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Flavan-3-ols intake is associated with numerous health benefits, but these are influenced by their conversion into smaller phenolic metabolites by the gut microbiota. Thus, the identification of bacteria that metabolize flavan-3-ols could lead to targeted interventions to enhance their benefits. To this end, we screened 47 Lactiplantibacillus plantarum strains for their ability to metabolize (+)-catechin, a flavan-3-ol. Then, we assessed these strains for their capacity to convert various flavan-3-ol structures. Out of the 47 isolates, 12 released 3-(3',4'-dihydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)-propan-2-ol (a form of diphenylpropan-2-ol) from (+)-catechin. All strains metabolized (+)-catechin, (-)-epicatechin, (-)-epigallocatechin, but only a subset transformed (-)-gallocatechin. Among these simple flavan-3-ol structures, (-)-epicatechin was metabolized the most. A hierarchical cluster analysis identified two groups of flavan-3-ol-metabolizing strains categorized as having "high" and "low" production of diphenylpropan-2-ols. Notably, the strains that produced higher levels of diphenylpropan-2-ol from (+)-gallocatechin and (+)-catechin also performed better with a camu-camu extract, which was studied as a complex source of flavan-3-ols and predominantly contained these two flavan-3-ols. These results demonstrate the interstrain variability in L. plantarum metabolism, which may be useful for developing tailored formulations to enhance the production of flavan-3-ols bioactive metabolites.

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Asynchronous ripening is a significant challenge in winemaking. Green berries reduce alcohol and pH while increasing acidity. Green berries are rich in bitter and astringent compounds, with an unknown impact on wine quality. The aim of this study was to evaluate the impact of harvest date and vineyard location on the polyphenolic composition of Plavac Mali wines in Dalmatia, Croatia. Experiments were conducted in two locations, Split and Zadar, producing fifteen wines per location from four harvest dates (H1-H4), including green berry wines from H1. The first harvest date occurred 27 days after véraison (DAV) and the last at 69 DAV, corresponding to overripeness. Green berry wines of H1 had low alcohol content up to 4.4% (v/v) in Split. Epigallocatechin was the main flavonoid in those wines, followed by dimer B1 in Split and catechin in Zadar. Green wines from Split had a higher concentration of phenolic acids, flavan-3-ol monomers and dimers. Wines of H3 had the highest concentration of malvidin-3-O-glucoside. With a later harvest date, a dramatic decrease in catechin and dimers was observed in wines from Split, and a decrease in epicatechin, epigallocatechin and dimer B1 in those from Zadar. The final expression of the physiochemical and polyphenolic composition of Plavac Mali wine is determined by the dynamics of harvest date, location and their interactions.

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Cardiovascular diseases (CVDs) are one of the main causes of mortality and morbidity worldwide. A healthy diet rich in plant-derived compounds such as (poly)phenols appears to have a key role in improving cardiovascular health. Flavan-3-ols represent a subclass of (poly)phenols of great interest for their possible health benefits. In this review, we summarized the results of clinical studies on vascular outcomes of flavan-3-ol supplementation and we focused on the role of the microbiota in CVD. Clinical trials included in this review showed that supplementation with flavan-3-ols mostly derived from cocoa products significantly reduces blood pressure and improves endothelial function. Studies on catechins from green tea demonstrated better results when involving healthy individuals. From a mechanistic point of view, emerging evidence suggests that microbial metabolites may play a role in the observed effects. Their function extends beyond the previous belief of ROS scavenging activity and encompasses a direct impact on gene expression and protein function. Although flavan-3-ols appear to have effects on cardiovascular health, further studies are needed to clarify and confirm these potential benefits and the rising evidence of the potential involvement of the microbiota.

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Potentially health-promoting concentrations of flavan-3-ols were previously shown to be retained in apple juices produced with the emerging spiral filter press. Due to the novelty of this technology, the factors governing the stability of flavan-3-ol-rich apple juices have only scarcely been studied. Therefore, we produced flavan-3-ol-rich apple juices and concentrates (16, 40, 70 °Brix) supplemented with ascorbic acid (0.0, 0.2, 1.0 g/L) according to common practice. Flavan-3-ols (DP1-7) and twelve flavan-3-ol reaction products were comprehensively characterized and monitored during storage for 16 weeks at 20 and 37 °C, employing RP-UHPLC- and HILIC-DAD-ESI(-)-QTOF-HR-MS/MS. Flavan-3-ol degradation followed a second-order reaction kinetic, being up to 3.5-times faster in concentrates (70 °Brix) than in single strength juices (16 °Brix). Furthermore, they diminished substantially faster compared to other phenolic compounds. For instance, after 16-weeks at 20 °C, the maximum loss of flavan-3-ols (-70 %) was greater than those of hydroxycinnamic acids (-18 %) and dihydrochalcones (-12 %). We observed that flavan-3-ols formed adducts with sugars and other carbonyls, such as 5-(hydroxymethyl)furfural and the ascorbic acid-derived L-xylosone. Increased degradation rates correlated particularly with increased furan aldehyde levels as found in concentrates stored at elevated temperatures. These insights could be used for optimizing production, distribution, and storage of flavan-3-ol-rich apple juices and other foods and beverages.

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The present investigation delved into the pharmacological mechanisms underlying the management of depression through Flavan-3-ols and Aromatic Resins, employing in silico and in vivo methodologies. Network pharmacology was utilized to identify targets associated with the antidepressant activity of Flavan-3-ols and Aromatic Resins. Protein-protein interaction and KEGG analyses were conducted to enrich and explore key pathways. Molecular docking and simulation studies were executed to assess the targets. The antidepressant effects were studied using the Forced Swim Test and Tail Suspension Test on both unstressed mice and those subjected to the chronic unpredictable mild stress (CUMS) paradigm. The Compound-Target network analysis revealed a substantial impact of the components on numerous targets, with 332 nodes and 491 edges. Protein-protein interaction analysis indicated significant interactions with targets implicated in depression. KEGG analysis highlighted major pathways, including neuroactive ligand-receptor interaction, dopaminergic synapse, and long-term depression. Docking studies on EGCG demonstrated binding energies of -7.2 kcal/mol for serotonin 1 A (5-HT1A), -7.9 kcal/mol for D2, and - 9.6 kcal/mol for MOA-A. Molecular dynamics simulation indicated minute fluctuation, hence suggesting stable complexes formed between small molecules and proteins. The combination of Flavan-3-ols and Aromatic Resins significantly increased mobility time (p < 0.05) in the Forced Swim Test and Tail Suspension Test, while significantly decreasing immobility time and time freezing (p < 0.05) in both unstressed and CUMS mice. This study demonstrated the antidepressant characteristics of Flavan-3-ols and Aromatic Resins, underscoring the need for further research to develop a novel antidepressant medication.

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Proanthocyanidins, natural polyphenolic compounds abundantly present in plants, exhibit diverse bioactivities, including antioxidative, anti-inflammatory, and antibacterial effects. These bioactivities are intricately linked to the degree of polymerization of these compounds. Through a comprehensive analysis of recent domestic and international research, this article synthesizes the latest advancements in the extraction process, degradation methods, as well as the biological activities and underlying mechanisms of proanthocyanidins. Furthermore, future research endeavors should prioritize the refinement of extraction techniques, the elucidation of bioactive mechanisms, and the development of formulations with enhanced potency. This will maximize the utilization of proanthocyanidins across diverse applications.

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Naturally colored cotton (NCC) offers an environmentally friendly fiber for textile applications. Processing white cotton fiber into textiles requires extensive energy, water, and chemicals, whereas processing of NCC skips the most polluting activity, scouring-bleaching and dyeing; therefore, NCC provides an avenue to minimize the harmful impacts of textile production. NCC varieties are suitable for organic agriculture since they are naturally insect and disease-resistant, salt and drought-tolerant. Various fiber shades, ranging from light green to tan and brown, are available in the cultivated NCC (Gossypium hirsutum L.) species. The pigments responsible for the color of brown cotton fiber are proanthocyanidins or their derivatives synthesized by the flavonoid pathway. Due to pigments, the NCC has excellent ultraviolet protection properties. Some brown cotton varieties exhibited superior thermal resistance of fiber that can be used to make fabrics with enhanced flame retardancy. Here, we review molecular mechanisms involved in the pigment production of brown cotton and challenges in breeding NCC varieties with a wide range of colors but without penalty in fiber quality. Also, we discuss opportunities for NCC with flame-retarding properties in textile applications.

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N-Ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) are a newly discovered compound class in tea with various bioactivities. This study aimed to develop a novel processing technique to enhance EPSF contents in white tea efficiently. Using optimal processing parameters of 125 °C and 30 min in a high-temperature sterilizing oven, total EPSF content significantly increased by 1.42-18.80-fold to 1.57-6.22 mg/g without impacting sensory characteristics. Metabolomics analysis revealed elevated levels of nucleosides, nucleotides, bases, theaflavins, flavonol aglycones, EPSFs, and most flavone-C-glycosides, as well as decreased levels of amino acids, procyanidins, theasinensins, several flavanols, and flavonol-O-glycosides after EPSF-enrichment treatment. Furthermore, the EPSF-enriched white tea exhibited notable anti-inflammatory effects, mitigating xylene-induced ear edema in mice and carrageenan-induced paw edema and cotton ball-induced granulomas in rats. This study developed a new processing technique for highly efficient enhancement of EPSFs in white tea and demonstrated that EPSF-enriched white tea has a potential to serve as effective anti-inflammatory dietary supplement.

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Flavonoids from green and black tea may benefit cardiovascular health. Brewed tea consumption and flavonoid intake in France have not been previously explored. This study assessed the dietary intake of flavonoids among French children and adults, using 3 days' dietary recall for 3896 persons aged >4 y in the Third French Individual and National Food Consumption Survey (INCA3). Foods consumed by INCA 3 participants were manually matched with the flavonoid content of foods from the French PhenolExplorer database and the US Department of Agriculture expanded flavonoid database (2018 version). The six subclasses of flavonoids were flavan-3-ols, flavanones, anthocyanidins, flavonols, flavones, and isoflavones. Flavonoid intake was stratified by age subgroups (children and adults separately) and examined using socio-demographics and tea consumption patterns. Mean flavonoid intake was 210 mg/d. Flavonoids in the French diet were predominantly flavan-3-ols (147 mg/d), of which tea is the main source. The effects of age, education, income, and socio-professional category (SPC) on flavonoid intake were all significant (p < 0.0001). Brewed tea consumers were 31.88% of French adults and 3.79% of children. Brewed tea consumption and flavonoid intake were highly correlated. The highest brewed tea and flavonoid intakes were found among individuals with the highest SPC and education levels. Flavonoid intake in France was associated with brewed tea consumption and with higher education and income.

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Flavan-3-ols are prominent phenolic compounds found abundantly in the young leaves of tea plants. The enzymes involved in flavan-3-ol biosynthesis in tea plants have been extensively investigated. However, the localization and associations of these numerous functional enzymes within cells have been largely neglected. In this study, we aimed to investigate the synthesis of flavan-3-ols in tea plants, particularly focusing on epigallocatechin gallate. Our analysis involving the DESI-MSI method to reveal a distinct distribution pattern of B-ring trihydroxylated flavonoids, primarily concentrated in the outer layer of buds. Subcellular localization showed that CsC4H, CsF3'H, and CsF3'5'H localizes endoplasmic reticulum. Protein-protein interaction studies demonstrated direct associations between CsC4H, CsF3'H, and cytoplasmic enzymes (CHS, CHI, F3H, DFR, FLS, and ANR), highlighting their interactions within the biosynthetic pathway. Notably, CsF3'5'H, the enzyme for B-ring trihydroxylation, did not directly interact with other enzymes. We identified cytochrome b5 isoform C serving as an essential redox partner, ensuring the proper functioning of CsF3'5'H. Our findings suggest the existence of distinct modules governing the synthesis of different B-ring hydroxylation compounds. This study provides valuable insights into the mechanisms underlying flavonoid diversity and efficient synthesis and enhances our understanding of the substantial accumulation of B-ring trihydroxylated flavan-3-ols in tea plants.

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Since the initial findings that food tannin/salivary protein interaction and subsequent precipitation is the main cause of the astringency development, numerous studies have concentrated on the supramolecular characterization of these bindings. Most of these works have focused on the low-molecular-weight salivary proteins, in particular proline-rich proteins, hardly considering the involvement of the high-molecular-weight salivary proteins (HMWSPs). Herein, different techniques such as fluorescence quenching, Isothermal Titration Calorimetry and HPLC-MS-DAD were employed to determine the occurrence of molecular interactions between three HMWSPs, namely, mucin, α-amylase and albumin, and a complex extract of tannins composed mainly of flavan-3-ols. The obtained results prove the capability of the three HMWSPs to effectively interact with the flavan-3-ol extract, involving different forces and action mechanisms. Flavan-3-ols are capable of interacting with mucins by a mechanism that includes the formation of stable ground-state complexes that led to approximately 90% flavan-3-ol precipitation, while for albumin and α-amylase, the interaction model of a "sphere of action" was established, which represented only 20% flavan-3-ol precipitation. These data highlight the relevance of including HMWSPs in astringency analyses, paying special heed to the role of mucins in the interaction and subsequent precipitation of dietary tannins.

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BACKGROUND AND AIMS: Flavonoids are a class of secondary plant metabolites that have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. This study was to explore the association between dietary flavonoid consumption and the prevalence of chronic respiratory diseases (CRDs) in adults. METHODS AND RESULTS: The six main types of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018 by the two 24-h recall interviews. The prevalence of CRDs, including asthma, emphysema, and chronic bronchitis, was determined through a self-administered questionnaire. The analysis included 15,753 participants aged 18 years or older who had completed a diet history interview. After adjustment for potential confounders, the inverse link was found with total flavonoids, anthocyanidins, flavanones, and flavones, with an OR (95%CI) of 0.86 (0.75-0.98), 0.84 (0.72-0.97), 0.80(0.69-0.92), and 0.85(0.73-0.98) for the highest group compared to the lowest group. WQS regression revealed that the mixture of flavonoids was negatively linked with the prevalence of CRDs (OR = 0.88 [0.82-0.95], P < 0.01), and the largest effect was mainly from flavanones (weight = 0.41). In addition, we found that flavonoid intake was negatively linked with inflammatory markers, and systemic inflammation significantly mediated the associations of flavonoids with CRDs, with a mediation rate of 12.64% for CRP (P < 0.01). CONCLUSION: Higher flavonoid intake was related with a lower prevalence of CRDs in adults, and this relationship may be mediated through systemic inflammation.

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The retention of flavan-3-ols and other phenolic compounds during apple juice production at pilot plant scale (200 kg, cv. Boskoop) was investigated. An oxygen-excluding spiral filter press and a conventional decanter were used with and without pectinase mash treatment. Phenolic compounds were comprehensively identified and quantitated by RP-UHPLC and HILIC, both coupled to DAD-FLD and DAD-ESI(-)-QTOF-HR-MS/MS. These techniques combined with using a NIST cocoa flavan-3-ol standard allowed for the first time an individual quantification of flavan-3-ol fractions (DP 1-7) in apple juices. Spiral filter-pressed juices were exposed to less oxidation and exhibited four times higher total phenolic compound levels than decanter-made juices (1016 vs. 262 mg/L). Apple juices derived from pectinase-treated mashes had lower total phenolic compound levels than their non-treated counterparts. However, those made by spiral filter press still retained significantly higher concentrations (780 vs. 104 mg/L). Flavan-3-ols were especially well retained by spiral filter press processing, reaching unprecedentedly high concentrations of up to 713 mg/L. A 280 mL serving of non-treated spiral filter-pressed juice would therefore suffice to provide the daily intake of 200 mg flavan-3-ols, equaling the dose of cocoa flavan-3-ols associated with an authorized European health claim for healthy blood flow.

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Quantification of nutritional biomarkers is crucial to accurately assess the dietary intake of different classes of (poly)phenols in large epidemiological studies. High-throughput analysis is mandatory to apply this methodology in large cohorts. However, the current validated methods to quantify (poly)phenols metabolites in biological fluids use ultra performance liquid chromatography (UPLC), leading to analysis time of several minutes per sample. To significantly reduce the run time, we developed and validated a method to quantify in urine the flavan-3-ols biomarkers, phenyl-γ-valerolactones (PVLs), using laser diode thermal desorption (LDTD). This mass spectrometry source allows direct introduction of sample extracts, resulting in analysis time of less than 10 s per sample. Also, to encompass the problem associated with the cost and availability of sulfated and glucuronide analytical standards, urine samples were subjected to enzymatic hydrolysis. Creatinine was also quantified to normalize the results obtained from the urinary spot. Results obtained with LDTD-MS/MS were cross-validated by UPLC-MS/MS using 155 urine samples. Coefficient of correlation was above 0.975 for PVLs and creatinine. For all analytes, the accuracy was between 90% and 113% by LDTD-MS/MS. Altogether, sample preparation was fully automated to demonstrate the application potential of this method to large cohorts.

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Background: Diabetes mellitus (DM) is a prominent health concern worldwide, leading to the high incidence of disability and mortality and bringing in heavy healthcare and social burden. Plant-based diets are reported associated with a reduction of DM risk. Plant-based diets are rich in flavonoids, which possess properties such as scavenging free radicals and exerting both anti-inflammatory and antioxidant effects. Purpose: However, whether dietary flavonoids are associated with the prevalence of DM remains controversial. The potential reasons for contradictory epidemiological outcomes on the association between dietary flavonoids and DM prevalence have not been determined. Methods: To address these limitations, we employed data from 22,481 participants in the National Health and Nutrition Examination Survey to explore the association between the intake of flavonoids and DM prevalence by weighted Logistic regression and weighted restricted cubic splines. Results: We found that the prevalence of DM was inversely associated with the intake of total flavonoids in the second quartile [Odds Ratio (OR) 0.78 95% confidence interval (CI) (0.63, 0.97), p = 0.028], in the third quartile [0.76 (0.60, 0.97), p = 0.031], and in the fourth quartile [0.80 (0.65, 0.97), p = 0.027]. However, the p for trend was not significant [0.94 (0.88, 1.01), p = 0.096]. Moreover, the association between DM prevalence and the intake of total flavonoids was significantly influenced by race (p for interaction = 0.006). In Mexican Americans, there was a significant positive association between DM prevalence and total flavonoid intake within the third quartile [1.04 (1.02, 1.07), p = 0.003]. Total flavan-3-ol and subtotal catechin intake exhibited a non-linear U-shaped association with DM prevalence (p for non-linearity < 0.0001 and p for non-linearity < 0.0001, respectively). Compared to the first quartile of corresponding intakes, consumption within the third quartile of subtotal catechins [0.70 (0.55, 0.89), p = 0.005] and total flavan-3-ols [0.65 (0.50, 0.84), p = 0.002] was associated with a lower prevalence of DM. Conclusion: Taken together, our study may provide preliminary research evidence for personalized improvement of dietary habits to reduce the prevalence of diabetes.

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Continuing caution is required against the potential emergence of SARS-CoV-2 novel mutants that could pose the next global health and socioeconomical threats. If virus in saliva can be inactivated by a beverage, such a beverage may be useful because the saliva of infected persons is the major origin of droplets and aerosols that mediate human-to-human viral transmission. We previously reported that SARS-CoV-2 was significantly inactivated by treatment in vitro with tea including green tea and black tea. Catechins and its derived compounds galloylated theaflavins (gTFs) bound to the receptor-binding domain (RBD) of the S-protein and blocked interaction between RBD and ACE2. Black tea is often consumed with sugar, milk, lemon juice, etc., and it remains unclarified whether these ingredients may influence the anti-SARS-CoV-2 effect of black tea. Here, we examined the effect of black tea on Omicron subvariants in the presence of these ingredients. The infectivity of Omicron subvariants was decreased to 1/100 or lower after treatment with black tea for 10 s. One or two teaspoons of milk (4~8 mL) completely blocked the anti-viral effect of a cup of tea (125 mL), whereas an addition of sugar or lemon juice failed to do so. The suppressive effect was dose-dependently exerted by milk casein but not whey proteins. gTFs were coprecipitated with casein after acidification of milk-supplemented black tea, strongly suggesting the binding of gTFs to casein. The present study demonstrates for the first time that an addition of milk cancelled the anti-SARS-CoV-2 effect of black tea due to binding of casein to gTFs.

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Avocado peel and seed are the main by-products of avocado processing and are considered as promising sources of phenolic compounds with biological activities. Thus, this research focuses on the establishment, for the first time, of ultrasound-assisted extraction of flavan-3-ols with high antioxidant activity from avocado peel and seed using a sonotrode. Indeed, 2 Box-Behnken designs were performed for 15 experiments, with each design having three independent factors (ratio ethanol/water (v/v), time (min) and amplitude (%)). In both models, the responses included total procyanidins (flavan-3-ols) measured via HPLC-FLD and antioxidant activity measured via DPPH, ABTS and FRAP. The results showed that applying the sonotrode extraction method could increase flavan-3-ols recovery by 54% and antioxidant activity by 62-76% compared to ultrasound bath technology. Therefore, this technology was demonstrated to be a non-thermal, low time-consuming and scalable method that allowed the recovery of flavan-3-ols from avocado by-products that could be used as functional ingredients.

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BACKGROUND: Phenyl-γ-valerolactones (PVLs) have been identified as biomarkers of dietary flavan-3-ol exposure, although their utility requires further characterization. OBJECTIVES: We investigated the performance of a range of PVLs as biomarkers indicative of flavan-3-ol intake. METHODS: We report the results of 2 companion studies: a 5-way randomized crossover trial (RCT) and an observational cross-sectional study. In the RCT (World Health Organization, Universal Trial Number: U1111-1236-7988), 16 healthy participants consumed flavan-3-ol-rich interventions (of apple, cocoa, black tea, green tea, or water [control]) for 1 d each. First morning void samples and 24-h urine samples were collected with diet standardized throughout. For each participant, 1 intervention period was extended (to 2 d) to monitor PVL kinetics after repeat exposure. In the cross-sectional study, 86 healthy participants collected 24-h urine samples, and concurrent weighed food diaries from which flavan-3-ol consumption was estimated using Phenol-Explorer. A panel of 10 urinary PVLs was quantified using liquid chromatography tandem mass spectrometry. RESULTS: In both studies, 2 urinary PVLs [5-(3'-hydroxyphenyl)-γ-valerolactone-4'-sulfate and putatively identified 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-glucuronide] were the principal compounds excreted (>75%). In the RCT, the sum of these PVLs was significantly higher than the water (control) after each intervention; individually, there was a shift from sulfation toward glucuronidation as the total excretion of PVLs increased across the different interventions. In the extended RCT intervention period, no accumulation of these PVLs was observed after consecutive days of treatment, and after withdrawal of treatment on the third day, there was a return toward negligible PVL excretion. All results were consistent, whether compounds were measured in 24-h urine or first morning void samples. In the observational study, the sum of the principal PVLs correlated dose dependently (Rs = 0.37; P = 0.0004) with dietary flavan-3-ol intake, with similar associations for each individually. CONCLUSIONS: Urinary 5-(3'-hydroxyphenyl)-γ-valerolactone-4'-sulfate and putatively identified 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-glucuronide are recommended biomarkers for dietary flavan-3-ol exposure.

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SCOPE: Dietary flavan-3-ols are known to mediate cardiovascular benefits. Currently, it is assumed that the levels of flavan-3-ol catabolites detected in humans, 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (γVL) and 5-(3',4'-dihydroxyphenyl)-γ-valeric acid (γVA), and their corresponding phase II metabolites, are determined exclusively by the action of the gut microbiome. However, a family of human proteins, paraoxonase (PON), can theoretically hydrolyze γVL metabolites into the corresponding γVAs. This study aims to determine if PON is involved in γVL and γVA metabolism in humans. METHODS AND RESULTS: A rapid conversion of γVL into γVA is detected in serum ex vivo (half-life = 9.8 ± 0.3 min) that is catalyzed by PON1 and PON3 isoforms. Phase II metabolites of γVL are also reacted with PON in serum. Following an intake of flavan-3-ol in healthy males (n = 13), the profile of γVA metabolites detected is consistent with that predicted from the reactivity of γVL metabolites with PON in serum. Furthermore, common PON polymorphisms are evaluated to assess the use of γVL metabolites as biomarkers of flavan-3-ol intake. CONCLUSION: PONs are involved in flavan-3-ol metabolic pathway in humans. PON polymorphisms have a minor contribution to inter-individual differences in the levels of γVL metabolites, without affecting their use as a nutritional biomarker.

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BACKGROUND: Dietary polyphenols, including flavan-3-ols (F3O), are associated with better health outcomes. The relationship of plasma phenyl-γ-valerolactones (PVLs), the products of colonic bacterial metabolism of F3O, with dietary intakes is unclear. OBJECTIVES: To investigate whether plasma PVLs are associated with self-reported intakes of total F3O and procyanidins+(epi)catechins. DESIGN: We measured 9 PVLs by uHPLC-MS-MS in plasma from adults (>60y) in the Trinity-Ulster-Department of Agriculture (TUDA study (2008 to 2012; n=5186) and a follow-up subset (2014 to 2018) with corresponding dietary data (n=557). Dietary (poly)phenols collected by FFQ were analyzed using Phenol-Explorer. RESULTS: Mean (95% confidence interval [CI]) intakes were estimated as 2283 (2213, 2352) mg/d for total (poly)phenols, 674 (648, 701) for total F3O, and 152 (146, 158) for procyanidins+(epi)catechins. Two PVL metabolites were detected in plasma from the majority of participants, 5-(hydroxyphenyl)-γ-VL-sulfate (PVL1) and 5-(4'-hydroxyphenyl)-γ-VL-3'-glucuronide (PVL2). The 7 other PVLs were detectable only in 1-32% of samples. Self-reported intakes (mg/d) of F3O (r = 0.113, P = 0.017) and procyanidin+(epi)catechin (r = 0.122, P = 0.010) showed statistically significant correlations with the sum of PVL1 and PVL 2 (PVL1+2). With increasing intake quartiles (Q1-Q4), mean (95% CI) PVL1+2 increased; from 28.3 (20.8, 35.9) nmol/L in Q1 to 45.2 (37.2, 53.2) nmol/L in Q4; P = 0.025, for dietary F3O, and from 27.4 (19.1, 35.8) nmol/L in Q1 to 46.5 (38.2, 54.9) nmol/L in Q4; P = 0.020, for procyanidins+(epi)catechins. CONCLUSIONS: Of 9 PVL metabolites investigated, 2 were detected in most samples and were weakly associated with intakes of total F3O and procyanidins+(epi)catechins. Future controlled feeding studies are required to validate plasma PVLs as biomarkers of these dietary polyphenols.

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