Carollo L, Lawson EA, Stanley TL
… +19 more, Wang J, Bhattacharya R, Bishop DJ, Carmichael O, Esser KA, Febbraio MA, Fielding RA, Fourman LT, Goodpaster BH, Goodyear LJ, Guseh JS, Haines MS, Hawley JA, Heymsfield SB, Lindholm ME, Long JZ, Snyder MP, Whitham M, Grinspoon SK
Am J Clin Nutr
· 2026 May · PMID 41812769
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Skeletal muscle is a crucial facilitator of many of the effects of exercise on metabolic health. Intrinsic myocellular mechanisms, exercise-induced myokine secretion, and crosstalk between multiple organ systems contribu...Skeletal muscle is a crucial facilitator of many of the effects of exercise on metabolic health. Intrinsic myocellular mechanisms, exercise-induced myokine secretion, and crosstalk between multiple organ systems contribute to the maintenance of energy homeostasis, cardiovascular health, strength, cognition, and quality of life. Investigating the molecular underpinnings of the skeletal muscle response to exercise from multiple perspectives, including the genetic, physiological, and environmental factors leading to metabolic dysfunction, has advanced our understanding of disease risk and helped identify avenues for the prevention and treatment of metabolic disorders and chronic diseases. The National Institutes of Health-funded Boston Area Nutrition Obesity Research Center, in partnership with the Harvard Medical School Division of Nutrition, hosted its 26th Annual Symposium, "Muscle Movement and Metabolism: Exercise and Skeletal Muscle as Mediators of Health," in June of 2025. Speakers presented novel research and unique perspectives on exercise and skeletal muscle as key determinants of health. This manuscript synthesizes the symposium's major themes: 1) physiological and molecular mechanisms of exercise, 2) clinical implications of physical inactivity and reduced muscle function, and 3) individual variability and personalized medicine. By bridging mechanistic and clinical insights with principles of personalized medicine, the symposium provided key insights into the current landscape of treatments for metabolic diseases and evidence-based strategies for disease prevention.
Am J Clin Nutr
· 2026 May · PMID 41802496
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BACKGROUND: Proton density fat fraction (PDFF) measured using magnetic resonance imaging (MRI) is considered a noninvasive reference measure of fat deposition in various tissues and has been proposed as a quantitative in...BACKGROUND: Proton density fat fraction (PDFF) measured using magnetic resonance imaging (MRI) is considered a noninvasive reference measure of fat deposition in various tissues and has been proposed as a quantitative indicator of tissue quality. Although the contraindications of MRI limit PDFF as a routine clinical tool, computed tomography (CT) scans are often available clinically. Currently, there are no standard methods to compare CT and MRI tissue density measures. OBJECTIVES: The objective of this study was to determine the relationship between CT and MRI tissue density values in skeletal muscle and subcutaneous adipose tissue (SAT). METHODS: Tissue density (using same-day CT and MRI) was assessed for both muscle and SAT in a healthy prospective clinical cohort [n = 50, 23 males, 27 females; mean age: 57 ± 5 y; BMI (kg/m): 27 ± 5]. Comparisons using small regions of interest and entire cross-sectional areas (CSAs) were made at both L1 and L3 vertebral levels. CT CSA was measured using automated artificial intelligence-based segmentation software. All other measurements were demarcated manually. Regressions with 95% confidence intervals were fitted separately for each comparison. RESULTS: A strong negative linear correlation was found for all CT Hounsfield unit (HU)-PDFF tissue density pairings. The strongest association for skeletal muscle tissue density was measured at L3 using CSA [PDFF (%) = -0.352 × mean CT attenuation (HU) + 26.4; r = 0.791]. The strongest linear correlation for SAT density was identified at L1 using CSA [PDFF (%) = -0.604 × mean CT attenuation (HU) + 31.2; r = 0.885]. CONCLUSIONS: It is feasible to convert density values from CT scans to accurate estimates of PDFF in skeletal muscle and SAT. Conversion of tissue density values from CT HU to estimated PDFF expands clinical measures of muscle quality and improves body composition assessment.
Cavero-Redondo I, Saz-Lara A, Bouzas C
… +16 more, Saz-Lara AD, Chiva-Blanch G, Konieczna J, Picó C, Fernández-Aranda F, Moreno-Aliaga MJ, Daimiel L, Martínez JA, Salas-Salvadó J, Portillo MP, Toledo E, Giralt M, Corella D, Moreno-Indias I, López de Las Hazas MC, Dávalos A
Am J Clin Nutr
· 2026 May · PMID 41796966
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BACKGROUND: Ultraprocessed foods (UPFs) contribute substantially to global energy intake and are consistently linked to adverse health outcomes. However, accurately assessing UPF intake remains challenging due to relianc...BACKGROUND: Ultraprocessed foods (UPFs) contribute substantially to global energy intake and are consistently linked to adverse health outcomes. However, accurately assessing UPF intake remains challenging due to reliance on self-reported data and retrospective processing classification, with performance highly dependent on reference method quality. OBJECTIVES: To evaluate the validity, reliability, agreement, and risk of bias of instruments used to quantify UPF intake according to the NOVA classification and to examine the agreement between food processing classification systems. METHODS: We conducted a 2020 PRISMA-compliant systematic review of PubMed/MEDLINE, Scopus, and Web of Science from inception to 12 January, 2026, without language restrictions. Two reviewers (IC-R and AS-L) independently screened studies, extracted data, and assessed methodological quality via the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) risk of bias checklist. The evidence was synthesized narratively and through structured visual summaries of test-retest reliability (intraclass correlation coefficients), relative (criterion/convergent) validity against dietary reference methods, classification agreement (Cohen's κ and prevalence-adjusted bias-adjusted κ), and internal consistency (Cronbach's α or McDonald's ω). RESULTS: Thirty studies were included: 19 evaluated basic dietary intake instruments (NOVA-oriented food frequency questionnaires, short screening tools, or UPF scores), 4 examined biomarker-based or indirect tools, and 7 assessed contextual or auxiliary instruments. The test-retest reliability of the dietary intake instruments was generally moderate-to-high (intraclass correlation coefficients ≈ 0.46-0.94). Relative validity against dietary reference methods was modest to moderate (correlations typically r ≈ 0.47-0.72), and agreement between processing classification systems ranged from fair-to-substantial (Cohen's κ and prevalence-adjusted bias-adjusted κ ≈ 0.36-0.84). The contextual and auxiliary instruments showed high internal consistency (Cronbach's α/McDonald's ω ≥0.74). Fifteen studies were rated as having a low risk of bias, and 15 were rated as unclear. CONCLUSIONS: Instruments assessing NOVA-defined UPF intake demonstrate acceptable reproducibility but variable, reference-dependent validity and system-specific classification uncertainty. Future research should prioritize higher-quality reference methods, transparent coding rules, calibration strategies, and routine evaluation of measurement error and responsiveness. This trial was registered at PROSPERO CRD420251135087.
Bennett JP, Wong MC, Tian IY
… +10 more, Bowen A, Liu YE, Kelly NN, Ramirez S, Chow D, Pujades S, Garber AK, Maskarinec G, Heymsfield SB, Shepherd JA
Am J Clin Nutr
· 2026 May · PMID 41796965
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BACKGROUND: Nutritional disturbances among United States children and adolescents have risen sharply in recent decades. Current guidelines emphasize assessing body composition to track changes in fat mass (FM) and fat-fr...BACKGROUND: Nutritional disturbances among United States children and adolescents have risen sharply in recent decades. Current guidelines emphasize assessing body composition to track changes in fat mass (FM) and fat-free mass (FFM) after interventions. Three-dimensional optical (3DO) imaging has been validated in cross-sectional pediatric samples, although its accuracy in detecting longitudinal change has not been studied. OBJECTIVES: This study evaluated the ability of 3DO imaging to monitor body composition over time in children and adolescents. METHODS: A subsample of 26 ethnically diverse healthy children and adolescents from the Shape Up! Kids study completed whole-body dual-energy X-ray absorptiometry (DXA) and 3DO scans at baseline and again ≥1 y later. 3DO meshes were registered to a standardized template for vertex correspondence, transformed into principal components with an established shape model, and used to estimate whole-body and regional body composition measures using published equations. Body composition changes from 3DO scans were compared with DXA using linear regression and root mean square error (RMSE) to quantify error. Duplicate baseline scans provided least significant change (LSC) estimates to assess whether observed 3DO imaging changes reflected true changes in body composition. RESULTS: At baseline, mean ± SD age was 10.2 ± 3.2 y, with a mean ± SD body mass index z-score of 0.56 ± 1.29. On average, there were 1.6 y (range: 12-18 mo) between baseline and follow-up. Agreement between 3DO imaging and DXA (R) for changes in total FM, FFM, and appendicular lean mass was 0.82, 0.81, and 0.77, respectively, with RMSEs of 2.29 kg, 2.79 kg, and 0.78 kg, respectively. Of the sample, 75% to 80% of significant changes in FM and FFM based on DXA LSCs were also categorized as significant by 3DO imaging. CONCLUSIONS: 3DO imaging is capable of monitoring body composition changes over time in children and adolescents. The accuracy, safety, and accessibility of this approach support its feasibility for risk screening in this population. This trial was registered at clinicaltrials.gov as NCT03706612.
Espinosa A, Pacheco LS, Wan Y
… +5 more, Sun Q, Hu FB, Tobias DK, Willett WC, Mattei J
Am J Clin Nutr
· 2026 May · PMID 41794180
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BACKGROUND: Whether habitually consuming artificially sweetened beverages (ASBs) in place of sugar-sweetened beverages (SSBs) is associated with weight changes is unclear. OBJECTIVES: To evaluate the association of incre...BACKGROUND: Whether habitually consuming artificially sweetened beverages (ASBs) in place of sugar-sweetened beverages (SSBs) is associated with weight changes is unclear. OBJECTIVES: To evaluate the association of increasing ASBs or water, as SSBs replacements, with changes in weight/body mass index (BMI). METHODS: We analyzed data from the Nurses' Health Study (NHS), NHS II, and Health Professionals Follow-up Study. Adults aged 26-65 y were followed for 24-32 y with biennial questionnaires updating medical, lifestyle, and anthropometric data. Multivariable-adjusted linear models estimated associations between changes in ASB intake, substitution of SSBs with ASBs or water, and 4-y weight and BMI changes. Latent class growth models and multinomial logistic models estimated the odds of weight-trajectory membership based on beverage intake. RESULTS: Among 143,409 participants (median follow-up 28 y), the mean weight gain per 4-y interval was 1.3 kg (5th-95th percentile: -6.3 to 9.1 kg). Each 3-serving/wk increase in ASB was associated with -0.18 kg weight change [95% confidence interval (CI): -0.26 kg, -0.11 kg] and -0.06 kg/m BMI change (95% CI: -0.09 kg/m, -0.03 kg/m) over 4-y intervals, with stronger inverse associations among adults with overweight/obesity and higher SSB intake. Replacing 3 SSB servings/wk with ASB was associated with lower weight (-1.39 kg, 95% CI: -1.50 kg, -1.28 kg) and BMI gains (-0.50 kg/m 95% CI: -0.54 kg/m, -0.45 kg/m), with larger SSB-to-ASB replacements associated with progressively less gains. Similar estimates were observed when replacing SSB with water (-1.39 kg, 95% CI: -1.48 kg, -1.30 kg and -0.49 kg/m, 95% CI: -0.53 kg/m, -0.46 kg/m). Replacing ASB with water was associated with modest reductions in weight (-0.11 kg, 95% CI: -0.19 kg, -0.03 kg) and BMI gains (-0.04 kg/m, 95% CI: -0.08 kg/m, -0.01 kg/m). Higher ASB or water intake were inversely associated with unhealthy weight trajectories. CONCLUSIONS: Increases in ASB intake were inversely associated with weight/BMI gains over time, particularly among adults with overweight/obesity and higher SSB intake. Replacing SSBs with ASBs-or ideally water-was associated with decreases in weight/BMI changes in a dose-dependent manner.
Am J Clin Nutr
· 2026 Mar · PMID 41781083
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BACKGROUND: Addressing the concurrent stunting and overweight (CSO) is essential for achieving Sustainable Development Goal 2.2 in low- and middle-income countries (LMICs). However, contemporary evidence on its prevalenc...BACKGROUND: Addressing the concurrent stunting and overweight (CSO) is essential for achieving Sustainable Development Goal 2.2 in low- and middle-income countries (LMICs). However, contemporary evidence on its prevalence and feeding-related determinants during the critical 6‒23-mo window remains insufficient in the post-2015 era. OBJECTIVES: To determine the contemporary prevalence of stunting, overweight, and CSO, and to investigate the associations of the 2021 World Health Organization (WHO)/United Nations Children's Fund infant and young child feeding indicators and socioeconomic factors with these outcomes across 40 LMICs. METHODS: We analyzed pooled demographic and health survey data (2015‒2024) from 107,208 children aged 6‒23 mo. Child nutritional status was classified into 4 categories (healthy, stunted only, overweight only, or CSO), according to the WHO child growth standards. Multilevel multinomial logistic regression was used to identify determinants of different nutritional phenotypes. RESULTS: The pooled prevalence was 25.4% for stunting only, 1.7% for overweight only, and 1.5% for CSO. National-level analysis revealed 2 distinct transition patterns: 1 in which CSO comprised the majority of overweight cases (e.g., Papua New Guinea and Timor-Leste) and another where CSO concentrated within a residual stunted subpopulation (e.g., Albania and Armenia). Higher household wealth and maternal education were associated with reduced stunting risk but increased overweight risk. Lower CSO risk was associated with female [adjusted relative risk ratio (RRR): 0.84; 95% confidence interval (CI): 0.72, 0.98)], higher birth order (adjusted RRR: 0.68; 95% CI: 0.54, 0.85), higher wealth (adjusted RRR: 0.56; 95% CI: 0.41, 0.77), and the timely introduction of solid/semisolid/soft foods (adjusted RRR: 0.72; 95% CI: 0.60, 0.86). CONCLUSIONS: Although stunting dominates in LMICs, CSO reveals 2 distinct patterns. The paradox-where maternal education reduces stunting but may raise overweight-combined with the roles of wealth and timely complementary feeding in reducing CSO, necessitates integrated, context-specific "double-duty" interventions.
Peake SL, Lange K, Van Mourik N
… +4 more, Ridley EJ, Williams PJ, Chapman M, TARGET Investigators
Am J Clin Nutr
· 2026 Mar · PMID 41781080
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BACKGROUND: Evidence guiding calorie delivery in the critically ill with obesity is limited, and international guidelines are inconsistent. OBJECTIVES: This study aims to evaluate the relationship between enteral calorie...BACKGROUND: Evidence guiding calorie delivery in the critically ill with obesity is limited, and international guidelines are inconsistent. OBJECTIVES: This study aims to evaluate the relationship between enteral calorie delivery and mortality in critically ill patients with obesity. METHODS: Mechanically ventilated adult patients enrolled in The Augmented versus Routine Approach to Giving Energy Trial multicenter, double-blind, randomized trial evaluating 1.5 kcal/mL compared with 1 kcal/mL enteral nutrition at 1 mL/kg ideal body weight (IBW)/h were included in this post hoc analysis. Obesity was classified as BMI ≥30 kg/m. The primary outcome was the relationship between calorie delivery and 90-d mortality according to intensive care admission BMI with probability of death analyzed using a log binomial mixed model and reported as relative risk (RR) [95% confidence intervals (CIs)]. RESULTS: Thirty-six percent of patients (1436/3957) were obese at baseline, median (IQR) BMI: 34.9 (32.1, 40.0) kg/m. Mean (±SEM) daily calorie delivery for the group with obesity compared with the nonobese was 24.7 ± 0.2 and 24.2 ± 0.1 kcal/kg IBW, P = 0.018, respectively. By day 90, 313 of 1423 patients with obesity (22.2%) and 715/2491 patients without obesity (28.7%) had died; unadjusted RR: 0.766 (95% CI: 0.683, 0.860); P < 0.001. Results were unchanged after adjustment for trial site and baseline covariates. For both cohorts, probability of death by day 90 increased progressively below ∼20 kcal/kg IBW/d; however, between 20 and 36 kcal/kg IBW/d, probability of death was relatively stable. For the group with obesity, the threshold for probability of death varied according to the method of calculating body weight: ∼15 kcal/kg/d for obesity-adjusted body weight and ∼10 kcal/kg/d for actual body weight. CONCLUSIONS: In this post hoc study of critically ill patients receiving enteral nutrition, obesity confers a relative survival advantage to 90 d. Reduced calorie delivery is associated with increased risk of death in the group with obesity and the nonobese, but calorie threshold for the group with obesity varies according to the method of body weight calculation. This study was registered at TARGET trial clinicaltrials.gov number as NCT02306746.
Ceglia L, Konieczynski E, Danico E
… +7 more, Trinquart L, Koethe B, Xiang Q, Fielding RA, Evans WJ, Shankaran M, Dawson-Hughes B
Am J Clin Nutr
· 2026 May · PMID 41780731
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BACKGROUND: Aging is accompanied by reduced muscle protein synthesis and increased circulating acid, both of which contribute to declines in muscle health. OBJECTIVES: To determine the effects of whey protein (WP) and al...BACKGROUND: Aging is accompanied by reduced muscle protein synthesis and increased circulating acid, both of which contribute to declines in muscle health. OBJECTIVES: To determine the effects of whey protein (WP) and alkali (potassium bicarbonate, KHCO) supplementation on muscle performance and mass in healthy older adults. METHODS: In this randomized, 2 × 2 factorial, placebo-controlled study, healthy adults aged ≥65 years were assigned to either WP (1.5 g/kg/d) plus KHCO (81 mmol/d), WP plus placebo-KHCO, placebo-WP plus KHCO, or double placebo. Double leg press muscle power (primary outcome), physical performance, lean mass by dual energy x-ray absorptiometry, muscle mass by D-creatine dilution, and serum insulin-like growth factor 1 (IGF-1) were measured at baseline and 24 weeks. Primary analyses estimated main effects of WP compared with placebo-WP and KHCO compared with placebo-KHCO using factorial comparisons "at-the-margins," following CONSORT/SPIRIT recommendations for factorial trials. Between-group differences in the 24-wk outcomes were estimated using analysis of covariance adjusted for baseline value, age, and sex. RESULTS: In the intention-to-treat sample (n = 128), 47.7% were female, mean ± SD age was 74 ± 6 y, and baseline protein intake was 0.85 ± 0.30 g/kg/d. Neither WP nor KHCO affected muscle power compared with their respective placebo {WP to placebo-WP difference 4.7 watts [95% confidence interval (CI): -21.1,30.5; P = 0.72]; KHCO to placebo-KHCO difference -13.6 watts [95% CI: -39.6, 12.4; P = 0.30]}. No group differences were noted in physical performance or muscle mass. However, 24-wk mean IGF-1 level was higher in the WP and KHCO groups compared with their respective placebo [WP to placebo-WP difference 14.2 ng/mL (95% CI: 7.5, 21.0; P < 0.01); KHCO to placebo-KHCO difference 7.2 ng/mL (95% CI: 0.4, 13.9; P = 0.04)]. CONCLUSIONS: In healthy free-living older adults reporting a protein intake at the current recommended daily allowance, neither increasing protein to 1.5 g/kg/d with WP nor adding a KHCO supplement for 24 wk improved measures of muscle power, physical performance, or muscle mass despite achieving higher circulating IGF-1 levels. CLINICAL TRIAL REGISTRY NUMBER: This trial was registered as NCT04048616 at https://clinicaltrials.gov/study/NCT04048616?term=ceglia&rank=1.
Trejo-Domínguez A, Benitez L, Crovetto F
… +18 more, Casas R, Youssef L, Larroya M, Ruiz-León AM, Nakaki A, Genero M, Casas I, Novoa RH, Encabo N, Rahman M, Wang X, O'Sullivan JF, Hegarty NR, Vieta E, Gratacós E, Estruch R, Crispi F, Castro-Barquero S
Am J Clin Nutr
· 2026 May · PMID 41780730
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BACKGROUND: Preeclampsia is a pregnancy-specific condition affecting 2%-8% of pregnant females and a leading cause of maternal and perinatal morbimortality. High ultraprocessed food (UPF) consumption has been associated...BACKGROUND: Preeclampsia is a pregnancy-specific condition affecting 2%-8% of pregnant females and a leading cause of maternal and perinatal morbimortality. High ultraprocessed food (UPF) consumption has been associated with the development of noncommunicable chronic diseases, but evidence on pregnancy outcomes is scarce. OBJECTIVES: To study the association of maternal UPF consumption and the risk of preeclampsia. METHODS: This study is a secondary analysis of the IMPACT BCN, a randomized clinical trial including 1221 pregnant females at high risk for small for gestational age newborns, conducted in Barcelona, Spain. Among these, 812 participants with complete dietary data at 2 timepoints during pregnancy (between weeks 19-23 of gestation and weeks 34-36 of gestation) were included in this analysis and classified into tertiles of change in UPF consumption during pregnancy. Dietary UPF consumption was assessed using NOVA classification with a validated 151-item food frequency questionnaire. Preeclampsia was defined as high blood pressure plus targeted organ involvement. Analyses were performed using logistic regression models adjusted for potential confounding factors. RESULTS: Associations between change of UFP consumption during pregnancy and overall preeclampsia were observed across tertiles [odds ratio (OR): 2.29; 95% confidence interval (CI): 1.06, 4.97, P-trend 0.026], but not when UPF change was modeled as a continuous variable [OR: 1.04; 95% CI: 0.95, 1.14]. Among UPF subclasses, pre-prepared dishes were significantly associated with preeclampsia risk [OR: 2.36; 95% CI: 1.09, 5.12]. CONCLUSIONS: In a high-risk population, a higher change in dietary intake of UPF consumption from the second to third trimester of pregnancy was associated with a higher risk of preeclampsia. This trial was registered at clinicaltrials.gov as NCT03166332.
Nicholas KM, Tone A, Beal T
… +5 more, Zamborain-Mason J, Eneroth H, Öhrvik V, Troell M, Golden CD
Am J Clin Nutr
· 2026 May · PMID 41765288
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Increasing attention has focused on the capacity of current global food systems to provide accessible, affordable, and sustainable food to a growing human population, particularly amid ongoing climate and environmental c...Increasing attention has focused on the capacity of current global food systems to provide accessible, affordable, and sustainable food to a growing human population, particularly amid ongoing climate and environmental changes. Concerns about the dysfunction of the global food system have led to the development of several initiatives to estimate current and predict future global nutrient supplies based on various climate, production, and demand scenarios. Yet none adequately accounts for differences in nutrient bioavailability across food groups. As nutrient bioavailability varies substantially between plant-source foods (PSFs) and animal-source foods (ASFs), accounting for these differences has important implications for global nutrient supplies and the environmental costs associated with their production. In this perspective, we highlight the variability in estimated bioavailabity across PSFs and ASFs for 27 key nutrients and the limited accounting for bioavailability in major studies and nutrition recommendations. We conclude with a discussion of current best practices, highlighting avenues for future research to account for bioavailability and to more accurately evaluate and propose nutritionally adequate diets. This perspective suggests that, although existing data limitations should not preclude food systems researchers from accounting for bioavailability, a concerted effort is needed to develop more consistent and representative estimates of bioavailability across a variety of nutrients.
Taren D, Matzeller K, Gilley SP
… +6 more, Hernandez M, Kemp JF, Armstrong M, Doenges K, Krebs NF, Tang M
Am J Clin Nutr
· 2026 May · PMID 41763581
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BACKGROUND: Early infant feeding and weight gain can impact the development of chronic diseases. 1,5 anhydroglucitol (1,5-AG) is a measure of hyperglycemic excursions (HEs) and decreases during HEs due to increased urina...BACKGROUND: Early infant feeding and weight gain can impact the development of chronic diseases. 1,5 anhydroglucitol (1,5-AG) is a measure of hyperglycemic excursions (HEs) and decreases during HEs due to increased urinary excretion. OBJECTIVES: We hypothesized that HEs as measured by 1,5-AG are associated with infant rapid weight gain (RWG). METHODS: Infants from the Maternal and Infant Nutrition Trial, a randomized controlled feeding trial, participated in this exploratory secondary analysis. Saliva from 127 infants aged 5 mo was collected before the introduction of complementary foods. Saliva 1,5-AG concentration was measured using liquid chromatography-mass spectrometry and log transformed for statistical analyses. Demographic, anthropometric, and feeding mode [exclusively human milk-fed (EHMF), exclusively formula fed (EFF), and mixed fed (MF)] data were collected. RWG was classified as an increase in the weight-for-age z-score (WAZ) >0.67 from birth to 5 mo. RESULTS: Saliva 1,5-AG concentrations were negatively correlated with an increase of WAZ at 5 mo (r = -0.238, P = 0.01). EHMF and MF infants had significantly greater log transformed 1,5-AG μg/dl values (-0.252 ± 0.639 and 0.332 ± 0.912, respectively) than EFF infants (-1.754 ± 0.705, P = 0.001). Birth weight, but not sex, age, or maternal body mass index, was positively associated with WAZ changes. Saliva 1,5-AG concentrations remained inversely associated with the change in WAZ values in adjusted regression models when controlling for birth weight (β: -0.214; 95% confidence interval: -0.38, -0.05), but not when mode of feeding was included. The odds ratio for 1,5-AG (0.50; 95% confidence interval: 0.28, 0.90) was also significantly associated with RWG using logistic regression controlling for birth weight. CONCLUSIONS: These results suggest that human milk-fed infants have fewer HEs than EFF infants. Lower saliva 1,5-AG concentrations were associated with an increase in WAZ and RWG. Additional analyses are needed to evaluate the underlying drivers of HEs and their association with infant growth and health. This study was registered at clinicaltrials.gov as NCT05012930.
Roberts AK, Panyard DJ, Hislop B
… +4 more, Ward CP, Snyder MP, Gardner CD, Haddad F
Am J Clin Nutr
· 2026 May · PMID 41740726
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BACKGROUND: An emerging concern is that weight-loss interventions can lead to disproportionate muscle loss. Few studies accurately quantify changes in lean soft tissue (LST) after weight loss or investigate associated mo...BACKGROUND: An emerging concern is that weight-loss interventions can lead to disproportionate muscle loss. Few studies accurately quantify changes in lean soft tissue (LST) after weight loss or investigate associated molecular signatures. OBJECTIVES: The objectives of this study were to quantify LST change after a diet-based weight-loss intervention and identify protein biomarkers associated with LST retention. METHODS: Using the Diet Intervention Examining The Factors Interacting with Treatment Success cohort, we analyzed LST from dual-energy X-ray absorptiometry in three ways: 1) by body region (appendicular and total body), 2) after removing bias from fat-free adipose tissue (FFAT), and 3) relative to body size (percentage predicted LST). We also assessed 242 proteins measured in Olink Cardiovascular II, III, and Inflammation panels as predictors of LST change. RESULTS: A total of 374 participants (61% female; mean age ± standard deviation (SD): 39.4 ± 6.7 y; mean body mass index ± SD: 32.3 ± 3.2 kg/m) who had been randomly assigned to healthy low-fat or low-carbohydrate diets were pooled and analyzed at baseline and 6 mo. Total mass changed by -5.9 kg (95% confidence interval [CI]: -6.51, -5.29) in females and -7.18 kg (95% CI: -8.2, -6.16) in males. Appendicular LST change was modest at -0.80 kg (95% CI: -0.92, -0.69) in females and -1.02 kg (95% CI: -1.22, -0.83) in males. Appendicular LST losses comprised <10% of total mass loss after adjusting for FFAT. Appendicular LST relative to body size also increased at 6 mo (P < 0.001). Changes in 10 proteins in females and 27 in males predicted LST change (5% false discovery rate), with protein delta homolog 1 (DLK1)-an inhibitor of adipogenesis-as the top predictor. CONCLUSIONS: Change in appendicular LST, a surrogate for skeletal muscle, was modest after 6 mo of diet-based weight loss. DLK1, an inhibitor of adipogenesis, emerged as the top protein biomarker linked to LST retention. This trial was registered at clinicaltrials.gov as NCT01826591.
Bondonno CP, Sundqvist ML, Shinde S
… +5 more, Croft K, Hodgson JM, Carlström M, Weitzberg E, Lundberg JO
Am J Clin Nutr
· 2026 May · PMID 41724486
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BACKGROUND: Inorganic nitrate from dietary sources has raised health concerns due to its possible conversion into carcinogenic N-nitrosamines, leading to strict regulations on nitrate concentrations in food and drinking...BACKGROUND: Inorganic nitrate from dietary sources has raised health concerns due to its possible conversion into carcinogenic N-nitrosamines, leading to strict regulations on nitrate concentrations in food and drinking water. OBJECTIVES: In this study, which was a part of a larger randomized controlled trial, we evaluated urinary excretion of N-nitrosamines in response to daily dietary nitrate intake over a 5-wk period using 2 different forms of nitrate administration. METHODS: A total of 231 participants with mild hypertension were randomly assigned into 3 groups. Group 1 (n = 78) consumed vegetables low in nitrate along with a placebo capsule (300 mg potassium chloride). Group 2 (n = 77) consumed the same low-nitrate vegetables plus a potassium nitrate supplement (300 mg). Group 3 (n = 77) consumed nitrate-rich leafy green vegetables providing 300 mg nitrate daily plus the placebo capsule. Twenty-four-hour urine samples were collected before and after the intervention. Nitrate was measured with high-pressure liquid chromatography and N-nitrosamine concentrations were quantified using ultra high-pressure liquid chromatography-tandem mass spectrometry. A paired t-test was used for statistical analyses. RESULTS: As expected, urinary nitrate increased ∼5- to 6-fold in participants consuming nitrate-rich vegetables or potassium nitrate compared with those consuming potassium chloride. Total urinary excretion of N-nitrosamines was low across all groups under basal conditions (<5 μg/24 h) and did not significantly change after the intervention. A similar lack of change was observed for each of the 7 individual N-nitrosamine species measured. CONCLUSIONS: These findings suggest that a 5-wk dietary intake of nitrate mostly exceeding the current consensus for upper limit of the acceptable daily intake (3.7 mg/kg/d), whether provided as a vegetable source or as a nitrate salt, does not increase urinary excretion of N-nitrosamines. This study was registered at clinicaltrials.gov as NCT02916615.
Am J Clin Nutr
· 2026 Apr · PMID 41722780
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BACKGROUND: The Planetary Health Diet (PHD), proposed by the EAT-Lancet Commission, seeks to optimize health while preserving the environment. Its benefits for chronic disease prevention are established, but its impacts...BACKGROUND: The Planetary Health Diet (PHD), proposed by the EAT-Lancet Commission, seeks to optimize health while preserving the environment. Its benefits for chronic disease prevention are established, but its impacts on birth outcomes are unclear. OBJECTIVES: To assess the association between PHD adherence during pregnancy and newborn outcomes. METHODS: This prospective study included 1431 mother-infant dyads from the New Hampshire Birth Cohort Study. Diet during pregnancy was assessed once at 24-28 wk gestation via a food-frequency questionnaire to calculate the Planetary Health Diet Index (PHDI). Gestational age, birth weight, length, and head circumference were abstracted from medical records. Dietary patterns were identified through self-organizing maps using PHDI components. Associations between PHD and birth outcomes were modeled using multivariable regressions. RESULTS: Highest PHDI tertile participants were older, had lower prepregnancy BMI, were more often nonsmokers, and had higher neighborhood socioeconomic status. In adjusted regression models, 10-unit increase in PHDI was associated with higher birth weight [β = 24.4 g, 95% confidence interval (CI): 1.21, 43.6], longer gestation (β = 0.10 wk; 95% CI: 0.03, 0.17) and reduced odds of being preterm [odds ratio (OR) = 0.86; 95% CI: 0.74, 0.98]. Three distinct dietary patterns were identified: plant-based, saturated fat-rich, and animal/added sugar-rich. Compared with the plant-based profile, the saturated fat-rich profile was associated with shorter gestation and higher odds of low birth weight (OR = 2.54; 95% CI: 1.23, 5.44). The animal/added sugar-rich profile correlated with lower birth weight (β = -82.4 g; 95% CI: -149.2, -15.6) and shorter length (β = -0.46 cm; 95% CI: -0.84, -0.08). Both nonplant-based profiles increased the odds of preterm birth (OR = 1.92 and OR = 1.66, respectively). CONCLUSIONS: Originally proposed for chronic disease prevention and planetary sustainability, higher adherence to the PHD during pregnancy may also benefit birth outcomes, particularly lower odds of preterm birth.