Shahin A, Ross AB, Turner RM
… +2 more, Mann J, Reynolds AN
Am J Clin Nutr
· 2026 Jan · PMID 41485875
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BACKGROUND: Specific metabolites detected in biofluids after food intake have been proposed as objective markers to address limitations with traditional dietary assessment methods. Although hundreds of metabolites have b...BACKGROUND: Specific metabolites detected in biofluids after food intake have been proposed as objective markers to address limitations with traditional dietary assessment methods. Although hundreds of metabolites have been associated with foods or food groups, they require validation. OBJECTIVES: The aim of this study was to develop a panel from the proposed biomarkers of dietary intake reflecting major food groups and compare them against known and self-reported dietary intakes. METHODS: A randomized crossover trial of 3 interventions, including a day of foods consumed under observation, was performed. Each feeding day was of 3 food groups (e.g., whole grains, dairy, and fish) with optional snacks (e.g., fruit, chicken, and legumes) but absent of 3 other food groups (e.g., meat, vegetables, nuts, and seeds). Fasted whole blood and 24-h urine samples were analyzed by liquid chromatography mass spectrometry to detect previously proposed biomarkers of food intake. Urinary sodium was measured. Pairwise correlation coefficients and generalized linear modeling (GLM) considered relationships between biomarkers and food groups. Comparisons were drawn between self-reported and known dietary intakes. RESULTS: Twenty-one participants [mean age 24.8, standard deviation (SD) 6.0 y, body mass index: 24.1; SD: 4.0] completed the trial. GLM coefficients indicated fish intake was associated with 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid [62.15 (95% confidence interval: 35.00, 89.29)], wholegrain intake with 3,5-dihydroxybenzoic acid [87.32 (24.28, 150.35)] and fruit intake with fructose [5.39 (2.53, 8.25)], and s-methylcysteine [5.91 (1.24, 10.58)]. GLM rate ratios indicated chicken intake was associated with 3-methylhistidine [0.19 (0.07, 0.31)], anserine [0.21 (0.05, 0.37)], and carnosine [0.11 (0.03, 0.19)], legume intake with glycine betaine [0.21 (0.02, 0.40)] and vegetable intake with sulforaphane [0.30 (0.20, 0.47)], S-methylcysteine [0.23 (0.14, 0.45)], methoxytyramine [0.21 (0.08, 0.35)], and β-carotene [0.05 (0.02, 0.08)]. There was no association between 24-h urinary sodium and known sodium intake [0.11 (-0.06, 0.28)]. Self-reported dietary intake was associated above acceptable level (r > 0.40) with known intake. CONCLUSIONS: We identified some previously reported associations between foods and proposed biomarkers, but not all, outlining the need for assessing dietary biomarkers across a range of study designs including food intakes within realistic ranges. This trial was registered at ACTRN as 12622001036707 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384292&isReview=true).
Am J Clin Nutr
· 2026 Jan · PMID 41485873
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BACKGROUND: Blood lipid concentrations are standard clinical biomarkers of cardiovascular disease risk. Replacing dietary saturated fat with unsaturated fat is expected to lower blood lipids. However, meta-analyses are l...BACKGROUND: Blood lipid concentrations are standard clinical biomarkers of cardiovascular disease risk. Replacing dietary saturated fat with unsaturated fat is expected to lower blood lipids. However, meta-analyses are lacking regarding quantifiable differences in blood lipid response between comparable diets rich in mono-(MUFA) and polyunsaturated fat (PUFA), considering food sources and dose-response. OBJECTIVES: The objective was to compare the effects of "high PUFA" compared with "high MUFA" diets on fasting blood lipids. METHODS: PubMed and Web of Science were searched through February 2025 for randomized clinical trials comparing "high PUFA" (≥10% of energy intake from PUFAs) and "high MUFA" (≥15% of energy intake from MUFAs) diets in adults. Reviewers extracted fasting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG). Eligible studies were pooled using random-effects models and expressed as mean differences with 95% confidence interval. RESULTS: Fifty-three records were included, representing 1690 adult participants. "High PUFA" diets reduced TC [-5.71 (-8.02, -3.40) mg/dL], LDL cholesterol [-3.31 (-5.39, -1.24) mg/dL], HDL cholesterol [-0.77 (-1.27, -0.26) mg/dL], and TG [-6.59 (-8.77, -4.42) mg/dL] compared with "high MUFA" diets. Subgroup analyses showed that the effects of LDL cholesterol (P = 0.03), and TG (P = 0.03) were stronger with oil compared with nut or diet interventions. Metaregressions revealed that the benefit of consuming a "high PUFA" compared with a "high MUFA" diet increases with total fat intake, with a ∼0.5 mg/dL greater reduction in TC (P = 0.01) and LDL cholesterol (P = 0.01) for every 1% increase in energy intake from fat. Cochrane Risk of Bias tool identified some concerns in most of the included records. CONCLUSIONS: High PUFA diets have a small, but significant, advantage for lowering blood lipids compared with high MUFA diets and may be a valuable strategy for improving blood lipids in some populations. This trial was registered at PROSPERO as CRD42023474301 (https://www.crd.york.ac.uk/PROSPERO/view/CRD42023474301).
Čad EM, Mars M, Pretorius L
… +6 more, van der Kruijssen M, Tang CS, de Jong HB, Balvers M, Appleton KM, de Graaf K
Am J Clin Nutr
· 2026 Jan · PMID 41485871
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BACKGROUND: Public health organizations currently recommend lowering the consumption of sweet-tasting foods, on the assumption that a lower exposure to sweet-tasting foods lowers preferences for sweet taste, decreasing s...BACKGROUND: Public health organizations currently recommend lowering the consumption of sweet-tasting foods, on the assumption that a lower exposure to sweet-tasting foods lowers preferences for sweet taste, decreasing sugar and energy intake, and aiding obesity prevention. However, empirical data supporting this narrative are lacking. OBJECTIVES: The objective of this study was to assess the effects of a 6-mo low, regular, and high dietary sweet taste exposure on liking for sweet taste. METHODS: In a parallel-groups randomized controlled intervention study, 180 healthy adults (female/male: 123/57; aged: 35 ± 15 y; body mass index (in kg/m): 23 ± 3) were provided with dietary advice and ∼50% daily energy needs for 6 mo, where 7% (low sweet taste exposure, n = 61), 35% (regular sweet taste exposure, n = 60), or 80% (high sweet taste exposure, n = 59) provided foods and beverages were sweet tasting from sugars, low-calorie sweeteners, fruits and dairy. Before, at 6 mo, and at a 4-mo follow-up, sweet taste liking, sweet taste intensity perception, food choice, energy intake, body weight, markers for diabetes and cardiovascular disease, and adverse events were assessed. RESULTS: Sweet food consumption varied between groups over the intervention period (self-reported dietary measures (percentage energy, percentage weight): smallest χ(16) = 59.4, P < 0.001; urinary markers for sucrose, sucralose, and saccharin: smallest χ(10) = 21.0, P = 0.02). However, from baseline to month 6, no differences between groups were found in sweet taste liking ( χ(40) = 37.9, P = 0.56), sweet taste intensity perception (χ(40) = 20.7, P = 0.99), sweet food choice (χ(10) = 10.1, P = 0.43), energy intake (χ(10) = 12.7, P = 0.24), body weight (χ(10) = 14.3, P = 0.16), markers for diabetes and cardiovascular disease (largest χ(10) = 15.9, P = 0.10) or adverse events. After the intervention, participants also spontaneously returned to baseline levels of sweet food intake. CONCLUSIONS: In the current trial, altering exposure to sweet-tasting foods did not change sweet taste liking, nor other outcomes. These results do not support public health advice to reduce exposure to sweet-tasting foods, independent of other relevant factors such as energy density and food form. This trial was registered at clinicaltrials.gov as NCT04497974.
Heughebaert L, Berger N, Moyersoen I
… +1 more, Stove CP
Am J Clin Nutr
· 2026 Mar · PMID 41485693
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BACKGROUND: Nutritional intake in population studies is typically estimated via food consumption surveys. However, because dietary intake does not always reflect the actual nutritional status, additional biomarker data a...BACKGROUND: Nutritional intake in population studies is typically estimated via food consumption surveys. However, because dietary intake does not always reflect the actual nutritional status, additional biomarker data are essential. Volumetric absorptive microsampling (VAMS) offers a convenient tool for large-scale (dried) whole blood collection, enabling direct biomarker measurement and thereby also offering a potential improvement in nutritional assessment. OBJECTIVES: The study aims to determine thiamine status in Belgian adults via microsampling-at-home and to evaluate the feasibility of microsampling for the purpose of large-scale biomarker data collection. METHODS: Capillary VAMS samples from 656 of the 1047 adults participating to the Finger prick study as part of the Belgian National Food Consumption Survey 2022-2023 (a nation-wide cross-sectional study) were analyzed. Thiamine diphosphate (TDP) concentrations were measured using a previously validated liquid chromatography-tandem mass spectrometry method. Habitual thiamine intake was assessed to estimate the proportion of individuals meeting the average requirement (AR) for thiamine and this was compared with the proportion of individuals with TDP concentrations within the healthy reference range. RESULTS: An overall successful participation-to-analysis rate of 63% (656/1047) was obtained with insufficient VAMS sample quality being responsible for 16% of the excluded samples (167/1047). The median TDP concentration derived for the adult Belgian population was 98.5 nmol/L [95% confidence interval (CI): 96.6, 100.8 nmol/L], with 11% (corresponding to the 11th percentile) having a TDP concentration below the lower limit of the healthy reference range (70-180 nmol/L). Dietary intake data indicated that <1% (mean of 0.24%, 95% CI: 0.08, 0.39%) of adults had a thiamine intake below the AR of 0.072 mg/MJ. CONCLUSIONS: Although nearly all Belgian adults met thiamine intake requirements, 11% showed biomarker concentrations indicative of thiamine insufficiency, underscoring the importance of biomarker-based nutritional assessments. This study also demonstrates that at-home VAMS microsampling is a feasible and convenient tool for large-scale biomarker collection.
Ventura EF, Selma-Royo M, Turjeman S
… +3 more, González S, Koren O, Collado MC
Am J Clin Nutr
· 2026 Mar · PMID 41482157
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BACKGROUND: Pregnancy complications like gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy, and obesity are rising. Emerging evidence suggests dietary strategies targeting maternal microbiota, such...BACKGROUND: Pregnancy complications like gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy, and obesity are rising. Emerging evidence suggests dietary strategies targeting maternal microbiota, such as increased fiber or polyphenols, may help manage these conditions. OBJECTIVES: This study aimed to 1) synthesize existing evidence on the relationship between maternal diet and the gut microbiota, with a focus on its potential link to gestational outcomes, and 2) provide insights based on the available literature to inform future pregnancy guidelines. METHODS: This systematic review included observational and interventional studies on pregnant females assessing maternal diet and gut microbiota. Searches were conducted in PubMed and Web of Science up to July 2025. Risk of bias was assessed using appraisal tool for cross-sectional studies, Risk Of Bias In Nonrandomized Studies - of Interventions, and Risk Of Bias 2 tools. Narrative synthesis and a correlational meta-analysis stratified findings by trimester and obstetric condition. RESULTS: Across 29 studies involving 3077 pregnant females, high-fiber and vegetarian diets were consistently associated with increased abundance of taxa such as Roseburia spp. and Bifidobacterium spp., alongside more favorable metabolic markers. In contrast, high-fat and Westernized diets were frequently linked to reduced microbial diversity and increased proinflammatory taxa including Collinsella and members of the Lachnospiraceae family. In GDM pregnancies, interventions like medical nutrition therapy were associated with favorable microbial profiles, whereas proinflammatory diets were associated with reduced diversity. Meta-analyses indicated that maternal health status significantly moderated associations between fat intake and Gram-negative bacteria [Likelihood Ratio Test (LRT) = 53.929, P = 0.020], and between protein intake and Gram-positive bacteria (LRT = 68.735, P = 0.009), suggesting differential microbial responses by metabolic risk profile. CONCLUSIONS: This systematic review found that specific dietary components, particularly fiber, omega-3 fatty acids, and micronutrients, were associated with differences in maternal gut microbiota, with potential relevance to metabolic outcomes such as GDM, obesity, and hypertensive disorders of pregnancy. Meta-analysis results indicate that maternal health status significantly moderated the associations between dietary fat and protein intake and microbial taxa, suggesting that precision nutrition interventions warrant evaluation in metabolically at-risk populations. This study was registered at PROSPERO as CRD420251085137.
Stewart CP, Arnold CD, Kumordzie SM
… +1 more, Engle-Stone R
Am J Clin Nutr
· 2026 Mar · PMID 41482156
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BACKGROUND: Anemia is of public health concern among females of reproductive age and young children. Population anemia surveys are challenging because of inaccuracy and imprecision in common field-friendly assessment met...BACKGROUND: Anemia is of public health concern among females of reproductive age and young children. Population anemia surveys are challenging because of inaccuracy and imprecision in common field-friendly assessment methods. However, there is uncertainty about how much error can be tolerated for effective surveillance. OBJECTIVES: Our objective was to quantify the influence of random and systematic errors in hemoglobin (Hb) measurement on prevalence bias under varying population characteristics using mathematical simulations. METHODS: We conducted a literature review to identify parameters of interest: means and standard deviations (SDs) in capillary and venous blood, the mean bias (capillary mean - venous mean), and the SD inflation ratio (capillary SD/venous SD). We generated reference Hb distributions with varying means (105-135 g/L) and SDs (10-16 g/L), assuming measurement using venous blood on an autoanalyzer. We then generated capillary blood comparison distributions with mean biases ranging from -5 to +11 g/L and SD inflation ratios ranging from 0.5 to 2.0. Using target prevalence accuracies of ±5 and ±10 percentage points (pp), we identified maximum tolerable mean biases and SD inflation ratios. RESULTS: Among 92 contrasts reported in 16 studies, 90% of mean biases were between -6.6 g/L and 10.7 g/L, and 90% of SD inflation ratios were between 0.79 and 1.54. In simulations, the prevalence bias was heavily influenced by the mean Hb bias, but less by the SD inflation ratio. To achieve the target prevalence accuracy, the mean bias would need to be within ±1 g/L (for 5 pp) or ±2.5 g/L (for 10 pp) and SD inflation ratio between 0.85 and 1.20 (for 5 pp) or 0.7-1.5 (for 10 pp). CONCLUSIONS: Random error (SD inflation ratio) has less influence than systematic error (mean bias) on anemia prevalence estimates. Efforts to reduce mean bias during data collection or through statistical adjustment may have a greater impact on anemia prevalence assessment.
Jiménez-Hernández E, Flores-Lujano J, Medina-Sansón A
… +21 more, Dorantes-Acosta EM, Espinoza-Hernández LE, Amador-Sanchez R, Peñaloza-Gonzalez JG, Valdez-Garibay B, Torres-Nava JR, Espinosa-Elizondo RM, Flores-Villegas LV, Pérez-Saldivar ML, Solis-Labastida KA, Rosas-Vargas H, Mata-Rocha M, Martín-Trejo JA, Jiménez-Morales S, García-Jiménez M, Zapata-Tarrés MM, Arellano-Galindo J, Meléndez-Zajgla J, Flores-Pérez FV, Núñez-Enríquez JC, Mejía-Aranguré JM
Am J Clin Nutr
· 2026 Feb · PMID 41478435
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BACKGROUND: Long-term survival rates for children with acute lymphoblastic leukemia (ALL) have not improved in some countries, with undernutrition and obesity identified as potential contributing factors. OBJECTIVES: To...BACKGROUND: Long-term survival rates for children with acute lymphoblastic leukemia (ALL) have not improved in some countries, with undernutrition and obesity identified as potential contributing factors. OBJECTIVES: To evaluate the relationship between undernutrition and obesity in long-term survival in Mexican children with ALL. METHODS: A cohort study included children <18 y, newly diagnosed with ALL between 2010 and 2013, treated at 8 public hospitals in Mexico City. Patients were followed from the diagnosis confirmation. Nutritional status at diagnosis was classified with body mass index (BMI) using the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) criteria. The primary outcome variables were relapse and death >5 y of follow-up. Hazard ratios (HR) with 95% confidence intervals (CI) were reported using a Cox proportional hazards model adjusting for sex, socioeconomic status, immunophenotype, NCI risk classification, and treatment protocol. RESULTS: A total of 1254 children were diagnosed with ALL. Information was complete for the WHO classification in 1072 patients (85.5%) and for the CDC classification in 997 patients (79.5%). Using WHO criteria, 7% of patients were undernourished, and 13% were overweight or obese; with CDC criteria, the corresponding prevalences were 14.8% and 27.1%. A higher risk of relapse was observed among patients with overweight and obesity (aHR = 1.43; 95% CI: 1.02, 2.00) using the WHO classification. Following the CDC classification, patients with obesity also showed an increased risk of relapse (aHR = 1.33; 95% CI: 0.94; 1.89). Additionally, a higher risk of death was noted among patients with overweight or obesity (aHR = 1.65; 95% CI: 1.25, 2.19) using WHO criteria, whereas under the CDC classification, the increased risk of death was observed in patients with obesity (aHR = 1.65; 95% CI: 1.24, 2.20). No significant associations were found between undernutrition and either relapse or death. CONCLUSIONS: Undernutrition was not associated with long-term survival in pediatric patients with ALL. However, overweight and obesity at diagnosis were associated with relapse and increased mortality, highlighting the importance of addressing these factors through interventions focused on nutritional optimization, especially regarding obesity prevention and management, at or prior to diagnosis, to improve outcomes in Mexican children with ALL.
Soler-Espejo E, Chen Y, Roldán V
… +3 more, Marín F, Rivera-Caravaca JM, Lip GY
Am J Clin Nutr
· 2026 Mar · PMID 41478434
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BACKGROUND: Obesity is a risk factor for atrial fibrillation (AF), but traditional measures such as body mass index (BMI) may not reflect true cardiometabolic risk. Novel adiposity indices better capture central fat, yet...BACKGROUND: Obesity is a risk factor for atrial fibrillation (AF), but traditional measures such as body mass index (BMI) may not reflect true cardiometabolic risk. Novel adiposity indices better capture central fat, yet their prognostic value in AF remains unclear. OBJECTIVES: This study aimed to assess the association of different adiposity indices with cardiovascular and bleeding outcomes in anticoagulated patients with AF. METHODS: Consecutive AF outpatients initiating oral anticoagulation between January 2016 and November 2021 were enrolled in this prospective study. BMI, conicity index (C-index), weight-adjusted waist index, waist-to-height ratio, body roundness index, and a body shape index were evaluated. Primary outcomes were thromboembolic events, major bleeding (MB)/clinically relevant non-MB (CRNMB), and major adverse cardiovascular events (MACE). Secondary outcomes included cardiovascular and all-cause death. Through restricted cubic spline (RCS), Cox models, and receiver operating characteristic analyses, we assessed associations with clinical outcomes. RESULTS: A total of 2070 patients [52.8% female; age 77 y (interquartile range: 70-83)] were included. During a 1.8-y (standard deviation: 0.5) follow-up, 18.1% of patients experienced a thromboembolic event, 13.5% experienced a MB/CRNMB, and 11.3% suffered a MACE. RCS analysis revealed associations between all adiposity indices and adverse outcomes, but only the conicity index (C-index) showed a nonlinear relationship. In multivariable models, as a categorical variable, high C-index (>1.34) was the only index independently associated with thromboembolic events [adjusted hazard ratio (aHR: 2.29; 95% confidence interval (CI): 1.58, 3.34)], MB/CRNMB (aHR: 2.10; 95% CI: 1.58, 2.79), and MACE (aHR: 2.48; 95% CI: 1.79, 3.43) compared with the low C-index group. A high C-index was also associated with cardiovascular and all-cause mortality. The C-index consistently showed the highest discriminative performance for all primary outcomes, which further improved when integrated with CHADS-VASc and HAS-BLED. CONCLUSIONS: In anticoagulated patients with AF, the C-index demonstrated the strongest and consistent prognostic value among all adiposity indices. Its integration into conventional risk scores may enhance risk stratification in this high-risk population.
Racette SB, Silver RE, Barry VG
… +5 more, DeGraff JJ, Gunning JA, Kebbe M, Gilhooly CH, Das SK
Am J Clin Nutr
· 2026 Mar · PMID 41475553
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BACKGROUND: Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) was the first randomized controlled trial of calorie restriction (CR) on biomarkers of aging and cardiometabolic health in...BACKGROUND: Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) was the first randomized controlled trial of calorie restriction (CR) on biomarkers of aging and cardiometabolic health in humans without obesity. OBJECTIVES: The aim of this secondary data analysis was to evaluate diet quality and nutritional adequacy during a 2-y CR intervention among healthy adults in the CALERIE trial. METHODS: CALERIE 2 was a multisite trial of healthy adults randomly assigned to 2 y of 25% CR or an ad libitum (AL) control condition. CR participants received extensive dietary education and support. Food records at baseline (BL) and months 6, 12, 18, and 24 were analyzed using Nutrition Data System for Research. Diet quality was evaluated using the Probability of Adequate Nutrient Intake (PANDiet) diet quality index, Healthy Eating Index (HEI), and Dietary Inflammatory Index (DII). Nutritional adequacy was defined using sex- and age-specific Estimated Average Requirement or Adequate Intake criteria for each nutrient. RESULTS: Two hundred eighteen participants began the trial and are included in the analyses [143 CR, 75 AL; 69.7% females, age 38.1 ± 7.2 y (mean ± SD), BL body mass index: 25.1 ± 1.7 kg/m]. One hundred eighty-eight participants completed the trial (82% CR, 95% AL). Average CR achieved during the 2-y intervention was 11.9% ± 7.2%. Diet quality scores improved during CR according to all 3 metrics, both within group and when compared with AL (all P < 0.01): PANDiet [CR BL 76.27%, 95% confidence interval: 75.45%, 77.09%; CR 2 y average 77.38% (76.58%, 78.19%)], HEI: [BL 59.40 (57.62, 61.18); 2 y average 66.83 (65.11, 68.55)], and DII: [BL -0.28 (-0.58, 0.01); 2 y average -1.05 (-1.35, -0.74)]. Nutritional adequacy was not compromised during the CR intervention. CONCLUSIONS: Diet quality improved and nutritional adequacy was maintained during a 2-y moderate CR intervention designed to enhance healthspan and comprised comprehensive nutrition counseling among healthy adults without obesity. The study was registered at clinicaltrials.gov as NCT00427193 (https://clinicaltrials.gov/study/NCT00427193?term=NCT00427193&rank=1).
Bournot AR, Hart KH, Johnsen S
… +7 more, Givens DI, Lovegrove JA, Ordóñez-Mena JM, de Lusignan S, Bartlett DB, Lanham-New SA, Darling AL
Am J Clin Nutr
· 2026 Feb · PMID 41475552
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BACKGROUND: Vitamin D status has been found to be inversely associated with risk of respiratory tract infections (RTIs). Although vitamin D status varies by ethnicity, the relationship between serum 25-hydroxyvitamin D (...BACKGROUND: Vitamin D status has been found to be inversely associated with risk of respiratory tract infections (RTIs). Although vitamin D status varies by ethnicity, the relationship between serum 25-hydroxyvitamin D (25[OH]D) and RTIs in United Kingdom ethnic groups remains unclear. OBJECTIVES: This study aimed to investigate the association between serum 25(OH)D status and hospitalization for RTI in United Kingdom adults. METHODS: An unmatched case-control study was conducted using data from United Kingdom Biobank, which includes 500k adults with serum 25(OH)D status and hospital episodes from linked records. Survival analyses and binary logistic regression models were used to explore the association between serum 25(OH)D and RTIs. RESULTS: Of the 36,258 participants included in the analysis, 34% were White, 28% Asian, 19% Black, 11% other, and 7% of mixed ethnicity. The RTI rate was 8.5% (median time to RTI, 14.8 y). Higher serum 25(OH)D (each +10 nmol/L increase) was significantly associated with a 4% lower hazard ratio (HR) for RTI hospitalization [HR: 0.96, 95% confidence interval (CI), 0.94, 0.99]. When stratifying for serum 25(OH)D, compared to those with ≥75 nmol/L (reference), those with <15 nmol/L had a higher HR for RTI hospitalization (HR: 1.33, 95% CI: 1.05, 1.67). Categories 15 to 24 nmol/L, 24 to 49 nmol/L, and 50 to 74 nmol/L were not statistically significant. Logistic regression models supported the above findings. Inclusion of an interaction term for 25(OH)D × ethnicity was trialed in the survival analysis, but the interaction term was not statistically significant. CONCLUSIONS: Serum 25(OH)D status <15 nmol/L is associated with 33% higher HR for RTI hospitalization among United Kingdom adults, compared with ≥75 nmol/L. Furthermore, studies are warranted to validate these findings and explore the mechanisms underlying the association between vitamin D status and RTIs in different ethnic groups.
Brunstrom JM, Schatzker M, Rogers PJ
… +3 more, Courville AB, Hall KD, Flynn AN
Am J Clin Nutr
· 2026 Mar · PMID 41475551
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BACKGROUND: In 2019, Hall et al. reported a randomized clinical trial showing that an ultraprocessed diet increases energy intake by ∼500 kcal/d compared with an unprocessed diet. OBJECTIVE: This post-hoc analysis assess...BACKGROUND: In 2019, Hall et al. reported a randomized clinical trial showing that an ultraprocessed diet increases energy intake by ∼500 kcal/d compared with an unprocessed diet. OBJECTIVE: This post-hoc analysis assessed whether participants selected meal components with specific nutritional characteristics and how this affected energy intake. METHODS: Twenty weight-stable adults received an ad libitum ultraprocessed or unprocessed diet for 2 wk, followed by the alternate diet. ANOVA and t tests assessed diet effects; a linear mixed model assessed predictors of meal size. RESULTS: With the unprocessed diet, participants selected components with a less-equal blend of energy from carbohydrate and fat ["blend index" difference; lunch = 0.22 (95% CI: 0.19, 0.26), P< 0.0001, d = 0.76; dinner = 0.24 (95% CI: 0.19, 0.28), P< 0.0001, d = 0.71]. These components formed meals that had a lower blend index (less balanced) than ultraprocessed meals [lunch, F(1, 19) = 18.49, P < 0.0004, partial η = 0.493; dinner, F(1, 19) = 24.85, P < 0.0001, partial η = 0.57]. With the unprocessed diet, participants preferentially chose low-energy-dense components (<1.0 kcal/g, mostly fruits and vegetables), creating meals lower in energy (unprocessed = 719.4 ± 11.6 kcal compared with ultraprocessed = 829.5 ± 12.51 kcal), [F(1,19) = 14.9, P < 0.001, ηG = 0.0457], yet significantly larger (57%) by mass (unprocessed = 665.5 ± 10.74 g compared with ultraprocessed = 423.5 ± 8.03 g), [F(1,19) = 82.9, P < 0.001, ηG = 0.274]. Modeled together, low-energy-dense mass and blend index strongly predict observed energy intakes (r = 0.78, df = 1676, P < 0.001). CONCLUSIONS: Unprocessed meals may reduce energy intake because: 1) they have a less balanced carbohydrate-fat blend; and 2) they promote a form of nutritional intelligence whereby a compromise is struck between consuming calories and consuming micronutrients, which we refer to as "micronutrient deleveraging." This trial was registered at clinicaltrials.gov as NCT03407053.
Conrad Z, Leu M, Wu S
… +13 more, Fulcher E, Keam B, Kim M, Kinsel D, Lozina S, DiStaso C, Kun J, Boston J, Peterson T, Roach B, Tupponce T, Phillips J, Wiipongwii T
Am J Clin Nutr
· 2026 Feb · PMID 41453618
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BACKGROUND: The historical disruption of Indigenous food systems in the United States has been a leading driver of contemporary nutrition-related health disparities. More information is needed to understand how climate c...BACKGROUND: The historical disruption of Indigenous food systems in the United States has been a leading driver of contemporary nutrition-related health disparities. More information is needed to understand how climate change may impact the capacity of Indigenous food systems to support diet quality in the future. OBJECTIVES: The objective of this study was to model the impact of climate change (global climate models GFDL 370, GISSG 245, GISSG 370, GISSH 245, and GISSH 370) on the agricultural capacity of all 24 tribal nations in Virginia, Maryland, and North Carolina to support recommended dietary intakes using prime agricultural land, and by expanding agricultural production onto subprime agricultural land. METHODS: A biophysical simulation model was used to evaluate the agricultural capacity of tribal lands to support a diet pattern that is consistent with the 2020-2025 United States Dietary Guidelines for Americans. The model represented a regional Indigenous food system as a series of integrated biological processes that transform user-inputted diet patterns into the agricultural resources needed to produce them. The model was parameterized for local conditions using primary data collected from partnering Indigenous tribes, data from a previously published geoclimatic model, and publicly available secondary data. RESULTS: Under near-future (2021-2040) climate conditions, prime agricultural land was not able to support all dietary recommendations for the population. By expanding agricultural production onto low/moderate-suitability land, and by importing red/orange vegetables (tomatoes, sweet potatoes, and winter squash), 18% to 59% of the population was estimated to meet their dietary recommendations. Further expansion onto marginal agricultural land was estimated to support 213% of the population's dietary needs without any imports. CONCLUSIONS: Under modeled conditions, we estimated that Indigenous agriculture in the eastern United States can support some, but not all, of the population's dietary needs. Greater efforts are needed to foster agricultural initiatives that promote food sovereignty and reduce nutrition-related health disparities, but their viability in this region will depend on future supply-demand dynamics that are influenced by changing political landscapes.
Sheinberg E, Tucker AC, Uriarte A
… +5 more, Weston CM, Antonacci CC, Laska MN, Wolfson JA, Leung CW
Am J Clin Nutr
· 2026 Feb · PMID 41429226
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BACKGROUND: Food insecurity is associated with poor diet quality. However, nutrition security may better predict diet quality as it specifically measures healthy food access. OBJECTIVES: This study aims to examine the as...BACKGROUND: Food insecurity is associated with poor diet quality. However, nutrition security may better predict diet quality as it specifically measures healthy food access. OBJECTIVES: This study aims to examine the associations between food security, nutrition security, and joint food and nutrition security status with diet quality. METHODS: Data came from 2 cross-sectional surveys of United States adults (n = 4554) and Supplemental Nutrition Assistance Program (SNAP) participants (n = 1463). For United States adults, food security was measured with the 18-item Household Food Security Survey Module, and diet quality was measured with the Prime Diet Quality Score (PDQS). For SNAP adults, food security was measured with the USDA's 6-item Food Security Survey, and diet quality was measured with the rapid PDQS (rPDQS). Nutrition security was measured with the Center for Nutrition and Health Impact's Household Nutrition Security (HNS) in both samples. Linear regression models analyzed the relationship between food and nutrition security and diet quality separately and jointly, adjusting for sociodemographic covariates. RESULTS: In the United States adult sample, 52.8% were food and nutrition secure (FS/NS), 16.4% were food insecure and nutrition secure (FI/NS), 4.2% were food secure and nutrition insecure (FS/NI), and 26.6% were food and nutrition insecurity (FI/NI). In the SNAP sample, 24.1% were FS/NS, 27.5% were FI/NS, 1.4% were FS/NI, and 46.9% were FI/NI. After multivariate adjustment, food insecurity was associated with lower diet quality in both samples [United States adults: β = -1.2 PDQS points; 95% confidence interval (CI): = -1.9, -0.54; SNAP sample: β=-0.92 rPDQS points; 95% CI: -1.7, -0.14]. Nutrition insecurity was not associated with lower diet quality for either sample. In both samples, joint food and nutrition insecurity was associated with the lowest diet quality compared with other groups. CONCLUSIONS: Further research is needed to understand the utility of the HNS because food insecurity was more strongly associated with lower diet quality than nutrition insecurity.
Chen J, Cao H, Xu Y
… +4 more, Chang Y, Qin X, Zhang Z, Yang W
Am J Clin Nutr
· 2026 Feb · PMID 41429225
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BACKGROUND: The association between light-to-moderate alcohol drinking (≤14 g/d for females; ≤28 g/d for males) and the risk of steatotic liver disease (SLD), including its metabolic dysfunction-associated subtype (MASLD...BACKGROUND: The association between light-to-moderate alcohol drinking (≤14 g/d for females; ≤28 g/d for males) and the risk of steatotic liver disease (SLD), including its metabolic dysfunction-associated subtype (MASLD), remains unclear, as does the role of related gut microbiota. OBJECTIVES: We investigated the association between light-to-moderate alcohol drinking and incident SLD/MASLD, identified gut microbial species associated with such drinking, and evaluated their associations with disease risk. METHODS: Among 1297 adults from a Chinese community-based cohort, alcohol intake was assessed by a validated questionnaire, and SLD was diagnosed by vibration-controlled transient elastography. In a subset with fecal samples at follow-up (n = 665), gut microbiota was profiled using shotgun metagenomic sequencing. We used the mean alcohol intake from baseline and follow-up to represent long-term drinking habits. Species differentially associated with alcohol intake were identified using zero-inflated Gaussian models with false discovery rate (FDR) correction. Cox and logistic regression were used to estimate hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), respectively. RESULTS: During follow-up (2020-2025), 513 incident SLD cases were identified. Light-to-moderate drinkers showed higher risks of SLD (HR = 1.27, 95% CI: 1.03, 1.58) and MASLD (HR = 1.27, 95% CI: 1.01, 1.59) compared with abstainers. For the same comparison, liquor consumption was positively associated with SLD (HR = 1.29, 95% CI: 1.01, 1.65). We identified 89 microbial species associated with alcohol intake and constructed a microbial score, which was positively associated with SLD (OR = 1.54, 95% CI: 1.03, 2.31, P = 0.05) and MASLD (OR = 1.50, 95% CI: 1.00, 2.26, P = 0.05). Among these species, Stenotrophomonas maltophilia AQ, Olsenella E timonensis, and Firm 11 sp., which were less abundant in drinkers, showed inverse associations with both conditions after FDR correction. CONCLUSIONS: Light-to-moderate alcohol consumption was associated with increased risks of SLD and MASLD. A gut microbial score based on alcohol-associated species also predicted higher disease risk.
Liu D, Zhang Y, Chen Z
… +3 more, Hong Y, Liu T, Chen LH
Am J Clin Nutr
· 2026 Feb · PMID 41429224
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BACKGROUND: In iodine-replete populations, hypothyroidism is mainly caused by autoimmune thyroiditis, which disproportionately affects females. Ultra-processed foods (UPFs) are linked to metabolic disturbances and chroni...BACKGROUND: In iodine-replete populations, hypothyroidism is mainly caused by autoimmune thyroiditis, which disproportionately affects females. Ultra-processed foods (UPFs) are linked to metabolic disturbances and chronic inflammation that may contribute to autoimmune-related hypothyroidism; however, evidence remains limited, particularly regarding sex-specific differences. OBJECTIVES: To examine the association between UPF intake and incident autoimmune-related hypothyroidism, and quantify mediation by circulating biomarkers, with emphasis on sex-specific effects. METHODS: We included 123,812 UK Biobank participants (68,456 females; 55,356 males) without thyroid disease at baseline who completed ≥2 24-h dietary recalls (2009-2012). UPF intake (percentage energy) was defined according to NOVA and modeled in sex-specific quintiles. Incident hypothyroidism was identified via linked health records to 2020. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographic, lifestyle, clinical, and dietary factors. Mediation analyses assessed the proportion of mediation via biomarkers involving renal, liver function, lipid, glucose metabolism, and immune-inflammatory status. Effect modification was evaluated by including cross-product interaction terms between UPF intake and potential modifiers. RESULTS: During a median of 11.2 y of follow-up, 2907 hypothyroidism cases occurred (2303 females; 604 males). Compared with the lowest UPF quintile, the highest quintile showed a higher risk of hypothyroidism (HR: 1.31; 95% confidence interval: 1.16, 1.49; P-trend < 0.001), consistent in females [1.28 (1.11, 1.48)] and males [1.36 (1.04, 1.79)]. Renal function biomarker cystatin C mediated the largest proportion of the association (35.5% in females; 26.3% in males), followed by cholesterol efflux-related biomarkers (apolipoprotein A and high-density lipoprotein cholesterol). Among females, associations were stronger with hormone replacement therapy (interaction HR: 1.06, P-interaction = 0.021). CONCLUSIONS: Higher UPF intake was associated with an increased risk of autoimmune-related hypothyroidism in both sexes, partly mediated by renal and lipid biomarkers. Risk may be amplified in females using hormone replacement therapy.
Tremblay JO, Swift SL, Rundek T
… +9 more, Sotres-Alvarez D, Raij L, Van Horn L, Daviglus M, Castaneda S, Cordero C, Franceschini N, Wassertheil-Smoller S, Elfassy T
Am J Clin Nutr
· 2026 Feb · PMID 41423133
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BACKGROUND: Associations between dietary sodium and potassium with cardiovascular disease (CVD) remain controversial. OBJECTIVES: This study aimed to evaluate the relationship of dietary sodium and potassium with inciden...BACKGROUND: Associations between dietary sodium and potassium with cardiovascular disease (CVD) remain controversial. OBJECTIVES: This study aimed to evaluate the relationship of dietary sodium and potassium with incident cardiovascular disease among diverse Hispanic/Latino adults. METHODS: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective cohort of 16,415 self-identifying Hispanic/Latino adults aged 18 to 74 y. At baseline (2008-2011), participants underwent a comprehensive examination by bilingual interviewers. Dietary sodium (mg/d) and potassium (mg/d) intake were assessed from the average of two 24-h dietary recall surveys. CVD events (heart failure, myocardial infarction, or stroke) occurring from baseline through 2021 were adjudicated by an expert panel of clinicians. Cox proportional hazards models were used to determine the associations between sodium, potassium, and the sodium-to-potassium ratio, with CVD, after adjusting for demographic, socioeconomic, behavioral, and clinical factors. All analyses accounted for the HCHS/SOL complex survey design. RESULTS: Among 14,947 participants without a self-reported history of CVD, mean age was 40 y, with 53% female. Over 11.5 y, there were 481 CVD events [2.7 per 1000 person years, 95% confidence interval (CI): 2.3, 3.2]. Nutrient intakes were associated with increased risk of CVD: by 19% for each 1 g/d increment of sodium [hazard ratio (HR): 1.19, 95% CI: 1.05, 1.34]; by 40% for each 1 g/d decrement of potassium (HR: 1.40, 95% CI: 1.13, 1.73); and by 146% for each 0.5 molar increment of sodium-to-potassium ratio (HR: 2.46, 95% CI: 1.71, 3.56). CONCLUSIONS: In a large and diverse sample of Hispanic/Latino adults, high dietary sodium and low dietary potassium were independently associated with an increased risk of CVD. Results underscore the importance of investing in public health interventions to improve dietary quality and reduce incident CVD.
Li Y, Novotny JA, Baer D
… +4 more, Hu Y, Sun Q, Zhang S, Sang S
Am J Clin Nutr
· 2026 Feb · PMID 41423132
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BACKGROUND: Betainized compounds are bioactive metabolites involved in 1-carbon metabolism and cellular osmoprotection. Whole grains (WGs) are important dietary sources of these compounds, but their postprandial and dail...BACKGROUND: Betainized compounds are bioactive metabolites involved in 1-carbon metabolism and cellular osmoprotection. Whole grains (WGs) are important dietary sources of these compounds, but their postprandial and daily metabolic responses in humans remain understudied. OBJECTIVES: To characterize the pharmacokinetic (PK) profiles and short-term accumulation of 16 betainized metabolites following WG wheat and oat intake and to identify WG intake-specific biomarkers. METHODS: Two randomized, controlled crossover trials were conducted. The first was a 2-period PK study involving 12 healthy adults, who consumed WG wheat and oat in a crossover design, with serial plasma and urine collection ≤24 h and 48 h, respectively. The second was a study with five 15-d controlled feeding periods separated by washout phases (∼8 mo total), in which 54 participants consumed wheat- or oat-based diets. Plasma and urine were collected on day 1 (baseline), day 8, and day 15 of each period. All samples were analyzed using liquid chromatography-mass spectrometry (LC-MS). PK parameters were calculated, and statistical analyses evaluated interindividual variability, temporal trends, and grain-specific effects. RESULTS: Valine betaine, isoleucine betaine, and glutamine betaine exhibited distinct PK profiles, peaking at 5 to 6 h after WG wheat consumption and coinciding with their major urinary excretion window. In the daily grain intake study, valine betaine increased from 1.2 ± 0.4 to 22.2 ± 1.8 nM in plasma and from 39.5 ± 2.2 to 218.5 ± 8.6 μmol/mmol creatinine in urine by day 15 (P < 0.05). Isoleucine betaine showed a similar trend, whereas glutamine betaine was only detected in urine, increasing from 5.7 ± 0.9 to 10.7 ± 0.6 μmol/mmol creatinine. These results demonstrate clear dose- and time-dependent accumulation consistent with their kinetic behavior. CONCLUSIONS: Valine betaine, isoleucine betaine, and glutamine betaine are specific biomarkers of WG wheat intake, not WG oat. Their distinct responses highlight the need for precision nutrition when evaluating the health benefits of WGs. This trial was registered at clinicaltrials.gov as NCT03783637 and NCT04104581.
Gletsu-Miller N, Wilcox ML, Spence LA
… +9 more, Wright AJ, Guarneiri LL, Nadeem MM, Hutter MJ, Sprague KL, Brown AW, Friedman AN, Kirkpatrick CF, Maki KC
Am J Clin Nutr
· 2026 Feb · PMID 41397527
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BACKGROUND: Limited high-quality evidence exists from controlled trials on the impact of avocado-containing diets on cardiometabolic risk factors. OBJECTIVES: The purpose of this randomized, double-blind, free-living, co...BACKGROUND: Limited high-quality evidence exists from controlled trials on the impact of avocado-containing diets on cardiometabolic risk factors. OBJECTIVES: The purpose of this randomized, double-blind, free-living, controlled feeding, crossover study in adults with increased cardiometabolic risk was to assess the effects of replacing energy from solid fats and added sugars with equivalent energy from 1 avocado daily on cardiometabolic risk factors. METHODS: For two 3-wk periods, separated by a 2-wk washout, healthy adults with elevated triglycerides (TG, 135-499 mg/dL) consumed an average American diet or a diet in which 1 avocado (∼180 g/d, ∼300 kcal/d) replaced energy from saturated fatty acids and added sugars. The same study products (muffins, granola bites, dressing, salsa, marinade, and pesto) delivered the avocado or control ingredients. Green food dye was added to the control study products to facilitate double blinding. Non-high-density lipoprotein (non-HDL) cholesterol (primary outcome), other lipoprotein lipids, fasting glucose and insulin, and fasting and postprandial blood pressures were measured at baseline and end of condition. Linear mixed models were used to generate estimates for percentage changes. RESULTS: Of 42 randomly assigned participants, 37 completed the avocado condition and 39 completed the control condition. An intention-to-treat analysis showed significantly larger percentage changes, 95% confidence intervals (CIs), from baseline after the avocado condition, compared with after the control condition, for non-HDL cholesterol (-4.65%; 95% CI: -9.01%, -0.08%; P = 0.047), very-low-density lipoprotein cholesterol (-9.30%; 95% CI: -15.3%, -2.82%; P = 0.007); TG (-17.4%; 95% CI: -25.0%, -8.99%; P < 0.001), small low-density lipoprotein subfraction cholesterol (-13.9%; 95% CI: -23.2%, -3.49%; P = 0.012), and total cholesterol:HDL cholesterol ratio (-6.56%; 95% CI: -12.0%, -0.79%; P = 0.028). Percentage changes for other lipoprotein lipids, glucose, insulin, and blood pressures did not significantly differ (P > 0.05) between conditions. CONCLUSIONS: Replacing solid fats and added sugars with avocado in a typical American diet improves the lipoprotein lipid profile in adults with elevated TG. This trial was registered at clinicaltrials.gov as NCT04990817 (https://clinicaltrials.gov/study/NCT04990817).