Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial.

BACKGROUND: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood. OBJECTIVES: Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors. METHODS: A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota. RESULTS: Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors. CONCLUSIONS: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

Adherence to a healthy lifestyle behavior composite score and cardiometabolic risk factors in Spanish children from the CORALS cohort.

To assess the associations between the adherence to a composite score comprised of 6 healthy lifestyle behaviors and its individual components with several cardiometabolic risk factors in Spanish preschool children. Cross-sectional analyses were conducted in 938 participants included in the CORALS cohort aged 3-6 years. Six recognized healthy lifestyle behaviors (breastfeeding, sleep duration, physical activity, screentime, adherence to the Mediterranean diet, and eating speed) were assessed in a composite score. Multiple linear and logistic regression models were fitted to assess the associations with cardiometabolic risk factors (weight status, waist circumference, fat mass index, blood pressure, fasting plasma glucose, and lipid profile). In the adjusted multiple linear and logistic regression models, compared with the reference category of adherence to the healthy lifestyle behavior composite score, those participants in the category of the highest adherence showed significant decreased prevalence risk of overweight or obesity [OR (95% CI), 0.4 (0.2, 0.6)] as well as significant lower waist circumference, fat mass index (FMI), systolic blood pressure and fasting plasma glucose concentration [ß (95% CI), - 1.4 cm (- 2.5, - 0.4); - 0.3 kg/m2 (- 0.5, - 0.1); and - 3.0 mmHg (- 5.2, - 0.9); - 1.9 mg/dL (- 3.5, - 0.4), respectively]. Slow eating speed was individually associated with most of the cardiometabolic risk factors.   Conclusions: Higher adherence to the healthy lifestyle behavior composite score was associated with lower waist circumference, FMI, other cardiometabolic risk factors, and risk of overweight or obesity in Spanish preschool children. Further studies are required to confirm these associations. What is Known: • Lifestyle is a well-recognized etiologic factor of obesity and its comorbidities. • Certain healthy behaviors such as adhering to a healthy diet, increasing physical activity, and decreasing screentime are strategies for prevention and treatment of childhood obesity. What is New: • Higher adherence to the healthy lifestyle behavior composite score to 6 healthy behaviors (breastfeeding, sleep duration, physical activity, screentime, eating speed, and adherence to the Mediterranean diet) was associated with decreased adiposity, including prevalence risk of overweight or obesity, and cardiometabolic risk in preschool children. • Slow eating and greater adherence to the Mediterranean diet were mainly associated to lower fasting plasma and serum triglycerides concentration, respectively.

Ultra-processed food consumption and semen quality parameters in the Led-Fertyl study.

STUDY QUESTION: Is ultra-processed food (UPF) consumption associated with semen quality parameters? SUMMARY ANSWER: Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age. WHAT IS KNOWN ALREADY: The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited. STUDY DESIGN SIZE DURATION: A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023. PARTICIPANTS/MATERIALS SETTING METHODS: UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm concentration (ß: -1.42 × 106 spz./ml; 95% CI: -2.72 to -0.12) and motility (ß: -7.83%; 95% CI: -15.16 to -0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption (ß: -1.50 × 106 spz.; 95% CI: -2.83 to -0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms. LIMITATIONS REASONS FOR CAUTION: Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out. WIDER IMPLICATIONS OF THE FINDINGS: This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-term designs, these novel findings could provide valuable insights for updating or even designing preventive and interventional programs to address infertility among men of reproductive age. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS), the European Union ERDF/ESF, 'A way to make Europe'/'Investing in your future' [PI21/01447], and the Diputació de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S. gratefully acknowledges the financial support of ICREA under the ICREA Academia program. C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI_B100108). M.Á.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045-Instituto de Salud Carlos III (ISCIII)). M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputació de Tarragona (2020-PMF-PIPF-8). All authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Plasma metabolite profile of legume consumption and future risk of type 2 diabetes and cardiovascular disease.

BACKGROUND: Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD. METHODS: The current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models. RESULTS: Specific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61-0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86-1.19; p = 0.817) over the follow-up period. CONCLUSIONS: This study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease. TRIAL REGISTRATION: ISRCTN35739639.

Is telomere length a biomarker of sperm quality? A systematic review and meta-analysis of observational studies.

BACKGROUND: Telomeres are essential for the integrity of chromosome ends during cell division and their involvement in different processes linked to aging has been established. These chromosome components are involved in spermatogenesis and seem to play an important role in fertilization and embryo development. Telomere length is shortened with each cell division. Recently, short sperm telomere length has been proposed as a potential biomarker of male infertility. OBJECTIVES: To conduct a systematic review and meta-analysis of studies exploring the association between spermatozoa and/or leukocyte telomere length with sperm quality parameters and different infertility conditions. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted with studies from Medline-PUBMED and Cochrane Library databases until May 2022. Eligible studies included cohort, cross-sectional and case-control studies, and telomere length in spermatozoa and/or leukocytes cells was defined as the exposure. Semen quality parameters or infertility conditions (e.g., oligozoospermia, asthenozoospermia, teratozoospermia, or other spermatogenic impairment combinations) were defined as the outcomes. RESULTS: Twenty-three observational studies were included. In the qualitative analysis, high heterogeneity was observed between studies regarding the associations between telomere length and semen parameters in different normozoospermic/fertile and oligozoospermic/infertile populations. In the meta-analysis, spermatozoa and leukocyte telomere length were shorter in infertile individuals than in fertile individuals (mean difference [95% confidence interval]: -1.43 [-1.66 to -1.21], p-value <0.001 and -1.67 [-2.02 to -1.31], p-value <0.001, respectively). Moreover, in terms of sperm telomere length, these differences were also significant between individuals with a normal seminogram and individuals with a low quantity of spermatozoa in the ejaculate (-0.97 [-1.32, -0.61], p-value <0.001). CONCLUSION: The current systematic review and meta-analysis suggests the potential role of spermatozoa or leukocyte telomere length as a reliable biomarker of semen quality, which may help distinguish between infertility conditions beyond the routine semen analysis.

Microbial Phenolic Metabolites Are Associated with Improved Cognitive Health.

SCOPE: Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk. METHODS AND RESULTS: A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores. CONCLUSIONS: These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.

Adherence to the Mediterranean diet and nuclear magnetic resonance spectroscopy biomarkers in older individuals at high cardiovascular disease risk: cross-sectional and longitudinal analyses.

BACKGROUND: The Mediterranean diet (MedDiet) has been related to a decreased risk of cardiovascular disease (CVD) and diabetes. OBJECTIVES: We aimed to prospectively assess the relationship between adherence to the MedDiet and advanced lipoprotein subclass profiles and glucose metabolism and inflammation markers, as determined by nuclear magnetic resonance (NMR) spectroscopy. DESIGN: We conducted cross-sectional and longitudinal analyses within the framework of the PREvención con DIeta MEDiterránea study in 196 participants from the Reus-Tarragona center. Adherence to the MedDiet was assessed using a 14-item validated questionnaire [Mediterranean Diet Adherence Score (MEDAS)]. Plasma lipoprotein subclasses and molecular metabolite profiles were determined using NMR spectra collected on a Vantera Clinical Analyzer at baseline and after 1 y of follow-up. Baseline and 1-y categories of MEDAS were related to measures of lipoprotein atherogenicity and diabetes risk using multivariable-adjusted analysis of covariance models. RESULTS: Compared with participants in the lowest category of baseline MEDAS, those in the highest category showed higher concentrations of total high-density lipoprotein (HDL) particles and H1P HDL, lower concentrations of very low-density lipoprotein (VLDL)-triglyceride, smaller size of VLDL, and lower concentrations of very large VLDL, as well as lower concentrations of branched-chain amino acids, leucine, and GlycA and reduced Diabetes Risk Index (DRI) scores. In addition, participants who increased by 3 or more points in their 1-y MEDAS showed an increase in concentrations of H7P-HDL, H5P-HDL, and citrate, and reduced acetone and DRI scores compared with those with lesser adherence increases. CONCLUSIONS: In older adults at high cardiometabolic risk, higher MEDAS was associated with modest beneficial changes in lipoprotein and glucose metabolism. The results suggest that lipoprotein subclass distribution and glycemic control are potential mechanisms behind the well-known salutary effects of MedDiet on CVD and diabetes risk. Future clinical trials exploring the effects of the MedDiet on advanced lipoprotein subclass profiles and glucose metabolism markers are needed to confirm the results of our study. TRIAL REGISTRATION NUMBER: This trial was registered at controlled-trials.com as ISRCTN35739639.

Plasma metabolite predictors of metabolic syndrome incidence and reversion.

BACKGROUND: Metabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion. METHODS: The study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was defined by not having MetS at baseline but meeting the MetS criteria at a follow-up visit. MetS reversion was defined by MetS at baseline but not meeting MetS criteria at a follow-up visit. Plasma metabolome was profiled by LC-MS. Multivariable-adjusted Cox regression models and elastic net regularized regressions were used to assess the association of 385 annotated metabolites with MetS incidence and MetS reversion after adjusting for potential risk factors. RESULTS: Of the 603 participants without baseline MetS, 298 developed MetS over the median 4.8-year follow-up. Of the 865 participants with baseline MetS, 285 experienced MetS reversion. A total of 103 and 88 individual metabolites were associated with MetS incidence and MetS reversion, respectively, after adjusting for confounders and false discovery rate correction. A metabolomic signature comprised of 77 metabolites was robustly associated with MetS incidence (HR: 1.56 (95 % CI: 1.33-1.83)), and a metabolomic signature of 83 metabolites associated with MetS reversion (HR: 1.44 (95 % CI: 1.25-1.67)), both p < 0.001. The MetS incidence and reversion signatures included several lipids (mainly glycerolipids and glycerophospholipids) and branched-chain amino acids. CONCLUSION: We identified unique metabolomic signatures, primarily comprised of lipids (including glycolipids and glycerophospholipids) and branched-chain amino acids robustly associated with MetS incidence; and several amino acids and glycerophospholipids associated with MetS reversion. These signatures provide novel insights on potential distinct mechanisms underlying the conditions leading to the incidence or reversion of MetS.

Olive oil consumption, plasma metabolites, and risk of type 2 diabetes and cardiovascular disease.

BACKGROUND: Olive oil consumption has been inversely associated with the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, the impact of olive oil consumption on plasma metabolites remains poorly understood. This study aims to identify plasma metabolites related to total and specific types of olive oil consumption, and to assess the prospective associations of the identified multi-metabolite profiles with the risk of T2D and CVD. METHODS: The discovery population included 1837 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) trial with available metabolomics data at baseline. Olive oil consumption was determined through food-frequency questionnaires (FFQ) and adjusted for total energy. A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation sample. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known candidate metabolites and olive oil consumption were assessed using elastic net regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite-weighted models and FFQ-derived olive oil consumption in each pair of training-validation data sets within the discovery sample. We further estimated the prospective associations of the identified plasma multi-metabolite profile with incident T2D and CVD using multivariable Cox regression models. RESULTS: We identified a metabolomic signature for the consumption of total olive oil (with 74 metabolites), VOO (with 78 metabolites), and COO (with 17 metabolites), including several lipids, acylcarnitines, and amino acids. 10-CV Pearson correlation coefficients between total olive oil consumption derived from FFQs and the multi-metabolite profile were 0.40 (95% CI 0.37, 0.44) and 0.27 (95% CI 0.22, 0.31) for the discovery and validation sample, respectively. We identified several overlapping and distinct metabolites according to the type of olive oil consumed. The baseline metabolite profiles of total and extra virgin olive oil were inversely associated with CVD incidence (HR per 1SD: 0.79; 95% CI 0.67, 0.92 for total olive oil and 0.70; 0.59, 0.83 for extra virgin olive oil) after adjustment for confounders. However, no significant associations were observed between these metabolite profiles and T2D incidence. CONCLUSIONS: This study reveals a panel of plasma metabolites linked to the consumption of total and specific types of olive oil. The metabolite profiles of total olive oil consumption and extra virgin olive oil were associated with a decreased risk of incident CVD in a high cardiovascular-risk Mediterranean population, though no associations were observed with T2D incidence. TRIAL REGISTRATION: The PREDIMED trial was registered at ISRCTN ( http://www.isrctn.com/ , ISRCTN35739639).

Vegetable and Fruit Intake Variety and Cardiovascular Health and Mortality: A Systematic Review and Meta-Analysis of Observational Studies.

INTRODUCTION: A multitude of evidence supports the consumption of a higher quantity of vegetables and fruits for their cardiovascular benefits. Nonetheless, the extent to which variety is associated with cardiovascular health remains unclear. OBJECTIVE: To conduct a systematic review and meta-analysis of observational studies (prospective cohort and cross-sectional studies) assessing the role of a variety of vegetable and fruit consumption in cardiovascular morbidity and mortality in adults. DATA SOURCES: MEDLINE-PubMed, Cochrane databases, and reference lists were searched through March 2023. DATA EXTRACTION: Two independent reviewers extracted data and assessed the risk of bias (National Heart, Lung, and Blood Institute Tool and Newcastle-Ottawa Scale). DATA ANALYSIS: Data were pooled (fixed and random [DerSimonian and Laird] effects for <5 and ≥5 study comparisons, respectively), and heterogeneity was assessed using the Cochran Q statistic and quantified (I2 statistic). The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the overall certainty of the evidence. Five cross-sectional (n = 45,761) and seven prospective studies (n = 253,422) met the eligibility criteria. Greater variety of vegetable and fruit consumption was prospectively related to decreased all-cause mortality (risk ratio, 0.89 [95% CI, 0.82-0.97], seven study comparisons, n = 196,925), while no significant associations were observed with assessed cardiovascular-related mortality or morbidity. For all outcomes, the certainty of the evidence was graded as "low" or "very low" owing to inconsistency and/or imprecision. CONCLUSIONS: Overall, this study shows that greater variety in vegetable and fruit consumption may reduce all-cause mortality and highlights the need for additional studies with a higher degree of evidence to better understand its role in cardiovascular health.

Exploring the Occurrence of Organic Contaminants in Human Semen through an Innovative LC-HRMS-Based Methodology Suitable for Target and Nontarget Analysis.

Understanding the potential impact of organic contaminants on male fertility is crucial, yet limited studies have examined these chemicals in semen, with most focusing on urine and blood. To address this gap, we developed and validated a robust LC-HRMS methodology for semen analysis, with a focus on polar and semipolar chemicals. Our methodology enables the quantitative (or semiquantitative) analysis of >2000 chemicals being compatible with suspect and nontarget strategies and providing unprecedented insights into the occurrence and potential bioaccumulation of diverse contaminants in this matrix. We comprehensively analyzed exogenous organic chemicals and associated metabolites in ten semen samples from Spanish participants collected in an area with a large presence of the chemical industry included in the LED-FERTYL Spanish study cohort. This investigation revealed the presence of various contaminants in semen, including plastic additives, PFAS, flame retardants, surfactants, and insecticides. Notably, prevalent plastic additives such as phthalic acid esters and bisphenols were identified, indicating potential health risks. Additionally, we uncovered previously understudied chemicals like the tire additive 2-mercaptobenzothiazole and specific organophosphate flame retardants. This study showcases the potential of our methodology as a valuable tool for large-scale cohort studies, providing insights into the association between contaminant exposure and the risk of male fertility impairments.

Associations between ultra-processed food consumption and kidney function in an older adult population with metabolic syndrome.

BACKGROUND & AIMS: Ultra-processed food (UPF) consumption has increased dramatically over the last decades worldwide. Although it has been linked to some cardiometabolic comorbidities, there is limited evidence regarding kidney function. This study aimed to cross-sectionally and longitudinally assess the association between UPF consumption and estimated-glomerular filtration rate (eGFR) based on Cystatin C (CysC). METHODS: Older adults (mean age 65 ± 5.0 years, 46% women) with overweight/obesity and metabolic syndrome (MetS) who had available data of CysC at baseline (n = 1909), at one-year and at 3-years of follow-up (n = 1700) were analyzed. Food consumption was assessed using a validated 143-item semi-quantitative food frequency questionnaire and UPF consumption (% of g/d) at baseline and changes after one-year of follow-up were estimated according to NOVA classification system. Multivariable-adjusted linear and logistic regression models were performed to evaluate the cross-sectional associations between UPF consumption with eGFR levels and decreased kidney function (eGFR <60 ml/min/1.73 m2) at baseline. Multivariable-adjusted mixed-effects linear regression models were fitted to investigate the associations between one-year changes in UPF and eGFR over 3-years of follow-up. RESULTS: Individuals with the highest baseline UPF consumption showed lower eGFR (ß: -3.39 ml/min/1.73 m2; 95% CI: -5.59 to -1.20) and higher odds of decreased kidney function (OR: 1.64; 95% CI: 1.21 to 2.22) at baseline, compared to individuals in the lowest tertile. Participants in the highest tertile of one-year changes in UPF consumption presented a significant decrease in eGFR after one-year of follow-up (ß: -1.45 ml/min/1.73 m2; 95% CI: -2.90 to -0.01) as well as after 3-years of follow-up (ß: -2.18 ml/min/1.73 m2; 95% CI: -3.71 to -0.65) compared to those in the reference category. CONCLUSIONS: In a Mediterranean population of older adults with overweight/obesity and MetS, higher UPF consumption at baseline and one-year changes towards higher consumption of UPF were associated with worse kidney function at baseline and over 3-years of follow-up, respectively. CLINICAL TRIAL REGISTRY NUMBER: ISRCTN89898870.

Dietary Iron, Anemia Markers, Cognition, and Quality of Life in Older Community-Dwelling Subjects at High Cardiovascular Risk.

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality.

An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition: An Interim Subgroup Analysis of the PREDIMED-Plus Randomized Clinical Trial.

Importance: Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. Objective: To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. Design, Setting, and Participants: The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. Intervention: Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. Main Outcomes and Measures: The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). Results: A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. Conclusions and Relevance: The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points. Trial Registration: isrctn.org Identifier: ISRCTN89898870.

Reproducibility and relative validity of a semi-quantitative food and beverage frequency questionnaire for Spanish children aged 3 to 11 years: the COME-Kids F&B-FQ.

A reliable food and beverage frequency questionnaire (F&B-FQ) to measure dietary intakes for children across Spain is currently unavailable. Thus, we designed and assessed the reproducibility and relative validity of a new F&B-FQ in 210 Spanish children aged 3-11 years. COME-Kids F&B-FQ contained 125 items to assess the usual diet intake in the past year among children. To explore the reproducibility, caregivers answered COME-Kids F&B-FQ twice over a 15-day period (± 1 week). To evaluate the relative validity, estimates from a third COME-Kids F&B-FQ administered at 1 year of follow-up were compared with the mean estimates from 3-day dietary records (3d-DR) collected at baseline, 6 months, and after 1 year of follow-up. Reproducibility and relative validity of the COME-Kids F&B-FQ in estimating food groups and nutrients were assessed using Pearson (r) and intra-class (ICC) correlation coefficients. We used the kappa index to evaluate the agreement in repeat administrations or with the 3d-DR. We used Bland-Altman plots to identify bias across levels of intake. A total of 195 children (105 boys, 90 girls) completed the study. The reproducibility of data estimated from COME-Kids F&B-FQ was substantial with mean r and ICC being 0.65 and 0.64 for food groups and 0.63 and 0.62 for nutrients, respectively. Validation assessments comparing the FFQ and 3d-DRs showed r = 0.36 and ICC = 0.30 for food groups and r = 0.29 and ICC = 0.24 for nutrients. The mean agreement for food group reproducibility and relative validity was 86% and 65%, respectively. These estimates were 85% for reproducibility and 64% for relative validity in the case of nutrients. For reproducibility and relative validity, the overall mean kappa index was 63% and 37% for all food groups and 52% and 27% for nutrients, respectively. Bland-Altman plots showed no specific bias relating to the level of intake of nutrients and several food groups. CONCLUSION: COME-Kids F&B-FQ showed substantial reproducibility and acceptable relative validity to assess food and beverage intake in Spanish children aged 3 to 11 years. Most children were correctly classified in relation to the intake of food groups and nutrients, and misclassification was unlikely with reference to 3d-DR. WHAT IS KNOWN: • The estimation of dietary intake in children is complex, especially in large cohorts. • The food frequency questionnaire is a well-recognized and the most frequently used method for assessing food consumption. WHAT IS NEW: • A new food and beverage frequency questionnaire including a beverage section and novel plant-based food items has been validated in Spanish children aged 3-11 years.

Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort.

BACKGROUND: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk. METHODS: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring. RESULTS: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HRadj (95%CI): 1.01 (1.00, 1.03)) and BMI (HRadj: 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk. CONCLUSIONS: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19. TRIAL REGISTRATION: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 ).

Plasma metabolite profiles associated with the World Cancer Research Fund/American Institute for Cancer Research lifestyle score and future risk of cardiovascular disease and type 2 diabetes.

BACKGROUND: A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk. METHODS: In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models. RESULTS: The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38-0.77 for dichotomous HL, and 0.22, 0.11-0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42-0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31-1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained or attenuated, respectively, for the 1-year metabolomic profile. CONCLUSIONS: In an elderly population at high risk of CVD, a set of metabolites was selected as potential metabolites associated with the HL pattern predicting the risk of T2D and, to a lesser extent, CVD. These results support previous findings that some of these metabolites are inversely associated with the risk of T2D and CVD. TRIAL REGISTRATION: The PREDIMED trial was registered at ISRCTN ( http://www.isrctn.com/ , ISRCTN35739639).

Two-Year Changes in Physical Activity and Concurrent Changes in Cognitive Function in a Cohort of Adults with Metabolic Syndrome.

BACKGROUND: It has been proposed that physical activity (PA) could prevent cognitive decline. OBJECTIVE: To evaluate the association between changes in PA and changes in cognitive function in a cohort of adults with metabolic syndrome. METHODS: Longitudinal observational study including 5,500 adults (mean age 65 years, SD = 5; women = 49.3% ) with metabolic syndrome. Participants underwent physical activity measurements and cognitive evaluation at baseline and at two-years of follow-up. PA was quantified using the Minnesota questionnaire-shortened version. Cognitive function was evaluated using a battery of tests: Mini-Mental Test Examination, Clock Drawing Test, Trail Making Test A and B, Verbal Fluency Test, and Digit Span. The primary outcome was two-year change in cognition, measured through the Global Composite Score (GCS) of all neuropsychological tests. Multivariable-adjusted linear regression models were fitted with baseline PA and their changes as the main exposures and changes in cognitive function as the outcome. RESULTS: No significant association was found between PA levels (or their changes) in the GCS of cognitive function. A greater increase in PA levels was associated with a more favorable two-year change in the Trail Making Test A (Q4 versus Q1: b = - 2.24s, 95% CI -4.36 to -0.12s; p-trend = 0.020). No significant association was found for other neuropsychological test. CONCLUSION: Our results do not support an association between increases in PA and the evolution of the global cognitive function at two-year in an intervention trial which included PA promotion in one of its two randomized arms, but they suggested a possible beneficial effect of PA on attentional function in older adults.

Yearly attained adherence to Mediterranean diet and incidence of diabetes in a large randomized trial.

BACKGROUND: Several large observational prospective studies have reported a protection by the traditional Mediterranean diet against type 2 diabetes, but none of them used yearly repeated measures of dietary intake. Repeated measurements of dietary intake are able to improve subject classification and to increase the quality of the assessed relationships in nutritional epidemiology. Beyond observational studies, randomized trials provide stronger causal evidence. In the context of a randomized trial of primary cardiovascular prevention, we assessed type 2 diabetes incidence according to yearly repeated measures of compliance with a nutritional intervention based on the traditional Mediterranean diet. METHODS: PREDIMED (''PREvención con DIeta MEDiterránea'') was a Spanish trial including 7447 men and women at high cardiovascular risk. We assessed 3541 participants initially free of diabetes and originally randomized to 1 of 3 diets: low-fat diet (n = 1147, control group), Mediterranean diet supplemented with extra virgin olive (n = 1154) or Mediterranean diet supplemented with mixed nuts (n = 1240). As exposure we used actual adherence to Mediterranean diet (cumulative average), yearly assessed with the Mediterranean Diet Adherence Screener (scoring 0 to 14 points), and repeated up to 8 times (baseline and 7 consecutive follow-up years). This score was categorized into four groups: < 8, 8-< 10, 10- < 12, and 12-14 points. The outcome was new-onset type 2 diabetes. RESULTS: Multivariable-adjusted hazard ratios from time-varying Cox models were 0.80 (95% confidence interval, 0.70-0.92) per + 2 points in Mediterranean Diet Adherence Screener (linear trend p = .001), and 0.46 (0.25-0.83) for the highest (12-14 points) versus the lowest (< 8) adherence. This inverse association was maintained after additionally adjusting for the randomized arm. Age- and sex-adjusted analysis of a validated plasma metabolomic signature of the Mediterranean Diet Adherence Screener (constituted of 67 metabolites) in a subset of 889 participants also supported these results. CONCLUSIONS: Dietary intervention trials should quantify actual dietary adherence throughout the trial period to enhance the benefits and to assist results interpretation. A rapid dietary assessment tool, yearly repeated as a screener, was able to capture a strong inverse linear relationship between Mediterranean diet and type 2 diabetes. Trial registration ISRCTN35739639.