Geometric cohesion in two-dimensional systems composed of star-shaped particles.

Using a discrete element method, we investigate the phenomenon of geometric cohesion in granular systems composed of star-shaped particles with 3 to 13 arms. This was done by analyzing the stability of columns built with these particles and by studying the microstructure of these columns in terms of density and connectivity. We find that systems composed of star-shaped particles can exhibit geometric cohesion (i.e., a solidlike behavior, in the absence of adhesive forces between the grains), depending on the shape of the particles and the friction between them. This phenomenon is observed up to a given critical size of the system, from which a transition to a metastable behavior takes place. We also have evidence that geometric cohesion is closely linked to the systems' connectivity and especially to the capability of forming interlocked interactions (i.e., multicontact interactions that hinder the relative rotation of the grains). Our results contribute to the understanding of the interesting and potentially useful phenomenon of geometric cohesion. In addition, our work supplements an important set of experimental observations and sheds light on the complex behavior of real, three-dimensional, granular systems.

Nonlinear effect of grain elongation on the flow rate in silo discharge.

By means of two-dimensional numerical simulations based on contact dynamics, we present a systematic analysis of the joint effects of grain shape (i.e., grain elongation) and system size on silo discharge for increasing orifice sizes D. Grains are rounded-cap rectangles whose aspect ratio are varied from 1 (disks) to 7. In order to clearly isolate the effect of grain shape, the mass of the grains is keeping constant as well as the condition of the discharge by reintroducing the exiting grains at the top of the silo. In order to quantify the possible size effects, the thickness W of the silos is varied from 7 to 70 grains diameter, while keeping the silos aspect ratio always equal to 2. We find that, as long as size effects are negligible, the flow rate Q increases as a Beverloo-like function with D, also for the most elongated grains. In contrast, the effects of grain elongation on the flow rate depend on orifice size. For small normalized orifice sizes, the flow rate is nearly independent with grain elongation. For intermediate normalized orifice sizes the flow rate first increases with grain elongation up to a maximum value that depends on the normalized size of the orifice and saturates as the grains become more elongated. For larger normalized orifice size, the flow rate is an increasing function of grains' aspect ratio. Velocity profiles and packing fraction profiles close to the orifice turn out to be self-similar for all grain shapes and for the whole range of orifice and system sizes studied. Following the methodology introduced by Janda et al. [Phys. Rev. Lett. 108, 248001 (2012)PRLTAO0031-900710.1103/PhysRevLett.108.248001], we explain the nonlinear variation of Q with grain elongation, and for all orifice sizes, from compensation mechanisms between the velocity and packing fraction measured at the center of the orifice. Finally, an equation to predict the evolution of Q as a function of the aspect ratio of the grains is deduced.

Compacting an assembly of soft balls far beyond the jammed state: Insights from three-dimensional imaging.

Very soft grain assemblies have unique shape-changing capabilities that allow them to be compressed far beyond the rigid jammed state by filling void spaces more effectively. However, accurately following the formation of these systems by monitoring the creation of new contacts, monitoring the changes in grain shape, and measuring grain-scale stresses is challenging. We developed an experimental method that overcomes these challenges and connects their microscale behavior to their macroscopic response. By tracking the local strain energy during compression, we reveal a transition from granular-like to continuous-like material. Mean contact geometry is shown to vary linearly with the packing fraction, which is supported by a mean field approximation. We also validate a theoretical framework which describes the compaction from a local view. Our experimental framework provides insights into the granular micromechanisms and opens perspectives for rheological analysis of highly deformable grain assemblies in various fields ranging from biology to engineering.

Grain size distribution does not affect the residual shear strength of granular materials: An experimental proof.

Granular materials are used in several fields and in a wide variety of processes. An important feature of these materials is the diversity of grain sizes, commonly referred to as polydispersity. When granular materials are sheared, they exhibit a predominant small elastic range. Then, the material yields, with or without a peak shear strength depending on the initial density. Finally, the material reaches a stationary state, in which it deforms at a constant shear stress, which can be linked to the residual friction angle ϕ_{r}. However, the role of polydispersity on the shear strength of granular materials is still a matter of debate. In particular, a series of investigations have proved, using numerical simulations, that ϕ_{r} is independent of polydispersity. This counterintuitive observation remains elusive to experimentalists, and especially for some technical communities that use ϕ_{r} as a design parameter (e.g., the soil mechanics community). In this Letter, we studied experimentally the effects of polydispersity on ϕ_{r}. In order to do so, we built samples of ceramic beads and then sheared these samples in a triaxial apparatus. We varied polydispersity, building monodisperse, bidisperse, and polydisperse granular samples; this allowed us to study the effects of grain size, size span, and grain size distribution on ϕ_{r}. We find that ϕ_{r} is indeed independent of polydispersity, confirming the previous findings achieved through numerical simulations. Our work fairly closes the gap of knowledge between experiments and simulations.

Experimental validation of a micromechanically based compaction law for mixtures of soft and hard grains.

In this Letter, we report on an experimental study which analyzes the compressive behavior of two-dimensional bidisperse granular assemblies made of soft (hyperelastic) and hard grains in varying proportions (κ is the portion of soft grains). By means of a recently developed uniaxial compression setup [Vu and Barés, Phys. Rev. E 100, 042907 (2019)]2470-004510.1103/PhysRevE.100.042907 and using an advanced digital image correlation method, we follow, beyond the jamming point, the evolution of the main mechanical observables, from the global scale down to the strain field inside each deformable grain. First, we validate experimentally and extend to the uniaxial case a recently proposed micromechanical compaction model linking the evolution of the applied pressure P to the packing fraction ϕ [Cantor et al., Phys. Rev. Lett. 124, 208003 (2020)]0031-900710.1103/PhysRevLett.124.208003. Second, we reveal two different linear regimes depending on whether the system is above or below a crossover strain unraveling a transition from a discrete to a continuous-like system. Third, the evolution of these linear laws is found to vary linearly with κ. These results provide a comprehensive experimental and theoretical framework that can now be extended to a more general class of polydisperse soft granular systems.

Three-dimensional compaction of soft granular packings.

This paper analyzes the compaction behavior of assemblies composed of soft (elastic) spherical particles beyond the jammed state, using three-dimensional non-smooth contact dynamic simulations. The assemblies of particles are characterized using the evolution of the packing fraction, the coordination number, and the von Misses stress distribution within the particles as the confining stress increases. The packing fraction increases and tends toward a maximum value close to 1, and the mean coordination number increases as a square root of the packing fraction. As the confining stress increases, a transition is observed from a granular-like material with exponential tails of the shear stress distributions to a continuous-like material characterized by Gaussian-like distributions of the shear stresses. We develop an equation that describes the evolution of the packing fraction as a function of the applied pressure. This equation, based on the micromechanical expression of the granular stress tensor, the limit of the Hertz contact law for small deformation, and the power-law relation between the packing fraction and the coordination of the particles, provides good predictions from the jamming point up to very high densities without the need for tuning any parameters.

Micromechanical description of the compaction of soft pentagon assemblies.

We analyze the isotropic compaction of assemblies composed of soft pentagons interacting through classical Coulomb friction via numerical simulations. The effect of the initial particle shape is discussed by comparing packings of pentagons with packings of soft circular particles. We characterize the evolution of the packing fraction, the elastic modulus, and the microstructure (particle rearrangement, connectivity, contact force, and particle stress distributions) as a function of the applied stresses. Both systems behave similarly: the packing fraction increases and tends asymptotically to a maximum value ϕ_{max}, where the bulk modulus diverges. At the microscopic scale we show that particle rearrangements occur even beyond the jammed state, the mean coordination increases as a square root of the packing fraction, and the force and stress distributions become more homogeneous as the packing fraction increases. Soft pentagons experience larger particle rearrangements than circular particles, and such behavior decreases proportionally to the friction. Interestingly, the friction between particles also contributes to a better homogenization of the contact force network in both systems. From the expression of the granular stress tensor we develop a model that describes the compaction behavior as a function of the applied pressure, the Young modulus, and the initial shape of the particles. This model, settled on the joint evolution of the particle connectivity and the contact stress, provides outstanding predictions from the jamming point up to very high densities.

Compaction of mixtures of rigid and highly deformable particles: A micromechanical model.

We analyze the isotropic compaction of mixtures composed of rigid and deformable incompressible particles by the nonsmooth contact dynamics approach. The deformable bodies are simulated using a hyperelastic neo-Hookean constitutive law by means of classical finite elements. We characterize the evolution of the packing fraction, the elastic modulus, and the connectivity as a function of the applied stresses when varying the interparticle coefficient of friction. We show first that the packing fraction increases and tends asymptotically to a maximum value ϕ_{max}, which depends on both the mixture ratio and the interparticle friction. The bulk modulus is also shown to increase with the packing fraction and to diverge as it approaches ϕ_{max}. From the micromechanical expression of the granular stress tensor, we develop a model to describe the compaction behavior as a function of the applied pressure, the Young modulus of the deformable particles, and the mixture ratio. A bulk equation is also derived from the compaction equation. This model lays on the characterization of a single deformable particle under compression together with a power-law relation between connectivity and packing fraction. This compaction model, set by well-defined physical quantities, results in outstanding predictions from the jamming point up to very high densities and allows us to give a direct prediction of ϕ_{max} as a function of both the mixture ratio and the friction coefficient.

Combined effects of contact friction and particle shape on strength properties and microstructure of sheared granular media.

We present a systematic numerical investigation concerning the combined effects of sliding friction and particle shape (i.e., angularity) parameters on the shear strength and microstructure of granular packings. Sliding friction at contacts varied from 0 (frictionless particles) to 0.7, and the particles were irregular polygons with an increasing number of sides, ranging from triangles to disks. We find that the effect of local friction on shear strength follows the same trend for all shapes. Strength first increases with local friction and then saturates at a shape-dependent value. In contrast, the effect of angularity varies, depending on the level of sliding friction. For low friction values (i.e., under 0.3), the strength first increases with angularity and then declines for the most angular shapes. For high friction values, strength systematically increases with angularity. At the microscale, we focus on the connectivity and texture of the contact and force networks. In general terms, increasing local friction causes these networks to be less connected and more anisotropic. In contrast, increasing particle angularity may change the network topology in different directions, directly affecting the macroscopic shear strength. These analyses and data constitute a first step toward understanding the joint effect of local variables such as friction and grain shape on the macroscopic rheology of granular systems.

Compaction Model for Highly Deformable Particle Assemblies.

The compaction behavior of deformable grain assemblies beyond jamming remains bewildering, and existing models that seek to find the relationship between the confining pressure P and solid fraction ϕ end up settling for empirical strategies or fitting parameters. Using a coupled discrete-finite element method, we analyze assemblies of highly deformable frictional grains under compression. We show that the solid fraction evolves nonlinearly from the jamming point and asymptotically tends to unity. Based on the micromechanical definition of the granular stress tensor, we develop a theoretical model, free from ad hoc parameters, correctly mapping the evolution of ϕ with P. Our approach unveils the fundamental features of the compaction process arising from the joint evolution of grain connectivity and the behavior of single representative grains. This theoretical framework also allows us to deduce a bulk modulus equation showing an excellent agreement with our numerical data.

The roasting process does not influence the extent of conjugation of coffee chlorogenic and phenolic acids.

Understanding the bioavailability and metabolism of coffee compounds will contribute to identify the unknown biological mechanism(s) linked to their beneficial effects. The influence of the roasting process on the metabolism of coffee chlorogenic acids in humans was evaluated. In a randomized, double-blind, crossover study, 12 healthy volunteers consumed four instant coffees namely, high roasted coffee (HRC), low roasted coffee (LRC), unroasted coffee (URC), and in vitro hydrolyzed unroasted coffee (HURC). The sum of areas under the curve (AUC) ranged from 8.65-17.6 to 30.9-126 µM/h (P < 0.05) for HRC, LRC, URC, and HURC, respectively. The AUC of HRC, LRC, and URC was correlated with the initial level of phenolic acids in the coffee drinks. Despite different absorption rates, the extent of conjugation was comparable between HRC, LRC, and URC coffees but different for HURC. The most abundant circulating metabolites during the first 5 H were dihydroferulic acid (DHFA), caffeic acid-3'-O-sulfate (CA3S) and isoferulic-3'-O-glucuronide (iFA3G). DHFA and 5-4-dihydro-m-coumaric acid (mDHCoA) were the main metabolites in the period of 5-24 H. The phenolic compounds after consumption of HURC were most rapidly absorbed (Tmax 1 H) compared with the other coffees (Tmax between 9 and 11 H). Using coffees with different degrees of roasting we highlighted that in spite of different absorption rates the extent of conjugation of phenolic acids was comparable. In addition, by using a hydrolyzed unroasted coffee we demonstrated an increased absorption of phenolic acids in the small intestine. © 2016 BioFactors, 42(3):259-267, 2016.

Structure- and dose-absorption relationships of coffee polyphenols.

Chlorogenic acids (CGAs) from coffee have biological effects related to human health. Thus, specific data on their bioavailability in the upper gastrointestinal tract are of high interest, since some molecules are absorbed here and so are not metabolized by colonic microflora. Up to now, no data on structure-absorption relationships for CGAs have been published, despite this being the most consumed group of polyphenols in the western diet. To address this gap, we performed ex vivo absorption experiments with pig jejunal mucosa using the Ussing chamber model (a model simulating the mucosa and its luminal/apical side). The main coffee polyphenols, caffeoylquinic acid (CQA), feruloylquinic acid (FQA), caffeic acid (CA), dicaffeoylquinic acid (diCQA), and D-(-)-quinic acid (QA), were incubated in individual experiments equivalent to gut lumen physiologically achievable concentrations (0.2-3.5 mM). Identification and quantification were performed with HPLC-diode array detection and HPLC-MS/MS. Additionally, the presence of ABC-efflux transporters was determined by Western blot analysis. The percentages of initially applied CGAs that were absorbed through the jejunal pig mucosa were, in increasing order: diCQA, trace; CQA, ≈ 1%; CA, ≈ 1.5%; FQA, ≈ 2%; and QA, ≈ 4%. No differences were observed within the CGA subgroups. Dose-absorption experiments with 5-CQA suggested a passive diffusion (nonsaturable absorption and a linear dose-flux relationship) and its secretion was affected by NaN3 , indicating an active efflux. The ABC-efflux transporters MDR 1 and MRP 2 were identified in pig jejunal mucosa for the first time. We conclude that active efflux plays a significant role in CGA bioavailability and, further, that the mechanism of CGA absorption in the jejunum is governed by their physicochemical properties.

Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults.

SCOPE: Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even though coffee intake has been associated with some health benefits in epidemiological studies, the bioavailability of coffee phenolics is not fully understood. OBJECTIVE AND STUDY DESIGN: We performed a dose-response study measuring plasma bioavailability of phenolics after drinking three increasing, but still nutritionally relevant doses of instant pure soluble coffee. The study design was a one treatment (coffee) three-dose randomized cross-over design, with a washout period of 2 wks between visits. RESULTS: CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose. Hence, the sum of area under the curve was significantly higher for the medium to low dose, and high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well absorbed in their intact form, regardless of the dose. CGA and phenolic acids appeared rapidly in plasma, indicating an early absorption in the gastrointestinal tract. Late-appearing metabolites were the most abundant, regardless of the dose. CONCLUSION: This study confirmed previous findings about coffee bioavailability but also showed that coffee phenolics appear in a positive dose-response manner in plasma when drank at nutritionally relevant doses.

Quantification of phenolic acids and their methylates, glucuronides, sulfates and lactones metabolites in human plasma by LC-MS/MS after oral ingestion of soluble coffee.

Chlorogenic acids and derivatives like phenolic acids are potentially bioactive phenolics, which are commonly found in many foods. Once absorbed, chlorogenic and phenolic acids are highly metabolized by the intestine and the liver, producing glucuronidated and/or sulphated compounds. These metabolites were analyzed in human plasma using a validated liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method. After protein precipitation, phenolic acids and their metabolites were extracted by using ethanol and chromatographic separation was achieved by reversed-phase using an Acquity UPLC BEH C18 column combined with a gradient elution system using 1% acetic acid aqueous solution and 1% acetic acid with 100% acetonitrile. The method was able to quantify 56 different compounds including 24 phenolic acids, 4 lactones, 15 sulfates and 13 glucuronides metabolites between 5 and 1000nM in plasma for most of them, except for m-dihydrocoumaric acid, 5-ferulloylquinic-glucuronide, 4-methoxycinnamic acid, 3-phenylpropionic acid, 3-(4-methoxyphenyl)propionic acid (25 to 1000nM) and p-dihydrocoumaric acid (50-1000nM). Values of repeatability and intermediate reproducibility were below 15% of deviation in general, and maximum 20% for the lowest concentrations. The validated method was successfully applied to quantify phenolic acids and their metabolites in plasma obtained after oral ingestion of soluble coffee. In conclusion, the developed and validated method is proved to be very sensitive, accurate and precise for the quantification of these possible dietary phenols.

Dose-response plasma appearance of green tea catechins in adults.

SCOPE: Tea is an infusion of the Camellia sinensis leaves. The most prevalent bioactive compounds in green tea are catechins (C), which are of great interest for their potential health-promoting effects. However, metabolism and bioavailability of C are not fully understood. METHODS AND RESULTS: This study investigates the human bioavailability (plasma appearance) of C after drinking three doses of infused green tea in a randomized cross-over design. The sum of area under the curve increased between the small (0.75% w/v, 180 mg total C) and medium (1.25%) dose of ingested green tea but not between the medium and the high (1.75%) dose. The overall pattern for the sum of C did not reflect the fate of individual C. While (-)-epigallocatechin and 4'-O-Me-epigallocatechin showed saturation in plasma between the medium and high green tea doses, (-)-epigallocatechin gallate and (-)-epicatechin did not "saturate" and increased proportionally with the ingested dose. Regardless of the dose, C appeared rapidly in plasma as monophasic curves, suggesting absorption in the small intestine and minimal entero-hepatic circulation. CONCLUSION: As a conclusion, when studying dose response of polyphenols and metabolites, one must look not only at the overall pattern of plasma appearance, but also at data specific for each metabolite.

Bioavailability of bioactive food compounds: a challenging journey to bioefficacy.

Bioavailability is a key step in ensuring bioefficacy of bioactive food compounds or oral drugs. Bioavailability is a complex process involving several different stages: liberation, absorption, distribution, metabolism and elimination phases (LADME). Bioactive food compounds, whether derived from various plant or animal sources, need to be bioavailable in order to exert any beneficial effects. Through a better understanding of the digestive fate of bioactive food compounds we can impact the promotion of health and improvement of performance. Many varying factors affect bioavailability, such as bioaccessibility, food matrix effect, transporters, molecular structures and metabolizing enzymes. Bioefficacy may be improved through enhanced bioavailability. Therefore, several technologies have been developed to improve the bioavailability of xenobiotics, including structural modifications, nanotechnology and colloidal systems. Due to the complex nature of food bioactive compounds and also to the different mechanisms of absorption of hydrophilic and lipophilic bioactive compounds, unravelling the bioavailability of food constituents is challenging. Among the food sources discussed during this review, coffee, tea, citrus fruit and fish oil were included as sources of food bioactive compounds (e.g. (poly)phenols and polyunsaturated fatty acids (PUFAs)) since they are examples of important ingredients for the food industry. Although there are many studies reporting on bioavailability and bioefficacy of these bioactive food components, understanding their interactions, metabolism and mechanism of action still requires extensive work. This review focuses on some of the major factors affecting the bioavailability of the aforementioned bioactive food compounds.

Dose-dependent absorption of chlorogenic acids in the small intestine assessed by coffee consumption in ileostomists.

SCOPE: Until now, the question of how the ingested doses of chlorogenic acids (CGA) from coffee influence their absorption and metabolism remains unresolved. To assess absorption in the small intestine, we performed a dose-response study with a randomized, double-blinded, crossover design with ileostomist subjects. METHODS AND RESULTS: After a polyphenol-free diet, the volunteers consumed, on three separate occasions, coffee with different total CGA contents (high 4525 µmol; medium 2219 µmol; low 1053 µmol). CGA concentrations in plasma, ileal effluent, and urine were subsequently determined by HPLC-DAD-ESI-MS and -ESI-MS/MS. The results show that the consumption of higher CGA concentrations leads to a faster ileal excretion. This corresponds to a renal excretion of 8.0 ± 4.9% (high), 12.1 ± 6.7% (medium), and 14.6 ± 6.8% (low) of total CGA and metabolites. Glucuronidation of CGA became slightly greater with increasing dose. After enzyme treatment, the area under the curve (AUC)(0-8h) for CGA metabolites in plasma was 4412 ± 751 nM × h(0-8) (-1) (high), 2394 ± 637 nM × h(0-8) (-1) (medium), 1782 ± 731 nM × h(0-8) (-1) (low), respectively. Additionally, we were able to identify new metabolites of CGA in urine and ileal fluid. CONCLUSION: We conclude that the consumption of high CGA concentrations via coffee might influence the gastrointestinal transit time and consequently affect CGA absorption and metabolism.

Absorption of dimethoxycinnamic acid derivatives in vitro and pharmacokinetic profile in human plasma following coffee consumption.

SCOPE: This study reports the 24 h human plasma pharmacokinetics of 3,4-dimethoxycinnamic acid (dimethoxycinnamic acid) after consumption of coffee, and the membrane transport characteristics of certain dimethoxycinnamic acid derivatives, as present in coffee. METHODS AND RESULTS: Eight healthy human volunteers consumed a low-polyphenol diet for 24 h before drinking 400 mL of commercially available coffee. Plasma samples were collected over 24 h and analyzed by HPLC-MS(2) . Investigation of the mechanism of absorption and metabolism was performed using an intestinal Caco-2 cell model. For the first time, we show that dimethoxycinnamic acid appears in plasma as the free aglycone. The time to reach the C(max) value of approximately 0.5 µM was rapid, T(max) = 30 min, and showed an additional peak at 2-4 h for several subjects. In contrast, smaller amounts of dimethoxy-dihydrocinnamic acid (C(max) ∼ 0.1 µM) peaked between 8 and 12 h after coffee intake. In the cell model, dimethoxycinnamic acid was preferentially transported in the free form by passive diffusion, and a small amount of dimethoxycinnamoylquinic acid hydrolysis was observed. CONCLUSION: These findings show that dimethoxycinnamic acid, previously identified in plasma after coffee consumption, was rapidly absorbed in the free form most likely by passive diffusion in the upper gastrointestinal tract.

Lesser in vitro anaerobic cecal isoflavone disappearance was associated with greater apparent absorption of daidzein and genistein in Golden Syrian hamsters.

Our hypothesis in this study was that in vitro disappearance of isoflavones from fecal or cecal contents of Golden Syrian hamsters paralleled the apparent absorption of these compounds, comparable with previous findings from in vitro human fecal incubations. Two studies were conducted to test this idea: one on in vitro fecal (study 1, n = 20/sex) and the other on in vitro cecal contents (study 2, n = 10/sex) ability to degrade isoflavones. According to HPLC analysis, urinary isoflavone excretion was significantly less by 2-4 fold in males compared with females in both studies. Fecal isoflavone excretion was not significantly different between sexes or isoflavones (study 1) and was <0.5% of ingested dose. In vitro anaerobic fecal isoflavone degradation rate constants from study 1 were minimal with no significant correlation between urinary and fecal isoflavone excretion. However, in vitro anaerobic cecal isoflavone degradation rate constants (study 2) were greater and significantly correlated with urinary excretion of daidzein (R = 0.90; p = 0.01) and genistein (R = 0.93; p = 0.004), but not glycitein (R = 0.50; p = 0.3). Both male and female hamsters showed a pattern of urinary isoflavone excretion similar to that found in humans (daidzein > genistein). Hamster in vitro cecal isoflavone degradation rate constants seemed to be analogous to human in vitro fecal isoflavone degradation rate constants for genistein and daidzein. The sex difference in isoflavone excretion in hamsters and the instability in glycitein excretion across studies coupled with the paucity of human data on this isoflavone deserve further investigation.

Identification of novel circulating coffee metabolites in human plasma by liquid chromatography-mass spectrometry.

This study reports a liquid chromatography-mass spectrometry method for the detection of polyphenol-derived metabolites in human plasma without enzymatic treatment after coffee consumption. Separation of available standards was achieved by reversed-phase ultra performance liquid chromatography and detection was performed by high resolution mass spectrometry in negative electrospray ionization mode. This analytical method was then applied for the identification and relative quantification of circulating coffee metabolites. A total of 34 coffee metabolites (mainly reduced, sulfated and methylated forms of caffeic acid, coumaric acid, caffeoylquinic acid and caffeoylquinic acid lactone) were identified based on mass accuracy (<4 ppm for most metabolites), specific fragmentation pattern and co-chromatography (when standard available). Among them, 19 circulating coffee metabolites were identified for the first time in human plasma such as feruloylquinic acid lactone, sulfated and glucuronidated forms of feruloylquinic acid lactone and sulfated forms of coumaric acid. Phenolic acid derivatives such as dihydroferulic acid, dihydroferulic acid 4'-O-sulfate, caffeic acid 3'-O-sulfate, dimethoxycinnamic acid, dihydrocaffeic acid and coumaric acid O-sulfate appeared to be the main metabolites circulating in human plasma after coffee consumption. The described method is a sensitive and reliable approach for the identification of coffee metabolites in biological fluids. In future, this analytical method will give more confidence in compound identification to provide a more comprehensive assessment of coffee polyphenol bioavailability studies in humans.