The effects and associations of whole-apple intake on diverse cardiovascular risk factors. A narrative review.

Apples are among the world's most consumed fruits. However, while the impact of whole-apple intake on cardiovascular disease (CVD) remains unknown. This narrative review summarizes a novel integrated view of whole-apple intake, CVD risk association (through observational studies; OSs), and the effects on CVD risk factors (randomized trials; RTs). In 8 OSs, whole-apple intake was associated with a reduced risk of CVD mortality, ischemic heart disease mortality, stroke mortality, all-cause mortality, and severe abdominal aortic calcification, as well as with lower C-reactive protein (CRP) concentrations. In 8 RTs, whole-apple consumption reduced total cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, pulse pressure, and plasma inflammatory cytokines, and noticeably reduced CRP, whereas it increased high-density lipoprotein cholesterol (HDLc) and improved endothelial function. Thus, consuming between 100 and 150 g/day of whole apples is associated with a lower CVD risk and decreases in blood pressure, pulse pressure, total cholesterol, low-density lipoprotein cholesterol, and inflammation status as well as with increases in HDLc and endothelial function. These results, support the regular consumption of whole apples as an aid in the prevention of CVD.

Phenyl-γ-valerolactones and phenylvaleric acids, the main colonic metabolites of flavan-3-ols: synthesis, analysis, bioavailability, and bioactivity.

Covering: 1958 to June 2018 Phenyl-γ-valerolactones (PVLs) and their related phenylvaleric acids (PVAs) are the main metabolites of flavan-3-ols, the major class of flavonoids in the human diet. Despite their presumed importance, these gut microbiota-derived compounds have, to date, in terms of biological activity, been considered subordinate to their parent dietary compounds, the flavan-3-ol monomers and proanthocyanidins. In this review, the role and prospects of PVLs and PVAs as key metabolites in the understanding of the health features of flavan-3-ols have been critically assessed. Among the topics covered, are proposals for a standardised nomenclature for PVLs and PVAs. The formation, bioavailability and pharmacokinetics of PVLs and PVAs from different types of flavan-3-ols are discussed, taking into account in vitro and animal studies, as well as inter-individual differences and the existence of putative flavan-3-ol metabotypes. Synthetic strategies used for the preparation of PVLs are considered and the methodologies for their identification and quantification assessed. Metabolomic approaches unravelling the role of PVLs and PVAs as biomarkers of intake are also described. Finally, the biological activity of these microbial catabolites in different experimental models is summarised. Knowledge gaps and future research are considered in this key area of dietary (poly)phenol research.

Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes.

PURPOSE: There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated. METHODS: Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites. RESULTS: (Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids. CONCLUSIONS: The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet.

Catabolism of citrus flavanones by the probiotics Bifidobacterium longum and Lactobacillus rhamnosus.

PURPOSE: Orange juice (OJ) flavanones undergo limited absorption in the upper gastrointestinal tract and reach the colon where they are transformed by the microbiota prior to absorption. This study investigated the ability of two probiotic bacteria, Bifidobacterium longum R0175 and Lactobacillus rhamnosus subsp. Rhamnosus NCTC 10302 to catabolise OJ flavanones. METHODS: The bacteria were incubated with hesperetin-7-O-rutinoside, naringenin-7-O-rutinoside, hesperetin and naringenin, and the culture medium and intracellular cell extracts were collected at intervals over a 48 h of incubation period. The flavanones and their phenolic acid catabolites were identified and quantified by HPLC-HR-MS. RESULTS: Both probiotics were able to subject hesperetin to ring fission yielding 3-(3'-hydroxy-4'-methoxyphenyl)propionic acid which was subsequently demethylated producing 3-(3',4'-dihydroxyphenyl)propionic acid and then via successive dehydroxylations converted to 3-(3'-hydroxyphenyl)propionic acid and 3-(phenyl)propionic acid. Incubation of both bacteria with naringenin resulted in its conversion to 3-(4'-hydroxyphenyl)propionic acid which underwent dehydroxylation yielding 3-(phenyl)propionic acid. In addition, only L. rhamnosus exhibited rhamnosidase and glucosidase activity and unlike B. longum, which was able to convert hesperetin-7-O-rutinoside and naringenin-7-O-rutinoside to their respective aglycones. The aglycones were then subjected to ring fission and further catabolised in a similar manner to that described above. The flavanones and their catabolites were found in the culture medium but not accumulated in the bacterial cells. CONCLUSIONS: These findings demonstrate the enzymatic potential of single strains of bifidobacterium and lactobacillus which may be involved in the colonic catabolism of OJ flavanones in vivo.

Chlorogenic acids and the acyl-quinic acids: discovery, biosynthesis, bioavailability and bioactivity.

Covering: 2000 up to late 2017This review is focussed upon the acyl-quinic acids, the most studied group within the ca. 400 chlorogenic acids so far reported. The acyl-quinic acids, the first of which was characterised in 1846, are a diverse group of plant-derived compounds produced principally through esterification of an hydroxycinnamic acid and 1l-(-)-quinic acid. Topics addressed in this review include the confusing nomenclature, quantification and characterisation by NMR and MS, biosynthesis and role in planta, and the occurrence of acyl-quinic acids in coffee, their transformation during roasting and delivery to the beverage. Coffee is the major human dietary source world-wide of acyl-quinic acids and consideration is given to their absorption and metabolism in the upper gastrointestinal tract, and the colon where the microbiota play a key role in the formation of catabolites. Evidence on the potential of the in vivo metabolites and catabolites of acyl-quinic acids to promote the consumer's health is evaluated.

In vitro studies on the stability in the proximal gastrointestinal tract and bioaccessibility in Caco-2 cells of chlorogenic acids from spent coffee grounds.

Spent coffee grounds are a potential commercial source of substantial amounts of chlorogenic acids (CGAs). The aim of this study was to evaluate the stability of spent coffee CGAs using in vitro simulated gastroduodenal digestion and to investigate their potential absorption using an in vitro Caco-2 model of human small intestinal epithelium. During in vitro digestion, lactones were partially degraded while caffeoylquinic and feruloylquinic acids were much more stable. Transport and metabolism studies showed that 1% of the total CGAs were absorbed and transported from the apical to the basolateral side of a Caco-2 cell monolayer after 1 h. Lactones and coumaroylquinic acids showed the rate of highest absorption. Caco-2 cells possessed low metabolic activity. In conclusion, spent coffee extracts contain large amounts of CGAs, which remained bioaccessible across the intestinal barrier, albeit to a relatively low degree.

Industrial and culinary treatments applied to Piquillo pepper (Capsicum annuum cv. Piquillo) impact positively on (poly)phenols' bioaccessibility and gut microbiota catabolism.

Thermal treatments applied to plant-based foods prior to consumption might influence (poly)phenols' bioaccessibility and the metabolization of these compounds by the gut microbiota. In the present research, the impact of industrial (grilling and canning) and culinary (microwaving and frying) treatments on the bioaccessibility and colonic biotransformations of (poly)phenols from Piquillo pepper (Capsicum annum cv. Piquillo) were evaluated by in vitro gastrointestinal digestion and colonic fermentation models and HPLC-ESI-MS/MS. The application of industrial treatments impacted positively on (poly)phenols' bioaccessibility compared to raw pepper. Microwaving also exerted a positive effect on (poly)phenols' bioaccessibility compared to canning whereas the addition of oil for frying seemed to negatively affect (poly)phenols' release from the food matrix. Throughout the 48 hours of the colonic fermentation process (poly)phenolic compounds were catabolized into different (poly)phenol derivatives whose formation was also positively affected by industrial and culinary treatments. Based on the concentration and time of appearance of these derivatives, catabolic pathways of (poly)phenols from Piquillo pepper were proposed. The major (poly)phenol derivatives identified (3-(3'-hydroxyphenyl)propanoic acid, 4-hydroxy-3-methoxyphenylacetic acid and benzene-1,2-diol) are considered of great interest for the study of their bioactivity and the potential effect on human health.

Exploring and disentangling the production of potentially bioactive phenolic catabolites from dietary (poly)phenols, phenylalanine, tyrosine and catecholamines.

Following ingestion of fruits, vegetables and derived products, (poly)phenols that are not absorbed in the upper gastrointestinal tract pass to the colon, where they undergo microbiota-mediated ring fission resulting in the production of a diversity of low molecular weight phenolic catabolites, which appear in the circulatory system and are excreted in urine along with their phase II metabolites. There is increasing interest in these catabolites because of their potential bioactivity and their use as biomarkers of (poly)phenol intake. Investigating the fate of dietary (poly)phenolics in the colon has become confounded as a result of the recent realisation that many of the phenolics appearing in biofluids can also be derived from the aromatic amino acids, l-phenylalanine and l-tyrosine, and to a lesser extent catecholamines, in reactions that can be catalysed by both colonic microbiota and endogenous mammalian enzymes. The available evidence, albeit currently rather limited, indicates that substantial amounts of phenolic catabolites originate from phenylalanine and tyrosine, while somewhat smaller quantities are produced from dietary (poly)phenols. This review outlines information on this topic and assesses procedures that can be used to help distinguish between phenolics originating from dietary (poly)phenols, the two aromatic amino acids and catecholamines.

Urinary excretion of organosulfur compounds after acute ingestion of black onion.

Onion (Allium cepa L.) and its newly derived product "black onion" are characterised by the presence of compounds with potential bioactivity, particularly organosulfur compounds (OSCs). However, little is known about the metabolism, distribution, and excretion of these compounds as they pass through the gastrointestinal tract. This study monitored healthy subjects after an acute intake of black onion and analysed the excretion of OSCs using UHPLC-HRMS. A total of 31 OSCs were detected in urine after the acute ingestion of black onion, the main components being S-methyl-L-cysteine sulfoxide (methiin) (13.6 ± 3.9 µmol), isoalliin (12.4 ± 4.7 µmol) and S-propyl-L-cysteine (deoxypropiin) (3.1 ± 0.7 µmol). Moreover, N-acetylated metabolites of the major OSCs detected in black onion, namely, N-acetyl-S-(1-propenyl)-L-cysteine sulfoxide (NAS1PCS) and N-acetyl-S-(1-propenyl)-L-cysteine (NAS1PC), were found in urine after black onion consumption. The N-acetylation reaction takes place in the kidneys and liver, and metabolism pathways are proposed to explain the excretion of OSCs in urine. The basis of the identification of OSCs as urinary metabolites after black onion consumption is described for the first time and provides the basis for further research.

LC-MS/MS Analysis Elucidates the Different Effects of Industrial and Culinary Processing on Total and Individual (Poly)phenolic Compounds of Piquillo Pepper (Capsicum annuum cv. Piquillo).

Pepper constitutes an important source of (poly)phenols, mainly flavonoids. Nevertheless, heat treatments applied prior to consumption may have an impact on these antioxidants, and thus may also affect their potential bioactivity. In this study, the effect of industrial and culinary treatments on the total and individual (poly)phenolic content of Piquillo pepper (Capsicum annuum cv. Piquillo) was thoroughly evaluated by high-performance liquid chromatography coupled to tandem mass spectrometry. A total of 40 (poly)phenols were identified and quantified in raw pepper. Flavonoids (10 flavonols, 15 flavones, and 2 flavanones) were the major compounds identified (62.6%). Among the 13 phenolic acids identified in raw samples, cinnamic acids were the most representative. High temperatures applied and subsequent peeling during industrial grilling drastically decreased the total (poly)phenolic content from 2736.34 to 1099.38 µg/g dm (59.8% reduction). In particular, flavonoids showed a higher reduction of 87.2% after grilling compared to nonflavonoids which only decreased by 14%. Moreover, 9 nonflavonoids were generated during grilling, modifying the (poly)phenolic profile. After culinary treatments, specifically frying, (poly)phenols appear to be better released from the food matrix, enhancing their extractability. Overall, industrial and culinary treatments differently affect both the total and individual (poly)phenolic compounds of pepper and, despite the reduction, they might also positively influence their bioaccessibility.

Bioavailability of Organosulfur Compounds after the Ingestion of Black Garlic by Healthy Humans.

The consumption of black garlic has been related to a decreased risk of many human diseases due to the presence of phytochemicals such as organosulfur compounds (OSCs). However, information on the metabolization of these compounds in humans is limited. By means of ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS), this study aims to determine the OSCs and their metabolites excreted in urine 24 h after an acute intake of 20 g of black garlic by healthy humans. Thirty-three OSCs were identified and quantified, methiin (17,954 ± 6040 nmol), isoalliin (15,001 ± 9241 nmol), S-(2-carboxypropyl)-L-cysteine (8804 ± 7220 nmol) and S-propyl-L-cysteine (deoxypropiin) (7035 ± 1392 nmol) being the main ones. Also detected were the metabolites N-acetyl-S-allyl-L-cysteine (NASAC), N-acetyl-S-allyl-L-cysteine sulfoxide (NASACS) and N-acetyl-S-(2-carboxypropyl)-L-cysteine (NACPC), derived from S-allyl-L-cysteine (SAC), alliin and S-(2-carboxypropyl)-L-cysteine, respectively. These compounds are potentially N-acetylated in the liver and kidney. The total excretion of OSCs 24 h after the ingestion of black garlic was 64,312 ± 26,584 nmol. A tentative metabolic pathway has been proposed for OSCs in humans.

Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer.

Drug combinations are key to circumvent resistance mechanisms compromising response to single anti-cancer targeted therapies. The implementation of combinatorial approaches involving MEK1/2 or KRASG12C inhibitors in the context of KRAS-mutated lung cancers focuses fundamentally on targeting KRAS proximal activators or effectors. However, the antitumor effect is highly determined by compensatory mechanisms arising in defined cell types or tumor subgroups. A potential strategy to find drug combinations targeting a larger fraction of KRAS-mutated lung cancers may capitalize on the common, distal gene expression output elicited by oncogenic KRAS. By integrating a signature-driven drug repurposing approach with a pairwise pharmacological screen, here we show synergistic drug combinations consisting of multi-tyrosine kinase PKC inhibitors together with MEK1/2 or KRASG12C inhibitors. Such combinations elicit a cytotoxic response in both in vitro and in vivo models, which in part involves inhibition of the PKC inhibitor target AURKB. Proteome profiling links dysregulation of MYC expression to the effect of both PKC inhibitor-based drug combinations. Furthermore, MYC overexpression appears as a resistance mechanism to MEK1/2 and KRASG12C inhibitors. Our study provides a rational framework for selecting drugs entering combinatorial strategies and unveils MEK1/2- and KRASG12C-based therapies for lung cancer.

New red-fleshed apple cultivars: a comprehensive review of processing effects, (poly)phenol bioavailability and biological effects.

Red-fleshed apple cultivars with an enhanced content of anthocyanins have recently attracted the interest of apple producers and consumers due to their attractive color and promising added health benefits. In this paper, we provide the first comprehensive overview of new hybrid red-fleshed apples, mainly focusing on their (poly)phenolic composition, the effect of processing, the (poly)phenolic bioavailability and the biological effects. Evidence so far from in vitro and in vivo studies supports their added beneficial effects compared to common apples on health outcomes such as cancer, cardiovascular disease, inflammation and immune function, which are mainly related to their specific (poly)phenol composition.

Trimethylamine N-oxide (TMAO) drives insulin resistance and cognitive deficiencies in a senescence accelerated mouse model.

It has been established that ageing is the major risk factor for cognitive deficiency and it is becoming increasingly evident that insulin resistance is another factor. Biological plausibility for a link between insulin resistance and dementia is relevant for understanding disease etiology, and to form bases for prevention efforts to decrease disease burden. In the present study, peripheral and central insulin resistance was found in SAMP8 mice (aging mouse model) accompanied by cognitive deficiencies. Furthermore, a marked peripheral inflammatory state was observed in SAMP8 mice, followed by neuroinflammation that could be due to a higher cytokine leaking into the brain across an aging-disrupted blood brain barrier. Moreover, aging-induced gut dysbiosis produces higher TMAO that could also contribute to the peripheral and central inflammatory tone as well as to the cognitive deficiencies observed in SAMP8 mice. All those alterations were reversed by DMB, a treatment that decreases TMAO levels. Data obtained from this project suggest that microbial dysbiosis and increased TMAO secretion could be a key link between aging, insulin resistance and dementia. Thus, pharmacological intervention that leads to decreased TMAO levels, such as DMB, could open a new avenue for the future treatment of neurodegenerative diseases.

In vivo study of the bioavailability and metabolic profile of (poly)phenols after sous-vide artichoke consumption.

Artichokes are a rich source of (poly)phenols, mainly caffeoylquinic acids, but little is known about their bioavailability from this source. This study investigated the absorption, metabolism and excretion of (poly)phenols after sous-vide artichoke consumption (5776 µmol of (poly)phenols) by healthy volunteers. Seventy-six (poly)phenol metabolites were identified by UHPLC-MS/MS using authentic standards, including acyl-quinic acids plus C6-C3, C6-C1, C6-C2, C6-C1-N, C6-C0 metabolites, and their phase-II conjugates. The major metabolites were 3'-methoxy-4'-hydroxycinnamic acid, 3'-methoxycinnamic acid-4'-sulfate, and 4'-hydroxycinnamic acid-3'-sulfate, which appeared early in plasma (Tmax < 4 h); plus 3-(3'-methoxy-4'-hydroxyphenyl)propanoic acid, 3-(4'-methoxyphenyl)propanoic acid-3'-glucuronide, 3-(3'-hydroxyphenyl) propanoic acid and hippuric acids, which appeared later (Tmax > 6 h). The 24 h urinary recovery averaged 8.9% (molar basis) of the (poly)phenols consumed. Hepatic beta-oxidation of 3',4'-dihydroxycinnamic acid and methylated conjugates occurred, but was limited (<0.04%). 3'-Methylation exceeded 4'-methylation and interindividual variability was high, especially for gut microbial metabolites (up to 168-fold).

Bioaccessibility of Tudela artichoke (Cynara scolymus cv. Blanca de Tudela) (poly)phenols: the effects of heat treatment, simulated gastrointestinal digestion and human colonic microbiota.

The aim of this study was to evaluate the bioaccessibility of (poly)phenolic compounds in Tudela artichokes (Cynara scolymus cv. Blanca de Tudela) after an in vitro gastrointestinal digestion and the effect of the human colonic microbiota. A total of 28 (poly)phenolic compounds were identified and quantified by LC-MS/MS in raw, boiled, sous vide and microwaved Tudela artichokes. Out of these, sixteen were phenolic acids, specifically caffeoylquinic acids (CQAs) and other minor hydroxycinnamic acid derivatives, ten flavonoids belonging to the family of flavones (apigenin and luteolin derivatives) and two lignans (pinoresinol derivatives). Sous vide and microwaving caused mainly transesterification reactions of CQAs but maintained or even augmented the total (poly)phenolic contents of artichokes, while boiling decreased (poly)phenolic compounds by 25% due to leaching into the boiling water. Heat treatment exerted a positive effect on the bioaccessibility of (poly)phenols after gastrointestinal digestion. In raw artichokes, only 1.6% of the total (poly)phenolic compounds remained bioaccessible after gastrointestinal digestion, while in artichoke samples cooked by sous vide, boiled and microwaved, the percentage of bioaccessibility was 60.38%, 59.93% and 39,03% respectively. After fecal fermentation, 20 native (poly)phenolic compounds and 11 newly formed catabolites were quantified. 48 h of fecal fermentation showed that native (poly)phenols are readily degraded by colonic microbiota during the first 2 h of incubation. The colonic degradation of artichoke (poly)phenols follows a major pathway that involves the formation of caffeic acid, dihydrocaffeic acid, 3-(3'-hydroxyphenyl)propionic acid, 3-phenylpropionic acid and phenylacetic acid, with 3-phenylpropionic acid being the most abundant end product. The catabolic pathways for colonic microbial degradation of artichoke CQAs are proposed.

Quantitative Assessment of Dietary (Poly)phenol Intake: A High-Throughput Targeted Metabolomics Method for Blood and Urine Samples.

Many studies have associated the consumption of (poly)phenol-rich diets with health benefits. However, accurate high-throughput quantitative methods for estimating exposure covering a broad spectrum of (poly)phenols are lacking. We have developed and validated a high-throughput method for the simultaneous quantification of 119 (poly)phenol metabolites in plasma and urine using ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry, with a very fast sample treatment and a single run time of 16 min. This method is highly sensitive, precise, accurate, and shows good linearity for all compounds (R2 > 0.992). This novel method will allow a quantitative assessment of habitual (poly)phenol intake in large epidemiological studies as well as clinical studies investigating the health benefits of dietary (poly)phenols.

Metabolic Fate and Cardiometabolic Effects of Phenolic Compounds from Red-Fleshed Apple in Hypercholesterolemic Rats: A Comparative Study with Common White-Fleshed Apple. The AppleCOR Study.

The present study aims to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds provided by a red-fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats are fed with high-fat diet (HFD) to induce hypercholesterolemia and supplemented with red-fleshed apple (HFD+R), white-fleshed apple (HFD+W), or an ACN-rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis, and phenol biological metabolites are determined. Plasma, urine, and feces show a significant increase of ACN metabolites after HFD+R and HFD+A, while flavan-3-ols are significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect is observed after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function is improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R and HFD+W) is also observed. The findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3-ols, together with dihydrochalcones, compose a phenolic phytocomplex in red- and white-fleshed apples, respectively, which can act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats.

Thermal and non-thermal processing of red-fleshed apple: how are (poly)phenol composition and bioavailability affected?

The present study evaluated the impact of different thermal (infrared-drying, hot air-drying and purée pasteurization) and non-thermal (freeze-drying) processing technologies on red-fleshed apple (poly)phenolic compounds. We further investigated the processing effect on the (poly)phenol bioavailability in a crossover postprandial study where three subjects consumed three apple products (freeze-dried snack, hot air-dried snack and pasteurized purée). (Poly)phenolic compounds present in the apple products and their biological metabolites in urine were analyzed using liquid chromatography coupled to mass spectrometry (UPLC-MS/MS). When comparing different processes, infrared-drying caused important losses in most of the apple (poly)phenolics, while hot air-drying and purée pasteurization maintained approximately 83% and 65% of total (poly)phenols compared with the freeze-dried snack, respectively. Anthocyanins in particular were degraded to a higher extent, and hot air-dried apple and pasteurized purée maintained respectively 26% and 9% compared with freeze-dried apple snack. The acute intake showed that pasteurized purée exhibited the highest (poly)phenol bioavailability, followed by hot air-drying and freeze-dried snack, highlighting the impact of processing on (poly)phenols absorption. In conclusion, for obtaining affordable new red-fleshed apple products with enhanced (poly)phenol bioavailability, purée pasteurization and hot air-drying represent viable techniques. However, to obtain a red-fleshed apple snack with high anthocyanin content, freeze-drying is the technique that best preserves them.

Plasma pharmacokinetics of (poly)phenol metabolites and catabolites after ingestion of orange juice by endurance trained men.

The health benefits of orange juice (OJ) consumption are attributed in part to the circulating flavanone phase II metabolites and their microbial-derived ring fission phenolic catabolites. The present study investigated these compounds in the bloodstream after acute intake of 500 mL of OJ. Plasma samples obtained at 0, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h after OJ intake were analysed by HPLC-HR-MS. Eleven flavanone metabolites and 36 phenolic catabolites were identified and quantified in plasma. The main metabolites were hesperetin-3'-sulfate with a peak plasma concentration (Cmax) of 80 nmol/L, followed by hesperetin-7-glucuronide (Cmax 24 nmol/L), hesperetin-3'-glucuronide (Cmax 18 nmol/L) and naringenin-7-glucuronide (Cmax 21 nmol/L). Among the main phenolic catabolites to increase in plasma after OJ consumption were 3'-methoxycinnamic acid-4'-sulfate (Cmax 19 nmol/L), 3-hydroxy-3-(3'-hydroxy-4'-methoxyphenyl)propanoic acid (Cmax 20 nmol/L), 3-(3'-hydroxy-4'-methoxyphenyl)propanoic acid (Cmax 19 nmol/L), 3-(4'-hydroxyphenyl)propanoic acid (Cmax 25 nmol/L), and 3-(phenyl)propanoic acid (Cmax 19 nmol/L), as well as substantial amounts of phenylacetic and hippuric acids. The comprehensive plasma pharmacokinetic profiles that were obtained are of value to the design of future ex vivo cell studies, aimed at elucidating the mechanisms underlying the potential health benefits of OJ consumption. CLINICAL TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT02627547.