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Background: Choline and betaine intakes have been related to cardiovascular health. Objectives: We aimed to explore the relation between 1-y changes in dietary intake of choline or betaine and 1-y changes in cardiometabolic and renal function traits within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial. Methods: We used baseline and 1-y follow-up data from 5613 participants (48.2% female and 51.8% male; mean ± SD age: 65.01 ± 4.91 y) to assess cardiometabolic traits, and 3367 participants to assess renal function, of the Spanish PREDIMEDPlus trial. Participants met ≥3 criteria of metabolic syndrome and had overweight or obesity [BMI (in kg/m2) ≥27 and ≤40]. These criteria were similar to those of the PREDIMED parent study. Dietary intakes of choline and betaine were estimated from the FFQ. Results: The greatest 1-y increase in dietary choline or betaine intake (quartile 4) was associated with improved serum glucose concentrations (−3.39 and −2.72 mg/dL for choline and betaine, respectively) and HbA1c levels (−0.10% for quartile 4 of either choline or betaine intake increase). Other significant changes associated with the greatest increase in choline or betaine intake were reduced body weight (−2.93 and −2.78 kg, respectively), BMI (−1.05 and −0.99, respectively), waist circumference (−3.37 and −3.26 cm, respectively), total cholesterol (−4.74 and −4.52 mg/dL, respectively), and LDL cholesterol (−4.30 and −4.16 mg/dL, respectively). Urine creatinine was reduced in quartile 4 of 1-y increase in choline or betaine intake (−5.42 and −5.74 mg/dL, respectively). Conclusions: Increases in dietary choline or betaine intakes were longitudinally related to improvements in cardiometabolic parameters. Markers of renal function were also slightly improved, and they require further investigation. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870. Am J Clin Nutr 2022;116:1565–1579., Ministerio de Ciencia e Innovacion through Proyectos de I+D+i "Retos Investigacion" RTI2018-095569-B-I00 Ministerio de Ciencia e Innovacion through Programacion Conjunta Internacional PCI2018-093009, European Research Council (ERC) European Commission 20142019 340918, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728 PI14/01471 PI16/00473, A Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441, The Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158, Especial Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus", Recercaixa grant 2013ACUP00194, ICREA (Catalan Institution for Research and Advanced Studies) under the ICREA Academia program SEMERGEN grant, Government of Navarra Department of Health 61/2015, Fundacio La Marato de TV3 grant 201630.10, AstraZeneca T2D 2017, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Center for Forestry Research & Experimentation (CIEF), European Commission PROMETEO/2017/017, Balearic Islands Government 35/2011, Spanish Ministerio de Ciencia e Innovacion y Ministerio de Universidades Spanish State Research Agency Juan de la Cierva Program FJC2018-038168-I

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.

Non-alcoholic fatty liver disease (NAFLD) shows liver fat depots without alcohol consumption. NAFLD does not have specific drug therapies, with a healthy lifestyle and weight loss being the main approaches to prevent and treat NAFLD. The aim was to assess the antioxidant and pro-inflammatory state in patients with NAFLD after 12-month-lifestyle intervention depending on the change in adherence to a Mediterranean diet (AMD). Antioxidant and inflammatory biomarkers were measured in 67 adults (aged 40–60 years old) diagnosed with NAFLD. Anthropometric parameters and dietary intake were measured by a validated semi-quantitative 143-item food frequency questionnaire. The nutritional intervention improved anthropometric and biochemical parameters after a 12-month follow-up. However, decreases in alanine aminotransferase (ALT) and C reactive protein (CRP) were higher in participants with high AMD, which also showed higher improvement in physical fitness (Chester step test) and intrahepatic fat contents. The intervention reduced plasma levels of malondialdehyde, myeloperoxidase, zonulin, and omentin, and increased resolvin D1 (RvD1), whereas the decrease in leptin, ectodysplasin-A (EDA), cytokeratin-18 (CK-18), interleukin-1ra (IL-1ra) and endotoxin was only significant in participants with higher AMD. The current study showed that a one-year nutritional intervention improved main NAFLD features such as body mass index, IFC, liver enzymes, and prooxidant and proinflammatory status. There was also a decrease in the concentration of plasmatic endotoxin, suggesting an improvement in intestinal permeability. These health benefits were more evident in participants that improved AMD to a greater extent. The trial was registered at ClinicalTrials.gov with registry number NCT04442620.

Introduction: Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies, usually with exposure assessment limited to baseline values. As BMI is a proxy for adiposity but does not capture fat tissue or its metabolically relevant distribution, precise measurements of distinct adipose tissues are needed, so the cardiometabolic impact of an anti-obesity effect can be assessed. Hypothesis: We assessed the hypothesis that an increase in coffee consumption is associated with a reduction in body fat, in particular with trunk fat and visceral adipose tissue (VAT). Methods: In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome. Changes in the consumption of caffeinated and decaffeinated coffee were derived from validated food frequency questionnaires at baseline, 6 months and yearly during follow-up. Fat tissue was measured with dual x-ray absorptiometry at baseline and after 6, 12 months and three years. Linear multilevel mixed effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue over three years. Results: After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤ 3 cups/ month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95 % CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95 % CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95 % CI: -0.13 to -0.01). However, changes to even higher levels (> 1 cup/day) showed no significant association. Conclusions: Moderate consumption of caffeinated coffee, but not high consumption, was associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with metabolic syndrome. Decaffeinated coffee was not linked to adiposity indicators. In conclusion, moderate consumption of caffeinated coffee may be part of a weight management strategy.

Background: Observed associations of high-protein diets with changes in insulin resistance are inconclusive.Objectives: We aimed to assess associations of changes in both reported and estimated protein (PRep; PEst) and energy intake (EIRep; EIEst) with changes in HOMA-IR, glycated hemoglobin (HbA1c), and BMI (in kg/m2), in 1822 decreasing to 833 adults (week 156) with overweight and prediabetes, during the 3-y PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study on weight-loss maintenance. Eating behavior and measurement errors (MEs) of dietary intake were assessed. Thus, observational post hoc analyses were applied.Methods: Associations of changes in EIEst, EIRep, PEst, and PRep with changes in HOMA-IR, HbA1c, and BMI were determined by linear mixed-model analysis in 2 arms [high-protein-low-glycemic-index (GI) diet and moderate-protein-moderate-GI diet] of the PREVIEW study. EIEst was derived from energy requirement: total energy expenditure = basal metabolic rate × physical activity level; PEst from urinary nitrogen, and urea. MEs were calculated as [(EIEst - EIRep)/EIEst] × 100% and [(PRep - PEst)/PEst] × 100%. Eating behavior was determined using the Three Factor Eating Questionnaire, examining cognitive dietary restraint, disinhibition, and hunger.Results: Increases in PEst and PRep and decreases in EIEst and EIRep were associated with decreases in BMI, but not independently with decreases in HOMA-IR. Increases in PEst and PRep were associated with decreases in HbA1c. PRep and EIRep showed larger changes and stronger associations than PEst and EIEst. Mean ± SD MEs of EIRep and PRep were 38% ± 9% and 14% ± 4%, respectively; ME changes in EIRep and En% PRep were positively associated with changes in BMI and cognitive dietary restraint and inversely with disinhibition and hunger.Conclusions: During weight-loss maintenance in adults with prediabetes, increase in protein intake and decrease in energy intake were not associated with decrease in HOMA-IR beyond associations with decrease in BMI. Increases in PEst and PRep were associated with decrease in HbA1c.This trial was registered at clinicaltrials.gov as NCT01777893.

Background Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment. Aim To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO2 emitted in an older adult population. Design and population Using a cross-sectional design, the association between the adherence to an energyreduced Mediterranean Diet (erMedDiet) score and dietary CO2 emissions in 6646 participants was assessed. Methods Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO2 emissions expressed in kg/day: Q1 (≤2.01 kg CO2), Q2 (2.02-2.34 kg CO2), Q3 (2.35-2.79 kg CO2) and Q4 (≥2.80 kg CO2). Results More men than women induced higher dietary levels of CO2 emissions. Participants reporting higher consumption of vegetables, fruits, legumes, nuts, whole cereals, preferring white meat, and having less consumption of red meat were mostly emitting less kg of CO2 through diet. Participants with higher adherence to the Mediterranean Diet showed lower odds for dietary CO2 emissions: Q2 (OR 0.87; 95%CI: 0.76-1.00), Q3 (OR 0.69; 95%CI: 0.69-0.79) and Q4 (OR 0.48; 95%CI: 0.42-0.55) vs Q1 (reference). Conclusions The Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO2 emissions. Mediterranean Diet index may be used as a pollution level index., official Spanish Institutions, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), European Commission PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI19/01226 PI19/00781 PI19/01560 Especial Action Project European Research Council (ERC) European Commission 340918, La Caixa Foundation 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Center for Forestry Research & Experimentation (CIEF), European Commission PROMETEO/2017/017, SEMERGEN grant, ICREA under the ICREA Academia programme, Canadian Institutes of Health Research (CIHR) MFE171207 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158 PI16/01873 PI16/01094 PI16/00501 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728 PI14/01471 PI16/00473 PI16/00662 PI19/01332 PI20/01802 PI20/00138

Project SWEET examined the barriers and facilitators to the use of non-nutritive sweeteners and sweetness enhancers (hereafter "S&SE") alongside potential risks/benefits for health and sustainability. The Beverages trial was a double-blind multi-centre, randomised crossover trial within SWEET evaluating the acute impact of three S&SE blends (plant-based and alternatives) vs. a sucrose control on glycaemic response, food intake, appetite sensations and safety after a carbohydrate-rich breakfast meal. The blends were: mogroside V and stevia RebM; stevia RebA and thaumatin; and sucralose and acesulfame-potassium (ace-K). At each 4 h visit, 60 healthy volunteers (53% male; all with overweight/obesity) consumed a 330 mL beverage with either an S&SE blend (0 kJ) or 8% sucrose (26 g, 442 kJ), shortly followed by a standardised breakfast (∼2600 or 1800 kJ with 77 or 51 g carbohydrates, depending on sex). All blends reduced the 2-h incremental area-under-the-curve (iAUC) for blood insulin (p 0.05 for all). Compared with sucrose, there was a 3% increase in LDL-cholesterol after stevia RebA-thaumatin (p

Excessive visceral adipose tissue (VAT) is associated with higher secretion of pro-inflammatory molecules, contributing to systemic inflammation and obesity-related metabolic disturbances.This prospective analysis includes 117 overweight/obese adults (55-75 years) from the PREDIMED-Plus study. Fourteen inflammatory markers and adipokines were 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 were categorized into tertiles according to changes in VAT after 1-year of follow-up, determined by dual-energy X-Ray absorptiometry. Participants allocated in tertile 3, which represent an increase of VAT content after 1-year of follow-up compared to tertile 1, showed significant differences in insulin (T3 versus 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).Our results evidenced that a reduction in VAT was 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 observed in obesity. This article is protected by copyright. All rights reserved.

Neck circumference (NC), neck circumference to height ratio (NHtR) and neck circumference to weight ratio (NWtR) appear to be good candidates for the non-invasive management of non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the ability of routine variables to assess and manage NAFLD in participants with obesity and NAFLD included in a 2-year nutritional intervention program. Anthropometric measurements, biochemical variables and imaging techniques were performed at different study time-points (baseline, 6, 12 and 24 months). The nutritional intervention significantly improved all anthropometric measurements as well as the glucose profile and the hepatic enzymes. NC and neck ratios combined with ALT levels and HOMA-IR showed good prediction ability for the hepatic fat content and hepatic steatosis at all the study time-points in a ROC analysis. The prediction ability of the combination panels improved when the weight loss variable was also considered. NC and neck ratios are easy anthropometric measurements that in combination with routine biochemical variables (ALT and HOMA-IR) showed good prediction ability of NAFLD. More research studies are necessary to validate the utility of these simple and easy variables as surrogate markers of NAFLD since their application could improve the prevention and management of this prevalent disease.

Purpose To assess the association between a score appraising adherence to the PaleoDiet and the risk of cardiovascular disease (CVD) in a Mediterranean cohort. Methods We included 18,210 participants from the Seguimiento Universidad de Navarra (SUN) cohort study. The PaleoDiet score comprised six food groups promoted within this diet (fruit, nuts, vegetables, eggs, meat and fish) and five food groups whose consumption is discouraged (cereals and grains, dairy products, legumes, culinary ingredients, and processed/ultra-processed foods). CVD was defined as acute myocardial infarction with or without ST elevation, non-fatal stroke and cardiovascular death. Cox proportional hazards models adjusted for potential confounders were fitted to assess the association between the PaleoDiet score and CVD risk, and the PaleoDiet and MedDiet indices to explore differences between both diets. Results During 12.2 years of follow-up, 165 incident CVD cases were confirmed. A significant inverse association was found between the PaleoDiet score and CVD (HR Q5 vs. Q1: 0.45, 95% CI 0.27–0.76, P for trend = 0.007). A weaker association that became non-significant was observed when the item for low consumption of ultra-processed foods was removed from the score. Joint analysis of PaleoDiet and MedDiet Trichopoulou scores suggested that the inverse association between PaleoDiet and CVD was mainly present when adherence to the MedDiet was also high (HR for high adherence vs low adherence to both diet scores: 0.22, 95% CI 0.08–0.64). Conclusions Our findings suggest that the PaleoDiet may have cardiovascular benefits in participants from a Mediterranean country. Avoidance of ultra-processed foods seems to play a key role in this inverse association.

Significance: In recent years, a number of studies have shown altered oxygen partial pressure at a tissue level in metabolic disorders, and some researchers have considered oxygen to be a (macro) nutrient. Oxygen availability may be compromised in obesity and several other metabolism-related pathological conditions, including sleep apnea-hypopnea syndrome, the metabolic syndrome (which is a set of conditions), type 2 diabetes, cardiovascular disease, and cancer. Recent Advances: Strategies designed to reduce adiposity and its accompanying disorders have been mainly centered on nutritional interventions and physical activity programs. However, novel therapies are needed since these approaches have not been sufficient to counteract the worldwide increasing rates of metabolic disorders. In this regard, intermittent hypoxia training and hyperoxia could be potential treatments through oxygen-related adaptations. Moreover, living at a high altitude may have a protective effect against the development of abnormal metabolic conditions. In addition, oxygen delivery systems may be of therapeutic value for supplying the tissue-specific oxygen requirements. Critical Issues: Precise in vivo methods to measure oxygenation are vital to disentangle some of the controversies related to this research area. Further, it is evident that there is a growing need for novel in vitro models to study the potential pathways involved in metabolic dysfunction to find appropriate therapeutic targets. Future Directions: Based on the existing evidence, it is suggested that oxygen availability has a key role in obesity and its related comorbidities. Oxygen should be considered in relation to potential therapeutic strategies in the treatment and prevention of metabolic disorders. Antioxid. Redox Signal. 35, 642-687.

Introduction: Carbohydrate intake and physical activity are related to glucose homeostasis, both being influenced by individual genetic makeup. However, the interactions between these 2 factors, as affected by genetics, on glycaemia have been scarcely reported. Objective: We focused on analysing the interplay between carbohydrate intake and physical activity levels on blood glucose, taking into account a genetic risk score (GRS), based on SNPs related to glucose/energy metabolism. Methods: A total of 1,271 individuals from the Food4Me cohort, who completed the nutritional intervention, were evaluated at baseline. We collected dietary information by using an online-validated food frequency questionnaire, a questionnaire on physical activity, blood biochemistry by analysis of dried blood spots, and by analysis of selected SNPs. Fifteen out of 31 SNPs, with recognized participation in carbohydrate/energy metabolism, were included in the component analyses. The GRS included risk alleles involved in the control of glycaemia or energy-yielding processes. Results: Data concerning anthropometric, clinical, metabolic, dietary intake, physical activity, and genetics related to blood glucose levels showed expected trends in European individuals of comparable sex and age, being categorized by lifestyle, BMI, and energy/carbohydrate intakes, in this Food4Me population. Blood glucose was inversely associated with physical activity level (β = −0.041, p = 0.013) and positively correlated with the GRS values (β = 0.015, p = 0.047). Interestingly, an interaction affecting glycaemia, concerning physical activity level with carbohydrate intake, was found (β = −0.060, p = 0.033), which also significantly depended on the genetic background (GRS). Conclusions: The relationships of carbohydrate intake and physical activity are important in understanding glucose homeostasis, where a role for the genetic background should be ascribed.

Neck circumference (NC) and its relationship to height (NHtR) and weight (NWtR) appear to be good candidates for the non-invasive management of non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the ability of routine variables to assess and manage NAFLD in 98 obese subjects with NAFLD included in a 2-year nutritional intervention program. Different measurements were performed at baseline, 6, 12 and 24 months. The nutritional intervention significantly improved the anthropometric, metabolic and imaging variables. NC was significantly associated with the steatosis degree at baseline (r = 0.29), 6 m (r = 0.22), 12 m (r = 0.25), and 24 m (r = 0.39) (all p < 0.05). NC was also significantly associated with visceral adipose tissue at all the study time-points (basal r = 0.78; 6 m r = 0.65; 12 m r = 0.71; 24 m r = 0.77; all p < 0.05). NC and neck ratios combined with ALT levels and HOMA-IR showed a good prediction ability for hepatic fat content and hepatic steatosis (at all time-points) in a ROC analysis. The model improved when weight loss was included in the panel (NC-ROC: 0.982 for steatosis degree). NC and ratios combined with ALT and HOMA-IR showed a good prediction ability for hepatic fat during the intervention. Thus, their application in clinical practice could improve the prevention and management of NAFLD.

Background: Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of liver alterations that can result in severe disease and even death. Consumption of ultra-processed foods (UPF) has been associated with obesity and related comorbidities. However, the link between UPF and NAFLD has not been sufficiently assessed. We aimed to investigate the prospective association between UPF consumption and liver health biomarkers. Methods: We followed for 1 year 5867 older participants with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus trial. A validated 143-item semi-quantitative food frequency questionnaire was used to evaluate consumption of UPF at baseline, 6, and 12 months. The degree of processing for foods and beverages (g/day) was established according to the NOVA classification system. The non-invasive fatty liver index (FLI) and hepatic steatosis index (HSI) were used to evaluate liver health at three points in time. The associations between changes in UPF consumption (percentage of total daily dietary intake (g)) and liver biomarkers were assessed using mixed-effects linear models with repeated measurements. Results: In this cohort, UPF consumption at baseline was 8.19% (SD 6.95%) of total daily dietary intake in grams. In multivariable models, each 10% daily increment in UPF consumption in 1 year was associated with significantly greater FLI ( 1.60 points, 95% CI 1.24;1.96 points) and HSI (0.43, 0.29; 0.57) scores (all p-values < 0.001). These associations persisted statistically significant after adjusting for potential dietary confounders and NAFLD risk factors. Conclusions: A higher UPF consumption was associated with higher levels of NAFLD-related biomarkers in older adults with overweight/obesity and MetS., European Research Council (ERC) European Commission 340918, Spanish National Health Institute of Health Carlos III (ISCIII), through CIBEROBN, European Commission PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206, Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, La Caixa Foundation 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018 RH-0024-2021, Center for Forestry Research & Experimentation (CIEF), European Commission PROMETEO/2017/017, SEMERGEN grant, Spanish Government IJC2019-042420-I, European Social Fund (ESF), Spanish National Health Institute of Health Carlos III (ISCIII) CPII20/00014 ICREA, The European Regional Development Fund PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 European Commission PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158 PI21/00465, "Fondo de Investigacion para la Salud" (FIS), European Commission PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728 PI14/01471 PI16/00473 PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183

The liver is a key organ involved in a wide range of functions, whose damage can lead to chronic liver disease (CLD). CLD accounts for more than two million deaths worldwide, becoming a social and economic burden for most countries. Among the different factors that can cause CLD, alcohol abuse, viruses, drug treatments, and unhealthy dietary patterns top the list. These conditions prompt and perpetuate an inflammatory environment and oxidative stress imbalance that favor the development of hepatic fibrogenesis. High stages of fibrosis can eventually lead to cirrhosis or hepatocellular carcinoma (HCC). Despite the advances achieved in this field, new approaches are needed for the prevention, diagnosis, treatment, and prognosis of CLD. In this context, the scientific com-munity is using machine learning (ML) algorithms to integrate and process vast amounts of data with unprecedented performance. ML techniques allow the integration of anthropometric, genetic, clinical, biochemical, dietary, lifestyle and omics data, giving new insights to tackle CLD and bringing personalized medicine a step closer. This review summarizes the investigations where ML techniques have been applied to study new approaches that could be used in inflammatory-related, hepatitis viruses-induced, and coronavirus disease 2019-induced liver damage and enlighten the factors involved in CLD development.

Background: COVID-19 lockdowns had a significant impact on people’s health, triggering levels of anxiety, perceived stress, and changes in food and nutritional status. Objectives: To assess the changes in dietary habits, metabolic syndrome (MetS) and liver parameters before and after the COVID-19 lockdown according to changes in intrahepatic fat content in adults with non-alcoholic fatty liver disease (NAFLD) and MetS. Design: Pre- and post-lockdown observation of the COVID-19 lockdown on fifty-nine 40–60-year-old participants with MetS and NAFLD, in a parallel group, randomised experiment intended to treat NAFLD. Methods: Anthropometrics, liver and MetS biochemical parameters, intrahepatic fat content by abdominal magnetic resonance imaging, and dietary assessment using a validated 148-item Food Frequency Questionnaire were collected pre-COVID-19 lockdown and post-lockdown. Results: COVID-19 lockdown led to negative changes in the liver of patients with NAFLD and MetS, with weight gain and increases in glycemia, ALT and intrahepatic fat content post lockdown. Participants with worsened liver status had low consumption of fibre, cheese, nuts and coffee, and high consumption of sweets and pastries. Participants who improved liver status ameliorated ALT values, waist circumference, and intrahepatic fat content, assessed by magnetic resonance imaging post-lockdown. Conclusions: The maintenance of healthy lifestyle habits is vital, especially for populations with NAFLD and MetS, to reduce unhealthy lifestyle patterns displayed during lockdown.

Unhealthy diet is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). Previous studies showed the benefits of a Mediterranean diet (MedDiet) on Metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases, which usually have a pathophysiological relationship with NAFLD. To assess the effect of adherence to a MedDiet on NAFLD in MetS patients after lifestyle intervention, this multicentre (Mallorca and Navarra, Spain) prospective randomized trial, with personalized nutritional intervention based on a customized MedDiet, coupled with physical activity promotion was performed to prevent, and reverse NAFLD among patients with MetS. The current analysis included 138 patients aged 40 to 60 years old, Body Mass Index (BMI) 27–40 kg/m2, diagnosed with NAFLD using MRI, and MetS according to the International Diabetes Federation (IDF). A validated food frequency questionnaire was used to assess dietary intake. Adherence to Mediterranean diet by means of a 17-item validated questionnaire, anthropometrics, physical activity, blood pressure, blood biochemical parameters, and intrahepatic fat contents (IFC) were measured. The independent variable used was changes in MedDiet adherence, categorized in tertiles after 6 months follow-up. Subjects with high adherence to the MedDiet showed higher decreases in BMI, body weight, WC, SBP, DBP, and IFC. An association between improvement in adherence to the MedDiet and amelioration of IFC after 6-month follow-up was observed. High adherence to the MedDiet is associated with better status of MetS features, and better values of IFC.

Background and aim Fecal microbiome disturbances are linked to different human diseases. In the case of obesity, gut microbiota seems to play a role in the development of low-grade inflammation. The purpose of the present study was to identify specific bacterial families and genera associated with an increased obesity-related inflammatory status, which would allow to build a regression model for the prediction of the inflammatory status of obese and overweight subjects based on fecal microorganisms. Methods A total of 361 volunteers from the Obekit trial (65 normal-weight, 110 overweight, and 186 obese) were classified according to four variables: waist/hip ratio (≥0.86 for women and ≥1.00 for men), leptin/adiponectin ratio (LAR, ≥3.0 for women and ≥1.4 for men), and plasma C-reactive protein (≥2 mg/L) and TNF levels (≥0.85 pg/mL). An inflammation score was designed to classify individuals in low (those subjects who did exceed the threshold value in 0 or 1 variable) or high inflammatory index (those subjects who did exceed the threshold value in 2 or more variables). Fecal 16 S rRNA sequencing was performed for all participants, and differential abundance analyses for family and genera were performed using the MicrobiomeAnalyst web-based platform. Results Methanobacteriaceae, Christensenellaceae, Coriobacteriaceae, Bifidobacteriaceae, Catabacteriaceae, and Dehalobacteriaceae families, and Methanobrevibacter, Eggerthella, Gemmiger, Anaerostipes, and Collinsella genera were significantly overrepresented in subjects with low inflammatory index. Conversely, Carnobacteriaceae, Veillonellaceae, Pasteurellaceae, Prevotellaceae and Enterobacteriaceae families, and Granulicatella, Veillonella, Haemophilus, Dialister Parabacteroides, Prevotella, Shigella, and Allisonella genera were more abundant in subjects with a high inflammatory index. A regression model adjusted by BMI, sex, and age and including the families Coriobacteriaceae and Prevotellaceae and the genus Veillonella was developed. Conclusion A microbiota-based regression model was able to predict the obesity-related inflammatory status (area under the ROC curve = 0.8570 ± 0.0092 Harrell's optimism-correction) and could be useful in the precision management of inflammobesity.

Background & aims: Ultra-processed food and drink products (UPF) consumption has been associated with obesity and its-related comorbidities. Excess of visceral fat, which appears with increasing age, has been considered as the culprit contributing to adiposity-associated adverse health outcomes. However, none of previous studies elucidated the link between UPF and directly quantified adiposity and its distribution. We aimed to prospectively investigate the association between concurrent changes in UPF consumption and objectively assessed adiposity distribution. Methods: A subsample of 1485 PREDIMED-Plus participants (Spanish men and women aged 55-75 years with overweight/obesity and metabolic syndrome) underwent body composition measurements. Consumption of UPF at baseline, 6 and 12 months was evaluated using a validated 143-item semiquantitative Food Frequency Questionnaire. Food items (g/day) were categorized according to their degree of processing using NOVA system. Regional adiposity (visceral fat (in g) and android-to-gynoid fat & nbsp; ratio) and total fat mass (in g) at three time points were measured with dual-energy X-ray absorpti-ometry (DXA) and were normalized using sex-specific z-scores. The association of changes in UPF consumption, expressed as the percentage of total daily intake (daily g of UPF/total daily g of food and beverage intake*10 0), with adiposity changes was evaluated using linear mixed-effects models. Results: On average, the consumption of UPF accounted for 8.11% (SD 7.41%) of total daily intake (in grams) at baseline. In multivariable-adjusted model, 10% daily increment in consumption of UPF was associated with significantly (all p-values

Nutrition is a global science that originally was envisaged to biologically analyse and integrate the processes related to food transformation into energy and nutritious components for cell functions and homeostasis.1 Noteworthy, it is now evident that such physical, chemical and metabolic reactions participate in human development to ensure life expectancy and well-being, with a growing and inseparable relevance for personal, population and planetary health.2 Nowadays, nutritional challenges and nutritionist’s interests are being focused on health and wellness involving physical, emotional, intellectual, cognitive, spiritual, environmental and occupational facets.3 Moreover, according to the newer emerging health scenarios, food intake should be assessed in relationship with social, satisfaction, satiety, security, safety and sustainable dimensions. In this context, two apparently alternative approaches, one derived from a global public health perspective and another derived from a precision-personalised nutrition paradigm, should be harmonised and deliberated since they are complementary to each other and as such, personalised, participative, preventive and predictive strategies are all needed in order to maintain a healthy status as well as to prevent and manage diseases.4 The evolving notion about precision nutrition concerns personalised nutrition guidelines and tailor-made dietary prescriptions for the prevention and treatment of obesity, diabetes, cardiovascular events and other chronic diseases. The management of metabolic impairments, inflammatory/haematological disturbances or neoplasia/tumorous diseases with nutritional approaches are needed for health maintenance as well as in clinical practice.5 In this context, precision nutrition not only considers an individual′s genomic background and nutrient-gene interactions but also a thorough phenotyping evaluation, including family and personal clinical features, perinatal feeding programming and expectantly a wide spectrum of bioinformatic data concerning metabolic pathways. This last aspect involves omics strategies and high-throughput technologies such as metabolomics, proteomics, (epi) genomics or metagenomics related to macronutrients and micronutrients metabolic utilisation.6 Indeed, the conceptual framework …

Background: The molecular mechanisms underlying the potential health benefits of a ketogenic diet are unknown and could be mediated by epigenetic mechanisms. Objective: To identify the changes in the obesity-related methylome that are mediated by the induced weight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenic diet (VLCKD). Methods: Twenty-one patients with obesity (n ¼ 12 women, 47.9 ± 1.02 yr, 33.0 ± 0.2 kg/m2 ) after 6 months on a VLCKD and 12 normal weight volunteers (n ¼ 6 women, 50.3 ± 6.2 yrs, 22.7 ± 1.5 kg/m2 ) were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes were obtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD (n ¼ 10) and at baseline in volunteers (n ¼ 12). Results were further validated by pyrosequencing in representative cohort of patients on a VLCKD (n ¼ 18) and correlated with gene expression. Results: After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes). The VLCKD altered methylation levels in patients with obesity had high resemblance with those from normal weight volunteers and was concomitant with a downregulation of DNA methyltransferases (DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein metabolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoring associated events were identified, including ZNF331, FGFRL1 (VLCKD-induced weight loss) and CBFA2T3, C3orf38, JSRP1, and LRFN4 (VLCKD-induced ketosis). Interestingly, ZNF331 and FGFRL1 were validated in an independent cohort and inversely correlated with gene expression. Conclusions: The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive of normal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss. This work was supported by the PronoKal Group® and grants from the Fondo de Investigacion Sanitaria as well as PI17/01287, PI20/00628 and PI20/00650 research projects and CIBERobn from the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigación; Fondo Europeo de Desarrollo Regional (FEDER) Ana B Crujeiras is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII, co-financed by the European Regional Development Fund (FEDER) and Xunta de Galicia-GAIN (IN607B2020). The funding source had no involvement in the study design or interpretation of the results

[Background & aims]: The Portfolio and Dietary Approaches to Stop Hypertension (DASH) diets have been shown to lower cardiometabolic risk factors in randomized controlled trials (RCTs). However, the Portfolio diet has only been assessed in RCTs of hyperlipidemic patients. Therefore, to assess the Portfolio diet in a population with metabolic syndrome (MetS), we conducted a longitudinal analysis of one-year data of changes in the Portfolio and DASH diet scores and their association with cardiometabolic risk factors in Prevención con Dieta Mediterránea (PREDIMED)-Plus trial. [Methods]: PREDIMED-Plus is an ongoing clinical trial (Trial registration: ISRCTN89898) conducted in Spain that includes 6874 older participants (mean age 65 y, 48% women) with overweight/obesity fulfilling at least three criteria for MetS. Data for this analysis were collected at baseline, six months and one year. Adherence to the Portfolio and DASH diet scores were derived from a validated 143-item food frequency questionnaire. We used linear mixed models to examine the associations of 1-SD increase and quartile changes in the diet scores with concomitant changes in cardiometabolic risk factors. [Results]: After adjusting for several potential confounders, a 1-SD increase in the Portfolio diet score was significantly associated with lower HbA1c (β [95% CI]: −0.02% [−0.02, −0.01], P < 0.001), fasting glucose (−0.47 mg/dL [−0.83, −0.11], P = 0.01), triglycerides (−1.29 mg/dL [−2.31, −0.28], P = 0.01), waist circumference (WC) (−0.51 cm [−0.59, −0.43], P < 0.001), and body mass index (BMI) (−0.17 kg/m2 [−0.19, −0.15], P < 0.001). A 1-SD increase in the DASH diet score was significantly associated with lower HbA1c (−0.03% [−0.04, −0.02], P < 0.001), glucose (−0.84 mg/dL [−1.18, −0.51], P < 0.001), triglycerides (−3.38 mg/dL [−4.37, −2.38], P < 0.001), non-HDL-cholesterol (−0.47 mg/dL [−0.91, −0.04], P = 0.03), WC (−0.69 cm [−0.76, −0.60 cm], P < 0.001), BMI (−0.25 kg/m2 [−0.28, −0.26 kg/m2], P < 0.001), systolic blood pressure (−0.57 mmHg [−0.81, −0.32 mmHg], P < 0.001), diastolic blood pressure (−0.15 mmHg [−0.29, −0.01 mmHg], P = 0.03), and with higher HDL-cholesterol (0.21 mg/dL [0.09, 0.34 mg/dL, P = 0.001]). Similar associations were seen when both diet scores were assessed as quartiles, comparing extreme categories of adherence. [Conclusions]: Among older adults at high cardiovascular risk with MetS, greater adherence to the Portfolio and DASH diets showed significant favourable prospective associations with several clinically relevant cardiometabolic risk factors. Both diets are likely beneficial for cardiometabolic risk reduction., The PREDIMED-Plus trial was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS) and co-funded by European Union ERDF/ESF, “A way to make Europe”/“Investing in your future” (five coordinated FIS projects led by JS-S and JVid, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183,PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332), the Special Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S, the European Research Council (Advanced Research Grant 2014–2019, 340918) to MÁM-G, the Recercaixa Grant to JS-S (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN grant, and funds from the European Regional Development Fund (CB06/03). This research was also partially funded by EU-H2020 Grant (EAT2BENICE/H2020-SFS-2016-2; Ref 728018). Study resulting from the SLT006/17/00246 grant, funded by the Department of Health of the Generalitat de Catalunya by the call “Acció instrumental de programes de recerca orientats en l'àmbit de la recerca i la innovació en salut”. We thank CERCA Programme/Generalitat de Catalunya for institutional support. This work is partially supported by ICREA under the ICREA Academia programme. IP-G receives a grant from the Spanish Ministry of Education, Culture and Sports (FPU 17/01925). MRBL was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER. AJG was supported by the Nora Martin Fellowship in Nutritional Sciences, the Banting & Best Diabetes Centre Tamarack Graduate Award in Diabetes Research, the Peterborough K.M. Hunter Charitable Foundation Graduate Award and an Ontario Graduate Scholarship. PH-A was supported by a postdoctoral fellowship (Juan de la Cierva-Formación), FJCI-2017–32205, funded by the Ministry of Science and Innovation. RE group has been supported by the ‘Ajut 2017-2021 SGR 1717 from the Generalitat de Catalunya. DJAJ was funded by the Government of Canada through the Canada Research Chair Endowment. JK was supported by the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017 annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands). JLS was funded by a Diabetes Canada Clinician Scientist Award.

dibenzop- furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited. Objective: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population. Methods: In 5899 participants aged 55–75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models. Results: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (β-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend, nstituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, European Research Council (ERC) European Commission 340918, La Caixa Foundation 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Center for Forestry Research & Experimentation (CIEF) PROMETEO/21/2021, MICIN/AEI/FEDER, UE CEX2021-001234-M, SEMERGEN grant, ICREA under the ICREA Academia program, Agencia de Gestio d'Ajuts Universitaris de Recerca (AGAUR FI) 2021FI_B 00145

Funding sponsor Funding number Acronym Balearic Islands Health Research Institute, EU-COST 35/2011, CA16112, Fondo de Investigación para la Salud, IDISBA CB12/03, CIBEROBN CB06/03, Margalida Comas DG R+D+I, Ministry of Science, Spain, European Commission 201630.10, EAT2BENICE_H2020_SFS2016, European Research Council 2013–2018, 340918, Generalitat Valenciana PROMETEO/2017/017, Instituto de Salud Carlos III, Funding sponsor Funding number Acronym Balearic Islands Health Research Institute EU-COST 35/2011, CA16112 Fondo de Investigación para la Salud IDISBA CB12/03, CIBEROBN CB06/03 Margalida Comas DG R+D+I Ministry of Science, Spain European Commission See opportunities by EC See opportunities (opens in new window) 201630.10, EAT2BENICE_H2020_SFS2016 EC European Research Council See opportunities by ERC See opportunities (opens in new window) 2013–2018, 340918 ERC Generalitat Valenciana See opportunities by GVA See opportunities (opens in new window) PROMETEO/2017/017 GVA Instituto de Salud Carlos III 2013ACUP00194, PI13/00233, PI13/00272, PI13/00462, PI13/00492, PI13/00673, PI13/00728, PI13/01056, PI13/01090, PI13/01123, PI13/02184, PI14/00618, PI14/00636, PI14/00696, PI14/00728, PI14/00853, PI14/00972, PI14/01206, PI14/01374, PI14/01471, PI14/01722, PI14/01919, PI16/00366, PI16/00381, PI16/00473, PI16/00501, PI16/00533, PI16/00662, PI16/01094, PI16/01120, PI16/01522, PI16/01873, PI17/00215, PI17/00508, PI17/00525, PI17/00532, PI17/00764, PI17/00855, PI17/00926, PI17/01183, PI17/01347, PI17/01441, PI17/01732, PI17/01827, PI19/00017, PI19/00309, PI19/00386, PI19/00576, PI19/00781, PI19/00957, PI19/01032, PI19/01226, PI19/01332, PI19/01560, PI20/00138, PI20/00339, PI20/00456, PI20/00557, PI20/00886, PI20/01158, PI20/01532, PI20/01802, Consejería de Salud y Familias, Junta de Andalucía PI0137/2018, PI0458/2013, PS0358/2016

BackgroundMechanisms underlying the associations of high levels of physical activity (PA) and adherence to the Mediterranean diet (MedDiet) with a better inflammatory profile remain unclear. Our objective was to assess the mediating role of changes in body mass index (BMI) and waist circumference (WC), as markers of body fat in the association of changes in PA and adherence to the MedDiet, with changes in the inflammatory profile.MethodThis study included 489 adults, aged 55–75 years, from the PREDIMED-Plus multicenter lifestyle intervention trial. An inflammatory score was calculated, based on 8 blood biomarkers: high-sensitivity C-reactive protein, interleukin 6, interleukin 8, interleukin 18, monocyte chemo-attractant protein-1, C-peptide, leptin, and regulated on activation, normal T-cell–expressed and secreted chemokine. Biomarkers, levels of PA, score of MedDiet adherence, BMI, and WC were measured at baseline and at 1-year follow-up. Linear regression models were fitted according to the Baron and Kenny framework for mediation analysis.ResultsChanges in BMI and WC mediated the association of both changes in PA and changes in the MedDiet adherence with the inflammatory score. Body mass index mediated 26% of the association of changes in total PA with the inflammatory profile, and 27% of the association of changes in the MedDiet, while WC mediated 13% and 12% of these associations, respectively.ConclusionIn older adults at high cardiovascular risk, increasing PA levels and adherence to a MedDiet during 1 year were associated with a lower inflammatory score, which was partly mediated by a reduction in body fat.Clinical Trials Registration NumberInternational Standard Randomized Controlled Trial Number: ISRCTN89898870; registration date July 24, 2014, retrospectively registered.

Gut microbiota dysbiosis has been described in several metabolic disruptions, such as non-alcoholic fatty liver disease (NAFLD). Administration of resveratrol has been claimed to elicit benefits against NAFLD along with modulating gut microbiota composition. This investigation aims to study the putative mediating role of gut microbiota in the potential hepato-protective effects of resveratrol in a diet-induced NAFLD rat model. The involvement of bacteria from the Ruminococcaceae family in such effects was also addressed. Resveratrol administration resulted in lowered liver weight and serum total and non-HDL cholesterol concentrations, as well as in increased serum HDL cholesterol levels. The administration of this polyphenol also prevented obesogenic diet-induced serum transaminase increases. In addition, histopathological analysis revealed that resveratrol administration ameliorated the dietary-induced liver steatosis and hepatic inflammation. Gut microbiota sequencing showed an inverse relationship between some bacteria from the Ruminococcaceae family and the screened hepatic markers, whereas in other cases the opposite relationship was also found. Interestingly, an interaction was found between UBA-1819 abundance and resveratrol induced liver weight decrease, suggesting that for this marker resveratrol induced effects were greater when the abundance of this bacteria was high, while no actions were found when UBA-1819 abundance was low. This research was funded by Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (grant number AGL-2015-65719-R MINECO/FEDER, UE), Instituto de Salud Carlos III CIBERobn (grant number CB12/03/30007); University of the Basque Country (grant number GIU 18/173) and Synergic R&D Projects in New and Emerging Scientific Areas on the Frontier of Science and Interdisciplinary Nature of The Community of Madrid (METAINFLAMATION-Y2020/BIO-6600).

Background: A Mediterranean diet (MedDiet) is recommended as a therapy for non-alcoholic fatty liver disease (NAFLD) because there is no specific pharmacological treatment for this disease. Objective: To assess the relationship between the adherence to the Mediterranean diet and the intrahepatic fat content (IFC), levels of oxidative stress, and inflammation biomarkers after a 6-month lifestyle intervention in NAFLD patients. Methods: Patients diagnosed with NAFLD (n = 60 adults; 40–60 years old) living in the Balearic Islands, Spain, were classified into two groups, according to the adherence to the MedDiet after 6 months of lifestyle intervention. Anthropometry, blood pressure, IFC, maximal oxygen uptake, and pro/antioxidant and inflammatory biomarkers were measured in plasma and in PBMCs before and after the intervention. Results: Reductions in weight, body mass index, IFC, blood pressure levels, circulating glucose, glycosylated hemoglobin, and markers of liver damage—aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and cytokeratin 18 (CK-18)—were observed after the intervention. The highest reductions were observed in the group with the best adherence to the MedDiet. A significant improvement in cardiorespiratory fitness was also observed in the group with a higher adherence. The activities of catalase in plasma and catalase and superoxide dismutase in blood mononuclear cells increased only in the group with a higher adherence, as well as the catalase gene expression in the blood mononuclear cells. The plasma levels of malondialdehyde and myeloperoxidase decreased, and resolvin-D1 increased in both groups after the intervention, whereas interleukin-6 levels decreased only in the group with a higher adherence to the MedDiet. Conclusions: A greater adherence to the MedDiet is related to greater improvements in IFC, cardiorespiratory fitness, and pro-oxidative and proinflammatory status in NAFLD patients after a 6-month nutritional intervention based on the MedDiet.

Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by the excessive accumulation of lipids in the liver parenchyma. To date, there is no effective pharmacological treatment against NAFLD. Objective: To assess the relationship between the improvement of the intrahepatic fat content (IFC) in patients with NAFLD and metabolic syndrome and biomarkers of oxidative stress and inflammation after 6 months of lifestyle intervention. Patients diagnosed with NAFLD (n = 60 adults; 40–60 years old) residing in the Balearic Islands, Spain, were distributed in tertiles attending the improvement of IFC calculated by magnetic resonance imaging (MRI). Anthropometrics, blood pressure, maximal oxygen uptake, and pro/antioxidant and inflammatory biomarkers were determined in plasma before and after the lifestyle intervention. The improvement in IFC levels was higher in tertile 3 with respect to tertiles 2 and 1. The greatest improvement in IFC is related to cardiorespiratory fitness and adherence to the Mediterranean diet (ADM). Higher reductions in weight, body mass index (BMI), and alanine aminotransferase (ALT) were observed in tertile 3 with respect to tertile 1 after 6 months of intervention. The improvement in catalase, irisin, and cytokeratin 18 plasma levels were higher in tertile 3, whereas no differences were observed in superoxide dismutase activity. Malondialdehyde and protein carbonyl levels, as biomarkers of oxidative damage, remained unchanged in all groups. The present data show that the reduction of IFC is associated with an improvement in pro/antioxidant and pro-inflammatory status and a better cardiorespiratory fitness in NAFLD patients.

Healthy and unhealthy lifestyles are tightly linked to general health and well-being. However, measurements of well-being have failed to include elements of health and easy to interpret information for patients seeking to improve lifestyles. Therefore, this study aimed to create an index for the assessment of general health and well-being along with two cut-off points: the lifestyle and well-being index (LWB-I). This was a cross-sectional analysis of 15,168 individuals. Internally valid multivariate linear models were constructed using key lifestyle features predicting a modified Short Form 36 questionnaire (SF-36) and used to score the LWB-I. Categorization of the LWB-I was based on self-perceived health (SPH) and analyzed using receiver operating characteristic curve analysis. Optimal cut-points identified individuals with poor and excellent SPH. Lifestyle and well-being were adequately accounted for using 12 lifestyle items. SPH groups had increasingly healthier lifestyle features and LWB-I scores; optimal cut-point for poor SPH were scores below 80 points (AUC: 0.80 (0.79, 0.82); sensitivity 75.7%, specificity 72.3%)) and above 86 points for excellent SPH (AUC: 0.67 (0.66, 0.69); sensitivity 61.4%, specificity 63.3%). Lifestyle and well-being were quantitatively scored based on their associations with a general health measure in order to create the LWB-I along with two cut points.