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Several randomized controlled trials (RCTs) and meta-analyses support the benefits of flavanols on cardiometabolic health, but the factors affecting variability in the responses to these compounds have not been properly assessed. The objectives of this meta-analysis were to systematically collect the RCTs-based-evidence of the effects of flavanol-containing tea, cocoa and apple products on selected biomarkers of cardiometabolic risk and to explore the influence of various factors on the variability in the responses to the consumption of these products. A total of 120 RCTs were selected. Despite a high heterogeneity, the intake of the flavanol-containing products was associated using a random model with changes (reported as standardized difference in means (SDM)) in body mass index (−0.15, p < 0.001), waist circumference (−0.29, p < 0.001), total-cholesterol (−0.21, p < 0.001), LDL-cholesterol (−0.23, p < 0.001), and triacylglycerides (−0.11, p = 0.027), and with an increase of HDL-cholesterol (0.15, p = 0.005). Through subgroup analyses, we showed the influence of baseline-BMI, sex, source/form of administration, medication and country of investigation on some of the outcome measures and suggest that flavanols may be more effective in specific subgroups such as those with a BMI ≥ 25.0 kg/m2, non-medicated individuals or by specifically using tea products. This meta-analysis provides the first robust evidence of the effects induced by the consumption of flavanol-containing tea, cocoa and apple products on weight and lipid biomarkers and shows the influence of various factors that can affect their bioefficacy in humans. Of note, some of these effects are quantitatively comparable to those produced by drugs, life-style changes or other natural products. Further, RCTs in well-characterized populations are required to fully comprehend the factors affecting inter-individual responses to flavanol and thereby improve flavanols efficacy in the prevention of cardiometabolic disorders info:eu-repo/semantics/publishedVersion

Prediction of retention times (RTs) is increasingly considered in untargeted metabolomics to complement MS/MS matching for annotation of unidentified peaks. We tested the performance of PredRet (http://predret.org/) to predict RTs for plant food bioactive metabolites in a data sharing initiative containing entry sets of 29–103 compounds (totalling 467 compounds, >30 families) across 24 chromatographic systems (CSs). Between 27 and 667 predictions were obtained with a median prediction error of 0.03–0.76 min and interval width of 0.33–8.78 min. An external validation test of eight CSs showed high prediction accuracy. RT prediction was dependent on shape and type of LC gradient, and number of commonly measured compounds. Our study highlights PredRet’s accuracy and ability to transpose RT data acquired from one CS to another CS. We recommend extensive RT data sharing in PredRet by the community interested in plant food bioactive metabolites to achieve a powerful community-driven open-access tool for metabolomics annotation., The authors acknowledge networking support by the European Cooperation in Science and Technology (COST) Action FA 1403 POSITIVe (Interindividual Variation in Response to Consumption of Plant Food Bioactives and Determinants Involved). Dorrain Low has received the support of EU H2020 in the framework of the FP7-Marie Curie-COFUND People Programme, through award of the AgreenSkills+ Fellowship (grant number 609398) and Nanyang Technological University, Singapore, through award of the Presidential Postdoctoral Fellowship (grant number 001991-00001). The MetaboHUB French infrastructure has supported the INRAE platform (PFEM, MetaboHUB-Clermont) involved in this work (grant number ANR-INBS-0010). Kateřina Valentová and Lucie Petrásková acknowledge financial support from the Czech Science Foundation (grant number 19-00043S). The Faculty of Pharmacy of Lisbon University acknowledges FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA and PORTUGAL 2020 for financial support of the Portuguese Mass Spectrometry Network (grant number LISBOA-01-0145-FEDER-402-022125). Kati Hanhineva and Ville Koistinen have received funding from the Academy of Finland (grant numbers 277986 and 312550), Lantmännen Foundation and EU H2020 FP7-Marie Curie-COFUND MoRE Programme (grant number 754412). Biocenter Finland has financially supported the LC-MS metabolomics unit of University of Eastern Finland. Cristina Andres-Lacueva and Raúl González-Domínguez thank CIBERFES and ISCIII projects AC19/00111 and AC19/00096 (co-funded by FEDER Program from EU, “A way to make Europe”), Generalitat de Catalunya’s Agency AGAUR (grant number 2017SGR1546), “Juan de la Cierva” program from MINECO (grant number IJC2019-041867-I) and ICREA Academia award 2018. Francisco A. Tomás-Barberán has received financial support from the Spanish National Research program (grant numbers AGL-2015-73107-EXP/AEI, CSIC 201870E014) and Fundación Seneca Región de Murcia (grant number 19900/GERM/15). Gesine Schmidt acknowledges support through the Norwegian Agriculture and Food Industry Research Funds (grant number 262300). Lars Dragsted and Jan Stanstrup thank the Carlsberg Foundation for a Semper Ardens grant to support this work. László Abrankó acknowledges the Hungarian Academy of Sciences for the János Bolyai Scholarship, and support of the EU and ESF co-financed project of SZIU (grant number EFOP-3.6.3-VEKOP-16-2017-00005). Sonia de Pascual-Teresa thanks the Spanish MINECO for financial support (grant number AGL2016-76832-R). Dilip K. Rai acknowledges Teagasc for the financial support through the Walsh Fellowship (grant number 2016038).

International audience; Oxylipins are considered biomarkers related to cardiovascular diseases (CVDs). They are generated in vivo via the oxygenation of polyunsaturated fatty acids as a result of oxidative stress and inflammation. Oxylipins are involved in vascular functions and are produced during foam cell formation in atherogenesis. Additionally, the consumption coffee is associated with the regulation on a particular oxylipin group, the F2t-isoprostanes (F2t-IsoPs). This function has been attributed to the chlorogenic acids (CGAs) from the coffee beverage. Considering the anti-inflammatory and antioxidant properties of CGAs, we evaluated the effects of two types of coffee that provided 787 mg CGAs/day (Coffee A) and 407 mg CGAs/day (Coffee B) by reducing 35 selected oxylipins in healthy subjects. Furthermore, we assessed the effect of CGAs on the cellular proatherogenic response in foam cells by using an oxidized LDL (oxLDL)-macrophage interaction model. After eight weeks of coffee consumption, the contents of 12 urine oxylipins were reduced. However, the effect of Coffee A showed a stronger decrease in IsoPs, dihomo-IsoPs, prostaglandins (PGs) and PG metabolites, probably due to its higher content of CGAs. Neither of the two coffees reduced the levels of oxLDL. Moreover, the in vitro oxylipin induction by oxLDL on foam cells was ameliorated by phenolic acids and CGAs, including the inhibition of IsoPs and PGs by caffeoylquinic and dicaffeoylquinic acids, respectively, while the phenolic acids maintained both antioxidant and anti-inflammatory activities. These findings suggest that coffee antioxidants are strong regulators of oxylipins related to CVDs. The clinical trial was registered on the International Clinical Trials Registry Platform, WHO primary registry (RPCEC00000168).

Part of: Nutrition Society Spring Meeting 2019 Conference on ‘Inter-individual differences in the nutrition response: from research to recommendations’; Food phytochemicals are increasingly considered to play a key role in the cardiometabolic health effects of plant foods. However, the heterogeneity in responsiveness to their intake frequently observed in clinical trials can hinder the beneficial effects of these compounds in specific subpopulations. A range of factors, including genetic background, gut microbiota, age, sex and health status, could be involved in these interindividual variations; however, the current knowledge is limited and fragmented. The European network, European Cooperation in Science and Technology (COST)-POSITIVe, has analysed, in a systematic way, existing knowledge with the aim to better understand the factors responsible for the interindividual variation in response to the consumption of the major families of plant food bioactives, regarding their bioavailability and bioefficacy. If differences in bioavailability, likely reflecting differences in human subjects’ genetics or in gut microbiota composition and functionality, are believed to underpin much of the interindividual variability, the key molecular determinants or microbial species remain to be identified. The systematic analysis of published studies conducted to assess the interindividual variation in biomarkers of cardiometabolic risk suggested some factors (such as adiposity and health status) as involved in between-subject variation. However, the contribution of these factors is not demonstrated consistently across the different compounds and biological outcomes and would deserve further investigations. The findings of the network clearly highlight that the human subjects’ intervention studies published so far are not adequate to investigate the relevant determinants of the absorption/metabolism and biological responsiveness. They also emphasise the need for a new generation of intervention studies designed to capture this interindividual variation.

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790., This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/).

Background A healthy diet and optimal lifestyle choices are amongst the most important actions for the prevention of cardiometabolic diseases. Despite this, it appears difficult to convince consumers to select more nutritious foods. Furthermore, the development and production of healthier foods do not always lead to economic profits for the agro-food sector. Most dietary recommendations for the general population represent a “one-size-fits-all approach” which does not necessarily ensure that everyone has adequate exposure to health-promoting constituents of foods. Indeed, we now know that individuals show a high variability in responses when exposed to specific nutrients, foods, or diets. Purpose This review aims to highlight our current understanding of inter-individual variability in response to dietary bioactives, based on the integration of findings of the COST Action POSITIVe. We also evaluate opportunities for translation of scientific knowledge on inter-individual variability in response to dietary bioactives, once it becomes available, into practical applications for stakeholders, such as the agro-food industry. The potential impact from such applications will form an important impetus for the food industry to develop and market new high quality and healthy foods for specific groups of consumers in the future. This may contribute to a decrease in the burden of diet-related chronic diseases., Key messages Individual differences in ADME (Absorption, Digestion, Metabolism and Excretion) is believed to underpin much of the inter-individual variation in responses.Recent developments in the area of food metabolome databases and fast improvements in innovative metabotyping technologies hold great promise for improved profiling of dietary intake, exposure to individual ingredients, foods and dietary patterns, as well as our ability to identify individual responsiveness.The food industry needs well-defined population clusters or targets in order to be able to design “personalized products”.There are indeed excellent industrial opportunities for foods that modulate gut microbiota, and thereby enable the delivery of food bioactive metabolites.It is currently not clear whether knowledge on individual nutrient needs, based on genetic or metagenomic data, would affect long-term dietary and health behaviours.Data to support the development of dietary recommendations may need to be generated by new n-of-1-based study designs in the future.

Purpose The quality of the study design and data reporting in human trials dealing with the inter-individual variability in response to the consumption of plant bioactives is, in general, low. There is a lack of recommendations supporting the scientific community on this topic. This study aimed at developing a quality index to assist the assessment of the reporting quality of intervention trials addressing the inter-individual variability in response to plant bioactive consumption. Recommendations for better designing and reporting studies were discussed. Methods The selection of the parameters used for the development of the quality index was carried out in agreement with the scientific community through a survey. Parameters were defined, grouped into categories, and scored for different quality levels. The applicability of the scoring system was tested in terms of consistency and effort, and its validity was assessed by comparison with a simultaneous evaluation by experts’ criteria. Results The “POSITIVe quality index” included 11 reporting criteria grouped into four categories (Statistics, Reporting, Data presentation, and Individual data availability). It was supported by detailed definitions and guidance for their scoring. The quality index score was tested, and the index demonstrated to be valid, reliable, and responsive. Conclusions The evaluation of the reporting quality of studies addressing inter-individual variability in response to plant bioactives highlighted the aspects requiring major improvements. Specific tools and recommendations favoring a complete and transparent reporting on inter-individual variability have been provided to support the scientific community on this field. Electronic supplementary material The online version of this article (10.1007/s00394-019-02069-3) contains supplementary material, which is available to authorized users., Key messages The reporting quality of human studies on inter-individual variation in response to plant bioactives is generally low and should be significantly improved.There is no specific guidance for reporting studies on inter-individual variation in response to plant bioactives.The assessment of reporting quality using a scale approach is considered a valuable tool in assessing compliance with the recommendations in the submission phase or during the reviewing process. It also provides a quantitative measure of the quality of studies to be used in meta-analysis.Eleven reporting criteria were developed and supported by detailed definitions and guidance for their scoring.The POSITIVe quality index was tested and demonstrated to be valid, reliable, and responsive.The use of the quality index and its supporting explanatory material (dictionary) as a guide for researchers, peer-reviewers, and journal editors will foster further complete and transparent reporting of data on inter-individual variability.The criteria used in the quality index can serve as additional guidance to inform the design and conduction of further studies on inter-individual variations in response to plant bioactives.Better reporting is expected to lead to a better understanding of the mechanisms and factors involved and thus better study designs with greater impact on policies and practice. Electronic supplementary material The online version of this article (10.1007/s00394-019-02069-3) contains supplementary material, which is available to authorized users.

Purpose The health-promoting potential of food-derived plant bioactive compounds is evident but not always consistent across studies. Large inter-individual variability may originate from differences in digestion, absorption, distribution, metabolism and excretion (ADME). ADME can be modulated by age, sex, dietary habits, microbiome composition, genetic variation, drug exposure and many other factors. Within the recent COST Action POSITIVe, large-scale literature surveys were undertaken to identify the reasons and extent of inter-individual variability in ADME of selected plant bioactive compounds of importance to cardiometabolic health. The aim of the present review is to summarize the findings and suggest a framework for future studies designed to investigate the etiology of inter-individual variability in plant bioactive ADME and bioefficacy. Results Few studies have reported individual data on the ADME of bioactive compounds and on determinants such as age, diet, lifestyle, health status and medication, thereby limiting a mechanistic understanding of the main drivers of variation in ADME processes observed across individuals. Metabolomics represent crucial techniques to decipher inter-individual variability and to stratify individuals according to metabotypes reflecting the intrinsic capacity to absorb and metabolize bioactive compounds. Conclusion A methodological framework was developed to decipher how the contribution from genetic variants or microbiome variants to ADME of bioactive compounds can be predicted. Future study design should include (1) a larger number of study participants, (2) individual and full profiling of all possible determinants of internal exposure, (3) the presentation of individual ADME data and (4) incorporation of omics platforms, such as genomics, microbiomics and metabolomics in ADME and efficacy studies., Key messages Human intervention studies are typically too small and do not report data from individuals to allow investigations of relevant determinants of inter-individual variability in ADME and bioefficacy.For some plant food bioactive compounds (isoflavones and ellagitannins), particular metabolites are produced only in a subset of the population, i.e., among individuals with a specific metabotype.Microbiota is an important determinant of the ADME of many bioactive compounds but microbial gene annotation is often lacking and interference with background diet and temporal variability is high: microbial metabolism capacity is, therefore, difficult to predict.Genetic variability is considered an important determinant of the ADME of some bioactive compounds, but there is a large gap in knowledge for many families of plant bioactive compounds regarding biotransformation enzymes and transport proteins.Information on other determinants such as age, sex, and diet is too incomplete to make firm conclusions about their impact on the inter-individual variability for most compounds investigatedMetabotyping individuals appears as essential to increase our understanding and improve prediction of ADME and health effects of plant bioactive compounds. Yet successful stratification examples are scarce and if available (e.g., urolithins), validation studies in larger cohorts are still required.

Interindividual Variability in Absorption, Distribution, Metabolism, and Excretion of Food Phytochemicals Should Be Reported

Phytoprostanes (PhytoPs) and phytofurans (PhytoFs) are oxylipins synthesized by nonenzymatic peroxidation of α-linolenic acid. These compounds are biomarkers of oxidative degradation in plant foods. In this research, the effect of environment and supplementation with salicylic acid (SA) on PhytoPs and PhytoFs was monitored by ultra-high-performance liquid chromatography coupled to electrospray ionization and triple quadrupole mass spectrometry (UHPLC-ESI-QqQ-MS/MS) on seven rice genotypes from Oryza sativa L. subsp. japonica. The plastic cover environment and spray application with 1 and 15 mM SA produced a reduction in the concentration of most of these newly established stress biomarkers [9-F1t-PhytoP, ent-16-F1t-PhytoP, ent-16- epi-16-F1t-PhytoP, 9-D1t-PhytoP, 9- epi-9-D1t-PhytoP, 16-B1-PhytoP, 9-L1-PhytoP, ent-16( RS)-9- epi-ST-Δ14-10-PhytoF, ent-9( RS)-12- epi-ST-Δ10-13-PhytoF, and ent-16( RS)-13- epi-ST-Δ14-9-PhytoF] by 60.7% on average. The modification observed in the level of PhytoPs and PhytoFs differed according to the specific oxylipins and genotype, demonstrating a close linkage between genetic features and resistance to abiotic stress, to some extent mediated by the sensitivity of plants to the plant hormone SA that participates in the physiological response of higher plants to stress. Thus, in plants exposed to stressing factors, SA contribute to modulating the redox balance, minimizing the oxidation of fatty acids and thus the syntheis of oxylipins. These results indicated that SA could be a promising tool for managing the thermotolerance of rice crop. However, it remains necessary to study the mechanism of action of PhytoPs and PhytoFs in biochemical processes related to the defense of plants and define their role as stress biomarkers through a nonenzymatic pathway., Facultad de Ciencias Agrarias y Forestales

A systematic review and meta-analysis of randomized controlled trials exploring the role of inter-individual variability on the effect of flavanols on insulin and HOMA-IR. 2018 Spring Conference on Nutrient-Nutrient Interaction

Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation., This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/). The authors thank the financial support of the COST Action FA1403 “POSITIVe” to conduct a short-term scientific mission to K.C. at CEBAS-CSIC (A.G.-S. and M.T.G.-C.) during which the data analysis was performed.

We acknowledge networking support by the COST Action FA 1403 POSITIVe (interindividual variation in response to consumption of plant food bioactives and determinants involved), supported by COST (European Cooperation in Science and Technology); Cardiometabolic disease, comprising cardiovascular diseases, type 2 diabetes, and their associated risk factors including metabolic syndrome and obesity, is the leading cause of death worldwide. Plant foods are rich sources of different groups of bioactive compounds, which might not be essential throughout life but promote health and well-being by reducing the risk of age-related chronic diseases. However, heterogeneity in the responsiveness to bioactive compounds can obscure associations between their intakes and health outcomes, resulting in the hiding of health benefits for specific population groups and thereby limiting our knowledge of the exact role of the different bioactive compounds for health. The heterogeneity in response suggests that some individuals may benefit more than others from the health effects of these bioactive compounds. However, to date, this interindividual variation after habitual intake of plant bioactive compounds has been little explored. The aim of this review is to provide an overview of the existing research that has revealed interindividual variability in the responsiveness to plant-food bioactive compound consumption regarding cardiometabolic outcomes, focusing on polyphenols, caffeine and plant sterols, and the identified potential determinants involved.

International audience; Oxylipins are lipid mediators involved in the physiopathology of all organs. Moreover, isoprostanes have been established as general and reliable in vivo oxidative stress biomarkers. Red wine has proved to exert several benefits through the maintenance of the oxidative balance of the organism. Antiradical scavenging capacity has been mainly attributed to polyphenols. However, melatonin and hydroxytyrosol should be taken into account as potent antiradical agents. The present research aimed to clarify the situation of enzymatic and oxidative injury and eicosanoid urinary excretion related to the intake of three kinds of red wines and their primary musts. Judging by the reduction in the excretion of isoprostanes, red wine consumption exhibited the highest antioxidant protection against oxidative stress, attributed to its OHTyr content (p < 0.05), and to a lesser extent to its MEL content. Similarly, the intake of red wine leads to the cardioprotective effect due to the reduction in the urinary excretion of the pro-inflammatory prostaglan-din 2,3-dinor-11-β-PGF 2α , besides the increase in the vasodilator prostaglandin PGE 1 , mediated by the melatonin (p < 0.05) and hydroxytyrosol (p < 0.05) contents. In conclusion, red wine (especially non-aged wine) exerts a higher in vivo antioxidant capacity than must or alcohol.

Bioactive compounds in plant-based foods have health properties that contribute to the prevention of age-related chronic diseases, particularly cardiometabolic disorders. Conclusive proof and understanding of these benefits in humans is essential in order to provide effective dietary recommendations but, so far, the evidence obtained from human intervention trials is limited and contradictory. This is partly due to differences between individuals in the absorption, distribution, metabolism and excretion of bioactive compounds, as well as to heterogeneity in their biological response regarding cardiometabolic health outcomes. Identifying the main factors underlying inter-individual differences, as well as developing new and innovative methodologies to account for such variability constitute an overarching goal to ultimately optimize the beneficial health effects of plant food bioactives for each and every one of us. In this respect, this position paper from the COST Action FA1403-POSITIVe examines the main factors likely to affect the individual responses to consumption of plant food bioactives and presents perspectives for assessment and consideration of inter-individual variability., The authors would like to acknowledge networking support by the COST Action FA 1403 POSITIVe (Inter-individual variation in response to consumption of plant food bioactives and determinants involved), supported by COST (European Cooperation in Science and Technology).

Bioactive phytoprostanes and phytofurans are synthesized in higher plants by non‐enzymatic oxidation of α‐linolenic acid (C18:3 n‐3), triggered by high concentrations of reactive oxygen species. In the current scenario of changing dietary patterns, additional information is needed on the concentrations of oxylipins in legumes and on the effect of sustained deficit irrigation on their concentration. The main objective of the work is to elucidate the phytoprostane and phytofuran profile (including eight and three compounds, respectively) of three Pisum sativum cultivars (“mangetout” (ssp. arvense), “BGE‐033620,” and “Lincoln”) and Phaseolus vulgaris (French bean cv. “Helda”), to unravel the oxidative response of these crops to sustained irrigation deficit in terms of oxidative stress, as well as in their importance as healthy dietary sources of new bioactive compounds. Phytoprostanes and phytofurans vary between varieties and species, with 9‐F₁ₜ‐PhytoP and ent‐16‐(RS)‐13‐epi‐ST‐Δ¹⁴‐9‐PhytoF being the most abundant. The level of phytoprostanes and phytofurans is also determined in sustained deficit irrigation (50% water needed), revealing modifications of their profile and concentration. In conclusion, bioactive phytoprostanes and phytofurans are present in legumes in high concentrations, being further modified by abiotic stress growing conditions, highlighting the importance of this plant food as a dietary source of these bioactive molecules. Practical Applications: This work is of high relevance from the lipidomic point of view, given that phytoprostanes and phytofurans have been promoted as new bioactive secondary metabolites due to their structural analogy with mammal oxylipins. These compounds can be further postulated as possible markers for the monitoring of the physiological status of legume plants under different agronomical conditions. The results obtained can contribute to the successful development of future research in the field of plant physiology and nutrition, significantly contributing to the advance of the current knowledge on the biological role of phytoprostanes and phytofurans in plants and complex biological systems. Species‐dependent modification of phytoprostanes and phytofurans by deficit irrigation in French‐bean, pea, and mangetout.

This article is based upon work from COST Action FA1403-POSITIVe "Interindividual variation in response to consumption of plant food bioactives and determinants involved" supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/). The authors thank the financial support of the COST Action FA1403 "POSITIVe" to conduct two short-term scientific missions to P.P. and A.G.-S. at the University of Glasgow (E.C.) during which the data analysis was performed, and to M.G.-A at the University College Dublin (E.G.) during which the protocol was developed. A.G.-S. is holder of a "Juan de la Cierva" contract from MINECO (Spain). S.P.-D. is in receipt of a CONACyT scholarship. T.R. and V.M. are supported by the Fund for scientific research of Goce Delcev University, Stip. RM acknowledges iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofunded by Fundacao para a Ciencia e Tecnologia/Ministerio da Ciencia e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement. C.A.-L. thanks the grant PCIN-2014-133 (FoodBAll project) from the Spanish Ministry of Economy and Competitiveness (MINECO) within the Joint Programming Initiative Healthy Diet for Healthy Life (JPI-HDHL); Several epidemiological studies have linked flavonols with decreased risk of cardiovascular disease (CVD). However, some heterogeneity in the individual physiological responses to the consumption of these compounds has been identified. This meta‐analysis aimed to study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood pressure and plasma glucose, as well as factors affecting their inter‐individual variability. Data from 18 human randomized controlled trials were pooled and the effect was estimated using fixed or random effects meta‐analysis model and reported as difference in means (DM). Variability in the response of blood lipids to supplementation with flavonols was assessed by stratifying various population subgroups: age, sex, country, and health status. Results showed significant reductions in total cholesterol (DM = −0.10 mmol/L; 95% CI: −0.20, −0.01), LDL cholesterol (DM = −0.14 mmol/L; Nutrients 2017, 9, 117 2 of 21 95% CI: −0.21, 0.07), and triacylglycerol (DM = −0.10 mmol/L; 95% CI: −0.18, 0.03), and a significant increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07). A significant reduction was also observed in fasting plasma glucose (DM = −0.18 mmol/L; 95%CI: −0.29, −0.08), and in blood pressure (SBP: DM = −4.84 mmHg; 95% CI: −5.64, −4.04; DBP: DM = −3.32 mmHg; 95% CI: -4.09, -2.55). Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and normal baseline values. In conclusion, flavonol consumption improved biomarkers of CVD risk, however, country of origin and health status may influence the effect of flavonol intake on blood lipid levels

Support: ANR Project ALIA-007-PhenoMeNEp; COST Action FA 1403 POSITIVe; JPI HDHL FoodBAll projectSupport: ANR Project ALIA-007-PhenoMeNEp; COST Action FA 1403 POSITIVe; JPI HDHL FoodBAll project; PhytoHub V1.4: A new release for the online database dedicated to food phytochemicals and their human metabolites. The 1. International Conference on Food Bioactives & Health