Current Developments in Nutrition

Outcomes from the COSMOS trial have reinforced the notion of flavanols as important plant-derived bioactives contributing to cardiovascular health. As discussions continue on whether specific dietary reference values for flavanols are warranted, it is possible that existing dietary guidelines emphasizing fruits and vegetables already yield sufficient flavanol intake levels. If this were the case, developing flavanol specific dietary reference values might be unnecessary. This study therefore aimed at assessing whether adherence to dietary recommendations for fruit and vegetable intake and overall diet quality achieves flavanol intake levels of 500 mg/day, the amount proven to mediate cardiovascular benefits in the COSMOS trial. Flavanol intake was objectively evaluated using two validated and complementary biomarkers, 5-(3{square},4{square}-dihydroxyphenyl)-{gamma}-valerolactone metabolites (gVLMB) and structurally related (-)-epicatechin metabolites (SREMB), in two geographically distinct studies: COSMOS (US; n=6,509) and EPIC-Norfolk (UK; n=24,154). The results showed that higher fruit and vegetable intakes and diet quality (assessed via the alternative healthy eating index-aHEI) were associated with increased flavanol intake in COSMOS. Nevertheless, fewer than 25% of participants meeting dietary guidelines achieved an estimated flavanol intake of [≥]500 mg/day. Similar findings were observed in EPIC-Norfolk as well as through flavanol intake simulations considering fruits and vegetables commonly consumed in the US diet. In conclusion, adherence to existing dietary guidelines does not yield flavanol intake levels comparable to those shown to provide cardiovascular benefits in COSMOS. Thus, specific dietary reference values for flavanols may still be necessary if aiming to increase the intake of these dietary compounds. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/26346949v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@24faeaorg.highwire.dtl.DTLVardef@1d52a29org.highwire.dtl.DTLVardef@1c2ff33org.highwire.dtl.DTLVardef@100a384_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundCaloric restriction (CR) improves markers of biological aging, yet long-term effects on the human metabolome remain unclear. ObjectiveThis study examined the effects of CR (2 years) in healthy adults without obesity on circulating metabolites linked to aging and metabolic adaptations. MethodsUntargeted metabolomics was performed using fasted plasma samples collected at baseline, 12, and 24 months (BL, 12M, 24M) from CALERIE participants randomized to CR or ad libitum (AL) control. A total of 864 known metabolites were identified and grouped into nine biologically coherent super pathways to support pathway-level interpretation (amino acid, peptide, carbohydrate, energy, lipid, nucleotide, cofactors and vitamins, xenobiotics, and partially characterized molecules). Principal component analysis (PCA) summarized metabolite variation, and linear mixed models assessed intervention effects on each PC in group-by-time interactions. ResultsThree principal components showed significant group-by-time interactions: PC2 (carbohydrate), PC5 (partially characterized molecules), and PC4 (lipid). Carbohydrate (PC2) and partially characterized metabolites (PC5) decreased from baseline to 12M in both groups; from 12M to 24M, levels stabilized in CR but increased in AL for PC2, while PC5 continued to decline in CR and increased in AL. Lipid metabolites (PC4) decreased in CR and increased in AL at 12M, with the pattern reversing from 12M to 24M. Key contributors included malto-saccharides and related carbohydrate intermediates for PC2, glutamine degradants and lactone sulfates for PC5, and sphingolipids for PC4. ConclusionThis study provided insights into metabolic changes during CR, particularly for carbohydrate and lipid metabolism. Carbohydrate and lipid metabolites that were reduced by CR during the weight loss phase (BL to 12M) followed by stabilization or compensatory responses during the weight maintenance phase (12M to 24M) may link CR-induced changes in metabolism to inflammation. Future research is needed to tease out CR adaptations versus diet related changes in metabolites and explore the functional significance of these metabolic changes during CR for aging and long-term metabolic health. ConclusionCR produced distinct, time-dependent shifts in carbohydrate and lipid pathways. Early reductions during weight loss followed by stabilization or compensatory responses during weight maintenance suggest dynamic metabolic remodeling that may relate to inflammation-linked mechanisms. Further work is needed to distinguish CR-specific adaptations from dietary influences and to clarify the functional significance of these metabolic changes for aging and long-term metabolic health.

BackgroundHuman milk (HM) bioactive components can have immune modulatory functions, impact the gut microbiome, and may result in functional benefits when added to infant formula (IF). In this single-arm, prospective, intervention study, we tested the effectiveness of an IF with a whey protein concentrate co-enriched in -lactalbumin, milk fat globule membrane (MFGM), and Sn-2 palmitate resulting in protein and lipid profiles observed in HM. The outcomes tested were feeding tolerance, Bifidobacteria abundance, and intestinal and immune health of Chinese infants. MethodsPredominantly formula-fed (FF) and breastfed (BF) infants were enrolled between 3 and 28 days and assigned to the FF (N= 60) or BF (N=60) group, per their feeding practice, for 6 weeks. The primary endpoint was Infant Gastrointestinal Symptom Questionnaire (IGSQ) index score assessed using a validated IGSQ-13 questionnaire after 6 weeks of intervention; non-inferiority of FF vs BF was tested. Secondary endpoints included fecal Bifidobacteria abundance assessed using shotgun metagenomics sequencing; fecal short chain fatty acids (SCFAs) analyzed by ultra-performance liquid chromatography-tandem mass spectrometry; fecal markers of immune response, inflammation, intestinal barrier integrity (secretory immunoglobulin A sIgA), cytokines, calprotectin, 1 antitrypsin, lipocalin-2) assessed using enzyme-linked immunosorbent assay; stool consistency assessed using gastrointestinal (GI) diary; anthropometric assessments; quality of life; physician reported adverse events; and use of medications. ResultsGood GI tolerance was observed in both groups at V2 (mean{+/-}SD IGSQ score FF: 19.9{+/-}7.4; BF: 16.8{+/-}4.2); difference of means 1.35 [95% CI: -1.312, 4.012]). After 6 weeks, Bifidobacterium genus relative abundance was not significantly different between the groups. Total SCFAs were significantly higher (p<0.05) in the FF versus BF group, driven by increased levels of valeric and propanoic acids (p<0.05 for both). The IGSQ domain scores, stool consistency, fecal markers of immunity, inflammation, and intestinal barrier integrity (except lipocalin-2 which was significantly higher in BF vs FF), anthropometric Z-scores, common illnesses, antibiotic use, and adverse events were not significantly different between groups at week 6. ConclusionsOur results support the effectiveness of this tested infant formula in supporting good GI tolerance, growth, specific intestinal and immune health markers, and Bifidobacteria abundance similar to that of the BF group. Trial registrationNCT04880083 (2021-05-06)

BackgroundThe surgical stress response is a predictable, physician-managed metabolic state triggered by anesthesia and tissue injury, marked by insulin resistance and hypercatabolism that create unique nutritional needs unmet by standard, pre-surgical fasting diets. We developed a multi-nutrient medical food to support perioperative metabolic homeostasis and piloted its safety/tolerability and exploratory outcomes. MethodsIn a single-center pilot trial (n=67) of adults undergoing elective abdominal, cardiac/thoracic, gynecological, or orthopedic surgery, participants were allocated to medical food or no-treatment control. The product was taken twice preoperatively (evening before and 4 h pre-op) with standard care. Primary safety outcomes were adverse events, postoperative nausea/vomiting (PONV), 30-day readmission, and infections. Exploratory outcomes were fasting glucose, HbA1c, electrolytes, cortisol, pre-operative emotional state, and post-operative pain. ResultsAll participants completed the intervention. No product-attributed adverse events occurred. Gastric clearance was achieved within 2 h in all, and there were no 30-day readmissions or infections. PONV occurred in 30.3% vs 35.3% (risk ratio 0.86, 95% CI 0.43-1.71, p=0.796). Post-operative glycemia favored the intervention; at 48 hr the intervention group showed lower glucose (HL -9 mg/dL, g=0.35, p=0.030), while earlier timepoints were nonsignificant. Post-operative magnesium was numerically lower with intervention (4.76 vs 5.10) without statistical significance; other electrolytes and cortisol showed minimal differences. Post-operative pain was 5.33 vs 5.62 (g=0.19, p=0.43). Positive pre-operative emotion was more frequent with intervention (17/33 vs 9/34; risk ratio 1.95, p=0.046). ConclusionThe medical food was safe and well tolerated without increased PONV or readmissions. Preliminary metabolic and emotional signals justify a larger, adequately powered efficacy trial. Clinical Relevancy StatementThis pilot trial demonstrates that a preoperative multi-nutrient medical food was well tolerated and feasible to administer in a routine clinical setting: all participants achieved gastric clearance within 2 hours of the pre-operative dose, with no increase in PONV and no readmissions. Exploratory findings indicate potential benefits that could nutritionally support recovery if confirmed. These results support the feasibility of administering a targeted nutrition intervention shortly before surgery and justify evaluation in a larger efficacy trial. Clinical Trial RegistrationNCT07359222

BackgroundFood systems--particularly livestock production--account for substantial greenhouse gas (GHG) emissions, while unhealthy diets, characterized by excessive animal-based and insufficient plant-based food consumption, are a major risk factor for all-cause mortality in Europe. Implementing climate mitigation policies related to the GHG emissions of the food system could therefore bring important health co-benefits. MethodsWe developed a health impact assessment model based on a life table approach and evaluated the mortality impact of transitions in food consumption through four contrasting scenarios leading to net-zero GHG emissions for France in 2050. These involved varying dietary shifts, all moving toward more plant-based foods. For each scenario, we modeled the evolution of the diet, as well as the impacts on all-cause mortality by applying the most recent and robust dose-response relationships derived from meta-analyses for 13 food groups. FindingsThe different trajectories of dietary shifts translated into a health impact ranging from 19% [uncertainty interval, UI: 17%-21%] to 24% [UI: 21%-26%] of all-cause mortality prevented in 2050 in the French population. Variation in intakes of nuts, red meat, processed meat, whole grains and legumes bring most of the health benefits. Whatever the parameters chosen in the sensitivity analyses, the results remained robust, with about 100,000-200,000 deaths that could be prevented yearly by 2050 in France. InterpretationThe present study highlights the considerable potential health benefits that trajectories toward net-zero emissions can bring, especially through shifts toward sustainable diets. These results reinforce the strong convergence of environmental and human health issues in the agri-food sector. FundingFrench High Council for the Future of Health Insurance (HCAAM) and the National Agency for Ecological Transition (Ademe). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSFood systems are a significant contributor to climate change and in parallel, dietary risks are one of the leading causes of all-cause mortality globally, notably in high-income countries such as France. A recent systematic review by Moutet et al. revealed that only two studies evaluating health co-benefits through dietary shifts in net-zero GHG emissions scenarios were published to date. This suggests a convergence and a possible win-win situation between climate change and human health challenges regarding food production and consumption. In order to face the climate crises, governments around the world, and particularly those of the countries historically the largest contributors to climate change, must cut their greenhouse gas emissions to achieve net-zero emission by 2050. Dietary shifts would be a major driver to pursue this objective and could bring important health benefits to the population conducting these changes. For instance, Hamilton et al. showed that dietary changes in line with the Paris Agreements could result in 188 deaths prevented per 100,000 persons in 2040 in Germany and 141 in the UK. Added value of this studyOf the two previously published studies, only one assumed a gradual implementation of changes in diets, combined with a time lag in health effects. We also made these assumptions and considered the gradual change in consumption of thirteen food groups for which recent meta-analyses provided all-cause mortality dose-response relationships with a high level of quality. This study is also among the first to combine nutritional and environmental optimization, through four scenarios; all of which are expected to lead to net-zero emission by 2050 via very contrasting climate change mitigation trajectories. Nevertheless, all of them require a dietary shift toward more plant-based foods. We conducted a health impact assessment for France and showed that achieving net-zero emission by 2050 while considering nutrition references set by national guidelines would provide health co-benefits. Depending on the scenarios, health gains could range from 19% to 24 % of all-cause mortality prevented in the adult French population in 2050, compared to a scenario assuming that we would maintain the current observed dietary habits in the future. Implications of all the available evidenceThis study adds to the available evidence that taking action to mitigate climate change is an opportunity to strongly improve public health. Engaging populations in a shift toward a healthier and more sustainable diet could bring major human health and environmental benefits.

The gut microbiota has been implicated in regulating body composition, insulin resistance, and energy metabolism through microbial metabolites, including short-chain fatty acids (SCFAs) and amino acids. However, evidence in adolescents, particularly regarding sex-specific differences and lifestyle such as alcohol intake, remains limited. Characterizing sex-specific metabolic signatures in adolescence may improve early identification of metabolic risk. To address this gap, we investigated associations between fecal metabolites, body composition, insulin resistance, and energy expenditure in 158 adolescents aged 18 from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000). Quantitative fecal metabolomics was performed using proton nuclear magnetic resonance (1H-NMR) spectroscopy, profiling 32 metabolites. Associations with body composition, insulin resistance, and energy expenditure were evaluated using sex-stratified univariate and multivariate modelling with false discovery rate (FDR [&le;] 0.05 and 0.2). Fecal acetate and ethanol were more associated with fat-free mass index (FFMI) and waist-to-height ratio (WHtR) than with body mass index (BMI) in females; in males, no associations remained after FDR. Lysine and leucine showed associations with BMI and insulin resistance in females. Acetate, butyrate, glucose, and methanol were associated with total energy expenditure (TEE) in females, whereas no association survived in males. Alcohol intake was positively associated with fecal ethanol, glucose, and methanol, and inversely with trimethylamine in females, while galactose showed a positive association in males. These findings demonstrate that gut microbiota-derived metabolites are related to body composition, insulin sensitivity, and energy balance in adolescents, particularly females, highlighting the utility of fecal metabolomics in exploring mechanisms underlying metabolic variation.

Poor sleep is linked to consumption of sugary foods/beverages and high neural responsivity to palatable food cues. Yet, whether hedonic liking for sweet taste explains these associations remains unclear. We examined cross-sectional associations of five sleep traits (chronotype, sleep duration, insomnia frequency, snoring, daytime dozing) and a composite sleep score with sweet food liking, and total and free sugar intake in 76,734 UK Biobank participants (39-72 years, 56.3% female). Models adjusted for age, sex, ethnicity, socioeconomic deprivation, and body mass index (Bonferroni-corrected =0.0025). Evening chronotype, more frequent insomnia and daytime dozing, and lower composite sleep score were associated with higher sweet food liking. Associations with intake were stronger for free than total sugar. Evening chronotype was associated with higher free sugar intake (g/day: {beta}=1.523, 1.309-1.737; g/1000 kcal: {beta}=0.450, 0.361-0.538), and daytime dozing showed a dose-response (dozing often vs never/rarely: g/day {beta}=6.307, 4.631-7.983). Snoring was associated with higher absolute (but not energy-adjusted) free sugar intake. A healthier sleep score was associated with lower free sugar intake (g/day {beta}=-2.193 [-2.464 to -1.922]; g/1000 kcal {beta}=-0.691 [-0.804 to -0.579]) but higher energy-adjusted total sugar intake ({beta}=0.633 [0.485-0.781]). Mediation analyses indicated sweet liking accounted for 15%-91% of several sleep trait and free sugar intake associations (indirect effects p<0.001). Poorer sleep health, particularly evening chronotype and daytime sleepiness, was associated with greater sweet liking and higher free sugar intake, with sweet liking partially mediating associations between sleep traits and sugar consumption. Sweet-taste liking may represent an underexamined pathway linking sleep/circadian disruption to free sugar intake.

Sleep architecture is essential for metabolic and cardiovascular health, yet the impact of day-to-day dietary variation on objective sleep physiology remains unclear. Using 4.8 thousand person-nights with real-time dietary logs and multi-stage wearable sleep recordings, we examined how prior-day nutrition relates to next-night sleep under free-living conditions. Higher fiber density was associated with increased restorative sleep, including +0.59 pp deep sleep, +0.76 pp REM sleep, -1.35 pp light sleep, and -1.14 bpm lower mean nocturnal heart rate. Greater plant diversity and higher whole-plant food intake were similarly associated with lower nocturnal heart rate (-0.72 to -0.94 bpm). Meal-timing behaviors primarily influenced sleep duration, sleep-onset latency, and autonomic tone: heavier evening meals were associated with +7.7 min longer total sleep time and +0.73 bpm higher nocturnal heart rate. In contrast, short-term variation in macronutrient energy distribution and micronutrient consumption showed no robust associations with sleep outcomes. When analyses were restricted to more extreme dietary contrasts, effect magnitudes increased while remaining directionally consistent. These findings indicate that routine daily dietary choices, particularly plant-forward composition and meal timing, have immediate and measurable effects on objective sleep architecture.

Societies are aging rapidly in parallel with the increasingly earlier onset of serious diseases in younger populations. These and other factors are creating a substantial disparity between healthspan, the period of life where an individual is free from serious chronic disease or disability, and lifespan -- expanding the morbidity span. Extending healthspan has thus become a major priority. To pursue an integrated strategy toward healthspan support, we launched DELTA, a prospective, open-label, interventional, and participatory N=1 study (NCT06630637) conducted on a healthy individual (DELTA001, author D.H.). The study was conducted with methodological rigor to support repeatability, transparency, and balanced reporting. The core focus of the DELTA protocol was to assess and enhance human biological resilience. This was demonstrated through the subjects adaptive capacity, revealed through changes and trajectories in cardiometabolic and pleiotropic biomarker levels based upon systematically administered challenges (e.g., fasting). Specifically, the interventional DELTA protocol integrates time-restricted eating (TRE, fasting), strength and cardiovascular fitness regimens, a Mediterranean-inspired dietary protocol, and supplementation alongside an analytics and reporting framework comprised of artificial intelligence (AI), digital health, and wearables-based sleep performance monitoring, microbiome assessment, and longitudinal tracking of biomarker dynamics and performance outcomes. This study introduces new methods and metrics for assessing these biomarker dynamics, including the development of digital biomarkers that reflect dynamic human functional resilience. Findings from DELTA may actionably guide the design of larger participatory human trials to monitor biomarker resilience, design appropriate interventions for dynamic administration, and subsequently fortify healthspan at a population level.

BackgroundPacked lunches are a common feature of early childhood food provision, yet evidence describing their nutritional composition in early years settings remains limited. Understanding the foods provided during this developmental period is important, given the potential influence of early dietary exposures on later health. AimTo characterise the composition, nutritional quality, cost, and dietary patterns of packed lunches brought from home in Early Childhood Education and Care settings, and to examine variation by child age and area-level deprivation. MethodsA cross-sectional analysis was conducted using a remote food photography method to assess packed lunches provided for children aged 1-4 years attending early years settings across Essex, UK. Food items were categorised into predefined groups, and nutrient composition was estimated. Area-level deprivation was determined using the English Index of Multiple Deprivation (2019). Non-parametric tests assessed between-group differences. Principal components analysis (PCA) was used to identify patterns of co-occurring foods. ResultsA total of 389 packed lunches were analysed. Starchy foods (82%), fruit (81%), dairy or alternatives (72%), and savoury snacks (74%) were commonly provided, while vegetables were less frequent and fish was rarely observed (1.5%). Overall, 97.7% of lunches contained at least one ultra-processed food (UPF), with a median of three UPF items per lunch and 74% of total energy derived from UPFs. Median energy provision was 400 kcal (IQR 309-518). Nutrient composition was broadly similar across deprivation groups, although cake and biscuit counts and UPF item counts were modestly higher in more deprived areas. The median estimated lunch cost was {pound}1.79 and did not differ by deprivation. ConclusionsPacked lunches in early years settings frequently contained ultra-processed foods and showed considerable variability in nutritional quality. Socioeconomic differences were limited, suggesting that contemporary packed lunch practices may reflect influences operating across population groups. Further research across diverse regions is warranted to better understand the provision of packed lunches and their implications for early dietary exposure.

The biomarker MetaboHealth represents a novel indicator of overall health in middle age and may potentially be suitable as actionable health check in prevention strategies. MetaboHealth is a blood-based metabolomic composite score that predicts a wide range of age-related conditions and mortality in large European cohorts. Here, we investigated whether MetaboHealth can be personalised and limited to clinically validated metabolomic markers. Next, we assessed whether the updated MetaboHealth score predicts all-cause mortality and cardiometabolic disease incidence and can be improved by a lifestyle intervention. To personalise MetaboHealth, we scaled the metabolomic markers using a Dutch reference population (i.e. the Biobanking and BioMolecular Research Infrastructure Netherlands) and, in addition, based the score solely on clinically validated metabolic markers. The novel version of the score, Personal-MetaboHealth, retained predictive accuracy for all-cause mortality and showed an even stronger association with incident cardiometabolic disease in the Leiden Longevity Study (LLS) in which 2,404 participants were followed for up to 22 and 16 years for mortality and morbidity, respectively. The association of Personal-MetaboHealth with all-cause mortality remained robust after adjusting for smoking, alcohol use, and medication, while the cardiometabolic disease association was partially driven by smoking. Each standard deviation decrease in Personal-MetaboHealth was associated with a 11.7 year earlier onset of the first cardiometabolic disease in the LLS. Next we showed that Personal-MetaboHealth can be improved by a 3-month combined lifestyle intervention in middle aged individuals (Growing Old Together study), specifically in those at risk with an unhealthy score at baseline. Personal-MetaboHealth thus offers a potential actionable health check in middle age for early prevention and extension of healthy lifespan.

IntroductionMechanistic research has shown that prior obesity induces durable transcriptomic and epigenetic reprogramming in adipose tissue that persists after weight loss and predisposes individuals to weight regain. This phenomenon, termed obesogenic memory (OM), is currently conceptualized primarily as a molecular process. We propose extending OM beyond adipose tissue biology to include interacting biological and sociocultural processes through which past exposures shape present physiological regulation and health-related behavior. MethodsIn-depth qualitative interviews were conducted with individuals living with obesity (n=31) and with healthcare professionals (n=18). The data were analyzed abductively to examine participants lived experiences of obesogenesis. ResultsWe developed a three-phase model of OM comprising memorizing, remembering, and rescribing. The memorizing phase describes the initial acquisition and encoding of biological and sociocultural obesogenic influences. The remembering phase captures the persistence of these influences, contributing to long-term obesity maintenance. The rescribing phase refers to processes through which obesogenic influences may be attenuated or reversed, creating conditions for sustainable health behavior change. ConclusionExtending OM to include sociocultural dimensions provides a more comprehensive understanding of obesity persistence. This integrative framework identifies multilevel targets for obesity prevention and treatment that acknowledge past exposures while supporting resilience and long-term weight management.

Iron deficiency (ID) is the most common nutritional deficiency worldwide, often caused by insufficient dietary intakes. Oral supplementation is one of the means to improve iron status. This study evaluated the efficacy and safety of two low-dose iron supplements - >Your< Iron Forte Capsules (YIFC) and Ferrous Sulfate Capsules (FSC) - in individuals with dietary ID. One hundred and one participants (mean age 30.6 years; 98% women) with low iron stores (mean serum ferritin 16.1 {micro}g/L) were randomized to receive either YIFC or FSC once daily for 12 weeks. Changes in blood indices and iron-related parameters were assessed at four and 12 weeks of intervention relative to baseline. The primary outcome was the change in hemoglobin (Hb) after 12 weeks. Eighty-seven participants completed the study. Both supplements significantly increased Hb at 12 weeks (YIFC: mean 6.52 g/L, p<0.001; FSC: mean 5.71 g/L, p<0.001). Product-related adverse events (AEs) were few (17% of all AEs) and of mild to moderate intensity only. One participant receiving FSC withdrew due to a probable product-related AE. The frequencies of product-related AEs were similar between study arms, however, statistically significantly more AEs judged to be definitely related to the product occurred in in the FSC arm. While product-related AEs were confined to the gastrointestinal tract in the YIFC arm, they affected multiple organ systems in the FSC arm. Supplementation with either YIFC or FSC proved as an effective, well-tolerated, and safe strategy for improving iron status in non-anemic dietary iron deficiency. In terms of the AE profile, supplementation with YIFC may offer advantages over supplementation with FSC.

Many Asian American (AA) subgroups experience disproportionate rates of cardiometabolic (CMB) conditions, yet the contextual drivers of these disparities remain unclear. Little is known about the role of Asian residential segregation, often conceptualized as Asian enclaves, with limited prior work largely ignoring region of origin and nativity. Using six years of population-based survey data from New York City (N>6,000 AAs) linked with multiple sources of community data, we examine how residence in ethnicity-specific enclaves relates to CMB risks (obesity, hypertension, and diabetes), whether these associations differ by nativity, and the extent to which neighborhood socioeconomic conditions, the built environment, social cohesion, and institutional support account for observed associations. Our combined concentration-based and spatial clustering analysis identified five East Asian enclaves and six South Asian enclaves, with no geographic overlap between the two. Logistic regression analyses show that residence in an East Asian enclave was associated with lower odds of obesity (OR=0.63), while residence in a South Asian enclave was linked to higher odds of diabetes (OR=1.42) and hypertension (OR=1.46). These associations were present only among foreign-born individuals. After adjusting for neighborhood characteristics, the lower obesity risk in East Asian enclaves persisted, while elevated risks in South Asian enclaves were partly reduced. Both suggest a role for unmeasured enclave factors, including cultural and food environments. Our findings challenge the view that Asian enclaves are monolithically health-promoting and redirects scholarly attention toward disaggregated approaches to investigating AA health disparities.

BackgroundOverweight and obesity are causing growing public health, economic and clinical burden, particularly within under-resourced communities. There is an urgent need to develop an in-depth understanding of experiences of weight management, and preferences for support within under-resourced communities, with a view to developing more effective weight management interventions. MethodsFocus groups were run in under-resourced communities using storyboarding; a method to facilitate inclusive communication (n=37). Thematic analysis was applied to textual and visual data, and a realist lens applied to provide in-depth insight into weight management experiences and needs. We believe this is the first study to use this combined methodology to explore weight management experiences and needs. ResultsCombining storyboarding with a realist lens, generated four themes. Living circumstances indicated that mental health, individual needs, and cost of weight management services were key contextual factors. Mechanisms of weight management identified emotional eating and portion control to be central to individual weight management. Yo-yo dieting centred on participants experiences of weight regain after attempting weight loss. Weight management intervention needs indicated psychological support was perceived as severely lacking, and the only route to attain sustained weight management. Offering both in-person and online support for weight management was considered important to reach more people. ConclusionMoving weight management support from short- to long-term and incorporating more robust psychological support would better serve the needs of people living in under-resourced communities who are overweight or obese. Ideally interventions should be multicomponent and tailored to individual needs and circumstances.

Diet is an essential factor influencing biological aging, yet few exsiting dietary indices were specifically developed to target biological aging. We developed a data-driven food-based Empirical Dietary Index for Slower Epigenetic Aging (EDISEA) in the US Health and Retirement Study (HRS, n=7,398), which predicted deceleration of GrimAge, an established DNA methylation-based epigenetic clock. Participants in the highest versus lowest EDISEA quintile had 4.65-year deceleration in GrimAge (P value <0.001). We externally validated EDISEA in an independent US cohort (n=23,830), where it showed consistent associations with several epigenetic clocks and lower all-cause mortality risk. In HRS and a UK aging cohort (n=4,895), EDISEA was associated with lower risks of several aging-related diseases and functional limitations. Outcome-wide analyses in the UK Biobank (n=187,035), together with integrative proteomic, metabolic, and neuroimaging assessments, revealed biological signatures of EDISEA implicating broad vascular, inflammatory, metabolic, and brain-structural pathways through which EDISEA was associated with biological aging. EDISEA provides a scalable, biologically anchored tool to inform the development of precision nutrition strategies aimed at slowing epigenetic aging and mitigating aging-related disease burden.

BACKGROUNDVisceral adipose tissue (VAT) has been associated with cardiovascular disease (CVD) mortality. However, the comparative performance of VAT-related clinical surrogates remains poorly characterized. OBJECTIVESTo evaluate the performance of seven VAT-related clinical surrogates for predicting CVD and cause-specific CVD mortality. METHODSWe analyzed data from the Mexico City Prospective Cohort, a population-based prospective cohort study, with baseline recruitmetn between 1998 - 2004 and ongoing mortality follow-up. CVD mortality included deaths from cardiac, stroke-related, and other vascular causes. Seven VAT-related surrogates (METS-VF, CVAI, EVA, DAAT, LAAP, VAI, and DAI) were estimated using clinical, biochemical, and anthropometric data at baseline. Associations with outcomes were evaluated using Cox regression models to estimate adjusted hazard ratios (aHRs). Discrimination was assessed with Harrells C-statistic (Cs) and fixed-point at 10-years receiver operating characteristic (ROC) curves, and calibration with slope plots. RESULTSIn a subsample of 102,385 participants (median age: 47 years; 67% female), 4,068 (3.97%) died from any CVD causes. METS-VF (Cs: 0.722; aHR: 1.17, 95% CI: 1.12-1.23), EVA (Cs: 0.72; 1.14, 1.12-1.23), CVAI (Cs: 0.70; 1.13, 1.09-1.18), and DAAT (Cs: 0.626; 1.13, 1.09- 1.18) were positively associated with CVD mortality and showed the highest predictive capacity among the surrogates. Adding METS-VF to a CVD risk score among individuals classified as intermediate risk improved discrimination for CVD mortality. CONCLUSIONSIn this large cohort of Mexican adults, four VAT-related clinical surrogates, particularly METS-VF, demonstrated good discriminatory performance for long-term CVD mortality. These indices could help to identify individuals with high VAT accumulation and high CVD risk in resource-limited settings.

IntroductionDepression is highly prevalent among young adults worldwide. While research links health behaviours, such as dietary intake, to depression, few studies have examined these associations among young adults in low- and middle-income countries, including South Africa. This study investigated whether dietary intake was associated with an increased risk of depression in a cohort of young South African adults, aged 20-30 years, as part of the Global burden of disease Lifestyle And mental Disorder (GLAD) project. MethodsThis five-year prospective cohort study was conducted in the North West Province of South Africa in accordance with the GLAD project protocol (DERR1-10.2196/65576). Dietary exposures were evaluated using three non-consecutive 24-hour dietary recalls, measuring daily intake of various food groups and nutrients as defined by the Global Burden of Disease study. Depression outcomes were assessed at baseline (N=1039) and follow-up (N=551) using the Patient Health Questionnaire (PHQ-9, cut-off [&ge;]10). Logistic and Poisson regression analyses were performed, with results presented as odds ratios (OR) and relative risk ratios (RR), respectively. Four models were run: unadjusted, sociodemographic-adjusted, total energy (TE) intake-adjusted and fully adjusted (including sociodemographic information and TE intake). For longitudinal analyses of incident depression, baseline depression cases were additionally excluded (n=403). ResultsParticipants (average age 24.55 years) had a balanced distribution of sex (51.4% female) and race (48.6% Black), and a 29.45% baseline prevalence of depression. Higher milk intake was associated with a lower risk of incident depression (RR=0.94, 95% CI 0.91-0.98) in the TE-adjusted longitudinal model. Cross-sectionally, higher sugar-sweetened beverage consumption associated with higher odds of depression, while higher calcium intake (OR=0.48, 95% CI 0.31; 0.76) and vegetable consumption (OR=0.74, 95% CI 0.61, 0.91) were associated with lower odds of depression after TE intake adjustment. Higher fibre intake was associated with lower odds of depression in the unadjusted model. ConclusionHigher daily milk intake was associated with a lower risk of depression, while higher calcium, vegetable, and fibre intake were associated with a lower prevalence of depression in young adults. These findings suggest that prevention strategies for common mental disorders could include dietary approaches within mental health care.

ObjectiveTo investigate the burden of environmental enteric dysfunction (EED) and its association with water, sanitation, and hygiene (WASH) and linear growth amongst infants in rural Central Java, Indonesia. Study designA longitudinal study of 119 infants aged between 5-19 months was conducted in five villages of Wonosobo District, Central Java, Indonesia. Anthropometric measurements of infants and their mothers were performed at baseline and 5-month follow-up alongside a quantitative questionnaire on household, socio-economic, WASH and caregiving variables and stool sample collection for the investigation of alpha-1-antitrypsin (AAT), neopterin (NEO), and myeloperoxidase (MPO) levels. Linear mixed-effects regression models estimated the associations between WASH and height-for-age z-score (HAZ) on log-transformed EED biomarkers. ResultsBiomarkers increased from baseline to follow-up despite a declining trend with age and 68.7%, 79.0%, and 71.4% of infants experienced elevated AAT, NEO, and MPO respectively follow-up. Infants had higher AAT if they averaged > 30 minutes playing on soiled surfaces per day ({beta} = 0.11, p<0.05). NEO was elevated in infants with diarrhoea ({beta} = 1.04, p<0.05), municipal water source ( = {beta} 0.71, p<0.05), and in infants who mouthed soiled fomites weekly ({beta} = 0.55, p<0.05). Infants in houses with municipal water source had higher MPO ({beta} = 0.56, p<0.05) and higher MPO if mouthing soil weekly ({beta} = 0.41, p<0.05). Compared to infants at risk of stunting, stunted infants at baseline had lower AAT at follow-up ({beta} = -0.39, p<0.05) while infants with HAZ > -1 had lower AAT at baseline ( = -0.43, p<0.05). HAZ at baseline was positively associated with NEO at follow-up ({beta} = 0.36, p<0.05). MPO was higher in infants with HAZ > -1 at follow-up ({beta} = 0.59, p<0.05) and stunted infants ({beta} = -0.54, p<0.05) compared to infants at risk of stunting. ConclusionElevated EED biomarker levels were frequent and associated weakly with WASH and HAZ with bi-directionality, highlighting the need for quality birth cohort studies to improve understanding of EED and develop interventions.

BackgroundAdjuvant abemaciclib+endocrine therapy (ET) improves long-term outcomes in high-risk, hormone receptor-positive (HR+)/HER2-negative early breast cancer (eBC). However, treatment is frequently complicated by diarrhea, affecting adherence and quality of life (QoL). Increasing evidence suggests that abemaciclib-induced gastrointestinal toxicity may involve gut microbiota alterations. We conducted a prospective case-control pilot study evaluating the efficacy of MBR-01, a standardized prebiotic/probiotic formulation, in mitigating abemaciclib-induced diarrhea. MethodsWe enrolled 20 patients with high-risk HR+/HER2-negative eBC considered unfit for adjuvant chemotherapy. Patients received abemaciclib+letrozole (control, n=10) or abemaciclib+letrozole+MBR-01 (experimental, n=10). The primary endpoint was the incidence and severity of diarrhea; secondary endpoints included treatment adherence, QoL assessments and exploratory baseline/week-12 microbiota characterization according to treatment arm. Trial registration number: ISRCTN11948182. ResultsDiarrhea occurred in all patients. In the control group, diarrhea was predominantly grade 1 (50%) or grade 2 (40%), with one grade 3 event (10%). In the MBR-01 group, diarrhea frequency and severity were reduced by [~]70% at the end of week-12; 80% of patients experienced only grade 1 diarrhea or none by week-12, and no grade [&ge;]3 events. Dose modification was only required in one control. Alpha-diversity and depletion of F.prausnitzii were associated with earlier diarrhea onset and longer duration; enrichment in E.coli correlated with higher grade events. MBR-01 supplementation seemed to preserve microbial diversity and limited E.coli expansion. QoL was significantly improved with MBR-01. ConclusionMBR-01 may effectively mitigate abemaciclib-induced diarrhea, likely through the achievement of stabilization of gut microbiota composition. Larger prospective studies are warranted to validate these preliminary findings. HighlightsO_LIMBR-01, a prebiotic/probiotic, was given to reduce abemaciclib-induced diarrhea. C_LIO_LIMBR-01 reduced diarrhea by [~]70%, most patients had G0-1, one G [&ge;]3 at week 12. C_LIO_LIMBR-01 patients keep abemaciclib drug dose; 10% of controls required reduction. C_LIO_LIMBR-01 halved stool frequency and improved quality of life. C_LIO_LIMBR-01 preserved gut diversity, maintaining F. prausnitzii and limiting E. coli. C_LI