BACKGROUND: Nutrition contributes to bone mineral density (BMD) during infancy and childhood; however, studies focusing on infant nutrition and BMD relationships in childhood are limited. OBJECTIVES: This study aimed to...BACKGROUND: Nutrition contributes to bone mineral density (BMD) during infancy and childhood; however, studies focusing on infant nutrition and BMD relationships in childhood are limited. OBJECTIVES: This study aimed to examine relationships of any breastfeeding (BF) duration and timing of complimentary foods and beverages (CFB) introduction with BMD outcomes in young Asian children from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort. METHODS: Healthy term-born children aged 6 y (n = 207) with available BF duration data (months) and dual-energy X-ray (DXA) absorptiometry scans of lumbar spine (LS) and whole body (WB) were included to examine the BF duration and CFB introduction associations with DXA-derived-BMD outcomes; cohort-specific z-scores of areal BMD (aBMD, grams per square centimeter) and bone mineral apparent density (BMAD, grams per cubic centimeter) of WB and LS. Multivariable models utilized regularized regression modeling [least absolute shrinkage and selection operator (LASSO)] to leverage multiple covariates without overfitting the available data. RESULTS: In univariable models, longer BF duration was associated with lower Z [-0.013 ± 0.006 (SE), P = 0.027] and Z (-0.012 ± 0.006, P = 0.045); in stratified analyses, longer BF duration was associated with lower Z (-0.023 ± 0.008, P = 0.004), Z (-0.020 ± 0.007, P = 0.006, and Z (-0.018 ± 0.008, P = 0.037) in females only. Most associations remained significant in adjusted LASSO models. Later CFB introduction was associated with lower Z (-0.130 ± 0.065, P = 0.045); in stratified analyses, later CFB introduction was associated with lower Z (-0.166 ± 0.078, P = 0.037) and Z (-0.205 ± 0.078, P = 0.010) in males only. These associations were no longer apparent in adjusted LASSO models. CONCLUSIONS: A longer BF duration and delayed CFB introduction may reflect reduced bone accrual in early childhood, inferred from bone density at age 6 y, and may vary by child's sex. Recognizing these relationships is crucial for optimizing early nutrition to support strong and healthy bone development. This trial was registered at clinicaltrials.gov as NCT01174875 (https://www. CLINICALTRIALS: gov/study/NCT01174875).
BACKGROUND: Breast cancer (BC) is the most common cancer in females. Combining metabolomic and dietary data provides an opportunity to explore metabolic pathways underlying BC risk, but few prospective studies have exami...BACKGROUND: Breast cancer (BC) is the most common cancer in females. Combining metabolomic and dietary data provides an opportunity to explore metabolic pathways underlying BC risk, but few prospective studies have examined these relationships. OBJECTIVES: This study aimed to identify plasma metabolites associated with incident BC, explore diet-metabolite associations, and assess whether metabolites mediate diet-BC associations. METHODS: Fifty-three plasma metabolites were measured by liquid chromatography-mass spectrometry in females from a prospective case-cohort nested within the French NutriNet-Santé study (2762 subcohort members, 306 total BC cases; median age 53.6 y). Dietary intake was assessed using repeated 24-h dietary records. Principal component (PC) analysis derived metabolite and dietary patterns. Cox models estimated hazard ratios (HRs) for metabolite-BC associations, adjusted for established risk factors. ElasticNet and linear regression identified dietary predictors of metabolites. Mediation analysis evaluated whether metabolites mediated diet-BC associations. RESULTS: A metabolite pattern enriched in conjugated bile acids (PC04) was positively associated with BC [HR: 1.14; 95% confidence interval (CI): 1.00, 1.30], including glycohyocholic acid (HR: 1.10; 95% CI: 1.03, 1.17), glycoursodeoxycholic acid (HR: 1.03; 95% CI: 1.00, 1.06), and taurocholic acid (HR: 1.04; 95% CI: 1.00, 1.09). A pattern enriched in unconjugated bile acids was inversely associated (HR: 0.86; 95% CI: 0.75, 0.99), as was linoleyl-carnitine (HR: 0.81; 95% CI: 0.68, 0.96) and, among premenopausal females, lysophosphatidylcholine (18:1) (HR: 0.60; 95% CI: 0.38, 0.96). Several dietary factors were associated with these metabolites; for example, vitamin K intake was inversely associated with glycohyocholic acid (β: ‒0.12 per standard deviation, 125.1 μg/d) and PC04 (β: ‒0.07). Mediation analysis indicated vitamin K intake was inversely associated with BC (HR: 0.82; 95% CI: 0.68, 0.93), with reductions in glycohyocholic acid and PC04 each explaining ∼4% of this association. CONCLUSIONS: BC incidence was positively associated with conjugated bile acids, including the novel glycohyocholic acid, and inversely associated with unconjugated bile acids, suggesting a potential role for bile acid conjugation in carcinogenesis. Multiple dietary factors were linked to these metabolites, highlighting potential metabolic pathways connecting diet and BC. This trial was registered at clinicaltrials.gov as NCT03335644.
BACKGROUND: Osteoporosis is a common age-related skeletal disorder, especially in postmenopausal females, underscoring the need for effective nutritional strategies to preserve bone health. Calcium-enriched permeate (CP)...BACKGROUND: Osteoporosis is a common age-related skeletal disorder, especially in postmenopausal females, underscoring the need for effective nutritional strategies to preserve bone health. Calcium-enriched permeate (CP) and inulin may enhance absorption and bone mineral density (BMD). OBJECTIVES: To assess the effects of daily supplementation of calcium-enriched permeate, with inulin (CP-Inu) or without inulin, and calcium carbonate (CC) on bone turnover markers and BMD in vitamin D-sufficient postmenopausal females. METHODS: In this 12-mo randomized, double-blind, multi-center trial, postmenopausal females were allocated to receive daily either a maltodextrin as placebo (P), 800 mg calcium as CC, CP, or CP-Inu split into 2 doses. All received 20 μg vitamin D per day. Primary outcome was C-terminal telopeptides of type I collagen; secondary outcomes were procollagen type I N-terminal propeptide and BMD. Linear mixed-effects models were used to assess fixed and random effects. adjusted for multiple outcomes. RESULTS: Of 417 participants (56.0 ± 4.2 y; BMI 25.5 ± 3.8), 316 (76%) completed the study with a mean 89% overall compliance. C-terminal telopeptides of type I collagen remained unchanged from baseline to 12 mo in the P group, whereas all intervention groups showed significant reductions compared with P (μg/L) [CC: β = -0.137; 95% confidence interval (CI): -0.193, -0.081, P = 2.59 × 10; CP: β: = -0.150; 95% CI: -0.208, -0.093, P = 1.62 × 10; CP-Inu β: = -0.149; 95% CI: -0.207, -0.090, P = 1.96 × 10]. Compared with P, procollagen type I N-terminal propeptide was significantly reduced in all intervention groups. By month 12, spine BMD (grams per square centimeter) was higher with CC: β = 0.0158, (0.0066, 0.0251), P = 0.0009; CP-Inu, β = 0.0142, (0.0046, 0.0238), P = 0.0040, and femoral neck BMD was higher with CP, β = 0.0116, (0.0042, 0.0190), P = 0.0022. No additional effects were observed in the CP-Inu group. CONCLUSIONS: Daily supplementation of 800 mg calcium in 2 doses from CP suppresses bone turnover markers and maintains BMD similarly to CC in vitamin D-sufficient postmenopausal females. Inulin provides no additional advantage. This trial was registered at clinicaltrials.gov as NCT04836637.
BACKGROUND: Precision nutrition strategies can be effective in optimizing health outcomes. We previously showed that dietary macronutrient modulation targeting tissue-specific insulin resistance (IR) phenotypes induced p...BACKGROUND: Precision nutrition strategies can be effective in optimizing health outcomes. We previously showed that dietary macronutrient modulation targeting tissue-specific insulin resistance (IR) phenotypes induced pronounced improvements in cardiometabolic health. It remains unclear whether these improvements may partially be explained by gut microbiota-related mechanisms. OBJECTIVES: We investigated whether 12-wk high monounsaturated fatty acid (HMUFA) and low-fat, high-protein, high-fiber diets (LFHP) impact gut microbiota composition and functionality in people with predominant muscle IR (MIR) compared with liver IR (LIR) in relation to cardiometabolic health improvements. METHODS: This 2-center, randomized, double-blind, dietary intervention trial included 179 individuals with LIR or MIR [40‒75 y, body mass index (in kg/m) 25‒40], who followed either a 12-wk isocaloric HMUFA or LFHP diet. A 7-point oral glucose tolerance test was performed to determine tissue-specific IR and cardiometabolic risk factors. Fecal microbiota composition was profiled using 16S ribosomal ribonucleic acid amplicon sequencing (V3‒V4 region), and GLP-1 and gut microbial products were determined in plasma and feces. RESULTS: The HMUFA diet induced significant shifts in overall gut microbial composition (P < 0.05) and short-chain fatty acid-producing bacteria (q < 0.05) in the LIR phenotype, but not in MIR. The LFHP diet induced only modest changes in gut microbiota features. We found phenotype-specific correlations between specific baseline taxa abundance and change in metabolic outcomes (MIR-HMUFA: Barnesiella-ΔMISI (Spearman ρ = 0.45, P < 0.001); LIR-HMUFA: Sutterella-Δplasma-C-reactive protein (Spearman ρ = 0.57, P = 0.0001) and a Rhodospirillales genus-Δhomeostasis model assessment of insulin resistance (Spearman ρ = ‒0.58, P < 0.001). CONCLUSIONS: Individuals with predominant LIR seem more prone to diet-induced gut microbiota-related improvements in cardiometabolic health than those with MIR, highlighting the importance of understanding heterogeneity in IR. Our findings support a role for the gut microbiota in precision nutrition targeting tissue-specific IR. CLINICALTRIALS: gov registration: This is a secondary analysis of the PERSonalized glucose Optimization through Nutritional intervention (PERSON) randomized trial. REGISTRATION NUMBER: NCT03708419, https://clinicaltrials.gov/study/NCT03708419.
Am J Clin Nutr
· 2026 May · PMID 42070893
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According to current scientific consensus, strategies that promote the availability of body carbohydrate (CHO) stores to meet the fuel needs of endurance sport represent the best approach to optimize performance. Such st...According to current scientific consensus, strategies that promote the availability of body carbohydrate (CHO) stores to meet the fuel needs of endurance sport represent the best approach to optimize performance. Such strategies are known to achieve a range of metabolic and nonmetabolic benefits during both high intensity exercise of short duration and more prolonged exercise of lower intensity. This debate considered a counter proposal to the concept that fat oxidation cannot supply ATP sufficiently rapidly to support performance in such events. Indeed, the "ketogenic low-CHO high-fat" diet can increase the athlete's capacity to oxidize the more plentiful body fat stores. Even here, however, CHO ingestion during exercise improves performance of prolonged events by preventing exercise-induced hypoglycemia. This debate sought to advance current understanding of the competing ideas that to maximize either their CHO or fat oxidation during exercise and so optimize their performance, endurance athletes should eat diets rich in either CHO or fat. Points of agreement include the muscle's capacity to be trained to increase oxidation of either fuel, whereas points of disagreement include whether strategies to promote highest rates of CHO oxidation provide advantages over the amounts needed to prevent hypoglycemia. Future research should target challenges in measuring both metabolism and performance.
Am J Clin Nutr
· 2026 May · PMID 42070892
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Over the past decade, randomized controlled trials have established that, after eating either a low-carbohydrate, high-fat or a high-carbohydrate, low-fat diet for 4-6 wk, trained athletes performed equally well during a...Over the past decade, randomized controlled trials have established that, after eating either a low-carbohydrate, high-fat or a high-carbohydrate, low-fat diet for 4-6 wk, trained athletes performed equally well during a maximum oxygen consumption (VOmax) test; during 5 and 1.6 km laboratory treadmill time trials; during a 6 × 800 m interval repetition session; and during a prolonged cycling test to exhaustion at 70%VOmax. Indeed, during the 6 × 800 m interval repetition session, some subjects achieved the highest rates of fat oxidation (2 g/min) ever reported in humans; whereas ingestion of 10 g carbohydrate/h improved prolonged cycling test performance by 22%, equally following either diet. These data establish that muscle glycogen is not an obligatory fuel for exercise. Rather, exercise-induced hypoglycemia due to depletion of glucose in the small glucose pool in the liver and bloodstream, prevented by minimal carbohydrate ingestion during exercise, is the main metabolic contributor to premature fatigue during more prolonged submaximal exercise.
Am J Clin Nutr
· 2026 May · PMID 42070891
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The complex determinants of endurance sports performance vary according to exercise demands, the specific event, and the individual athlete. A key issue is the availability and integration of the oxidative use of muscle...The complex determinants of endurance sports performance vary according to exercise demands, the specific event, and the individual athlete. A key issue is the availability and integration of the oxidative use of muscle fat and carbohydrate (CHO) stores to supply energy. Current competition nutrition guidelines promote "high CHO availability," using personalized strategies pre-, during, or between events to match glycogen and blood glucose supplies to the specific event demands. Alternatively, adaptation to a ketogenic low CHO high-fat (LCHF) diet makes fat the principal fuel, but impairs performance in some scenarios. Indeed, at oxidative thresholds, important in high-performance sport, metabolic pathways of fat oxidation provide a lower energy yield, leading to lower power/speed. Moreover, the consumption of CHO during exercise in keto-adapted athletes often enhances endurance capacity or performance. Therefore, the LCHF diet alone is suboptimal for endurance performance, as is as a one-size-fits-all approach to sports nutrition.
Am J Clin Nutr
· 2026 May · PMID 42070888
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BACKGROUND: The profile for human milk (HM) nutrient composition jointly used by Canada and the United States [Standard Reference (SR), legacy] is largely based on >40-y-old studies. In 2018, it was deemed unsuitable by...BACKGROUND: The profile for human milk (HM) nutrient composition jointly used by Canada and the United States [Standard Reference (SR), legacy] is largely based on >40-y-old studies. In 2018, it was deemed unsuitable by the United States Department of Agriculture for estimating current nutrient exposures. OBJECTIVES: To review data available in the literature to develop interim HM nutrient profile data values. METHODS: Two reviewers screened and extracted data from 3 recent systematic reviews covering the period from 1980‒2022 and 1 large Canadian biomonitoring study. Eligible studies: reported quantitative concentrations of ≥1 component of interest (energy, macronutrients, vitamins, minerals, or fatty acids), included data specific to United States or Canadian participants, reported on mature milk (>21 d postpartum) for term-born infants (>37 wk of gestation), had samples collected within the first 6 mo of lactation, and used appropriate methods for milk collection and nutrient analysis. Studies were combined as weighted means and pooled standard deviations and compared with the existing SR and international literature. RESULTS: Updated data were identified for >40 HM components, including some that had previously been assigned 0 in SR legacy (e.g., DHA), or estimated from other foods (e.g., vitamin K). Concentrations for interim HM nutrient profile data differed by >20% from values in the SR legacy for total fat, iron, manganese, and most vitamins and fatty acids. Eligible data were lacking for niacin, vitamin B-12, vitamin C, and total vitamin D, and were only available from single studies for manganese, β-carotene, thiamin, riboflavin, pantothenic acid, vitamin B6, total choline, 25-hydroxyvitamin D, vitamin E, cholesterol, and some fatty acids. CONCLUSIONS: These findings summarize data available to develop an interim nutrient profile for North American HM that could be used until an empirically measured profile can be developed. They also highlight gaps in the literature to be addressed by future studies.
Zeitoun T, Chen ZH, Burgner D
… +11 more, MacKechnie G, Huntington P, Mansell T, Longmore D, Mandhane PJ, Simons E, Turvey SE, Subbarao P, Moraes TJ, Sellen DW, Miliku K
Am J Clin Nutr
· 2026 May · PMID 42070887
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BACKGROUND: Guidelines in Canada, the United States, and other countries recommend that children switch from whole (3.25%) to reduced-fat milk after age 2 years to limit saturated fat intake and prevent obesity, despite...BACKGROUND: Guidelines in Canada, the United States, and other countries recommend that children switch from whole (3.25%) to reduced-fat milk after age 2 years to limit saturated fat intake and prevent obesity, despite these recommendations being derived primarily from adult studies. Emerging pediatric evidence challenges this approach, but prospective data in early school-aged children are scarce. OBJECTIVES: To test for cross-sectional and longitudinal associations of cow milk-fat content at age 5 years and adiposity indicators and obesity status among 5- and 8-year-old Canadian children. METHODS: We analyzed data from the CHILD Cohort Study, a national longitudinal prospective pregnancy cohort study. At age 5 years, caregivers reported the fat content of cow milk consumed (skim [0%], 1%, 2%, and whole [3.25%]). Anthropometric measures at ages 5 years (N = 2043) and 8 years (N = 1574) included body mass index (BMI) and waist-to-height ratio z-scores; and at age 8 years, fat mass percentage (measured by bioelectric impedance analysis) and obesity (defined using World Health Organization criteria and the new clinical obesity Lancet Commission definitions). Multivariable linear and logistic regression models were adjusted for sociodemographic, lifestyle, and other dietary factors. RESULTS: At age 5 years, most children consumed 2% (48.9%) or 3.25% (23.9%) fat from cow milk. Compared with skimmed cow milk, whole (3.25%) cow milk consumption was associated with lower BMI z-score at age 5 years [β: -0.34; 95% confidence interval (CI): -0.54, -0.13] and lower odds of living with obesity [odds ratio (OR): 0.22; 95% CI: 0.07, 0.67]. Whole cow milk consumption at 5 years was also inversely associated with BMI z-score (β: -0.42; 95% CI: -0.72, -0.11), waist-to-height ratio z-score (β: -0.35; 95% CI: -0.63, -0.07), fat mass (β: -1.58; 95% CI: -3.10, -0.06), obesity (OR: 0.31; 95% CI: 0.12, 0.80), and preclinical obesity (OR: 0.25; 95% CI: 0.09, 0.70) at age 8 years. CONCLUSIONS: Whole cow milk consumption at age 5 years was associated with lower adiposity and obesity indicators in middle childhood. These findings challenge current recommendations to limit milk fat in children and may inform future dietary guidelines.
AlEssa HB, Xia T, Mousavi SM
… +4 more, Sawicki C, Willett WC, Bhupathiraju SN, Hu FB
Am J Clin Nutr
· 2026 Jul · PMID 42069223
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BACKGROUND: Numerous carbohydrate quality metrics (CQMs) have been suggested, yet the optimal one(s) associated with the lowest type 2 diabetes (T2D) risk remains unknown. OBJECTIVES: We aimed to systematically compare 2...BACKGROUND: Numerous carbohydrate quality metrics (CQMs) have been suggested, yet the optimal one(s) associated with the lowest type 2 diabetes (T2D) risk remains unknown. OBJECTIVES: We aimed to systematically compare 23 CQMs with T2D risk, identify the 5 strongest associations, propose an alternate Carbohydrate Quality Index (aCQI), and compare it with the existing CQI regarding T2D risk and cardiometabolic biomarkers. METHODS: We included participants of 3 prospective cohort studies [Nurses' Health Study I (1984-2020) and II (1991-2019), and Health Professionals Follow-up Study (1986-2020)], who were free of cancer, diabetes, and cardiovascular disease. Our primary outcome was incident T2D. We examined 13 plasma biomarkers in relation to CQIs among a subset. RESULTS: During 5,628,955 person-years of follow-up among 213,704 adults, 22,351 cases of incident T2D were ascertained. In multivariable-adjusted models, comparing Q5 to Q1, intakes of cereal fiber [relative risk (RR): 0.77 (0.74-0.81)], whole-fruit carbohydrates [RR: 0.80 (0.76-0.84)], glycemic index [RR: 1.20 (1.14-1.26)], sugar from sugar-sweetened beverages [RR: 1.22 (1.17-1.28)], and whole-grain carbohydrates [RR: 0.86 (0.82-0.91)] had the strongest associations with T2D risk. The aCQI [RR: 0.71 (0.68-0.75)], comprising these variables, had a larger magnitude of association with T2D risk than the original CQI [RR: 0.82 (0.79-0.87)], which included total fiber intake, glycemic index, the ratios of whole to total grains, and solid to total carbohydrates. The aCQI had significant associations with a larger percentage of differences in cardiometabolic biomarker concentrations, such as C-peptide, leptin, and LDL cholesterol, than the CQI (all P-trend ≤ 0.001). CONCLUSIONS: The novel aCQI, comprised carbohydrates from whole fruits, whole grains, sugar-sweetened beverages, cereal fiber, and glycemic index, was more strongly associated with risk of T2D and cardiometabolic biomarkers than its individual components or the existing CQI, necessitating further research.
BACKGROUND: Although recent trials have shown daily prenatal low-dose 500 mg calcium supplementation to be noninferior to the recommended high-dose 1500 mg regimen for prevention of preeclampsia, its effects on maternal...BACKGROUND: Although recent trials have shown daily prenatal low-dose 500 mg calcium supplementation to be noninferior to the recommended high-dose 1500 mg regimen for prevention of preeclampsia, its effects on maternal anemia and iron status remain unclear. OBJECTIVES: This study evaluated the effects of 500 mg daily calcium supplementation as compared to 1500 mg calcium supplementation during pregnancy on maternal anemia and iron indices. METHODS: We conducted two individually randomized, noninferiority trials in India and Tanzania (N = 11,000 each) comparing daily 500 to 1500 mg calcium supplementation during pregnancy. All participants received standard iron and folic acid (IFA) (60 mg iron) and were counseled to take calcium supplements several hours apart from the IFA. All participants had hemoglobin measured at baseline and at 32 wk of gestation, whereas a random subset of participants had ferritin quantified at the same time points. Using an intention-to-treat approach, we assessed effects of 500 mg compared with 1500 mg calcium supplementation on mean hemoglobin and inflammation-adjusted serum ferritin (log-scale) using generalized linear models, and on anemia and iron deficiency anemia using log-binomial models. RESULTS: Third-trimester hemoglobin and serum ferritin were measured in 8953 and 1336 participants in India, respectively. In Tanzania, 8496 participants had hemoglobin, and 882 had ferritin assessed. In both trials, there was no difference between 500 and 1500 mg calcium supplementation on third-trimester hemoglobin [India: mean difference (MD) 0.01 (95% confidence interval (CI): -0.03, 0.04); Tanzania: MD -0.02 (95% CI: -0.07, 0.03)], anemia [India: relative risk (RR) 1.01 (95% CI: 0.95, 1.07); Tanzania: RR 1.00 (95% CI: 0.96, 1.05)], or iron deficiency anemia [India: RR 1.20 (95% CI: 0.93, 1.57); Tanzania: RR 0.94 (95% CI: 0.77, 1.15)]. CONCLUSIONS: Low- and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes. Future studies should assess the effects of coadministering or combining calcium and IFA into a single tablet on adherence and bioavailability of iron. This trial was registered at ClinicalTrials.gov as NCT03350516; at Clinical Trials Registry India as CTRI/018/2/12119; and at Tanzania Medicines and Medical Devices Au-thority Trials Registry as TFDA0018/TR/010/.
Lee MR, Barad A, Bender E
… +4 more, Thompson J, Gu Z, Pressman EK, O'Brien KO
Am J Clin Nutr
· 2026 Jun · PMID 42044770
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BACKGROUND: Healthy adult females of East Asian (EA) ancestry have been reported to have higher iron (Fe) stores and Fe absorption and alterations in Fe regulatory hormones when compared with adult females of Northern Eu...BACKGROUND: Healthy adult females of East Asian (EA) ancestry have been reported to have higher iron (Fe) stores and Fe absorption and alterations in Fe regulatory hormones when compared with adult females of Northern European (NE) ancestry. OBJECTIVES: This cross-sectional study collected data on menstrual characteristics among adult females of genetically confirmed EA or NE ancestry and evaluated the potential impact of this factor on Fe status. METHODS: Data were obtained from premenopausal females aged 18 to 50 y [BMI (in kg/m) 18-30] who were enrolled in the FeGenes study, which recruited healthy individuals of genetically confirmed EA or NE ancestry. Data on age at menarche, cycle frequency, menstrual bleeding duration, and use of menstrual products were collected from self-reported questionnaires, and menstrual blood loss (MBL) scores were calculated. Fe status was assessed through serum ferritin (microgram per liter), hepcidin (nanograms per milliliter), soluble transferrin (TF) receptor (milligram per liter), TF (milligram per deciliter), and calculated total body Fe (milligrams per kilogram). Group comparisons and associations with Fe status biomarkers were examined. RESULTS: EA females had an earlier median age at menarche [EA: 12.0 (IQR: 11.0, 13.0) y; NE: 13.0 (IQR: 12.0, 13.3) y; P = 0.002] and a higher MBL score [EA: 24.0 (IQR:17.5, 31.5); NE: 16.0 (IQR: 10.5, 27.9); P < 0.001] than NE females. In NE individuals, a higher MBL score was significantly associated with lower log-transformed serum ferritin (β: ‒0.01; SE: 0.005; P = 0.004), total body Fe (β: ‒0.06; SE: 0.02; P = 0.002), and higher log-transformed soluble TF receptor (β: 0.005; SE: 0.001; P = 0.002). No associations between MBL score and Fe status were evident in EA females. CONCLUSIONS: Higher MBL scores are associated with lower Fe status in NE but not EA females. Greater attention and validated metrics are needed to evaluate MBL and better quantify Fe needs in reproductive-aged females. This trial was registered at clinicaltrials.gov as NCT04198545.
Chalitsios CV, Chan WC, Markozannes G
… +44 more, Aglago EK, Berndt SI, Buchanan DD, Campbell PT, Cao Y, Dimou N, Drew DA, French AJ, Gallinger S, Georgeson P, Giannakis M, Gruber SB, Gunter MJ, Harrison TA, Brenner H, Hoffmeister M, Urruchúa-Rodríguez MJ, Hsu L, Huang WY, Hullar MA, Huyghe JR, Jenkins MA, Jayasekara H, Moreno V, Newton CC, Nowak JA, Obón-Santacana M, Ogino S, Pellatt AJ, Peoples A, Qu C, Schmit SL, Steinfelder RS, Sun W, Thomas CE, Toland AE, Trinh QM, Ugai T, Um CY, Van Guelpen B, Zaidi SH, Peters U, Phipps AI, Tsilidis KK
Am J Clin Nutr
· 2026 Jun · PMID 42031341
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BACKGROUND: Alcohol consumption is associated with colorectal cancer (CRC) risk, yet its association with distinct molecular subtypes remains unclear. Clarifying this could reveal insights into alcohol's carcinogenic mec...BACKGROUND: Alcohol consumption is associated with colorectal cancer (CRC) risk, yet its association with distinct molecular subtypes remains unclear. Clarifying this could reveal insights into alcohol's carcinogenic mechanisms. OBJECTIVES: We examined the association between alcohol consumption and the risk of CRC subtypes defined by individual tumor markers (and marker combinations), namely microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) status, BRAF, and KRAS mutations. METHODS: Pooled observational (n = 11,826, n = 10,888; n = 10) and genome-wide association data (n = 8178, n = 10,472; n = 10) were used. Multivariable logistic regression models and Mendelian randomization (MR) analyses were conducted to assess the association between alcohol consumption, modeled in MR as genetically predicted mean drinks per week per 1 SD increase (≈2.9 drinks/wk), and risk of CRC subtypes defined by individual tumor markers (and marker combinations). Case-only analyses tested for differences between molecular subtypes. Bonferroni correction was applied for multiple tests. RESULTS: Among drinkers, each additional 14 g/d of alcohol was associated with a 10% higher CRC risk [odds ratio (OR) = 1.10; 95% confidence interval (CI): 1.07, 1.13], but this association was primarily driven by heavy alcohol consumption (>28 g/d). Including nondrinkers revealed a J-shaped association (P-nonlinearity = 0.002). The associations with higher alcohol consumption were stronger in males compared with females. No significant heterogeneity was observed across MSI, CIMP, BRAF, or KRAS-defined subtypes. All associations were similar across smoking status, folate intake, tumor anatomical site, study design, early/late-onset CRC, and across individual studies (P-heterogeneity > 0.05). MR analyses supported that higher genetically predicted alcohol consumption was associated with CRC risk (OR = 1.25; 95% CI: 1.01, 1.57), but similarly to the observational analysis, without evidence of heterogeneity across molecular subtypes. CONCLUSIONS: Heavy alcohol consumption may initiate colorectal carcinogenesis through mechanisms that operate across all examined molecular pathways for CRC. Although the largest available data were used, power is lower for subtype heterogeneity analyses, and modest interaction effects cannot be excluded.
Li C, Pokharel P, Sim M
… +11 more, Murray K, Bondonno CP, Parmenter BH, Zhong L, Dupuy M, Meteran H, Jakobsen J, Linneberg A, Kühn T, Cassidy A, Bondonno NP
Am J Clin Nutr
· 2026 Jun · PMID 42025963
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BACKGROUND: Vitamin K-dependent proteins are important for maintaining lung structure and function, yet few studies have examined dietary vitamin K intake in relation to chronic respiratory disease. OBJECTIVES: This stud...BACKGROUND: Vitamin K-dependent proteins are important for maintaining lung structure and function, yet few studies have examined dietary vitamin K intake in relation to chronic respiratory disease. OBJECTIVES: This study aimed to investigate the associations between dietary intakes of vitamin K and vitamin K and the incidence of chronic obstructive pulmonary disease (COPD), asthma, and lung function. METHODS: We analyzed data from 179,062 UK Biobank participants without COPD or asthma. Associations between dietary vitamin K and K intakes, estimated using the Oxford WebQ 24-h recall, and incident COPD and asthma, identified through hospital, death, and primary care records, were examined using Cox proportional hazards models. In cross-sectional analyses, associations of vitamin K intake with forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), and the FEV/FVC ratio were assessed using splines within multiple regression. Stratified analyses were performed by sex, smoking status, and occupation. RESULTS: Over 10.5-y follow-up, higher vitamin K intakes were associated with lower COPD rates, with inverse associations reaching a plateau above ∼250 μg/d [HR: 0.84; 95% confidence interval (CI): 0.75, 0.94], whereas no association was observed for vitamin K. No associations were observed between vitamin K or vitamin K intakes and asthma. Higher vitamin K intakes (Q5 compared with Q1) were associated with better lung function (FVC: 44 mL; 95% CI: 35, 53 mL and FEV: 32 mL; 95% CI: 25, 40 mL), whereas vitamin K showed weaker and nonlinear associations. Stronger associations between vitamin K and lung function were evident in smokers and participants with high-risk occupations. CONCLUSIONS: Higher dietary vitamin K intake was associated with better lung function and a lower rate of COPD. As vitamin K is abundant in green leafy vegetables (e.g., ∼1 serving of kale, ∼1½-2 cups), higher consumption of these foods within a healthy diet may be associated with favorable respiratory health.
Bonaccio M, Costanzo S, Di Castelnuovo A
… +7 more, Ruggiero E, Panzera T, Esposito S, Cerletti C, Donati MB, de Gaetano G, Iacoviello L
Am J Clin Nutr
· 2026 Jun · PMID 42001954
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BACKGROUND: The potential impact of food processing on breast cancer (BC) has not been extensively addressed. OBJECTIVES: This study sought to examine the association of food consumption according to the Nova classificat...BACKGROUND: The potential impact of food processing on breast cancer (BC) has not been extensively addressed. OBJECTIVES: This study sought to examine the association of food consumption according to the Nova classification with BC incidence in a large cohort of Italian females. METHODS: Longitudinal analyses were conducted on 11,442 cancer-free females recruited in the Moli-sani Study (2005‒2010). Food intake was assessed at baseline using a 188-item food frequency questionnaire, and categorized into 4 mutually exclusive groups based on the extent and purpose of processing according to the Nova classification: 1) unprocessed/minimally processed foods; 2) processed culinary ingredients; 3) processed foods; and ultraprocessed foods. Each Nova group was expressed as its proportion (grams per day) of total food eaten (grams per day). Incident BC cases were ascertained by direct linkage with hospital discharge forms and validated through medical records. Associations between dietary exposures and BC outcomes were assessed using multivariable cause-specific Cox proportional hazard models controlled for known risk factors. RESULTS: Over a median follow-up of 13.1 y (146,522 person-years), 295 BC cases were recorded. Multivariable-adjusted hazard ratios (HRs) for overall BC risk associated with highest compared with lowest quartile of consumption of unprocessed/minimally processed foods, culinary ingredients, processed food, and ultraprocessed foods were 1.10 [95% confidence interval (CI): 0.75, 1.59], 1.03 (95% CI: 0.74, 1.44), 1.55 (95% CI: 1.10, 2.17), and 1.04 (95% CI: 0.72, 1.51), respectively. When alcoholic beverages were removed from processed foods, the associated HR was 0.94 (95% CI: 0.67, 1.33) for quartile 4 compared with quartile 1. Food processing was not associated with BC subtypes, including menopausal status and hormone receptor status. CONCLUSIONS: In this cohort of Italian females, food consumption based on the degree of processing was not associated with BC incidence. Although a higher intake of processed foods appeared linked to increased risk, this was largely explained by alcoholic beverages. These findings are in agreement with previous research, which overall remains inconclusive about the link between food processing and BC.