Blueberry polyphenols alter gut microbiota & phenolic metabolism in rats.

Consuming polyphenol-rich fruits and vegetables, including blueberries, is associated with beneficial health outcomes. Interest in enhancing polyphenol intakes via dietary supplements has grown, though differences in fruit versus supplement matrix on gut microbiota and ultimate phenolic metabolism to bioactive metabolites are unknown. To evaluate this, 5-month-old, ovariectomized, Sprague-Dawley rats were gavaged for 90 d with a purified extract of blueberry polyphenols (0, 50, 250, or 1000 mg total polyphenols per kg bw per d) or lyophilized blueberries (50 mg total polyphenols per kg bw per d, equivalent to 150 g fresh blueberries per day in humans). Urine, feces, and tissues were assessed for gut microbiota and phenolic metabolism. Significant dose- and food matrix-dependent effects were observed at all endpoints measured. Gut microbial populations showed increased diversity at moderate doses but decreased diversity at high doses. Urinary phenolic metabolites were primarily observed as microbially derived metabolites and underwent extensive host xenobiotic phase II metabolism. Thus, blueberry polyphenols in fruit and supplements induce differences in gut microbial communities and phenolic metabolism, which may alter intended health effects.

Increasing Doses of Blueberry Polyphenols Alters Colonic Metabolism and Calcium Absorption in Ovariectomized Rats.

SCOPE: Blueberries are rich sources of bioactive polyphenols that may provide health benefits when consumed regularly, leading to their increased marketing as dietary supplements. However, the metabolic changes associated with consuming concentrated doses of purified polyphenols, as may be present in dietary supplements, are unknown, especially when considering the colonic metabolites formed. This study aimed to evaluate the pharmacokinetics of high doses of purified blueberry polyphenols. METHODS AND RESULTS: 5-month old, ovariectomized Sprague-Dawley rats are acutely dosed with purified blueberry polyphenols (0, 75, 350, and 1000 mg total polyphenols per kg body weight (bw)) and 45 Ca to measure calcium absorption. Blood and urine are collected for 48 h after dosing and phenolic metabolites measured via ultra high-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The most prominent metabolites are colonically generated cinnamic and hippuric acids. Smaller amounts of other phenolic acids, flavonols, and anthocyanins are also detected. Most metabolites follow a dose-response relationship, though several show saturated absorption. Maximal metabolite concentrations are reached within 12 h for a majority of compounds measured, while some (e.g., hippuric acid) peaked up to 24 h post-dosing. Calcium absorption is significantly increased in the highest dose group (p = 0.03). CONCLUSION: These results indicate that increased doses of blueberry polyphenols induce changes in intestinal phenolic metabolism and increase calcium absorption.

Phenolics of Green Pea (Pisum sativum L.) Hulls, Their Plasma and Urinary Metabolites, Bioavailability, and in Vivo Antioxidant Activities in a Rat Model.

Increased processing of pulses generates large volumes of hulls, which are known as an excellent source of phenolic antioxidants. However, the bioavailability and in vivo activity of these phenolics are rarely reported. This research was therefore carried out to study the absorption, metabolism, and in vivo antioxidant activities of green pea hull (GPH) phenolics using ultrahigh-pressure liquid chromatography with a linear ion trap-high-resolution Orbitrap mass spectrometry and an oxidative stress rat model. A total of 31 phenolics, including 4 phenolic acids, 24 flavonoids, and 3 other phenolics, were tentatively identified. Ten of these phenolics and 49 metabolites were found in the plasma and urine of rats, which helped to explain the favorable changes by GPH phenolics in key antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and glutathione) and indicators (total antioxidant capacity, malondialdehyde) in the plasma and different tissues of rats. This is the first comprehensive report on dry pea hull phenolics and their bioavailability, metabolic profiles, and mechanisms of in vivo antioxidant activities.

UPLC-Q-TOF/MS-based metabolic profiling comparison of four major bioactive components in normal and CKD rat plasma, urine and feces following oral administration of Cornus officinalis Sieb and Rehmannia glutinosa Libosch herb couple extract.

Cornus officinalis-Rehmannia glutinosa herb couple is widely used herb medicine in clinical practice to treat chronic kidney disease (CKD). However, the in vivo integrated metabolism of its main bioactive components in CKD rats remains unknown. In this study, UPLC-Q-TOF/MS technique combined with Metabolynx™ software, was developed and successfully applied for analysis of metabolic profiles of the bioactive components of the herb couple in normal and CKD rat biological samples. Main parent components of the herb couple extract such as loganin, morroniside and catalpol were absorbed into the blood circulation of the normal and CKD rats. Another parent component acteoside was almost completely degraded. Seventeen metabolites involved in the in vivo metabolism processes were tentatively identified. These metabolites indicated that loganin was mainly metabolized to the demethylated product, and morroniside was firstly deglycosylated to the aglycone and the latter was subsequently demethylated and acetylated. Additionally, hydrogenation and deglycosylation were the principal metabolic reactions of catalpol; while O-glucuronide and O-sulphate conjugates were observed as major metabolites for methylated caffeic acid and hydroxytyrosol released from acteoside. Compared with the normal group, the CKD rat showed lower conversion capability. Few kinds and minor amounts of the metabolites appeared in the CKD rat samples. While considerable amounts of the parent compounds were detected in the CKD plasma. This will help maintain a high blood drug concentration which might be beneficial for the treatment of CKD. The proposed method could develop an integrated template approach to analyze screening and identification of the bioactive components in plasma, urine and feces after oral administration of herb medicines. Additionally, this investigation might provide helpful chemical information for further pharmacology and active mechanism research on herb medicines.

First Trimester Urinary Bisphenol and Phthalate Concentrations and Time to Pregnancy: A Population-Based Cohort Analysis.

Background: Increasing evidence suggests that exposure to synthetic chemicals such as bisphenols and phthalates can influence fecundability. The current study describes associations of first trimester urinary concentrations of bisphenol A (BPA), BPA analogs, and phthalate metabolites with time to pregnancy (TTP). Methods: Among 877 participants in the population-based Generation R pregnancy cohort, we measured first trimester urinary concentrations of bisphenols and phthalates [median gestational age, 12.9 weeks (interquartile range, 12.1, 14.4)]. We used fitted covariate-adjusted Cox proportional hazard models to examine associations of bisphenol and phthalate concentrations with TTP. Participants who conceived using infertility treatment were censored at 12 months. Biologically plausible effect measure modification by folic acid supplement use was tested. Results: In the main models, bisphenol and phthalate compounds were not associated with fecundability. In stratified models, total bisphenols and phthalic acid were associated with longer TTP among women who did not use folic acid supplements preconceptionally [respective fecundability ratios per each natural log increase were 0.90 (95% CI, 0.81 to 1.00) and 0.88 (95% CI, 0.79 to 0.99)]. Using an interaction term for the exposure and folic acid supplement use showed additional effect measure modification by folic acid supplement use for high-molecular-weight phthalate metabolites. Conclusions: We found no associations of bisphenols and phthalates with fecundability. Preconception folic acid supplementation seems to modify effects of bisphenols and phthalates on fecundability. Folic acid supplements may protect against reduced fecundability among women exposed to these chemicals. Further studies are needed to replicate these findings and investigate potential mechanisms.

Bisphenol and phthalate concentrations and its determinants among pregnant women in a population-based cohort in the Netherlands, 2004-5.

BACKGROUND: Exposure to bisphenols and phthalates in pregnancy may lead to adverse health effects in women themselves and their offspring. OBJECTIVE: To describe first trimester bisphenol and phthalate urine concentrations, including bisphenol and phthalate replacements, and determine nutritional, socio-demographic and lifestyle related determinants. METHODS: In a population-based prospective cohort of 1396 mothers, we measured first trimester bisphenol, phthalate and creatinine urine concentrations (samples collected in 2004-2005, median gestational age 12.9 weeks [inter-quartile range (IQR) 12.1-14.4]). We examined associations of potential determinants with log-transformed bisphenol and phthalate concentrations. Outcomes were back-transformed. Nutritional analyses were performed in a subgroup of 642 Dutch participants only, as the Food Frequency Questionnaire was aimed at Dutch food patterns. RESULTS: Bisphenol A, bisphenol S, and bisphenol F were detected in 79.2%, 67.8% and 40.2% of the population, respectively. Mono-n-butylphthalate, mono-(2-ethyl-5-hydroxyhexyl)phthalate and monobenzylphthalate were detected in > 90% of the population. Nutritional intake was not associated with bisphenol and phthalate concentrations after correction for multiple testing was applied. Obesity was associated with higher high-molecular-weight phthalate concentrations and the lack of folic acid supplement use with higher di-n-octylphthalate concentrations (respective mean differences were 46.73nmol/l [95% CI 14.56-93.72] and 1.03nmol/l [0.31-2.06]). CONCLUSION: Bisphenol S and F exposure was highly prevalent in pregnant women in the Netherlands as early as 2004-5. Although associations of dietary and other key factors with bisphenol and phthalate concentrations were limited, adverse lifestyle factors including obesity and the lack of folic acid supplement use seem to be associated with higher phthalate concentrations in pregnant women. The major limitation was the availability of only one urine sample per participant. However, since phthalates are reported to be quite stable over time, results concerning determinants of phthalate concentrations are expected to be robust.

Identification of phenolic metabolites in human urine after the intake of a functional food made from grape extract by a high resolution LTQ-Orbitrap-MS approach.

Grape pomace (GP) is known to be a rich source of polyphenols with biological activity which may be used as functional ingredients for the development of new health-promoting products. Numerous studies have reported that bioactive compounds may act through multiple mechanisms. In order to verify the oral absorption and metabolism of grape polyphenols, we performed a prospective, randomised and cross-over acute study in 12 volunteers with two interventions: 500mL of a functional beverage enriched with 200mL of GP and 500mL of a control beverage without GP. In this work, liquid chromatography coupled with an electrospray ionization hybrid linear ion trap quadrupole-Orbitrap-mass spectrometry (LC/ESI-LTQ-Orbitrap-MS) technique has been used to accurately identify phenolics in GP and human urine. In GP, 41 phenolic compounds were identified mainly procyanidins, phenolic acids and flavonols, and in human urine over 70 metabolites of phenolic compounds including microbiota metabolites, glucuronides and sulfate derivatives were detected. Overall, high resolution mass spectrometry (HR-MS) enhances the identification of a large variety of polyphenols and their metabolites with great mass accuracies for all molecular ions.

Influence of omega-3 PUFAs on the metabolism of proanthocyanidins in rats.

Studies of the bioavailability of proanthocyanidins usually consider them independently of other dietary constituents, while there is a tendency in the field of functional foods towards the combination of different bioactive compounds in a single product. This study examined the long-term effects of ω-3 polyunsaturated fatty acids of marine origin on the metabolic fate of grape proanthocyanidins. For this, female adult Wistar-Kyoto rats were fed (18weeks) with a standard diet supplemented or not with eicosapentaenoic acid/docosahexaenoic acid (1:1, 16.6g/kg feed), proanthocyanidin-rich grape seed extract (0.8g/kg feed) or both. A total of 39 microbial-derived metabolites and 16 conjugated metabolites were detected by HPLC-MS/MS either in urine or in the aqueous fraction of feces. An unexpected significant increase in many proanthocyanidin metabolites in urine and feces was observed in the group supplemented with ω-3 polyunsaturated fatty acids group as compared to the animals fed a standard diet, which contains a small amount of polyphenols. However, proanthocyanidin metabolites in rats given ω-3 polyunsaturated fatty acids and grape seed extract did not significantly differ from those in the group supplemented only with grape seed extract. It was concluded that ω-3 polyunsaturated fatty acids collaborate in the metabolism of polyphenols when present at low doses in the feed matrix, while the capacity of ω-3 polyunsaturated fatty acids to induce microbiota transformations when proanthocyanidins are present at high doses is not relevant compared to that of polyphenols themselves.

Influence of Ingesting a Flavonoid-Rich Supplement on the Metabolome and Concentration of Urine Phenolics in Overweight/Obese Women.

This study evaluated the effect of ingesting a flavonoid-rich supplement (329 mg/d) on total urine phenolics and shifts in plasma metabolites in overweight/obese female adults using untargeted metabolomics procedures. Participants (N = 103, 18-65 y, BMI ≥ 25 kg/m2) were randomized to flavonoid (F) or placebo (P) groups for 12 weeks with blood and 24 h urine samples collected prestudy and after 4 and 12 weeks in a parallel design. Supplements were prepared as chewable tablets and included vitamin C, wild bilberry fruit extract, green tea leaf extract, quercetin, caffeine, and omega 3 fatty acids. At 4 weeks, urine total phenolics increased 24% in F versus P with similar changes at 12 weeks (interaction effect, P = 0.041). Groups did not differ in markers of inflammation (IL-6, MCP-1, CRP) or oxidative stress (oxLDL, FRAP). Metabolomics data indicated shifts in 63 biochemicals in F versus P with 70% from the lipid and xenobiotics superpathways. The largest fold changes in F were measured for three gut-derived phenolics including 3-methoxycatechol sulfate, 3-(3-hydroxyphenyl)propanoic acid sulfate, and 1,2,3-benzenetriol sulfate (interaction effects, p ≤ 0.050). This randomized clinical trial of overweight/obese women showed that 12 weeks ingestion of a mixed flavonoid nutrient supplement was associated with a corresponding increase in urine total phenolics and gut-derived phenolic metabolites.

Exposure to endocrine disrupting chemicals among residents of a rural vegetarian/vegan community.

BACKGROUND & AIMS: Endocrine-disrupting chemicals (EDCs) are increasingly thought to be involved in the rising prevalence of disorders such as obesity, diabetes, and some hormone-dependent cancers. Several lines of evidence have indicated that vegetarian and vegan diets may offer some protection from such diseases. We hypothesized that exposure to selected EDCs among residents of the unique vegetarian/vegan community of Amirim would be lower than what has recently been reported for the omnivorous population in the first Israel Biomonitoring Study (IBMS). METHODS: We studied 42 Amirim residents (29 vegetarians/13 vegans; 24 women/18men, aged 50.7±13.7y). Subjects answered detailed lifestyle, and multipass, memory-based 24-hr dietary recall questionnaires. Concentrations of bisphenol A (BPA), 11 phthalate metabolites, and the isoflavone phytoestrogens (genistein and daidzein) were determined by GC or LC tandem mass-spectrometry on a spot urine sample. The results were compared to those obtained following the same methodology in the Jewish subgroup of the IBMS (n=184). RESULTS: While a vegetarian/vegan nutritional pattern had no effect on exposure to BPA, it seemed to confer a modest protection (~21%) from exposure to high molecular weight phthalates. Furthermore, the summed metabolites of the high molecular weight phthalate DiNP were 36% lower in vegans compared to vegetarians (P<0.05). In contrast, Amirim residents exhibited a level of exposure to isoflavone phytoestrogens about an order of magnitude higher than in the IBMS (P<0.001). CONCLUSIONS: In Israel, a country whose inhabitants demonstrate exposure to EDCs comparable to that of the US and Canada, a voluntary lifestyle of vegetarianism and preference for organic food has a modest, but possibly valuable, impact on exposure to phthalates, while it is associated with a very steep increase in the exposure to phytoestrogens. Major reduction in exposure to EDCs will require regulatory actions.

New metabolites of acteoside identified by ultra-performance liquid chromatography/quadrupole-time-of-flight MS(E) in rat plasma, urine, and feces.

Acteoside, which belongs to the family of phenylethanoid glycosides (PhGs), has extensive biological activities, including strong antioxidant, anti-inflammatory, hepatoprotect, and cell apoptosis regulation. Like other PhGs compounds, the fate of acteoside in the gut for both parent polyphenols and their degradation products, small phenolic acid and aromatic catabolites cannot be ignored. Therefore, in this work, expanded and systematical investigation for metabolism characteristic profiles of acteoside in vivo by ultra-performance liquid chromatography/ quadrupole-time-of-flight and a new MS(E) data collection technology had been studied. This was equivalent to non-slective MS/MS scans and helpful to explore new metabolites. After oral administration of 200mg/kg acteoside, He et al. (2011) a total of 44 metabolites was detected and identified, and 37 of them were reported for the first time. Among them, 35 were parent drug metabolites classified in 14 groups. Owen et al. (2003) Through the comprehensive metabolites study in plasma, urine and feces, acteoside systemical metabolites profiles and characteristics elaborated firstly. The relative content of metabolites research showed that acteoside could exist stably and the process for biotransformation of acteoside in blood keep extreme short time. Pan and Hori (1996) The significant new transformation of isomerization from acteoside to isoacteoside had been firstly found and confirmed. The results of this work provided new information for the clarification of the metabolism of acteoside and rendered a very valuable theoretical basis for the development of novel ideal dosage forms of acteoside in the future.

Virgin Olive Oil Enriched with Its Own Phenols or Complemented with Thyme Phenols Improves DNA Protection against Oxidation and Antioxidant Enzyme Activity in Hyperlipidemic Subjects.

The effects of virgin olive oil (VOO) enriched with its own phenolic compounds (PC) and/or thyme PC on the protection against oxidative DNA damage and antioxidant endogenous enzymatic system (AEES) were estimated in 33 hyperlipidemic subjects after the consumption of VOO, VOO enriched with its own PC (FVOO), or VOO complemented with thyme PC (FVOOT). Compared to pre-intervention, 8-hydroxy-2'-deoxyguanosine (a marker for DNA damage) decreased in the FVOO intervention and to a greater extent in the FVOOT with a parallel significant increase in olive and thyme phenolic metabolites. Superoxide dismutase (AEES enzyme) significantly increased in the FVOO intervention and to a greater extent in the FVOOT with a parallel significant increase in thyme phenolic metabolites. When all three oils were compared, FVOOT appeared to have the greatest effect in protecting against oxidative DNA damage and improving AEES. The sustained intake of a FVOOT improves DNA protection against oxidation and AEES probably due to a greater bioavailability of thyme PC in hyperlipidemic subjects.

Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction.

CONTEXT: Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known. OBJECTIVE: The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. SETTING: The study was conducted in a fertility center in a teaching hospital. DESIGN: We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake. MAIN OUTCOME MEASURE: Live birth rates per initiated treatment cycle were measured. RESULTS: Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. CONCLUSION: Soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a potential interaction between soy and BPA in humans, they should be further evaluated in other populations.

Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China.

BACKGROUND: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA) and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. METHODS: In this study, BPA and phytoestrogens in urine specimens (n = 256) collected from children in China were measured by liquid chromatography (LC)-tandem mass spectrometry (MS/MS). RESULTS: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. CONCLUSIONS: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S.

Metabolite Profile of Salidroside in Rats by Ultraperformance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry and High-Performance Liquid Chromatography Coupled with Quadrupole-Linear Ion Trap Mass Spectrometry.

In the present work, the salidroside metabolite profile in rat urine was investigated, and subsequently the metabolic pathways of salidroside were proposed. After administrations of salidroside at an oral dose of 100 or 500 mg/kg, rat urine samples were collected and pretreated with methanol to precipitate the proteins. The pretreated samples were analyzed by an Acquity ultraperformance liquid chromatography (UPLC) coupled with an HSS T3 column and detected by quadrupole time-of-flight mass spectrometry (Q-TOF-MS) or high-performance liquid chromatography coupled with hybrid triple-quadrupole linear ion trap mass spectrometry (HPLC/Q-trap-MS). A total of eight metabolites were detected and identified on the basis of the characteristics of their protonated ions in the urine samples. The results elucidated that salidroside was metabolized via glucuronidation, sulfation, deglycosylation, hydroxylation, methylation, and dehydroxylation pathways in vivo.

Effect of consuming a grape seed supplement with abundant phenolic compounds on the oxidative status of healthy human volunteers.

BACKGROUND: Diverse enzymatic and non-enzymatic antioxidants provide protection against reactive oxygen species in humans and other organisms. The nonenzymatic antioxidants include low molecular mass molecules such as plant-derived phenols. AIM OF STUDY: This study identified the major phenolic compounds of a grape seed extract by HPLC and analyzed the effect of consumption of biscuits enriched with this extract on the urinary oxidative status of healthy subjects by measurement of urine redox potential. METHODS: The major phenolic compounds were characterized in a red grape seed extract separated by HPLC with detection by a photodiode array (PDA), fluorescence (FL) and quadrupole mass spectrometer (MS). A nutritional study in a healthy volunteers group was done. Each volunteer ate eight traditional biscuits with no red grape seed extract supplementation. The second day each volunteer ate eight traditional biscuits supplemented with 0.6% (wt/wt) of grape seed extract. An overnight urine sample was obtained for each treatment. The redox potential was measured at 25 °C using a potentiometer in each urine sample. RESULTS: Epicatechin, catechin, procyanidin dimers B1 to B4, and the procyanidin trimer C2 were the major phenolic components in the extract. Epicatechin gallate and procyanidin dimers B1-3-G and B2-3'-G were the major galloylated flavan-3-ols. The forty-six healthy volunteers each shown a reduction of the urine redox potential after the treatment by traditional biscuits supplemented with the grape seed extract. CONCLUSIONS: This simple dietary intervention significantly reduced (33%) the urine redox potential, reflecting an overall increase in antioxidant status. Incorporation of plant-derived phenols in the diet may increase anti-oxidative status.

Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial.

The leaves of the olive plant (Olea europaea) 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 ex vivo IL-8 production were significantly reduced (P< 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 in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

A sensitive and efficient method for trace analysis of some phenolic compounds using simultaneous derivatization and air-assisted liquid-liquid microextraction from human urine and plasma samples followed by gas chromatography-nitrogen phosphorous detection.

In present study, a simultaneous derivatization and air-assisted liquid-liquid microextraction method combined with gas chromatography-nitrogen phosphorous detection has been developed for the determination of some phenolic compounds in biological samples. The analytes are derivatized and extracted simultaneously by a fast reaction with 1-flouro-2,4-dinitrobenzene under mild conditions. Under optimal conditions low limits of detection in the range of 0.05-0.34 ng mL(-1) are achievable. The obtained extraction recoveries are between 84 and 97% and the relative standard deviations are less than 7.2% for intraday (n = 6) and interday (n = 4) precisions. The proposed method was demonstrated to be a simple and efficient method for the analysis of phenols in biological samples.

Uptake and bioavailability of anthocyanins and phenolic acids from grape/blueberry juice and smoothie in vitro and in vivo.

The goal of eating five servings of fruits and vegetables a day has not yet been achieved. The intake of polyphenols such as anthocyanins (ACN) could be improved by consuming smoothies and juices that are increasingly popular, especially in children; however, bioavailability data concerning food matrix effects are scarce. Thus, we conducted a randomised, cross-over, bioavailability study (n 10) to determine the bioavailability of ACN and their metabolites from an ACN-rich grape/blueberry juice (841 mg ACN/litre) and smoothie (983 mg ACN/litre) in vivo, and the uptake of a corresponding grape/blueberry extract in vitro. After the intake of beverage (0·33 litres), plasma and fractionated urine samples were collected and analysed by ultra-performance liquid chromatography coupled to MS. The most abundant ACN found in plasma and urine were malvidin and peonidin as native ACN and as glucuronidated metabolites as well as 3,4-dihydroxybenzoic acid (3,4-DHB); minor ACN (delphinidin, cyanidin and petunidin) were only detected as native glycosides. Plasma pharmacokinetics and recoveries of urinary metabolites of ACN were not different for juice or smoothie intake; however, the phenolic acid 3,4-DHB was significantly better bioavailable from juice in comparison to smoothie. In vitro data with absorptive intestinal cells indicated that despite their weak chemical stability, ACN and 3,4-DHB could be detected at the basal side in their native forms. Whether smoothies as well as juices should be recommended to increase the intake of potentially health-promoting ACN and other polyphenols requires the consideration of other ingredients such as their relatively high sugar content.

Effects of Korean red ginseng (Panax Ginseng Meyer) on bisphenol A exposure and gynecologic complaints: single blind, randomized clinical trial of efficacy and safety.

BACKGROUND: Korean red ginseng (KRG) is a processed ginseng from raw ginseng to enhance safety, preservation and efficacy, known having beneficial effects on women's health due to its estrogen like function. While estrogen supplementation showed some modulation of endocrine disrupting chemicals, bisphenol A (BPA) has been focused as a potential endocrine disrupting chemical. In this study, we examined the efficacy and safety outcomes of KRG against BPA, focusing on female quality of life (QOL). Individual variations in susceptibility to KRG were also investigated with the Sasang Typology, the personalized medicine used for hundred years in Korea. METHODS: We performed a single-blind randomized clinical trial. Study subjects were young women (N = 22), consumed 2.7 g of KRG or placebo per day for 2 weeks and filled up questionnaires regarding gynecologic complaints at the 4 time spots. We analyzed urinary total BPA and malondialdehyde (MDA), an oxidative stress biomarker, with GC/MS and HPLC/UVD respectively, and diagnosed their Sasang Typology with the questionnaire for the Sasang constitution Classification (QSCC II). RESULTS: KRG consumption decreased urinary BPA and MDA levels (ps < 0.05) and alleviated 'menstrual irregularity', 'menstrual pain', and 'constipation' (ps < 0.05). SoEum type (Lesser Yin person) among the Sasang types showed significant alleviation in insomnia, flushing, perspiration and appetite by KRG consumption, rather than other Sasang types. During the intervention, no one experienced any aggravated side effects. CONCLUSION: We suggest KRG is efficient for protection for female QOL and BPA- exposure and - related oxidative stress. However, individual variation in susceptibility to KRG should be further considered for identifying ideal therapy. TRIAL REGISTRATION: KCT0000920.