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Background and aims: Mastitis is one of the main complications during breastfeeding and contributes to the cessation of breastfeeding. However, the etiopathogenesis and diagnosis of mastitis are complex and not yet well defined. We aimed to identify metabolic and lipidic changes in human milk during acute and subacute mastitis in order to detect potential biomarkers of mastitis. Methods: We conducted a pilot case–control study including 14 breastfeeding women with acute mastitis, 32 with subacute mastitis symptoms, and 19 without any mastitis symptoms (control). Milk samples were collected and analyzed by proton nuclear magnetic resonance (H-NMR) for metabolomics analysis. To assess the association between the significant metabolites and lipids and the development of acute and subacute mastitis, multi-adjusted logistic regression models were developed. Results: The NMR-based metabolomics approach was able to identify and quantify a total of 40 metabolites in breast milk samples. After adjusting for confounding variables, acute mastitis was significantly associated with acetate (OR 3.9 IC 1.4–10.8), total cholesterol (OR 14 CI 3.2–62), esterified cholesterol (OR 3.3 CI 1.9–5.8), and sphingomyelin (OR 2.6 CI 1.2–5.8). The other metabolites presented weak association (OR < 2.5). Subacute mastitis was significantly associated with glutamine, lysophosphatidylcholine, phosphatidylcholine, plasmalogen, and total polyunsaturated fatty acids, but only cholesterol showed a strong association (OR > 2.5) with an OR of 2.6 (IC 1.1–6.6). Conclusions: Metabolic alteration in breast milk occurs during a process of both acute and subacute mastitis. Acetate, esterified cholesterol, lysophostidylcholine, and polyunsaturated fatty acids increased in both acute and subacute mastitis. However, according to the multi-adjusted regression logistic models, the candidate biomarkers for acute and subacute mastitis are cholesterol, lysophosphatidylcoholine, phosphatidylcholine, plasmalogen, and polyunsaturated fatty acids.

ScopeThis work aims to evaluate changes in the fecal metabolomic profile due to grape seed extract (GSE) intake by untargeted and targeted analysis using high resolution mass spectrometry in conjunction with multivariate statistics.Methods and resultsAn intervention study with six crossbred female pigs was performed. The pigs followed a standard diet for 3 days, then they were fed with a supplemented diet containing 1% (w/w) of MegaNatural® Gold grape seed extract for 6 days. Fresh pig fecal samples were collected daily. A combination of untargeted high resolution mass spectrometry, multivariate analysis (PLS-DA), data-dependent MS/MS scan, and accurate mass database matching was used to measure the effect of the treatment on fecal composition. The resultant PLS-DA models showed a good discrimination among classes with great robustness and predictability. A total of 14 metabolites related to the GSE consumption were identified including biliary acid, dicarboxylic fatty acid, cholesterol metabolites, purine metabolites, and eicosanoid metabolites among others. Moreover, targeted metabolomics using GC-MS showed that cholesterol and its metabolites fecal excretion was increased due to the proanthocyanidins from grape seed extract.ConclusionThe results show that oligomeric procyanidins from GSE modifies bile acid and steroid excretion, which could exert a hypocholesterolemic effect.

(1) Background: To explore the association between microbial phenolic metabolites (MPM) and metabolic syndrome (MetS) and its clinical features in adolescents aged 12.02 ± 0.41 years. (2) Methods: a cross-sectional study was conducted in 560 participants at baseline in the SI! Program for Secondary Schools trial. The following MPM, coumaric acids (m-, o-, p-coumaric acids), dihydroxyphenylpropionic acid, dihydroresveratrol, enterolignans, gallic acid, hydroxybenzoic acids, hydroxyphenylacetic acid, hydroxytyrosol, protocatechuic acid, syringic acid, urolithins (A, B), and vanillic acid, were analyzed by HPLC-LTQ-Orbitrap-HRMS. MetS and its clinical features were defined in accordance with the International Diabetes Federation. (3) Results: Out of all MPM, urolithin A was inversely associated with the diastolic blood pressure z-score. Urolithin B was inversely associated with the MetS score and waist circumference z-score. Additionally, higher levels of gallic acid were associated with lower odds of presenting MetS (OR = 0.85, 95% CI: 0.77; 0.93) and abdominal obesity (OR = 0.93, 95% CI: 0.89; 0.98). Higher urolithin B levels were inversely associated with abdominal obesity (OR = 0.94, 95% CI: 0.89; 0.98) and high blood glucose (OR = 0.92, 95% CI:0.88; 0.96); (4) Conclusions: gallic acid, urolithin A and B were associated with lower odds of presenting MetS or some of its clinical features in adolescents. This is the first study that evaluates several MPM with MetS in adolescents, highlighting the importance of MPM on cardiometabolic health at early life stages.

Proanthocyanidin (PAC) consumption has been linked to better colonic health, but PACs are poorly absorbed, making them a target for colonic metabolism. The resulting metabolites are low molecular weight and could potentially be absorbed. To understand the effects of dietary PACs it would be important to resolve the metabolic issue and link these changes to microbial population changes in a suitable model for human digestion. Here, six crossbred female pigs were fed a diet containing 1% (w/w) of MegaNatural® Gold grape seed extract (GSE) daily for 6 days. Fecal samples were analyzed by normal phase LC coupled to fluorescence detection and LC-MS/ToF. DNA was extracted from pig fecal samples and the V3/V4 region of the 16S rRNA gene was sequenced using an Illumina MiSeq. Intact parent PACs (dimer-pentamer) were observed in the feces on days 3 and 6 at similar high levels (∼400 mg kg(-1) total) during ingestion of GSE but were absent 48 h post-feeding. The major phenolic metabolites were 4-hydroxyphenylvaleric acid and 3-hydroxybenzoic acid which increased by ∼30 and 3 mg kg(-1) respectively. The GSE diet also caused an ecological shift in the microbiome, dramatically increasing Lachnospiraceae, Clostridales, Lactobacillus and Ruminococcacceae. The relationship between dietary PACs and colon health may be attributable to the altered bacterial populations or phenolic compounds in the colon.

Persimmon leaves have played an important role in Chinese medicine. Persimmon extracts and formulations have been shown to possess a wide range of pharmacological activities, including antioxidant, hypolipidaemic and antidiabetic, and they have been used to treat cardiovascular disease, improve homeostasis, as antibacterial and anti-inflammatory agents, and as a beauty treatment. In this work, liquid chromatography coupled to hybrid linear ion trap quadrupole Orbitrap mass spectrometry was used to accurately identify persimmon leaf polyphenols. Forty-one phenolic compounds, including simple phenolic acids, hydroxybenzoic acids, hydroxycinnamic acids, flavanols, flavonols, flavanones, flavone-chalcones, tyrosols and their conjugated derivatives, were identified and quantified using high mass accuracy data and confirmed by MS2 experiments. To the best of our knowledge, this is the most extensive study of persimmon leaf polyphenols performed so far, since 33 phenolic compounds are reported for the first time.

Maqui (Aristotelia Chilensis) berry features a unique profile of anthocyanidins that includes high amounts of delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside and has shown positive effects on fasting glucose and insulin levels in humans and murine models of type 2 diabetes and obesity. The molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance was investigated in high fat diet-induced obese mice supplemented with a lyophilized maqui berry. Maqui-dietary supplemented animals showed better insulin response and decreased weight gain but also a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, multilocular lipid droplet formation and thermogenesis in subcutaneous white adipose tissue (scWAT). These changes correlated with an increased expression of the carbohydrate response element binding protein b (Chrebpb), the sterol regulatory binding protein 1c (Srebp1c) and Cellular repressor of adenovirus early region 1A–stimulated genes 1 (Creg1) and an improvement in the fibroblast growth factor 21 (FGF21) signaling. Our evidence suggests that maqui dietary supplementation activates the induction of fuel storage and thermogenesis characteristic of a brown-like phenotype in scWAT and counteracts the unhealthy metabolic impact of an HFD. This induction constitutes a putative strategy to prevent/treat diet-induced obesity and its associated comorbidities.

Consumption of organic products is increasing yearly due to perceived health-promoting qualities. Several studies have shown higher amounts of phytochemicals such as polyphenols and carotenoids in foods produced by this type of agriculture than in conventional foods, but whether this increase has an impact on humans still needs to be assessed. A randomized, controlled and crossover study was carried out in nineteen healthy subjects aged 18−40 years, who all followed an organic and conventional healthy diet, both for a 4-week period. Analysis of biological samples revealed a significant increase on the excretion of 4-hydroxybenzoic acid (4-HBA), a phenolic metabolite with biological activity, after the organic intervention. However, no changes were observed in the other variables analyzed.

Extra-virgin olive oil (EVOO) is largely appreciated for its proven nutritional properties. Additionally, organic foods are perceived as healthier by consumers. In this context, the aim of the present study was to compare the phenolic profiles of EVOO from olives of the Hojiblanca variety, cultivated under organic and conventional systems. The quantification and identification of individual polyphenols was carried out by liquid chromatography coupled to mass spectrometry in tandem mode (LC-MS/MS). Significantly higher levels (p < 0.05) of phenolic compounds were found in organic EVOOs. The methodology used was able to detect previously unreported differences in bioactive components between organic and conventional EVOOs.

Olive oil is the main source of fat in the Mediterranean diet and the most frequently used ingredient in Mediterranean cuisine. Cooking with olive oil has been attracting attention because it can act as a food excipient, thereby increasing the bioaccessibility and bioavailability of ingested bioactive compounds. The aim of this study was to understand the effect of cooking with olive oil on the bioactive components in other ingredients (tomato, onion, and garlic) of sofrito sauce, a representative model of Mediterranean cuisine. After the cooking process, polyphenols from tomato, onion, and garlic were detected in the olive oil, especially naringenin, ferulic acid, and quercetin, as well as a high content of carotenoid Z-isomers, which are more bioavailable than the E-isomers. Therefore, traditional Mediterranean cuisine could play an important role in the health-improving effects of the Mediterranean diet.

Persimmon leaves have played an important role in Chinese medicine. Persimmon extracts and formulations have been shown to possess a wide range of pharmacological activities, including antioxidant, hypolipidaemic and antidiabetic, and they have been used to treat cardiovascular disease, improve homeostasis, as antibacterial and anti-inflammatory agents, and as a beauty treatment. In this work, liquid chromatography coupled to hybrid linear ion trap quadrupole Orbitrap mass spectrometry was used to accurately identify persimmon leaf polyphenols. Forty-one phenolic compounds, including simple phenolic acids, hydroxybenzoic acids, hydroxycinnamic acids, flavanols, flavonols, flavanones, flavone-chalcones, tyrosols and their conjugated derivatives, were identified and quantified using high mass accuracy data and confirmed by MS 2 experiments. To the best of our knowledge, this is the most extensive study of persimmon leaf polyphenols performed so far, since 33 phenolic compounds are reported for the first time. [ABSTRACT FROM AUTHOR]

Background and aims : Mastitis is one of the main complications during breastfeeding and contributes to the cessation of breastfeeding. However, the etiopathogenesis and diagnosis of mastitis are complex and not yet well defined. We aimed to identify metabolic and lipidic changes in human milk during acute and subacute mastitis in order to detect potential biomarkers of mastitis. Methods: We conducted a pilot case-control study including 14 breastfeeding women with acute mastitis, 32 with subacute mastitis symptoms, and 19 without any mastitis symptoms (control). Milk samples were collected and analyzed by proton nuclear magnetic resonance (H-NMR) for metabolomics analysis. To assess the association between the significant metabolites and lipids and the development of acute and subacute mastitis, multi-adjusted logistic regression models were developed. Results: The NMR-based metabolomics approach was able to identify and quantify a total of 40 metabolites in breast milk samples. After adjusting for confounding variables, acute mastitis was significantly associated with acetate (OR 3.9 IC 1.4-10.8), total cholesterol (OR 14 CI 3.2-62), esterified cholesterol (OR 3.3 CI 1.9-5.8), and sphingomyelin (OR 2.6 CI 1.2-5.8). The other metabolites presented weak association (OR < 2.5). Subacute mastitis was significantly associated with glutamine, lysophosphatidylcholine, phosphatidylcholine, plasmalogen, and total polyunsaturated fatty acids, but only cholesterol showed a strong association (OR > 2.5) with an OR of 2.6 (IC 1.1-6.6). Conclusions : Metabolic alteration in breast milk occurs during a process of both acute and subacute mastitis. Acetate, esterified cholesterol, lysophostidylcholine, and polyunsaturated fatty acids increased in both acute and subacute mastitis. However, according to the multi-adjusted regression logistic models, the candidate biomarkers for acute and subacute mastitis are cholesterol, lysophosphatidylcoholine, phosphatidylcholine, plasmalogen, and polyunsaturated fatty acids.

Introduction: Despite the benefits of breastfeeding, the worldwide breastfeeding rate is low and in order to increase breastfeeding rates, women need to receive appropriate support, resources and reliable information. mHealth interventions have proven to be a successful tool to support breastfeeding. LactApp is a free mobile mHealth application developed to support breastfeeding, it is available worldwide., Objective: To assess the usability and utility of LactApp as a mobile application for breastfeeding support., Materials and Methods: A prospective cross-sectional survey. The questionnaire was sent to LactApp users registered between January and September of 2022 via e-mail. Participants filled out the survey that consisted of the modified MAUQ questionnaire (mHealth App Usability Questionnaire) along with questions about participants' socio-demographic data, mothers' and nursing infants' clinical data, breastfeeding practices, and satisfaction with the lactation support received., Results: A total of 1,191 users that completed the whole questionnaire. The mMAUQ scores for LactApp with a mean score of 5.9 (±0.88) (ranged from 1 to 7). 80.9 % of the respondents agreed that using LactApp they felt supported in their breastfeeding experience, LactApp helped them to manage their breastfeeding experience (75.3 % of the respondents), LactApp was useful for their health and well-being (86.7 %), and overall, they were satisfied with LactApp (87.8 % of the respondents). User's age, previous experience in breastfeeding and type of breastfeeding significantly affected scores of the total m-MAUQ questionnaire., Conclusions: The results of our study show that LactApp is highly usable. Users evaluated LactApp very positively and was useful for their breastfeeding experience., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [A.P.A created and designed the LactApp. L.A.C serves as a consultant at LactApp. Nevertheless, none of these potential conflicts affected the study design, the collection, analysis and interpretation of data, or the writing of the manuscript produced by P.Q.R and D.M.T.]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Mobile applications (apps) are increasingly used during pregnancy, postpartum and lactation. To ensure the utility and usability of breastfeeding support apps, they need to be evaluated using a reliable scale specific to mHealth apps and breastfeeding users., Objective: To translate the original the mHealth App Usability Questionnaire (MAUQ) questionnaire into Spanish and to adapt it to breastfeeding support apps environment., Materials and Methods: The questionnaire was translated by one high English proficiency translator and was back translated. The items of the questionnaire were modified for Spanish readers and for breastfeeding users. The modified questionnaire was assessed for content validity with a panel of 5 experts and 12 users and the modified kappa statistic was used to determine the interrater agreement among the raters. The reliability of the questionnaire was assessed in a mobile application for breastfeeding support (LactApp) by 202 users. The structure of the questionnaire was validated using exploratory factor analysis., Results: All items of the questionnaire were relevant, clear or comprehensible with content validity index values higher than 0.79. The modified kappa agreement for each item of the modified MAUQ (m-MAUQ) proved an excellent agreement (κ = 0.9-1.0). Factor analysis of the m-MAUQ showed four subscales. The internal consistency of the complete questionnaire was high (Cronbach α = 0.89)., Conclusions: The Spanish and modified MAUQ demonstrated high reliability and validity and it might be used to evaluate the usability, utility and acceptability of mHealth apps aiming to support lactating women., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.P.A created and designed the LactApp. L.A.C serves as a consultant at LactApp. Nevertheless, none of these potential conflicts affected the study design, the collection, analysis and interpretation of data, or the writing of the manuscript produced by P.Q.R and D.M.T., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: To uncover novel candidate metabolomic and lipidomic biomarkers in newly-diagnosed type 1 diabetes (T1DM) after achieving optimal glucose control., Methods: Comprehensive lipidomic and metabolomic analysis was performed in serum of 12 adults with T1DM at onset and after achieving optimal glycemic control (HbA1c < 7 %) (after 2-6 months)., Results: After intensive therapy, subjects (mean age 25.2 years, 58.3 % men) showed decreases in blood glucose (p < 0.001), HbA1c [11.5 % (9.2-13.4) to 6.2 % (5.2 - 6.7); p < 0.001] and changes in 51 identified lipids. Among these changes, we found that triglycerides (TG) containing medium chain fatty acids (TG45:0, TG47:1), sphingomyelins (SM) (SM(d18:2/20:0), SM42:4)), and phosphatidylcholines (PC) (PC(O-26:2), PC(O-30:0), PC(O-32:0), PC(O-42:6), PC(O-44:5), PC(O-38:3), PC(O-33:0), PC(O-46:8), PC(O-44:6), PC(O-40:3), PC(O-42:4), PC(O-46:7), PC(O-46:6), PC(O-44:5), PC(O-42:3), PC(O-44:4)) decreased; whereas PC(35:1), PC(37:1) and TG containing longer chain fatty acids (TG(52:1), TG(55:7), TG(51:2), TG(53:3), TG52:2), TG(53:2), TG(57:3), TG(61:3), TG(61:2) increased. Further, dihydro O-acylceramide (18:1/18:0/16:0), diacylglycerophosphoethanolamine (PE(34:1)), diacylglycerophosphoinositol (PI(38:6), and dihydrosphingomyelins (dihydroSM(36:0), dihydroSM(40:0), dihydroSM(41:0), dihydroSM(42:0)) increased. Uric acid, mannitol, and mannitol-1-acetate levels also increased., Conclusions: Our data uncovered potential favorable changes in the metabolism of glycerophospholipids, glycerolipids, and sphingolipids in new-onset T1DM after achieving optimal glycemic control. Further research on their potential role in developing diabetes-related complications is needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

(1) Background: To explore the association between microbial phenolic metabolites (MPM) and metabolic syndrome (MetS) and its clinical features in adolescents aged 12.02 ± 0.41 years. (2) Methods: a cross-sectional study was conducted in 560 participants at baseline in the SI! Program for Secondary Schools trial. The following MPM, coumaric acids ( m -, o -, p -coumaric acids), dihydroxyphenylpropionic acid, dihydroresveratrol, enterolignans, gallic acid, hydroxybenzoic acids, hydroxyphenylacetic acid, hydroxytyrosol, protocatechuic acid, syringic acid, urolithins (A, B), and vanillic acid, were analyzed by HPLC-LTQ-Orbitrap-HRMS. MetS and its clinical features were defined in accordance with the International Diabetes Federation. (3) Results: Out of all MPM, urolithin A was inversely associated with the diastolic blood pressure z-score. Urolithin B was inversely associated with the MetS score and waist circumference z-score. Additionally, higher levels of gallic acid were associated with lower odds of presenting MetS (OR = 0.85, 95% CI: 0.77; 0.93) and abdominal obesity (OR = 0.93, 95% CI: 0.89; 0.98). Higher urolithin B levels were inversely associated with abdominal obesity (OR = 0.94, 95% CI: 0.89; 0.98) and high blood glucose (OR = 0.92, 95% CI:0.88; 0.96); (4) Conclusions: gallic acid, urolithin A and B were associated with lower odds of presenting MetS or some of its clinical features in adolescents. This is the first study that evaluates several MPM with MetS in adolescents, highlighting the importance of MPM on cardiometabolic health at early life stages.

Introduction: Breastfeeding is an unquestionable right of mothers and their children; however, it is not a one-woman job. For breastfeeding to succeed, women must have access to appropriate support and guidance. The COVID-19 pandemic and subsequent restriction measures and lockdown to reduce community spread of the disease have negatively impacted breastfeeding support from health services and thus, in mothers' breastfeeding experiences. Objective: The present study aims at evaluating the impact of the COVID-19 pandemic on breastfeeding consultations in LactApp (a mobile application [app] for m-Health focused on breastfeeding support, www.lactapp.com) during the COVID-19 pandemic. Materials and Methods: We conducted an observational, descriptive, and retrospective study with LactApp data recorded between July 2018 and March 2021, including 9,151,456 queries classified in 48 topics among 137,327 active users. We used the Interrupted time series model to evaluate the increase of the number of queries consulted and active users due to the COVID-19 pandemic. Wilcoxon test was used to study the increase of certain topics due to the COVID-19 pandemic. Results: LactApp active users increased by 12,092 users ( p < 0.001) during the COVID-19 outbreak and confinement and queries consulted in LactApp also significantly increased by 10,899 queries per month after the pandemic outbreak. The breastfeeding topics that significantly increased are those related to growth spurts, breastfeeding stages, breastfeeding technique, breast pain and mastitis, problems with infants not gaining weight correctly, hypogalactia, increased milk demand, and relactation. These findings are important to understand the potential of online tools when face-to-face professional support is unavailable. Conclusions: Critical issues in breastfeeding establishment were highly consulted and significantly increased in the app during the pandemic. We believe that LactApp was a useful tool for breastfeeding support when women could not obtain appropriate support elsewhere. LactApp might be considered a powerful tool to identify critical issues of breastfeeding and trends in an automatized manner.

Due to the health benefits associated with proanthocyanidins (PAs), it is useful to identify dietary PA biomarkers that can be determined by simple methods. Since increased levels of circulating PA metabolites are associated with increased fecal PA content, this study explores the spectrophotometric measurement of fecal PA content and its use as a biomarker of PA intake. To this end, fecal PA content was measured using an adaptation of Porter's spectrophotometric method in samples from a preclinical study and an observational study. In the former, excretion of 250-400 mg PA polymer equivalents/100 g feces was observed during supplementation and the day after, together with a significant association (p < 0.05) between PA intake and the excretion of both intact PAs and some PA metabolites, i.e., (+)-catechin, (-)-epicatechin and syringic acid. No relationship between intake and excretion was found in the observational study, either for the entire group (mean excretion of 240 ± 226 mg PA polymer equivalents/100 g feces) or after stratification into tertiles of consumption. In conclusion, the spectrophotometric determination of total PA content in feces proved to be a valid compliance marker in a preclinical study, but it was not associated with PA intake in free-living subjects. The potential of total PA excretion in observational studies, determined in fecal samples collected the day before dietary recall or in several fecal samples from the same subject, remains to be elucidated, as does a complete validation of the method proposed here., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Most of daily eaten food are cooked, which helps in absorbing nutrients and phytochemicals, but at the same time it can decrease its content. Currently, the impact of cooking has been studied that could influence food health related compounds, but they have a limited view of compounds by not consider molecular structural modifications and new compounds formation. An untargeted approach using LC-ESI-LQT-Orbitrap-MS/MS and univariate/multivariate statistical analysis was applied to understand how the preparation of a recipe, varying its ingredients (olive oil, 5-10%; onion, 20-40%; and garlic, 2-4%) and cooking time, could modulate the chemical profile of a tomato sofrito sauce. The presence of unexplored compounds that may have a beneficial effect on health, such as phytoprostanes, hydroxycinnamic acid amides and compounds such as 3,4 dihydroxyphenylglycone was revealed. Moreover, cooking was able to modulate the content of compounds like aminoacids, thiosulfates or phenolics and could be used as a tool to increase these molecules. The untargeted approach on cooking allows to use a recipe as a tool to improve a chemical profile of a dish, which opens the view for new dietary recommendations by cuisine to improve our diet, habits and health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Sofrito, a basic culinary technique widely used in the Mediterranean, may preserve dietary polyphenols and enhance their intake in the Mediterranean population. The aim of this study was to investigate if the sofrito technique improves the polyphenol extractability in a tomato-based sofrito sauce., Results: A full factorial design was applied using mathematical models. The content of chlorogenic acid, ferulic acid hexoside and naringenin was higher in the sofrito sauce than in raw tomato. The bioaccessibility of some tomato polyphenols was enhanced by the presence of olive oil and they were protected from oxidation during the cooking process by the use of onion., Conclusion: The use of olive oil and onion in Mediterranean cooking as a base for sauces and dishes, with an appropriate cooking time, preserve the polyphenol content of food. Thus, Mediterranean cuisine may contribute to the health effects of the Mediterranean diet. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Maqui ( Aristotelia Chilensis ) berry features a unique profile of anthocyanidins that includes high amounts of delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside and has shown positive effects on fasting glucose and insulin levels in humans and murine models of type 2 diabetes and obesity. The molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance was investigated in high fat diet-induced obese mice supplemented with a lyophilized maqui berry. Maqui-dietary supplemented animals showed better insulin response and decreased weight gain but also a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, multilocular lipid droplet formation and thermogenesis in subcutaneous white adipose tissue (scWAT). These changes correlated with an increased expression of the carbohydrate response element binding protein b ( Chrebpb ), the sterol regulatory binding protein 1c ( Srebp1c ) and Cellular repressor of adenovirus early region 1A-stimulated genes 1 ( Creg1 ) and an improvement in the fibroblast growth factor 21 (FGF21) signaling. Our evidence suggests that maqui dietary supplementation activates the induction of fuel storage and thermogenesis characteristic of a brown-like phenotype in scWAT and counteracts the unhealthy metabolic impact of an HFD. This induction constitutes a putative strategy to prevent/treat diet-induced obesity and its associated comorbidities.

Consumption of organic products is increasing yearly due to perceived health-promoting qualities. Several studies have shown higher amounts of phytochemicals such as polyphenols and carotenoids in foods produced by this type of agriculture than in conventional foods, but whether this increase has an impact on humans still needs to be assessed. A randomized, controlled and crossover study was carried out in nineteen healthy subjects aged 18-40 years, who all followed an organic and conventional healthy diet, both for a 4-week period. Analysis of biological samples revealed a significant increase on the excretion of 4-hydroxybenzoic acid (4-HBA), a phenolic metabolite with biological activity, after the organic intervention. However, no changes were observed in the other variables analyzed.

Extra-virgin olive oil (EVOO) is largely appreciated for its proven nutritional properties. Additionally, organic foods are perceived as healthier by consumers. In this context, the aim of the present study was to compare the phenolic profiles of EVOO from olives of the Hojiblanca variety, cultivated under organic and conventional systems. The quantification and identification of individual polyphenols was carried out by liquid chromatography coupled to mass spectrometry in tandem mode (LC-MS/MS). Significantly higher levels ( p < 0.05) of phenolic compounds were found in organic EVOOs. The methodology used was able to detect previously unreported differences in bioactive components between organic and conventional EVOOs.

Olive oil is the main source of fat in the Mediterranean diet and the most frequently used ingredient in Mediterranean cuisine. Cooking with olive oil has been attracting attention because it can act as a food excipient, thereby increasing the bioaccessibility and bioavailability of ingested bioactive compounds. The aim of this study was to understand the effect of cooking with olive oil on the bioactive components in other ingredients (tomato, onion, and garlic) of sofrito sauce, a representative model of Mediterranean cuisine. After the cooking process, polyphenols from tomato, onion, and garlic were detected in the olive oil, especially naringenin, ferulic acid, and quercetin, as well as a high content of carotenoid Z -isomers, which are more bioavailable than the E -isomers. Therefore, traditional Mediterranean cuisine could play an important role in the health-improving effects of the Mediterranean diet.

Sofrito is a Mediterranean tomato-based sauce that typically also contains olive oil, onion, and garlic. The preparation of sofrito modifies the bioactive compounds (carotenoids and polyphenols) in the ingredients to more bioavailable forms, promoting cis -lycopene formation and polyphenol bioaccessibility. To evaluate the health benefits of this cooking technique, the effect of consuming an acute dose of sofrito on the inflammatory status was studied. In a clinical trial, 22 healthy male subjects consumed a single dose of sofrito (240 g/70 kg) after three days without ingesting any tomato products and following a low-antioxidant diet the day before the intervention. Plasma carotenoids and total polyphenol excretion (TPE) were evaluated, as well as the inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL-6), interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α). After the sofrito intake, a significant decrease in CRP ( p = 0.010) and TNF-α ( p = 0.011) was observed, but only TNF-α was inversely correlated with an increase in TPE and plasma β -carotene (not the major carotenoid, lycopene). The positive health effects of this tomato-based product may be attributed not only to lycopene, but to the bioactive compounds of all the ingredients.

Bioactive dietary compounds play a critical role in health maintenance. The relation between bioactive compound intake and cardiovascular health-related biomarkers has been demonstrated in several studies, although mainly with participants who have altered biochemical parameters (high blood pressure, high cholesterol, metabolic syndrome, etc.). The aim of this study was to evaluate if adopting a diet low in polyphenol-rich food for two weeks would affect vascular biomarkers in healthy men. In a crossover study, 22 healthy men were randomly assigned to their usual diet (UD), consuming healthy food rich in polyphenols, or to a low antioxidant diet (LAD), with less than two servings of fruit and vegetables per day and avoiding the intake of cocoa products, coffee and tea. As a marker of compliance, total polyphenols in urine were significantly lower after the LAD than after the UD (79 ± 43 vs. 123 ± 58 mg GAE/g creatinine). Nitric oxide levels were also reduced (52 ± 28 in LAD vs. 80 ± 34 µM in UD), although no significant changes in cellular adhesion molecules and eicosanoids were observed; however, an increasing ratio between thromboxane A₂ (TXA₂) and prostaglandin I₂ (PGI₂) was reached ( p = 0.048). Thus, a slight dietary modification, reducing the consumption of polyphenol-rich food, may affect vascular biomarkers even in healthy individuals.

Scope: The aim of this work was to study the urinary metabolomics changes of participants that consumed beer, nonalcoholic beer (na-beer), and gin., Methods and Results: Thirty-three males at high cardiovascular risk between 55 and 75 years old participated in an open, randomized, crossover, controlled trial with three nutritional interventions consisting of beer, na-beer, and gin for 4 wk. Diet and physical activity was monitored throughout the study and compliance was assessed by measurement of urinary isoxanthohumol. Metabolomic analysis was performed in urine samples by LC coupled to an LTQ-Orbitrap mass spectrometer combined with univariate and multivariate statistical analysis. Ten metabolites were identified. Eight were exogenous metabolites related to beer, na-beer, or gin consumption, but two of them were related to endogenic changes: hydroxyadipic acid linked to fatty acid oxidation, and 4-guanidinobutanoic acid, which correlated with a decrease in urinary creatinine. Plasmatic acylcarnitines were quantified by targeted MS. A regular and moderate consumption of beer and na-beer decreased stearoylcarnitine concentrations., Conclusion: Humulinone and 2,3-dihydroxy-3-methylvaleric acid showed to be potential biomarkers of beer and na-beer consumption. Moreover, the results of this trial provide new evidence that the nonalcoholic fraction of beer may increase fatty oxidation., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Phenolic compounds are present in human fluids (plasma and urine) mainly as glucuronidated and sulfated metabolites. Up to now, due to the unavailability of standards, enzymatic hydrolysis has been the method of choice in analytical chemistry to quantify these phase II phenolic metabolites. Enzymatic hydrolysis procedures vary in enzyme concentration, pH and temperature; however, there is a lack of knowledge about the stability of polyphenols in their free form during the process. In this study, we evaluated the stability of 7 phenolic acids, 2 flavonoids and 3 prenylflavanoids in urine during enzymatic hydrolysis to assess the suitability of this analytical procedure, using three different concentrations of β-glucuronidase/sulfatase enzymes from Helix pomatia. The results indicate that enzymatic hydrolysis negatively affected the recovery of the precursor and free-form polyphenols present in the sample. Thus, enzymatic hydrolysis does not seem an ideal analytical strategy to quantify glucuronidated and sulfated polyphenol metabolites.

Background: The study of dietary patterns is gaining interest. Although the health benefits of yogurt and lignans have been investigated separately, to our knowledge there are no studies on their associative effects., Objective: The aim of this study was to evaluate a possible association between yogurt and lignans using biomarkers of cardiovascular disease risk in an elderly population., Design: We conducted a cross-sectional analysis of the association between baseline dietary information and cardiovascular risk parameters using food frequency questionnaires., Participants: We enrolled 7,169 Spanish participants of the PREDIMED (Prevención con Dieta Mediterránea) study (elderly men and women at high cardiovascular risk) from June 2003 to June 2009., Main Outcome Measures: Cardiovascular risk parameters, including cholesterol, triglycerides, glucose, body mass index, weight, waist circumference, and blood pressure were measured., Statistical Analysis: General linear models were used to assess the relationship between categorical variables (yogurt, total dairy intake, lignans, and yogurt plus lignans) and cardiovascular risk parameters., Results: The consumption of either yogurt or lignans seems to have beneficial effects on human health, but the consumption of both showed greater improvement in some cardiovascular health parameters. Indeed, participants with a higher consumption of both yogurt and lignans showed lower total cholesterol (estimated β-coefficients=-6.18; P=0.001) and low-density lipoprotein cholesterol levels (β=-4.92; P=0.005). In contrast, participants with lower yogurt and lignan consumption had a higher body mass index (β=0.28; P=0.007) and weight (β=1.20; P=0.008)., Conclusions: High lignan and yogurt consumption is associated with a better cardiovascular risk parameters profile in an elderly Mediterranean population. Further research is warranted to determine the mechanisms and consequences of this potential effect., (Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

As common constituents of tomatoes and other fruits and/or vegetables, naringenin and quercetin are usually ingested together, so for a clearer understanding of their bioavailability, metabolic fates and health benefits, it is more insightful to study them together. The purpose of the present work was to study how co-administration of naringenin and quercetin at realistic doses (3.5 μg ml(-1) and 2.36 μg ml(-1), respectively) influences their absorption and intestinal first-pass metabolism. A single-pass intestinal perfusion model in mice (n = 4-6) was used. Perfusate (every 10 minutes), blood (at 60 min) and bile samples were analysed by an UPLC-ESI-MS/MS method to evaluate the presence of the aglycones and their metabolites. Both naringenin and quercetin showed high permeability coefficients when administered separately (7.71 ± 0.82 × 10(-4) cm s(-1)vs. 7.30 ± 1.95 × 10(-4) cm s(-1), respectively), but these values decreased by 50% with co-administration (4.09 ± 0.89 × 10(-4) cm s(-1) for naringenin and 3.18 ± 0.45 × 10(-4) cm s(-1) for quercetin). Moreover, the level of phase II metabolites in perfusion, plasma and bile samples increased when naringenin and quercetin were administered together. The higher biliary excretion of these metabolites could thus favour the entero-hepatic recycling of the aglycones and metabolites. The results of this study may have several useful applications: to know and consider the possible interactions between polyphenols and drugs that use the same mechanism of absorption and elimination; when polyphenol-rich nutritional supplements are supplied, and in our regular diets to optimize the health benefits afforded by the biological activities of such aglycones and/or metabolites.

Beer is the second most consumed alcoholic beverage in Europe and shown by the European Prospective Investigation into Cancer and Nutrition cohort study to be the main food contributor to hydroxybenzoic acid intake. About 70-80% of the total polyphenol content in beer comes from malt, and the remaining 30-20% from hops. In this work, liquid chromatography coupled with an electrospray ionization hybrid linear ion trap quadrupole Orbitrap mass spectrometry technique has been used for an accurate identification of beer polyphenols. 47 phenolic compounds were identified using high mass accuracy and confirmed by MS(2) experiments, including simple phenolic acids, hydroxycinnamoylquinics, flavanols, flavonols, flavones, alkylmethoxyphenols, alpha- and iso-alpha-acids, hydroxyphenylacetic acids and prenylflavonoids. As far as we know, 7 of these compounds have been recognised in beer for the first time: feruloylquinic acid, caffeic acid-O-hexoside, coumaric acid-O-hexoside, sinapic acid-O-hexoside, catechin-O-dihexoside, kaempferol-O-hexoside, and apigenin-C-hexoside-pentoside., (Copyright © 2014. Published by Elsevier Ltd.)

Trans-piceid (T-Pc) is abundant in Polygonum cuspidatum and in grapes and grape products such as wine. Piceid reaches high levels in the stomach and intestine with rapid oral absorption. Tissues, such as liver tissue, can deglycosylate piceid to release resveratrol, so piceid can be considered a source of resveratrol, which has numerous biological activities such as antiproliferative effects. Therefore, the aim of this work was to analyze the action of T-Pc on intestinal epithelial cell growth. Our results show that T-Pc has antioxidant activity similar to that of trans-resveratrol (T-Rv) and higher than that of Trolox. Moreover, T-Pc (1-50 μM) inhibited Caco-2 cell growth and DNA synthesis in a concentration-dependent manner. We observed an increase in the percentage of cells in G0/G1 phase induced by T-Pc and the induction of apoptosis. Furthermore, we observed that Caco-2 cells did not have β-glucosidase activity and that Caco-2 cell cultures did not significantly deglycosylate T-Pc in our experimental conditions. On the basis of our results we propose, for the first time, that T-Pc must not be considered exclusively as a T-Rv source, and presents antiproliferative effects on intestinal epithelial cells through the modulation of the cell cycle and apoptosis by itself. Moreover, a synergistic action of T-Pc and T-Rv can be considered.

Rationale: Moderate alcohol consumption is associated with a decrease in cardiovascular risk, but fermented beverages seem to confer greater cardiovascular protection due to their polyphenolic content. Circulating endothelial progenitor cells (EPC) are bone-marrow-derived stem cells with the ability to repair and maintain endothelial integrity and function and are considered as a surrogate marker of vascular function and cumulative cardiovascular risk. Nevertheless, no study has been carried out on the effects of moderate beer consumption on the number of circulating EPC in high cardiovascular risk patients., Objective: To compare the effects of moderate consumption of beer, non-alcoholic beer and gin on the number of circulating EPC and EPC-mobilizing factors., Methods: In this crossover trial, 33 men at high cardiovascular risk were randomized to receive beer (30 g alcohol/d), the equivalent amount of polyphenols in the form of non-alcoholic beer, or gin (30 g alcohol/d) for 4 weeks. Diet and physical exercise were carefully monitored., Results: The number of circulating EPC and EPC-mobilizing factors were determined at baseline and after each intervention. After the beer and non-alcoholic beer interventions, the number of circulating EPC significantly increased by 8 and 5 units, respectively, while no significant differences were observed after the gin period. In correlation, stromal cell derived factor 1 increased significantly after the non-alcoholic and the beer interventions., Conclusions: The non-alcoholic fraction of beer increases the number of circulating EPC in peripheral blood from high cardiovascular risk subjects., Clinical Trial Registration: http://www.controlled-trials.com/ISRCTN95345245 ISRCTN95345245., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Biomarkers of food consumption are a powerful tool to obtain more objective measurements of dietary exposure and to monitor compliance in clinical trials. In this study, we evaluated the effectiveness of urinary isoxanthohumol (IX) excretion as an accurate biomarker of beer consumption. A dose-response clinical trial, a randomized, crossover clinical trial, and a cohort study were performed. In the dose-response trial, 41 young volunteers (males and females, aged 28 ± 3 y) consumed different doses of beer at night and a spot urine sample was collected the following morning. In the clinical trial, 33 males with high cardiovascular risk (aged 61 ± 7 y) randomly were administered 30 g of ethanol/d as gin or beer, or an equivalent amount of polyphenols as nonalcoholic beer for 4 wk. Additionally, a subsample of 46 volunteers from the PREDIMED (Prevenciόn con Dieta Mediterránea) study (males and females, aged 63 ± 5 y) was also evaluated. Prenylflavonoids were quantified in urine samples by liquid chromatography coupled to mass spectrometry. IX urinary recovery increased linearly with the size of the beer dose in male volunteers. A significant increase in IX excretion (4.0 ± 1.6 μg/g creatinine) was found after consumption of beer and nonalcoholic beer for 4 wk (P < 0.001). Receiver operating characteristic curves showed that IX is able to discriminate between beer consumers and abstainers with a sensitivity of 67% and specificity of 100% (positive predictive value = 70%, negative predictive value = 100% in real-life conditions). IX in urine samples was found to be a specific and accurate biomarker of beer consumption and may be a powerful tool in epidemiologic studies.

This paper describes for the first time a complete characterisation of the phenolic compounds in different anatomical parts of the Albariño grape. The application of high-performance liquid chromatography coupled with two complementary techniques, hybrid quadrupole time-of-flight and triple-quadrupole mass spectrometry, allowed the phenolic composition of the Albariño grape to be unambiguously identified and quantified. A more complete phenolic profile was obtained by product ion and precursor ion scans, while a neutral loss scan at 152 u enabled a fast screening of procyanidin dimers, trimers and their galloylated derivatives. The compounds were confirmed by accurate mass measurements in QqToF-MS and QqToF-MS/MS modes at high resolution, and good fits were obtained for all investigated ions, with errors ranging from 0.2 to 4.5 mDa. To the best of our knowledge, two flavanol monomer hexosides were detected in the grape berry for the first time., (Copyright © 2013 Elsevier Ltd. All rights reserved.)