The American Journal of Clinical Nutrition

Background: Black adults bear a disproportionate burden of cardiometabolic dysfunction, yet most dietary trial evidence comes from predominantly White cohorts. Objective: To evaluate whether a personalized whole-food dietary intervention improves cardiometabolic outcomes more in Black than White young adults with overweight or obesity. Methods: In this 8-week randomized, controlled trial (ClinicalTrials.gov: NCT04635917), 112 Black and White adults (18-35 years; BMI 25-45 kg/m2) were block-randomized by race to a personalized dietary intervention providing whole foods (PD, n=57) or conventional dietary counseling at baseline (BL) using MyPlate guidelines (CD, n=55). Primary outcomes were Matsuda Index and fasting and OGTT-derived glucose, insulin, and non-esterified fatty acids. Other glucoregulatory, cardiovascular, anthropometric, appetite, and cognitive outcomes were also assessed. Outcomes were analyzed using baseline-adjusted linear models with sensitivity analyses adjusting for baseline BMI and food security score. Results: Compliance with study food consumption was 85-91%. Diet quality was higher in PD than CD (P < 0.05), with larger gains in vegetable-related outcomes among Black participants (group x race, P < 0.05). HOMA-{beta} was lower in PD than CD overall (P < 0.05). In sensitivity analyses, Black PD participants had greater fasting insulin reductions than White, especially in the latter half of intervention (week x group x race, P < 0.05), with a similar tendency for HOMA-IR. Glucose AUC 0-30 min was higher in White than Black PD participants (group x race, P < 0.05). Concentration performance was higher in PD than CD overall (P < 0.05), with larger gains in processing speed and accuracy among Black than White participants (group x race, P < 0.05). No effects were observed for cardiovascular or appetite outcomes. Conclusions: The personalized whole-food intervention produced differential effects in fasting insulin and early-phase glucose handling, and greater benefits in attention, in Black compared with White young adults with overweight or obesity during weight maintenance.

The modern Western diet (MWD) provides high linoleic acid (LA) exposure, typically contributing 6-9% of total caloric intake. These high LA levels have fueled a longstanding debate regarding whether this dietary pattern confers benefit or risk. Importantly, LA intake is disproportionately elevated among lower socioeconomic populations due to greater reliance on industrial seed oils and ultra-processed foods. Despite decades of research, controlled dietary intervention studies directly evaluating the biological consequences of varying LA exposure remain limited. The current randomized, double-blind intervention compared the effects of a 12-week Low LA diet (2.5% energy) versus a High LA diet (10.0% energy) in healthy adults. Primary outcomes included plasma highly unsaturated fatty acid (HUFA) concentrations and ex vivo zymosan-stimulated whole-blood oxylipin generation. Fifty- two participants completed the intervention. High LA exposure resulted in a marked reduction in plasma n-3 eicosapentaenoic acid (EPA) concentrations compared with the LowLA arm. In contrast, levels of arachidonic acid (ARA), dihomo-gamma-linolenic acid (DGLA) and docosahexaenoic acid (DHA) did not differ by dietary LA exposure. Analysis of oxylipin species revealed that levels of EPA-derived relative to ARA-derived mediators were significantly reduced in the High LA arm. These findings reveal that higher dietary LA selectively suppresses EPA pools and EPA-derived oxylipins without altering ARA, shifting the lipid mediator balance toward a more n-6-dominant profile.

1.Traditional nutrition science often proceeds under the assumption of a universal metabolic return to healthy eating, yet social environments may fundamentally modify these biological associations. This investigation utilized survey-weighted data from the National Health and Nutrition Examination Survey (NHANES 2017-2023) representing a weighted population of 286 million adults aged 20 years and older to test for association heterogeneity in the dietglycemia relationship. Dietary exposure was operationalized as energy-adjusted nutrient density scores derived via the residual method to measure the healthfulness of intake independent of total caloric volume. The primary outcome was HPLC-measured glycated hemoglobin (HbA1c) modeled as a continuous variable. Multivariable interaction models evaluated the Income-to-Poverty Ratio (PIR) as a formal effect modifier, adjusting for age, sex, race/ethnicity, body mass index, and smoking status. Analysis demonstrated that while quality-weighted nutrient intake levels remained statistically uniform across income tiers (p=0.207), multivariable interaction models identified significant modification of the diet-HbA1c association by socioeconomic position (p=0.028 for interaction). In the low-income reference group, higher quality nutrient intake was associated with a significant protective decline in HbA1c ({beta}=-6.11x10-5 percentage points per kilocalorie, p=0.017). Conversely, this protective association was attenuated to non-significance for the middle-income stratum ({beta}=3.31x10-6, p=0.849). Sensitivity analysis restricted to participants without clinical diabetes showed the interaction was non-significant (p=0.859), identifying an observed boundary condition where differential associations are most evident in pathological states. These findings suggest association heterogeneity where identical dietary behaviors relate to divergent glycemic patterning across socioeconomic groups. Socioeconomic position appears to function as an effect modifier of the diet-HbA1c relationship rather than a mere confounder. Such patterns suggest that the metabolic correlates of healthy eating are socially patterned, potentially due to structural factors that constrain the associations expected from improved nutrition.

BackgroundSeveral genetic variants have been identified to modify the effects of fish oil supplementation (FOS) on increasing circulating omega-3 fatty acids, but it remains unexplored whether polygenic predisposition to low circulating omega-3 fatty acids modifies these effects. ObjectiveTo test if polygenic scores (PGS) for circulating omega-3 fatty acids modify the associations of FOS with corresponding circulating concentrations. MethodsWe developed PGS models for absolute circulating concentrations of total omega-3 fatty acids (Omega-3), docosahexaenoic acid (DHA), and their relative percentages in total fatty acids (Omega-3% and DHA%), using a multi-ethnic genome-wide association study (N=136,016). PGS models were validated in 437,803 UK Biobank participants of European (EUR), Central/South Asian (CSA), African, and East Asian genetic ancestries. Linear models tested PGS-by-FOS interactions on corresponding observed circulating concentrations. Discovery analysis was performed separately in 237,380 EUR participants and each non-EUR group. Replication analyses were performed using oily fish intake and in another 178,935 EUR participants. ResultsIn EUR participants, PGS explained 5.3-11.1% of the phenotypic variance, and significant PGS-by-FOS interactions were detected across all four circulating omega-3 traits. Among participants in the bottom 5% of the PGS distribution, FOS was significantly associated with a 0.40 SD (95% CI: 0.39-0.44) increase in Omega-3. This association effect was 11.1% larger than the population average ({beta} = 0.36; 95% CI: 0.35-0.37; PInt = 0.016) and 42.8% larger than that in participants in the top 5% of the PGS distribution ({beta} = 0.28 SD; 95% CI: 0.25-0.32; PInt = 4.03X10-10). These interaction patterns were consistently observed in CSA ancestry and confirmed in replication and sensitivity analyses. ConclusionsPGS modify the associations of FOS with circulating omega-3 fatty acids in EUR and CSA populations, with larger FOS effects in participants with lower PGS. These findings support the development of genome-informed precision nutrition.

Background: Diet is a modifiable risk factor for cardiometabolic disease, yet establishing causality remains challenging. Mendelian randomisation (MR) leverages genetic variants as instrumental variables (IVs) to enable causal inference. Method: Using two-sample MR, we assessed the causal effects of four principal component-derived dietary patterns (DPs) - Unhealthy, Healthy, Meat-based, Pescatarian - on twelve cardiometabolic outcomes: body mass index, coronary artery disease, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, type 2 diabetes, fasting glucose and insulin, and glycated haemoglobin. Two sets of IVs were employed: conventional genome-wide significant variants associated with each DP, rigorously filtered for pleiotropy and directionality; and biologically informed variants in chemosensory receptor genes, given the role of taste and smell perception in shaping food choices. Results: Using conventional IVs, the Pescatarian DP reduced fasting insulin ({beta}IVW = -0.10 pmolL-1 per SD increase in Pescatarian DP score, 95% Confidence interval [CI] [-0.15, -0.04]; P = 1.19x10-3), which survived multiple sensitivity analyses. Associations between the Unhealthy DP and elevated blood pressure and glycated haemoglobin were likely undermined by heterogeneity and pleiotropy, with insufficient IVs for robust sensitivity testing. Chemosensory receptors yielded null findings, reflecting insufficient power. Conclusion: Rigorously filtered conventional IVs supported the causal nature of well-established diet-disease relationships, demonstrating MR's utility in strengthening causal inference in nutritional epidemiology. Chemosensory IVs demonstrated limited utility for DPs, likely reflecting the heterogeneous and complex sensory profiles of overall diets. Future efforts should consider using guideline-based dietary scores to facilitate translation of findings.

BackgroundCollege-attending young adults frequently experience declines in diet quality, physical activity, and psychological well-being during the transition to independent living, contributing to weight gain during the first year of college. Although multicomponent lifestyle interventions have been developed to address these behaviors, the responsiveness to such programs could differ across demographic factors associated with health behaviors, such as sex, race, and ethnicity. Hence, this secondary analysis of large-scale college health trials evaluated whether the effectiveness of such interventions differed by these demographic factors. MethodsData were combined from two multi-site randomized controlled trials: Young Adults Eating and Active for Health (YEAH) trial and the Get FRUVED trial. Both interventions used theory-based approaches to promote healthy weight management through improvements in diet quality, physical activity, and stress management. Baseline-adjusted linear regression models evaluated the effects of group (intervention, control) and its interactions with sex, race (White, Black, Other), or Hispanic ethnicity. Models were adjusted for baseline outcome values, baseline BMI, study (YEAH vs. FRUVED), and state of data collection. ResultsIntervention participants reported higher fruit and vegetable intake, lower processed meat intake, and longer sleep duration compared with controls. However, there was significant heterogeneity in these dietary outcomes by ethnicity, race, and sex. Non-Hispanic participants in the intervention group had higher fruit and vegetable intake compared to controls (p < 0.05). And, within the intervention group, Hispanic females had lower bacon/sausage intake than Hispanic males and non-Hispanic females (p < 0.05). With respect to race, Black participants reported higher total processed meat intake than White and Other race participants in the intervention group (p <0.05). These demographic factors did not moderate the interventions impact on physical activity, sleep duration, and perceived stress. Overall, the intervention appeared to be the least effective for Hispanic males who exhibited higher body weight and waist circumference compared with Hispanic females and non-Hispanic males (p < 0.05). ConclusionsMulticomponent lifestyle interventions can improve selected dietary outcomes among college students, but effectiveness may differ across demographic subgroups. Culturally and sex-tailored strategies that consider the intersecting influences of sex, race, and ethnicity may enhance intervention effectiveness during the transition to college.

BackgroundChronic malnutrition in early childhood is a multifactorial condition associated with long-term impairments, yet the physiological and gut microbial pathways underlying differential growth trajectories remain poorly understood. ObjectiveWe aimed to characterize phenotypic growth trajectories and identify the associated gut microbial and body composition signatures in infants during the first year of life. MethodsWe analyzed longitudinal data from birth to 12 months in a South African cohort (Soweto, n=45). Individual linear growth trajectories were modeled using the Jenss-Bayley equation, and children were clustered based on model parameters to identify phenotypic subgroups. Body composition (fat-free mass and fat mass) was measured via deuterium dilution at 6 and 12 months, and gut microbiome development was assessed using 16S rRNA gene amplicons at 4, 6, and 12 months. ResultsWe identified distinct phenotypic subgroups including healthy growth, catch-up growth, and growth faltering, that were obscured at the cohort level. These trajectories diverged most dynamically within the first 6 months of life. Integrated analysis revealed that in the growth faltering cluster, height-for-age and fat-free mass z-scores stabilized between 6 and 12 months, whereas fat mass z-scores (FMZ) declined. This trade-off is consistent with a catabolic state where energy reserves are prioritized for lean tissue and bone growth. Furthermore, at 6 months, the growth faltering cluster was enriched with opportunistic pathobionts (e.g., Paraclostridium). In contrast, the catch-up cluster exhibited a transient enrichment of facultative anaerobes (e.g., Enterobacter), supporting a hypothesis that these oxygen-tolerant taxa may help bridge a transitional microbial state in partially oxygenated or inflamed environments to enable physiological recovery. ConclusionsEarly childhood chronic malnutrition phenotypes in South African infants can be defined by distinct microbial and body composition signatures that diverge within six months of life. Integrated interventions should target both host anabolic state and microbiome transitions to support recovery.

BackgroundDiet is central to cardiovascular disease (CVD) prevention, yet free-living studies rarely capture what people eat at home or how closely they follow an assigned diet due to limitations in self-reporting. Short-term inpatient feeding studies, with all meals provided and supervised intake, allow direct assessment of the physiological effects of dietary patterns. Objectivesi) To compare the short-term effects of a UK-National Institute for Health and Care Excellence (NICE) aligned diet versus a Western-style diet on CVD risk factors, metabolic phenotypes and microbiome; ii) To evaluate whether urinary metabolic phenotyping can objectively classify dietary adherence in adults with increased CVD risk. MethodsIn a controlled inpatient randomized crossover trial, 18 adults at elevated CVD risk completed two 72 h isocaloric diets: NICE-compliant and Western-style. Repeated-measures MCCV-PLS-DA assessed NMR fasting serum and 24 h urine metabolomic phenotypes. Univariate analyses examined CVD markers, urinary metabolites, serum SCFAs, and gut microbial richness and -diversity. ResultsDiet modulated CVD risk markers, with the NICE compliant diet lowering systolic blood pressure and atherogenic lipid parameters, whereas the Western-style diet increased these measures (all q < 0.05). The Western-style diet reduced microbial richness and tended towards lower -diversity. Urinary metabolic phenotyping identified 27 discriminatory metabolites between the diets reflecting food intake. Most diet-linked metabolites diverged from baseline within 24 h; microbiome derived metabolites demonstrated early and sustained divergence across 72 h. The urinary MCCV-PLS-DA model extended from a previously published framework in healthy adults, robustly classified dietary adherence (Q2Y=0.96), and correctly predicted allocated dietary intervention at earlier timepoints (24-48 h). ConclusionsUrinary metabolic phenotyping offers a sensitive and non-invasive tool for objectively assessing dietary intake. Short-term adherence to contrasting dietary patterns produced rapid, diet-specific metabolic and microbial effect in individuals at elevated CVD risk and differentially impacted cardiovascular risk profiles. This trial was registered at the ISRCTN registry (https://www.isrctn.com/ISRCTN44705179).

Introduction Acute malnutrition in children aged 6-23 months remains critical in Tigray, Ethiopia, where global acute malnutrition (GAM) rates have reached emergency levels. Small-quantity lipid-based nutrient supplements (SQ-LNS) show promise for prevention, but evidence from post-conflict settings is limited. Objective This study evaluated SQ-LNS effectiveness in preventing acute malnutrition and rightward shifting in the distribution of weight-for-height among young children in post-conflict Tigray, Ethiopia. Methods A non-randomized cluster trial enrolled 8,442 children aged 6-23 months across four districts. The intervention group (n=6,838) received daily 20g SQ-LNS sachets for six months plus behavior change communication; the control group (n=1,604) received standard nutrition programming. Primary outcomes were acute malnutrition prevalence (WHZ < -2 or MUAC < 12.5cm) and distribution of weight-for-height z-scores. Data were collected biweekly and analyzed using longitudinal comparisons and difference-in-differences (DiD) estimation. Results Acute malnutrition declined from 22.1% to 4.2% in the intervention group (17.9 percentage point reduction) versus 19.6% to 11.4% in controls (8.2-point reduction). Mean WHZ scores increased from -0.35 to +0.33 in the intervention group (gain of +0.68 z-scores), while controls improved from -0.79 to -0.63 (gain of +0.16). The net intervention effect (DiD) showed a 4.9 percentage point reduction in WHZ-defined GAM and a 9.7-point reduction in MUAC-defined GAM. Mean WHZ and MUAC increased significantly more in the intervention group (DiD: +0.52 z-scores and +3.88 mm, respectively). Critically, the entire WHZ distribution shifted rightward, indicating population-level nutritional improvement, not merely reduced caseloads. Conclusions Six months of daily SQ-LNS effectively prevented acute malnutrition and shifted the entire weight-for-height distribution rightward among young children in post-conflict Tigray. Benefits extended beyond treatment, lifting whole-population nutritional status and building resilience. Findings support SQ-LNS inclusion in post-conflict nutrition packages and highlight the importance of assessing distributional outcomes, not just prevalence, when evaluating nutritional interventions. Trial registration number This trial was registered as NCT06103084.

Produce prescription programs (PRx) targeting different populations and conditions have been found to be effective. However, few have focused on pregnant women. The objectives of this study were to assess the impact of the Food4Moms (F4M) PRx on 1) healthy eating stages of change 2) intake of fresh produce, and 3) household food security among pregnant Latina women. F4M recruited low-income Latinas living in Greater Hartford, Connecticut that received a "produce prescription" from a Registered Dietitian based at the community-based organization (CBO) where the program was implemented. Participants were offered $100 per month for 10 months through Fresh Connect debit cards to purchase fresh produce from two food retailers or the equivalent value in fresh produce delivered at home. To be fully enrolled in F4M, participants had to complete a baseline survey and the first nutrition education interactive session. Enrolled participants were offered additional nutrition education sessions at the CBO and received text messages with nutrition tips as well as reminders to spend their remaining benefit balances towards the end of each month. A single-group pre-post study design was used to assess the impact of F4M 10 months after the card activation. No attrition bias was detected when comparing the characteristics of those completing (N=113) vs. those not completing the endline survey (N=41). Pre-post Wilcoxon signed-test or paired t-test analyses showed that F4M had a positive impact on healthy eating readiness (p < 0.001), the consumption of fruits (p < 0.001) and vegetables (p < 0.001), and household food security (p = 0.034). F4M is a promising community-engaged PRx program that may improve readiness for healthy eating, produce intake, and household food security. Implementation research is needed to find out how to effectively scale out and sustain programs like F4M. The study was registered in ClinicalTrials.gov (identifier: NCT05907616).

Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) are candidate preventive agents for breast cancer. With emerging evidence of epigenetic regulation of the tumor microenvironment, tissue-level epigenetic effects may represent an important target for cancer prevention. In a randomized Phase II sub-study (high-dose 5 g/day vs low-dose 1 g/day for 12 months; n = 17; Clinicaltrials.gov: NCT02295059), DNA methylation (DNAm) of the breast environment was profiled by reduced-representation bisulfite sequencing (RRBS). DNAm was assessed genome-wide, at individual gene promoters, and for locus-level heterogeneity which has been linked to epigenetic dysregulation that can precede breast cancer. Both doses induced promoter DNAm changes, but their responses diverged: low-dose samples showed increased CpG variance and more differentially methylated promoters without pathway enrichment, whereas high-dose samples had reduced DNAm heterogeneity and promoter enrichment in inflammation signaling pathways. Many overlapping differentially methylated promoters changed in opposite directions between doses. The finding that high-dose n-3 PUFA affects DNAm fidelity in the breast adipose suggests a new potential mechanism for n-3 PUFA-mediated prevention of breast cancer development. Together with the dose-specific, directionally discordant DNAm responses in breast adipose, this study has important implications for both advancing n-3 PUFA for breast cancer prevention and dose selection in future n-3 PUFA supplementation trials.

BackgroundHigher-quality diets have been associated with lower levels of ectopic fat deposited in the viscera and liver, which is hypothesized to be mediated in part by the gut microbiota. ObjectivesWe tested this hypothesis in a multi-ethnic imaging study using global (microbiome-wide) testing as well as a high-dimensional multiple-mediators regression framework to identify bacterial genera in the human gut that mediate the association between diet quality and ectopic adiposity. MethodsWe analyzed the cross-sectional data of 1,400 older adults (age 60-77) from five racial/ethnic groups in the Multiethnic Cohort Adiposity Phenotype Study (2013-2016). Overall diet quality was defined by adherence to the MIND diet. The relative abundance of 151 bacterial genera was quantified from 16S rRNA gene sequencing of the stool samples. Visceral fat, liver fat, and the presence of MASLD (metabolic dysfunction-associated steatotic liver disease) were determined based on magnetic resonance imaging (MRI). We used high-dimensional mediation analysis (HDMA) to estimate gut microbial mediation in the linear regression of visceral fat or liver fat, or in logistic regression of MASLD, on the MIND adherence score, adjusted for potential confounders. ResultsHigher diet quality was associated with lower ectopic adiposity: 12% less visceral fat area, 23% less liver fat, and a 49% less likelihood of having MASLD, comparing the highest to the lowest quartile of the MIND score. Using a distance-based global test, we confirmed overall significant microbial mediation of the inverse diet-ectopic fat association. From HDMA, four bacterial genera were identified as mediating the protective association with visceral fat, with the largest mediation conferred by Lachnospiraceae UCG.001 (12.2%). Two genera (Lachnoclostridium, Weissella) were shown to mediate the MIND association with both liver fat and MASLD. In particular, Lachnoclostridium mediated 13.6% of the liver fat association and 10.8% of the MASLD association, and Lachnospiraceae UCG.001 additionally mediated 12.1% of the liver fat association. ConclusionsOur results support the hypothesis that the gut microbiota contributes to conveying the effect of diet quality on preferred body fat distribution, e.g., involving bacteria that are known to produce short-chain fatty acids (Lachnospiraceae) or secondary bile acids (Lachnoclostridium).

Introduction High consumption of ultra-processed foods (UPF) is associated with adverse health outcomes and weight gain. Despite increasing calls for behavioural strategies to reduce UPF intake, no theory-informed intervention targeting UPF reduction has been evaluated in UK adults in alignment with national dietary guidance. We assessed the feasibility, acceptability, and preliminary behavioural and clinical outcomes of a multi-component intervention designed to reduce UPF consumption (and increase physical activity (PA)/minimally processed food (MPF) intake). Methods In this exploratory single-arm pre-post study, adults (N=45) living with overweight or obesity and habitual UPF intake [&ge;]50% of total energy were offered a 6-month behavioural intervention following a controlled feeding phase (UPDATE trial, stage 1). The intervention was developed using the Behaviour Change Wheel and Capability, Opportunity, Motivation-Behaviour (COM-B) model and included one-to-one sessions with a behavioural scientist, tailored print and digital materials, peer-support meetings, and a moderated group chat. Feasibility outcomes included uptake, retention, and intervention fidelity. Secondary outcomes included COM-B constructs, dietary intake, PA, clinical and self-reported outcomes, and qualitative feedback. Results Uptake was 91% (41/45). Retention at 6 months was 68% (28/41), with 83% (34/41) providing follow-up data (intention-to-treat). Median attendance at one-to-one sessions was 86% (interquartile range (IQR): 57-100) with 56% (23/41) attending all sessions (per-protocol). Fidelity to core behaviour change techniques was high. At 6 months, COM-B scores improved for healthy eating (+7%, standard deviation (SD): 8; p<0.001) and physical activity (+5%, SD: 9; p=0.013). UPF intake decreased by 25% of total energy (95% confidence interval (95%CI): -32, -17), with a corresponding increase in minimally processed foods (+23%; 95%CI: 17, 29). Vigorous physical activity increased (+60 min/week, IQR: 0-180), weekday sitting time decreased (-61 min/day, SD: 110), and weight reduced by 3.8 kg (IQR: -8.5-1.0; p=0.001). Findings were similar in per-protocol analyses. Qualitative data indicated perceived improvements in wellbeing and habit formation. Conclusion This theory-informed intervention demonstrated good feasibility and acceptability and was associated with improvements in targeted behavioural mechanisms and health-related outcomes. A randomised controlled pilot trial is warranted to evaluate effectiveness and refine implementation.

BackgroundThe timing of energy intake could be important in the development of obesity. However, most observational evidence stems from adults, anthropometric defined obesity outcomes, single meal timing phenotyping, and traditional regression modeling. ObjectiveWe aimed to describe meal timing patterns in adolescents and determine if they associated with fat mass by modeling the median and all other percentiles of the frequency distribution. MethodsWe analyzed data from the Sleep and Growth Study 2 (S-Grow2, N=286, 12-13y). Participants completed 3-day 24-hour dietary recalls and time stamped eating occasions were used to define 8 meal timing traits, with aide from self-reported wake and bed timing. Principal component analysis (PCA) identified multi-dimensional meal timing patterns. Fat mass index (FMI) was estimated using dual energy X-ray absorptiometry. Quantile regression assessed if there were associations between meal timing traits and FMI across the entire FMI frequency distribution. ResultsThe typical first and last eating occasions were 8:00am (40 minutes after waking) and 8:00pm (2.7 hours before sleep), respectively, thus the eating period typically lasted 11.5 hours per day. The typical eating period midpoint was 2:15pm, and the timing when 50% of energy intake was consumed typically occurred at 3:15pm. PCA revealed three meal timing patterns: 1) "Delayed Start, Condensed Eating Period" (43% of variance; shorter eating period and delayed timing of first eating); 2) "Late, Sleep Proximal Eating" (30% of variance; later timing of last eating and extended eating period), and 3) "Later Energy Intake" (10% of variance; delayed energy intake midpoint). Higher scores for the "Delayed Start, Condensed Eating Period" pattern associated with higher body mass index and FMI at the upper tails of their distributions. ConclusionsDistinct multidimensional meal timing patterns emerged in early adolescence, with the delayed start, condensed eating period pattern potentially associated with higher adiposity. Clinical Trials Registry Site and NumberN/A

Assigning glycemic index (GI) values to food composition databases is a critical bottleneck in nutritional epidemiology. We developed an in-context learning approach using large language models (LLMs), in which a structured knowledge system (termed a skill) loads GI reference databases ([~]11,000 entries), expert decision rules, and error-correction heuristics into the models context window ([~]300,000 tokens). The LLM performs GI assignments without scripted logic, functioning simultaneously as a semantic matching engine, numerical reasoning system, and expert curator. We validated this approach in two experiments. In Validation Study 1, the skill predicted the expert-curated US National GI Database (9,428 foods) using only European reference data, achieving within {+/-}10 agreement of 73.7% without manual review - compared with 31.3% retention of previously published cosine-similarity approach. In Validation Study 2, the skill was augmented with US GIDB and applied to 1,157 European food descriptions classified using the EFSA FoodEx2 system, achieving ICC = 0.79 with the expert (weighted {kappa} = 0.65; triplicate ICC = 0.88). We then applied the skill prospectively to extend US dietary GI and GL surveillance to two additional NHANES cycles (2019-2023), identifying a continued decline in energy-adjusted glycemic load. Reproducibility was assessed through triplicate runs (temperature = 0, pinned model version). The skill architecture is described in sufficient detail to inform future applications of in-context learning for nutritional database construction. STATEMENT OF SIGNIFICANCEThis paper introduces a fundamentally new approach to glycemic index (GI) database construction. Rather than using programmatic text-matching algorithms followed by extensive manual curation, we demonstrate that a large language model (LLM), when loaded with the complete GI reference literature and formalized expert decision rules, can perform one-shot GI assignments at accuracy levels comparable to human expert ratings (ICC = 0.79 with expert, weighted {kappa} = 0.65 for GI category agreement). The approach is validated across two independent food databases spanning US and European food supplies. The method reduces the time required to assign GI values to a new national food database from months of expert labor to hours of computation, while maintaining reproducibility through a structured, versionable skill architecture. This has immediate practical implications for enabling GI-based dietary surveillance and epidemiologic research in countries that currently lack GI databases or need to update existing databases.

Understanding how nutritional interventions alter food evaluations may help clarify mechanisms of dietary behavior change; however, most studies focus on intake outcomes and rarely assess within-person changes in subjective food evaluation. We developed a brief, image-based rating tool that measures two core dimensions of food evaluation, liking and perceived healthiness, using standardized food images. The tool was piloted in adults with type 2 diabetes participating in a medically supervised intervention that included structured glucose monitoring and professional dietary guidance. Ratings were collected at baseline, post-monitoring, and follow-up. In line with the methodological aim of this study, we examined whether the tool demonstrates internal coherence, sensitivity to change, and external validity against expert ratings and physiological measures, and whether it can capture item-level patterns relevant to eating behavior. Results provide preliminary evidence that the tool is feasible, it is low-burden, and capable of detecting coherent relationships between food liking and health perceptions, including coordinated within-person changes over time and meaningful associations with external benchmarks. To support scalability and self-administration, we also developed an online smartphone-based demonstration version to exemplify the task structure and user experience. Overall, this pilot study suggests that a short, flexible rating task can serve as a practical measurement tool for tracking intervention-relevant changes in food evaluation and for informing the design of future nutritional interventions.

Gene-environment interactions (GEI) contribute to circulating polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) profiles. GEI may partly explain differences in trait variance across genotype groups. To identify GEI for circulating unsaturated fatty acids, we adopted a two-stage strategy. First, we detected quantitative trait loci associated with trait variance (vQTLs). Second, we tested these vQTLs for interaction with fish oil supplements (FOS). We performed genome-wide vQTL screens for 14 plasma PUFA and MUFA phenotypes in a UK Biobank subset of 200,478 participants. At the genome-wide significance threshold (p < 5.0 x 10-8), we identified 172 vQTL-trait pairs across all 14 traits, and 16 of these vQTLs had no marginal genetic effect on the corresponding trait. We found 46 non-overlapping loci across all phenotypes, with an average of 12 vQTLs per trait. Omega-6% and PUFA% had the most independent vQTLs (N = 24) while DHA% and Omega-3% had the least (N = 1 and 2, respectively). For each of the 172 vQTL-trait pairs, we tested the interaction effect of the vQTL with FOS on the corresponding trait. We found six significant interaction signals in DHA, DHA%, Omega-3, Omega-3%, LA, and Omega-6/Omega-3 ratio around the FADS1/2, ZPR1, and SUGP1/TM6SF2 genes. Our results provide a comprehensive resource of vQTLs and gene-FOS interactions shaping the circulating levels of unsaturated fatty acids.

IntroductionLactoferrin and lysozyme are milk derived proteins with antimicrobial and anti-inflammatory properties. We tested if these supplements improved time-to-nutritional-recovery and reduced the incidence of new moderate or severe diarrhea (MSD) among children presenting to hospital with wasting and diarrhea. MethodsMedically-stable children aged 6-24 months with diarrhea and wasting were randomized to a 16-week course of lactoferrin, lysozyme, a combination of both, or placebo. Time-to-nutritional-recovery (mid-upper arm circumference [&ge;] 12.5cm) and incidence of new onset MSD were the primary outcomes observed over 6-months follow-up. Subgroup analyses included efficacy by wasting status (severe vs. moderate), stunting, age, inpatient/outpatient, and adherence. ResultsAmong the 600 children randomized, 531 (88.5%) nutritionally recovered within 16-weeks; 63% among severely wasted children and 95% in children with moderate wasting. The wasting recovery rate in the combination arm was non significantly higher (HR: 1.23, 95%CI: 0.97, 1.57; p=0.083) than the placebo group. Children randomized to lactoferrin alone and lysozyme alone had nutritional recovery rates similar to placebo (HR: 0.94, 95% CI 0.74, 1.20; p=0.607 and HR: 0.91, 95% CI: 0.71, 1.17; p=0.462, respectively). Among severely wasted children, the combination arm had a higher recovery rate than placebo (HR: 2.76, 95% CI 1.49, 5.09; p=0.001), but not the individual lactoferrin (HR: 1.29, 95% CI 0.69, 2.41; p=0.427) and lysozyme (HR: 0.80, 95% CI: 0.40, 1.60; p=0.530) arms. Children randomized to intervention arms had comparable incidence of MSD (82.3-97.0 per 100 child-years) to the placebo arm (75.3 per 100 child-years). ConclusionsThe combination of lactoferrin and lysozyme for 16 weeks modestly improved nutritional recovery time particularly among severely wasted children. If confirmed, there may be a role for enteric-targeted therapeutics as adjuvants to severe wasting management. Additional strategies are needed for the post-acute diarrhea recovery period.

Although the co-occurrence of diarrhea and malnutrition is well documented, research has largely focused on the acute management of diarrheal illness. Despite its importance, longitudinal evidence characterizing post-diarrheal recovery trajectories is sparse. We sought to characterize post-diarrheal nutritional recovery trajectories among children aged 6-35 months who were malnourished at enrollment using data from the Enterics for Global Health (EFGH) Shigella Surveillance study (2022-2024). EFGH enrolled children aged 6-35 months presenting with medically-attended diarrhea and followed them at 4 weeks and 3 months post-enrollment. This analysis included children with baseline wasting, stunting, or underweight (z-score < -2) and complete anthropometric follow-up. Latent class mixed-effects models were used to identify distinct post-diarrheal growth trajectories based on changes in anthropometric z-scores over time. Multinomial modified Poisson regression models examined associations between baseline factors and trajectory membership. Among 9,480 enrolled children, 16.5% (n=1,561) were wasted, 22.7% (n=2,155) stunted, and 21.0% (n=1,994) underweight at baseline. Wasting showed greater recovery potential (80.8%) compared with stunting (38.5%) and underweight (40.3%). Recovery was shaped by factors across multiple levels. Clinical severity markers ( prolonged diarrhea, dehydration, and hypoxemia) increased the risk of nutritional failure. Age also influenced outcomes: infants were more likely to worsen, whereas older toddlers more often experienced stagnation. Interventions including exclusive breastfeeding, oral rehydration therapy, appropriate antibiotics, and zinc supplementation, improved outcomes, while unimproved sanitation undermined recovery. These findings highlight the need for integrated strategies combining infection control, nutritional rehabilitation, and water, sanitation, and hygiene interventions tailored to the childrens developmental stage. Key MessagesO_LIPost-diarrheal nutritional recovery is highly heterogeneous, with wasting showing the greatest potential for improvement, while stunting and underweight often result in persistent growth stagnation. C_LIO_LIBaseline anthropometric deficits alone are insufficient to predict recovery, highlighting the need for dynamic monitoring and individualized management. C_LIO_LIInfants are particularly vulnerable to acute nutritional deterioration, while older toddlers frequently experience growth stagnation. C_LIO_LIModifiable protective factors including exclusive breastfeeding, ORS, zinc, and appropriate antibiotics, improved outcomes, whereas poor sanitation undermined recovery. C_LIO_LIIntegrated strategies, tailored to a childs developmental stage, combining clinical care, nutrition, and environmental interventions are critical to support sustained child growth and development. C_LI

BackgroundAffecting 40% of infants and young children worldwide, anaemia in sub-Saharan Africa hampers cognitive and physical development, often in ways that cannot be reversed. Iron-based micronutrient powders (MNPs) are recommended to combat anaemia, but concerns remain about their safety and effectiveness in malaria-endemic areas. We evaluated the impact of iron-based MNPs on growth measurements and malaria-related anaemia among preschool children in Ghana. MethodsWe conducted a secondary analysis of a cluster-randomized, double-blind, placebo-controlled trial in the Bono Region, Ghana. Children aged 6-35 months (n=1,958) received daily MNP containing 12{middle dot}5mg elemental iron or placebo for five months. Anthropometric indices, haemoglobin, and malaria parasitaemia were assessed at baseline and endline. Adjusted analysis of covariance (ANCOVA) models estimated effects on height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z scores. Binomial regression with identity link estimated risk differences for malaria-induced anaemia. Cluster-robust standard errors were applied at the compound level, and intracluster correlation coefficients (ICCs) were estimated. Results1,815 (92{middle dot}7%) children completed the endline survey, but 1,806 were included in the final analysis. Baseline characteristics were balanced between groups. Iron-containing MNP had no significant effect on endline HAZ ({beta}=0{middle dot}026, p=0{middle dot}609), WAZ ({beta}=-0{middle dot}015, p=0{middle dot}719), or WHZ ({beta}=-0{middle dot}035, p=0{middle dot}463). However, the intervention reduced the risk of malaria-induced anaemia (risk difference 0{middle dot}050, 95% CI 0{middle dot}004-0{middle dot}096; p=0{middle dot}032). Female sex was associated with higher HAZ ({beta}=0{middle dot}149, p=0{middle dot}005). ConclusionIron-containing MNP did not improve short-term growth but was associated with a modest reduction in malaria-induced anaemia. These findings support the safe use of iron fortification in malaria-endemic settings while underscoring the need for integrated strategies to address persistent growth faltering and gender specificity. TRIAL REGISTRATION clinicaltrials.gov IdentifierNCT01001871. Registered 27/10/2009, http://www.ClinicalTrials.gov/NCT01001871.