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Usually found bound to other complex molecules (e.g., lignin, hemicellulose), phenolic compounds (PC) are widely present in agro-industrial by-products, and their extraction is challenging. In recent times, research is starting to highlight the bioactive roles played by bound phenolics (BPC) in human health. This review aims at providing a critical update on recent advances in green techniques for the recovery of BPC, focusing on enzymatic-assisted (EAE) and fermentation-assisted extraction (FAE) as well as in the combination of technologies, showing variable yield and features. The present review also summarizes the most recent biological activities attributed to BPC extracts until now. The higher antioxidant activity of BPC-compared to FPC-coupled with their affordable by-product source make them medicinally potent and economically viable, promoting their integral upcycling and generating new revenue streams, business, and employment opportunities. In addition, EAE and FAE can have a biotransformative effect on the PC itself or its moiety, leading to improved extraction outcomes. Moreover, recent research on BPC extracts has reported promising anti-cancer and anti-diabetic activity. Yet further research is needed to elucidate their biological mechanisms and exploit the true potential of their applications in terms of new food products or ingredient development for human consumption.

Background: Plant-based diets have been associated with a lower risk of several chronic diseases, but the relationship with PD is unknown., Objectives: We examined the association of three different plant-based diets with PD incidence in the UK Biobank cohort., Methods: We conducted a prospective study among 126,283 participants from the UK Biobank cohort. Three plant-based diet indices (overall plant-based diet index, PDI; healthful plant-based diet index, hPDI; and unhealthful plant-based diet index, uPDI) were derived from 24-hour dietary recalls based on 17 food groups. Multivariable Cox regression models were used to estimate the risk of PD across quartiles of the PDIs and for each of the food groups that constituted the score. Further analyses were carried out to assess potential heterogeneity in associations between hPDI and PD across strata of some hypothesized effect modifiers., Results: During 11.8 years of follow-up (1,490,139 person-years), 577 cases of PD incidence were reported. After multivariable adjustment, participants in the highest hPDI and overall PDI quartile had lower risk of PD (22% and 18%, respectively), whereas a higher uPDI was associated with a 38% higher PD risk. In food-based analyses, higher intakes of vegetables, nuts, and tea were associated with a lower risk of PD (28%, 31% and 25%, respectively). Stratifying by Polygenic Risk Score (PRS), results were significant only for those with a lower PRS for PD., Conclusions: Following a healthful plant-based diet and in particular the inclusion of readily achievable intakes of vegetables, nuts and tea in the habitual diet are associated with a lower risk of PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Metabolic syndrome (MS), a condition related to adiposity and oxidative stress, can develop in adolescence, a critical stage in life that impacts health in adulthood. However, there is scarce scientific research about the relationship between lifestyle factors, emotion management, and oxidative stress in this phase of life., Aim: To analyze whether nutritional parameters, lifestyle factors, emotion management, and MS in adolescents are associated with oxidative stress measured by the biomarker 8-isoprostane., Methods: A cross-sectional study was carried out in 132 adolescents (48.5% girls, aged 12 ± 0.48 years) and data were collected on nutritional parameters (anthropometric measurements, biochemical analyzes, and blood pressure), lifestyle factors (physical activity, sleep, and diet), and emotion management (self-esteem, emotional eating, and mood). 8-isoprostane was analyzed in spot urine samples. The study population was categorized in three groups (healthy, at-risk, and with MS) using the International Diabetes Federation definition of MS in adolescents. To capture more complex interactions, a multiple linear regression was used to analyze the association between 8-isoprostane and the aforementioned variables., Results: Urinary 8-isoprostane levels were significantly higher in the MS group compared to the healthy group (1,280 ± 543 pg./mg vs. 950 ± 416 pg./mg respectively). In addition, univariable analysis revealed positive significant associations between 8-isoprostane and body mass index, waist circumference, waist-to-height ratio, body fat percentage, blood lipid profile and glucose, emotional eating, and refined cereal intake. Conversely, a negative significant association was found between 8-isoprostane and sleep duration and fish intake. The multiple linear regression analysis revealed associations between 8-isoprostane and LDL-c ( β  = 0.173 value of p  = 0.049), emotional eating (low β  = 0.443, value of p  = 0.036; high β  = 0.152, value of p  = 0.470), refined cereal intake ( β =0.191, value of p  = 0.024), and fish intake ( β  = -0.187, value of p  = 0.050)., Conclusion: The MS group, LDL-c, emotional eating, and high refined cereals and low fish intakes were associated with higher levels of oxidative stress in an adolescent population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ramírez-Garza, Laveriano-Santos, Moreno, Bodega, de Cos-Gandoy, de Miguel, Santos-Beneit, Fernández-Alvira, Fernández-Jiménez, Martínez-Gómez, Ruiz-León, Estruch, Lamuela-Raventós and Tresserra-Rimbau.)

Aims: Large studies linking adolescents' objectively measured sleep duration and adiposity markers are lacking. We characterized sleep duration and its cross-sectional and longitudinal associations with adiposity markers in adolescence., Methods and Results: Seven-day accelerometry was performed in a cohort of adolescents enrolled in the SI! Program for Secondary Schools trial in Spain at approximately ages 12 (1216 adolescents, 49.6% girls), 14 (1026 adolescents, 51.3% girls), and 16 (872 adolescents, 51.7% girls) years. Participants were classified as very short sleepers (VSS; <7 h), short sleepers (SS; 7-<8 h), or recommended-time sleepers (RTS; 8-10 h). Adjusted associations between sleep duration and adiposity markers were analysed using generalized linear and Poisson models. At ∼12 years, 33.7% of adolescents met sleep recommendations, and this percentage decreased with advancing age (22.6% at ∼14 and 18.7% at ∼16 years). Compared with RTS, overweight/obesity prevalence ratios at ∼12, 14, and 16 years among SS were 1.19 [95% confidence interval (CI): 1.09-1.30], 1.41 (95% CI: 1.34-1.48), and 0.99 (95% CI: 0.77-1.26) and among VSS were 1.30 (95% CI: 1.28-1.32), 1.93 (95% CI: 1.41-2.64), and 1.32 (95% CI: 1.26-1.37). Compared with adolescents who always met sleep recommendations, the prevalence of overweight/obesity was ∼5 times higher in those never meeting recommendations or meeting them only once. Similar trends were observed for the waist-to-height ratio (P = 0.010) and fat mass index (P = 0.024)., Conclusion: Most adolescents did not meet sleep recommendations. Shorter sleep duration was independently associated with unfavourable adiposity markers, and such adverse impact was cumulative. Health promotion programmes should emphasize the importance of good sleep habits., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: School-based interventions offer an opportunity for health promotion in adolescence., Objective: To assess the effect of 2 multicomponent educational health promotion strategies of differing duration and intensity on adolescents' cardiovascular health (CVH)., Design, Setting, and Participants: The SI! Program for Secondary Schools is a 4-year cluster randomized clinical intervention trial conducted in 24 secondary schools from Barcelona and Madrid, Spain, from September 7, 2017, to July 31, 2021. Eligible participants were adolescents enrolled in the first grade of secondary school., Interventions: Schools and their participants were randomized to receive a health promotion intervention (SI! Program) over 4 school years (long-term intervention [LTI], 8 schools, 412 adolescents) or 2 school years (short-term intervention [STI], 8 schools, 504 adolescents) or to receive the standard curriculum (control, 8 schools, 441 adolescents)., Main Outcome and Measures: The primary end point was the between-group difference at 2 and 4 years in the change from baseline of the overall CVH score, as defined by the American Heart Association (range, 0-14 points, with a higher score indicating a healthier CVH profile). Intervention effects were tested with multilevel mixed-effects models. A complete-case intention-to-treat analysis was performed as the primary analysis., Results: Of the randomized students, the study enrolled 1326 adolescents (684 [51.6%] boys, mean [SD] age, 12.5 [0.4] years at recruitment) with a study completion rate of 86.0%. Baseline overall CVH scores were 10.3 points in the LTI group, 10.6 points in the STI group, and 10.5 points in the control group. After 2 years, at halfway through the LTI and at the end of the STI, the difference in the CVH score change was 0.44 points (95% CI, 0.01-0.87; P = .04) between the LTI group and the control group and 0.18 points (95% CI, -0.25 to 0.61; P = .39) between the STI group and the control group. At 4 years, differences for the LTI and STI groups vs control were 0.12 points (LTI: 95% CI, -0.19 to 0.43; P = .42) and 0.13 points (STI: 95% CI, -0.17 to 0.44; P = .38). No adverse events were reported., Conclusions and Relevance: Overall, the tested school-based health promotion strategies in this randomized clinical trial had a neutral effect on the CVH of the adolescents. Although there was evidence of a marginal beneficial effect at a point halfway through implementation in the LTI group, such a benefit was not noted at 4 years. Further research is warranted into the efficacy of school-based health promotion programs., Trial Registration: ClinicalTrials.gov Identifier: NCT03504059.

Background: Several unhealthy lifestyle behaviors in adolescence are often linked to overweight/obesity. Some of them may be present simultaneously, leading to combined effects on health. Therefore, the clustering of several unhealthy behaviors in adolescents might be associated with adiposity excess., Purpose: To identify lifestyle patterns and analyze their association with adiposity in early adolescents., Methods: A cross-sectional cluster analysis was performed in 1183 adolescents (50.5% girls) with a mean age of 12.5 (0.4) years included in the SI! Program for Secondary Schools in Spain to identify lifestyle patterns based on healthy diet, step counts, sleep time, and leisure screen time. Generalized mixed models were applied to estimate the association between lifestyle patterns and adiposity indices., Results: Four lifestyle patterns were derived: Cluster 1-higher screen time and poorer diet (n = 213), Cluster 2-lower activity and longer sleepers (n = 388), Cluster 3-active and shorter sleepers (n = 280), and Cluster 4-healthiest (n = 302). Except for the number of steps (12,008 (2357) day), the lifestyle behaviors in our sample presented levels far below the recommendations, especially for sleep duration. Cluster 4 included the largest proportion of adolescents from high socioeconomic status families (47.7%) and the lowest prevalence of overweight/obesity (23.1%). Compared to Cluster 4-healthiest, adolescents in the remaining clusters presented a higher prevalence of overweight/obesity and central obesity, showing Cluster 3 the highest prevalences (PR:1.31 [95%CI: 1.31, 1.31] and PR:1.40 [95%CI: 1.33, 1.47])., Conclusions: Clustering of lifestyle patterns in early adolescence allows the identification of individuals with excess adiposity, in whom health promotion strategies should be stressed, especially in socioeconomically disadvantaged groups., Trial Registration: Clinical Trial Registry, NCT03504059. Registered 20/04/2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03504059 ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Chronic inflammation is associated with noncommunicable diseases, including obesity, metabolic syndrome (MetS), and CVDs. The Mediterranean diet has been shown to have strong anti-inflammatory effects, attributed in part to the polyphenol richness of many of its components., Objectives: This study aimed to assess the value of polyphenols as a urinary biomarker of an anti-inflammatory diet and their influence on MetS status., Methods: A longitudinal analysis was performed in Spain considering 543 participants with high CVD risk in a PREDIMED study. Approximately 52% of the participants were women and 48% were men with a mean age of 67.5 (5.9) y. Total polyphenol excretion (TPE) in urine was determined at baseline and 5 y of intervention using a validated Folin-Ciocalteu spectrophotometric method, and the dietary inflammatory index (DII) was calculated from a validated 137-item food-frequency questionnaire. Three categories were built according to tertiles of change in the DII score. Multivariable linear regression analyses were performed to assess the association of changes in TPE with changes in the DII scores and with MetS status at 5 y., Results: Tertiles 2 and 3 compared with tertile 1 presented a lower anti-inflammatory potential of the diet and were inversely associated with TPE in women [-0.30 mg gallic acid equivalent (GAE)/g creatinine; 95% CI: -0.46, -0.15; P value = 0.006 and -0.29 mg GAE/g creatinine; 95% CI: -0.43, -0.15; P value = 0.005], respectively. The mean changes in TPE were 7.9 (56.1) mg GAE/g creatinine in women and 7.7 (48.2) mg GAE/g creatinine in men. In addition, TPE was inversely associated with changes in MetS status [-0.06 (-0.09; -0.02), P value = 0.009] in both men and women., Conclusions: Urinary polyphenols may be a potential biomarker of anti-inflammatory diet consumption in women and are prospectively associated with improvement in MetS., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Scope: Excessive visceral adipose tissue (VAT) is associated with higher secretion of pro-inflammatory molecules, contributing to systemic inflammation and obesity-related metabolic disturbances., Methods and Results: This prospective analysis includes 117 overweight/obese adults (55-75 years) from the PREDIMED-Plus study. Fourteen inflammatory markers and adipokines are measured using a Bio-Plex assay with multiplex technology: insulin, glucagon, IL-6, visfatin, ghrelin, GLP-1, TNF-α, MCP-1, PAI-1, resistin, C-peptide, leptin, adipsin, and adiponectin. Participants are categorized into tertiles according to changes in VAT after 1-year of follow-up, determined by dual-energy X-Ray absorptiometry. Participants allocate in tertile 3, which represent an increase of VAT content after 1-year of follow-up compared to tertile 1, show significant differences in insulin (T3 vs T1, fully adjusted model: p = 0.037, p for trend 0.042), PAI-1 (fully adjusted model: p = 0.05, p for trend 0.06), c-peptide (fully adjusted model: p = 0.037, p for trend 0.042), and TNF-α (fully adjusted model p = 0.037, p for trend 0.042)., Conclusion: The results evidence that a reduction in VAT is associated with clinical improvements in several inflammatory and adiposity markers, mainly in insulin, c-peptide, and PAI-1 levels, and these improvements may contribute to a reduction in cardiometabolic disturbances observe in obesity., (© 2022 Wiley-VCH GmbH.)

Introduction: Osteoporosis is a chronic progressive bone disease characterized by low bone mineral density (BMD) and micro-architectural deterioration of bone tissue, leading to an increase in bone fragility and the risk of fractures. A well-known risk factor for bone loss is postmenopausal status. Beer may have a protective effect against osteoporosis associated with its content of silicon, polyphenols, iso-α-acids and ethanol, and its moderate consumption may therefore help to reduce bone loss in postmenopausal women., Methods: Accordingly, a 2-year controlled clinical intervention study was conducted to evaluate if a moderate daily intake of beer with (AB) or without alcohol (NAB) could have beneficial effects on bone tissue. A total of 31 postmenopausal women were assigned to three study groups: 15 were administered AB (330 mL/day) and six, NAB (660 mL/day), whereas, the 10 in the control group refrained from consuming alcohol, NAB, and hop-related products. At baseline and subsequent assessment visits, samples of plasma and urine were taken to analyze biochemical parameters, and data on medical history, diet, and exercise were collected. BMD and the trabecular bone score (TBS) were determined by dual-energy X-ray absorptiometry. Markers of bone formation (bone alkaline phosphatase [BAP] and N -propeptide of type I collagen [PINP]) and bone resorption ( N -telopeptide of type I collagen [NTX] and C-telopeptide of type I collagen [CTX]) were determined annually., Results: Bone formation markers had increased in the AB and NAB groups compared to the control after the 2-year intervention. However, the evolution of BMD and TBS did not differ among the three groups throughout the study period., Discussion: Therefore, according to the findings of this pilot study, moderate beer intake does not seem to have a protective effect against bone loss in early post-menopausal women., Competing Interests: Authors RL-R and AT-R had received funding from The European Foundation for Alcohol Research (ERAB). Author RL-R had received lecture fees and travel support from Cerveceros de España and Wine in Moderation. Author RE was a Board Membership of Cerveza y Salud, Madrid (Spain), Fundación para la Investigación del Vino y la Nutrición (FIVIN, Madrid, Spain), and Fundación Dieta Mediterránea, Barcelona (Spain) and had received lecture fees and travel support from Brewers of Europe, Brussels (Belgium). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Trius-Soler, Tresserra-Rimbau, Moreno, Peris, Estruch and Lamuela-Raventós.)

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

Nitric oxide (NO) is important to cardiovascular health (CVH), and its bioavailability could be regulated by the antioxidant effect of polyphenols, improving endothelial function and consequently blood pressure (BP). However, scant research has been carried out on NO and CVH correlates in adolescent populations. Therefore, our aim was to investigate the association between NO and the CVH status and other health factors in adolescents. NO, total polyphenol excretion (TPE), anthropometric measurements, BP, blood lipid profile, blood glucose, diet, physical activity, and smoking status were recorded, while CVH score was classified as ideal, intermediate, and poor. Negative associations were observed between NO and body mass index, body fat percentage, BP, and triglycerides; and positive associations between NO and skeletal muscle percentage, HDL-cholesterol, fruit and vegetable intake, and TPE was observed. To capture more complex interactions among different factors, multiple linear regression was performed, obtaining a significant association between NO and fruit and vegetable intake (β = 0.175), TPE (β = 0.225), and systolic BP (β = -0.235). We conclude that urinary NO levels are positively associated with the consumption of fruits and vegetables rich in antioxidants such as polyphenols and negatively associated with systolic BP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Desaturase enzyme activities (DEA) are associated with several metabolic diseases. The aim of the present study was to assess the relationship between estimated plasma DEA and the metabolic syndrome (MetS), as well as their relationship with individual components of the MetS. We conducted a longitudinal study of 148 participants recruited at random from the PREDIMED trial (Hospital Clinic site). At baseline and after 1 year of follow-up, DEA were estimated from product/precursor ratios of individual plasma fatty acids. Logistic regressions were used to assess the relationship of estimated DEA MetS, adjusted for potential cofounders. Estimated Δ5 desaturase (D5D) activity was associated with lower risk of MetS, whereas stearoyl-CoA (SCD)-16 and SCD-18 were negatively associated with MetS status. SCD-16, SCD-18, and Δ6 desaturase (D6D) were positively associated with triglycerides, SCD-18 was inversely associated with HDL-cholesterol. Estimated D6D activity was found to be associated with increases in diastolic blood pressure. In contrast, D5D was negatively associated with triglycerides, diastolic blood pressure and waist circumference. The present longitudinal study suggests that estimated SCD-16, SCD-18, and D6D have a negative impact in MetS and its components, whereas D5D may have beneficial effects for metabolic health., Competing Interests: Author ER reports grants, personal fees, non-financial and other from the California Walnut Commission while the study was carried out; grants, personal fees, non-financial support and other from Alexion; and personal fees and other from Amarin, outside the submitted work. Author RL-R reports personal fees from Cerveceros de España, personal fees and other from Adventia, Wine in Moderation, Ecoveritas S.A., outside the submitted work. Author RE reports grants from the Fundación Dieta Mediterránea (Spain), and Cerveza y Salud (Spain), and personal fees for given lectures from Brewers of Europe (Belgium), the Fundación Cerveza y Salud (Spain), Pernaud-Ricard (Mexico), Instituto Cervantes (Alburquerque, United States), Instituto Cervantes (Milan, Italy), Instituto Cervantes (Tokyo, Japan), Lilly Laboratories (Spain), and the Wine and Culinary International Forum (Spain), as well as non-financial support for the organization of a National Congress on Nutrition and feeding trials with products from Grand Fountain and Uriach Laboratories (Spain). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Domínguez-López, Arancibia-Riveros, Tresserra-Rimbau, Castro-Barquero, Casas, Vázquez-Ruiz, Ros, Fitó, Estruch, López-Sabater and Lamuela-Raventós.)

Background Dietary polyphenol intake has been associated with a decreased risk of hyperuricemia, but most of this knowledge comes from preclinical studies. The aim of the present study was to assess the association of the intake of different classes of polyphenols with serum uric acid and hyperuricemia. Methods and Results This cross-sectional analysis involved baseline data of 6332 participants. Food polyphenol content was estimated by a validated semiquantitative food frequency questionnaire and from the Phenol-Explorer database. Multivariable-adjusted linear regression models with serum uric acid (milligrams per deciliter) as the outcome and polyphenol intake (quintiles) as the main independent variable were fitted. Cox regression models with constant follow-up time (t=1) were performed to estimate the prevalence ratios (PRs) of hyperuricemia (≥7 mg/dL in men and ≥6 mg/dL in women). An inverse association between the intake of the phenolic acid class (β coefficient, -0.17 mg/dL for quintile 5 versus quintile 1 [95% CI, -0.27 to -0.06]) and hydroxycinnamic acids (β coefficient, -0.19 [95% CI, -0.3 to -0.09]), alkylmethoxyphenols (β coefficient, -0.2 [95% CI, -0.31 to -0.1]), and methoxyphenols (β coefficient, -0.24 [95% CI, -0.34 to -0.13]) subclasses with serum uric acid levels and hyperuricemia (PR, 0.82 [95% CI, 0.71-0.95]; PR, 0.82 [95% CI, 0.71-0.95]; PR, 0.80 [95% CI, 0.70-0.92]; and PR, 0.79 [95% CI, 0.69-0.91]; respectively) was found. The intake of hydroxybenzoic acids was directly and significantly associated with mean serum uric acid levels (β coefficient, 0.14 for quintile 5 versus quintile 1 [95% CI, 0.02-0.26]) but not with hyperuricemia. Conclusions In individuals with metabolic syndrome, a higher intake of some polyphenol subclasses (hydroxycinnamic acids, alkylmethoxyphenol, and methoxyphenol) was inversely associated with serum uric acid levels and hyperuricemia. Nevertheless, our findings warrant further research.

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [-2.79 mg/dl (95% CI: -4.25, -1.34) and -5.15 mg/dl (95% CI: -7.38, -2.93), p -values = 0.0002 and <0.00001 in women and men, respectively], lower levels of plasma saturated fatty acids [-0.09% (95% CI: -0.14, -0.03) and -0.15 % (95% CI: -0.23, -0.08), p -values = 0.001 and 0.0001 in women and men, respectively], and higher levels of plasma polyunsaturated fatty acids [(0.12 % (95% CI: -0.01, 0.25) and 0.39 % (95% CI: 0.19, 0.59), p -values = 0.065 and 0.0001 in women and men, respectively] in the whole population. Plasma carotenoid concentrations were also associated with higher plasma HDL-cholesterol in women [0.47 mg/dl (95% CI: 0.23, 0.72), p -value: 0.0002], and lower fasting plasma glucose in men [-1.35 mg/dl (95% CI: -2.12, -0.59), p -value: 0.001]., Competing Interests: JS-S reported receiving research support from the Instituto de Salud Carlos III, Ministerio de Educación y Ciencia, Departament de Salut Pública de la Generalitat de Catalunya, the European Commission, the USA National Institutes of Health; receiving consulting fees or travel expenses from Eroski Foundation, Instituto Danone, Mundipharma, receiving non-financial support from Hojiblanca, Patrimonio Comunal Olivarero, the Almond Board of California, Pistachio Growers and Borges S.A.; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and personal fees from Instituto Danone; Serving in the Scientific Board of Danone Institute International. DC reported receiving grants from Instituto de Salud Carlos III. RE reported receiving grants from Instituto de Salud Carlos III, Fundación Dieta Mediterránea and Cerveza y Salud and olive oil for the trial from Fundación Patrimonio Comunal Olivarero and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes in Albuquerque, Milano and Tokyo, Pernod Ricard, Fundación Dieta Mediterránea (Spain), Wine and Culinary International Forum and Lilly Laboratories; non-financial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories. ER reports grants, personal fees, non-financial support, and other from California Walnut Commission, during the conduct of the study; grants, personal fees, non-financial support, and other from Alexion; personal fees and other from Amarin, outside the submitted work. RL-R reports personal fees from Cerveceros de España, personal fees and other from Adventia, other from Ecoveritas, S.A., outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marhuenda-Muñoz, Domínguez-López, Langohr, Tresserra-Rimbau, Martínez González, Salas-Salvadó, Corella, Zomeño, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Delgado-Rodríguez, Matía-Martín, Vidal, Vázquez, Daimiel, Ros, Toledo, Fernández de la Puente Cervera, Barragán, Fitó, Tojal-Sierra, Gómez-Gracia, Zazo, Morey, García-Ríos, Casas, Gómez-Pérez, Santos-Lozano, Vázquez-Ruiz, Atzeni, Asensio, Gili-Riu, Bullon, Moreno-Rodriguez, Lecea, Babio, Peñas Lopez, Gómez Melis and Lamuela-Raventós.)

Background: Cocoa-based products are a good source of flavonoids, which may have beneficial effects on metabolic health., Objective: The aim of this study is to assess the relationship between flavonoids from cocoa-based products and adiposity parameters in adolescents., Methods: A cross-sectional study was conducted involving 944 adolescents aged 11-14 years enrolled in the SI! Program for Secondary Schools trial in Spain with available baseline data from food frequency questionnaires and anthropometric measurements [weight, height, waist circumference (WC), and fat mass percentage (% FM) by bioimpedance analysis]. Fat mass index (FMI) and waist-to-height ratio (WHtR) were obtained by dividing fat mass by height and WC by height, respectively. Body mass index (BMI), WC, and FMI for age and gender z-score were calculated. Overweight/obesity was defined as BMI ≥ 85th percentile and excess adiposity as %FM or FMI ≥ 75th percentile. WC ≥ 90th percentile and WHtR with a 0.5 threshold were considered as criteria of abdominal obesity. Multilevel mixed-effect regressions were used to evaluate the association between flavonoids from cocoa-based products and adiposity parameters. Municipalities and schools were considered random effects., Results: Participants with a higher flavonoid intake from cocoa-based products had lower WC z-score [B = -0.04, 95% CI (-0.07; -0.01), P-for trend = 0.045] and WHtR [B = -0.01, 95% CI (-0.02; -0.01), P- for trend < 0.001]. They also had lower probability of having abdominal obesity [OR 0.66, 95% CI (0.52; 0.85), P- for trend = 0.001]. Inverse associations were observed between flavonoids from cocoa powder and BMI z-score [B = -0.08, 95% CI (-0.12; -0.05), P < 0.001], WC z-score [B = -0.06, 95% CI (-0.11; -0.02), P = 0.003], WHtR [B = -0.01, 95% CI (-0.01; -0.00), P < 0.001], %FM [B = -1.11, 95% CI (-1.48; -0.75), P < 0.001], and FMI z-score [B = -0.18, 95% CI (-0.20; -0.17), P < 0.001]. Regarding dark chocolate, an inverse association only with WC z-score [B = -0.06, 95% CI (-0.08; -0.05), P < 0.001] was found. However, no association was observed between flavonoids from milk chocolate intake and anthropometric parameters., Conclusions: A higher intake of flavonoids from cocoa-based products was associated with lower adiposity parameters and a lower probability of presenting abdominal obesity., Competing Interests: RL-R reports receiving lecture fees from Cerveceros de España and receiving lecture fees and travel support from Adventia and Idilia Foods SL. RE reports grants from Fundación Dieta Mediterránea, Spain, Cerveza y Salud, Spain, personal fees for given lectures from Brewers of Europe, Belgium, Fundación Cerveza y Salud, Spain, Pernaud-Ricard, Mexico, Instituto Cervantes, Alburquerque, USA, Instituto Cervantes, Milan, Italy, Instituto Cervantes, Tokyo, Japan, Lilly Laboratories, Spain, Wine and Culinary International Forum, Spain, non-financial support to organize a National Congress on Nutrition, and also feeding trials with products from Grand Fountain and Uriach Laboratories, Spain. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Laveriano-Santos, Arancibia-Riveros, Tresserra-Rimbau, Castro-Barquero, Ruiz-León, Estruch, Casas, Bodega, de Miguel, de Cos-Gandoy, Martínez-Gómez, Rodríguez, Santos-Beneit, Fernández-Alvira, Fernández-Jiménez and Lamuela-Raventós.)

This study aimed to develop and validate a liquid chromatography/electrospray ionization-linear ion trap quadrupole-Orbitrap-high-resolution mass spectrometry (HPLC/ESI-LTQ-Orbitrap-HRMS) method to identify and quantify urinary microbial phenolic metabolites (MPM), as well as to explore the relationship between MPM and dietary (poly)phenols in Spanish adolescents. A total of 601 spot urine samples of adolescents aged 12.02 ± 0.41 years were analyzed. The quantitative method was validated for linearity, limit of detection, limit of quantification, recovery, intra- and inter-day accuracy and precision, as well as postpreparative stability according to the criteria established by the Association of Official Agricultural Chemists International. A total of 17 aglycones and 37 phase II MPM were identified and quantified in 601 spot urine samples. Phenolic acids were the most abundant urinary MPM, whereas stilbenes, hydroxytyrosol, and enterodiol were the least abundant. Urinary hydroxycoumarin acids (urolithins) were positively correlated with flavonoid and total (poly)phenol intake. An HPLC-ESI-LTQ-Orbitrap-HRMS method was developed and fully validated to quantify MPM. The new method was performed accurately and is suitable for MPM quantification in large epidemiological studies. Urinary lignans and urolithins are proposed as potential biomarkers of grain and nut intake in an adolescent population.

Introduction and Objectives: Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores., Methods: This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire, adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses., Results: Total polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale., Conclusions: An inverse association was found between consumption of the 'other polyphenols' class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Nutrition education resources are of interest for cancer patients and survivors throughout the cancer continuum. We examined the web-based nutrition information in Spanish for cancer patients and survivors provided by national cancer organizations (NCOs). The Guide to Internet Resources for Cancer and the membership list of the Union for International Cancer Control were searched to identify the NCOs. The International Patients Decisions Aid Standards (IPDAS) was used to describe the quality of the available information. We identified 20 NCOs that provided nutrition information aimed at a general audience on their websites. Web-based resources of nine NCOs were selected for presentation in this review. Website scores ranged between 20 and 24 in the IPDAS scale (maximum score = 31). The selected NCOs offered reliable and safe information. Healthy eating information for cancer patients and management of side-effects was provided by all websites. Information was more limited for cancer survivors. We recommend that NCOs increase the possibilities for personalized recommendations and interaction with the content by including instrumental tools on their websites.

Scope: Plasma fatty acids (FAs) are associated with the development of cardiovascular diseases and metabolic syndrome. The aim of our study is to assess the relationship between fruit and vegetable (F&V) consumption and plasma FAs and their subtypes., Methods and Results: Plasma FAs are assessed in a cross-sectional analysis of a subsample of 240 subjects from the PREDIMED-Plus study. Participants are categorized into four groups of fruit, vegetable, and fat intake according to the food frequency questionnaire. Plasma FA analysis is performed using gas chromatography. Associations between FAs and F&V consumption are adjusted for age, sex, physical activity, body mass index (BMI), total energy intake, and alcohol consumption. Plasma saturated FAs are lower in groups with high F&V consumption (-1.20 mg cL -1 [95% CI: [-2.22, -0.18], p-value = 0.021), especially when fat intake is high (-1.74 mg cL -1 [95% CI: [-3.41, -0.06], p-value = 0.042). Total FAs and n-6 polyunsaturated FAs tend to be lower in high consumers of F&V only in the high-fat intake groups., Conclusions: F&V consumption is associated with lower plasma saturated FAs when fat intake is high. These findings suggest that F&V consumption may have different associations with plasma FAs depending on their subtype and on the extent of fat intake., (© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Background and Aims: Total fruit consumption is important for cardiovascular disease prevention, but also the variety and form in which is consumed. The aim of the study was to assess the associations between total fruit, subgroups of fruits based on their color and fruit juices consumption with different cardiometabolic parameters., Methods and Results: A total of 6633 elderly participants (aged 55-75 years) with metabolic syndrome from the PREDIMED-Plus study were included in this analysis. Fruit and fruit juice consumption was assessed using a food frequency questionnaire. Linear regression models were fitted to evaluate the association between exposure variables (total fruit, subgroups based on the color, and fruit juices) and different cardiometabolic risk factors. Individuals in the highest category of total fruit consumption (≥3 servings/d) had lower waist circumference (WC) (β = -1.04 cm; 95%CI:-1.81, -0.26), fasting glucose levels (β = -2.41 mg/dL; 95%CI(-4.19, -0.63) and LDL-cholesterol (β = -4.11 mg/dL; 95%CI:-6.93, -1.36), but, unexpectedly, higher systolic blood pressure (BP) (β = 1.84 mmHg; 95%CI: 0.37, 3.30) and diastolic BP (β = 1.69 mmHg; 95%CI:0.83, 2.56) when compared to those in the lowest category of consumption (<1 servings/d). Participants consuming ≥1 serving/day of total fruit juice had lower WC (β = -0.92 cm; 95%CI:-1.56, -0.27) and glucose levels (β = -1.59 mg/dL; 95%CI:-2.95, -0.23) than those consuming <1 serving/month. The associations with cardiometabolic risk factors differed according to the color of fruits., Conclusion: Fruit consumption is associated with several cardiometabolic risk factors in Mediterranean elders with metabolic syndrome. The associations regarding BP levels could be attributed, at least partially, to reverse causality bias inherent to the cross-sectional design of the study., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest related to this article., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Carotenoids are naturally occurring pigments of autotroph organisms that have been related to many health benefits and this is not only because some of them are precursors of vitamin A. Individual or whole carotenoid consumption has been associated with a lower risk of developing cancer, cardiovascular and metabolic diseases among others. However, the blood levels of carotenoids vary largely from person to person due to different factors. Diet is the most important one because of the dietary patterns that different populations follow, the time of the year of consumption or the personal preferences. Nevertheless, the intrinsic host factors such as the absorption, distribution, metabolism and excretion genetic polymorphisms, the volume of distribution and the person's microbiota and others such as carotenoid interactions are also inducing this so called inter-individual variability. Besides, culinary methods and processing produce changes in the foods that directly affect carotenoid content and hence their blood profile. Different types of studies have been performed to understand the between-subject variation of the carotenoid profile in human plasma. This research is focused on this matter as levels of carotenoids in human plasma could be useful for the prediction of some diseases. The Mediterranean diet is probably the most carotenoid rich diet stemming from its high proportion of fruits and vegetables. Its differences with other diets and the effect on the carotenoid blood profile of the consumers are currently a very interesting topic of study.

The objective of this study was to evaluate the prospective associations between dietary glycemic index (GI) and glycemic load (GL) and the risk for invasive breast cancer incidence in postmenopausal women at high cardiovascular disease (CVD) risk. This study was conducted within the framework of the PREvención con DIeta MEDiterránea (PREDIMED) study, a nutritional intervention trial for primary cardiovascular prevention. We included 4010 women aged between 60 and 80 years who were initially free from breast cancer but at high risk for CVD disease. Dietary information was collected using a validated 137-item food frequency questionnaire. We assigned GI values using the International Tables of GI and GL values. Cases were ascertained through yearly consultation of medical records and through consultation of the National Death Index. Only cases confirmed by results from cytology tests or histological evaluation were included. We estimated multivariable-adjusted hazard ratios for invasive breast cancer risk across tertiles of energy-adjusted dietary GI/GL using Cox regression models. We repeated our analyses using yearly repeated measures of GI/GL intakes. No associations were found between baseline dietary GI/GL and invasive breast cancer incidence. The multivariable hazard ratio and 95% confidence interval (CI) for the top tertile of dietary GI was 1.02 (95% CI: 0.42-2.46) and for dietary GL was 1.00 (95% CI: 0.44-2.30) when compared with the bottom tertile. Repeated-measures analyses yielded similar results. In sensitivity analyses, no significant associations were observed for women with obesity or diabetes. Dietary GI and GL did not appear to be associated with an increased risk for invasive breast cancer in postmenopausal women at high CVD risk.

Several observational and intervention studies have found an inverse association between the risk of cardiovascular disease and the consumption of polyphenol-rich foods and beverages such as cocoa, fruit and vegetables, tea, virgin olive oil and wine. We present here an overview of the latest research on the beneficial effect of dietary polyphenols on blood pressure, focusing on the development of urine biomarkers for an accurate estimation of polyphenol intake. Total polyphenols (TP) excreted in spot urine samples have been successfully used as a biomarker of the consumption, bioavailability and accumulation of TP in a cross-sectional clinical trial. In addition, we describe how the vasoprotective effect of dietary polyphenols has been related to their ability to increase endothelial synthesis of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)-mediated responses.