further investigation through simultaneous measurement alongside cognitive function

Modulation of (-)-epicatechin metabolism by coadministration with other polyphenols in caco-2 cell model

Widely consumed beverages such as red wine, tea, and cocoaderived products are a great source of flavanols. Epidemiologic and interventional studies suggest that cocoa flavanols such as (- )-epicatechin may reduce the risk of cardiovascular diseases. The interaction of ( - )-epicatechin with food components including other polyphenols could modify its absorption, metabolism, and finally its bioactivity. In the present study we investigate (- )-epicatechin absorption and metabolism when coexposed with other polyphenols in the intestinal absorptive Caco-2 cell model. Depending on the type of polyphenols coadministered, the total amount of 39-O-methyl-epicatechin and 3 ′- O-sulfate-epicatechin conjugates found both in apical and basal compartments ranged from 19 to 801 nM and from 6 to 432 nM, respectively. The coincubation of ( - )-epicatechin with flavanols, chlorogenic acid, and umbelliferone resulted in similar amounts of 3′-O-methyl-epicatechin effluxed into the apical compartment relative to control. Coincubation with isorhamnetin, kaempferol, diosmetin, nevadensin, chrysin, equol, genistein, and hesperitin promoted the transport of 3′-O-methyl-epicatechin toward the basolateral side and decreased the apical efflux. Quercetin and luteolin considerably inhibited the appearance of this ( - )-epicatechin conjugate both in the apical and basolateral compartments. In conclusion, we could demonstrate that the efflux of ( - )-epicatechin conjugates to the apical or basal compartments of Caco-2 cells is modulated by certain classes of polyphenols and their amount. Ingesting ( - )-epicatechin with specific polyphenols could be a strategy to increase the bioavailability of (-)-epicatechin and to modulate its metabolic profile

Effect of Glucuronidation on the Potential of Kaempferol to Inhibit Serine/Threonine Protein Kinases

To study the effect of metabolic conjugation of flavonoids on the potential to inhibit protein kinase activity, the inhibitory effects of the dietary flavonol kaempferol and its major plasma conjugate kaempferol-3-O-glucuronide on protein kinases were studied. To this end, the inhibition of the phosphorylation activity of recombinant protein kinase A (PKA) and of cell lysate from the hepatocellular carcinoma cell line HepG2 on 141 putative serine/threonine phosphorylation sites derived from human proteins was assessed. Glucuronidation reduced the inhibitory potency of kaempferol on the phosphorylation activity of PKA and HepG2 lysate on average about 16 and 3.5 times, respectively, but did not appear to affect the target selectivity for kinases present in the lysate. The data demonstrate that, upon glucuronidation, kaempferol retains part of its intrinsic kinase inhibition potential, which implies that K3G does not necessarily need to be deconjugated to the aglycone for a potential inhibitory effect on protein kinases.</p

Effect of Glucuronidation on the Potential of Kaempferol to Inhibit Serine/Threonine Protein Kinases

To study the effect of metabolic conjugation of flavonoids on the potential to inhibit protein kinase activity, the inhibitory effects of the dietary flavonol kaempferol and its major plasma conjugate kaempferol-3-O-glucuronide on protein kinases were studied. To this end, the inhibition of the phosphorylation activity of recombinant protein kinase A (PKA) and of cell lysate from the hepatocellular carcinoma cell line HepG2 on 141 putative serine/threonine phosphorylation sites derived from human proteins was assessed. Glucuronidation reduced the inhibitory potency of kaempferol on the phosphorylation activity of PKA and HepG2 lysate on average about 16 and 3.5 times, respectively, but did not appear to affect the target selectivity for kinases present in the lysate. The data demonstrate that, upon glucuronidation, kaempferol retains part of its intrinsic kinase inhibition potential, which implies that K3G does not necessarily need to be deconjugated to the aglycone for a potential inhibitory effect on protein kinases.</p