J. Nutr. [JOURNAL]
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200 papers
Diet Quality, Physical Activity, and Epigenetic Aging in the Finnish Working-Age Population.
Autio I, Saarinen A, Marttila S … +13 more , Raitoharju E, Mishra PP, Pahkala K, Männistö S, Mononen N, Kähönen M, Fogelholm M, Tammelin T, Rovio S, Keltikangas-Järvinen L, Viikari J, Raitakari O, Lehtimäki T
J Nutr · 2026 Jun · PMID 41997491 · Full text
BACKGROUND: The role of diet in epigenetic aging over long follow-up periods and the possible moderating role of physical activity have remained unclear. OBJECTIVES: We examined: 1) whether dietary habits over follow-ups...
BACKGROUND: The role of diet in epigenetic aging over long follow-up periods and the possible moderating role of physical activity have remained unclear. OBJECTIVES: We examined: 1) whether dietary habits over follow-ups of 17-32 y are associated with the level or change of epigenetic aging over a 7-y follow-up, and 2) whether physical activity moderates these associations. METHODS: The prospective population-based Young Finns Study data (n = 1039) were used. Epigenetic aging was measured in 2011 and 2018 using PhenoAge and GrimAge age deviation (AgeDev, AgeDev) and Dunedin pace of aging computed from the epigenome (DunedinPACE). Food Frequency Questionnaires were used in 2001, 2007, 2011, and 2018 to calculate 5 diet indices: Mediterranean Diet Index, Findiet Index, Alternative Healthy Eating Index (AHEI) Dietscore (additionally used in 1986), and Baltic Sea Diet Index. The applied physical activity index included, e.g., frequency and intensity of exercise. Covariates included cardiovascular and metabolic factors, other health behaviors, and socioeconomic factors. RESULTS: More favorable scores in: 1) all diet indices except Dietscore were associated with decelerated AgeDev cross-sectionally (β = -0.08 to -0.06, P = 0.003-0.022), 2) the means of all diet indices over follow-ups of 17-32 y were associated with slower epigenetic aging in all 3 epigenetic clocks (β = -0.01 to -0.23, P = 2e-5-0.042), and 3) AHEI and Findiet Index were most consistently associated with a decelerated change in AgeDev and AgeDev over a 7-y follow-up. Modest interaction effects were also observed: among those with high physical activity, epigenetic aging was approximately similar irrespective of diet healthiness, whereas among those with low physical activity, more favorable diet index scores were associated with less accelerated epigenetic aging. CONCLUSIONS: Healthier eating over the follow-up was associated with decelerated epigenetic changes across different diet indices. In terms of biological aging, having a healthy diet may be especially crucial for those with low levels of physical activity.
Ammoniated Beef Improves Metabolic Outcomes and Adipose Tissue Function in Diet-Induced Obese Male and Female Mice.
Madura BM, Menikdiwela KR, Kalupahana NS … +3 more , Yosofvand M, Moussa H, Moustaid-Moussa N
J Nutr · 2026 Jun · PMID 41997490 · Publisher ↗
BACKGROUND: Long-term consumption of fatty meats is associated with metabolic diseases, partly because of the induction of low-grade metabolic acidosis. OBJECTIVES: Our objective was to test the metabolic effects of pH-e...
BACKGROUND: Long-term consumption of fatty meats is associated with metabolic diseases, partly because of the induction of low-grade metabolic acidosis. OBJECTIVES: Our objective was to test the metabolic effects of pH-enhanced (ammoniated) beef in diet-induced obese C57BL/6J mice. We hypothesized that adipose tissue function would be improved by consuming a diet containing pH-enhanced ammoniated beef, compared with non-pH-enhanced beef, and these effects would be modulated by dietary fat content and sex. METHODS: Eighty C57BL/6J mice were randomly assigned into 4 groups (n = 20 per group; 10 males and 10 females) and fed diets differing in pH enhancement (ammoniation using ammonium hydroxide) and fat content for 12 wk [low-fat beef (LFB), ammoniated LFB, high-fat beef (HFB), and ammoniated HFB]. Body weights were measured weekly. Visceral (gonadal) white adipose tissue was collected for histology, RNA (qRT-PCR), and protein (Western blotting) analyses. A three-way analysis of variance was performed to identify main effects of fat content, ammoniation, sex, and their interactions. RESULTS: Interactions between sex and dietary fat content modulated results for weight gain [F (1, 64) = 9.601, P = 0.0029], fat pad mass [F (1, 63) = 36.48, P < 0.0001], and adipocyte area [F (1, 39) = 24.47, P < 0.0001]. Interactions between sex and ammoniation significantly affected fat pad mass [F (1, 63) = 4.341, P = 0.0413] and adipocyte area [F (1, 39) = 4.171, P = 0.0479]. Importantly, ammoniation significantly improved glucose tolerance [F (1, 59) = 16.74, P = 0.0001], irrespective of sex and dietary fat. Interactions between sex and dietary fat content modulated other results throughout the study. CONCLUSIONS: Diets containing ammoniated beef reduced gonadal fat pad mass and adipocyte size, and improved glucose tolerance in mice with diet-induced obesity, whereas interactions between dietary fat content and sex modulated results throughout.
Nationally Representative Within-Person to Between-Person Variance Ratios of Nutrient Intakes and Their Application for Estimating Usual Nutrient Intake Distributions Using 1-Day Dietary Data in Japan.
Oono F, Matsumoto M, Sugimoto M … +1 more , Asakura K
J Nutr · 2026 Jun · PMID 41997489 · Publisher ↗
BACKGROUND: Collecting multiple-day dietary data is generally recommended to estimate usual intake distributions; however, in the National Health and Nutrition Survey (NHNS) in Japan, only 1-d dietary data are available....
BACKGROUND: Collecting multiple-day dietary data is generally recommended to estimate usual intake distributions; however, in the National Health and Nutrition Survey (NHNS) in Japan, only 1-d dietary data are available. OBJECTIVES: This study aimed to calculate within-person to between-person variance ratios (WBVRs) of nutrient intake using multiple-day dietary data and to estimate usual nutrient intake distributions by applying the WBVRs to a 1-d dietary record (DR) of the National Health and Nutrition Survey (NHNS). Estimation robustness was also assessed. METHODS: The WBVRs were calculated from nonconsecutive 8-d paper-based DRs including 1375 males and 1422 females nationwide. Distributions of individual usual nutrient intake (food only; excluding supplements) were estimated from 1-d household-based DRs (paper-based) of 5053 males and 5652 females in the NHNS (2018-2019) by adapting the Best-Power method. We examined the influence of sex, age group, and sample size on WBVR values and the influence of WBVR values on estimated distributions. RESULTS: The WBVRs did not vary substantially by sex or age group but did vary by nutrient, ranging from 0.71 for potassium to 3.08 for n-3 (ω-3) fatty acids in males and from 0.79 for potassium to 3.77 for vitamin D in females. The estimated usual intake distributions were narrower than 1-d intake; for example, the 90th percentiles of protein intake were 103 g/d for usual and 114 g/d for crude 1-d, whereas those for vitamin A were 738 and 875 μg retinol activity equivalents/d in males. Considerable variation in the calculated WBVR values was observed when a small number of participants and survey days were randomly selected from the multiple-day DRs. WBVR variation affected estimated distributions. CONCLUSIONS: This study estimated nationally representative usual nutrient intake distributions in Japan. The WBVRs estimated in this study, derived from a large and nationwide dataset, may be the best presently available for use in future 1-d dietary surveys aimed at estimating usual nutrient intake distributions in Japan.
Human Milk Feeding Practices and Pubertal Timing: Insights from the Generation XXI Population-Based Birth Cohort.
da Costa MP, Severo M, Lopes C … +3 more , Anguita-Ruiz A, Araújo J, Vilela S
J Nutr · 2026 Jun · PMID 41985746 · Publisher ↗
BACKGROUND: Evidence regarding the potential influence of human milk feeding on pubertal timing remains inconsistent. OBJECTIVES: This study explored the association between human milk feeding (never, nonexclusive, or ex...
BACKGROUND: Evidence regarding the potential influence of human milk feeding on pubertal timing remains inconsistent. OBJECTIVES: This study explored the association between human milk feeding (never, nonexclusive, or exclusive) and its duration with pubertal timing, using longitudinal data from a population-based birth cohort. METHODS: The sample included 4745 children from the population-based Portuguese birth cohort Generation XXI, with data on human milk feeding, feeding duration, and Tanner stages at 10 years of age. A Puberty score was derived from Tanner stages (range: 2-10). Human milk feeding was categorized according to exclusivity and duration (never; nonexclusive; exclusive < 4 mo; and exclusive ≥ 4 mo). Multinomial logistic regression and Cox proportional hazard models were used to estimate the association between human milk feeding categories and both puberty score and age at menarche, adjusting for maternal and child characteristics. RESULTS: After adjustment for confounders, females who received human milk had lower odds ratio (OR) of a higher puberty score at 10 y of age (exclusive ≥4 mo-OR: 0.33; 95% CI: 0.24, 0.47) than those never fed human milk. Exclusive human milk feeding was associated with later age at menarche. No significant associations were found in males, except that those receiving "any but never exclusive" human milk feeding, who had lower OR of being in the highest puberty score (≥5; OR: 0.48; 95% CI: 0.25, 0.94). CONCLUSIONS: These findings suggest that human milk feeding, particularly exclusive human milk feeding for ≥4 mo, may be associated with later pubertal timing among females.
Reply to C. Thanchonnang et al.
Dai Q, Sun S, Shrubsole MJ … +1 more , Zhu X
J Nutr · 2026 Jun · PMID 41980676 · Publisher ↗
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Machine Learning and Artificial Intelligence in Nutrition Research: Analytical Methods, Applications, and Key Considerations.
Southey NL, Zhu R, Holscher HD
J Nutr · 2026 Jun · PMID 41966331 · Full text
BACKGROUND: Nutrition research is increasingly using artificial intelligence and machine learning to address analytical challenges posed by high-dimensional data and to enable personalized recommendations and health pred...
BACKGROUND: Nutrition research is increasingly using artificial intelligence and machine learning to address analytical challenges posed by high-dimensional data and to enable personalized recommendations and health predictions. OBJECTIVE: This review provides an overview of machine learning techniques and their application in nutrition research. METHODS: The article is structured according to the steps of a typical analysis pipeline. First, we outline data quality control, preprocessing, and classical statistical tests for detecting group differences, assessing covariate associations, and prescreening input features. Next, dimension reduction and visualization methods such as principal component analysis, t-distributed stochastic neighbor embedding, and uniform manifold approximation and projection are presented to simplify high-dimensional data and reveal nutrition indicators. Supervised learning approaches that support classification and outcome prediction are then reviewed, followed by unsupervised learning methods for clustering unlabeled observations. Integrative tools combining approaches such as canonical correlation analysis and supervised multiblock methods are discussed for their suitability in multiomics and multimodal studies. A comparison of commonly used supervised approaches is presented, including random forest, gradient boosting regression, penalized regression methods, least absolute shrinkage and selection operator, support vector machines, and k-nearest neighbors. Deep learning techniques, including convolutional neural networks, recurrent neural networks, long short-term memory models, natural language processing, and large language models, are highlighted for analyzing unstructured, sequential, and text-based data. To ensure the reproducibility and generalizability of findings, we discuss strategies for model validation, including cross-validation, external replication, and permutation testing. We also discuss practical considerations for implementing advanced analytical approaches in nutrition research, such as interpretability, sample size constraints, and overfitting, to guide responsible implementation. RESULTS: A range of manuscripts were reviewed to provide vignettes exemplifying the use of artificial intelligence and machine learning in nutrition research, highlighting key methodological approaches and representative applications across diverse data types. CONCLUSIONS: Collectively, this review provides a framework for understanding and thoughtfully applying machine learning approaches to nutrition research.
Clover Honey Limits Survival of Enterotoxigenic Escherichia coli in an In Vitro Gastric Model and Reduces In Vitro Fermentation pH of Small Intestine Microbes.
Traxler S, Storms D, Faso A … +4 more , Alkan Z, Bowlus CL, Lemay DG, Kable ME
J Nutr · 2026 Jun · PMID 41962904 · Publisher ↗
BACKGROUND: Honey has well-described antimicrobial properties in wound healing, but little is known about its effects within the gastrointestinal tract. OBJECTIVE: We used in vitro gastric digestion and fermentation of c...
BACKGROUND: Honey has well-described antimicrobial properties in wound healing, but little is known about its effects within the gastrointestinal tract. OBJECTIVE: We used in vitro gastric digestion and fermentation of clover honey to investigate its potential interactions with small intestine bacteria (SIB), the foodborne pathogen enterotoxigenic Escherichia coli (ETEC), and small intestine epithelial cells. METHODS: In vitro gastric digestions of sterile-filtered honey, and a simple sugar control were performed with 1 × 10 colony-forming units (CFU)/mL ETEC H10407. ETEC CFU and pH were measured, and the resulting digesta were added to batch fermentations with SIB, in the form of a mock community or ileal aspirate from 6 healthy donors. SIB fermentations were characterized by 16S rRNA amplicon sequencing and application of fermentation supernatants to mature Caco-2 cell monolayers for analysis of changes in transepithelial electrical resistance (TEER) and interleukin (IL)-8 production. Differential abundance of bacterial taxa detected by 16S rRNA sequencing between the honey and sugar conditions was tested using an Analysis of Compositions of Microbiomes with Bias Correction 2. Differences in ETEC CFU, media pH, and changes in TEER and IL-8 production between the honey and sugar conditions were tested by linear mixed effects modeling with post hoc least-squares means analysis. RESULTS: Under pH 2.5 in vitro gastric digestion conditions, ETEC CFU decreased significantly (P < 0.0001) more in the presence of clover honey (0.0035% input) than in a sugar control (0.036% input). The pH of SIB fermentation media was significantly reduced (P < 0.0001) with digested honey relative to sugar. Honey fermentation supernatant from human ileal communities challenged with ETEC elicited a greater improvement in TEER (3.68 compared with -0.80, P = 0.0479) relative to the same fermentations performed with control. CONCLUSIONS: Honey limits the survival of ETEC H10407 within an in vitro gastric environment at low pH. Clover honey may also impart decreased pH and potential improvement in in vitro epithelial cell barrier integrity in the presence of a pathogen.
Causal Forests in Practice: Lessons on Detecting Heterogeneous Treatment Effects in a Randomized Controlled Trial of a Healthy Food Subsidy Program in Canada.
Aktary ML, Lalani I, Chen Y … +9 more , Shakeri Z, McCormack GR, Dunn S, Sajobi T, O'Hara H, Leblanc P, Godley J, Doan N, Lee Olstad D
J Nutr · 2026 Jun · PMID 41962903 · Full text
BACKGROUND: There is limited guidance on the use of causal forests in moderately sized randomized controlled trials (RCTs). OBJECTIVES: This study aimed to apply and evaluate a causal forest to estimate heterogeneous tre...
BACKGROUND: There is limited guidance on the use of causal forests in moderately sized randomized controlled trials (RCTs). OBJECTIVES: This study aimed to apply and evaluate a causal forest to estimate heterogeneous treatment effects of a healthy food subsidy program using data from a moderately sized RCT. METHODS: Using data from an RCT of the British Columbia Farmers' Market Nutrition Coupon Program (FMNCP) (n = 263), a causal forest analysis examined heterogeneous treatment effects on Healthy Eating Index-2015 scores (HEI-2015; 0-100) postintervention. Treatment effect heterogeneity was assessed in the following 3 ways: 1) using the best linear prediction test to measure covariance between predicted and true treatment effects, 2) comparisons of high versus low treatment effect groups, and 3) estimating rank-weighted average treatment effects on a targeting operator characteristics (TOC) curve and estimating the area under the TOC (AUTOC). A simulation-based power analysis examined the sample size at which the causal forest could detect a 5-point difference in HEI-2015 scores between participants with high compared with low educational attainment. RESULTS: The best linear prediction test showed poor calibration and did not detect heterogeneous treatment effects (β = 0.44, P = 0.27). Heterogeneity was not detected when comparing groups with high compared with low treatment effects [-2.25, 95% confidence interval (CI): -13.53, 9.03]. The TOC curve was flat with wide CIs, and the AUTOC was not significant (-1.02; P = 0.77). Based on the simulation-based power analysis, 1050 participants were required to achieve 80% power, whereas our sample provided 40% power. CONCLUSIONS: A causal forest did not detect heterogeneous treatment effects of the FMNCP on the diet quality of adults with low incomes. Simulation results indicated that the trial was underpowered, underscoring the need for larger trials. Nevertheless, with careful application and evaluation, causal forests remain a useful tool to explore heterogeneous treatment effects in moderately sized trials when the sample size is adequate. This trial was registered at clinicaltrials.gov as NCT03952338 (https://clinicaltrials.gov/ct2/home).
Quadruple Burden of Young Child Malnutrition in the Children's Healthy Living Program, United States-Affiliated Pacific.
Novotny R, Dela Cruz R, Hammond K … +8 more , Yamanaka AB, Wilkens LR, Shallcross L, Coleman P, Aflague TF, Fleming T, Deenik J, Butel J
J Nutr · 2026 Jun · PMID 41962902 · Full text
BACKGROUND: The Pacific region has undergone nutrition transition. OBJECTIVES: This study aimed to examine the quadruple burden of malnutrition in children among jurisdictions of the United States-affiliated Pacific (USA...
BACKGROUND: The Pacific region has undergone nutrition transition. OBJECTIVES: This study aimed to examine the quadruple burden of malnutrition in children among jurisdictions of the United States-affiliated Pacific (USAP) region. METHODS: A total of 3480 children in 11 jurisdictions from the USAP region [Alaska, American Samoa, Commonwealth of the Mariana Islands (CNMI), Federated States of Micronesia (FSM), Guam, Hawai'i]. Jurisdictions were categorized according to the World Bank income categories of lower middle income (FSM), upper middle income [American Samoa, Palau, Republic of the Marshall Islands (RMI)], and high income (Hawai'i, Alaska, Guam, CNMI). The following 4 population indicators were evaluated: 1) obesity and 2) stunting using standardized measured anthropometry, 3) inadequacy, and 4) excess of dietary intake of micronutrients of concern globally (iron, zinc, and vitamin A) and in the region (vitamin D, vitamin E, calcium, niacin, folate, and sodium). Frequencies of each malnutrition form were computed. RESULTS: Across the USAP region, there were ≥10% of children with each form of malnutrition. The overall prevalence of stunting across all jurisdictions was 11.4%; varying from a low in American Samoa at 1.7% to a high in RMI at 40%. Overall prevalence of obesity was 13.6%, ranging from a low in RMI of 0% to a high in American Samoa of 25.4%. Overall prevalence of (any of the 9 studied) micronutrient inadequacies was 98.1%, driven by dietary vitamin D inadequacy (96.0%). Overall prevalence of micronutrient excess was 96.2%, driven by sodium excess (92.4%). CONCLUSIONS: There is a quadruple burden of malnutrition in the USAP. Micronutrient inadequacy and excess are the most important forms of malnutrition at 98.1% and 96.2%, respectively. Nutrition promotion should focus on healthy diets, especially in regions undergoing nutrition transition.
The Ins and Outs of Manganese: ZIP14 Facilitates Manganese Efflux from the Mouse Brain.
Zou J, Thorn TL, Wang Z … +2 more , Wang Y, Aydemir TB
J Nutr · 2026 Jun · PMID 41946442 · Publisher ↗
BACKGROUND: Manganese (Mn) is essential for brain function, but excess accumulation causes neurotoxicity. Mechanisms regulating Mn transport across the blood-brain barrier (BBB) remain incompletely defined. ZIP14 (SLC39A...
BACKGROUND: Manganese (Mn) is essential for brain function, but excess accumulation causes neurotoxicity. Mechanisms regulating Mn transport across the blood-brain barrier (BBB) remain incompletely defined. ZIP14 (SLC39A14) is implicated in systemic Mn homeostasis, but its endothelial role at the BBB is unclear. OBJECTIVES: To define the role of endothelial ZIP14 in Mn transport at the BBB and its contribution to brain and systemic Mn homeostasis. METHODS: Endothelial-specific Zip14 knockout (EKO) mice (C57BL/6, both sexes) and littermate controls were studied. Mn transport was assessed using nasal and subcutaneous Mn delivery. ZIP14 localization was examined by expansion microscopy and immunofluorescence. Directional transport was evaluated in primary mouse brain endothelial cells and ZIP14-overexpressing hCMEC/D3 cells using Transwell assays. Data were analyzed by t-test or analysis of variance (P < 0.05). RESULTS: ZIP14 localized to brain endothelial cells and colocalized with PECAM1 (r ≈ 0.70-0.77). Mn exposure increased ZIP14 expression and basolateral localization. EKO mice showed elevated blood Mn and increased brain Mn accumulation (P < 0.01). After nasal Mn delivery, EKO mice exhibited greater brain Mn retention at 1 h (P < 0.05), indicating impaired efflux, whereas subcutaneous delivery did not alter uptake. In vitro, ZIP14 mediated basolateral-to-apical Mn transport (P < 0.01). CONCLUSIONS: In mice and endothelial cells, ZIP14 mediates basolateral-to-apical Mn transport at the BBB, supporting brain-to-blood Mn movement. Endothelial Zip14 deletion disrupts Mn homeostasis, increasing circulating and brain Mn levels.
Use of Compartmental Modeling to Study Long-Term Adaptation to Increases or Decreases in Daily Vitamin A Intake in Theoretical Women.
Green MH, Green JB, Avila-Prado J … +1 more , Lopez-Teros V
J Nutr · 2026 Jun · PMID 41941963 · Publisher ↗
BACKGROUND: Whole-body vitamin A (VA) stores, an index of VA status, result from the cumulative difference between VA input (dietary intake times fractional absorption) and output (disposal). OBJECTIVES: Our objective wa...
BACKGROUND: Whole-body vitamin A (VA) stores, an index of VA status, result from the cumulative difference between VA input (dietary intake times fractional absorption) and output (disposal). OBJECTIVES: Our objective was to apply compartmental modeling to determine how long-term changes in VA intake influence VA storage and disposal in theoretical subjects. METHODS: We generated 7 theoretical women with VA total body stores (TBS) of 225-1140 μmol and VA intakes [1.92-2.95 μmol/d (549-844 μg RAE/d)] that maintained a VA steady state [steady state (SS); i.e., VA balance]. Using Simulation, Analysis and Modeling software, we either adjusted VA intakes to 0.25, 0.5, 2, and 3 times initial SS intakes or added a daily supplement (3.5 μmol/d); then, we simulated TBS over 3 decades, with plasma VA homeostatically controlled, to determine whether and if so, when, a new VA SS was attained and by what amount stores changed. RESULTS: After >5 y, the specified decreases or increases in VA intake led to a new SS TBS plateau, with mean fractional changes reaching 0.14 (at 0.25× initial SS intake), 0.43 (0.5×), 2.1 (2×), and 3.2 (3×). Similarly, adding 3.5 μmol/d above SS intake led to a new SS TBS after >5 y, with TBS increasing 426-1666 μmol; the greatest gain was in subjects with higher initial stores. CONCLUSIONS: For these subjects, the VA intake required to maintain VA balance increased with TBS. Results have implications for dietary VA recommendations: assuming that 1) only a small part of total VA disposal is related to essential VA functions and 2) functional needs do not change with TBS, one wonders whether one's VA needs should be viewed as the intake needed to support functional requirements, with higher recommendations providing a buffer that includes nonfunctional VA disposal and a moderate store.
Do the Effects of Early Time-Restricted Eating Vary by Cardiometabolic Phenotype, Age, Sex, or Race? A Secondary Analysis of a Randomized Controlled Trial.
Rehman Z, Altonji OM, Steger FL … +4 more , Jamshed H, Richman JS, Warriner AH, Peterson CM
J Nutr · 2026 Jun · PMID 41941962 · Full text
BACKGROUND: Time-restricted eating (TRE), the most popular form of intermittent fasting, induces weight loss and may improve cardiometabolic health, but less is known about the effects in certain populations. OBJECTIVES:...
BACKGROUND: Time-restricted eating (TRE), the most popular form of intermittent fasting, induces weight loss and may improve cardiometabolic health, but less is known about the effects in certain populations. OBJECTIVES: We performed a secondary analysis to determine the effectiveness of early TRE (eTRE) in subgroups with elevated cardiometabolic risk factors and to determine whether the effects vary by age, sex, or race. METHODS: Adults aged 25-75 y with obesity (BMI: 30-60 kg/m) undergoing weight-loss treatment were randomized to eat in an 8-h period from 07:00 to 15:00 (eTRE) or over a ≥12-h period (control) for 14 wk. We performed subgroup analyses to: 1) assess the effects of eTRE in individuals with hypertension, prediabetes, insulin resistance, hypercholesterolemia, and severe obesity, and 2) determine whether the effects differ by age, sex, or race. RESULTS: eTRE lowered diastolic blood pressure by 9 ± 4 mm Hg (P = 0.047) in adults with systolic blood pressure ≥130 mm Hg and by 4 ± 2 mm Hg (P = 0.04) in adults with hypertension relative to the control group. In prediabetic adults, eTRE lowered hemoglobin A1c by 0.3% ± 0.1% (P = 0.04), whereas in adults with hypercholesterolemia, it reduced HOMA-IR by 2.96 ± 1.46 (P = 0.04). Interestingly, in adults with severe obesity, eTRE increased total and low-density lipoprotein cholesterol by 21 ± 9 and 17 ± 7 mg/dL, respectively (P = 0.03). There were no differences by sex or age. eTRE improved blood pressure and glycemic endpoints more in Black participants than White participants, although the number of Black participants was small (n = 13). CONCLUSIONS: The results of this exploratory analysis suggest eTRE may be a promising intervention to treat hypertension and prediabetes. Any differences by sex and age are likely minor. eTRE's effects on cholesterol in adults with severe obesity and potential racial differences merit further investigation. This trial was registered at clinicaltrials.gov as NCT03459703.
Beyond the 24-Hour Recall: Aligning Dietary Diversity Metrics with Nutrient Physiology.
Zerfu T, Tareke AA, Chekol DA
J Nutr · 2026 Jun · PMID 41941961 · Publisher ↗
Dietary diversity indicators, such as the Minimum Dietary Diversity for Women (MDD-W), are widely used to assess diet quality in low- and middle-income countries. These metrics typically rely on 24-h recall data to appro...
Dietary diversity indicators, such as the Minimum Dietary Diversity for Women (MDD-W), are widely used to assess diet quality in low- and middle-income countries. These metrics typically rely on 24-h recall data to approximate micronutrient adequacy. Although repeated 24-h recalls can estimate usual intake distributions at the population level, they remain anchored in discrete daily intake measures that may not fully capture nutrients with episodic consumption patterns or longer physiological retention. Although the MDD-W is intended for population-level assessment, systematic misclassification at the individual level may aggregate into population-level bias. This limitation arises from insufficient alignment with nutrient biology, including variation in physiological retention, turnover, and depletion kinetics. Nutrients such as vitamin A and vitamin B-12 can be stored over extended periods, whereas others require more frequent intake. We propose a tiered recall framework that aligns dietary assessment periods with nutrient physiology, improving interpretive precision while maintaining feasibility for large-scale surveys.
Greek Yogurt Compared with Whey Protein Supplementation in Adolescent Athletes Throughout a Competitive Season.
Bell M, Narciso PH, Miskolczi E … +5 more , Retsidou MI, Roy BD, Josse AR, Falk B, Klentrou P
J Nutr · 2026 Jun · PMID 41941960 · Full text
BACKGROUND: Protein intake during adolescence may influence bone development and immune status, yet the comparative effects of wholefood protein sources compared with protein isolates in adolescent athletes remain unclea...
BACKGROUND: Protein intake during adolescence may influence bone development and immune status, yet the comparative effects of wholefood protein sources compared with protein isolates in adolescent athletes remain unclear. OBJECTIVES: To compare the effects of Greek yogurt (GY) and whey protein (WP) supplementation on bone and inflammation markers in adolescent athletes throughout a competitive season. METHODS: Athletes completed an initial control period on their habitual diets (weeks 0‒8), followed by randomization to GY (n = 24; 15.8 ± 1.1 y; 11 females) or WP (n = 23; 16.0 ± 1.4 y; 10 females) for a 16-wk intervention (weeks 8‒24). GY consumed 2 servings per day of 175 g GY (17 g protein); WP received an isonitrogenous WP supplement. Blood samples and body composition assessments were obtained at weeks 0, 8, 16, and 24. RESULTS: Procollagen type I N-terminal propeptide, insulin-like growth factor-1, and receptor activator of nuclear factor κB ligand remained stable. Osteocalcin and osteoprotegerin showed sex-specific between-group differences: osteocalcin declined throughout weeks 0‒24 in GY males, whereas osteoprotegerin declined during weeks 0‒16 in GY females and was elevated at the end of the control period in WP females. C-terminal telopeptide of type I collagen and sclerostin showed intervention group-dependent, but not sex-dependent, differences. C-terminal telopeptide of type I collagen increased transiently from week 8 to week 16 and returned to baseline by week 24 only in GY. Sclerostin concentrations fluctuated, and at 24 wk, were not different from baseline in GY but were higher than baseline in WP. At week 16, interleukin (IL)-1β increased in WP, and IL-6 decreased in GY. IL-10 and tumor necrosis factor α increased during the control period and decreased with WP only in females. CONCLUSIONS: Increased protein intake, independent of source, was associated with modest, often sex-specific fluctuations in bone and inflammatory markers in adolescent athletes, potentially influenced by growth and training-related factors across the competitive season. This trial was registered at clinicaltrials.gov as NCT05922462.
Characterization of Blood DNA Methylation Changes in a Murine Model of Prediabetes Induced by Fructose and Its Reversal.
Mencucci MV, Lacunza E, Abba MC … +8 more , Ahrtz L, Dumrauf B, Villagarcía HG, Castro MC, Román CL, Flores LE, Francini F, Maiztegui B
J Nutr · 2026 Jun · PMID 41936848 · Publisher ↗
BACKGROUND: DNA methylation is implicated in type 2 diabetes (T2D); however, its role in prediabetes remains poorly understood. OBJECTIVES: This study identified blood DNA methylation changes in a rodent model of prediab...
BACKGROUND: DNA methylation is implicated in type 2 diabetes (T2D); however, its role in prediabetes remains poorly understood. OBJECTIVES: This study identified blood DNA methylation changes in a rodent model of prediabetes induced by fructose and tracked its evolution during prediabetes reversal after removing the fructose supplement. METHODS: Adult male Sprague-Dawley rats were divided into 3 groups (n = 8/group): control, prediabetic (PD), and reversal groups. Animals were fed a standard nonpurified chow. The control group consumed water, while PD group received 10% fructose solution for 70 d. The reversal group received fructose for 21 d to induce prediabetes, followed by water. Glucose tolerance test was performed in a subgroup of rats. Whole-genome bisulfite sequencing was conducted on whole blood samples collected at day 70. DNA methylation data were analyzed using Rfastp and Bismark. Differential methylation analysis was performed using methylKit. Genomation package and STRING website were used for annotation and functional analysis. RESULTS: PD and reversal (21 d) animals showed higher triglyceride and insulin resistance index and impaired glucose tolerance (P < 0.05 compared with the control group), confirming the establishment of prediabetes. On day 70, 4339 differentially methylated (DM) cytosine-guanine dinucleotide (CpG) sites were identified across PD compared with control, reversal compared with PD, and reversal compared with control, associated with 842 genes. Hypermethylation predominated in PD compared with control (54%), reversal compared with control (69%), and reversal compared with PD (65%). Most changes occurred in intergenic regions and outside CpG islands. Oxidative phosphorylation was the main affected pathway in prediabetes and persisted in reversal, accompanied by altered expression of mitochondrial genes (mt-Nd2 and mt-Cytb). Under more stringent criteria, 41 DM CpG sites associated with 17 genes were identified, with most alterations (95%) observed in reversal condition, particularly in Uxs1 and Emb. CONCLUSIONS: These findings identify novel DNA methylation changes associated with fructose-induced prediabetes and its reversal, providing insights into early epigenetic alterations involved in T2D pathogenesis.
Maternal Nutrition and Hypothalamic Programming of Offspring Metabolic Health.
Mall S, Oladun B, Kim MH
J Nutr · 2026 Jun · PMID 41933839 · Full text
The hypothalamus plays a central role in regulating metabolism by integrating hormonal and nutrient-derived signals to maintain energy homeostasis across the life span. Maternal nutritional status during critical windows...
The hypothalamus plays a central role in regulating metabolism by integrating hormonal and nutrient-derived signals to maintain energy homeostasis across the life span. Maternal nutritional status during critical windows of development is a major environmental factor that can permanently alter this regulation. Both maternal overnutrition and undernutrition have been shown to disturb circulating leptin, insulin, and glucagon-like peptide-1 (GLP-1), and to disrupt the normal development of hypothalamic nuclei implicated in energy balance. Experimental and clinical studies indicate that these insults miswire proopiomelanocortin (POMC) and neuropeptide Y/agouti-related peptide (NPY/AgRP) pathways, alter leptin and insulin receptor signaling, trigger neuroinflammation, glial and vascular changes, and are accompanied by enduring epigenetic alterations, including DNA methylation and chromatin remodeling at genes such as Pomc, Npy, Mc4r, Lepr, and Insr. Together, these adaptations establish new set points for appetite, energy expenditure, and glucose regulation, thereby increasing the lifelong risk of obesity and type 2 diabetes in the offspring. In this narrative review, we synthesize evidence from animal models and human studies linking maternal nutrition to hypothalamic programming via leptin, insulin, and GLP-1. We also highlight major gaps, including limited data on GLP-1 in maternal undernutrition, the specific role of individual micronutrients, and the timing and reversibility of hypothalamic programming, to inform future mechanistic, translational, and preventive research.
Free Sugar Intake and Dementia Risk: A Swedish Cohort Study on Dietary Sources and Dementia Subtypes.
Zhang N, Andresen J, Janzi S … +7 more , Glans I, Samuelsson J, Nägga K, Borné Y, Palmqvist S, Hansson O, Sonestedt E
J Nutr · 2026 Jun · PMID 41933838 · Full text
BACKGROUND: Dementia is a growing public health concern, and although diet is a modifiable potential risk factor, the role of free sugar intake remains unclear. Excess sugar has been linked to metabolic and cardiovascula...
BACKGROUND: Dementia is a growing public health concern, and although diet is a modifiable potential risk factor, the role of free sugar intake remains unclear. Excess sugar has been linked to metabolic and cardiovascular dysfunction, both associated with cognitive decline, but evidence regarding specific sugar sources is limited. OBJECTIVES: This study aimed to investigate the associations between free sugar intake, its dietary sources, and the risk of all-cause dementia, Alzheimer's disease, and vascular dementia, and to assess potential modification by apolipoprotein E (APOE) ε4 status. METHODS: We included 27,786 participants without dementia at baseline (mean age: 58 y; 61% females) from the Malmö Diet and Cancer Study, a population-based prospective cohort. Dietary intake was assessed using a validated diet history method. Dementia diagnoses were obtained from national registers and validated by memory clinic physicians. During a median follow-up of 25 y, 3224 participants (11.6%) were diagnosed with dementia. RESULTS: Free sugar intake was not significantly associated with all-cause dementia or Alzheimer's disease. However, a U-shaped association was observed for vascular dementia, with moderate intake (10%-12.5% of energy) associated with lower risk [hazard ratio (HR): 0.70; 95% confidence interval (CI): 0.52, 0.95]. Sugar-sweetened beverage intake showed no association with dementia risk. High chocolate intake was associated with lower risks of all-cause [HR for quintile 5 (Q5) compared with Q1: 0.81; 95% CI: 0.72, 0.91] and vascular dementia (HR for Q5 compared with Q1: 0.68; 95% CI: 0.50, 0.92), whereas high jam/marmalade intake was linked to a lower risk of all-cause dementia (HR: 0.86; 95% CI: 0.77, 0.97 for >10 servings per week compared with <0.5 servings per week). No significant interactions with APOE ε4 status were observed. CONCLUSIONS: Free sugar intake was not associated with overall dementia risk, but moderate intake may reduce the risk of vascular dementia. These findings suggest that future dietary guidelines for cognitive health should consider not only sugar quantity but also its food source.
Pilot Randomized Controlled Trial of Krill Oil Supplementation for Chronic Musculoskeletal Pain in Older Adults.
Tamargo JA, Carvajal E, Simic K … +3 more , Przkora R, Anton SD, Cruz-Almeida Y
J Nutr · 2026 Jun · PMID 41933837 · Full text
BACKGROUND: Chronic musculoskeletal (MSK) pain is highly prevalent in older adults and the leading cause of disability. Long-chain omega-3 (ω-3) polyunsaturated fatty acids have anti-inflammatory and analgesic properties...
BACKGROUND: Chronic musculoskeletal (MSK) pain is highly prevalent in older adults and the leading cause of disability. Long-chain omega-3 (ω-3) polyunsaturated fatty acids have anti-inflammatory and analgesic properties, yet intake and circulating levels are low in older US adults. Krill oil, a phospholipid-bound source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that also contains astaxanthin and choline, may represent a feasible nutrition-based intervention for chronic MSK pain. OBJECTIVES: To evaluate the feasibility and acceptability of krill oil supplementation in older adults with chronic MSK pain and to characterize changes in ω-3 status and exploratory pain outcomes. METHODS: A 12-wk, randomized, double-blind, placebo-controlled pilot trial in 40 community-dwelling adults aged ≥60 y with moderate chronic MSK pain. Participants were stratified by sex and randomly assigned 1:1 to krill oil (4 g/d; 1288 mg EPA+DHA) or placebo. Primary outcomes were feasibility metrics (recruitment, retention, adherence, and acceptability). Secondary outcomes included biomarkers of ω-3 status and inflammation. Exploratory outcomes included pain intensity, pain interference, pain distribution, and global improvement. RESULTS: Recruitment targets were met within 8 mo; retention was 95%, adherence exceeded prespecified thresholds (>70%) in both groups, and overall acceptability was rated 7.7 ± 2.3 of 10. Krill oil supplementation increased the ω-3 index from 4.3% to 7.4%, approaching levels consistent with lower cardiometabolic risk (≥8%), whereas the placebo group showed no meaningful change. Preliminary analyses showed trends favoring krill oil for reduced pain intensity (ΔKO - ΔP = ‒1.05), fewer pain sites (rate ratio: 0.59; 95% confidence interval: 0.41, 0.84), and global improvement (adjusted odds ratio: 4.35; 95% confidence interval: 0.97, 19.55). No serious adverse events occurred. CONCLUSIONS: Krill oil supplementation was feasible and acceptable among older US adults with chronic MSK pain. These findings support a fully powered randomized controlled trial to evaluate krill oil as a nutritional strategy for pain management in aging populations. This trial was registered at clinicaltrials.gov as NCT06580912.
Adding Small Quantity Lipid-Based Nutrient Supplements to an Enhanced Homestead Food Production Program Improves Child Hemoglobin, Iron and Vitamin A Status in Rural Burkina Faso: A Cluster-Randomized Controlled Trial.
Bliznashka L, Becquey E, Ruel MT … +3 more , Pedehombga A, Nordhagen S, Olney DK
J Nutr · 2026 Jun · PMID 41932365 · Publisher ↗
BACKGROUND: Enhanced homestead food production programs (EHFP) including nutrition behavior change communication and women's empowerment activities have limited impacts on child nutrition. This may be due to short progra...
BACKGROUND: Enhanced homestead food production programs (EHFP) including nutrition behavior change communication and women's empowerment activities have limited impacts on child nutrition. This may be due to short program duration or the absence of interventions to improve water, sanitation, and hygiene (WASH), as well as access to nutritious foods. OBJECTIVES: We assessed impacts on child anemia, micronutrient status, and anthropometry of prior village exposure to an EHFP, and of adding WASH alone or WASH with daily small quantity-lipid based nutrient supplements (SQ-LNS). METHODS: This 2-y longitudinal cluster-randomized controlled trial (2014-2016) included 60 villages in Burkina Faso randomized to 4 groups (15 per group): 1) EHFP-2014; 2) EHFP-2014+WASH; 3) EHFP-2010+WASH; and 4) EHFP-2010+WASH+SQ-LNS. Groups 3 and 4 had previously received EHFP (2010-2012). We assessed impacts on child anemia and micronutrient status (n = 1704; 3-12.9 mo at baseline) and anthropometry (n = 2308; 0-12.9 mo at baseline) using difference-in-difference (DID) specifications. We controlled for covariates, adjusted for clustering, and assessed interactive effects by child age at baseline. The trial was registered with clinicaltrials.gov (NCT02236468). RESULTS: We found no impact of prior exposure to EHFP (groups 2 compared with 3) on the outcomes examined. Adding WASH (groups 1 compared with 2) reduced anemia [hemoglobin (Hb) <11 g/dL] (DID = 9.43 pp, P < 0.01) and led to a decline in weight-for-age Z-score (DID -0.11 ± 0.04, P = 0.01). Adding SQ-LNS (groups 3 compared with 4) increased Hb (DID = 0.26 ± 0.13 g/dL, P < 0.05), plasma ferritin (DID = 7.61 ± 2.69 μg/L, P < 0.01), and retinol binding protein (DID = 0.07 ± 0.02 μmol/L, P < 0.01) concentrations. Effects were larger in children <6 mo at baseline, where providing SQ-LNS (>6 mo) positively impacted Hb, plasma ferritin, height-for-age Z-score, weight-for-age Z-score, and underweight. CONCLUSIONS: Using EHFP to deliver WASH and SQ-LNS reduced child anemia and improved micronutrient status. Anthropometric improvements were found in children who joined the program before 6 mo of age and were exposed for the whole complementary feeding period.
Whole-Body Protein Balance during Arctic Military Training Is Unaffected by Dietary Essential Amino Acid or Energy Density.
Howard EE, Teien HK, Hatch-McChesney A … +12 more , Robillard JT, Murphy NE, Carrigan CT, Tansø R, Varanoske AN, Martini S, Stenberg PH, Karl JP, Gwin JA, Margolis LM, Ferrando AA, Pasiakos SM
J Nutr · 2026 Jun · PMID 41932364 · Publisher ↗
BACKGROUND: Energy deficit severity and dietary protein intake are primary determinants of negative whole-body protein balance during strenuous military training. OBJECTIVES: This work aimed to determine whether attenuat...
BACKGROUND: Energy deficit severity and dietary protein intake are primary determinants of negative whole-body protein balance during strenuous military training. OBJECTIVES: This work aimed to determine whether attenuating energy deficits by providing low-volume energy-dense foods that may promote energy intake or consuming essential amino acid (EAA)-dense foods to facilitate an anabolic state preserves whole-body protein balance during strenuous cold-weather military training. METHODS: This randomized, controlled trial enrolled Norwegian soldiers participating in an 8-d Arctic training exercise. Participants were randomly assigned to 3 groups that received 3 standard rations plus 4 supplemental bars that were EAA-dense (EAA-Dense; n = 27), energy-dense (EN-Dense; n = 22), or high-carbohydrate controls (CON; n = 19) each day. Energy expenditure (doubly labeled water) and dietary intake were measured daily. Whole-body protein flux, synthesis (PS), breakdown (PB), and net balance (NB = PS - PB) were measured overnight before (PRE) and after the training (POST) using N-alanine. RESULTS: Energy expenditure (5341 ± 674 kcal/d), energy intake (4045 ± 738 kcal/d), and energy deficits (-1257 ± 599 kcal/d; 24 ± 11%) were not different (P > 0.05) between groups. Protein intake was >1.6 g/kg/d in all treatments. PRE to POST increases (P < 0.05) in protein flux (1.21 ± 0.23 vs. 1.34 ± 0.36 g N/kg/d), PS (3.46 ± 2.06 vs. 5.43 ± 2.86 g/kg/d), PB (6.26 ± 1.35 vs. 6.95 ± 2.12 g/kg/d), and NB (-2.80 ± 1.61 vs. -1.51 ± 1.60 g/kg/d) occurred independent of treatment. CONCLUSIONS: Soldiers achieved high protein intakes and modest energy deficits when provided 3 standard rations and 4 supplemental bars daily during cold-weather training. Supplemental bar energy or EAA density did not affect whole-body protein balance under these conditions, suggesting protein utilization remains independent of the macronutrient formulation of supplemental bars during military training scenarios with high protein intakes and moderate energy deficits. This trial was registered at clinicaltrials.gov as NCT05210205.
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