The effects of grape-seed polyphenols against the development of hypertension and other cardiometabolic conditions associated with the metabolic syndrome (MetS) were studied in rats fed a high-fat, high-carbohydrate diet, known as the cafeteria (CAF) diet. Two groups of Wistar rats were fed standard (STD) or CAF diets for 12 weeks. The CAF diet-fed rats were administered different doses of a low-molecular-weight grape-seed polyphenol extract (LM-GSPE) (25, 100 and 200 mg/kg per d) or vehicle daily, and the STD diet-fed rats were administered LM-GSPE (100 mg/kg per d) or vehicle using ten animals per group. Body weight (BW), waist perimeter (WP) and systolic and diastolic blood pressures (BP) by the tail-cuff method were recorded weekly. The animals were housed in metabolic chambers every 2 weeks to estimate daily food and liquid intakes and to collect faeces and urine samples. The plasma lipid profile was analysed at time 0 and on the 4th, 7th, 10th and 12th weeks of the experiment. Moreover, plasma leptin was measured at the end of the experiment. Results demonstrated that LM-GSPE, when administered with the CAF diet, attenuated the increase in BP, BW, WP and improved lipid metabolism in these animals. However, although the 25- and 100-mg/kg per d doses were sufficient to produce beneficial effects on BP and lipid metabolism, a 200-mg/kg per d dose was necessary to have an effect on BW and WP. The present findings suggest that LM-GSPE is a good candidate for a BP-lowering agent that can also ameliorate other conditions associated with the MetS.

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-mediated vasodilation (FMD)) that plateaued after 2 weeks. Subsequently, in a randomised, controlled, double-masked, parallel-group dietary intervention trial (Clinicaltrials.gov: NCT01799005), 100 healthy, middle-aged (35–60 years) men and women consumed either the CF-containing drink (450 mg) or a nutrient-matched CF-free control bi-daily for 1 month. The primary end point was FMD. Secondary end points included plasma lipids and blood pressure, thus enabling the calculation of Framingham Risk Scores and pulse wave velocity. At 1 month, CF increased FMD over control by 1·2 % (95 % CI 1·0, 1·4 %). CF decreased systolic and diastolic blood pressure by 4·4 mmHg (95 % CI 7·9, 0·9 mmHg) and 3·9 mmHg (95 % CI 6·7, 0·9 mmHg), pulse wave velocity by 0·4 m/s (95 % CI 0·8, 0·04 m/s), total cholesterol by 0·20 mmol/l (95 % CI 0·39, 0·01 mmol/l) and LDL-cholesterol by 0·17 mmol/l (95 % CI 0·32, 0·02 mmol/l), whereas HDL-cholesterol increased by 0·10 mmol/l (95 % CI 0·04, 0·17 mmol/l). By applying the Framingham Risk Score, CF predicted a significant lowering of 10-year risk for CHD, myocardial infarction, CVD, death from CHD and CVD. In healthy individuals, regular CF intake improved accredited cardiovascular surrogates of cardiovascular risk, demonstrating that dietary flavanols have the potential to maintain cardiovascular health even in low-risk subjects.

Dietary interventions with flavan-3-ols have shown beneficial effects on vascular function. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations. Therefore, in the present study, we assessed the habitual intake of flavan-3-ol monomers, proanthocyanidins (PA) and theaflavins in the European Union (EU) and determined their main food sources using the EFSA (European Food Safety Authority) Comprehensive European Food Consumption Database. Data for adults aged 18–64 years were available from fourteen European countries, and intake was determined using the FLAVIOLA Flavanol Food Composition Database, developed for the present study and based on the latest US Department of Agriculture and Phenol-Explorer databases. The mean habitual intake of flavan-3-ol monomers, theaflavins and PA ranged from 181 mg/d (Czech Republic) to 793 mg/d (Ireland). The highest intakes of flavan-3-ol monomers and theaflavins were observed in Ireland (191/505 mg/d) and the lowest intakes in Spain (24/9 mg/d). In contrast, the daily intake of PA was highest in Spain (175 mg/d) and lowest in The Netherlands (96 mg/d). Main sources were tea (62 %), pome fruits (11 %), berries (3 %) and cocoa products (3 %). Tea was the major single contributor to monomer intake (75 %), followed by pome fruits (6 %). Pome fruits were also the main source of PA (28 %). The present study provides important data on the population-based intake of flavanols in the EU and demonstrates that dietary intake amounts for flavan-3-ol monomers, PA and theaflavins vary significantly across European countries. The average habitual intake of flavan-3-ols is considerably below the amounts used in most dietary intervention studies.

A considerable number of epidemiological investigations and intervention studies have supported an association between the intake of flavanol- and proanthocyanidin-containing foods and a decreased risk of metabolic diseases. Nonetheless, less is know about the capacity of tissues to accumulate flavanols and/or their metabolites. The main objective of the present study was to determine (n 20) plasma bioavailability and disposition in the liver, muscle, brown adipose tissue (BAT) and white adipose tissues (mesenteric and perirenal) in rats after a long-term consumption of three doses of grape seed phenolic extract (5, 25 and 50 mg/kg body weight) for 21 d in order to determine whether there is a dose–response relationship. Glucuronidated conjugates (total glucuronidated conjugates: C5mg/kg 1·9; C25mg/kg 6·4; C50mg/kg 27·7 μmol/l plasma) followed by methyl glucuronidated conjugates (total methyl glucuronidated conjugates: C5mg/kg 1·98; C25mg/kg 4·48; C50mg/kg 12·5 μmol/l plasma) were the main flavanol metabolites quantified in plasma, also detecting a dimer in its free form (C25mg/kg 0·74; C50mg/kg 0·79 μmol/l plasma). Each of the studied organs has a particular behaviour of accumulation and response to the assayed grape seed extract doses, with an exponential bioavailability–dose relationship in BAT, in which flavanols could play an important role in the reduction or prevention of obesity, modulating the functionality of that tissue.

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 134 (se 2) mmHg, diastolic BP (DBP) 87 (se 2) mmHg) were randomised to consume single servings of either a high-flavanol (HF, 701 mg) or a low-flavanol (LF, 22 mg) cocoa beverage in a double-blind, cross-over design with 3–7-d washout between treatments. Two hours after cocoa consumption, FMD was measured, followed by continuous beat-to-beat assessment (Finapres™) of BP before and during 10 min of cycling at 75 % of age-predicted maximum heart rate. Averaged data from two assessments on each type of beverage were compared by analysis of covariance using pre-exercise BP as the covariate. Pre-exercise BP was similar after taking LF and HF (153 (se 3)/88 (se 3) v. 153 (se 4)/87 (se 2) mmHg, respectively, P>0·05). However, the BP response to exercise (area under BP curve) was attenuated by HF compared with LF. BP increases were 68 % lower for DBP (P = 0·03) and 14 % lower for mean BP (P = 0·05). FMD measurements were higher after taking HF than after taking LF (6·1 (se 0·6) % v. 3·4 (se 0·5) %, P < 0·001). By facilitating vasodilation and attenuating exercise-induced increases in BP, cocoa flavanols may decrease cardiovascular risk and enhance the cardiovascular benefits of moderate intensity exercise in at-risk individuals.

The present study evaluates for the first time in dogs, the kinetics of green tea catechins and their metabolic forms in plasma and urine. Ten beagles were administered 173 mg (12·35 mg/kg body weight) of catechins as a green tea extract, in capsules. Blood samples were collected during 24 h after intake and urine samples were collected during the following periods of time: 0–2, 2–6, 6–8 and 8–24 h. Two catechins with a galloyl moiety and three conjugated metabolites were detected in plasma. Most of the detected forms in plasma reached their maximum plasma concentration (Cmax) at around 1 h. Median Cmax for ( − )-epigallocatechin-3-gallate (EGCG), ( − )-epicatechin-3-gallate (ECG), ( − )-epigallocatechin glucuronide (EGC-glucuronide), ( − )-epicatechin glucuronide (EC-glucuronide), ( − )-epicatechin sulphate (EC-sulphate) were 0·3 (range 0·1–1·9), 0·1 (range 0–0·4), 0·8 (range 0·2–3·9), 0·2 (range 0·1–1·7) and 1 (range 0·3–3·4) μmol/l, respectively. The areas under the plasma concentration v. time curves (AUC0 → 24) were 427 (range 102–1185) μmol/l × min for EGC-glucuronide, 112 (range 53–919) μmol/l × min for EC-sulphate, 71 (range 26–306) μmol/l × min for EGCG, 40 (range 12–258) μmol/l × min for EC-glucuronide and 14 (range 0·1–124) μmol/l × min for ECG. The values of mean residence time (MRT0 → 24) were 5 (range 2–16), 2 (range 1–11), 10 (range 2–13), 3 (range 2–16) and 2·4 (range 1–18) h for EGCG, ECG, EGC-glucuronide, EC-glucuronide and EC-sulphate, respectively. In urine, catechins were present as conjugated forms, suggesting bile excretion of EGCG and ECG. Green tea catechins are absorbed following an oral administration and EGC-glucuronide is the metabolic form that remains in the organism for a longer period of time, suggesting that this compound could suffer an enterohepatic cycle.

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 human large intestine. Incubation of ( − )-epicatechin or (+)-catechin (150 mg/l or 1000 mg/l) with faecal bacteria, led to the generation of 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, 5-phenyl-γ-valerolactone and phenylpropionic acid. However, the formation of these metabolites from (+)-catechin required its initial conversion to (+)-epicatechin. The metabolism of both flavanols occurred in the presence of favourable carbon sources, notably sucrose and the prebiotic fructo-oligosaccharides, indicating that bacterial utilisation of flavanols also occurs when preferential energy sources are available. (+)-Catechin incubation affected the growth of select microflora, resulting in a statistically significant increase in the growth of the Clostridium coccoides–Eubacterium rectale group, Bifidobacterium spp. and Escherichia coli, as well as a significant inhibitory effect on the growth of the C. histolyticum group. In contrast, the effect of ( − )-epicatechin was less profound, only significantly increasing the growth of the C. coccoides–Eubacterium rectale group. These potential prebiotic effects for both (+)-catechin and ( − )-epicatechin were most notable at the lower concentration of 150 mg/l. As both ( − )-epicatechin and (+)-catechin were converted to the same metabolites, the more dramatic change in the growth of distinct microfloral populations produced by (+)-catechin incubation may be linked to the bacterial conversion of (+)-catechin to (+)-epicatechin. Together these data suggest that the consumption of flavanol-rich foods may support gut health through their ability to exert prebiotic actions.