Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables:Evidence from in vitro models and a human bioavailability study

The aim was to incorporate vegetables containing the phytochemicals quercetin, apigenin, glucoraphanin and carotenoids into a processed potato-based snack and assess their bioaccessibility and bioavailability. Three different processing routes were tested for incorporation and retention of phytochemicals in snacks using individually quick frozen or freeze-dried vegetables. No significant differences in the uptake or transport of quercetin or apigenin between a vegetable mix or snacks were observed using the CaCo-2 transwell model. Simulated in vitro digestions predicted a substantial release of quercetin and apigenin, some release of glucoraphanin but none for carotenes from either the snack or equivalent steamed vegetables. In humans, there were no significant differences in the bioavailability of quercetin, apigenin or glucoraphanin from the snack or equivalent steamed vegetables. We have shown that significant quantities of freeze-dried vegetables can be incorporated into snacks with good retention of phytochemicals and with similar bioavailability to equivalent steamed vegetables

Lack of acute or chronic effects of epicatechin-rich and procyanidin-rich apple extracts on blood pressure and cardiometabolic biomarkers in adults with moderately elevated blood pressure: a randomized, placebo-controlled crossover trial

Background: The reported effects of flavanol-rich foods such as cocoa, dark chocolate, and apples on blood pressure and endothelial function may be due to the monomeric flavanols [mainly (–)-epicatechin (EC)], the oligomeric flavanols [procyanidins (PCs)], or other components. Reports of well-controlled intervention studies that test the effects of isolated oligomeric flavanols on biomarkers of cardiovascular health are lacking. Objective: We studied the acute and chronic effects of an EC-rich apple flavanol extract and isolated apple PCs on systolic blood pressure (BP) and other cardiometabolic biomarkers. Design: Forty-two healthy men and women with moderately elevated BP completed this randomized, double-blind, placebo-controlled, 4-arm crossover trial. Participants ingested a single dose of an apple flavanol extract (70 mg monomeric flavanols, 65 mg PCs), a double dose of this extract (140 mg monomeric flavanols, 130 mg PCs), an apple PC extract (130 mg PCs, 6.5 mg monomeric flavanols), or placebo capsules once daily for 4 wk, in random order. Biomarkers of cardiovascular disease risk and vascular function were measured before and 2 h after ingestion of the first dose and after the 4-wk intervention. Results: Compared with placebo, none of the isolated flavanol treatments significantly (P < 0.05) changed systolic or diastolic BP (peripheral and aortic), plasma nitric oxide (NO) reaction products, or measures of arterial stiffness (carotid femoral pulse-wave velocity, brachial-ankle pulse-wave velocity, or Augmentation Index) after 2 h or 4 wk of the intervention. There were no changes in plasma endogenous metabolite profiles or circulating NO; endothelin 1; total, HDL, or LDL cholesterol; triglycerides; fasting glucose; fructosamine; or insulin after 4 wk of the intervention. Conclusions: Our data suggest that, in isolation, neither monomeric flavanols nor PCs affect BP, blood lipid profiles, endothelial function, or glucose control in individuals with moderately elevated BP. The reported benefits of consuming flavanol-rich cocoa, chocolate, and apple products appear to be dependent on other components, which may work in combination with monomeric flavanols and PCs. This trial was registered at www.clinicaltrials.gov as NCT02013856

Meta-Analysis of the Effects of Foods and Derived Products Containing Ellagitannins and Anthocyanins on Cardiometabolic Biomarkers: Analysis of Factors Influencing Variability of the Individual Responses

peer-reviewedUnderstanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/). The authors thank the financial support of the COST Action FA1403 “POSITIVe” to conduct a short-term scientific mission to K.C. at CEBAS-CSIC (A.G.-S. and M.T.G.-C.) during which the data analysis was performed

Urinary excretion of strawberry anthocyanins is dose dependent for physiological oral doses of fresh fruit

There is considerable interest in coloured fruits and berries as sources of biologically active anthocyanins. To examine the relationship between the oral dose and the amount excreted for anthocyanins from a food source across a physiological range of doses, volunteers were fed, in random order, four portions (100–400 g) of fresh strawberries as part of a standard breakfast. Urine was collected at 2 h intervals up to 8 h, and for the period 8–24 h. Fresh strawberries contained pelargonidin-3-glucoside as the major anthocyanin with smaller amounts of cyanidin-3-glucoside and pelargonidin-3-rutinoside. Anthocyanins were detected in the urine of all volunteers for all doses, predominantly as pelargonidin glucuronide and sulphate metabolites. There was a strong, linear relationship between oral dose and anthocyanin excretion (Pearson's product moment correlation coefficient = 0.692, p < 0.001, n = 40) which indicated that on an average, every additional unit of dose caused 0.0166 units of excretion. Within individuals, dose – excretion data fitted a linear regression model (median R2 = 0.93). We conclude that strawberry anthocyanins are partially bioavailable in humans with a linear relationship between oral dose and urinary excretion for doses up to 400 g fresh fruit

Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo-controlled, crossover trial

Scope: Flavanol-rich foods are known to exert beneficial effects on cardiovascular health. The biological effects depend on bioavailability of flavanols which may be influenced by food matrix and dose ingested. We compared the bioavailability and dose-response of epicatechin from whole apple and an epicatechin-rich extract, and the effects on plasma and urinary nitric oxide (NO) metabolites. Methods and results: In a randomized, placebo-controlled, crossover trial, subjects consumed drinks containing 70 and 140 mg epicatechin from an apple extract and an apple puree containing 70 mg epicatechin. Blood and urine samples were collected for 24 h post ingestion. Maximum plasma concentration, AUC(0–24 h), absorption and urinary excretion were all significantly higher after ingestion of both epicatechin drinks compared with apple puree (p 2-fold higher after ingestion of the 140 mg epicatechin drink compared to the 70 mg epicatechin drink (p < 0.05). Excretion of NO metabolites was higher for all test products compared with placebo, which was significant for the high dose drink (p = 0.016). Conclusions: Oral bioavailability of apple epicatechin increases at higher doses, is reduced by whole apple matrix and has the potential to increase NO bioavailability

Lack of effect of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on platelet function

BACKGROUNDThe health benefits of fruit and vegetable-rich diets may be partly due to modulation of platelet activity by bioactive phytochemicals. The aim of this study was to investigate the effects of bioactive-rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples (n =15 subjects) were treated with extracts of bioactive-rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Platelet function was assessed using the PFA-100. RESULTSNone of the extracts containing various flavonoids, glucosinolates and other bioactives, or isolated bioactive metabolites of quercetin or sulforaphane, caused significant changes in PFA-100 closure time (CT). In contrast, the positive controls (aspirin and Abciximab) consistently caused significant increases in CT for the platelet agonists epinephrine and ADP, respectively. CONCLUSIONThese data do not support the notion that these plant bioactives can improve human platelet function

Cardiovascular disease risk biomarkers and liver and kidney function are not altered in postmenopausal women after ingesting an elderberry extract rich in anthocyanins for 12 weeks

Growing evidence supports a cardio-protective role for anthocyanins; however, there is limited evidence on their efficacy and safety following the consumption of relatively high but dietarily achievable doses in humans. We conducted a parallel-designed, randomized, placebo-controlled study to examine the effect of chronic consumption of anthocyanins on biomarkers of cardiovascular disease (CVD) risk and liver and kidney function in 52 healthy postmenopausal women (n = 26 in treatment and placebo groups). Volunteers (BMI, 24.7 +/- 3.6 kg/m(2); age, 58.2 +/- 5.6 y) consumed 500 mg/d anthocyanins as cyanidin glycosides (from elderberry) or placebo for 12 wk (2 capsules twice/d). At the beginning (wk 0) and end of the 12-wk intervention, levels of anthocyanins and biomarkers of CVD (inflammatory biomarkers, platelet reactivity, lipids, and glucose) and liver and kidney function (total bilirubin, albumin, urea, creatinine, alkaline phosphatase, alanine aminotransferase, and gamma-glutyl transferase) were assessed in fasted blood. Anthropometric, blood pressure, and pulse measurements were also taken. In addition, postprandial plasma anthocyanins were measured (t = 1, 2, 3 h) following a 500-mg oral bolus dose. After 12 wk of chronic exposure to anthocyanins, there was no significant change in biomarkers of CVD risk and liver and kidney function remained within clinically acceptable ranges. We observed no plasma accumulation of anthocyanins; however, postprandial metabolism increased (P = 0.02). In conclusion, these data suggest that chronic consumption of 500 mg/d of elderberry extract for 12 wk is apparently safe, but ineffective in altering biomarkers of CVD risk in healthy postmenopausal women

Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion

Oranges are rich sources of flavonoids that are bioactive and may protect against age-related diseases. The absorption of orange flavanones may be affected by factors such as processing and subject anthropometric variables, and the bioactivity of the absorbed phytochemicals depends on how they are metabolised during absorption. In a randomised cross-over study, twenty subjects consumed a single portion of orange fruit (150 g) or juice (300 g) that contained the flavanones narirutin and hesperidin, and an additional 109 subjects across a broad age range (18–80 years) consumed the juice. Flavanone metabolites were measured in regularly collected samples of plasma and urine. After consumption of fruit or juice, flavanone conjugates, but not the aglycones, were detected in plasma and urine. The flavanone conjugates were shown to include the 7- and 4′-O-monoglucuronides of naringenin, the 7- and 3′-O-monoglucuronides of hesperetin, two hesperetin diglucuronides and a hesperetin sulfo-glucuronide, but no aglycones or rutinosides. Analysis of the plasma pharmacokinetic and urinary excretion data on a dose-adjusted basis indicated no difference in absorption or excretion of either flavanone between the fruit and juice matrices. In the extended urinary excretion dataset the individual variation was very large (range 0–59 % urinary yield). There was a small but significant (P < 0·05) decrease in the excretion of hesperetin (but not naringenin) with increasing age (P < 0·05), but the effects of sex, BMI and contraceptive pill use were shown not to be associated with the variation in flavanone excretion

Stable isotope pilot study of exchangeable copper kinetics in human blood plasma

To develop further our understanding of initial dietary copper metabolism, a method has been developed to separate plasma copper that is bound to albumin, from that bound to ceruloplasmin. This method has been tested using plasma samples from a pilot study involving six human volunteers who consumed 3mg oral doses of the stable isotope (65)Cu and gave blood samples at timed intervals up to 7 days. The results suggest that this method can be used to monitor dynamic fluctuations in newly absorbed copper over a short time frame