Metabolism Of Polyphenols Research Articles

Impact of Polyphenols and Polyphenol-Rich Dietary Sources on Gut Microbiota Composition

Gut microbiota plays a key role in host physiology and metabolism. Indeed, the relevance of a well-balanced gut microbiota composition to an individual's health status is essential for the person's well-being. Currently, investigations are focused on analyzing the effects of pre- and probiotics as new therapeutic tools to counteract the disruption of intestinal bacterial balance occurring in several diseases. Polyphenols exert a wide range of beneficial health effects. However, although specific attention has been paid in recent years to the function of this "biological entity" in the metabolism of polyphenols, less is known about the modulatory capacity of these bioactive compounds on gut microbiota composition. This review provides an overview of the latest investigations carried out with pure polyphenols, extracts rich in polyphenols, and polyphenol-rich dietary sources (such as cocoa, tea, wine, soy products, and fruits) and critically discusses the consequences to gut microbiota composition which are produced.

Influence of a Polyphenol-Enriched Protein Powder on Exercise-Induced Inflammation and Oxidative Stress in Athletes: A Randomized Trial Using a Metabolomics Approach

ObjectivesPolyphenol supplementation was tested as a countermeasure to inflammation and oxidative stress induced by 3-d intensified training.MethodsWater soluble polyphenols from blueberry and green tea extracts were captured onto a polyphenol soy protein complex (PSPC). Subjects were recruited, and included 38 long-distance runners ages 19–45 years who regularly competed in road races. Runners successfully completing orientation and baseline testing (N = 35) were randomized to 40 g/d PSPC (N = 17) (2,136 mg/d gallic acid equivalents) or placebo (N = 18) for 17 d using double-blinded methods and a parallel group design, with a 3-d running period inserted at day 14 (2.5 h/d, 70% VO2max). Blood samples were collected pre- and post-14 d supplementation, and immediately and 14 h after the third day of running in subjects completing all aspects of the study (N = 16 PSPC, N = 15 placebo), and analyzed using a metabolomics platform with GC-MS and LC-MS.ResultsMetabolites characteristic of gut bacteria metabolism of polyphenols were increased with PSPC and 3 d running (e.g., hippurate, 4-hydroxyhippurate, 4-methylcatechol sulfate, 1.8-, 1.9-, 2.5-fold, respectively, P<0.05), an effect which persisted for 14-h post-exercise. Fatty acid oxidation and ketogenesis were induced by exercise in both groups, with more ketones at 14-h post-exercise in PSPC (3-hydroxybutyrate, 1.8-fold, P<0.05). Established biomarkers for inflammation (CRP, cytokines) and oxidative stress (protein carbonyls) did not differ between groups.ConclusionsPSPC supplementation over a 17-d period did not alter established biomarkers for inflammation and oxidative stress but was linked to an enhanced gut-derived phenolic signature and ketogenesis in runners during recovery from 3-d heavy exertion.Trial RegistrationClinicalTrials.gov, U.S. National Institutes of Health, identifier: NCT01775384

Targeted analysis of polyphenol metabolism during development of hop (Humulus lupulus L.) cones following treatment with prohexadione-calcium

Hops (Humulus lupulus), a main ingredient in beer, are valued as a source of bitter flavour and biologically active polyphenols. We treated immature hop cones with prohexadione-calcium (Pro-Ca), a flavanone-3-hydroxylase (F3H) inhibitor, to perturb the flavonoid pathway, and conducted a targeted analysis of 29 compounds from the phenolic acid, flavonoid, and terpenophenolic pathways, using photodiode array (UHPLC-PDA), and time of flight mass spectrometry (LC-TOF-MS) analysis. Hop cones were analysed over four stages of development spanning 22days following Pro-Ca treatment. The content of terpenophenolics as well as metabolic precursors upstream from F3H significantly increased, and levels of flavonoid products downstream from F3H decreased. The methods developed here serve to compliment flavour analysis of polyphenol rich foods, and our results suggest ways to improve upon traditional agricultural methods to produce hops with altered chemical profiles.

Fecal microbial metabolism of polyphenols and its effects on human gut microbiota

We investigated the biotransformation of four common dietary polyphenols, rutin, quercetin, chlorogenic acid and caffeic acid, in an in vitro mixed culture model of human intestinal microbiota, to determine effects on human gut bacteria. All four compounds were biotransformed rapidly, disappearing from the medium within 0.5 h and later replaced by known phenolic acid breakdown products, at concentrations up to hundreds of micromolar, much higher than in no-polyphenol control experiments. Quantitative PCR was used to measure effects of the polyphenols on the balance between the major groups of intestinal bacteria that are known to influence gut health, i.e., Bifidobacterium spp., Bacteroidetes, and Firmicutes. Fermentation of polyphenols stimulated proliferation of bifidobacteria and decreased the ratio of Firmicutes to Bacteroidetes, relative to controls. Polyphenols also stimulated short chain fatty acid production by the bacteria. Pure bifidobacterial cultures were treated separately with either fermented media isolated from the incubations, the pure test polyphenols, or the biotransformation products detected in the fermentations. Growth stimulation was observed only with fermented polyphenol media and the pure biotransformation products. It appears that dietary polyphenols may have the ability to modify the gut microbial balance, but this effect is indirect, i.e., it is mediated by biotransformation products, rather than the original plant compounds.

Bioavailability of dietary antioxidants in Acanthopanax sieboldianus Makino leaves

We have investigated the intestinal absorption and metabolism of the polyphenols contained in Acanthopanax sieboldianus Makino (Ukogi in Japanese) in rat plasma using a liquid chromatography/mass spectrometry (LC/MS). Ukogi mainly contained chlorogenic acid, rutin, and kaempferol 3-O-rutinoside. These polyphenols were detected in non-hydrolyzed rat plasma 0.5 hour after oral administration, and the concentration of rutin was 13.6 ± 3.65 nM. The metabolized compounds of kaempferol sulfoglucuronide and 3’-O-methylquercetin sulfoglucuronide were identified by exact mass determination and exact mass mass spectrometry/mass spectrometry (MS/MS) in the plasma of rats fed a 5 % Ukogi diet for 8-24 days. Antioxidant potential of the metabolized compounds is discussed concerning a beneficial effect in the body via antioxidation caused by not only scavenging superoxide but also blocking superoxide generation.

Intrinsic isotopic 13C labelling of polyphenols

The intrinsic isotopic labelling of plants with 13CO2 is an effective method to generate highly labelled compounds using photosynthesis and avoiding labour-intensive complex organic syntheses. In this study, the intrinsic isotopic labelling of polyphenols in parsley, spinach and peppermint is shown for the first time. The plants were grown in an atmosphere where 12CO2 was replaced by 13CO2, in order to generate highly labelled compounds. The total content of 13C as well as the individual polyphenols were analysed by Isotopic Ratio-MS and HPLC–Iontrap-MSn.After 34days of plant growth under 13CO2, degree of labelling was found to be higher than 90atom% 13C for most polyphenols, predominantly consisting of highly and fully labelled isotopomers; the total plant material contained more than 88atom% 13C. Such highly labelled compounds can be used in future studies to dissect both metabolism and bioavailability of polyphenols in humans.

Polyphenol gene expression and changes in anthocyanins and polyphenols in the skin of ‘Braeburn’ apples after the autumn application of prohexadione-calcium

Prohexadione-calcium (Pro-Ca) transient inhibits 2-Oxoglutarate-dependent dioxygenases and causes significant changes in the flavonoid spectrum of apple. In the present study the influence of two autumn preharvest applications of Pro-Ca on the polyphenol metabolism in apple peel during the advanced maturation was investigated. Pro-Ca was sprayed in two doses, approximately five and 3 weeks before the technological maturity. Changes in the concentrations of hydroxycinnamic acids, dihydrochalcones, flavonols, flavanols and anthocyanins as well as their related gene expression and enzyme activities in the apple peel were monitored six times during the advanced maturation until the technological maturity of the fruits. To evaluate its influence on red coloration differences in the chromatic values a*, h° and L* between the treated and untreated apples were monitored. The parameters showed a temporary effect of Pro-Ca on the intensity of red coloration, which was not detected anymore at the technological maturity of apples. The application of Pro-Ca decreased the flavanone 3-hydroxylase activity and slightly inhibited activities of all the enzymes analyzed. Concomitantly, the concentrations of anthocyanins in the peel of the treated apples decreased, whereas the concentrations of hydroxycinnamic acids, dihydrochalcones and flavan 3-ols increased. Flavonol concentrations, however, remained unchanged. The expression of ANS, ANR, FGT and MYB10 was downregulated after the Pro-Ca treatment. The results indicate that the autumn application of Pro-Ca modulates the biosynthetic pathway resulting in distinct changes in the flavonoid composition in the apple peel of ‘Braeburn’ apples. However, the changes are temporary and are generally suspended during apple storage.

Levels of urinary isoflavones and lignan polyphenols in Japanese women

High consumption of soybean products has been associated with a reduced risk of hormone-sensitive tumors. Soybean products contain phytoestrogens, such as daidzein, and sesame seeds contain secoisolariciresinol. These compounds are further metabolized to equol, enterodiol, and enterolactone by intestinal bacteria. However, individual differences in the metabolizing potential remain unclear. The aim of this study was to evaluate the urinary daidzein, equol, enterodiol, and enterolactone concentrations in women from several different regions of Japan according to age group. Five hundred urine samples collected from Japanese women living in Sapporo, Sendai, Kyoto, Kochi, and Naha were analyzed for daidzein, equol, enterodiol, and enterolactone concentration by gas chromatography-mass spectrometry. The urinary isoflavone and lignan polyphenol levels did not differ significantly among the sampling sites, except for daidzein, which was highest in urine collected at Naha. The prevalence of equol producers was 39 % in the total study cohort. In equol producers, a positive correlation was observed between the urinary daidzein and equol levels (r = 0.399, p < 0.001). However, there was no significant difference between daidzein concentrations in equol producers and non-producers. Moreover, the levels of enterodiol and enterolactone were higher in equol producers than in equol non-producers. In the multivariate logistic analyses, two factors, Sendai dwelling and current smoking, were found to be significant [equol producers to non-producers: odds ratio 2.15 (95 % confidence interval: 1.17-4.02) and odds ratio 0.32 (0.15-0.63), respectively]. Our data suggest that geographic factors and smoking status should be considered during the evaluation of equol in urine samples and that the same pathway may be responsible for the metabolism of both isoflavones and lignan polyphenols.

Chronic coffee consumption alters gut microbiome: potential mechanism to explain the protective effects of coffee on type 2 diabetes?

Cumulative epidemiological studies indicate a negative relationship between coffee consumption and type 2 diabetes (T2D). However, the specific mechanisms by which coffee reduces T2D is unknown but may involve the metabolism of polyphenols in coffee by the gut microbiome. To this end, we examined the impact of chronic coffee consumption on the gut microbiome in lean and diet‐induced obese rats. Male Sprague‐Dawley rats (n=40) were randomized into chow (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) dietary groups. Each group was further divided into groups consuming water or coffee for 8wk, consuming food and fluid ad libitum (n=10/treatment). Coffee consumption was associated with lower weight gain and body fat percentage in both CH and HF (p&lt;0.05). Oral glucose and insulin tolerance tests showed HF (p&lt;0.05) but not coffee consumption to alter insulin action. Compared to CH, HF resulted in a reduction in Total Eubacteria levels in water but not coffee treatment (p&lt;0.05). Lactobacillus was decreased in the HF‐water group but not HF‐coffee suggesting coffee had a protective effect. Alterations in the gut microbiome were supported by analysis of serum metabolites by proton nuclear magnetic resonance spectroscopy (1H NMR) and gas chromatography mass spectrometry (GC‐MS). This data indicate that gut microbiota‐host metabolic interactions may mediate the beneficial effects of coffee on the development of T2D.

Sensorial, biochemical and molecular changes in Raboso Piave grape berries applying “Double Maturation Raisonnée” and late harvest techniques

At ripening, Vitis vinifera cv Raboso Piave grapes have high acidity, which results in an astringent wine that is not easy to drink. To overcome this limitation, several researches have attempted to alter the polyphenols profile mainly by applying different harvest techniques.The aim of this work was to investigate sensorial, biochemical, and molecular changes in Raboso Piave grape berries subjected to delayed harvests as Late Harvest (LH) and “Double Maturation Raisonnée” (DMR) techniques. At the molecular level, a microarray study was conducted comparing Traditional Harvest berries (TH) to LH and DMR ones. Gene ontology enrichment analysis pointed out that LH and DMR techniques affected metabolism of acids, sugars and polyphenols. A Principal Component Analysis, performed on transcriptomic data, pointed out that malate catabolism as well as some branches of flavonoids biosynthesis are significantly affected by DMR. In DMR grape berries, the flavonol and catechin accumulations were induced and depressed, respectively. In parallel, the transcription of flavonol synthase and leucoanthocyanidin-reductase 2, the main genes responsible for flavonol and catechin biosynthesis, were similarly induced and down-regulated. These changes resulted in a brighter colored wine with lower astringency.

An anthocyanin-rich extract from Kamchatka honeysuckle increases enzymatic activity within the gut and ameliorates abnormal lipid and glucose metabolism in rats

ObjectiveThe berries of blue honeysuckle (Lonicera caerulea L.), including an edible Kamchatka variety (var. kamtschatica Sevast.), are a potential but relatively unknown source of anthocyanins, which are thought to have favorable effects on diabetes and cardiovascular disease (CVD). The aim of this study was to examine whether the dietary addition of a Kamchatka honeysuckle berry extract (KHBE, 327 mg anthocyanins/g) is able to limit the disorders related to these diseases induced by a high-fructose diet in rats. MethodsThe experiment was conducted using 24 adult male Wistar rats distributed into 3 groups of 8 animals each and fed semipurified casein diets differentiated by the carbohydrate source for 4 wk, as follows: a control cornstarch diet (681 g/kg) or a high-fructose diet (633 g/kg), with or without the addition of KHBE (2 g/kg). ResultsThe mucosal lactase activity in the small intestine was increased in the rats fed the KHBE-containing diet compared with the rats fed the control diet. In the cecal digesta, the dietary KHBE considerably increased bacterial α- and β-glucosidase activity. Furthermore, hyperlipidemia, hyperinsulinemia, insulin resistance, and impaired glucose tolerance were detected in the rats fed the high-fructose diet. The dietary KHBE normalized the plasma triglyceride concentration and atherogenicity, whereas plasma non-HDL cholesterol, insulin concentration, and insulin resistance were ameliorated to levels comparable with the rats fed the control diet. ConclusionAn anthocyanin-rich Kamchatka honeysuckle berry extract supplemented to an unbalanced diet is able to ameliorate the disturbances in lipid and glucose metabolism that are the fundamental risk factors for CVD and diabetes. Moreover, the extract stimulates enzymatic activity within the gut that seems to be related to the metabolism of polyphenols.

Impact of polyphenols from black tea and red wine/grape juice on a gut model microbiome

Food and beverage products derived from fruit and vegetables contain polyphenols, which have been associated with various health benefits. Polyphenols may influence health through direct uptake in the intestine but also upon interaction with the gut microbiota for example by modification of the microbial composition or by conversion of the polyphenols to further bioactive compounds. So far, there are limited studies of complex polyphenols on the human gut microbiota especially using modern molecular technologies. Most studies investigating effects of dietary polyphenols have focused on single molecules or bacterial strains. In the current study, an in vitro gut microbial ecosystem, namely simulator of the intestinal microbial ecosystem (SHIME), was challenged with either a black tea or a red wine grape extract (RWGE), both containing complex dietary polyphenol mixtures. Within the context of the model system, the effects of these interventions on both microbial numbers and composition as well as metabolite levels were assessed. Antimicrobial effects, largely confined to unculturable members of the ecosystem, were revealed by complementary microbiological techniques. Pyrosequencing analysis showed a shift in the Firmicutes:Bacteroidetes ratio for both interventions. Black tea stimulated Klebsiella, enterococci and Akkermansia and reduced bifidobacteria, B. coccoides, Anaeroglobus and Victivallis. RWGE promoted growth of Klebsiella, Alistipes, Cloacibacillus, Victivallis and Akkermansia while bifidobacteria, B. coccoides, Anaeroglobus, Subdoligranulum and Bacteroides were decreased.The study shows that these complex polyphenols in the context of a model system can modulate select members of the human gut microbiota. These members represent novel targets of polyphenol degrading or resistant microbes to be validated under physiological conditions in vivo and further investigated for polyphenol metabolism or resistance mechanisms.

Gastrointestinal absorption and metabolism of apple polyphenols ex vivo by the pig intestinal mucosa in the Ussing chamber

Polyphenols contained in food have various positive effects on human health. The absorption and metabolism of polyphenols in the intestinal tract needs to be studied to estimate these effects. The Ussing chamber technique was used to investigate the transport behavior of apple polyphenols through pig small intestinal mucosa, which served as a model for human gastrointestinal mucosa. The identities and concentrations of polyphenols and their metabolites in the half-chambers (luminal and basolateral) within an incubation period of 4 h were determined by HPLC-MS/MS and HPLC-DAD (DAD = diode-array detection). Flux values were also measured. It was found that 5-caffeoylquinic acid and caffeic acid were absorbed and translocated to the basolateral side (1.9 and 3.7%, respectively), but other compounds, including glycosides of phloretin and quercetin, were observed without translocation. A Ussing chamber utilizing pig small intestinal mucosa is a suitable model for assessing the effect of apple polyphenols on mucosal integrity and nutrition absorption across porcine mucosa.

A pilot study to investigate bioavailability of strawberry anthocyanins and characterize postprandial plasma polyphenols absorption patterns by Q-TOF LC/MS in humans

BACKGROUND: Information on absorption and metabolism of strawberry polyphenols is limited. OBJECTIVE: The aim of this study was to characterize and quantify plasma polyphenols/anthocyanins across 4 doses of strawberry using Q-TOF LC/MS and LC-MS/MS analysis. METHOD: Plasma was collected from 5 subjects (n = 5) every 30–60 min for 6 h after consuming beverages containing 0, 10, 20 or 40 g freeze-dried strawberry powder with a meal. RESULTS: Q-TOF LC/MS and LC-MS/MS analysis of plasma revealed 33 compounds; 7 not reported previously. Pelargonidin-O-glucuronide (PG) was the most abundant metabolite. Maximum concentrations (Cmax) of PG were achieved at 148 ± 31 min and were significantly different among beverages containing 0, 10, 20, 40 g strawberry powder: 0, 93.4 ± 21.9, 166.5 ± 16.2 and 226.7 ± 36.7 nmol/L, respectively (P < 0.05). Area under the concentration curve (AUC) also increased with dose (P < 0.05); however, Cmax and AUC of PG was reduced as a percent of pelargonidin-3-O-glucoside (P3G) delivered in the strawberry beverages (P < 0.05). CONCLUSION: Use of both Q-TOF LC/MS and LC-MS/MS allowed for detection of compounds in plasma not previously reported, which may be a useful approach for characterizing postprandial plasma metabolites of lesser known plant foods. Additionally, higher concentrations of key strawberry compounds/metabolites are achieved with eating more strawberry; however, saturation of absorptive capacity of pelargonidin-based anthocyanins was suggested.

Labile carbon in biological soil crusts in the Tabernas desert, SE Spain

Decomposition processes are extremely important in biological soil crusts (BSCs). Although the effects of temperature and moisture on such processes have been widely studied, little is known about the influence of the readily metabolizable substrate (labile C) and how this substrate varies in different types of BSCs. In the present study, BSCs formed by cyanobacteria (CYANO) and by lichens (DIPLOS and LEPRA) were incubated at 25 °C (optimum temperature) and different moisture levels, for evaluation of the pool of labile C in the crust layers. Labile C was estimated as the sum of CO2–C emitted and the C extracted with hot water (80 °C) at the end of the incubation period. In all crusts, the relationship between emission and moisture fitted a quadratic model. For the different moisture contents, the sum of CO2–C emitted and C extracted with hot water converged to a constant value for each type of crust. This value, considered as the maximum content of labile C in the crust, was extremely high in DIPLOS, reaching up to 40% of the total organic C (TOC) initially present. In all crusts, and independently of the consumption of labile C, simple sugars (sucrose, glucose) remained at the end of the incubation period, which suggests that these sugars may play a protective role in BSCs. The presence of mannitol suggests that the fructose released during hydrolysis of sucrose was reduced to mannitol, thus enabling electron transport during moments of intense respiratory stress. The intense respiration in DIPLOS is partly due to the metabolism of polyphenols, which are possibly derived from the growth and death of free-living fungi that proliferate during incubation of the crusts. These results demonstrate that the metabolic processes in BSCs differ depending on the type of organisms that form the crusts and that there is a high risk of C loss from Diploschistes BSCs after heavy rainfall events.

Gut Microbial Metabolism of Polyphenols from Black Tea and Red Wine/Grape Juice Is Source-Specific and Colon-Region Dependent

The colonic microbial degradation of a polyphenol-rich black tea extract (BTE) and red wine/grape juice extract (RWGE) was compared in a five-stage in vitro gastrointestinal model (TWINSHIME). Microbial metabolism of BTE and RWGE polyphenols in the TWINSHIME was studied subsequently in single- and continuous-dose experiments. A combination of liquid or gas chromatography with mass spectrometry (LC-MS or GC-MS) and NMR-based metabolic profiling was used to measure selected parent polyphenols, their microbial degradation into phenolic acids, and the production of short-chain fatty acids (SCFAs) in different colon compartments. Acetate production was increased by continuous feeding of BTE but not RWGE. During RWGE feeding, gallic acid and 4-hydroxyphenylpropionic acid remained elevated throughout the colon, while during BTE feeding, they were consumed in the distal colon, while 3-phenylpropionic acid was strongly produced. Gut microbial production of phenolics and SCFAs is dependent on colon location and polyphenol source, which may influence potential health benefits.

Colonic Metabolism of Polyphenols From Coffee, Green Tea, and Hazelnut Skins

Dietary polyphenolic compounds are poorly absorbed in the small intestine. The absorbed fraction follows the common metabolic pathway of drugs, undergoing phase II enzymatic detoxification with the conjugation of glucuronic acid, sulfate, and methyl groups. However, the unabsorbed fraction can reach the colon, becoming available for the wide array of enzymes produced by the local commensal microbiota. Gut bacteria can hydrolyze glycosides, glucuronides, sulfates, amides, esters, and lactones and are able to break down the polyphenolic skeleton and perform reactions of reduction, decarboxylation, demethylation, and dehydroxylation. These complex modifications generate several low-molecular-weight metabolites that can be efficiently absorbed in situ, subsequently undergoing further phase II metabolism, locally and/or at the liver level, before entering the systemic blood circulation and finally being excreted in urine in substantial quantities that exceed the excretion of phenolic metabolites formed in the upper gastrointestinal tract. This brief work focuses on the phenolic composition and colonic microbial transformation of 2 of the most polyphenol-rich dietary sources, namely, green tea and coffee, and a new interesting and innovative ingredient, hazelnut skin, recently evaluated as one of the richest edible sources of polyphenolic compounds.

Taking a metagenomic view of human nutrition

Humans harbor microbial communities throughout the gastrointestinal tract that both respond to and modify orally ingested macronutrients, bioactive compounds, and xenobiotics; for example, the metabolism of polyphenols, heterocyclic amines, and phosphatidylcholine. However, the composition and physiological impact of our diet is also linked to the methods of food production, preparation, and consumption, which are altered by environmental and food-borne microbial communities. Metagenomic analyses spanning these various steps in human nutrition will be critical for a more comprehensive view. Studies in humans and animal models have highlighted the key role that diet plays in shaping gut microbial ecology, and how the trillions of microbes in the gut (microbiota) enable the digestion of substrates inaccessible to our own human enzymes. These transformations have been implicated in a variety of diseases and disorders, ranging from obesity, inflammatory bowel disease, heart disease, to cancer. In order to move towards personalized nutrition and medicine, it is important to take into account both our host and microbial genomes. The resulting metagenomic view of human nutrition, ranging from the initial biotransformations of food to digestion and the end result on human physiology, could have wide-ranging implications for food science, human evolutionary biology, and microbial ecology.

Following the metabolism of polyphenols and proanthocyanins in an in-vitro digestion model

Following the metabolism of polyphenols and proanthocyanins in an in-vitro digestion model

Phenol-Explorer 2.0: a major update of the Phenol-Explorer database integrating data on polyphenol metabolism and pharmacokinetics in humans and experimental animals

Phenol-Explorer, launched in 2009, is the only comprehensive web-based database on the content in foods of polyphenols, a major class of food bioactives that receive considerable attention due to their role in the prevention of diseases. Polyphenols are rarely absorbed and excreted in their ingested forms, but extensively metabolized in the body, and until now, no database has allowed the recall of identities and concentrations of polyphenol metabolites in biofluids after the consumption of polyphenol-rich sources. Knowledge of these metabolites is essential in the planning of experiments whose aim is to elucidate the effects of polyphenols on health. Release 2.0 is the first major update of the database, allowing the rapid retrieval of data on the biotransformations and pharmacokinetics of dietary polyphenols. Data on 375 polyphenol metabolites identified in urine and plasma were collected from 236 peer-reviewed publications on polyphenol metabolism in humans and experimental animals and added to the database by means of an extended relational design. Pharmacokinetic parameters have been collected and can be retrieved in both tabular and graphical form. The web interface has been enhanced and now allows the filtering of information according to various criteria. Phenol-Explorer 2.0, which will be periodically updated, should prove to be an even more useful and capable resource for polyphenol scientists because bioactivities and health effects of polyphenols are dependent on the nature and concentrations of metabolites reaching the target tissues. The Phenol-Explorer database is publicly available and can be found online at http://www.phenol-explorer.eu.Database URL: http://www.phenol-explorer.eu