RESUMO
Elevated circulating cholesterol levels are a risk factor for CVD which is also associated with sub-optimal vascular function. There is emerging evidence that anthocyanins can cause beneficial cardio-protective effects by favourably modulating lipoprotein profiles. We compared the effects of blood orange juice which is rich in anthocyanins and blonde orange juice without anthocyanins on LDL-cholesterol and other biomarkers of CVD risk, vascular function and glycaemia. In all, forty-one participants (aged 25-84 years) with a waist circumference >94 cm (men) and >80 cm (women) completed a randomised, open label, two-arm cross-over trial. For 28 d participants ingested (i) 500 ml blood orange juice providing 50 mg anthocyanins/d and (ii) 500 ml blonde orange juice without anthocyanins. There was a minimum 3-week washout period between treatments. LDL-cholesterol and other biomarkers associated with CVD risk and glycaemia were assessed at the start and end of each treatment period. No significant differences were observed in total, HDL- and LDL-cholesterol, TAG, glucose, fructosamine, nitric oxide, C-reactive protein, aortic systolic blood pressure and diastolic blood pressure or carotid-femoral and brachial-ankle pulse wave velocity after 28 d ingestion of blood orange juice compared with standard orange juice. The lack of effect on LDL-cholesterol may be due to the modest concentration of anthocyanins in the blood orange juice.
Assuntos
Antocianinas/farmacologia , Doenças Cardiovasculares/sangue , LDL-Colesterol/sangue , Citrus sinensis/química , Sucos de Frutas e Vegetais , Hiperglicemia/sangue , Extratos Vegetais/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Hiperglicemia/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Understanding 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.
Assuntos
Antocianinas/química , Antocianinas/farmacologia , Biomarcadores , Dieta , Metabolismo Energético/efeitos dos fármacos , Alimentos , Taninos Hidrolisáveis/química , Taninos Hidrolisáveis/farmacologia , Miocárdio/metabolismo , Antocianinas/efeitos adversos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Suplementos Nutricionais , Humanos , Taninos Hidrolisáveis/efeitos adversos , Fatores de RiscoRESUMO
We hypothesised that consumption of flavanol-containing apple puree would modulate platelet activity and increase nitric oxide metabolite status, and that high flavanol apple puree would exert a greater effect than low flavanol apple puree. 25 subjects consumed 230 g of apple puree containing 25 and 100mg epicatechin (low and high flavanol apple puree, respectively) and aspirin (75 mg) in random order. Measurements were made at baseline, acutely after treatment (2, 6 and 24 h), and after 14 d of treatment. Low flavanol apple puree significantly attenuated ADP and epinephrine-induced integrin-ß3 expression 2 h and 6 h after consumption and ADP and epinephrine-induced P-selectin expression within 2h of consumption. High flavanol apple puree attenuated epinephrine and ADP-induced integrin-ß3 expression after 2 and 6h. ADP and epinephrine-induced integrin-ß3 expression was significantly attenuated 2, 6 and 24 h after consumption of aspirin, whilst 14 d aspirin consumption attenuated collagen-induced P-selectin expression only. The plasma total nitric oxide metabolite conc. was significantly increased 6h after consumption of both low and high flavanol apple purees. In conclusion, consumption of apple purees containing ⩾25 or 100 mg flavanols transiently attenuated ex vivo integrin-ß3 and P-selectin expression and increased plasma nitric oxide metabolite conc. in healthy subjects, but the effect was not enhanced for the high flavanol apple puree.
Assuntos
Plaquetas/efeitos dos fármacos , Catequina/análise , Catequina/farmacologia , Ingestão de Alimentos , Manipulação de Alimentos , Malus/química , Óxido Nítrico/metabolismo , Adulto , Ácido Ascórbico/sangue , Biomarcadores/sangue , Plaquetas/fisiologia , Proteína C-Reativa/metabolismo , Catequina/urina , Endotelina-1/sangue , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: There is increasing evidence that consumption of plant bioactives such as polyphenols and glucosinolates reduces cardiovascular disease risk and improves endothelial function. In the Black Sea area, a number of plants are consumed alone and as ingredients in traditional foods, and dill, nettle, kale, Sideritis and persimmon were identified as bioactive-rich traditional food plants. The present study investigated the effects of plant extracts on cellular markers of endothelial function (eNOS activation and expression and ET-1 secretion). RESULTS: Treatment of human umbilical vein endothelial cells with persimmon extract significantly increased Akt and eNOS phosphorylation and nitric oxide metabolites and significantly decreased secretion of ET-1 to the media after 24 h compared with a vehicle control (all P < 0.01). None of the other plant extracts significantly altered any markers of endothelial function. CONCLUSION: These findings suggest that persimmon fruit contains bioactives that can improve endothelial function via activation of eNOS and reduction in ET-1 secretion, but that dill, kale, Sideritis and nettle do not.
Assuntos
Diospyros/química , Endotelina-1/metabolismo , Endotélio Vascular/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Extratos Vegetais/farmacologia , Anethum graveolens/química , Mar Negro , Brassica/química , Bulgária , Cultura , Meios de Cultivo Condicionados/química , Endotélio Vascular/metabolismo , Ativação Enzimática/efeitos dos fármacos , Alimentos , Frutas , República da Geórgia , Células Endoteliais da Veia Umbilical Humana , Humanos , Nitratos/análise , Nitritos/análise , Fenóis/análise , Romênia , Federação Russa , Sérvia , Sideritis/química , Turquia , Ucrânia , Urtica dioica/químicaRESUMO
BACKGROUND: The 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. RESULTS: None 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. CONCLUSION: These data do not support the notion that these plant bioactives can improve human platelet function.
Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Frutas/química , Extratos Vegetais/farmacologia , Verduras/química , Adulto , Anethum graveolens/química , Mar Negro , Brassica/química , Cultura , Diospyros/química , Feminino , Flavonoides/análise , Alimentos , Glucosinolatos/análise , Humanos , Isotiocianatos/farmacologia , Lythraceae/química , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/química , Inibidores da Agregação Plaquetária/farmacologia , Testes de Função Plaquetária , Polifenóis/análise , Quercetina/farmacologia , Sideritis/química , Sulfóxidos , Urtica dioica/químicaRESUMO
BACKGROUND: The beneficial effect of fruit- and vegetable-rich diets on cardiovascular health is partly attributed to the effect of their bioactive compounds on platelet function. The aim of this study was to investigate the effects of bioactive-rich plant extracts and isolated bioactive metabolites on platelet function. Blood samples from healthy subjects (n = 4) and subjects with metabolic syndrome (n = 4) were treated with six extracts of bioactive-rich plants consumed as traditional foods in the Black Sea region, or with human metabolites of the bioactives quercetin and sulforaphane. Markers of arachidonic acid induced platelet activation and platelet-leucocyte aggregation were assessed using flow cytometry. RESULTS: In subjects with metabolic syndrome, kale extract significantly inhibited agonist induced P-selectin expression (P = 0.004). Sulforaphane-cysteine-glycine, a human plasma metabolite of the related glucosinolate, glucoraphanin, significantly inhibited P-selectin and GPIIb-IIIa expression (P = 0.020 and 0.024, respectively) and platelet-neutrophil aggregation (P = 0.027). Additionally, pomegranate extract significantly inhibited GPIIb-IIIa expression (P = 0.046) in subjects with metabolic syndrome. In healthy subjects only dill extract significantly inhibited agonist induced P-selectin expression (P = 0.025). CONCLUSION: These data show that bioactive-rich extracts of kale and pomegranate that are consumed as traditional plant foods of Black Sea area countries were effective in modulating platelet function.
Assuntos
Brassica/química , Lythraceae/química , Extratos Vegetais/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Anethum graveolens/química , Ácido Araquidônico/farmacologia , Mar Negro , Plaquetas/efeitos dos fármacos , Cultura , Diospyros/química , Alimentos , Frutas/química , Humanos , Isotiocianatos/sangue , Isotiocianatos/farmacologia , Síndrome Metabólica/sangue , Selectina-P/sangue , Folhas de Planta/química , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/análise , Quercetina/sangue , Quercetina/farmacologia , Sideritis/química , Sulfóxidos , Urtica dioica/químicaRESUMO
SCOPE: Some dietary interventions with berry fruits, berry fruit extracts, and purified anthocyanins have been reported to beneficially alter lipoprotein profiles in hyperlipidemic participants. The major anthocyanins in human diets are glycosides of cyanidin and delphinidin, and structure can influence both absorption and bioactivity. The aim of this study is to determine the effects of two major types of anthocyanins on low-density lipoprotein cholesterol and other cardiometabolic markers for cardiovascular disease (CVD) risk in hyperlipidemic individuals. METHODS AND RESULTS: Fifty-two hyperlipidemic participants complete this randomized, placebo-controlled, double-blind, three arm crossover trial. Participants ingest capsules containing 320 mg of anthocyanins (bilberry trihydroxy-type or black rice dihydroxy-type) or placebo once daily for 28 days. Biomarkers of CVD risk are measured before and after the intervention period. Compared to the placebo, neither anthocyanin treatment significantly (p < 0.05) changes circulating levels of lipoproteins (total-/high-density lipoprotein (HDL)-/low-density lipoprotein (LDL)-cholesterol, triglycerides, Apolipoprotein B (ApoB)), biomarkers of glycemic control (fasting glucose, fructosamine), biomarkers of HDL function (ApoA1, HDL3, paraoxonase-1 (PON1) arylesterase, and lactonase activities), or plasma bile acids. CONCLUSIONS: These data do not support the notion that regular consumption of anthocyanins beneficially affects glycemic control or lipoprotein profiles or functions. It is possible the no effect observation is due to the relatively short duration of treatments.
Assuntos
Doenças Cardiovasculares , Hipercolesterolemia , Oryza , Vaccinium myrtillus , Adulto , Humanos , LDL-Colesterol , Antocianinas/análise , Frutas/química , Hipercolesterolemia/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Cross-Over , Biomarcadores , Colesterol , Lipoproteínas HDL , ArildialquilfosfataseRESUMO
SCOPE: The majority of ingested flavanols reach the colon where they are catabolized by the microbiota to form hydroxyphenyl-γ-valerolactones (HGVLs). It is not known if the HGVLs are catabolic products of monomeric (epi)catechins (EPC), oligomeric procyanidins (OPCs), or both. Using data from a randomized, double-blind, placebo-controlled crossover trial the relative contributions of catechins and OPC to the bioavailable pool of HGVLs are estimated. METHODS AND RESULTS: Participants ingested an apple extract once daily for 28 days that delivered the following: i) 70 mg EPC and 65 mg OPC (low dose EPC), ii) 140 mg EPC and 130 mg OPC (high dose EPC), iii) 6 mg EPC and 130 mg OPC (OPC), and iv) a placebo control. Urine is collected over a 24-h period before and after treatments. The median urinary excretion of HGVLs after ingestion of the high dose EPC is tenfold higher than that excreted after ingestion of the OPC that provided an equivalent dose of PC. Approximately 22% of catechins are converted to HGVLs in contrast to PC, for which there is limited conversion. CONCLUSION: Monomeric catechins are efficiently converted to derived HGVLs that are absorbed and excreted in human urine, whereas oligomeric PCs are much less efficiently converted.
Assuntos
Catequina/farmacocinética , Microbioma Gastrointestinal/fisiologia , Lactonas/metabolismo , Proantocianidinas/farmacocinética , Idoso , Disponibilidade Biológica , Pressão Sanguínea/efeitos dos fármacos , Catequina/química , Catequina/urina , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Lactonas/química , Lactonas/urina , Masculino , Malus/química , Pessoa de Meia-Idade , Variações Dependentes do Observador , Placebos , Extratos Vegetais/química , Proantocianidinas/químicaRESUMO
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.
Assuntos
Antocianinas/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Extratos Vegetais/uso terapêutico , Pós-Menopausa , Sambucus , Biomarcadores/sangue , Proteína C-Reativa/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Feminino , Flavonoides/uso terapêutico , Humanos , Interleucina-6/sangue , Testes de Função Renal , Testes de Função Hepática , Pessoa de Meia-Idade , Placebos , Medição de Risco , Segurança , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
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.
Assuntos
Citrus sinensis/química , Anticoncepcionais Orais/farmacologia , Flavanonas/farmacocinética , Frutas/química , Adolescente , Adulto , Idoso , Envelhecimento/sangue , Envelhecimento/urina , Antropometria/métodos , Bebidas/análise , Índice de Massa Corporal , Cromatografia Líquida de Alta Pressão/métodos , Estudos Cross-Over , Feminino , Flavanonas/sangue , Flavanonas/urina , Análise de Alimentos/métodos , Humanos , Absorção Intestinal/efeitos dos fármacos , Absorção Intestinal/fisiologia , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Adulto JovemRESUMO
Blackcurrant (BC) fruits are a rich source of biologically active anthocyanins but little is known of the anthocyanin content of commonly consumed BC products or how processing affects the absorption. We report that whereas fresh and frozen whole BC were a rich source of anthocyanins, containing 897 and 642mg (100gFW)(-1) of total anthocyanins the levels in all other products were substantially lower (0.05-10.3% of the levels in fresh fruit). Further, when the absorption and excretion of BC was assessed in volunteers consuming a portion (100g) of frozen whole BC (642mg total anthocyanins) and, 300g of a BC drink made by diluting concentrated syrup (33.6mg total anthocyanins), only small quantities of BC anthocyanins were excreted in urine (fruit, 0.053±0.022%; drink, 0.036±0.043%; mean percent urinary yield±SD) and they were not detected in plasma. These data indicate that fresh and frozen BC, but not processed products, are rich sources of anthocyanins but, regardless of the food source, these anthocyanins are poorly bioavailable.
RESUMO
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.
RESUMO
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.
Assuntos
Biflavonoides/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Catequina/farmacologia , Hipertensão/sangue , Malus/química , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Idoso , Biomarcadores/sangue , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Women have an increased risk of iron deficiency during pregnancy because of the demands of the developing fetus. Iron supplements are commonly advocated as a prophylactic treatment and are generally taken with meals to reduce side effects, but iron can interfere with the absorption of zinc. OBJECTIVE: The aim was to determine the effect of consuming an iron supplement (100 mg Fe/d as ferrous gluconate) with meals from 16 wk gestation to term on zinc status and absorption. DESIGN: Stable-isotope techniques were used to measure zinc status (exchangeable zinc pool, EZP) and fractional zinc absorption (FZA) in early and late pregnancy from a meal consumed at a different time from that of iron supplement or placebo consumption in 6 women given iron supplements and 7 given a placebo. RESULTS: FZA increased during pregnancy, independent of iron supplementation. FZA was significantly higher (P < 0.001) at week 34 than at weeks 16 and 24, and urinary zinc excretion was higher at week 34 than at week 16 (P = 0.02). The size of the EZP remained unchanged throughout pregnancy and was unaffected by iron supplementation. The iron status of iron-supplemented women was higher than that of the placebo group. CONCLUSIONS: In iron-replete pregnant women who consumed a Western diet, no detectable adverse effects on zinc metabolism were observed after ingestion of 100 mg Fe/d. An increase in the efficiency of zinc absorption was observed during late pregnancy.
Assuntos
Absorção Intestinal/efeitos dos fármacos , Ferro da Dieta/farmacologia , Estado Nutricional , Gravidez/metabolismo , Zinco/farmacocinética , Administração Oral , Adolescente , Adulto , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Feminino , Humanos , Ferro da Dieta/administração & dosagem , Ferro da Dieta/efeitos adversos , Cuidado Pré-Natal , Método Simples-Cego , Zinco/sangue , Zinco/urinaRESUMO
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.
Assuntos
Radioisótopos de Cobre/sangue , Plasma/química , Albuminas/metabolismo , Ceruloplasmina/metabolismo , Radioisótopos de Cobre/farmacocinética , Humanos , Projetos PilotoRESUMO
There is a lack of data for individual oligomeric procyanidins in apples and apple extracts. Our aim was to develop, validate and evaluate an analytical method for the separation, identification and quantification of monomeric and oligomeric flavanols in apple extracts. To achieve this, we prepared two types of flavanol extracts from freeze-dried apples; one was an epicatechin-rich extract containing â¼30% (w/w) monomeric (-)-epicatechin which also contained oligomeric procyanidins (Extract A), the second was an oligomeric procyanidin-rich extract depleted of epicatechin (Extract B). The parameters considered for method optimisation were HPLC columns and conditions, sample heating, mass of extract and dilution volumes. The performance characteristics considered for method validation included standard linearity, method sensitivity, precision and trueness. Eight laboratories participated in the method evaluation. Chromatographic separation of the analytes was best achieved utilizing a Hilic column with a binary mobile phase consisting of acidic acetonitrile and acidic aqueous methanol. The final method showed linearity for epicatechin in the range 5-100µg/mL with a correlation co-efficient >0.999. Intra-day and inter-day precision of the analytes ranged from 2 to 6% and 2 to 13% respectively. Up to dp3, trueness of the method was >95% but decreased with increasing dp. Within laboratory precision showed RSD values <5 and 10% for monomers and oligomers, respectively. Between laboratory precision was 4 and 15% (Extract A) and 7 and 30% (Extract B) for monomers and oligomers, respectively. An analytical method for the separation, identification and quantification of procyanidins in an apple extract was developed, validated and assessed. The results of the inter-laboratory evaluation indicate that the method is reliable and reproducible.
Assuntos
Biflavonoides/análise , Catequina/análise , Cromatografia Líquida de Alta Pressão , Malus/química , Extratos Vegetais/química , Proantocianidinas/análise , Biflavonoides/isolamento & purificação , Catequina/isolamento & purificação , Liofilização , Limite de Detecção , Malus/metabolismo , Proantocianidinas/isolamento & purificação , Estereoisomerismo , TemperaturaRESUMO
BACKGROUND: An improved understanding of copper metabolism is needed to derive more precise estimates of dietary requirements. OBJECTIVES: The objectives were to validate a method for estimating endogenous losses of copper, test whether a simple model can predict true absorption from the plasma appearance of labeled copper, and develop a compartmental model for copper metabolism by using stable isotopes. DESIGN: A stable isotope of copper was intravenously administered to 6 men, and fecal samples were collected for 14 d. Four weeks later the study was repeated, but with an oral dose, and blood samples were collected for 7 d and fecal samples for 14 d. RESULTS: There was no significant difference (P = 0.48) in the estimated endogenous loss of copper calculated by using either the excreted intravenous dose (x +/- SD: 32 +/- 5%) or the absorbed and excreted oral dose (35 +/- 2%). A simple mathematical model fitted to plasma isotope appearance data estimated true absorption to be 8 +/- 2% compared with 48-49% measured by fecal monitoring. A more complicated compartmental model predicted that, when newly absorbed copper first enters the blood, 74% is removed by the liver and 99% is bound to ceruloplasmin in the plasma. The exchangeable pool of copper was estimated to be 43 +/- 30 mg. Daily endogenous losses were predicted to be 2.4 mg. CONCLUSIONS: The results showed that fecal monitoring is the only method that can reliably measure labeled copper absorption, and it is not necessary to administer an intravenous dose of copper to estimate endogenous losses. The compartmental model provides new insights into human copper metabolism.
Assuntos
Cobre/metabolismo , Fezes/química , Modelos Biológicos , Administração Oral , Adulto , Cobre/administração & dosagem , Cobre/sangue , Humanos , Infusões Intravenosas , Absorção Intestinal , Masculino , Pessoa de Meia-IdadeRESUMO
SCOPE: Excessive concentrations of vascular endothelial growth factor (VEGF) drive angiogenesis and cause complications such as increased growth of tumours and atherosclerotic plaques. The aim of this study was to determine the molecular mechanism underlying the potent inhibition of VEGF signalling by polyphenols. METHODS AND RESULTS: We show that the polyphenols epigallocatechin gallate from green tea and procyanidin oligomers from apples potently inhibit VEGF-induced VEGF receptor-2 (VEGFR-2) signalling in human umbilical vein endothelial cells by directly interacting with VEGF. The polyphenol-induced inhibition of VEGF-induced VEGFR-2 activation occurred at nanomolar polyphenol concentrations and followed bi-phasic inhibition kinetics. VEGF activity could not be recovered by dialysing VEGF-polyphenol complexes. Exposure of VEGF to epigallocatechin gallate or procyanidin oligomers strongly inhibited subsequent binding of VEGF to human umbilical vein endothelial cells expressing VEGFR-2. Remarkably, even though VEGFR-2 signalling was completely inhibited at 1 µM concentrations of polyphenols, endothelial nitric oxide synthase was shown to still be activated via the PI3K/Akt signalling pathway which is downstream of VEGFR-2. CONCLUSION: These data demonstrate for the first time that VEGF is a key molecular target for specific polyphenols found in tea, apples and cocoa which potently inhibit VEGF signalling and angiogenesis at physiological concentrations. These data provide a plausible mechanism which links bioactive compounds in food with their beneficial effects.
Assuntos
Biflavonoides/metabolismo , Catequina/análogos & derivados , Proantocianidinas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Biflavonoides/farmacologia , Sítios de Ligação , Catequina/metabolismo , Catequina/farmacologia , Simulação por Computador , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Malus/química , Fosforilação/efeitos dos fármacos , Proantocianidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Chá/química , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
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 < 0.05). Time to maximum plasma concentration was significantly later for the puree compared with the drinks (p < 0.01). Epicatechin bioavailability was >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.
Assuntos
Bebidas/análise , Catequina/farmacocinética , Suplementos Nutricionais , Flavonoides/análise , Malus/química , Extratos Vegetais/química , Idoso , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Óxido Nítrico/urinaRESUMO
SCOPE: Sulforaphane (a potent anticarcinogenic isothiocyanate derived from glucoraphanin) is widely considered responsible for the protective effects of broccoli consumption. Broccoli is typically purchased fresh or frozen and cooked before consumption. We compared the bioavailability and metabolism of sulforaphane from portions of lightly cooked fresh or frozen broccoli, and investigated the bioconversion of sulforaphane to erucin. METHODS AND RESULTS: Eighteen healthy volunteers consumed broccoli soups produced from fresh or frozen broccoli florets that had been lightly cooked and sulforaphane thio-conjugates quantified in plasma and urine. Sulforaphane bioavailability was about tenfold higher for the soups made from fresh compared to frozen broccoli, and the reduction was shown to be due to destruction of myrosinase activity by the commercial blanching-freezing process. Sulforaphane appeared in plasma and urine in its free form and as several thio-conjugates forms. Erucin N-acetyl-cysteine conjugate was a significant urinary metabolite, and it was shown that human gut microflora can produce sulforaphane, erucin, and their nitriles from glucoraphanin. CONCLUSION: The short period of blanching used to produce commercial frozen broccoli destroys myrosinase and substantially reduces sulforaphane bioavailability. Sulforaphane was converted to erucin and excreted in urine, and it was shown that human colonic flora were capable of this conversion.