Development of a (Poly)phenol Metabolic Signature for Assessing (Poly)phenol-Rich Dietary Patterns.

The objective assessment of habitual (poly)phenol-rich diets in nutritional epidemiology studies remains challenging. This study developed and evaluated the metabolic signature of a (poly)phenol-rich dietary score (PPS) using a targeted metabolomics method comprising 105 representative (poly)phenol metabolites, analyzed in 24 h of urine samples collected from healthy volunteers. The metabolites that were significantly associated with PPS after adjusting for energy intake were selected to establish a metabolic signature using a combination of linear regression followed by ridge regression to estimate penalized weights for each metabolite. A metabolic signature comprising 51 metabolites was significantly associated with adherence to PPS in 24 h urine samples, as well as with (poly)phenol intake estimated from food frequency questionnaires and diaries. Internal and external data sets were used for validation, and plasma, spot urine, and 24 h urine samples were compared. The metabolic signature proposed here has the potential to accurately reflect adherence to (poly)phenol-rich diets, and may be used as an objective tool for the assessment of (poly)phenol intake.

Dietary (poly)phenols and cardiometabolic health: from antioxidants to modulators of the gut microbiota.

(Poly)phenols are plant secondary metabolites widely abundant in plant foods and beverages comprising a very large number of compounds with diverse structure and biological activities. Accumulating evidence indicates that these compounds exert beneficial effects against cardiometabolic diseases, and this review will provide a summary of current knowledge in this area. Epidemiological and clinical data collectively suggest that intake of flavonoids reduces the risk of cardiovascular disease (CVD), with the evidence being particularly strong for the flavan-3-ol subclass. However, to provide adequate dietary recommendations, a better understanding of their estimated content in foods and intake among the general public is needed. Regarding mechanisms of action, we now know that it is unlikely that (poly)phenols act as direct antioxidants in vivo, as it was hypothesised for decades with the popularity of in vitro antioxidant capacity assays. One of the reasons is that upon ingestion, (poly)phenols are extensively metabolised into a wide array of circulating metabolites with different bioactivities than their precursors. Well-conducted in vitro and in vivo studies and human nutrigenomic analysis have revealed new molecular targets that may be underlying the health benefits of (poly)phenols, such as the nitric oxide pathway. Recently, a bi-directional relationship was established between (poly)phenols and the gut microbiota, suggesting that individual gut microbial metabolising capacity may be a key factor explaining the variability in the cardiometabolic response to (poly)phenols. Future research is needed to elucidate which are the key factors affecting such capacity, and whether it can be modulated, along with the mechanisms of action.

Development of a novel (poly)phenol-rich diet score and its association with urinary (poly)phenol metabolites.

Background: Estimating (poly)phenol intake is challenging due to inadequate dietary assessment tools and limited food content data. Currently, a priori diet scores to characterise (poly)phenol-rich diets are lacking. This study aimed to develop a novel (poly)phenol-rich diet score (PPS) and explore its relationship with circulating (poly)phenol metabolites. Methods: A total of 543 healthy free-living participants aged 18-80 years completed a food frequency questionnaire (FFQ) (EPIC-Norfolk) and provided 24 h urine samples. The PPS was developed based on the relative intake (quintiles) of 20 selected (poly)phenol-rich food items abundant in the UK diet, including tea, coffee, red wine, whole grains, chocolate and cocoa products, berries, apples and juice, pears, grapes, plums, citrus fruits and juice, potatoes and carrots, onions, peppers, garlic, green vegetables, pulses, soy and soy products, nuts, and olive oil. Foods included in the PPS were chosen based on their (poly)phenol content, main sources of (poly)phenols, and consumption frequencies in the UK population. Associations between the PPS and urinary phenolic metabolites were investigated using linear models adjusting energy intake and multiple testing (FDR adjusted p < 0.05). Result: The total PPS ranged from 25 to 88, with a mean score of 54. A total of 51 individual urinary metabolites were significantly associated with the PPS, including 39 phenolic acids, 5 flavonoids, 3 lignans, 2 resveratrol and 2 other (poly)phenol metabolites. The total (poly)phenol intake derived from FFQs also showed a positive association with PPS (stdBeta 0.32, 95% CI (0.24, 0.40), p < 0.01). Significant positive associations were observed in 24 of 27 classes and subclasses of estimated (poly)phenol intake and PPS, with stdBeta values ranging from 0.12 (0.04, 0.20) for theaflavins/thearubigins to 0.43 (0.34, 0.51) for flavonols (p < 0.01). Conclusion: High adherence to the PPS diet is associated with (poly)phenol intake and urinary biomarkers, indicating the utility of the PPS to characterise diets rich in (poly)phenols at a population level.

(Poly)phenol intake, plant-rich dietary patterns and cardiometabolic health: a cross-sectional study.

Diet is an important modifiable risk factor for cardiometabolic diseases. Plant foods contain a complex mixture of nutrients and bioactive compounds such as (poly)phenols. Plant-rich dietary patterns have been associated with reduced cardiometabolic risk in epidemiological studies. However, studies have not fully considered (poly)phenols as a mediating factor in the relationship. A cross-sectional analysis was conducted in 525 healthy participants, aged 41.6 ± 18.3 years. Volunteers completed the validated European Prospective Investigation into Diet and Cancer (EPIC) Norfolk Food Frequency Questionnaire (FFQ). We investigated the associations between plant-rich dietary patterns, (poly)phenol intake, and cardiometabolic health. Positive associations were found between (poly)phenols and higher adherence to dietary scores, except for the unhealthy Plant-based Diet Index (uPDI), which was negatively associated with (poly)phenol intake. Correlations were significant for healthy PDI (hPDI), with positive associations with proanthocyanidins (r = 0.39, p < 0.01) and flavonols (r = 0.37, p < 0.01). Among dietary scores, Dietary Approaches to Stop Hypertension (DASH) showed negative associations with diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (Non-HDL-C) (stdBeta -0.12 to -0.10, p < 0.05). The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) score was positively associated with flow-mediated dilation (FMD, stdBeta = 0.10, p = 0.02) and negatively associated with the 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk score (stdBeta = -0.12, p = 0.01). Higher intake of flavonoids, flavan-3-ols, flavan-3-ol monomers, theaflavins, and hydroxybenzoic acids (stdBeta: -0.31 to -0.29, p = 0.02) also showed a negative association with a 10-year ASCVD risk score. Flavanones showed significant associations with cardiometabolic markers such as fasting plasma glucose (FPG) (stdBeta = -0.11, p = 0.04), TC (stdBeta = -0.13, p = 0.03), and the Homeostasis Model Assessment (HOMA) of beta cell function (%B) (stdBeta = 0.18, p = 0.04). Flavanone intake was identified as a potential partial mediator in the negative association between TC and plant-rich dietary scores DASH, Original Mediterranean diet scores (O-MED), PDI, and hPDI (proportion mediated = 0.01% to 0.07%, p < 0.05). Higher (poly)phenol intake, particularly flavanone intake, is associated with higher adherence to plant-rich dietary patterns and favourable biomarkers of cardiometabolic risk indicating (poly)phenols may be mediating factors in the beneficial effects.

Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial.

BACKGROUND: Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown. METHODS: A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry. RESULTS: A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found. CONCLUSIONS: Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.

Plant-based dietary patterns and their association with mood in healthy individuals.

Background: Healthy, plant-based dietary patterns, particularly the Mediterranean diet (MD), have been associated with positive effect on mood symptoms and have been proposed to help prevent age-related cognitive decline. However, to date no study has investigated which existing plant-based dietary pattern might be most likely to be associated with better mood in the general population. The aim of this study was to evaluate the relationship between different plant-rich dietary patterns and current mood in healthy individuals across a broad age range. Methods: We evaluated 333 healthy participants aged 8-79, who previously participated in dietary intervention studies. Current mood was assessed with the Positive and Negative Affect Schedule (PANAS) questionnaire, standardised by Z scores. Dietary patterns were estimated using food consumption data obtained from the European Prospective Investigation into Cancer (EPIC) Food Frequency Questionnaires (FFQ), and included the Plant-based Diet Index (PDI), Dietary Approaches to Stop Hypertension Diet (DASH), Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND), Original Mediterranean Diet (oMED) and Alternate Mediterranean Diet (aMED). Results: PDI, DASH, oMED and aMED diet scores were all significantly associated with positive mood (rs = 0.12-0.16), but not with negative mood. Linear regression models suggested that after adjusting for potential confounders (sex and age), only the oMED and aMED diet scores were still significantly associated with positive mood (ß = 0.119, p = 0.031 and ß = 0.111, p = 0.048, respectively). Furthermore, the relationship between PDI diet scores and positive mood was only significant in children (ß = 0.663, p = 0.003), pointing to a potential moderating effect of age in the relationship between PDI and positive mood. Conclusion: Adherence to oMED and aMED diets is associated with better mood in healthy adults, while the PDI diet might be more specifically associated with positive mood in children.

Flow-mediated dilation reference values for evaluation of endothelial function and cardiovascular health.

AIMS: Endothelial function is essential for cardiovascular health, and flow-mediated dilation (FMD) is an established technique to measure it. This paper aims to assess FMD values in apparently healthy individuals and provides reference values to facilitate wider clinical use. METHODS AND RESULTS: In 1,579 apparently healthy individuals (aged 18-76), fasted FMD values (data from 44 studies, 6 institutions, 22 operators) were normally distributed and inversely univariately correlated with age, body mass index, glucose, cholesterol, blood pressure, and brachial artery (BA) diameter. Significant multivariate predictors of FMD were age (-0.4%/decade), BMI (0.04%/kg/m2), smoking (-0.7%), and BA diameter (-0.44%/mm) that together explained 19% of the variability independent of operator, institution or ultrasound machine. Individuals in the high FMD tertile (>6.8%) were younger, had smaller BA diameter, lower blood pressure and cholesterol. In individuals with low- and intermediate fatal cardiovascular risk (SCORE), 26% and 53% of individuals, respectively, had FMD values in the low tertile (<5.4%). After adding data from 385 patients with stable coronary artery disease (CAD), ROC analysis (c = 0.841, P < 0.001) showed that FMD of >6.5% excluded CAD (95% sensitivity; 60% specificity) and FMD <3.1% excluded 95% healthy individuals (95% specificity, 31% sensitivity). A meta-analysis and meta-regression of 82 clinical trials (11 countries, n = 3,509) using similar FMD methodology showed that despite considerable heterogeneity (I2 = 0.97) FMD in healthy individuals was on average 6.4% (95%CI: 6.2%, 6.7%) with no significant differences between countries but a significant age-dependent decline (-0.3%/decade, R2 = 0.13). CONCLUSIONS: We provide an age-adapted frame of FMD reference intervals in apparently healthy individuals for use as a biomarker of cardiovascular health. As the degree of vascular endothelial function integrates environmental and genetic factors with classical CV risk factors, FMD may more comprehensively classify individuals with and without standard modifiable cardiovascular risk factors and serve as a target for cardiovascular prevention.

Cocoa flavanol consumption improves lower extremity endothelial function in healthy individuals and people with type 2 diabetes.

Background: diabetes and age are major risk factors for the development of lower extremity peripheral artery disease (PAD). Cocoa flavanol (CF) consumption is associated with lower risk for PAD and improves brachial artery (BA) endothelial function. Objectives: to assess if femoral artery (FA) endothelial function and dermal microcirculation are impaired in individuals with type 2 diabetes mellitus (T2DM) and evaluate the acute effect of CF consumption on FA endothelial function. Methods: in a randomised, controlled, double-blind, cross-over study, 22 individuals (n = 11 healthy, n = 11 T2DM) without cardiovascular disease were recruited. Participants received either 1350 mg CF or placebo capsules on 2 separate days in random order. Endothelial function was measured as flow-mediated dilation (FMD) using ultrasound of the common FA and the BA before and 2 hours after interventions. The cutaneous microvasculature was assessed using optical coherence tomography angiography. Results: baseline FA-FMD and BA-FMD were significantly lower in T2DM (FA: 3.2 ± 1.1% [SD], BA: 4.8 ± 0.8%) compared to healthy (FA: 5.5 ± 0.7%, BA: 6.0 ± 0.8%); each p < 0.001. Whereas in healthy individuals FA-FMD did not significantly differ from BA-FMD (p = 0.144), FA-FMD was significantly lower than BA-FMD in T2DM (p = 0.003) indicating pronounced and additional endothelial dysfunction of lower limb arteries (FA-FMD/BA-FMD: 94 ± 14% [healthy] vs. 68 ± 22% [T2DM], p = 0.007). The baseline FA blood flow rate (0.42 ± 0.23 vs. 0.73 ± 0.35 l min-1, p = 0.037) and microvascular dilation in response to occlusion in hands and feet were significantly lower in T2DM subjects than in healthy ones. CF increased both FA- and BA-FMD at 2 hours, compared to placebo, in both healthy and T2DM subgroups (FA-FMD effect: 2.9 ± 1.4%, BA-FMD effect 3.0 ± 3.5%, each pintervention< 0.001). In parallel, baseline FA blood flow and microvascular diameter significantly increased in feet (3.5 ± 3.5 µm, pintervention< 0.001) but not hands. Systolic blood pressure and pulse wave velocity significantly decreased after CF in both subgroups (-7.2 ± 9.6 mmHg, pintervention = 0.004; -1.3 ± 1.3 m s-1, pintervention = 0.002). Conclusions: individuals with T2DM exhibit decreased endothelial function that is more pronounced in the femoral than in the brachial artery. CFs increase endothelial function not only in the BA but also the FA both in healthy individuals and in those with T2DM who are at increased risk of developing lower extremity PAD and foot ulcers.

Betalain-rich dragon fruit (pitaya) consumption improves vascular function in men and women: a double-blind, randomized controlled crossover trial.

BACKGROUND: Betalains are natural red color pigments abundant in red-fleshed dragon fruit (Hylocereus polyrhizus). Recent research has shown that dragon fruit consumption may help improve blood glucose and lipid profile. However, investigations of its cardioprotective properties in human trials, especially in nutritionally achievable amounts, remain nonexistent. OBJECTIVES: The aim of this study was to investigate the effects of acute and short-term consumption of dragon fruit on vascular function in a healthy population. METHODS: A randomized, double-blind, placebo-controlled, crossover trial was conducted in 19 young, healthy, nonsmoking men and women assigned to consume 24 g whole dragon fruit powder (33 mg betalains) or a nutrient-matched placebo, daily for 14 d. Flow-mediated dilation (FMD), arterial stiffness, and blood pressure (BP) were measured at 0 h, 1 h, 2 h, 3 h, and 4 h and finally at 14 d after daily consumption. RESULTS: A total of 18 participants completed the trial. Dragon fruit consumption significantly improved acute FMD at 2 h (+0.8 ± 0.3%, P = 0.01), 3 h (+1.0 ± 0.3%, P = 0.001), and 4 h (+1.3 ± 0.4%, P < 0.001) postconsumption compared with placebo. This effect was sustained up until 14 d (+1.3 ± 0.2%, P < 0.001). Pulse-wave velocity was acutely significantly reduced at 3 h (-0.5 ± 0.2 m/s, P = 0.003), whereas augmentation index (AIx) also improved after 14 d (-7.0 ± 3.3%, P = 0.02) when compared with placebo. No differences were found in either peripheral or central BP across all time points. CONCLUSIONS: Acute and short-term consumption of dragon fruit in dietary achievable amounts improved endothelial function and arterial stiffness in healthy individuals. This implies that regular dragon fruit consumption may have a meaningful impact on cardiovascular disease risk likely due to the high betalain content. This trial was registered at ClinicalTrials.gov as NCT03995602.

Flavanol Consumption in Healthy Men Preserves Integrity of Immunological-Endothelial Barrier Cell Functions: Nutri(epi)genomic Analysis.

SCOPE: While cocoa flavanol (CF) consumption improves cardiovascular risk biomarkers, molecular mechanisms underlying their protective effects are not understood. OBJECTIVE: To investigate nutri(epi)genomic effects of CF and identify regulatory networks potential mediating vascular health benefits. METHODS AND RESULTS: Twenty healthy middle-aged men consume CF (bi-daily 450 mg) or control drinks for 1 month. Microarray analysis identifies 2235 differentially expressed genes (DEG) involved in processes regulating immune response, cell adhesion, or cytoskeleton organization. Distinct patterns of DEG correlate with CF-related changes in endothelial function, arterial stiffness, and blood pressure. DEG profile negatively correlates with expression profiles of cardiovascular disease patients. CF modulated DNA methylation profile of genes implicates in cell adhesion, actin cytoskeleton organization, or cell signaling. In silico docking analyses indicate that CF metabolites have the potential of binding to cell signaling proteins and transcription factors. Incubation of plasma obtained after CF consumption decrease monocyte to endothelial adhesion and dose-dependently increase nitric oxide-dependent chemotaxis of circulating angiogenic cells further validating the biological functions of CF metabolites. CONCLUSION: In healthy humans, CF consumption may mediate vascular protective effects by modulating gene expression and DNA methylation towards a cardiovascular protective effect, in agreement with clinical results, by preserving integrity of immunological-endothelial barrier functions.

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).

Polyphenols Could Prevent SARS-CoV-2 Infection by Modulating the Expression of miRNAs in the Host Cells.

Coronaviruses (CoVs) are single-stranded RNA viruses which following virus attachment and entry into the host cell, particularly type 2 pneumocytes but also endothelial cells, release RNA into cytosol where it serves as a matrix for the host translation machinery to produce viral proteins. The viral RNA in cytoplasm can interact with host cell microRNAs which can degrade viral RNA and/or prevent viral replication. As such host cellular miRNAs represent key cellular mediators of antiviral defense. Polyphenols, plant food bioactives, exert antiviral properties, which is partially due to their capacity to modulate the expression of miRNAs. The objective of this work was to assess if polyphenols can play a role in prevention of SARS-CoV-2 associated complications by modulating the expression of host miRNAs. To test this hypothesis, we performed literature search to identify miRNAs that could bind SARS-CoV-2 RNA as well as miRNAs which expression can be modulated by polyphenols in lung, type 2 pneumocytes or endothelial cells. We identified over 600 miRNAs that have capacity to bind viral RNA and 125 miRNAs which expression can be modulated by polyphenols in the cells of interest. We identified that there are 17 miRNAs with both the capacity to bind viral RNA and which expression can be modulated by polyphenols. Some of these miRNAs have been identified as having antiviral properties or can target genes involved in regulation of processes of viral replication, apoptosis or viral infection. Taken together this analysis suggests that polyphenols could modulate expression of miRNAs in alveolar and endothelial cells and exert antiviral capacity.

Effects of daily consumption of wild blueberry on cognition and urinary metabolites in school-aged children: a pilot study.

PURPOSE: Acute intervention with wild blueberry (WBB) has previously revealed positive cognitive and mood effects in typically developing children; however, it is unclear whether effects persist after daily supplementation. In addition, no data have been published exploring the metabolite profiles of children following berry consumption, to our knowledge. A study of this kind could provide insight into a mechanism of action for the cognitive and mood improvements observed previously in children. The aim of this pilot study was to assess cognitive performance and urinary metabolite concentrations in healthy 7-10-year-old children across a 4 week daily WBB drink intervention. METHODS: This pilot study examined the effects of daily WBB consumption for 4 weeks (766 mg total polyphenols; 253 mg anthocyanins; equivalent to 240 g fresh blueberries per day) on cognition and mood in 15 healthy 7-10-year-old children. Polyphenol metabolites were measured in 24 h urine before and after the 4 week intervention. RESULTS: Chronic WBB-related benefits were seen on cognitively demanding trials on the modified attention network task, a task measuring executive functioning. Specifically, the WBB group maintained significantly higher accuracy on incongruent trials (96%; SE 0.03) compared with placebo participants (85%; SE 0.03; p = 0.038) after the 4 week intervention, suggesting WBB was of most benefit on the more difficult aspects of the task. No significant WBB-related effects were observed on the auditory verbal learning task or the child's version of the positive and negative affect schedule. Urinary metabolite analyses indicated significant increases in different metabolites in WBB and placebo groups after 4 week consumption. CONCLUSION: The research demonstrates 24 h WBB bioavailability in a child cohort for the first time with increases in urinary hippuric acid excretion during 2 week daily WBB consumption. This study highlights the importance of conducting a larger study in children investigating the mechanism of action behind cognitive effects using bioavailability data.

(Poly)phenols in Inflammatory Bowel Disease and Irritable Bowel Syndrome: A Review.

(Poly)phenols (PPs) may have a therapeutic benefit in gastrointestinal (GI) disorders, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The aim of this review is to summarise the evidence-base in this regard. Observational evidence does not give a clear indication that PP intake has a preventative role for IBD or IBS, while interventional studies suggest these compounds may confer symptomatic and health-related quality of life improvements in known patients. There are inconsistent results for effects on markers of inflammation, but there are promising reports of endoscopic improvement. Work on the effects of PPs on intestinal permeability and oxidative stress is limited and therefore conclusions cannot be formed. Future work on the use of PPs in IBD and IBS will strengthen the understanding of clinical and mechanistic effects.

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.

Alcoholic and Non-Alcoholic Beer Modulate Plasma and Macrophage microRNAs Differently in a Pilot Intervention in Humans with Cardiovascular Risk.

Beer is a popular beverage and some beneficial effects have been attributed to its moderate consumption. We carried out a pilot study to test if beer and non-alcoholic beer consumption modify the levels of a panel of 53 cardiometabolic microRNAs in plasma and macrophages. Seven non-smoker men aged 30-65 with high cardiovascular risk were recruited for a non-randomised cross-over intervention consisting of the ingestion of 500 mL/day of beer or non-alcoholic beer for 14 days with a 7-day washout period between interventions. Plasma and urine isoxanthohumol were measured to assess compliance with interventions. Monocytes were isolated and differentiated into macrophages, and plasma and macrophage microRNAs were analysed by quantitative real-time PCR. Anthropometric, biochemistry and dietary parameters were also measured. We found an increase in plasma miR-155-5p, miR-328-3p, and miR-92a-3p after beer and a decrease after non-alcoholic beer consumption. Plasma miR-320a-3p levels decreased with both beers. Circulating miR-320a-3p levels correlated with LDL-cholesterol. We found that miR-17-5p, miR-20a-5p, miR-145-5p, miR-26b-5p, and miR-223-3p macrophage levels increased after beer and decreased after non-alcoholic beer consumption. Functional analyses suggested that modulated microRNAs were involved in catabolism, nutrient sensing, Toll-like receptors signalling and inflammation. We concluded that beer and non-alcoholic beer intake modulated differentially plasma and macrophage microRNAs. Specifically, microRNAs related to inflammation increased after beer consumption and decreased after non-alcoholic beer consumption.

Recommendations for standardizing nomenclature for dietary (poly)phenol catabolites.

There is a lack of focus on the protective health effects of phytochemicals in dietary guidelines. Although a number of chemical libraries and databases contain dietary phytochemicals belonging to the plant metabolome, they are not entirely relevant to human health because many constituents are extensively metabolized within the body following ingestion. This is especially apparent for the highly abundant dietary (poly)phenols, for which the situation is compounded by confusion regarding their bioavailability and metabolism, partially because of the variety of nomenclatures and trivial names used to describe compounds arising from microbial catabolism in the gastrointestinal tract. This confusion, which is perpetuated in online chemical/metabolite databases, will hinder future discovery of bioactivities and affect the establishment of future dietary guidelines if steps are not taken to overcome these issues. In order to resolve this situation, a nomenclature system for phenolic catabolites and their human phase II metabolites is proposed in this article and the basis of its format outlined. Previous names used in the literature are cited along with the recommended nomenclature, International Union of Pure and Applied Chemistry terminology, and, where appropriate, Chemical Abstracts Service numbers, InChIKey, and accurate mass.

Comparative dietary sulfated metabolome analysis reveals unknown metabolic interactions of the gut microbiome and the human host.

The gut microbiome converts dietary compounds that are absorbed in the gastrointestinal tract and further metabolized by the human host. Sulfated metabolites are a major compound class derived from this co-metabolism and have been linked to disease development. In the present multidisciplinary study, we have investigated human urine samples from a dietary intervention study with 22 individuals collected before and after consumption of a polyphenol rich breakfast. These samples were analyzed utilizing our method combining enzymatic metabolite hydrolysis using an arylsulfatase and mass spectrometric metabolomics. Key to this study is the validation of 235 structurally diverse sulfated metabolites. We have identified 48 significantly upregulated metabolites upon dietary intervention including 11 previously unknown sulfated metabolites for this diet. We observed a large variation in subjects based on their potential to sulfate metabolites, which may be the foundation for classification of subjects as high and low sulfate metabolizers in future large cohort studies. The reported sulfatase-based method is a robust tool for the discovery of unknown microbiota-derived metabolites in human samples.