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).

Associations between the New DNA-Methylation-Based Telomere Length Estimator, the Mediterranean Diet and Genetics in a Spanish Population at High Cardiovascular Risk.

Biological aging is a relevant risk factor for chronic diseases, and several indicators for measuring this factor have been proposed, with telomere length (TL) among the most studied. Oxidative stress may regulate telomere shortening, which is implicated in the increased risk. Using a novel estimator for TL, we examined whether adherence to the Mediterranean diet (MedDiet), a highly antioxidant-rich dietary pattern, is associated with longer TL. We determined TL using DNA methylation algorithms (DNAmTL) in 414 subjects at high cardiovascular risk from Spain. Adherence to the MedDiet was assessed by a validated score, and genetic variants in candidate genes and at the genome-wide level were analyzed. We observed several significant associations (p < 0.05) between DNAmTL and candidate genes (TERT, TERF2, RTEL1, and DCAF4), contributing to the validity of DNAmTL as a biomarker in this population. Higher adherence to the MedDiet was associated with lower odds of having a shorter TL in the whole sample (OR = 0.93; 95% CI: 0.85-0.99; p = 0.049 after fully multivariate adjustment). Nevertheless, this association was stronger in women than in men. Likewise, in women, we observed a direct association between adherence to the MedDiet score and DNAmTL as a continuous variable (beta = 0.015; SE: 0.005; p = 0.003), indicating that a one-point increase in adherence was related to an average increase of 0.015 ± 0.005 kb in TL. Upon examination of specific dietary items within the global score, we found that fruits, fish, "sofrito", and whole grains exhibited the strongest associations in women. The novel score combining these items was significantly associated in the whole population. In the genome-wide association study (GWAS), we identified ten polymorphisms at the suggestive level of significance (p < 1 × 10-5) for DNAmTL (intergenics, in the IQSEC1, NCAPG2, and ABI3BP genes) and detected some gene-MedDiet modulations on DNAmTL. As this is the first study analyzing the DNAmTL estimator, genetics, and modulation by the MedDiet, more studies are needed to confirm these findings.

Ultra-processed foods consumption as a promoting factor of greenhouse gas emissions, water, energy, and land use: A longitudinal assessment.

BACKGROUND: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability. OBJECTIVES: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use. DESIGN: A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome. METHODS: Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse® 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models. RESULTS: Participants with major reductions in their UPF consumption reduced their impact by -0.6 kg of CO2eq and -5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced. CONCLUSIONS: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection. TRIAL REGISTRATION: ISRCTN, ISRCTN89898870. Registered 05 September 2013, http://www.isrctn.com/ISRCTN89898870.

DNA-Methylation Signatures of Tobacco Smoking in a High Cardiovascular Risk Population: Modulation by the Mediterranean Diet.

Biomarkers based on DNA methylation are relevant in the field of environmental health for precision health. Although tobacco smoking is one of the factors with a strong and consistent impact on DNA methylation, there are very few studies analyzing its methylation signature in southern European populations and none examining its modulation by the Mediterranean diet at the epigenome-wide level. We examined blood methylation smoking signatures on the EPIC 850 K array in this population (n = 414 high cardiovascular risk subjects). Epigenome-wide methylation studies (EWASs) were performed analyzing differential methylation CpG sites by smoking status (never, former, and current smokers) and the modulation by adherence to a Mediterranean diet score was explored. Gene-set enrichment analysis was performed for biological and functional interpretation. The predictive value of the top differentially methylated CpGs was analyzed using receiver operative curves. We characterized the DNA methylation signature of smoking in this Mediterranean population by identifying 46 differentially methylated CpGs at the EWAS level in the whole population. The strongest association was observed at the cg21566642 (p = 2.2 × 10-32) in the 2q37.1 region. We also detected other CpGs that have been consistently reported in prior research and discovered some novel differentially methylated CpG sites in subgroup analyses. In addition, we found distinct methylation profiles based on the adherence to the Mediterranean diet. Particularly, we obtained a significant interaction between smoking and diet modulating the cg5575921 methylation in the AHRR gene. In conclusion, we have characterized biomarkers of the methylation signature of tobacco smoking in this population, and suggest that the Mediterranean diet can increase methylation of certain hypomethylated sites.

Single and Combined Associations of Plasma and Urine Essential Trace Elements (Zn, Cu, Se, and Mn) with Cardiovascular Risk Factors in a Mediterranean Population.

Trace elements are micronutrients that are required in very small quantities through diet but are crucial for the prevention of acute and chronic diseases. Despite the fact that initial studies demonstrated inverse associations between some of the most important essential trace elements (Zn, Cu, Se, and Mn) and cardiovascular disease, several recent studies have reported a direct association with cardiovascular risk factors due to the fact that these elements can act as both antioxidants and pro-oxidants, depending on several factors. This study aims to investigate the association between plasma and urine concentrations of trace elements and cardiovascular risk factors in a general population from the Mediterranean region, including 484 men and women aged 18−80 years and considering trace elements individually and as joint exposure. Zn, Cu, Se, and Mn were determined in plasma and urine using an inductively coupled plasma mass spectrometer (ICP-MS). Single and combined analysis of trace elements with plasma lipid, blood pressure, diabetes, and anthropometric variables was undertaken. Principal component analysis, quantile-based g-computation, and calculation of trace element risk scores (TERS) were used for the combined analyses. Models were adjusted for covariates. In single trace element models, we found statistically significant associations between plasma Se and increased total cholesterol and systolic blood pressure; plasma Cu and increased triglycerides and body mass index; and urine Zn and increased glucose. Moreover, in the joint exposure analysis using quantile g-computation and TERS, the combined plasma levels of Zn, Cu, Se (directly), and Mn (inversely) were strongly associated with hypercholesterolemia (OR: 2.03; 95%CI: 1.37−2.99; p < 0.001 per quartile increase in the g-computation approach). The analysis of urine mixtures revealed a significant relationship with both fasting glucose and diabetes (OR: 1.91; 95%CI: 1.01−3.04; p = 0.046). In conclusion, in this Mediterranean population, the combined effect of higher plasma trace element levels (primarily Se, Cu, and Zn) was directly associated with elevated plasma lipids, whereas the mixture effect in urine was primarily associated with plasma glucose. Both parameters are relevant cardiovascular risk factors, and increased trace element exposures should be considered with caution.

Association between Microbiome-Related Human Genetic Variants and Fasting Plasma Glucose in a High-Cardiovascular-Risk Mediterranean Population.

Background and Objectives: The gut microbiota has been increasingly recognized as a relevant factor associated with metabolic diseases. However, directly measuring the microbiota composition is a limiting factor for several studies. Therefore, using genetic variables as proxies for the microbiota composition is an important issue. Landmark microbiome-host genome-wide association studies (mbGWAS) have identified many SNPs associated with gut microbiota. Our aim was to analyze the association between relevant microbiome-related genetic variants (Mi-RSNPs) and fasting glucose and type 2 diabetes in a Mediterranean population, exploring the interaction with Mediterranean diet adherence. Materials and Methods: We performed a cross-sectional study in a high-cardiovascular-risk Mediterranean population (n = 1020), analyzing the association of Mi-RSNPs (from four published mbGWAS) with fasting glucose and type 2 diabetes. A single-variant approach was used for fitting fasting glucose and type 2 diabetes to a multivariable regression model. In addition, a Mendelian randomization analysis with multiple variants was performed as a sub-study. Results: We obtained several associations between Mi-RSNPs and fasting plasma glucose involving gut Gammaproteobacteria_HB, the order Rhizobiales, the genus Rumminococcus torques group, and the genus Tyzzerella as the top ranked. For type 2 diabetes, we also detected significant associations with Mi-RSNPs related to the order Rhizobiales, the family Desulfovibrionaceae, and the genus Romboutsia. In addition, some Mi-RSNPs and adherence to Mediterranean diet interactions were detected. Lastly, the formal Mendelian randomization analysis suggested combined effects. Conclusions: Although the use of Mi-RSNPs as proxies of the microbiome is still in its infancy, and although this is the first study analyzing such associations with fasting plasma glucose and type 2 diabetes in a Mediterranean population, some interesting associations, as well as modulations, with adherence to the Mediterranean diet were detected in these high-cardiovascular-risk subjects, eliciting new hypotheses.

Influence of DNA-Polymorphisms in Selected Circadian Clock Genes on Clock Gene Expression in Subjects from the General Population and Their Association with Sleep Duration.

Background and Objectives: Circadian rhythms have an important implication in numerous physiological and metabolic processes, including the sleep/wake cycle. Inter-individual differences in factors associated with circadian system may be due to gene differences in gene expression. Although several studies have analyzed the association between DNA polymorphisms and circadian variables, the influence on gene expression has been poorly analyzed. Our goal was to analyze the association of genetic variations in the clock genes and the gene expression level. Materials and Methods: We carried out a cross-sectional study of 102 adults (50.9% women). RNA and DNA were isolated from blood and single-nucleotide polymorphisms (SNPs), and the main circadian clock genes were determined. Gene expression of CLOCK, PER1, and VRK2 genes was measured by Reverse-transcription polymerase chain reaction (RT-PCR). The association between the DNA-SNPs and gene expression was analyzed at the gene level. In addition, a polygenic risk score (PRS), including all the significant SNPs related to gene expression, was created for each gene. Multivariable model analysis was performed. Results: Sex-specific differences were detected in PER1 expression, with these being higher in women (p = 0.034). No significant differences were detected in clock genes expression and lifestyle variables. We observed a significant association between the ARNTL-rs7924734, ARNTL-rs10832027, VRK2- rs2678902 SNPs, and CLOCK gene expression; the PER3-rs228642 and PER3-rs10127838 were related to PER1 expression, and the ARNTL-rs10832027, ARNTL-rs11022778, and MNTR1B-rs10830963 were associated with VRK2 gene expression (p < 0.05). The specific PRS created was significantly associated with each of the gene expressions analyzed (p < 0.001). Finally, sleep duration was associated with PER3-rs238666 (p = 0.008) and CLOCK-rs4580704 (p = 0.023). Conclusion: We detected significant associations between DNA-SNPs in the clock genes and their gene expression level in leukocytes and observed some differences in gene expression per sex. Moreover, we reported for the first time an association between clock gene polymorphisms and CLOCK, PER1, and VRK2 gene expression. These findings need further investigation.

Dairy Product Consumption and Changes in Cognitive Performance: Two-Year Analysis of the PREDIMED-Plus Cohort.

SCOPE: Dairy consumption has been suggested to impact cognition; however, evidence is limited and inconsistent. This study aims to longitudinally assess the association between dairy consumption with cognitive changes in an older Spanish population at high cardiovascular disease risk. METHODS AND RESULTS: Four thousand six hundred sixty eight participants aged 55-75 years, completed a validated food frequency questionnaire at baseline and a neuropsychological battery of tests at baseline and 2-year follow-up. Multivariable linear regression models are used, scaled by 100 (i.e., the units of ß correspond to 1 SD/100), to assess associations between baseline tertile daily consumption and 2-year changes in cognitive performance. Participants in the highest tertile of total milk and whole-fat milk consumption have a greater decline in global cognitive function (ß: -4.71, 95% CI: -8.74 to -0.69, p-trend = 0.020 and ß: -6.64, 95% CI: -10.81 to -2.47, p-trend = 0.002, respectively) compared to those in the lowest tertile. No associations are observed between low fat milk, yogurt, cheese or fermented dairy consumption, and changes in cognitive performance. CONCLUSION: Results suggest there are no clear prospective associations between consumption of most commonly consumed dairy products and cognition, although there may be an association with a greater rate of cognitive decline over a 2-year period in older adults at high cardiovascular disease risk for whole-fat milk.

Taxonomic and Functional Fecal Microbiota Signatures Associated With Insulin Resistance in Non-Diabetic Subjects With Overweight/Obesity Within the Frame of the PREDIMED-Plus Study.

Objective: An altered gut microbiota has been associated with insulin resistance, a metabolic dysfunction consisting of cellular insulin signaling impairment. The aim of the present study is to determine the taxonomic and functional fecal microbiota signatures associated with HOMA-IR index in a population with high cardiovascular risk. Methods: A total of 279 non-diabetic individuals (55-75 years aged) with overweight/obesity and metabolic syndrome were stratified according to tertiles of HOMA-IR index. Blood biochemical parameters, anthropometric measurements and fecal samples were collected at baseline. Fecal microbial DNA extraction, 16S amplicon sequencing and bioinformatics analysis were performed. Results: Desulfovibrio, Odoribacter and Oscillospiraceae UCG-002 were negatively associated with HOMA-IR index, whereas predicted total functional abundances revealed gut metabolic modules mainly linked to amino acid degradation. Butyricicoccus, Erysipelotrichaceae UCG-003, Faecalibacterium were positively associated with HOMA-IR index, whereas predicted total functional abundances revealed gut metabolic modules mainly linked to saccharide degradation. These bacteria contribute differentially to the gut metabolic modules, being the degree of contribution dependent on insulin resistance. Both taxa and gut metabolic modules negatively associated to HOMA-IR index were linked to mechanisms involving sulfate reducing bacteria, improvement of intestinal gluconeogenesis and production of acetate. Furthermore, both taxa and gut metabolic modules positively associated to HOMA-IR index were linked to production and mechanisms of action of butyrate. Conclusions: Specific taxonomic and functional fecal microbiota signatures associated with insulin resistance were identified in a non-diabetic population with overweight/obesity at high cardiovascular risk. These findings suggest that tailoring therapies based on specific fecal microbiota profiles could be a potential strategy to improve insulin sensitivity.

Association between the Prime Diet Quality Score and depressive symptoms in a Mediterranean population with metabolic syndrome. Cross-sectional and 2-year follow-up assessment from PREDIMED-PLUS study.

The burden of depression is increasing worldwide, specifically in older adults. Unhealthy dietary patterns may partly explain this phenomenon. In the Spanish PREDIMED-Plus study, we explored (1) the cross-sectional association between the adherence to the Prime Diet Quality Score (PDQS), an a priori-defined high-quality food pattern, and the prevalence of depressive symptoms at baseline (cross-sectional analysis) and (2) the prospective association of baseline PDQS with changes in depressive symptomatology after 2 years of follow-up. After exclusions, we assessed 6612 participants in the cross-sectional analysis and 5523 participants in the prospective analysis. An energy-adjusted high-quality dietary score (PDQS) was assessed using a validated FFQ. The cross-sectional association between PDQS and the prevalence of depression or presence of depressive symptoms and the prospective changes in depressive symptoms were evaluated through multivariable regression models (logistic and linear models and mixed linear-effects models). PDQS was inversely associated with depressive status in the cross-sectional analysis. Participants in the highest quintile of PDQS (Q5) showed a significantly reduced odds of depression prevalence as compared to participants in the lowest quartile of PDQS (Q1) (OR (95 %) CI = 0·82 (0·68, 0·98))). The baseline prevalence of depression decreased across PDQS quintiles (Pfor trend = 0·015). A statistically significant association between PDQS and changes in depressive symptoms after 2-years follow-up was found (ß (95 %) CI = -0·67 z-score (-1·17, -0·18). A higher PDQS was cross-sectionally related to a lower depressive status. Nevertheless, the null finding in our prospective analysis raises the possibility of reverse causality. Further prospective investigation is required to ascertain the association between PDQS and changes in depressive symptoms along time.

Transcriptional response to a Mediterranean diet intervention exerts a modulatory effect on neuroinflammation signaling pathway.

Background: The Traditional Mediterranean Diet (TMD) is known to have beneficial effects on several chronic diseases. However, data concerning the whole transcriptome modulation of the TMD are scarce.Objective: We aimed to explore the effects of the TMD on the whole transcriptome of individuals at high cardiovascular risk.Methods: Thirty-four participants at high cardiovascular risk were randomly assigned to a TMD enriched with extra-virgin olive oil (TMD + VOO), mixed nuts (TMD + Nuts), or a control diet based on low-fat diet recommendations. A microarray analysis in circulating peripheral blood mononuclear cells of the participants was conducted before and after 3 months of the intervention. The association of changes in gene expression was modeled into canonical pathways by conducting an untargeted functional analysis with the Ingenuity Pathway Analysis® (IPA). Effects were considered significant when the absolute z-score values were ≥2.0 and the logarithm P (adjusted by the Benjamini-Hochberg procedure [BH]) values were ≥1.30.Results: According to IPA, interventions with TMD + Nuts, TMD + VOO, and control diet downregulated neuroinflammation, triggering receptor expressed on myeloid cells 1 , and cholecystokinin/gastrin-mediated signaling pathways, respectively. The gene expression among these pathways included cytokines, T-cell activation receptors, nuclear factor kappa ß/inflammasome components, pro-inflammatory enzymes and cell cycle regulators.Conclusion: The current findings suggest that the TMD enriched with mixed nuts or VOO downregulate transcriptomic pathways, including those related to neuroinflammation, which could influence development of neurodegenerative diseases. Our data should be corroborated in other tissue cells, such as neurons and glial cells. The PREDIMED trial was registered at https://www.controlled-trials.com (ISRCTN35739639).

Mediterranean, DASH, and MIND Dietary Patterns and Cognitive Function: The 2-Year Longitudinal Changes in an Older Spanish Cohort.

Background and Aims: Plant-forward dietary patterns have been associated with cardiometabolic health benefits, which, in turn, have been related to cognitive performance with inconsistent findings. The objective of this study was to examine the relationship between baseline adherence to three a priori dietary patterns (Mediterranean, DASH, and MIND diets) with 2-year changes in cognitive performance in older adults with overweight or obesity and high cardiovascular disease risk. Methods: A prospective cohort analysis was conducted within the PREDIMED-Plus trial, involving 6,647 men and women aged 55-75 years with overweight or obesity and metabolic syndrome. Using a validated, semiquantitative 143-item food frequency questionnaire completed at baseline, the dietary pattern adherence scores were calculated. An extensive neuropsychological test battery was administered at baseline and 2-year follow-up. Multivariable-adjusted linear regression models were used to assess associations between 2-year changes in cognitive function z-scores across tertiles of baseline adherence to the a priori dietary patterns. Results: Adherence to the Mediterranean diet at baseline was associated with 2-year changes in the general cognitive screening Mini-Mental State Examination (MMSE, ß: 0.070; 95% CI: 0.014, 0.175, P-trend = 0.011), and two executive function-related assessments: the Trail Making Tests Part A (TMT-A, ß: -0.054; 95% CI: -0.110, - 0.002, P-trend = 0.047) and Part B (TMT-B, ß: -0.079; 95% CI: -0.134, -0.024, P-trend = 0.004). Adherence to the MIND diet was associated with the backward recall Digit Span Test assessment of working memory (DST-B, ß: 0.058; 95% CI: 0.002, 0.114, P-trend = 0.045). However, higher adherence to the DASH dietary pattern was not associated with better cognitive function over a period of 2 years. Conclusion: In older Spanish individuals with overweight or obesity and at high cardiovascular disease risk, higher baseline adherence to the Mediterranean dietary pattern may be associated with better cognitive performance than lower adherence over a period of 2 years.

A molecular signature for the metabolic syndrome by urine metabolomics.

BACKGROUND: Metabolic syndrome (MetS) is a multimorbid long-term condition without consensual medical definition and a diagnostic based on compatible symptomatology. Here we have investigated the molecular signature of MetS in urine. METHODS: We used NMR-based metabolomics to investigate a European cohort including urine samples from 11,754 individuals (18-75 years old, 41% females), designed to populate all the intermediate conditions in MetS, from subjects without any risk factor up to individuals with developed MetS (4-5%, depending on the definition). A set of quantified metabolites were integrated from the urine spectra to obtain metabolic models (one for each definition), to discriminate between individuals with MetS. RESULTS: MetS progression produces a continuous and monotonic variation of the urine metabolome, characterized by up- or down-regulation of the pertinent metabolites (17 in total, including glucose, lipids, aromatic amino acids, salicyluric acid, maltitol, trimethylamine N-oxide, and p-cresol sulfate) with some of the metabolites associated to MetS for the first time. This metabolic signature, based solely on information extracted from the urine spectrum, adds a molecular dimension to MetS definition and it was used to generate models that can identify subjects with MetS (AUROC values between 0.83 and 0.87). This signature is particularly suitable to add meaning to the conditions that are in the interface between healthy subjects and MetS patients. Aging and non-alcoholic fatty liver disease are also risk factors that may enhance MetS probability, but they do not directly interfere with the metabolic discrimination of the syndrome. CONCLUSIONS: Urine metabolomics, studied by NMR spectroscopy, unravelled a set of metabolites that concomitantly evolve with MetS progression, that were used to derive and validate a molecular definition of MetS and to discriminate the conditions that are in the interface between healthy individuals and the metabolic syndrome.

Data-Driven Clustering Approach to Derive Taste Perception Profiles from Sweet, Salt, Sour, Bitter, and Umami Perception Scores: An Illustration among Older Adults with Metabolic Syndrome.

BACKGROUND: Current approaches to studying relations between taste perception and diet quality typically consider each taste-sweet, salt, sour, bitter, umami-separately or aggregately, as total taste scores. Consistent with studying dietary patterns rather than single foods or total energy, an additional approach may be to study all 5 tastes collectively as "taste perception profiles." OBJECTIVE: We developed a data-driven clustering approach to derive taste perception profiles from taste perception scores and examined whether profiles outperformed total taste scores for capturing individual variability in taste perception. METHODS: The cohort included 367 community-dwelling adults [55-75 y; 55% female; BMI (kg/m2): 32.2 ± 3.6] with metabolic syndrome from PREDIMED-Plus, Valencia. Cluster analysis identified subgroups of individuals with similar patterns in taste perception (taste perception profiles); quantitative criteria were used to select the cluster algorithm, determine the optimal number of clusters, and assess the profiles' validity and stability. Goodness-of-fit parameters from adjusted linear regression evaluated the individual variability captured by each approach. RESULTS: A k-means algorithm with 6 clusters best fit the data and identified the following taste perception profiles: Low All, High Bitter, High Umami, Low Bitter & Umami, High All But Bitter and High All But Umami. All profiles were valid and stable. Compared with total taste scores, taste perception profiles explained more variability in bitter and umami perception (adjusted R2: 0.19 vs. 0.63, respectively; 0.40 vs. 0.65, respectively) and were comparable for sweet, salt, and sour. In addition, taste perception profiles captured differential perceptions of each taste within individuals, whereas these patterns were lost with total taste scores. CONCLUSIONS: Among older adults with metabolic syndrome, taste perception profiles derived via data-driven clustering may provide a valuable approach to capture individual variability in perception of all 5 tastes and their collective influence on diet quality. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870.

Circulating Adiponectin and Its Association with Metabolic Traits and Type 2 Diabetes: Gene-Diet Interactions Focusing on Selected Gene Variants and at the Genome-Wide Level in High-Cardiovascular Risk Mediterranean Subjects.

Adiponectin is gaining renewed interest since, in addition to its possible protective role against insulin resistance and arteriosclerosis, recent studies suggest other additional favorable effects. However, the influence of gene-diet interactions on plasma adiponectin levels is still little understood. We analyzed the association between plasma adiponectin levels and various metabolic traits in a high-cardiovascular risk Mediterranean population, as well as the genetic effect of four candidate single-nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and their interactions with the Mediterranean dietary pattern. Additionally, we explored, at the genome-wide level, the SNPs most associated with plasma adiponectin levels, as well as gene-diet interactions with the Mediterranean diet. In the 954 participants studied (aged 55-80 years), plasma adiponectin levels were strongly associated with plasma HDL-C concentrations (p = 6.6 × 10-36) and inversely related to triglycerides (p = 4.7 × 10-18), fasting glucose (p = 3.5 × 10-16) and type 2 diabetes (p = 1.4 × 10-7). Of the four pre-selected ADIPOQ candidate SNPs, the one most associated with plasma adiponectin was the -11391G > A (rs17300539) promoter SNP (p = 7.2 × 10-5, in the multivariable adjusted model). No significant interactions with the Mediterranean diet pattern were observed for these SNPs. Additionally, in the exploratory genome-wide association study (GWAS), we found new SNPs associated with adiponectin concentrations at the suggestive genome-wide level (p < 1 × 10-5) for the whole population, including the lead SNP rs9738548 (intergenic) and rs11647294 in the VAT1L (Vesicle Amine Transport 1 Like) gene. We also found other promising SNPs on exploring different strata such as men, women, diabetics and non-diabetics (p = 3.5 × 10-8 for rs2850066). Similarly, we explored gene-Mediterranean diet interactions at the GWAS level and identified several SNPs with gene-diet interactions at p < 1 × 10-5. A remarkable gene-diet interaction was revealed for the rs2917570 SNP in the OPCML (Opioid Binding Protein/Cell Adhesion Molecule Like) gene, previously reported to be associated with adiponectin levels in some populations. Our results suggest that, in this high-cardiovascular risk Mediterranean population, and even though adiponectin is favorably associated with metabolic traits and lower type 2 diabetes, the gene variants more associated with adiponectin may be population-specific, and some suggestive gene-Mediterranean diet interactions were detected.

Sweet Taste Preference: Relationships with Other Tastes, Liking for Sugary Foods and Exploratory Genome-Wide Association Analysis in Subjects with Metabolic Syndrome.

Taste perception and its association with nutrition and related diseases (type 2 diabetes, obesity, metabolic syndrome, cardiovascular, etc.) are emerging fields of biomedicine. There is currently great interest in investigating the environmental and genetic factors that influence sweet taste and sugary food preferences for personalized nutrition. Our aims were: (1) to carry out an integrated analysis of the influence of sweet taste preference (both in isolation and in the context of other tastes) on the preference for sugary foods and its modulation by type 2 diabetes status; (2) as well as to explore new genetic factors associated with sweet taste preference. We studied 425 elderly white European subjects with metabolic syndrome and analyzed taste preference, taste perception, sugary-foods liking, biochemical and genetic markers. We found that type 2 diabetic subjects (38%) have a small, but statistically higher preference for sweet taste (p = 0.021) than non-diabetic subjects. No statistically significant differences (p > 0.05) in preferences for the other tastes (bitter, salty, sour or umami) were detected. For taste perception, type 2 diabetic subjects have a slightly lower perception of all tastes (p = 0.026 for the combined "total taste score"), bitter taste being statistically lower (p = 0.023). We also carried out a principal component analysis (PCA), to identify latent variables related to preferences for the five tastes. We identified two factors with eigenvalues >1. Factor 2 was the one with the highest correlation with sweet taste preference. Sweet taste preference was strongly associated with a liking for sugary foods. In the exploratory SNP-based genome-wide association study (GWAS), we identified some SNPs associated with sweet taste preference, both at the suggestive and at the genome-wide level, especially a lead SNP in the PTPRN2 (Protein Tyrosine Phosphatase Receptor Type N2) gene, whose minor allele was associated with a lower sweet taste preference. The PTPRN2 gene was also a top-ranked gene obtained in the gene-based exploratory GWAS analysis. In conclusion, sweet taste preference was strongly associated with sugary food liking in this population. Our exploratory GWAS identified an interesting candidate gene related with sweet taste preference, but more studies in other populations are required for personalized nutrition.

Associations between Taste Perception Profiles and Empirically Derived Dietary Patterns: An Exploratory Analysis among Older Adults with Metabolic Syndrome.

Taste perception is a primary driver of food choices; however, little is known about how perception of all five tastes (sweet, salt, sour, bitter, umami) collectively inform dietary patterns. Our aim was to examine the associations between a multivariable measure of taste perception-taste perception profiles-and empirically derived dietary patterns. The cohort included 367 community-dwelling adults (55-75 years; 55% female; BMI = 32.2 ± 3.6 kg/m2) with metabolic syndrome from PREDIMED-Plus, Valencia. Six taste perception profiles were previously derived via data-driven clustering (Low All, High Bitter, High Umami, Low Bitter and Umami, High All But Bitter, High All But Umami); three dietary patterns were derived via principal component analysis (% variance explained = 20.2). Cross-sectional associations between profiles and tertials of dietary pattern adherence were examined by multinomial logistic regression. Overall, there were several significant differences in dietary pattern adherence between profiles: the vegetables, fruits, and whole grains pattern was significantly more common for the High All But Umami profile (OR range for high vs. low adherence relative to other profiles (1.45-1.99; 95% CI minimum lower, maximum upper bounds: 1.05, 2.74), the non-extra virgin olive oils, sweets, and refined grains pattern tended to be less common for Low All or High Bitter profiles (OR range: 0.54-0.82), while the alcohol, salty foods, and animal fats pattern tended to be less common for Low Bitter and Umami and more common for High All But Bitter profiles (OR range: 0.55-0.75 and 1.11-1.81, respectively). In conclusion, among older adults with metabolic syndrome, taste perception profiles were differentially associated with dietary patterns, suggesting the benefit of integrating taste perception into personalized nutrition guidance.

Effect of Physical Activity, Smoking, and Sleep on Telomere Length: A Systematic Review of Observational and Intervention Studies.

Aging is a risk factor for several pathologies, restricting one's health span, and promoting chronic diseases (e.g., cardiovascular and neurodegenerative diseases), as well as cancer. Telomeres are regions of repetitive DNA located at chromosomal ends. Telomere length has been inversely associated with chronological age and has been considered, for a long time, a good biomarker of aging. Several lifestyle factors have been linked with telomere shortening or maintenance. However, the consistency of results is hampered by some methodological issues, including study design, sample size, measurement approaches, and population characteristics, among others. Therefore, we aimed to systematically review the current literature on the effects of three relevant lifestyle factors on telomere length in human adults: physical activity, smoking, and sleep. We conducted a qualitative systematic review of observational and intervention studies using the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic literature search covered articles published in MEDLINE and EMBASE databases (from 2010 to 2020). A total of 1400 studies were identified; 83 were included after quality control. Although fewer sedentary activities, optimal sleep habits, and non- or ex-smoker status have been associated with less telomere shortening, several methodological issues were detected, including the need for more targeted interventions and standardized protocols to better understand how physical activity and sleep can impact telomere length and aging. We discuss the main findings and current limitations to gain more insights into the influence of these lifestyle factors on the healthy aging process.

Chronological Age Interacts with the Circadian Melatonin Receptor 1B Gene Variation, Determining Fasting Glucose Concentrations in Mediterranean Populations. Additional Analyses on Type-2 Diabetes Risk.

Gene-age interactions have not been systematically investigated on metabolic phenotypes and this modulation will be key for a better understanding of the temporal regulation in nutrigenomics. Taking into account that aging is typically associated with both impairment of the circadian system and a decrease in melatonin secretion, we focused on the melatonin receptor 1B (MTNR1B)-rs10830963 C>G variant that has been associated with fasting glucose concentrations, gestational diabetes, and type-2 diabetes. Therefore, our main aim was to investigate whether the association between the MTNR1B-rs10830963 polymorphism and fasting glucose is age dependent. Our secondary aims were to analyze the polymorphism association with type-2 diabetes and explore the gene-pregnancies interactions on the later type-2 diabetes risk. Three Mediterranean cohorts (n = 2823) were analyzed. First, a cross-sectional study in the discovery cohort consisting of 1378 participants (aged 18 to 80 years; mean age 41 years) from the general population was carried out. To validate and extend the results, two replication cohorts consisting of elderly individuals were studied. In the discovery cohort, we observed a strong gene-age interaction (p = 0.001), determining fasting glucose in such a way that the increasing effect of the risk G-allele was much greater in young (p = 5.9 × 10-10) than in elderly participants (p = 0.805). Consistently, the association of the MTNR1B-rs10830963 polymorphism with fasting glucose concentrations in the two replication cohorts (mean age over 65 years) did not reach statistical significance (p > 0.05 for both). However, in the elderly cohorts, significant associations between the polymorphism and type-2 diabetes at baseline were found. Moreover, in one of the cohorts, we obtained a statistically significant interaction between the MTNR1B polymorphism and the number of pregnancies, retrospectively assessed, on the type-2 diabetes risk. In conclusion, the association of the MTNR1B-rs10830963 polymorphism with fasting glucose is age-dependent, having a greater effect in younger people. However, in elderly subjects, associations of the polymorphism with type-2 diabetes were observed and our exploratory analysis suggested a modulatory effect of the number of past pregnancies on the future type-2 diabetes genetic risk.

Ultra-Performance Liquid Chromatography-Ion Mobility Separation-Quadruple Time-of-Flight MS (UHPLC-IMS-QTOF MS) Metabolomics for Short-Term Biomarker Discovery of Orange Intake: A Randomized, Controlled Crossover Study.

A major problem with dietary assessments is their subjective nature. Untargeted metabolomics and new technologies can shed light on this issue and provide a more complete picture of dietary intake by measuring the profile of metabolites in biological samples. Oranges are one of the most consumed fruits in the world, and therefore one of the most studied for their properties. The aim of this work was the application of untargeted metabolomics approach with the novel combination of ion mobility separation coupled to high resolution mass spectrometry (IMS-HRMS) and study the advantages that this technique can bring to the area of dietary biomarker discovery, with the specific case of biomarkers associated with orange consumption (Citrus reticulata) in plasma samples taken during an acute intervention study (consisting of a randomized, controlled crossover trial in healthy individuals). A total of six markers of acute orange consumption, including betonicines and conjugated flavonoids, were identified with the experimental data and previous literature, demonstrating the advantages of ion mobility in the identification of dietary biomarkers and the benefits that an additional structural descriptor, as the collision cross section value (CCS), can provide in this area.