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J. Nutr. [JOURNAL]

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Prior Pregnancies Deplete Maternal Folate Status and Increase Risks of Neural Tube Defects in Addis Ababa, Ethiopia.

Molla HT, Joy EJ, Gashu D … +4 more , Bikila D, Garomsa TL, Stoecker B, Sandalinas F

J Nutr · 2026 Jun · PMID 42269931 · Publisher ↗

BACKGROUND: Folate is essential for fetal neural development, and maternal deficiency during early pregnancy increases risk of neural tube defects (NTDs). Ethiopia has among the highest NTD rates globally, yet data on fo... BACKGROUND: Folate is essential for fetal neural development, and maternal deficiency during early pregnancy increases risk of neural tube defects (NTDs). Ethiopia has among the highest NTD rates globally, yet data on folate status determinants among pregnant women are scarce. OBJECTIVES: This study aimed to identify the role of dietary and demographic factors in determining maternal folate status and to interpret these findings in the context of NTD prevention. METHODS: We conducted a cross-sectional study among pregnant women (n = 404) attending their first antenatal care visit at 3 public health centers in Addis Ababa, Ethiopia. Serum folate was measured using electrochemiluminescence immunoassay. Increased risk of NTD was defined by serum folate <24.3 nmol/L. Sociodemographic, dietary, and clinical data were collected by questionnaire. We examined factors associated with serum folate concentrations using linear regression models. RESULTS: A total of 61% of women had concentrations below levels estimated to be protective against NTDs. Supplement use was rare (<3%). After adjustment for wealth, residency, dietary intake, body mass index, inflammation and trimester, serum folate was lower among women with 2 (β = -2.2 nmol/L; P = 0.04), 3 (β = -6.2 nmol/L; P < 0.001), 4 (β = -11.2 nmol/L; P < 0.001), and 5 (β = -13.7 nmol/L; P < 0.001) prior pregnancies compared with primigravidae. Serum folate was higher in the second than the first trimester (β = 3.90 nmol/L; P = 0.003). CONCLUSIONS: Higher gravidity is strongly associated with lower folate status, consistent with maternal depletion. Multiparous women may be at increased risk of NTD-affected pregnancies. Interventions to improve folate status before conception, including supplementation, food fortification, and strategies to lengthen interpregnancy intervals, should be prioritized in Ethiopia.

Letter to the Editor: Rethinking TRPM7 as a Target in Colorectal Polyp Prevention.

Thanchonnang C, Rattanapitoon SK, La N … +1 more , Rattanapitoon NK

J Nutr · 2026 Jun · PMID 42264598 · Publisher ↗

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Association of Fish Consumption with the Omega-3 Index and Vitamin D Status among Adolescent Females in the Southwest Coastal Zone of Bangladesh.

Ara G, de Roos B, Little DC … +6 more , Mamun AA, Hassan R, Grieve E, Ali SD, Ahmed T, Roos N

J Nutr · 2026 Jun · PMID 42264597 · Full text

BACKGROUND: Omega-3 fatty acids (O3FA) and vitamin D are essential for growth, bone accrual, and neurodevelopment during adolescence and may affect future maternal and birth outcomes. Fish is a major dietary source of O3... BACKGROUND: Omega-3 fatty acids (O3FA) and vitamin D are essential for growth, bone accrual, and neurodevelopment during adolescence and may affect future maternal and birth outcomes. Fish is a major dietary source of O3FA and vitamin D. However, evidence linking fish intake with O3FA and vitamin D status among adolescent females in Bangladesh remains limited. OBJECTIVES: This study aimed to investigate the associations of fish consumption with the Omega-3 Index (O3I) and serum 25-hydroxyvitamin D [25(OH)D] among adolescent females living across salinity gradients in southwest coastal Bangladesh. METHODS: Two repeated cross-sectional surveys were conducted among 295 females during dry (August-September 2017) and wet (April-May 2018) seasons. Fish intake over the past week was assessed. Whole-blood eicosapentaenoic and docosahexaenoic acids were used to derive O3I, and serum 25(OH)D was measured. Associations between tertiles of fish intake and biomarker outcomes were examined using multivariable linear and logistic regression. RESULTS: Mean O3I was 4.3% during dry season and 4.9% in wet season. Vitamin D insufficiency (<50 nmol/L) affected 25% of females during dry season and 39% in wet season. Compared with T1, adolescents in T3 of total fish intake had higher O3I (dry: β = 0.57; wet: β = 1.26) and greater odds of achieving O3I ≥4% [dry: adjusted odds ratio (AOR) = 2.12; wet: AOR = 7.98]. Tilapia consumption showed the strongest associations: females in T3 had higher O3I (dry: β = 1.08; wet: β = 1.63) and higher odds of O3I ≥4% (dry: AOR = 3.65; wet: AOR = 23.85). During wet season, higher total fish and tilapia intake were associated with higher 25(OH)D (β = 5.06 and 7.96) and lower odds of insufficiency for tilapia consumers (AOR = 0.25). CONCLUSIONS: Higher fish consumption, particularly tilapia, was associated with improved O3I and vitamin D status among adolescent females in coastal Bangladesh, with the strongest effects observed during wet season. Ensuring year-round access to diverse fish species, including saline-raised tilapia, may help address ω-3 and vitamin D insufficiency in this nutritionally vulnerable population.

Interpersonal Communication and Maternal Behavioral Practice: A Case Study of Explanatory Causal Machine Learning in Nepal.

Kelcey B, Cunningham K, Frongillo EA

J Nutr · 2026 Jun · PMID 42264183 · Publisher ↗

BACKGROUND: There is increasing interest not only in whether a program produced impacts but also the mechanisms through which the impacts were produced. Studies of nutrition interventions have frequently highlighted the... BACKGROUND: There is increasing interest not only in whether a program produced impacts but also the mechanisms through which the impacts were produced. Studies of nutrition interventions have frequently highlighted the role of nutrition education interventions, but few studies have investigated the paths through which those interventions achieve impact. OBJECTIVES: We assessed the total effect of maternal exposure to interpersonal communication with a frontline worker on behavioral practice and the degree to which that effect operated through 2 key pathways: improved awareness and knowledge. We also conducted a comparative case study examining the differences between machine learning (ML) and structural equation model (SEM) approaches. METHODS: We used data from the endline cross-sectional survey of the quasi-experimental Suaahara study of 2040 mothers with a child <2 y of age. We estimated the total effect of maternal exposure to interpersonal communication with a frontline worker on her nutrition-related practices and the indirect effects through improvements in awareness and knowledge using ML and conventional SEMs. Models were adjusted for household, child, and maternal factors as well as household location. RESULTS: Maternal exposure to interpersonal communication with a frontline worker translated into practicing more of the ideal, promoted nutrition-related practices. Both methods suggested a similar total effect-ML: 0.58 (95% CI: 0.37, 0.78) and SEM: 0.60 (95% CI: 0.49, 0.72). ML models, however, attributed a much larger proportion of that total effect to indirect effects operating through awareness and knowledge (ML: 0.24; 95% CI: 0.15, 0.33; SEMs: 0.16; 95% CI: 0.09, 0.21). CONCLUSIONS: Exposure to interpersonal communication is important for improving nutrition-related practices, in part due to increasing one's awareness and knowledge. The disparities in results between ML and SEMs suggested that the production of effects is a more complex, nonlinear and interactive function of awareness, knowledge, treatment and covariates than what is captured by simple linear models.

Inverse Association between the ω-3 Index and Neutrophil-Lymphocyte Ratio: Pooled Results from Four Supplementation Trials.

McBurney MI, Tintle NL, Westra J … +6 more , Plourde M, Flock M, Mutch DM, Stephensen CB, Newman JW, Harris WS

J Nutr · 2026 Jun · PMID 42263943 · Publisher ↗

BACKGROUND: The Omega-3 Index [O3I, erythrocyte eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) content] has been inversely correlated with neutrophil-lymphocyte ratio (NLR) and red blood cell distribution wi... BACKGROUND: The Omega-3 Index [O3I, erythrocyte eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) content] has been inversely correlated with neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in observational studies. OBJECTIVES: We evaluated the effects of omega-3 interventions (EPA + DHA) on O3I, NLR, and RDW values in healthy adults and tested the hypothesis that changes in O3I (ΔO3I) modified NLR and, separately, RDW. METHODS: We performed a de novo, individual-level analysis of baseline (b) and post (p) intervention O3I, NLR, and RDW values from 3 randomized, placebo-controlled trials and 1 ω-3 supplementation trial, followed by an equivalent duration washout (combined n =436). Primary outcome effect estimates were obtained using linear mixed effects models with a statistical significance threshold set at 0.05. RESULTS: EPA + DHA supplementation (mean dose = 1160 mg/d) increased O3I (ΔO3I = 3.28%, P < 0.001, n = 253), whereas O3I decreased (ΔO3I = -0.62, P < 0.001, n = 183) in the CONTROL group. NLR decreased in individuals treated with EPA + DHA (ΔNLR = -0.15, P < 0.001) compared with CONTROL (-0.02, 95% confidence interval: -0.10, 0.06), a statistically significant difference (P < 0.05). In contrast, EPA + DHA supplementation was not associated with changes in RDW (P = 0.62), whereas RDW increased by ∼1% in CONTROL individuals (ΔRDW = 0.09, P < 0.01). ΔNLR values were inversely correlated with ΔO3I in unadjusted (model 1, r = -0.08, P < 0.05) and models that adjusted for baseline NLR, age, and sex (model 2, r = -0.07, P < 0.05). There was no evidence of an association between ΔO3I and ΔRDW (model 2, r = 0.003, P = 0.37). CONCLUSIONS: In healthy adults, EPA + DHA increased O3I and reduced NLR. ΔO3I was inversely correlated with ΔNLR but not with ΔRDW. Further clinical trials are needed to determine if ω-3 supplementation causes biologically relevant changes in NLR, and possibly RDW, to affect clinical outcomes in individuals with elevated NLR and RDW, and their associated increased risk of morbidity and mortality.

Dietary Patterns and Risk of Cardiovascular Disease and All-Cause Mortality in Adults with Untreated or Uncontrolled Hypertension.

Chen SH, Liu B, Cheng HM … +2 more , Liang L, Hu FB

J Nutr · 2026 Jun · PMID 42263942 · Publisher ↗

BACKGROUND: Although higher dietary quality scores for several established dietary indices have been consistently associated with lower risk of cardiovascular disease (CVD) and total mortality in the general population,... BACKGROUND: Although higher dietary quality scores for several established dietary indices have been consistently associated with lower risk of cardiovascular disease (CVD) and total mortality in the general population, limited evidence exists regarding their potential benefits among individuals with established hypertension. OBJECTIVES: The aims of this study were to examine the associations of dietary quality scores of multiple established dietary patterns with risks of incident CVD and all-cause death among adults with hypertension and to evaluate whether different dietary constructs exhibit heterogeneous prognostic relevance in this high-risk population. METHODS: We analyzed 83,248 UK Biobank participants with hypertension and no prior CVD at baseline. Diet quality was assessed using repeated 24-h recall questionnaires and scored according to 5 dietary indices: the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index-2010 (AHEI-2010), the Alternate Mediterranean Diet (AMED) score, the healthful Plant-Based Diet Index (hPDI), and the Empirical Dietary Inflammatory Pattern (EDIP). Each score was categorized into quintiles for analysis. The primary outcomes include a composite of nonfatal CVD events and cardiovascular death and all-cause mortality. Subgroup and interaction analyses were conducted across predefined clinical strata. RESULTS: During 1,230,983 person-years of follow-up, 4889 primary CVD events were documented. After adjustment for demographic and cardiovascular disease risk factors, compared with the lowest quintile, the highest quintile of the DASH score was associated with significantly lower CVD risk [hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.77, 0.93], as was the reversed EDIP score (HR: 0.89; 95% CI: 0.81, 0.97). The AHEI-2010 score also showed a significant association (HR: 0.91; 95% CI: 0.83, 1.00), whereas the AMED (HR: 1.02; 95% CI: 0.93, 1.11) and hPDI (HR: 0.95; 95% CI: 0.86, 1.03) scores were not significantly associated with CVD risk. All 5 dietary scores were inversely associated with all-cause mortality (Q5 compared with Q1 HRs: 0.78-0.85; all P < 0.01), with the strongest association again observed for the DASH score. Food group-based analysis showed that higher intake of vegetables, whole grains, nuts and legumes, fruits, and dairy was significantly associated with lower CVD or mortality risk, whereas greater consumption of sugar-sweetened beverages and meats was significantly associated with higher risk (all P < 0.05). CONCLUSIONS: Among adults with hypertension, higher dietary quality scores of healthy dietary patterns, especially the DASH diet and reversed EDIP, were associated with lower risks of CVD and all-cause mortality.

Protective Effect of Apiaceous Vegetables against Total Western Diet- and Dextran Sulfate Sodium-Induced Colitis in Mice.

Lee HS, Ibarra LE, Zuo B … +7 more , Zhao J, Fox R, Read QD, Gurung M, Yeruva L, Chen C, Trudo SP

J Nutr · 2026 Jun · PMID 42259440 · Publisher ↗

BACKGROUND: Western-style dietary patterns are associated with colitis and colon cancer. Existing data indicate that intake of apiaceous (API) vegetables (e.g., celery, parsnip) may prevent inflammation-associated diseas... BACKGROUND: Western-style dietary patterns are associated with colitis and colon cancer. Existing data indicate that intake of apiaceous (API) vegetables (e.g., celery, parsnip) may prevent inflammation-associated diseases. OBJECTIVES: We investigated in mice the effect of API supplementation to the total Western diet (TWD) against dextran sulfate sodium-induced colitis. METHODS: Male C57BL/6J mice (8-wk-old; 15 per group) were fed TWD supplemented with 21% or 42% fresh API (wt/wt) and given 2% dextran sulfate sodium to induce colitis. Diet intake, body weight, and disease activity index were monitored. Serum was collected for cytokine/chemokine analysis and colonic tissues for histology and Western blot. Fecal samples were analyzed by 16S ribosomal ribonucleic acid gene sequencing and targeted/untargeted metabolomics. Phenotypic data were analyzed by analysis of variance with Tukey's test. Microbiome data were centered log-ratio (CLR) transformed and analyzed using linear mixed models with adjusted pairwise comparisons. RESULTS: API supplementation attenuated colitis phenotypes including weight loss (44% recovery; P < 0.001), colon shortening (57% recovery; P < 0.01), disease activity (59% lower; P < 0.001), cytokine/chemokine release (35%‒73% reductions; P < 0.05), and mucosal F4/80+ cells infiltration (80% reduction; P < 0.001). API also improved gut microbiota diversity and composition, increasing α diversity metrics (4.4%‒13.8%; P < 0.05), suppressing pathogenic bacteria (Paraclostridium, Enterococcus, Eubacterium; estimated CLR difference: -1.8 to -6.7; P < 0.001), and enriching beneficial bacteria (Lachnospiraceae and Blautia; estimated CLR difference: +1.6 to +3.0; P < 0.05). Furthermore, metabolomics indicated TWD consumption increased arachidonic acid and aliphatic aldehydes (by 109%‒510%; P < 0.001), and decreased short-chain and unsaturated fatty acids (by 30%‒91%; P < 0.001). API supplementation also mitigated TWD-derived functional metabolites (including bile acids; P < 0.05). CONCLUSIONS: These data indicate that API intake is beneficial for risk reduction of diseases associated with Western diets. However, further investigations are warranted to determine the mechanism behind these beneficial effects.

Effect of an Acute Prolonged Overnight Fast on Skeletal Muscle Insulin and Anabolic Sensitivity in Healthy Men.

Mallinson JE, Keeton M, Nixon A … +6 more , Sheth A, Jones R, Pabla P, Senden JM, van Loon LJ, Tsintzas K

J Nutr · 2026 Jun · PMID 42259439 · Publisher ↗

BACKGROUND: Repeated prolonged overnight fasting enhances anabolic sensitivity and preserves myofibrillar protein synthesis. Whether a single fasting episode can enhance dietary protein-derived amino acid incorporation i... BACKGROUND: Repeated prolonged overnight fasting enhances anabolic sensitivity and preserves myofibrillar protein synthesis. Whether a single fasting episode can enhance dietary protein-derived amino acid incorporation into skeletal muscle protein remains unclear. OBJECTIVE: To investigate the effect of a single 16-h compared with 10-h overnight fast on postprandial insulin and anabolic sensitivity in humans. METHODS: Randomized, crossover study. On 2 occasions, healthy participants (n = 9; age 22.6 ± 3.5 y; body mass index: 24.0 ± 2.5 kg/m; homeostasis model assessment of insulin resistance 1.00 ± 0.54) ingested a liquid meal, which consisted of specifically produced, intrinsically [1-C]phenylalanine-labeled milk protein (0.35 g/kg body mass, bm) and dextrose (0.8 g/kg bm), dissolved in 6 mL/kg bm water, after either a 10-h (Control) or 16-h (prolonged overnight fast trial, Long OF) overnight fast. Skeletal muscle and blood samples were obtained before, during, and 3 h after meal ingestion. RESULTS: Postprandial incorporation of dietary protein-derived [1-C]phenylalanine into myofibrillar protein did not differ between Control and Long OF (0.018 ± 0.005 compared with 0.022 ± 0.005 mole percent excess, d = 0.22, P = 0.56). Forearm branched amino acid uptake incremental area under the curve [D (95% confidence interval, CI) 103 (-1618, 1823) mmol/min180 min, d = 0.05, P = 0.892] and glucose uptake [D (95% CI) 24.7 (-25.3, 74.8) mmol/min, ηp = 0.16, P = 0.280] also did not differ between treatments, but the postprandial serum insulin response [D (95% CI) -7.4 (-14.4, -0.4) mIU/L, ηp = 0.42, P = 0.042] was lower in Long OF. CONCLUSIONS: A single prolonged overnight fast does not enhance postprandial skeletal muscle insulin sensitivity or dietary protein-derived amino acid incorporation into skeletal muscle protein in healthy, young adults. Whether susceptible populations, such as older, insulin-resistant individuals, may benefit from a more prolonged overnight fast warrants investigation. This study was registered at clinicaltrials.gov as NCT05420181.

Associations of Healthy Dietary Patterns with Plasma Biomarkers of Inflammation and Coagulation in Adults with and without Type 1 Diabetes.

Basu A, Richardson LA, Izuora K … +2 more , Alman AC, Snell-Bergeon JK

J Nutr · 2026 Jun · PMID 42251900 · Publisher ↗

BACKGROUND: Type 1 diabetes (T1D) poses a higher risk of developing cardiovascular disease (CVD) compared with individuals without diabetes. Circulating homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), f... BACKGROUND: Type 1 diabetes (T1D) poses a higher risk of developing cardiovascular disease (CVD) compared with individuals without diabetes. Circulating homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) have been positively associated with CVD. Not much is known about how dietary patterns are associated with these biomarkers. OBJECTIVES: This study aims to examine longitudinal associations of healthy dietary patterns with plasma Hcy, hs-CRP, fibrinogen, and PAI-1 in adults with and without T1D. METHODS: We used data from the "Coronary Artery Calcification in Type 1 Diabetes" study over a 3-y follow-up period. Dietary data obtained from food frequency questionnaires were used to calculate scores for adherence to the Alternate Healthy Eating Index-2010, the Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean-Style Dietary Pattern Score (MSDPS) at each visit. Mixed-effect models were used to examine longitudinal associations with plasma biomarkers in models adjusted for age, sex, diabetes status (combined analyses only), calories, visit, BMI, systolic blood pressure, lipids, smoking status, and physical activity. Plasma biomarkers were log-transformed. Therefore, for every 1-point increase in the specified dietary pattern score, there is a percentage change (%change) in the specified plasma biomarker. RESULTS: A total of 563 T1D and 692 adults without diabetes were included in the current analysis. Hcy decreased by -0.56% [95% confidence interval (CI): -1.01%, -0.12%] in the T1D group and -0.54% (95% CI: -0.83%, -0.24%) in the nondiabetes group for every 1-point increase in the DASH diet. Hcy had a significant inverse association with every 1-point increase in the MSDPS and AHEI-2010 scores in T1D and nondiabetes groups, respectively. A 1-point increase in the DASH diet was inversely associated with PAI-1 in the nondiabetes group [%change: -1.31% (-2.18%, -0.43%)] and in the T1D group [%change: -0.99% (-2.19%, -0.22%)]. CONCLUSIONS: All 3 dietary patterns revealed significant inverse associations with Hcy, but the associations varied based on diabetes status. The DASH score was associated with lower levels of Hcy and PAI-1 when adjusted for relevant covariates.

Intestinal Permeability Is Associated with Mortality and Readmission in Children Hospitalized with Severe Acute Malnutrition.

Sturgeon JP, Chasekwa B, Tome J … +13 more , Dumbura C, Majo FD, Ngosa D, Mutasa K, Besa E, Nathoo KJ, Bourke CD, Haider T, Ntozini R, Bwakura-Dangarembizi M, Amadi B, Kelly P, Prendergast AJ

J Nutr · 2026 Jun · PMID 42251899 · Publisher ↗

BACKGROUND: Severe acute malnutrition (SAM) is the most critical form of undernutrition, associated with high inpatient and postdischarge mortality. It is hypothesized that malnutrition enteropathy contributes to systemi... BACKGROUND: Severe acute malnutrition (SAM) is the most critical form of undernutrition, associated with high inpatient and postdischarge mortality. It is hypothesized that malnutrition enteropathy contributes to systemic inflammation by allowing translocation of intestinal pathogen-associated molecular patterns across the damaged epithelium. OBJECTIVES: Assess intestinal permeability, markers of bacterial translocation, and correlate these with inflammatory markers in children admitted with SAM and during 1 y after discharge. METHODS: In a substudy of the longitudinal Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition observational study, we recruited 264 children with complicated SAM on admission to hospital at 3 centers in Zimbabwe and Zambia. We measured gut permeability by urinary lactulose:mannitol ratio (LMR); plasma lipopolysaccharide (LPS) using the limulus amoebocyte lysate assay; and plasma inflammatory biomarkers by enzyme-linked immunosorbent assay and Luminex, at admission, discharge, 12- and 48-wk postdischarge. Values were compared with 173 adequately nourished community controls. Data were analyzed using mixed effects models for longitudinal data, regression for associations between groups, and Cox proportional hazards models for survival. RESULTS: Gut permeability, as measured by LMR, was 2.5-fold higher in children with SAM compared with community controls [95% confidence interval (CI): 1.4, 4.5], and only resolved by 48-wk postdischarge. Higher inpatient gut permeability was associated with increased risk of death or readmission over the following year [hazard ratio 6.14 (95% CI: 1.03, 36.8) per 10-fold increase in LMR]. Children with high gut permeability had higher levels of the intestinal biomarker glucagon-like peptide-2 and lower L-selectin. Children with higher plasma LPS had independently higher concentrations of circulating inflammatory markers [tumor necrosis factor-α, interleukin (IL)-6, IL-1ra, C-reactive protein, IL-8, chemokine ligand 3, and chemokine ligand 4]. CONCLUSIONS: Collectively, these results highlight the central role of the gut in children with SAM. Malnutrition enteropathy may represent a suitable target for therapeutic interventions to improve clinical outcomes in this high-risk population.

Impact of a Prenatal Nutrition Package with Balanced Energy Supplementation on Gestational Weight Gain in Amhara, Ethiopia.

Kang Y, Workneh F, Yibeltal K … +18 more , Fasil N, Baye E, Tsegaye S, Kidane WT, Berhane YY, Van Dyk F, North K, Chan GJ, Isanaka S, Molina RL, Tadesse AW, Perumal N, Mullany LC, Worku A, Wylie BJ, Christian P, Berhane Y, Lee AC

J Nutr · 2026 Jun · PMID 42251898 · Publisher ↗

BACKGROUND: Suboptimal gestational weight gain (GWG) is associated with adverse pregnancy outcomes; however, evidence on the impact of nutritional interventions on GWG in low-income settings remains limited. OBJECTIVES:... BACKGROUND: Suboptimal gestational weight gain (GWG) is associated with adverse pregnancy outcomes; however, evidence on the impact of nutritional interventions on GWG in low-income settings remains limited. OBJECTIVES: This study aims to examine the effectiveness of an enhanced nutrition package (ENP), including a balanced energy protein (BEP) supplement, on GWG compared with routine care. METHODS: We conducted a pragmatic cluster-randomized effectiveness study among pregnant women <24 wk of gestation in rural Amhara, Ethiopia. Twelve health centers were randomized to provide either ENP, including a daily BEP supplement for women with mid-upper arm circumference ≤23 cm, or routine care. GWG and GWG rate (kg/wk) were calculated from enrollment to late pregnancy weight measurement. Intention-to-treat (ITT), cluster-level analysis compared GWG outcomes between study arms. Primary analyses were restricted to women with observed third-trimester weights. Secondary dose-response analysis within the ENP arm examined associations between BEP consumption duration and GWG outcomes. RESULTS: A total of 2392 women were enrolled and randomly assigned (n = 1210 ENP; n = 1189 routine care), with 2170 followed up until birth. In the ENP arm, 37% were eligible for BEP supplementation. ITT analysis showed no differences between arms in GWG rate [diff = -0.006 kg/wk; 95% confidence interval (CI): -0.042 kg/wk, 0.030 kg/wk] or observed GWG (diff = 0.009 kg; 95% CI: -0.687 kg, 0.706 kg). Among BEP-eligible women, GWG outcomes also did not differ between arms (ΔGWG rate = 0.006 kg/wk; 95% CI: -0.027 kg/wk, 0.030 kg/wk); observed ΔGWG = 0.201 kg (95% CI: -0.443 kg, 0.845 kg). In dose-response analysis within the ENP arm, women consuming BEP for 61-90 and >90 d had a higher GWG rate (61-90 d: 0.46 kg/wk, 95% CI: 0.003 kg/wk, 0.090 kg/wk); >90 d: 0.059 kg/wk; 95% CI: 0.018 kg/wk, 0.099 kg/wk) and observed GWG (61-90 d: 0.895 kg, 95% CI: 0.004 kg, 1.786 kg; >90 d: 1.206 kg, 95% CI: 0.331 kg, 2.081 kg) compared with those consuming BEP for <30 d. CONCLUSIONS: The ENP package, including BEP, did not improve GWG compared with routine care in this pragmatic study in the Ethiopian health system. Longer duration of prenatal BEP adherence (≥60 d) may benefit GWG and GWG rates among undernourished women. This trial was registered as ISRCTN15116516.

Milk Fat Globule Membrane in a Novel High-Fat Spread Does Not Acutely Affect Postprandial Lipidemia in Healthy Individuals-A Randomized, Double-Blind Crossover Trial.

Voigt JH, Zubanovic NB, Møller AB … +5 more , Suwal SK, Andersen U, Andersen HJ, Rittig N, Søndergaard E

J Nutr · 2026 Jun · PMID 42251897 · Publisher ↗

BACKGROUND: Observational studies report neutral or inverse associations between some milk fat-containing dairy foods and cardiometabolic disease risk. Milk fat globule membrane (MFGM), a complex trilayered membrane surr... BACKGROUND: Observational studies report neutral or inverse associations between some milk fat-containing dairy foods and cardiometabolic disease risk. Milk fat globule membrane (MFGM), a complex trilayered membrane surrounding milk fat droplets, has been proposed as a mechanistic contributor to these effects, but its specific role, independent of other components of the dairy matrix, remains unclear. OBJECTIVES: We investigated whether MFGM content and structure affect postprandial lipidemia in healthy adults. METHODS: In a randomized, double-blind, controlled, crossover study, 12 healthy adults completed 3 study visits conducted inside whole-room indirect calorimeters separated by a ≥1-wk washout. To isolate the effects of MFGM presence and structural integrity, we developed 3 isocaloric high-fat spreads matched for protein, fat, and carbohydrate content and differing only in their MFGM characteristics: intact (iMFGM), disrupted (dMFGM), or absent. At each study visit, participants consumed 2 high-fat sandwich meals, each composed of 60 g (including 40 g milk fat) high-fat dairy spread containing either iMFGM, dMFGM, or no MFGM; the MFGM-containing meals provided ∼120 mg phospholipids per meal. The primary outcome was postprandial plasma triglyceride incremental area under the curve (iAUC). Secondary outcomes included gastric emptying assessed by the acetaminophen test, energy expenditure, and respiratory exchange ratio measured continuously by indirect calorimetry, appetite ratings, and ad libitum energy intake. RESULTS: Postprandial iAUC for triglycerides were not different between test meals {iMFGM: 179.5 mmol/L/min [95% confidence interval (CI): 76.9, 282.2 mmol/L/min]; dMFGM: 155.0 mmol/L/min (95% CI: 83.5, 226.5 mmol/L/min); no MFGM: 133.4 mmol/L/min (95% CI: 75.2, 191.6 mmol/L/min); P = 0.9}. Glucose-dependent insulinotropic polypeptide concentration increased more for MFGM than for dMFGM and no MFGM (P = 0.02). Free fatty acid concentrations were higher for MFGM than for dMFGM (P = 0.01). No differences in other secondary outcomes were observed. CONCLUSIONS: The presence or structural integrity of MFGM in a novel high-fat spread incorporated into 2 standardized sandwich meals does not acutely influence postprandial lipidemia in healthy individuals. This study was registered at clinicaltrails.gov as NCT06340412.

Bovine Leukemia Virus as a One Health Challenge in Nutrition, Food Security, and Public Health: A Narrative Review.

Scull TF, Benitez OJ

J Nutr · 2026 Jun · PMID 42251896 · Publisher ↗

Bovine leukemia virus (BLV) is among the most prevalent infectious diseases of dairy cattle, with herd-level infection rates exceeding 80% in many regions worldwide. Although only a minority of infected animals develop c... Bovine leukemia virus (BLV) is among the most prevalent infectious diseases of dairy cattle, with herd-level infection rates exceeding 80% in many regions worldwide. Although only a minority of infected animals develop clinical enzootic bovine leukosis, subclinical effects are widespread and extend beyond animal health. This narrative review examines BLV through a One Health lens, emphasizing its nutritional, food security, and public health dimensions. Relevant literature was identified through targeted searches of major scientific databases using terms related to BLV, milk composition, nutrition, food security, and One Health. Evidence suggests that BLV infection reduces milk yield and alters composition, particularly in cows with high proviral load. Decreases in fat, protein, and bioactive components diminish milk's caloric density and functional quality, potentially lowering consumers' dietary intake of essential fatty acids, fat-soluble vitamins, and immunomodulatory proteins. Increased susceptibility to mastitis due to BLV-associated immune dysfunction further exacerbates nutrient losses, compounding inefficiencies in milk production. Collectively, these changes undermine dairy's nutritional value, especially for populations that rely heavily on milk as a staple food, including young children, low-income households, and communities in low- and middle-income countries where dairy products may provide important dietary energy, protein, and micronutrients. At the systems level, BLV contributes to economic inefficiency through reduced herd productivity. These losses aggregate into a significant drag on dairy supply, with implications for affordability, accessibility, and environmental sustainability. Although definitive evidence of zoonotic transmission is lacking, recurring detection of BLV deoxyribonucleic acid, proteins, and antibodies in human tissue raises questions regarding potential public health risks. Taken together, BLV represents an underappreciated One Health challenge, encompassing animal productivity, human nutrition, economic access, and possible zoonotic implications. Future research should quantify BLV's economic and nutritional impacts on consumers and clarify risks to human health to support interventions aligned with animal health, food security, and sustainable nutrition.

What Is Driving Energy Intake after Weight Loss? A Longitudinal Mediation Analysis in Adolescents with Obesity.

Moore H, Hopkins M, Lazzer S … +6 more , Isacco L, Pereira B, Montaurier C, Blundell JE, Boirie Y, Thivel D

J Nutr · 2026 Jun · PMID 42251895 · Publisher ↗

BACKGROUND: It has been posited that fat and lean tissues have a direct role in driving energy intake after significant weight loss, but this has yet to be demonstrated in adolescents with obesity. OBJECTIVES: The aim of... BACKGROUND: It has been posited that fat and lean tissues have a direct role in driving energy intake after significant weight loss, but this has yet to be demonstrated in adolescents with obesity. OBJECTIVES: The aim of this study was to elucidate the changes in direct and indirect associations between body composition, resting metabolic rate (RMR), and energy intake (EI) before and after weight loss after a multidisciplinary intervention in adolescents with obesity. METHOD: This was a secondary analysis of 26 adolescents with obesity (age: 14.1 ± 1.6 y; BMI z-score: 2.8 ± 0.8; 14 females) enrolled in a 9-mo inpatient multidisciplinary intervention and followed for 4 mo thereafter. Body composition, RMR, substrate metabolism, and EI over 24 h were measured on 3 separate occasions in a metabolic chamber at baseline (T0), postintervention (T1), and after follow-up (T2). RESULTS: EI was significantly lower at both T1 (P < 0.001) and T2 (P < 0.001) after weight loss. Reductions in BMI z-score (P = 0.014) and protein metabolism (P < 0.001) with weight loss from T0 to T1 were negatively and positively associated with decreases in EI, respectively. Longitudinal mediation analyses revealed no direct effect of RMR change [β: 0.019; 95% highest posterior density interval (HPDI): -0.282, 0.344] or indirect effect of fat-free mass (FFM) change (β: -0.001; 95% HPDI: -0.264, 0.247) on EI change postintervention. However, the direct effect of fat mass (FM) change (β: 0.408; 95% HPDI: 0.128, 0.716) on EI change was significantly independent of changes in RMR and FFM. CONCLUSIONS: Although direct effects of FM and FFM independent of RMR were evident after weight loss, only changes in FM were associated with changes in EI. Improvement in whole-body protein turnover with weight loss could be relevant to regulation of dietary intake.

Orange Peel Powder Improves Constipation-Related Phenotypes and Is Associated with Coordinated Colonic and Brain-Related Changes in a Doxorubicin- and Loperamide-Treated Rat Model.

Xu K, Zhang Y, Hou G … +2 more , Zhao Y, Xi X

J Nutr · 2026 Jun · PMID 42250650 · Publisher ↗

OBJECTIVES: This study aimed to determine whether orange peel powder (OP) improves constipation-related phenotypes in a doxorubicin- and loperamide-treated rat model and whether such improvement is accompanied by coordin... OBJECTIVES: This study aimed to determine whether orange peel powder (OP) improves constipation-related phenotypes in a doxorubicin- and loperamide-treated rat model and whether such improvement is accompanied by coordinated histological and molecular changes in colon and brain tissues. METHODS: Forty-eight 12-wk-old male Sprague-Dawley rats were randomly assigned to 6 groups (n = 8/group): blank control (BC), aging control (AG), aging constipation control (ACG), and low-, medium-, and high-dose OP groups (0.1575, 0.315, and 0.63 g/kg, respectively). An aging-like phenotype was induced by intraperitoneal doxorubicin (2 mg/kg) for 4 wk, followed by loperamide gavage (2 mg/kg) for 14 d. OP was then administered by gavage for 4 wk. Body weight, defecation frequency, fecal moisture content, and small-intestinal propulsion rate were assessed. Gastrointestinal hormones, inflammatory markers, and oxidative stress indices were measured in serum and/or colon tissue. Colon and brain histology were examined by hematoxylin-eosin staining. Tight junction proteins (ZO-1, occludin, and claudin-1) and endocannabinoid system-related proteins (CB1, CB2, and FAAH) in colon and brain tissues were assessed by western blotting. RESULTS: Compared with the BC group, the AG and ACG groups showed lower body weight gain and worse constipation-related phenotypes. The ACG group also exhibited a higher inflammatory and oxidative stress-related burden, altered gastrointestinal hormone profiles, histological abnormalities in the colon and brain, and lower expression of tight junction proteins in the colon and brain. OP intervention, particularly at the medium dose, improved defecation frequency, fecal moisture content, and small-intestinal propulsion rate; reduced interleukin-6, tumor necrosis factor-α, vasoactive intestinal peptide, and malondialdehyde; increased gastrin, motilin, and total superoxide dismutase activity; and upregulated ZO-1, occludin, and claudin-1 expression in the colon and brain. CONCLUSIONS: OP improved constipation-related phenotypes in this composite model and was associated with coordinated systemic, colonic, and brain-related changes. These findings are descriptive and do not establish restoration of barrier function or a direct gut-brain mechanistic pathway.

Dietary Fiber Intake, FTO Genotypes, and Their Interactions on Obesity-Related Measures: The Fukuoka Diabetes Registry.

Ohkuma T, Iwase M, Higashi T … +2 more , Sakamoto W, Ago T

J Nutr · 2026 Jun · PMID 42250582 · Publisher ↗

BACKGROUND: Higher dietary fiber intake has been associated with weight reduction and favorable cardiovascular disease risk profiles in individuals with type 2 diabetes. Variants in the fat mass and obesity-associated (F... BACKGROUND: Higher dietary fiber intake has been associated with weight reduction and favorable cardiovascular disease risk profiles in individuals with type 2 diabetes. Variants in the fat mass and obesity-associated (FTO) gene have been associated with obesity as well as higher energy and fat intake, but it remains unclear whether these obesogenic genetic variants alter the association between dietary fiber intake and obesity, particularly in East Asian populations. OBJECTIVES: The aim of this study was to investigate the associations between dietary fiber intake, genetic variants of the FTO gene, and their interaction with obesity-related indices in individuals with type 2 diabetes. METHODS: A total of 4868 Japanese individuals with type 2 diabetes were included. Participants were categorized according to quintiles of dietary fiber intake and FTO (rs12149832) genotype. Associations with body mass index [BMI (in kg/m)], body weight, waist circumference, and waist-to-height ratio were examined cross-sectionally. RESULTS: Higher dietary fiber intake was linearly associated with lower BMI (P-trend <0.001); the multivariable-adjusted difference in BMI between the highest quintile (Q5) and the lowest quintile (Q1) was -1.24 [95% confidence interval (CI): -1.60, -0.88]. BMI increased linearly with the number of obesity-associated A alleles in FTO (P-trend <0.001). The inverse association between dietary fiber intake and BMI was more pronounced in individuals with the GA or AA genotype than in those with the GG genotype (P-interaction = 0.009); BMI differences between highest quintile (Q5) and lowest quintile (Q1) were -1.80 (95% CI: -2.39, -1.20) for GA/AA and -0.88 (95% CI: -1.34, -0.42) for GG. Similar associations were observed for body weight, waist circumference, and waist-to-height ratio. CONCLUSIONS: Higher dietary fiber intake was associated with lower BMI in individuals with type 2 diabetes, with stronger associations observed among carriers of the obesity-related FTO risk allele. A personalized dietary approach considering genetic background may be beneficial for managing obesity and diabetes.

Does Local System Strengthening Improve Nutrition Program Coverage and Child Growth: Evidence from a Large-Scale Program Initiative in India.

Gune S, Alderman H, Nguyen PH … +1 more , Chakrabarti S

J Nutr · 2026 Jun · PMID 42248251 · Publisher ↗

BACKGROUND: Acknowledging the importance of the first 1000 d of life, the Indian government is delivering nutrition-specific and -sensitive interventions targeting mothers and young children. However, implementation chal... BACKGROUND: Acknowledging the importance of the first 1000 d of life, the Indian government is delivering nutrition-specific and -sensitive interventions targeting mothers and young children. However, implementation challenges at the district level prevent achieving coverage at scale. The government, in collaboration with multiple development partners, introduced system-strengthening models to improve the intervention delivery between 2016 and 2020 in 64% of districts. OBJECTIVES: This study aimed to assess the effectiveness of system-strengthening models in improving coverage of interventions and child growth. METHODS: We used data from the 2015-2016 (N = 185,101) and 2019-2021 (N = 172,426) National Family Health Surveys. We assessed the impact of system-strengthening models on coverage of interventions and child nutrition using a difference-in-differences study design. We compared districts that received additional support to those that only received usual programming. Among supported districts, 98.0% received a base package of input features consisting of human resources, community mobilization, and technological support. In addition, 76.3% received an enhanced package that included capacity building, finance, performance-based incentives, and infrastructure. Therefore, we additionally tested for potential additive effects from receiving an enhanced package of input features. RESULTS: Coverage of nutrition-specific [range of significant (P < 0.05) coefficients: 5.8-14.5 percentage points (pp)] and nutrition-sensitive interventions (range of significant coefficients: 4.1-13.6 pp) improved at a faster rate in supported districts compared with usual programming districts between 2016 and 2020. Children in supported districts also experienced significantly faster improvements in height-for-age z-scores (0.18 SDs) relative to children in districts with usual programming. Although receiving the enhanced package on top of the base was associated with significant additive improvements in coverage of nutrition-specific interventions, no similar synergistic effect was observed for nutrition-sensitive interventions or child growth. CONCLUSIONS: Targeted support at the district level can help to address implementation challenges and lead to improvements in coverage and nutrition.

Host Genetics, Diet, and the Gut Microbiome: Addressing Methodological and Reproducibility Challenges in Human Studies.

Ortega-Reyes D, Asami S, Suda W … +1 more , Ohno H

J Nutr · 2026 Jun · PMID 42248250 · Publisher ↗

The interplay among host genetics, diet, and the gut microbiome is a key focus in human health research. However, progress has been slowed by substantial methodological differences and limited reproducibility across stud... The interplay among host genetics, diet, and the gut microbiome is a key focus in human health research. However, progress has been slowed by substantial methodological differences and limited reproducibility across studies. This narrative review examines major sources of variability throughout the research process, with a focus on design, measurement, and analysis. It highlights how factors such as cohort structure, confounder control, dietary assessment, sample collection and preservation, deoxyribonucleic acid extraction, sequencing methods, and statistical approaches can significantly influence microbiome taxonomic assignments and abundances, and hinder the replication of host-microbiome-diet associations. We discuss how these issues complicate the interpretation of microbiome heritability estimates, genome-wide association signals, and reported gene-diet-microbiome links, which often have small effects and depend heavily on context. We then review ongoing efforts to improve reproducibility and harmonization, including consensus reporting standards, protocol harmonization, and validation techniques such as standardized workflows, mock communities, controls, and absolute quantification methods. Finally, we outline key priorities to enhance cross-study comparability and meta-analyses, including thorough confounder assessment, transparent reporting, and diverse, longitudinal study designs to advance the application of precision nutrition and microbiome-based public health strategies.

Hydration and Water Intake among Children and Parents.

Seal AD, Suh H, Emmanuel H … +7 more , Colburn AT, Summers L, Bottin J, Zemdegs J, Vanhaecke T, Mauromoustakos A, Kavouras SA

J Nutr · 2026 Jun · PMID 42248249 · Publisher ↗

BACKGROUND: Studies show that 80% of children in the United States do not meet the dietary guidelines for water intake, and 65% have elevated urine osmolality (UOsm), indicative of underhydration. OBJECTIVES: This study... BACKGROUND: Studies show that 80% of children in the United States do not meet the dietary guidelines for water intake, and 65% have elevated urine osmolality (UOsm), indicative of underhydration. OBJECTIVES: This study aims to examine the relationship between parental-child hydration habits and identify parental factors associated with children's water intake and hydration. METHODS: A cross-sectional study was conducted in 729 parent-child pairs (children aged 3-13 y) from Northwest Arkansas and Phoenix, Arizona. Participants completed a food and fluid diary and collected a 24-h urine sample for hydration assessment. Associations between parental and child hydration indicators, including total water intake (TWI), plain water intake (PWI), sugar-sweetened beverage (SSB) intake, and UOsm, were assessed using linear regression and multivariable models. RESULTS: Children's fluid intake habits were significantly associated with those of their parents. Positive associations were observed between parent and child TWI (β = 0.12, P <0.001), PWI (β = 0.159, P <0.001), SSB intake (β = 6.251, P<0.001), and 24-h UOsm (β = 0.177, P < 0.001). Children whose parents were underhydrated (UOsm >500 mmol/kg) had 1.54 times greater odds of also presenting with UOsm >500 mmol/kg (95% confidence interval: 1.05, 2.26, P = 0.03). Multivariable analysis revealed that higher parental PWI and water intake from food were associated with greater TWI in children. Child-specific factors, including older age, male sex, higher BMI, physical activity, and energy/protein intake, also predicted higher TWI. CONCLUSIONS: Parental fluid intake habits are strongly associated with children's hydration status and habits. These findings underscore the importance of parental role modeling in promoting healthy hydration practices in children and highlight the need for family-centered interventions to improve hydration outcomes. This trial was registered at clinicaltrials.gov as NCT02937038.

Novel Erythroid Indices Have Better Prognostic Accuracy than Conventional Erythroid Indices for Early Diagnosis of Iron Deficiency and Associated Brain Metabolomic Changes in Nonhuman Primate Infants.

Rao RB, Kang Z, Ennis-Czerniak KM … +5 more , Lubach GR, Lock EF, Kling PJ, Georgieff MK, Coe CL

J Nutr · 2026 Jun · PMID 42248248 · Full text

BACKGROUND: Hemoglobin (Hgb) lacks sensitivity for early detection of iron deficiency (ID) and associated brain metabolic dysregulation in infancy. The utility of newer erythroid indices for early diagnosis of ID and alt... BACKGROUND: Hemoglobin (Hgb) lacks sensitivity for early detection of iron deficiency (ID) and associated brain metabolic dysregulation in infancy. The utility of newer erythroid indices for early diagnosis of ID and altered brain metabolome is unknown. OBJECTIVES: This study aimed to compare conventional and newer erythroid indices for predicting ID, anemia, and altered brain metabolome using a nonhuman primate model of infantile ID. METHODS: Serum iron panel and erythroid indices were determined at 2 wk and 2, 4, and 6 months in male and female infant rhesus monkeys born to mothers consuming a 180 mg Fe/kg diet (n = 51). Cerebrospinal fluid (CSF) metabolomic profiles were obtained at 2 and 4 months in a subset of ID and iron-sufficient infants (n = 10). Accuracy for prediction of ID [transferrin saturation (TSAT) <20%], anemia (Hgb <10 g/dL), and CSF metabolomic changes was evaluated using t tests, regression models, and canonical correlation analysis (CCA). RESULTS: Twenty infants (39.2%) developed ID and 13 (25.5%) progressed to anemia. At 2 wk, newer erythroid indices-immature reticulocyte fraction, reticulocyte hemoglobin equivalent (RET-He), and difference between hemoglobin in reticulocytes and that in mature red blood cells (Delta-He)-were altered in infants who subsequently developed ID, and, along with percentage hypohemoglobinized and hyperhemoglobinized erythrocytes, predicted the future likelihood of ID and anemia (false discovery rate <0.05). Hgb was not predictive of ID or anemia until 2 mo. Among erythroid indices, Delta-He was the best predictor, with an accuracy of 84% for both, and was comparable with TSAT. CCA demonstrated correlations between 4-mo CSF metabolomic profile and 2-wk (r = 0.71), 2-mo (r = 0.82), and 4-mo (r = 0.79) erythroid profiles. Mean corpuscular hemoglobin and RET-He were the largest contributors to the correlations between the 2-wk and 2-mo erythroid profiles and the 4-mo CSF metabolomic profile. CONCLUSIONS: Newer erythroid indices detect ID, anemia, and brain metabolomic alterations earlier than conventional indices in infant monkeys.
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