The American Journal Of Clinical Nutrition[JOURNAL]
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200 papers
Plasma n6 polyunsaturated fatty acid levels and risk for dementia: a prospective observational study from the United Kingdom Biobank.
Sala-Vila A, Tintle N, Westra J … +5 more , DeJong E, Clark T, Miller P, Belury MA, Harris WS
Am J Clin Nutr · 2026 Apr · PMID 41617088 · Publisher ↗
BACKGROUND: Some recent observational studies have linked higher blood linoleic acid (LA) concentration with lower risk of cardiometabolic diseases. However, these associations have not been observed for other n-6 polyun...
BACKGROUND: Some recent observational studies have linked higher blood linoleic acid (LA) concentration with lower risk of cardiometabolic diseases. However, these associations have not been observed for other n-6 polyunsaturated fatty acids (PUFAs), which, in some settings, have been linked to higher disease risk, and thus the controversy over the health effects of n-6 PUFAs remains. Dementia is a paradigmatic case of it. OBJECTIVES: To investigate the association of LA and non-LA n-6 PUFAs with the risk of incident dementia. METHODS: We included 273,795 participants from the UK Biobank free of dementia at baseline for whom plasma n-6 PUFAs data were available. We modeled the relationships between LA and, separately, non-LA n-6 PUFAs and incident dementia by quintile (Q) and using continuous linear model using Cox proportional hazards models, adjusting for variables reported to relate to incident dementia. RESULTS: A total of 5799 incident dementia cases were ascertained (median follow-up: 15.06 y; 25 and 75 percentiles: 14.22 to 15.80 y). Compared with participants at Q1 (lowest quintile) of LA, those at Q5 (highest quintile) showed a lower risk of dementia [adjusted hazard ratio (95% confidence interval) = 0.82 (0.74, 0.91)]. In contrast, participants at Q5 of plasma non-LA n-6 PUFAs were at a higher risk of incident dementia compared with Q1 [1.21 (1.10, 1.33)]. Similar patterns were observed when considering LA and non-LA n-6 PUFAs continuously. CONCLUSIONS: We observed heterogeneous associations between different types of n-6 PUFAs and risk of dementia, supporting the increasing view that n-6 PUFAs should not be treated homogeneously. Future research should investigate whether dietary LA (which drives plasma LA concentrations) may help reduce risk for dementia. REGISTRATION: This research has been conducted using the UK Biobank Resource under Application Number 85092.
Associations between breastfeeding, childhood BMI and pubertal onset: findings from a prospective cohort study.
Ramirez-Luzuriaga MJ, Sinha M, Hanson RL
Am J Clin Nutr · 2026 Mar · PMID 41611091 · Full text
BACKGROUND: Early onset of puberty, often characterized by an accelerated linear growth spurt, is a recognized risk factor for a range of metabolic and cardiovascular conditions. Although increased breastfeeding has been...
BACKGROUND: Early onset of puberty, often characterized by an accelerated linear growth spurt, is a recognized risk factor for a range of metabolic and cardiovascular conditions. Although increased breastfeeding has been associated with later onset of puberty, the potential mediating role of prepubertal BMI in these associations remains poorly understood. OBJECTIVES: This study aimed to examine the longitudinal associations of breastfeeding duration with adolescent growth parameters, including pubertal timing, and to assess whether prepubertal BMI mediates these associations. METHODS: Adolescent growth parameters were estimated from the height growth trajectories of 613 participants (312 females and 301 males) across 6 cohorts in the Environmental Influences on Child Health Outcomes Program. These parameters were derived by fitting the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, in participants with ≥3 height measurements spanning the whole period of growth. Linear regression models were used to examine associations of breastfeeding duration with adolescent growth parameters. Mediation analysis was conducted to explore whether prepubertal BMI mediated the association between breastfeeding and pubertal timing. RESULTS: After adjusting for socioeconomic, maternal, and infant characteristics, children exclusively breastfed for ≥3 mo reached age at peak velocity and age at maturation later than those who were not exclusively breastfed [β = 0.32 y; 95% confidence interval (CI): 0.05, 0.60, and β = 0.30 y; 95% CI: 0.04, 0.56, respectively]. In adjusted models, each additional 3 mo of any breastfeeding was associated with a later age at take-off (β = 0.07 y; 95% CI: 0.00, 0.15), and later age at peak velocity (β = 0.11 y; 95% CI: 0.01, 0.20). Prepubertal BMI did not significantly mediate these associations. CONCLUSIONS: Exclusive breastfeeding and longer breastfeeding duration were associated with later onset of puberty in boys and girls. Prepubertal BMI did not mediate the observed associations.
Health-related quality of life, compliance and sustained adherence on a low-carbohydrate high-fat diet compared with a high-carbohydrate low-fat diet in people with type 2 diabetes.
Petersen EE, Hansen JK, Torp N … +15 more , Gram-Kampmann E, Andersen P, Johansen S, Villesen IF, Bech KT, Thorhauge KH, Schnefeld HL, Gjøl CMB, Jensen EL, Detlefsen S, Højlund K, Thiele M, Israelsen M, Krag A, Hansen CD
Am J Clin Nutr · 2026 Apr · PMID 41611090 · Full text
BACKGROUND: Health-related quality of life (HRQoL) is a central aspect of overall health and a crucial factor in dietary interventions, as it may determine both dietary compliance and sustained adherence. OBJECTIVES: We...
BACKGROUND: Health-related quality of life (HRQoL) is a central aspect of overall health and a crucial factor in dietary interventions, as it may determine both dietary compliance and sustained adherence. OBJECTIVES: We assessed the effect on HRQoL between: 1) the low-carbohydrate high-fat (LCHF) diet and 2) the high-carbohydrate low-fat (HCLF) diet and evaluated the impact on dietary compliance and sustained adherence. METHODS: This is a prespecified secondary analysis from a randomized controlled trial in people with type 2 diabetes. Participants were randomly assigned 2:1 to follow either LCHF or HCLF for 6 mo with a postintervention visit 9 mo after inclusion. Liver biopsies were performed at baseline and after 6 mo, the Diabetes-39 HRQoL questionnaire, standard clinical and compliance assessments were conducted at baseline, 3 mo, 6 mo, and 9 mo (postintervention). Sustained adherence was assessed at the postintervention visit. RESULTS: We randomly assigned 165 participants; 96 (58%) were female. At baseline, the median age was 56 [interquartile range (IQR) 50-63] y, mean body mass index was 33 + 7 kg/m, total median HRQoL score was 88 (IQR, 70-111), mean hemoglobin A1c was 56+10 mmol/mol, and 141 (88%) had metabolic dysfunction-associated steatotic liver disease. After 6-mo intervention, HRQoL improved in both groups {LCHF: -14.5 [95% confidence interval (CI): -20.7, -8.36]; P < 0.001; HCLF; -13.7 (95% CI: -22.7, -4.6); P = 0.003} with no mean difference in change between groups (Δ) P = 0.855. Higher improvements in HRQoL were associated with a higher compliance with the diets (Spearman's rho; -0.183; P = 0.0378) and increased the likelihood of sustained adherence to the LCHF diet. CONCLUSIONS: HRQoL improved in both dietary intervention groups with no difference between groups. Dietary compliance was associated with improved HRQoL and may play a role in sustained adherence to the LCHF diet. This trial was registered at clinicaltrials.gov as NCT03068078.
Changes in dietary sodium knowledge, attitudes and behaviors among Canadian adults in 2011 and 2024: a repeated cross-sectional study.
Al Ghali R, Prashad M, Lou W … +2 more , L'Abbe M, Arcand J
Am J Clin Nutr · 2026 Apr · PMID 41611089 · Full text
BACKGROUND: Excess sodium intake is a leading modifiable risk for noncommunicable diseases. Despite some national sodium-reduction initiatives, no population-level updates to sodium-related knowledge, attitudes, behavior...
BACKGROUND: Excess sodium intake is a leading modifiable risk for noncommunicable diseases. Despite some national sodium-reduction initiatives, no population-level updates to sodium-related knowledge, attitudes, behaviors (KAB) have been available since 2011. OBJECTIVES: This study aimed to compare sodium-related KAB among Canadian adults in 2011 and 2024 and examine differences by sex and age, hypothesizing limited changes due to insufficient national sodium-reduction initiatives. METHODS: Repeated cross-sectional national surveys were conducted in 2011 (n = 2603) and 2024 (n = 3267), readministering the same sodium KAB questions from the 2011 survey. Knowledge responses were coded as correct/incorrect, and 5-point Likert-scale items were recoded or dichotomized. Data were weighted to the Canadian census. Rao-Scott adjusted χ, t-tests and regression models assessed changes over time, stratifying by sex and age. RESULTS: The proportion of adults actively limiting sodium intake declined from 57.4% in 2011 to 37.3% in 2024 (P < 0.001). Concurrently, engagement in nearly all sodium-reduction behaviors decreased in 2024, including avoiding processed foods (69.3%-52.3%), not adding salt at the table (69.2%-58.1%), avoiding salt during cooking (62.3%-43.4%) (all P < 0.001), and reading Nutrition Facts labels (54.2%-49.6%, P = 0.005). Paradoxically, overall population sodium concern remained high and unchanged (66.3%-65.9%, P = 0.812). Food label interpretation and awareness of recommended sodium intake improved (P < 0.001), but knowledge of health-related conditions linked to sodium such as blood pressure, heart disease, and stroke decreased (all P < 0.001). Reported barriers to sodium reduction included cost, taste, time constraints, and lack of social support. CONCLUSIONS: Many indices of sodium-related KAB deteriorated from 2011 to 2024 among Canadian adults, despite their continued concern about sodium intake. These findings highlight a widening knowledge-to-action gap and reinforce the need for comprehensive public health efforts to support population-wide dietary sodium reduction.
Fiber intake and laxation in people with normal bowel function: a systematic review.
Balk EM, Couch E, Mai HJ … +9 more , Chen Y, Adam GP, Kanaan G, Caputo EL, Trikalinos TA, Williams G, Duncanson K, Talley NJ, Lichtenstein AH
Am J Clin Nutr · 2026 Mar · PMID 41611088 · Full text
BACKGROUND: Optimal evidence-based dietary recommendations for dietary fiber have not been established. OBJECTIVES: This study aims to conduct a systematic review of fiber and gut motility (laxation) in noninfants with n...
BACKGROUND: Optimal evidence-based dietary recommendations for dietary fiber have not been established. OBJECTIVES: This study aims to conduct a systematic review of fiber and gut motility (laxation) in noninfants with normal bowel function. METHODS: We searched PubMed, Embase, and CINAHL from inception through 4 March, 2025, and existing systematic review reference lists. We included randomized controlled trials (RCTs) in the general population without bowel dysfunction that compared fiber amounts or types and assessed stool consistency, fecal weight, fecal frequency, or gut transit time. We categorized fibers according to their solubility, viscosity, and fermentability and performed hierarchical Bayesian regression models and spline analyses across reported total and added fiber intake doses, with subanalyses by fiber type. We assessed study risk of bias and strength of evidence (SoE). RESULTS: We identified 113 eligible trials, with low or moderate risk of bias. Models provided moderate SoE that increasing fiber intake (per g/d total fiber) yields softening stool consistency [0.013 units, 95% credible interval (CrI): 0.009, 0.016 on the Bristol Stool Scale], increasing total fecal weight (1.76 g/d, 95% CrI: 1.58, 1.94) and dry fecal weight (0.47 g/d, 95% CrI: 0.42, 0.51), increasing fecal frequency (0.053 additional bowel movements/wk, 95% CrI: 0.042, 0.065), and shortening gut transit times (-0.24 h, 95% CrI: -0.36, -0.12). Associations between fiber intake and outcomes varied across fiber doses and type. Low-solubility and low-fermentability fibers had the strongest associations with laxation outcomes, with low to medium SoE. However, findings are indirect, based on models, and there is insufficient evidence in specific subpopulations. CONCLUSIONS: RCTs support small to modest effects of dietary fiber on laxation in generally healthy people with normal bowel function. Low-solubility and low-fermentability fibers yielded the strongest effects. Future studies should better characterize fiber properties, assess wider ranges of fiber doses, and comprehensively report participants' total and background fiber intake. This study was registered at PROSPERO as CRD42024522380.
Folic acid fortification of iodized salt improves the folate status of nonpregnant adult Ethiopian females and does not impair their iodine status: a community-based, household-randomized, dose-response trial.
Tessema M, Nane D, Woldeyohannes M … +11 more , Agbemafle I, McDonald CM, Arnold CD, Fereja M, Challa F, Martinez H, Tesfaye B, Tollera G, Arabi M, Brown KH, Collaborating Laboratories
Am J Clin Nutr · 2026 Mar · PMID 41611087 · Publisher ↗
BACKGROUND: Folic acid (FA) fortification of cereal grains reduces the prevalence of folate insufficiency among adult females and related neural tube defects (NTDs) in their offspring. However, fortifiable cereal grains...
BACKGROUND: Folic acid (FA) fortification of cereal grains reduces the prevalence of folate insufficiency among adult females and related neural tube defects (NTDs) in their offspring. However, fortifiable cereal grains have limited reach in many lower-income countries, so additional fortification options need to be developed and evaluated. OBJECTIVES: This study assessed the effects of FA fortification of iodized salt on women's discretionary salt intakes, biomarkers of folate and iodine status, and the occurrence of adverse events. METHODS: We conducted a community-based, 3-arm, household-randomized dose-response trial among 360 nonpregnant Ethiopian females 18 to 49 y of age. We delivered iodized salts containing 32 parts per million (ppm) iodine and 99, 36, or 0 ppm FA to households bi-weekly for 26 wk. We measured participants' fasting red blood cell (RBC) folate, serum folate, homocysteine, thyroglobulin, vitamin B-12 biomarkers, glucose, and insulin, and urinary iodine/creatinine ratios before and during the intervention. We quantified participants' salt intakes using weighed food records, and we systematically recorded adverse events. RESULTS: The overall median (IQR) RBC folate concentration at baseline was 476 (371, 580) nmol/L. Participants' mean usual intakes of study salts (7.8 ± 1.8 g/d) did not differ by study arm (P = 0.58). The final median (IQR) RBC folate concentrations were 1275 (1120, 1521) nmol/L, 1004 (819, 1212) nmol/L, and 468 (366, 596) nmol/L in the respective study arms (all significantly different, P < 0.001). There were no group-wise differences in urinary iodine/creatinine ratios, serum thyroglobulin, insulin resistance, or reported adverse events. CONCLUSIONS: FA fortification of salt is an effective and safe method to improve women's folate status and thereby reduce the risk of NTD-affected pregnancies. This trial was registered on the ClinicalTrials.gov website (registration number NCT06223854): https://clinicaltrials.gov/study/NCT06223854?term=Transcobalamin%20Deficiency&viewType=Table&rank=4.
Predictive equations commonly used in the clinic underestimate resting energy expenditure compared with whole-room indirect calorimetry in colorectal cancer survivors.
Eklo RR, Alavi DT, Konglevoll DM … +5 more , Kolle Å, Henriksen HB, Rising R, Blomhoff R, Olsen T
Am J Clin Nutr · 2026 Mar · PMID 41611086 · Full text
BACKGROUND: Accurate methods for estimating resting energy expenditure (REE) are important to ensure adequate nutritional treatment in colorectal cancer (CRC) survivors. OBJECTIVES: This study aims to determine the agree...
BACKGROUND: Accurate methods for estimating resting energy expenditure (REE) are important to ensure adequate nutritional treatment in colorectal cancer (CRC) survivors. OBJECTIVES: This study aims to determine the agreement between REE estimated by commonly used predictive equations and by whole-room indirect calorimetry (WRIC). METHODS: This cross-sectional study included 31 CRC survivors {age: 53-78 y; mean [standard deviation (SD)]; body mass index 28.7 [4.28] kg/m}, who underwent curative surgery. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Predicted REE from equations in clinical use and derived from DXA and bioelectrical impedance analysis (BIA) were compared against REE measured by 30-min WRIC. Equations included Harris-Benedict, Mifflin-St. Jeor, Food and Agriculture Organization (FAO)/World Health Organization (WHO)/United Nations University (UNU), Henry, Mifflin-St. Jeor and FAO/WHO/UNU. Paired sample t-test, Lin's concordance correlation coefficient, and Bland-Altman analysis were used to determine the agreement between measured REE and predicted REE. Accuracy was defined as the percentage of predicted REE values that fell within ± 10% of REE. RESULTS: Mean (SD) REE was 1710 kcal/d (353), and respiratory quotient was 0.79 (0.05). Most equations underestimated REE. Overall, Harris-Benedict, Henry, and FAO/WHO/UNU showed the best overall agreement with REE. However, these equations showed low accuracy with 65%, 68%, and 62% of predicted REE values within ± 10% of REE, respectively. CONCLUSIONS: Most predictive equations tended to underestimate REE in CRC survivors compared with REE. The Harris-Benedict, Henry and FAO/WHO/UNU equations showed both best accuracy and agreement with WRIC. They were still inaccurate, with individual variability for a relevant part of the sample. Future studies need to develop improved predictive equations for CRC survivors. This study was registered at clinicaltrials.gov as NCT01570010 (https://clinicaltrials.gov/study/NCT01570010?locStr=Norway&country=Norway&cond).
Corrigendum to Sex differences in the inhibition of γ-tocopherol metabolism by a single dose of dietary sesame oil in healthy subjects [Am J Clin Nutr 2008; 87: 1723-1729].
Frank J, Lee S, Leonard SW … +3 more , Atkinson JK, Kamal-Eldin A, Traber MG
Am J Clin Nutr · 2026 Mar · PMID 41587757 · Publisher ↗
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Bridging Knowledge and Care: A Summer in Clinical Nutrition.
Bedor S, Twillman G, Tuncer D … +1 more , Owen-Michaane M
Am J Clin Nutr · 2026 Apr · PMID 41581666 · Publisher ↗
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Leucine supplementation does not attenuate the decline in daily muscle protein synthesis rates or preserve leg muscle mass during leg immobilization in young or older adults: a double-blind randomized trial.
Churchward-Venne TA, Pinckaers PJ, Smeets JS … +8 more , Marzuca-Nassr GN, Gorissen SH, Fuchs CJ, Senden JM, Goessens JP, Gijsen AP, Wodzig WK, van Loon LJ
Am J Clin Nutr · 2026 Apr · PMID 41580240 · Full text
BACKGROUND: Muscle disuse leads to muscle atrophy that has been attributed to declines in basal and postprandial muscle protein synthesis (MPS) rates. Leucine regulates MPS and may attenuate disuse-induced declines in MP...
BACKGROUND: Muscle disuse leads to muscle atrophy that has been attributed to declines in basal and postprandial muscle protein synthesis (MPS) rates. Leucine regulates MPS and may attenuate disuse-induced declines in MPS rates and muscle mass. OBJECTIVES: The purpose of this study was to evaluate the capacity of leucine supplementation to attenuate disuse-induced declines in MPS rates and muscle mass in young and older adults. METHODS: In a randomized, double-blind, parallel-group design, 24 young (23 ± 4 y) and 24 older (69 ± 4 y) recreationally active adults (equal sex distribution) underwent 3 d of unilateral knee immobilization (leg casting) and received a leucine [group of adult study participants who supplemented with 5 g of leucine 3 × daily with each main meal during 3 d of unilateral knee immobilization by means of a full leg cast (LEU)] or energy-matched carbohydrate [group of adult study participants who supplemented with 5 g of carbohydrate 3 × daily with each main meal during 3 d of unilateral knee immobilization by means of a full leg cast (PLA)] supplement. Preimmobilization and postimmobilization, quadriceps muscle cross-sectional area (CSA) was assessed in the immobilized (IM) and nonimmobilized (NO-IM) leg by computed tomography. MPS rates were assessed in both legs during immobilization via HO coupled with saliva, blood, and muscle biopsy sampling. RESULTS: In young and older adults, MPS rates were ∼15% and ∼23% lower in the IM compared with NO-IM leg (1.28 ± 0.29 compared with 1.50 ± 0.26 and 1.10 ± 0.16 compared with 1.46 ± 0.28%/d, respectively; leg: both P < 0.001), with no differences between LEU compared with PLA treatments (treatment: P = 0.932 and P = 0.742, respectively). CSA decreased by ∼1.2% and ∼1.1% in the IM leg in young and older adults (from 7162 ± 1148 to 7076 ± 1129 mm and from 5813 ± 1092 to 5750 ± 1096 mm, respectively; leg × time interaction: both P < 0.001), with no differences between LEU compared with PLA (treatment: P = 0.374 and P = 0.998). IM leg MPS rates were lower in older compared with young adults [difference: -0.18 (95% confidence interval: -0.31, -0.04) %/d; P = 0.013]. No differences were observed in the absolute (mm) or relative (%) decline in CSA between young and older adults (both P > 0.05). CONCLUSIONS: Leucine supplementation does not attenuate the decline in daily MPS rates or muscle mass during short-term limb immobilization in young or older adults. Clinical Trial Register No. (Netherlands Trial Register): NL-OMON45771.
Metabolome contribution to sex differences in the link between alcohol consumption and type 2 diabetes: a prospective analysis in the Hispanic Community Health Study/Study of Latinos.
Wang B, Luo K, Ma W … +9 more , Zhang Y, Cordero C, Pirzada A, Daviglus M, Perreira KM, Yu B, Boerwinkle E, Kaplan RC, Qi Q
Am J Clin Nutr · 2026 Mar · PMID 41577136 · Full text
BACKGROUND: Light-to-moderate alcohol consumption has been linked to improved insulin resistance and lower type 2 diabetes (T2D) risk predominantly in females but not males. Potential mechanisms underlying this sex diffe...
BACKGROUND: Light-to-moderate alcohol consumption has been linked to improved insulin resistance and lower type 2 diabetes (T2D) risk predominantly in females but not males. Potential mechanisms underlying this sex difference remain unclear. OBJECTIVES: This study evaluated associations of sex-specific alcohol-associated metabolomic signatures (AMSs) with insulin resistance and T2D risk in United States Hispanic/Latino adults. METHODS: We analyzed serum metabolome data in the Hispanic Community Health Study/Study of Latinos, a prospective, multicenter, community-based study of Hispanics/Latinos, aged 18 to 74 y old, enrolled from 4 United States metropolitan areas between 2008 and 2011. Sex-specific AMSs were developed using an elastic net to identify serum metabolites uniquely associated with alcohol consumption in females (n = 2747) and males (n = 1737) without diabetes at baseline, respectively, excluding heavy drinkers. Poisson regression was used to examine the cross-sectional associations of AMSs with insulin resistance (homeostasis model assessment of insulin resistance ≥2.5) and the prospective associations of AMSs with T2D risk in females (n = 2265) and males (n = 1290) over ∼6 y, adjusting for demographic, socioeconomic, and behavioral factors. RESULTS: We identified 40 and 54 metabolites uniquely associated with light-to-moderate alcohol consumption in females and males, respectively. Cross-sectionally, female-specific AMS (FAMS) was inversely associated with insulin resistance and various T2D-related metabolic traits in females, whereas male-specific AMS was positively associated with insulin resistance and metabolic traits in males. Prospectively, females in the highest quartile of FAMS had ∼82% (95% confidence interval: 70%, 89%) lower T2D risk compared with those in the lowest quartile. The favorable association between alcohol consumption and risk of T2D was attenuated after adjusting for FAMS. In males, there was no statistically significant association between male-specific AMS and T2D risk. CONCLUSIONS: Our results suggested distinct blood metabolomic signatures associated with alcohol consumption in females and males, which might contribute to sex differences in the relationship between alcohol consumption and T2D.
Interactions between genetic predisposition to obesity, insulin resistance and type 2 diabetes risk, and food or beverage intake for incident type 2 diabetes: European Prospective Investigation into Cancer and Nutrition (EPIC) InterAct case-cohort study.
Li SX, Imamura F, Sharp SJ … +29 more , Schulze MB, Zheng JS, Amiano P, Ardanaz E, Bergmann MM, Chirlaque MD, Fagherazzi G, Franks PW, Grioni S, Ibsen DB, Jakszyn P, Johansson I, Katzke VA, Laouali N, Mancini FR, Overvad K, Palli D, Panico S, Redondo-Sánchez D, Ricceri F, Rolandsson O, Srour B, Tjønneland A, Tong TY, van der Schouw YT, Riboli E, Langenberg C, Forouhi NG, Wareham NJ
Am J Clin Nutr · 2026 Mar · PMID 41548598 · Full text
BACKGROUND: Limited evidence exists for effect modification of genetic characteristics on the associations of food consumption and incident type 2 diabetes (T2D). OBJECTIVES: We aimed to investigate whether the food-T2D...
BACKGROUND: Limited evidence exists for effect modification of genetic characteristics on the associations of food consumption and incident type 2 diabetes (T2D). OBJECTIVES: We aimed to investigate whether the food-T2D association would vary by genetic susceptibility to metabolic traits. METHODS: We analyzed data from 9542 incident T2D cases and a subcohort of 12,477 participants nested within the 340,234-participant cohort recruited in 1991-1998 and followed up for 10.9 y on average in 8 European countries. Polygenic risk scores (PRSs) for higher body mass index, insulin resistance, and T2D were constructed. Fifteen dietary variables potentially associated with T2D, obtained with cohort-specific self-reported dietary assessment, were examined: fruits, green leafy vegetables, root vegetables, wholegrains, rice, legumes, nuts and seeds, fermented dairy, red meat, processed meat, fish, eggs and egg products, sugar-sweetened beverages, coffee, and tea. A cross-product term between each PRS and each food/beverage was evaluated by genotyping chip and country with Prentice-weighted Cox regression for incident T2D, and stratum-specific estimates were meta analyzed, followed by Benjamini-Yekutieli multiple-testing correction. RESULTS: Accounting for multiple tests of 3 PRSs × 15 dietary items, no evidence of statistical interaction was evident on either a multiplicative or additive scale, with exp(β for a multiplicative interaction) (95% confidence interval) ranging from 0.84 (0.64, 1.10) (root vegetables and PRS for T2D) to 1.45 (0.78-2.76) (fish and PRS for T2D). CONCLUSIONS: Genetic susceptibility to high-risk metabolic traits did not modify the diet-T2D associations in European populations. Acknowledging the limitations of current PRS-based methods to detect gene-diet interactions, research should continue into the potential for precision nutrition and tailored food-based dietary guidance for T2D prevention.
Biomarkers for dietary fatty acid densities among postmenopausal United States females derived using a habitual-diet human feeding study.
Prentice RL, Tinker LF, Neuhouser ML … +11 more , Lampe JW, Raftery D, Gowda GN, Song X, Navarro SL, Huang Y, Vasan S, Orchard TS, Brasky TM, Manson JE, Zheng C
Am J Clin Nutr · 2026 Mar · PMID 41544713 · Full text
BACKGROUND: Although measures of blood and tissue fatty acid (FA) concentrations are available, objective measures of dietary FA densities (grams per kilocalories) are generally lacking. OBJECTIVES: We aimed to explore t...
BACKGROUND: Although measures of blood and tissue fatty acid (FA) concentrations are available, objective measures of dietary FA densities (grams per kilocalories) are generally lacking. OBJECTIVES: We aimed to explore the development of biomarkers for specific and composite dietary FA densities, not including contributions from dietary supplements, using metabolite profiles from serum and 24-h urine, along with separately measured serum phospholipid FA concentrations in the Women's Health Initiative. METHODS: Potential biomarker equations were based on linear regression of feeding study dietary FA densities on metabolite concentrations, each log-transformed, among participants in a habitual-diet human feeding study (n = 153) within the Women's Health Initiative. Corresponding biomarker equations were also considered for total SFA, MUFA, and PUFA densities and for total n-3 and n-6 PUFA densities. Dietary FA density estimates derived from these equations were evaluated by correlation with feeding study intake densities, and by other important biomarker criteria. RESULTS: Regression cross-validated R values >30% for specific SFAs were 64.7 butyric, 60.9 caprioc, 48.7 caprylic, 53.0 capric, 39.9 lauric, 61.0 myristic, 42.2 palmitic, 34.2 stearic, 34.8 arachidic, 49.9 decosanoic; for specific MUFAs were 31.3 oleic; and for specific PUFAs were 51.7 linoleic, 50.1 α-linolenic, 39.7 arachidonic, 40.2 EPA, 53.5 decosapentaenoic acid, and 47.9 DHA. Corresponding values were 46.4, 52.8, 46.1, and 52.4 for total SFA, total PUFA, total n-3, and total n-6 densities. Many FA density equations had contributions from multiple metabolites, mostly serum metabolites, and from total energy expenditure. Sensitivity and specificity criteria are plausibly satisfied for proposed biomarkers, based on the feeding study design and on the sets of selected metabolites. CONCLUSIONS: Combinations of log-transformed metabolite concentrations can lead to objective intake density estimates for multiple FAs in the diets of United States postmenopausal females, with relevance to the reliable study of dietary FA densities and chronic disease risk. This study was registered at clinicaltrials.gov as NCT00000611 https://clinicaltrials.gov/study/NCT00000611).
Maternal smoking, lactation, and risk of incident irritable bowel syndrome in offspring: a large-scale prospective cohort study.
Li Y, Liu S, Zhang Q … +3 more , Zhang S, Zhu S, Wu S
Am J Clin Nutr · 2026 Mar · PMID 41544712 · Publisher ↗
BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder; however, evidence regarding its association with early-life factors is lacking. OBJECTIVES: We aimed to examine the association...
BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder; however, evidence regarding its association with early-life factors is lacking. OBJECTIVES: We aimed to examine the association between early-life factors, including maternal smoking and lactation, and risk of incident IBS in offspring within a large prospective cohort. METHODS: Participants free of IBS at baseline and with available data on maternal smoking and lactation were included. Maternal smoking was defined as regular cigarette smoking during the perinatal period, and lactation was defined as any breastfeeding during the infant period. Participants exposed to maternal smoking or to lactation during infancy were defined as exposure groups. The primary outcome was incident IBS. Cox proportional hazards model was conducted to estimate the associated risk. RESULTS: Among 290,962 participants, 81,186 (27.90%) participants were exposed to maternal smoking and 211,954 (72.85%) were exposed to lactation as infants. Over a median of 14.6 y of follow-up, 6222 incident IBS cases were identified. After multivariable adjustment, participants with maternal smoking had a 16.0% higher risk of incident IBS compared with those without maternal smoking [hazard ratio (HR): 1.16; 95% confidence interval (CI): 1.09, 1.22], whereas those exposed to lactation had a 9% lower risk of IBS than those not exposed to lactation (HR: 0.91; 95% CI: 0.86, 0.97). Notably, participants exposed to both maternal smoking and no lactation exhibited an even higher risk of developing IBS compared with those with lactation exposure but without maternal smoking (HR: 1.23; 95% CI: 1.14, 1.34). Additionally, an evidently higher IBS risk was observed in those with both maternal smoking and individual previous/current smoking (HR: 1.30; 95% CI: 1.21, 1.41). CONCLUSIONS: Maternal smoking is associated with a higher risk of incident IBS, whereas exposure to lactation is associated with a lower risk. These findings underscore the potential impact of early-life exposures on gastrointestinal health.
Concurrent and predictive validity of different tools for malnutrition diagnosis in adult critically ill patients: a systematic review with meta-analysis of observational studies.
Stello BB, Zucatti KP, Freitas IM … +4 more , Burgel CF, Milesi BM, Jobim Milanez DS, Silva FM
Am J Clin Nutr · 2026 Mar · PMID 41544711 · Publisher ↗
BACKGROUND: Malnutrition is common in critically ill patients and is associated with poor clinical outcomes. It can be more accurately diagnosed using integrative tools. OBJECTIVES: This study aimed to pool malnutrition...
BACKGROUND: Malnutrition is common in critically ill patients and is associated with poor clinical outcomes. It can be more accurately diagnosed using integrative tools. OBJECTIVES: This study aimed to pool malnutrition prevalence in critically ill adults and estimate the accuracy of different tools and its association with clinical outcomes. METHODS: We conducted a systematic review and meta-analysis of observational studies reporting malnutrition prevalence in patients admitted to intensive unit care (ICUs). PubMed, Embase, Scopus, and Web of Science were searched until 18 September, 2024, without any restrictions. Studies using ≥1 integrative tool were eligible. Outcomes tested for predictive validity included ICU or hospital mortality and length of stay. Two reviewers independently screened studies and extracted data. Risk of bias and publication bias were assessed. Meta-analyses were performed using a random-effects model. Concurrent validity of global leadership international malnutrition (GLIM) and Academic Nutrition and Dietetics and American Society of Parenteral and Enteral Nutrition (AND-ASPEN) criteria were tested with subjective global assessment as reference. Certainty of evidence was rated by Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Sixty-six studies were included (66.7% prospective cohorts, 83.3% single-center, and 24.2% from Brazil). Malnutrition prevalence (n = 64 studies, 19,718 patients) was 45.0% [95% confidence interval (CI): 41.0%, 50.0%, I = 97.4%], influenced by the ICU type, continent, and diagnostic tool. GLIM showed specificity of 81.2% (95% CI: 74.1%, 86.1%) and sensitivity of 86.7% (95% CI: 80.1%, 90.9%). AND-ASPEN specificity and sensitivity were 84.2% (95% CI: 78.5%, 87.6%) and 84.8% (95% CI: 79.4%, 88.2%), respectively. Malnutrition was associated with higher mortality risk (relative risk = 2.00, 95% CI: 1.68, 2.39, I = 72.8%), longer ICU stay [mean difference (MD) = 1.60 d, 95% CI: 0.54, 2.67, I = 96.6%], and longer hospital stay (MD = 4.04 d, 95% CI: 0.60, 7.47, I = 97.2%). Most studies had a high risk of bias, and the certainty of evidence was very low for all outcomes. CONCLUSIONS: The prevalence of malnutrition was 45%, associated with an increased risk of death and longer ICU and hospital stays, but the certainty of evidence was very low.
Genetic influences on diet in young Swedish adults: a twin study.
Kastenbom L, Haworth S, Eriksson L … +3 more , Kuja-Halkola R, Johansson I, Esberg A
Am J Clin Nutr · 2026 Mar · PMID 41539396 · Full text
BACKGROUND: Dietary choices are shaped by both genetic predisposition and environmental exposures, yet the relative influence of these factors remains insufficiently understood across populations and age groups. Young ad...
BACKGROUND: Dietary choices are shaped by both genetic predisposition and environmental exposures, yet the relative influence of these factors remains insufficiently understood across populations and age groups. Young adulthood represents a critical period when long-term eating habits take form, and clarifying the determinants of dietary behavior in this life stage may inform strategies to promote sustained health. OBJECTIVES: This twin study aimed to estimate genetic and environmental contributions to food, energy, and nutrient intakes, and taste preferences in young adults in Sweden. METHODS: The study included 2832 Swedish twins (858 monozygotic and 1974 dizygotic; mean age 24 y; 59.5% female). Participants completed a validated dietary questionnaire assessing food intake frequencies and taste preferences. Additive genetic (A), shared environmental (C), and nonshared environmental (E) influences on a priori dietary indices, specific food and nutrient intakes, and taste preferences were estimated using classical ACE twin models and nested models fitted in OpenMx. RESULTS: Heritability estimates across dietary traits ranged from 20% to 61%. Genetic influences on overall dietary pattern indices exceeded 40%. Heritability varied across food groups (e.g., 61% for venison; 24% for potatoes) and nutrient intakes (50% for fiber; 20% for sodium), indicating differing degrees of genetic impact across dietary components. Taste preferences also showed substantial genetic contributions (21%-61%), with the strongest effects observed for bitter foods (e.g., black coffee, grapefruit), followed by sweet foods (e.g., jam/marmalade). CONCLUSIONS: This large-scale twin study provides a comprehensive overview of genetic and environmental influences on dietary behavior in young adults, showing substantial genetic and nonshared environmental contributions across diverse dietary traits. These results provide a foundation for future research on diet-disease relationships and may support the development of prevention and intervention strategies, including emerging precision-nutrition approaches.
Prediabetes, diabetes, and folate status among United States women of reproductive age: NHANES 2011-March 2020.
Crider KS, Adisa O, Pfeiffer CM … +8 more , Wang A, Zhou Y, Yeung LF, Bullard KM, Qi YP, Rose C, Fazili Z, Williams JL
Am J Clin Nutr · 2026 Mar · PMID 41525878 · Full text
BACKGROUND: Pregestational diabetes increases the risk of adverse outcomes including congenital malformations, stillbirth, developmental disabilities, and maternal morbidity. Periconceptional glycemic control and folic a...
BACKGROUND: Pregestational diabetes increases the risk of adverse outcomes including congenital malformations, stillbirth, developmental disabilities, and maternal morbidity. Periconceptional glycemic control and folic acid (FA) supplementation are 2 of the most effective birth defects prevention strategies. OBJECTIVES: The objectives are to describe the proportion of and risk factors for diabetes and prediabetes and assess the association of folate status and diabetes among a nationally representative sample of nonpregnant women of reproductive age (WRA). METHODS: WRA (12‒49 y) from the NHANES 2011‒March 2020 (n = 3731) were included. Diabetes status was defined by glycated hemoglobin (HbA1c) ≥6.5%, fasting plasma glucose (FPG) ≥126 mg/dL, or self-report. Prediabetes was defined as HbA1c ≥5.7 <6.5% or FPG ≥100 <126 mg/dL. The associations were assessed by multivariate regression models. RESULTS: Among all WRA, 32.3% [95% confidence interval (CI): 30.0%, 34.7%] had prediabetes and 5.3% (95% CI: 4.4%, 6.3%) had diabetes [1.8% undiagnosed, 95% CI: 1.4%, 2.3%; 3.1% diagnosed but uncontrolled (HbA1c ≥5.7), 95% CI: 2.5, 4.0; 0.4% diagnosed but controlled (HbA1c<5.7), 95% CI: 0.2, 0.6]. The prevalence of diabetes was associated with increased age, BMI, serum pyrazino-s-triazine, an oxidation form of 5'-methyltetrahydrofolate (MeFox), and red blood cell (RBC) folate concentrations (all P < 0.0001) but not unmetabolized FA. Among WRA ≥35 y, 10.5% (95% CI: 8.5%, 12.8%) had diabetes and 40.3% (95% CI: 37.1%, 43.5%) had prediabetes. In adjusted regression models, diabetes was associated with altered folate metabolism [i.e., high (>90th %) RBC folate concentrations with lower (<400 μg/d) FA intake; adjusted odds ratio 2.28 (95% CI: 1.23, 4.24)]. Among those with diabetes, high serum MeFox and RBC folate concentrations were lower with euglycemia. CONCLUSIONS: Diabetes and prediabetes were common among WRA. Diabetes was associated with high RBC folate concentration and high MeFox despite low FA intake; however, these associations were reduced among those with good glycemic control. Screening for and preventing the progression of prediabetes, diagnosis, and glycemic control among those with diabetes has the potential to prevent adverse outcomes.
Comparing postprandial inflammatory responses to a plant-based meat alternative, grass-finished beef, and grain-finished beef in healthy middle-aged adults: a 3-group randomized crossover trial.
Cloward J, Mason O, DeJesus I … +4 more , Broadbent J, Payne T, Wengreen HJ, van Vliet S
Am J Clin Nutr · 2026 Mar · PMID 41519303 · Publisher ↗
BACKGROUND: Consumer interest in grass-finished meat and plant-based meat alternatives is growing because of concerns about health and environmental sustainability. Although these options differ in nutrient composition,...
BACKGROUND: Consumer interest in grass-finished meat and plant-based meat alternatives is growing because of concerns about health and environmental sustainability. Although these options differ in nutrient composition, their acute effects on postprandial inflammation remain unclear. OBJECTIVES: This study aimed to compare acute postprandial inflammatory responses after the consumption of grass-finished beef, a plant-based meat alternative, and grain-finished beef. Secondary outcomes included subjective measures of hunger, fullness, and thirst. METHODS: In a randomized crossover trial, 36 middle-aged adults [mean ± standard deviation (SD): 46.5 ± 8 y; 47% male, 53% female] with a body mass index (BMI) 25-35 kg/m (mean ± SD: 29.6 ± 3) consumed 3 dietary interventions: ground grass-finished beef, plant-based meat alternative, and ground grain-finished beef. Blood was collected at baseline and multiple time points over 5 h after eating to measure C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Hunger, fullness, and thirst were assessed using visual analog scales. Data were analyzed using linear mixed models, adjusting for baseline inflammation. RESULTS: No significant differences in postprandial inflammatory markers were observed across interventions (P = 0.64). CRP increased slightly (+0.05 to +0.38 mg/L), TNF-α decreased moderately (-0.75 to -1.08 pg/mL), and IL-6 increased slightly (+1.29 to +1.92 pg/mL) across interventions (all P > 0.05). Exploratory analyses indicated a marginal association between age and inflammatory responses (P = 0.12), with no effects of BMI or sex (P = 0.60 and 0.56). Subjective ratings of hunger, fullness, and thirst did not differ between interventions. CONCLUSIONS: Despite differences in nutrient composition, acute consumption of grass-finished beef, a plant-based meat alternative, and grain-finished beef did not elicit significantly different postprandial inflammatory responses. These findings suggest that, in the short term, the choice between these protein sources may not meaningfully impact inflammation. Further research is needed to explore potential long-term health implications. CLINICAL TRIAL REGISTRY: This was registered at https://clinicaltrials.gov/study/NCT05690061.
Alignment with front-of-package labeling policy and risk of hospitalization: evidence from Canadian National Nutrition Survey linked to routinely collected health administrative databases.
Buttar A, Hu N, Sobolev B … +2 more , Kuramoto L, Jessri M
Am J Clin Nutr · 2026 Mar · PMID 41519302 · Full text
BACKGROUND: Nutrient-specific front-of-package (FOP) schemes are expanding internationally, but no validated, population-level measures exist to monitor adherence or link adherence to healthcare burden. Leveraging Canada...
BACKGROUND: Nutrient-specific front-of-package (FOP) schemes are expanding internationally, but no validated, population-level measures exist to monitor adherence or link adherence to healthcare burden. Leveraging Canada's FOP thresholds, we introduce reproducible alignment indexes designed for surveillance and evaluate their predictive validity using hospital bed-day outcomes. OBJECTIVES: This study aims to construct a priori dietary indexes reflecting alignment with Canadian FOP thresholds and assess their ability to predict all-cause hospital bed-day rates over 5 and 10 y among Canadian adults aged 20-79. METHODS: Data from the Canadian Community Health Survey-Nutrition linked longitudinally with individual hospital records (n = 14,249 after exclusions) were used. Food items were classified according to FOP nutrition labeling regulations to create the FOP-compliance index (FOP-CI) dietary index. A 10-y follow-up sensitivity analysis and 2 policy scenarios were included: 1 removing exemptions (FOP-compliance index without policy exemptions) and 1 including fast food and restaurant items (FOP-compliance index including fast food and restaurant items). The Dietary Approaches to Stop Hypertension index served as a reference. Weighted multivariable zero-inflated negative binomial models estimated the relative rate (RR) of hospital bed-days across alignment quintiles. RESULTS: Quintile 5 (lower FOP-CI alignment) had a higher rate of all-cause hospital bed-days than quintile 1 [RR: 1.52; 90% confidence interval (CI): 1.05, 2.19] over 5 y. After accounting for the probability of hospitalization across the entire cohort, this corresponds to an estimated difference of 500,108 annual bed-days. The increased bed-day rate for nonalignment held across policy scenarios and a 10-y follow-up (RR: 1.34; 90% CI: 1.02,1.77). Sex-stratified models showed consistent directions, with stronger and significant associations for males at 10 y of follow-up (FOP-CI, RR: 1.50; 90% CI: 1.00, 2.25). CONCLUSIONS: In this exploratory analysis, greater alignment with FOP policy was associated with a lower hospital bed-day rate over5 and 10 y. Sex-tailored risk-reduction strategies may be warranted with the strongest association in males. These findings reinforce the value of the "high-in" symbol; however, the nutrient-specific focus may still miss broader dimensions of diet quality. Complementary, whole-diet guidance remains essential to maximize population-level benefits and health-system savings.
Validation of food intake biomarkers is key to advancing the potential use in assessment of dietary intake.
Brennan L
Am J Clin Nutr · 2026 Jan · PMID 41485876 · Publisher ↗
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