The American Journal of Clinical Nutrition

Background & aims: Autophagy activation is a promising strategy to counteract age-related cellular dysfunction. While preclinical studies suggest dietary protein restriction can induce autophagy via mTORC1 inhibition, direct human evidence using dynamic, flux-based measurements remains limited. The aim of this study was to determine whether a low protein diet could modulate autophagic flux in humans. Methods: We conducted a randomized crossover trial in which 74 healthy adults were randomized to receive two 4-week interventions of either average-protein (20% energy) or reduced-protein (10% energy) diets prescribed to maintain calculated energy balance, separated by a 4-week washout period. The primary outcome was autophagic flux measured in whole blood using a validated assay that preserves PBMCs in their physiological environment during lysosomal inhibition. Secondary outcomes included metabolic markers, body composition, and self-reported health metrics. Results: Sixty-three participants completed both interventions (mean {+/-} SD age 29.5 {+/-} 7.2 yrs; BMI 24.0 {+/-} 3.2 kg/m2). Reducing protein intake did not alter autophagic flux (adjusted mean difference: -8.46 ng LC3B-II/mg protein/h; 95% CI: -24.06 to 7.14; p = 0.28). Metabolomic profiling confirmed effective dietary separation, with lower circulating urea following reduced protein intake. Small differences in body weight and muscle mass were observed, while fat mass was unaffected. Fasting glucose, insulin, lipids, blood pressure, and quality of life did not differ between the two diets. Conclusions: Moderate protein restriction does not increase basal autophagy in circulating immune cells of healthy adults, suggesting protein reduction alone, without caloric deficit, may be insufficient to activate autophagy in human blood.

The Healthy Eating Index (HEI-2020) is conventionally computed by aggregating intake across days before scoring. Digital food logging enables an alternative: scoring each day and averaging daily scores. These methods are not equivalent. The HEI's density-based structure and component caps cause aggregation to inflate adequacy scores when intake is irregular. Using Food & You data, we show daily HEI correlates more strongly with microbiome diversity, and recommend co-reporting both metrics.

Background: Chronic kidney disease (CKD) is associated with alterations in the gut microbiome that promote the accumulation of gut-derived uremic solutes and contribute to systemic inflammation, vascular dysfunction, and disease progression. Dietary fiber has emerged as a promising modulator of gut microbial metabolism, yet the influence of fiber physicochemical properties, particularly fermentability and viscosity, on uremic metabolite production in CKD remains poorly understood. Objective: To systematically evaluate the effects of isolated dietary fiber interventions, classified by fermentability and viscosity, on gut microbial metabolites in CKD across experimental rodent models and randomized clinical trials, and to determine whether these fiber properties modify microbial metabolites. Methods: A systematic search of PubMed, Embase, CINAHL, and Cochrane Library (through June 2026) identified randomized controlled trials and controlled rodent studies assessing isolated dietary fiber in CKD. Eligible studies reported at least one gut-derived metabolite (i.e., indoxyl sulfate (IS), p-cresyl sulfate (PCS), trimethylamine-N-oxide (TMAO), tryptophan-derived indoles, or short-chain fatty acids (SCFAs)). Random-effects models were used for pooled estimates using weighted mean differences (WMD) for human studies and standardized mean differences (SMD) for animal studies. Subgroup analyses evaluated fiber fermentability, viscosity, intervention dose, duration, and CKD stage. Risk of bias was assessed with ROB-2 and SYRCLE, and evidence certainty with GRADE. Results: Twenty-eight studies (13 human, 15 animal) met eligibility criteria, comprising 511 participants and 312 animals with CKD. Isolated fiber supplementation, primarily fermentable and non-viscous fibers, reduced IS (human: -0.13 mg/dL; 95% CI: -0.25, -0.01; p = 0.03; animal: -1.99; 95% CI: -3.06, -0.92; p < 0.0001) and pCS (human: -0.23 mg/dL; 95% CI: -0.46, 0.001; p = 0.051; animal: -1.56; 95% CI: -2.08, -1.03; p < 0.0001). SCFAs increased in animal studies, including cecal acetate (2.00, 95% CI: 0.78 to 3.22; p = 0.001) and circulating propionate (1.51, 95% CI: 0.054 to 2.96; p=0.04). There were no dose-dependent effects, but longer interventions (>8 weeks) tended to lower pCS (-0.26 mg/dL, 95% CI: -0.55 to 0.02; p=0.06). Some heterogeneity and low-to-moderate certainty were observed. Conclusion: Isolated dietary fiber reduces major gut-derived uremic solutes in CKD, with fermentability influencing metabolic responsiveness, but with minimal studies on viscous fibers. Larger, longer-duration trials with standardized reporting of total fiber intake and clinical endpoints are needed to guide evidence-based dietary recommendations in CKD.

Background: Dietary fiber comprises a heterogeneous group of compounds with distinct physicochemical properties and biological effects. As such, functional outcomes observed for one fiber cannot be generalized to others. Some fermentable fibers, such as arabinoxylan, may exert biologically selective effects across multiple physiological domains, highlighting the need to evaluate individual ingredients for their domain-specific activity in controlled human studies. Methods: In this randomized, double-blind, parallel, 3-arm, placebo-controlled trial, healthy, overweight adults were assigned to consume one of two low doses of an arabinoxylan dietary fiber (3.5g or 5g) or placebo over the intervention period. Self-reported appetite sensations were assessed as the primary outcome using validated visual analogue scales. Secondary and exploratory endpoints included lipid parameters, gastrointestinal outcomes, mood-related measures, and gut microbiota composition and fermentation-derived metabolites. Analyses were conducted in the full analysis set and a high-compliance population to assess responses under sustained intake conditions, as per the intended dosing regimen. Results: The primary endpoint of appetite sensations did not differ between either arabinoxylan group and placebo. In contrast, evidence of microbial fermentation and selective microbiota engagement was observed. These responses occurred alongside consistent and favorable changes in lipid parameters under conditions of sustained intake, including reductions in low-density lipoprotein cholesterol and triglycerides. Additional outcomes, including gastrointestinal symptoms and mood, demonstrated domain-specific responses. Conclusion: This study demonstrates that supplementation with low doses of arabinoxylan dietary fiber elicit biologically selective, domain-specific effects across metabolic, microbial, gastrointestinal, and behavioral outcomes, particularly under conditions of sustained intake. These responses occurred independently of changes in appetite sensation, indicating that functional effects were not mediated through appetite-related pathways. Collectively, the findings highlight the ingredient's biological versatility and contextual responsiveness across physiological systems, and suggest its prebiotic potential through alignment with ISAPP's definition of a prebiotic, supporting further investigation of specific mechanistic pathways. Clinical trial registration: https://clinicaltrials.gov/study/NCT06884449, identifier: NCT06884449

Background: Many epidemiological studies rely on dietary exposures taken from baseline only. This limits our understanding of diet-disease associations because it requires assuming a level of temporal stability, either by individuals or dietary pattern composition. Objectives: This study aimed to evaluate these analytic assumptions of pattern structure consistency and baseline adherence using a cohort of US Black women with repeated measures of food frequency questionnaires (FFQ). Methods: Data from 6151 Black women aged 21-69 from the Black Women's Health Study with complete FFQ data in 1995, 2001, 2013, and 2021 were evaluated for temporal stability. Baseline dietary patterns were derived using an overfitted latent class model. Parameter estimates from the baseline model were then applied to subsequent waves to track individual transitions between existing patterns. Dietary patterns were also derived at each time point using an overfitted latent class model and assessed for changes in pattern composition over time. Results: Five baseline dietary patterns were identified in 1995. Only 18% of participants remained in the same baseline dietary pattern across all four time points, while all others transitioned to a different baseline-derived pattern. Dietary patterns derived independently at subsequent time points, yielded a different number of dietary patterns at each time point (2001: 6 patterns, 2013: 5 patterns, 2021: 4 patterns). Correlation strength of subsequent derived patterns and baseline patterns significantly weakened in strength after 2001 (40% pairings > 0.5), with no patterns correlated greater than 0.5 in 2021. Conclusion: Prospective studies that rely on baseline dietary exposure data cannot assume stability of pattern composition or individual pattern adherence over time, as it ignores changes in dietary habits and may bias our understanding of the diet-disease pathway.

Low dietary diversity is a risk factor for micronutrient deficiencies. Agricultural interventions that support crop production and livestock rearing may promote dietary diversity and achieve better nutritional outcomes, particularly among low-income households. Their effectiveness may be strengthened when integrated within microfinance platforms. The objective of this study was to estimate the association between an agricultural intervention delivered within a group-based microfinance program and dietary diversity in rural Western Kenya, and determined effect modification by sex. We conducted a cross-sectional design from June to August 2025 in two village wards of Webuye sub-County in rural Western Kenya, using a validated dietary diversity scale to assess the total number of food groups consumed in the previous 24 hours. We interviewed 312 microfinance participants, 156 of whom were in agricultural intervention comprised of farm input subsidies and training, while 156 were not in the intervention. We specified modified Poisson models to estimate the association between intervention receipt and dietary diversity, and tested whether the estimated association differed by sex. Participation in the agricultural intervention was associated with higher diversity among microfinance program members [adjusted PR (95% CI): 1.46 (1.02, 2.06)]. We did not find evidence that the association differed by sex (Wald p-value for interaction term=0.83). Participation in an agricultural intervention was associated with improved dietary diversity. Future prospective using large samples studies should build on these findings to establish temporal ordering, and assess the feasibility and sustainability of integrating agricultural support into microfinance platforms to improve dietary diversity in low-resource settings.

Background: Almost 1 in 2 adults in the US has obesity, with women facing the highest prevalence of severe obesity. Emerging evidence shows that the gut microbiome and its metabolites play a key role in metabolic regulation, acting as signals in active metabolic tissues such as adipose and skeletal muscle, thereby contributing to the deterioration of cardiometabolic health in individuals with obesity. Recent findings suggest that functional characteristics of the gut microbiome, rather than compositional changes alone, may partially explain why some individuals experience greater metabolic benefits from exercise than others. We designed a pilot trial to assess the acute response to an exercise bout across distinct obesity phenotypes and to identify microbial signatures associated with lifestyle interventions. Methods: We proposed a pilot trial in which 40 young adults (21 to 40 years old) with distinct exercise (< 150 minutes per week or > 4 hours per week) and body compositions (body mass index [BMI] 18.5 to 24.99 or > 30 kg/m2) would undergo an acute exercise bout. The outcomes of this pilot trial are as follows: (1) Examine the effects of a 30-minute bout of moderate-intensity aerobic exercise (60 to 70% heart rate reserve) on the abundance and functional activity of short-chain fatty acid (SCFA)-producing gut bacteria across different obesity phenotypes in women; (2) Assess the acute effects of the same exercise bout on SCFA concentrations in stool and circulating plasma metabolomic profiles. Discussion: The results of this pilot study will inform the feasibility of a larger trial to establish the gut-synthesized

Objective To develop and evaluate an automated large language model (LLM)-based framework for conducting meta-analyses of nutrition-related exposures and the risk of breast, ovarian, and uterine cancers. Design We developed MetaFemina, an automated evidence-synthesis pipeline for women's cancers that integrates keyword-based literature retrieval, LLM-assisted evidence extraction, and random-effects meta-analysis. We evaluated its performance against two recently published peer-reviewed meta-analyses and compared exposure-outcome associations across the three cancer types. Data sources PubMed articles identified through keyword-based searches of titles and abstracts. Methods MetaFemina was developed as a web platform that identifies relevant scientific articles, automatically extracts relevant information using LLMs, and synthesizes extracted evidence using random-effects meta-analysis. Additional analyses included assessment of heterogeneity, publication bias, and leave-one-out sensitivity analyses. The platform also provides sample size calculations based on synthesized effect sizes and generates visual summaries and plain-language interpretations. Results Compared with two recent peer-reviewed meta-analyses of folate and vitamin E intake in relation to breast cancer risk, MetaFemina demonstrated high sensitivity (81.82% and 80%, respectively) in identifying eligible studies and additionally retrieved relevant articles that had been missed by manual screening (27 and 13, respectively). Among 226 exposures considered, lutein and beta-carotene were significantly associated with lower risks of breast, ovarian, and uterine cancers. Vitamin D, antioxidants, and soy were significantly associated with lower risks of both breast and ovarian cancers, whereas calcium and folic acid were significantly associated with lower risks of both breast and uterine cancers. In contrast, iron, red meat, and copper were significantly associated with higher risks of both breast and uterine cancers. omega-6 fatty acids showed contrasting associations, being significantly associated with higher breast cancer risk but lower ovarian cancer risk. After restriction to dietary-intake studies, these cross-cancer significant associations remained statistically significant except for copper, which no longer met the two-study threshold for either breast or uterine cancer. Additionally, calcium became significantly associated with lower ovarian cancer risk, resulting in significant negative associations across all three cancer types, while vitamin E became significantly associated with lower breast cancer risk and remained significantly associated with lower ovarian cancer risk. Conclusions MetaFemina demonstrated high sensitivity for identifying relevant scientific literature, extracts key evidence, and performs statistically rigorous automated meta-analyses. The framework may facilitate more rapid evidence synthesis in nutritional epidemiology and may support researchers in study design, hypothesis generation, and interpretation of emerging evidence.

Background: Yeast (Saccharomyces cerevisiae) is a model organism in agricultural and industrial fermentation with nutritional benefits, yet less is understood about its nutritional value for supporting whole-body protein synthesis in vivo, and its comparison to animal-based protein. Objective: This study aimed to determine the effect of microbial-based protein (yeast) compared to a high (whey) and low (collagen) quality animal-based protein on the ability to support whole-body protein synthesis using the indicator amino acid oxidation technique. Methods: Thirteen healthy participants (M: n=6, 24{+/-}4 yr; F: n=7, 27{+/-}7 yr) consumed eight hourly yeast (Y), whey (W), or collagen (CH) protein beverages at 0.9 g{middle dot}kg-1{middle dot}d-1 supplemented with L-[1-13C]phenylalanine in a randomized, cross-over, counterbalanced design. Breath and urine were collected to measure fraction of expired 13CO2 (F13CO2) and [1-13C]Phe oxidation (PheOx) as inverse correlates of whole-body protein synthesis. An a priori 20% noninferiority margin was used to determine equivalency between protein sources. A Visual Analog Scale (VAS) was provided to assess fullness and hunger by protein sources. Results: Protein source had no effect on F13CO2 (P=0.15) or PheRa (P=0.10). PheOx was greater in CH compared to both Y (14.94{+/-}2.16 vs. 12.93{+/-}2.80 mol{middle dot}kg BM-1{middle dot}h-1, P<0.05) and W (14.94{+/-}2.16 vs. 12.50{+/-}2.75 mol{middle dot}kg BM-1{middle dot}h-1, P<0.05) whereas there was no significant difference between Y and W (P=0.59). Change in PheOx (mean difference [90% CI]) between CH and W (2.44 mol{middle dot}kg BM-1{middle dot}h-1 [0.98, 3.90], P<0.05) and between Y and W (0.44 mol{middle dot}kg BM-1{middle dot}h-1 [-1.34, 2.21], P>0.99) confirmed respective inferiority and noninferiority to W compared to the 20% noninferiority margin (2.50 mol{middle dot}kg BM-1{middle dot}h-1), while Y was superior to CH (-2.00 mol{middle dot}kg BM-1{middle dot}h-1 [-3.01, -0.99], P<0.05). Protein source did not significantly influence satiety (P=0.32) or hunger scores (P=0.15). Conclusion: EAA-enriched whey and yeast protein similarly reduced PheOx as compared to EAA-deficient collagen hydrolysate, suggesting these proteins were similarly superior in supporting whole-body protein synthesis.

Background: Monitoring urinary iodine concentration (UIC) after sustained exposure informs iodine delivery strategies. We aimed to compare endline UIC among women of reproductive age (WRA) and preschool children (PSC) receiving multiple micronutrient-fortified (MMF) vs. iodine-only bouillon, and to describe population iodine status at baseline and endline. Methods: This pre-specified secondary outcome analysis used Condiment Micronutrient Innovation Trial (CoMIT) data. Non-pregnant, non-lactating WRA (15-49 years) and PSC (2-5 years) were enrolled at the household level. Households received MMF or iodine-only bouillon for 9 months (38 weeks); both contained iodine (KIO3) at 30 ug/g. Baseline and endline UIC (ug/L) were measured by modified Sandell-Kolthoff reaction in spot urine samples. ANCOVA models, adjusted for baseline log-UIC and recruitment site, compared endline geometric mean UIC between trial arms. Median UIC at both timepoints was compared to WHO cut-offs (ug/L): <100 (insufficient), 100-199 (adequate), 200-299 (above requirements), and >=300 (excessive); the prevalence of UIC <50 ug/L was calculated. Results: Endline UIC data were available for 611 WRA and 630 PSC. Adjusted endline UIC did not differ by arm (geometric mean ratio [95% CI]: WRA 0.97 [0.86-1.10]; PSC 0.96 [0.84-1.10]). With arms combined, median UIC increased among WRA (100.5 to 124.6 ug/L) and PSC (109.6 to 136.9 ug/L), with fewer samples <50 ug/L at endline. Conclusions: Adjusted endline UIC did not differ between trial arms. After 9 months' use of iodine-fortified bouillon, median UIC remained adequate among WRA and PSC, with fewer samples <50 ug/L at endline.

Introduction: Infant neurodevelopment is associated with maternal nutritional status, yet few studies have evaluated the effects of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation. Methods: The Maternal Infant Nutrition Trial (NCT03668977) was a 2x2 factorial, household randomized, unblinded, efficacy trial conducted in Sarlahi District, Nepal. Pregnant women were randomized to daily fortified BEP supplementation or no supplementation, and those with a live birth were re-randomized after delivery to supplementation or not until 6-months postpartum. The first 100 infants in each of the four intervention groups were enrolled in a neurodevelopment substudy. At 6-months, these infants underwent a cognitive, motor, language, and socioemotional assessment using the Bayley Scales of Infant and Toddler Development, fourth edition. Results: Baseline characteristics were similar across the four trial groups. A significant interaction (p< 0.05) between pregnancy and lactation supplementation groups was observed in the language domain only. Infants born to mothers who received BEP supplementation during pregnancy did not differ in standard scores for cognitive (mean difference (MD): 2.0, 95% confidence interval (CI): -0.29, 4.29), motor (MD: 0.98, 95% CI: -1.41, 3.36), or socioemotional (MD: -2.35, 95% CI: -5.27, 0.57) domains compared to the pregnancy control group. Similarly, for these three domains, there were no significant differences among infants whose mothers received BEP in lactation period vs. not. Infants born to mothers supplemented in both pregnancy and lactation had significantly higher mean language standard scores of 2.12 (95% CI: 0.16, 4.08; p-interaction = 0.015), driven by the expressive communication subtest, compared to those with no BEP supplementation in either period. Conclusion: BEP supplementation during pregnancy and/or lactation was not associated with improvements in cognitive, motor, or socioemotional domains at 6 months; however, infants of women supplemented in pregnancy and lactation had significant improvements in the language domain. Evaluation at later ages is warranted.

Consumer-grade bioelectrical impedance analyzers have become widely used for body composition assessment, yet their accuracy varies considerably across devices. The Hume Pod is a popular consumer-grade analyzer marketed as being highly accurate, but independent validation is lacking. The purpose of this study was to evaluate the reliability and validity of the Hume Pod relative to both a four-compartment (4C) model and dual-energy X-ray absorptiometry (DXA). Sixty-seven adults (42 females, 25 males; age 37.2 +/- 13.5 years, body mass index: 24.6 +/- 4.9 kg/m2, body fat percentage [BF%]: 26.4 +/- 10.2%) completed duplicate Hume Pod assessments alongside DXA and 4C evaluations. Reliability was evaluated using the technical error of measurement (TEM) and intraclass correlation coefficients (ICC). Validity was assessed using equivalence testing, Lin's concordance correlation coefficient (CCC), standard error of the estimate (SEE), Bland-Altman analysis, and additional tests. The Hume Pod demonstrated strong reliability, with ICCs >/= 0.993 and TEMs of 0.8% for BF% and 0.6 kg for fat mass (FM) and fat-free mass (FFM). Relative to the 4C model, BF%, FM, and FFM estimates were statistically equivalent (all p<0.05), with strong agreement (CCC=0.95-0.98), low SEE values (3.1%, 2.3 kg, and 2.2 kg, respectively), moderate limits of agreement (+/-6.1%, +/-4.5 kg, and +/-4.5 kg), and no proportional bias. Compared with DXA, generally strong agreement was also observed. These findings indicate that the Hume Pod demonstrates strong reliability and validity compared with laboratory reference methods for body composition estimation, supporting its potential use as a consumer body composition assessment.

While substantial research has examined the role of infant nutrition in early brain and cognitive development, the links between later childhood nutrition, brain development, and cognitive and academic skills remain less explored. In this work, we investigated for the first time the direct and indirect associations between nutrition intake, white matter microstructure and structural connectivity, and cognitive and academic outcomes. Using longitudinal data from typically developing children aged 2 to 14 years, we combined neuroimaging, dietary, and cognitive measures to test direct associations between nutrition and brain structure and connectivity, as well as cognitive and learning outcomes, and to assess whether brain development mediated these relationships. We found that specific nutrients, including DHA, sphingomyelin, iron, niacin, choline, and palmitoleic acid (omega-7), were associated with improved brain structure and connectivity, as well as better cognitive and learning outcomes. We also found that brain development partly mediated the association between childhood nutrition and learning outcomes. To our knowledge, this is the first study to show such a pathway in school-age children. These results add to the growing literature demonstrating the ongoing importance of nutrition beyond infancy in supporting childhood brain and cognitive development.

Background: The U.S. Food and Nutrient Database for Dietary Studies (FNDDS) is updated across NHANES dietary cycles and is central to U.S. nutrition surveillance. However, multi-cycle food-code-level changes in nutrient composition have not been comprehensively characterized across the full WWEIA nutrient panel. Objective: To characterize ten-year temporal patterns in nutrient composition across five FNDDS cycles, evaluate pandemic-period food-code compositional stability, and distinguish exploratory mean-level signals from distributional heterogeneity that may reflect reformulation, database coverage, or food-code definition changes. Methods: We analyzed five consecutive FNDDS biennial releases: 2013-14, 2015-16, 2017-18, 2019-20, and 2021-23. Nutrient values were extracted from the public FNDDS/FoodData Central release files and standardized to per-100-g food-code-level records. Cycle midpoints, 2013.5, 2015.5, 2017.5, 2019.5, and 2022.0, served as the independent variable in an exploratory ordinary least squares (OLS) regression. Mann-Kendall testing assessed monotonic rank trends, Welch's ANOVA assessed food-code-level distributional heterogeneity, and pairwise Welch comparisons with Cohen's d summarized pre-pandemic, pandemic-period, and post-pandemic differences. Equivalence testing using TOST with +/-10% bounds was restricted to the 2019-20 versus 2021-23 stability comparison. OLS sensitivity analyses were repeated after excluding the structurally atypical 2017-18 cycle. Results: Sixty-three nutrients were analyzed. Eight nutrients showed nominal OLS trends, p < 0.05, but none remained significant after Bonferroni correction. Mann-Kendall testing identified two nominal monotonic signals, and none after adjustment. Welch's ANOVA detected cycle-level distributional differences for 61 of 63 nutrients at nominal p < 0.05 and 57 of 63 after adjustment. Pairwise pandemic-period analyses showed many adjusted differences when the pre-pandemic baseline was compared with 2019-20 or 2021-23, but standardized effects were small, with all absolute Cohen's d values < 0.20. No nutrient differed after adjustment between 2019-20 and 2021-23, and 39 of 48 primary analytes met +/-10% TOST equivalence criteria for that comparison. Slope estimates were directionally stable after excluding 2017-18, but nominal significance status remained sensitive to the short time series. Conclusions: FNDDS food composition varied across cycles, but there was no clear decade-long linear trend for most nutrients. The main signal was a possible increase in total PUFA and linoleic acid, which may reflect changes in fat quality. The 2021-23 cycle was very similar to 2019-20, suggesting no major post-pandemic shift in the foods represented. These findings should be interpreted as food-database signals, not as direct estimates of what people consumed.

Background. Obesity is a modifiable risk factor for osteoarthritis and may contribute to pain, functional impairment, inflammation, and cartilage degradation. Resveratrol has potential anti-inflammatory and chondroprotective effects, but its efficacy as an adjunct to dietary intervention remains unclear. Objective. This study evaluated whether resveratrol supplementation provides additional benefits when combined with a low-calorie diet in postmenopausal women with obesity and knee osteoarthritis. Methods. A total of 97 postmenopausal women with obesity and knee osteoarthritis were included in this randomized controlled clinical study. Participants received either a 10-day low-calorie diet alone or the same diet combined with 150 mg/day trans-resveratrol. Anthropometric parameters, body composition, biochemical markers, pain intensity, functional status, and urinary CTX-II were assessed at baseline and follow-up. Results. Both interventions were associated with reductions in body weight, BMI, waist and hip circumferences, fat mass, glucose, HOMA-IR, lipid parameters, hsCRP, VAS, WOMAC, LAI, and urinary CTX-II. Compared with diet alone, resveratrol supplementation did not provide additional benefits for anthropometric parameters, glucose metabolism, lipid profile, or WOMAC score. However, the resveratrol group showed a greater reduction in hsCRP and urinary CTX-II. The obesity class did not modify the treatment effect. Conclusion. A short-term low-calorie diet improved metabolic, inflammatory, and osteoarthritis-related parameters in postmenopausal women with obesity and knee osteoarthritis. The addition of resveratrol did not enhance weight loss or improve most metabolic outcomes but was associated with greater reductions in hsCRP and urinary CTX-II. These findings suggest a potential anti-inflammatory and cartilage-related effect of resveratrol, which requires confirmation in longer randomized trials.

Efficiently summarizing dietary records at scale remains a persistent bottleneck in nutritional epidemiology. We present FoodScribe, which translates free-text meal descriptions into quantitative nutrient profiles by combining ingredient parsing with nutrient retrieval by querying the USDA FoodData Central (FDC) database. Benchmarked using three LLM providers using Nutribench dataset, FoodScribe completed annotation of 3,807 meal descriptions in 2.5 hours, a task otherwise requiring substantial manual effort from trained nutritionists. FoodScribe achieved accuracy across macronutrient estimation (F1=0.79-0.89), with models performing better for protein than fat estimation. Application to a Mediterranean diet intervention cohort indicated dietary shifts consistent with the intervention pattern based on model-derived estimates. Integration with metabolomics data suggested that fiber and vegetable intake were positively associated with a fecal metabolite cluster.

The Dietary Approaches to Stop Hypertension (DASH) diet reduces blood pressure and cholesterol. However, the mechanisms underlying these effects are unclear, and no randomized studies have evaluated the long-term benefits on health outcomes such as coronary artery disease (CAD) or type 2 diabetes (T2D). We performed a series of Mendelian randomization analyses of 71 serum proteins perturbed by the DASH diet in previous randomized controlled feeding studies to understand their potential mechanistic role on health outcomes. Four proteins (ANGPTL3, INHBC, PCOLCE, PLXNB2) had causal evidence of beneficial effects on risk factors that aligned with diet-induced changes in protein levels. Missense variants in INHBC and PLXNB were associated with lower risks of CAD and T2D respectively, and these effects are directionally concordant with DASH diet-induced changes in protein levels, providing causal evidence that these proteins influence disease risk. Combining molecular phenotyping in randomized interventional studies with human genetics evidence identified molecular regulators of the long-term cardioprotective effects of the DASH diet.

Background: Chemotherapy is a cornerstone of breast cancer treatment but is often accompanied by metabolic, hematological, and psychological changes that may negatively affect patients' health and quality of life. Dietary intake during chemotherapy may influence these treatment-related outcomes; however, prospective evidence based on repeated dietary assessments and comprehensive clinical outcomes remains limited. Objective: The primary objective of this study is to investigate the association between dietary intake during chemotherapy and changes in a predefined composite cardiometabolic risk profile in women with breast cancer. Secondary objectives are to evaluate associations of dietary intake with selected biochemical and psychological outcomes. Methods: In this prospective cohort study, 100 women with histologically confirmed breast cancer undergoing chemotherapy in Tehran, Iran, will be followed from the initiation of chemotherapy until completion of the planned chemotherapy course. Dietary intake will be assessed using nine repeated dietary records collected during the early, mid, and late phases of chemotherapy, and mean intake will represent overall dietary exposure during treatment. Cardiometabolic, biochemical, and psychological outcomes will be assessed at baseline and post-chemotherapy using clinical measurements, laboratory data, and validated questionnaires. Descriptive within-participant changes will be defined as post-chemotherapy minus baseline values and evaluated using paired tests. The primary analysis will examine the association between dietary intake during chemotherapy and the post-chemotherapy composite cardiometabolic risk score using multivariable linear regression adjusted for age, baseline BMI, mean energy intake during chemotherapy, physical activity level at the end of chemotherapy, tumor stage, treatment type, and the baseline composite score. Secondary analyses will use the same baseline-adjusted framework for selected biochemical and psychological outcomes. Exploratory analyses will also examine end-of-chemotherapy serum vitamin D concentration as a concurrent biomarker associated with end-of-treatment outcomes. Results will be reported as beta coefficients with 95% confidence intervals. Conclusion: This study will provide prospective evidence on the relationship of dietary intake and end-of-chemotherapy serum vitamin D status with treatment-related cardiometabolic, biochemical, and psychological changes in women with breast cancer. Keywords: Breast cancer; Chemotherapy; Dietary intake; Cardiometabolic risk factors; Quality of life; Prospective cohort study.

Abstract Background: Iron deficiency anaemia remains a major public health problem in low- and middle-income countries (LMICs), particularly among children, adolescents, women of reproductive age, and pregnant women. Although daily oral iron supplementation is the standard treatment, uncertainty remains regarding whether intermittent dosing provides comparable efficacy with better tolerability and acceptability. We conducted a systematic review and meta-analysis to compare the effectiveness and safety of daily versus intermittent oral iron or iron-folic acid supplementation for treating anaemia in LMICs. Methods: Four electronic databases (PubMed/MEDLINE, Embase, Scopus, and Web of Science) were searched from inception to July 2025. Randomised controlled trials, quasi-experimental studies, and prospective cohort studies conducted in LMICs among anaemic children, adolescents, women of reproductive age, and pregnant women were included. Primary outcomes were changes in haemoglobin concentration and serum ferritin from baseline to study end. Secondary outcomes included adherence, adverse effects, anaemia recovery, and maternal and fetal outcomes. Random-effects meta-analysis, subgroup analysis, and GRADE certainty assessment were performed. Results: Fourteen studies met the inclusion criteria, with 13 studies (19 comparisons; 724 participants receiving daily supplementation and 948 receiving intermittent supplementation) included in the meta-analysis. Daily iron supplementation was associated with a small but statistically significant increase in haemoglobin compared with intermittent regimens (MD=0.34 g/dL; 95% CI: 0.08, 0.60; I2=87.8%). Subgroup analysis demonstrated benefits among children (MD=0.44 g/dL; 95% CI: 0.19, 0.68; I2=68.1%) and pregnant women (MD=0.79 g/dL; 95% CI: 0.04, 1.55; I2=87.8%), whereas no significant difference was observed among adolescents. Daily supplementation also resulted in higher serum ferritin concentrations (MD=4.48 ug/L; 95% CI: 0.37, 8.59). Intermittent regimens were associated with higher adherence and fewer gastrointestinal adverse effects. Conclusion: Very low-certainty evidence suggests daily supplementation may produce a small increase in haemoglobin and serum ferritin compared with intermittent regimens, although the magnitude and clinical significance of these differences remain uncertain. Intermittent regimens were associated with fewer gastrointestinal side effects and better adherence. Where adherence or treatment tolerability is a concern, intermittent regimens may represent a pragmatic alternative to daily supplementation, particularly in resource-constrained LMIC settings. Keywords: Anaemia, iron supplementation, daily, intermittent, haemoglobin, serum ferritin.

Background Growth faltering during infancy remains a major public health concern in low- and middle-income countries. We examined whether birth size, infant gut microbiome, growth and inflammatory biomarkers, and breast milk macro and micronutrients mediated the effects of an integrated intervention package on infant growth at 6 months of life. Methods This mediation analysis was nested within the Women and Infants Integrated Interventions for Growth Study (WINGS), a factorial randomized controlled trial conducted in urban low- and middle-income communities in Delhi, India. The intervention package included nutrition, health, water, sanitation and hygiene (WASH), and psychosocial support delivered during the preconception, pregnancy, and early childhood. The analysis included 296 mother-infant dyads from the group received intervention from preconception throughout pregnancy and childhood and the group received routine care. Using a counterfactual causal mediation framework, we assessed the mediating roles of birth size, infant biomarkers at 3 months; insulin-like growth factor-1 [IGF-1], C-reactive protein [CRP], and Bifidobacterium breve species, and breast milk biomarkers at three months (vitamin B12 and total protein). Outcomes included length-for-age z-score (LAZ), weight-for-age z-score (WAZ), weight-for-length z-score (WLZ) at 6 months, and changes in these anthropometric indices between 3 and 6 months. Multiple mediators were evaluated simultaneously using parametric regression models adjusted for maternal height, maternal body mass index, family possess below poverty line card, and place of birth. Results The intervention package significantly improved WAZ at 6 months (total effect 0.31; 95% CI 0.04-0.58). This effect was significantly mediated through birth size; reduction of small for gestational age (SGA) (average causal mediation effect 0.15; 95% CI 0.04-0.28), accounting for approximately 44% of the total effect. Conclusions Improved fetal growth, reflected by reduced SGA, was the principal biological pathway through which the integrated intervention package mediated infant growth at six months.