[Show abstract][Hide abstract] ABSTRACT: 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.
The British journal of nutrition 09/2015; 114:1-10. DOI:10.1017/S0007114515002822 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidemiological evidence suggests that chronic consumption of fruit-based flavonoids is associated with cognitive benefits; however, the acute effects of flavonoid-rich (FR) drinks on cognitive function in the immediate postprandial period require examination. The objective was to investigate whether consumption of FR orange juice is associated with acute cognitive benefits over 6 h in healthy middle-aged adults.
Males aged 30-65 consumed a 240-ml FR orange juice (272 mg) and a calorie-matched placebo in a randomized, double-blind, counterbalanced order on 2 days separated by a 2-week washout. Cognitive function and subjective mood were assessed at baseline (prior to drink consumption) and 2 and 6 h post consumption. The cognitive battery included eight individual cognitive tests. A standardized breakfast was consumed prior to the baseline measures, and a standardized lunch was consumed 3 h post-drink consumption.
Change from baseline analysis revealed that performance on tests of executive function and psychomotor speed was significantly better following the FR drink compared to the placebo. The effects of objective cognitive function were supported by significant benefits for subjective alertness following the FR drink relative to the placebo.
These data demonstrate that consumption of FR orange juice can acutely enhance objective and subjective cognition over the course of 6 h in healthy middle-aged adults.
European Journal of Nutrition 08/2015; DOI:10.1007/s00394-015-1016-9 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The leaves of the olive plant (
) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and
IL-8 production were significantly reduced (
< 0·05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8–24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production
, adding to growing evidence that olive phenolics could be beneficial for health.
The British journal of nutrition 06/2015; 114(1):1-9. DOI:10.1017/S0007114515001269 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There has recently been increasing interest in the potential of flavanols, plant-derived compounds found in foods such as fruit and vegetables, to ameliorate age-related cognitive decline. Research suggests that cocoa flavanols improve memory and learning, possibly as a result of their anti-inflammatory and neuroprotective effects. These effects may be mediated by increased cerebral blood flow (CBF), thus, stimulating neuronal function.
The present study employed arterial spin labelling functional magnetic resonance imaging to explore the effect of a single acute dose of cocoa flavanols on regional CBF.
CBF was measured pre- and post-consumption of low (23 mg) or high (494 mg) 330 ml equicaloric flavanol drinks matched for caffeine, theobromine, taste and appearance according to a randomized counterbalanced crossover double-blind design in eight males and ten females, aged 50-65 years. Changes in perfusion from pre- to post-consumption were calculated as a function of each drink.
Significant increases in regional perfusion across the brain were observed following consumption of the high flavanol drink relative to the low flavanol drink, particularly in the anterior cingulate cortex and the central opercular cortex of the parietal lobe.
Consumption of cocoa flavanol improves regional cerebral perfusion in older adults. This provides evidence for a possible acute mechanism by which cocoa flavanols are associated with benefits for cognitive performance.
[Show abstract][Hide abstract] ABSTRACT: 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 symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging. In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 22 young (<35 years) and 20 elderly (50-80 year) healthy, male non-smokers consumed either a CF-containing drink (450 mg CF) or nutrient-matched, CF-free control drink bi-daily for 14 days. The primary endpoint was endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints included cardiac output, vascular stiffness, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Following 2 weeks of CF intake, FMD improved in young (6.1 ± 0.7 vs. 7.6 ± 0.7 %, p < 0.001) and elderly (4.9 ± 0.6 vs. 6.3 ± 0.9 %, p < 0.001). Secondary outcomes demonstrated in both groups that CF intake decreased pulse wave velocity and lowered total peripheral resistance, and increased arteriolar and microvascular vasodilator capacity, red cell deformability, and diastolic blood pressure, while cardiac output remained affected. In the elderly, baseline systolic blood pressure was elevated, driven by an arterial-stiffness-related augmentation. CF intake decreased aortic augmentation index (-9 %) and thus systolic blood pressure (-7 mmHg; Clinicaltrials.gov: NCT01639781). CF intake reverses age-related burden of cardiovascular risk in healthy elderly, highlighting the potential of dietary flavanols to maintain cardiovascular health.
Age 06/2015; 37(3):9794. DOI:10.1007/s11357-015-9794-9 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Flavonoids are a group of phenolic secondary plant metabolites that are ubiquitous in plant-based diets. Data from anthropological, observational and intervention studies have shown that many flavonoids are bioactive. For this reason, there is an increasing interest in investigating the potential health effects of these compounds. 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.
The objective of this study is to determine the habitual intake and main sources of anthocyanidins, flavanols, flavanones, flavones, flavonols, proanthocyanidins, theaflavins and thearubigins in the European Union.
We use food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database to estimate intake of flavonoids.
Mean (±SEM) intake of total flavonoids in Europe was 428±49 mg/d, of which 136±14 mg/d were monomeric compounds. Gallated flavan-3-ols (53±12 mg/d) were the main contributor. The lowest flavonoid intake was observed in Mediterranean countries (monomeric compounds: 95±11 mg/d). The distribution of intake was skewed in many countries, especially in Germany (monomeric flavonoids; mean intake: 181 mg/d; median intake: 3 mg/d).
The habitual intake of flavonoids in Europe is below the amounts found to have a significant health effect.
PLoS ONE 05/2015; 10(5):e0128132. DOI:10.1371/journal.pone.0128132 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Intra-individual variability of SREM was assessed in 7 young subjects, after consuming 10.7 mg CF/kg body weight (BW) on two occasions separated by one week. The effect of age on flavanols ADME was assessed in 20 young (18-35y) and 20 elderly (65-80y) 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 3 days separated by 1 week of wash-out. Blood and urine samples were collected for 24 h post consumption. The intra-individual variation, measured as CV(%) with respect to the area-under-the-curve of the concentration over time (AUC(0-6h) ) of SREM, was 16%, whilst the inter-individual 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'-β-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 (γ-VL) metabolites were lower in the elderly.
Cocoa flavanols are absorbed, metabolized, and excreted in healthy young and elderly subjects with relatively small differences between the two groups. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Coffee is a relatively rich source of chlorogenic acids (CGA), which, as other polyphenols, have been postulated to exert preventive effects against CVD and type 2 diabetes. As a considerable proportion of ingested CGA reaches the large intestine, CGA may be capable of exerting beneficial effects in the large gut. Here, we utilise a stirred, anaerobic, pH-controlled, batch culture fermentation model of the distal region of the colon in order to investigate the impact of coffee and CGA on the growth of the human faecal microbiota. Incubation of coffee samples with the human faecal microbiota led to the rapid metabolism of CGA (4 h) and the production of dihydrocaffeic acid and dihydroferulic acid, while caffeine remained unmetabolised. The coffee with the highest levels of CGA (P< 0·05, relative to the other coffees) induced a significant increase in the growth of Bifidobacterium spp. relative to the control vessel at 10 h after exposure (P< 0·05). Similarly, an equivalent quantity of CGA (80·8 mg, matched with that in high-CGA coffee) induced a significant increase in the growth of Bifidobacterium spp. (P< 0·05). CGA alone also induced a significant increase in the growth of the Clostridium coccoides-Eubacterium rectale group (P< 0·05). This selective metabolism and subsequent amplification of specific bacterial populations could be beneficial to host health.
The British journal of nutrition 03/2015; 113(08):1-8. DOI:10.1017/S0007114514003948 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cocoa is rich in a subclass of flavonoids known as flavanols, whose cardiovascular health benefits have been extensively reported. The appearance of flavanol metabolites in the systemic circulation after flavanol-rich foods consumption are 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. Secondly, 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.
Journal of Agricultural and Food Chemistry 02/2015; 63(35). DOI:10.1021/acs.jafc.5b00443 · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Data from epidemiological and human intervention studies have highlighted potential cardiovascular benefits of soy isoflavone-containing foods. In humans, genistein and daidzein are extensively metabolized after absorption into glucuronides and sulfate metabolites. However, limited data exist on isoflavone cellular metabolism, in particular in endothelial cells. We investigated the uptake and cellular metabolism of genistein, daidzein and its major in vivo microbial metabolite, equol, in human endothelial (HUVEC), liver (HepG2) and intestinal epithelial cells (Caco-2 monolayer). Our results indicate that genistein and daidzein are taken up by endothelial cells, and metabolized into methoxy-genistein-glucuronides, methoxy-genistein-sulfates and methoxy-daidzein-glucuronides. In contrast, equol was taken up but not metabolized. In HepG2 and Caco-2 cells, glucuronide and sulfate conjugates of genistein and daidzein and a sulfate conjugate of equol were formed. Our findings suggest that endothelial cell metabolism needs to be taken into account when investigating the cardioprotective mechanisms of action of isoflavones.
[Show abstract][Hide abstract] ABSTRACT: Background: Monitoring of fruit and vegetable (F&V) intake is fraught with difficulties. Available dietary assessment methods are associated with considerable error, and the use of biomarkers offers an attractive alternative. Few studies to date have examined the use of plasma biomarkers to monitor or predict the F&V intake of volunteers consuming a wide range of intakes from both habitual F&V and manipulated diets. Objective: This study tested the hypothesis that an integrated biomarker calculated from a combination of plasma vitamin C, cholesterol-adjusted carotenoid concentration and Ferric Reducing Antioxidant Power (FRAP) had more power to predict F&V intake than each individual biomarker. Methods: Data from a randomized controlled dietary intervention study FLAVURS (Flavonoids University of Reading Study); n = 1541 in which the test groups observed sequential increases of 2.3, 3.2, and 4.2 portions of F&Vs every 6 wk across an 18-wk period were used in this study. Results: An integrated plasma biomarker was devised that included plasma vitamin C, total cholesterol adjusted carotenoids, and FRAP values, which better correlated with F&V intake (r = 0.47, P < 0.001) than the individual biomarkers (r = 0.33, P < 0.01; r = 0.37, P < 0.001; and r = 0.14, respectively; P = 0.099). Inclusion of urinary potassium concentration did not significantly improve the correlation. The integrated plasma biomarker predicted F&V intake more accurately than did plasma total cholesterol adjusted carotenoid concentration, with the difference being significant at visit 2 (P < 0.001) and with a tendency to be significant at visit 1 (P = 0.07). Conclusion: Either plasma total cholesterol adjusted carotenoid concentration or the integrated biomarker could be used to distinguish between high- and moderate-F&V consumers. This trial was registered at www.controlled-trials.com as ISRCTN47748735.
Journal of Nutrition 11/2014; 144(11):1866-72. DOI:10.3945/jn.114.192856 · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ScopeBlueberries are a rich source of flavonoids and phenolic acids. Currently, little information is available regarding the impact of processing on the bioavailability and the bioactivity of blueberry (poly)phenols.Methods and resultsIn a randomized, controlled crossover trial, ten healthy volunteers consumed (a) blueberry-containing baked products, (b) an unprocessed blueberry drink containing the same amount of freeze-dried blueberry powder as used in the baked products, and (c) matched control baked products. Endothelial function was measured as flow-mediated dilation (FMD) and plasma samples taken at baseline and at 1, 2, 4, and 6 h post-consumption. Although processing did not significantly change the total (poly)phenolic amount, the processed products contained significantly less anthocyanins (-42%), more chlorogenic acid (23%), no flavanol nonamers or decamers, and significantly more flavanol dimers and trimers (36% and 28%, respectively). FMD increased after 1, 2, and 6 h consumption of the baked products to a similar degree as the unprocessed blueberries, despite significant differences in the levels of individual plasma metabolites. No changes were observed after the consumption of the control product.Conclusion
Careful processing can preserve important biological activities of blueberries despite changing the blueberry (poly)phenol composition and plasma metabolite profile.This article is protected by copyright. All rights reserved
[Show abstract][Hide abstract] ABSTRACT: Parkinson's disease is characterized by the progressive and selective loss of dopaminergic neurons in the substantia nigra. It has been postulated that endogenously formed 5-S-cysteinyldopamine (CysDA) and its metabolites may be, in part, responsible for this selective neuronal loss, although the mechanisms by which they contribute to such neurotoxicity are not understood. Exposure of neurons in culture to CysDA caused cell injury, apparent 12-48 h post-exposure. A portion of the neuronal death induced by CysDA was preceded by a rapid uptake and intracellular oxidation of CysDA, leading to an acute and transient activation of ERK2 and caspase 8. The oxidation of CysDA also induced the activation of apoptosis signal-regulating kinase 1 via its de-phosphorylation at Ser-967, the phosphorylation of c-jun N-terminal kinase (JNK) and c-Jun (Ser-73) as well as the activation of p38, caspase 3, caspase 8, caspase 7 and caspase 9. Concurrently, the inhibition of complex I by the dihydrobenzothiaine DHBT-1, formed from the intracellular oxidation of CysDA, induces complex I inhibition and the subsequent release of cytochrome c which further potentiates pro-apoptotic mechanisms. Our data suggest a novel, comprehensive mechanism for CysDA that may hold relevance for the selective neuronal loss observed in Parkinson's disease.
[Show abstract][Hide abstract] ABSTRACT: Consumption of flavanol-rich foods is associated with an improvement in endothelial function. However, the specific biologically active flavanol metabolites involved in this benefit, as well as their molecular mechanisms of action have not been identified. The aim of this work was to examine the effect of plasma flavanol metabolites on adhesion of monocytes to TNF-α-activated endothelial cells and identify potential underlying mechanisms.
4'-O-methyl(-)-epicatechin, 4'-O-methyl(-)-epicatechin-7-β-d-glucuronide, and (-)-epicatechin-4'-sulfate decreased the adhesion of monocytes to endothelial cells at physiologically relevant concentrations, from 0.2 to 1 μM. Transcriptomic studies showed that each of the flavanol metabolites affected the expression of different genes in endothelial cells. However, these genes are involved in the cellular processes that control adhesion and migration of monocytes to vascular endothelium, most notably those regulating cell adhesion, cell-cell junctions, focal adhesion, and cytoskeleton remodeling. Gene expression profiles obtained suggest lower monocyte recruitment, in agreement with results from cell adhesion assays. The nutrigenomic effect of metabolites seems to be mediated through their capacity to modulate phosphorylation of p65 and p38 cell-signaling proteins.
Our study provides findings into the molecular mechanisms by which plasma flavanol metabolites could be efficient to preserve vascular endothelium integrity in nutritionally relevant conditions.
[Show abstract][Hide abstract] ABSTRACT: The fruit of the date palm (Phoenix dactylifera L.) is a rich source of dietary fibre and polyphenols. We have investigated gut bacterial changes induced by the whole date fruit extract (digested date extract; DDE) and its polyphenol-rich extract (date polyphenol extract; DPE) using faecal, pH-controlled, mixed batch cultures mimicking the distal part of the human large intestine, and utilising an array of microbial group-specific 16S rRNA oligonucleotide probes. Fluorescence microscopic enumeration indicated that there was a significant increase in the growth of bifidobacteria in response to both treatments, whilst whole dates also increased bacteroides at 24 h and the total bacterial counts at later fermentation time points when compared with DPE alone. Bacterial metabolism of whole date fruit led to the production of SCFA, with acetate significantly increasing following bacterial incubation with DDE. In addition, the production of flavonoid aglycones (myricetin, luteolin, quercetin and apigenin) and the anthocyanidin petunidin in less than 1 h was also observed. Lastly, the potential of DDE, DPE and metabolites to inhibit Caco-2 cell growth was investigated, indicating that both were capable of potentially acting as antiproliferative agents in vitro, following a 48 h exposure. This potential to inhibit growth was reduced following fermentation. Together these data suggest that consumption of date fruits may enhance colon health by increasing beneficial bacterial growth and inhibiting the proliferation of colon cancer cells. This is an early suggestion that date intake by humans may aid in the maintenance of bowel health and even the reduction of colorectal cancer development.
[Show abstract][Hide abstract] ABSTRACT: Chlorogenic acids (CGA) are a class of polyphenols noted for their health benefits. These compounds were identified and quantified, using LC-MS and HPLC, in commercially available coffees which varied in processing conditions. Analysis of ground and instant coffees indicated the presence of caffeoylquinic acids (CQA), feruloylquinic acids (FQA) and dicaffeoylquinic acids (diCQA) in all 18 samples tested. 5-CQA was present at the highest levels, between 25 and 30% of total CGA; subsequent relative quantities were: 4-CQA>3-CQA>5-FQA>4-FQA>diCQA (sum of 3,4, 3,5 and 4,5-diCQA). CGA content varied greatly (27.33-121.25mg/200ml coffee brew), driven primarily by the degree of coffee bean roasting (a high amount of roasting had a detrimental effect on CGA content). These results highlight the broad range of CGA quantity in commercial coffee and demonstrate that coffee choice is important in delivering optimum CGA intake to consumers.
[Show abstract][Hide abstract] ABSTRACT: 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.
The British journal of nutrition 12/2013; 111(8):1-11. DOI:10.1017/S0007114513003930 · 3.45 Impact Factor