The American Journal Of Clinical Nutrition[JOURNAL]
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200 papers
Association of vegetable and fruit intake with risk of dementia: three prospective studies and meta-analysis of cohort studies.
Huang L, Hailili G, Zhao M … +10 more , Chen H, Shen J, Yan M, Shen T, Wu M, Fei L, Liu X, Xu W, Agarwal P, Yuan C
Am J Clin Nutr · 2026 Jun · PMID 42364910 · Publisher ↗
BACKGROUND: Evidence linking total and specific types of vegetable and fruit intake to dementia remains scarce. This study examined associations between total and subgroup intake of vegetables and fruits and dementia ris...
BACKGROUND: Evidence linking total and specific types of vegetable and fruit intake to dementia remains scarce. This study examined associations between total and subgroup intake of vegetables and fruits and dementia risk across three prospective cohorts and a meta-analysis. METHODS: Data were drawn from the Health and Retirement Study (HRS), the Framingham Heart Study Offspring cohort (FOS), and Whitehall II study (WHII). Average daily intakes of total vegetables and fruits and seven subgroups were assessed using food frequency questionnaires. Incident dementia was identified using cohort-specific definitions. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). We also performed a meta-analysis that incorporating our results and findings from 13 previous cohort studies. RESULTS: Among 18,339 participants aged ≥45 years (HRS: 6,750; FOS: 3,068; WHII: 8,521), 949 dementia cases occurred over an average of 7-13 years' follow-up. After multivariable adjustment, intake of fruits and vegetables combined was associated with a lower risk of dementia in the highest versus the lowest tertile (HR was 0.74, 95%CI: 0.61, 0.89, P-trend=0.165). Additionally, green leafy vegetables demonstrated a protective association (pooled HR per serving increment: 0.82; 95% CI: 0.70, 0.96, P -trend=0.015). No significant pooled associations were observed for other vegetable or fruit subgroups. Findings pooled from a meta-analysis of 222,108 participants showed that a higher intake of fruits and vegetables was associated with a lower risk of dementia compared to a lower intake (pooled HR : 0.80; 95% CI: 0.71, 0.91). Significant inverse associations were also observed for vegetable intake (pooled HR : 0.87; 95% CI: 0.82, 0.92) and fruit intake (pooled HR : 0.90; 95% CI: 0.85, 0.95). CONCLUSIONS: Our study supports an inverse association of vegetable and fruit intake with dementia risk. Further studies on specific subgroups are warranted.
Adherence to Empirically Derived Dietary Patterns and Risk of Depression Symptoms and Anxiety Disorder: The Maastricht Cohort Study.
Mirjalili F, Jambarsang S, Farashahi Yazd E … +8 more , Dianati-Nasab M, Eussen SJPM, Schram MT, Koster A, Salehi-Abargouei A, Yu EY, Zeegers MP, Wesselius A
Am J Clin Nutr · 2026 Jun · PMID 42362117 · Publisher ↗
BACKGROUND: Previous studies have yielded inconsistent findings regarding the relationship between dietary patterns (DPs) and psychological disorders, with most evidence derived from cross-sectional studies. OBJECTIVE: T...
BACKGROUND: Previous studies have yielded inconsistent findings regarding the relationship between dietary patterns (DPs) and psychological disorders, with most evidence derived from cross-sectional studies. OBJECTIVE: To examine the association between major DPs and the risk of depression symptoms (DepS) and anxiety disorder (AnxD). METHODS: This study used data from The Maastricht Study [participants included in analyses for DepS: n=6967, mean age (SD): 59.94(8.66) years, female: 49.40%; for AnxD: n=6634, mean age (SD): 59.94(8.60) years, female: 49.40%]. A validated food-frequency questionnaire was used to assess dietary intakes. DPs were derived using principal component analysis. The Patient Health Questionnaire-9 and the Generalized Anxiety Disorder 7-item questionnaire were used annually to assess DepS and AnxD, respectively. A Cox proportional hazards regression analysis was incorporated to examine the associations. Stratified analyses were performed based on diabetes status, sex, body mass index, and smoking status. RESULTS: Three DPs were identified: "high vegetables and legumes", "high fast food and sugar", and the "vegetarian-like" DPs. After adjustment for all possible confounders, adherence to the "high fast food and sugar" DP was associated with a higher risk of DepS [HR(95%CIs) : 2.13(1.55,2.92), P<0.001, P<0.001] and AnxD [HR(95%CIs) : 2.03(1.33,3.10), P=0.001, P<0.001] in the total population. No association was found for other DPs in the total population. A significant interaction was observed between the "vegetarian-like" DP and smoking status on the risk of AnxD [Interaction term, HR(95%CIs): 0.76(0.64,0.90), P= 0.001]. Opposite but non-significant associations were noted in never-smokers [HR(95%CIs) : 1.47(0.83,2.60), P=0.19, P=0.06] and former/current smokers [HR (95%CIs) : 0.62(0.37, 1.04), P =0.07, P= 0.046]. CONCLUSIONS: A diet high in fast foods, confectionery, fried potatoes, sauces, sugar-sweetened beverages, and refined grains might be associated with an increased risk of depression and anxiety in adults.
Ultra-Processed Food Consumption and the Global Burden of Non-Communicable Disease: A 45-Country Comparative Risk Assessment.
Nguyen TA, Nguyen NN, Nguyen HS … +4 more , Linh TTD, Nguyen NTK, Hoang YN, Ho DKN
Am J Clin Nutr · 2026 Jun · PMID 42362116 · Publisher ↗
BACKGROUND: Ultra-processed foods (UPFs) increasingly contribute to diets in high-income countries (HIC) and are rapidly displacing traditional food systems in low- and middle-income settings (LMIC). Recent meta-analyses...
BACKGROUND: Ultra-processed foods (UPFs) increasingly contribute to diets in high-income countries (HIC) and are rapidly displacing traditional food systems in low- and middle-income settings (LMIC). Recent meta-analyses have established dose-response associations between UPF consumption and multiple non-communicable diseases (NCDs), yet the global disease burden attributable to these foods remains unquantified across diverse populations. OBJECTIVE: To estimate population attributable fractions (PAFs) and attributable burden, including disability-adjusted life years (DALYs) and deaths, for eight NCD outcomes associated with UPF consumption across 47 country/regional estimates spanning all World Bank income groups, with attributable burden derived for the 45 with matching World Health Organization (WHO) Global Health Estimates (GHE) cause data and type 2 diabetes (T2D) as the pre-specified primary outcome. METHODS: We conducted a comparative risk assessment (CRA) using UPF consumption data (% energy from NOVA Group 4 foods) from 47 dietary surveys, dose-response relative risks per 10% energy increment from meta-analyses, and the 2021 WHO GHE. PAFs were computed with a theoretical minimum risk exposure level (TMREL) of 10% energy and Monte Carlo simulation (10,000 iterations) for uncertainty quantification. RESULTS: A clear income gradient was observed: mean T2D PAFs were 20.2% in HICs (n=32), 14.2% in upper-middle-income countries (UMICs; n=6; excluding Lebanon), 0.9% in LMICs (n=6), and 2.7% in low-income countries (LICs; n=2). UPF consumption ranged from 4.0% (Ethiopia) to 57.5% (United States). Country-specific T2D PAFs reached 41.4% (95% confidence interval [CI]: 29.2, 52.2) in the United States, 40.8% (28.4, 51.6) in the United Kingdom, 36.2% (24.6, 46.6) in the Netherlands, and 35.5% (24.2, 45.5) in Norway. UPF consumption above the TMREL was associated with an estimated 3.4 million all-cause deaths (95% CI: 1.3, 6.0 million) and 5,670 thousand (3,266-8,348) T2D DALYs annually. Results were stable across TMREL sensitivity analyses (aggregate all-cause attributable deaths range 2,469-6,590 thousand for TMREL bracketing 0-15%; primary 3,362 thousand at TMREL=10%). CONCLUSIONS: UPF consumption above a 10% energy threshold is associated with a sizeable NCD burden that varies markedly across countries and is concentrated in high-income settings. The income gradient points to an opportunity for early preventive food policy in countries undergoing the nutrition transition.
Effect of icosapent ethyl treatment on colorectal tissue marine omega-3 polyunsaturated fatty acid levels among patients with a history of adenoma: a prospective, single-arm clinical trial.
Chen Y, Bae S, Wang K … +37 more , Du M, Lu Y, Sun Q, Labelle PA, Caraballo A, Lachut K, Husain A, Hote L, Koehn M, Prezioso E, Reinicke T, Schuck M, Sethurathnam J, Solowey J, Woo J, Carolan PJ, Chung DC, Colizzo FP, Gala M, Khalili H, Nishioka NS, Richter JM, Staller K, Yarze JC, Ma W, Pratt D, Singh A, Nguyen LH, Jacobson BC, Luther J, Kuo B, Dougan M, Rosner B, Magicheva-Gupta M, Drew DA, Chan AT, Song M
Am J Clin Nutr · 2026 Jun · PMID 42349681 · Publisher ↗
BACKGROUND: Icosapent ethyl (IPE), an ethyl ester of eicosapentaenoic acid (EPA, C20:5n-3), is thought to have immunomodulatory properties and may protect against colorectal cancer (CRC). OBJECTIVES: This study aimed to...
BACKGROUND: Icosapent ethyl (IPE), an ethyl ester of eicosapentaenoic acid (EPA, C20:5n-3), is thought to have immunomodulatory properties and may protect against colorectal cancer (CRC). OBJECTIVES: This study aimed to assess the effect of IPE on changing total marine omega-3 polyunsaturated fatty acid (PUFA) and individual fatty acid composition in colorectal tissue. METHODS: We conducted a prospective, single-arm clinical trial of 4g/d IPE (VASCEPA®) treatment for 8-12 weeks among patients with a recent history of adenoma. We collected pre- and post-treatment colorectal biopsies through flexible sigmoidoscopy, and participants' diet and lifestyle via questionnaires. The primary outcome was the change in total marine omega-3 PUFA in colorectal tissue measured by gas-liquid chromatography. We examined changes in individual fatty acids exploratorily. RESULTS: Among a total of 81 patients enrolled, 72 had paired pre- and post-treatment tissue fatty acid data. After intervention, the tissue composition (median [interquartile range]) of total marine omega-3 PUFA increased from 2.10% (0.96%) to 5.21% (1.97%), with a fold change of 2.40 (0.82). With a slight decrease in omega-6 PUFA (fold change = 0.96 [0.27]), the ratio of marine omega-3 to omega-6 PUFA increased (fold change = 2.58 [0.81]). Among individual fatty acids, EPA increased the most (fold change: 5.88 [3.63]). The cumulative amount of IPE treatment, rather than daily dosage, showed a positive correlation with changes in tissue EPA composition (Spearman's ρ=0.23, P=0.051). The treatment effect on tissue EPA changes appeared to be stronger for participants with lower than higher dietary EPA intake at baseline, although the interaction tests did not reach statistical significance (P for interaction=0.26). CONCLUSIONS: IPE treatment substantially increased incorporation of marine omega-3 PUFA, particularly EPA, into the colorectal tissue while reducing tissue omega-6 PUFA composition. TRIAL REGISTRATION: The PREvention using EPA against coloREctal cancer (PREPARE) trial was registered as ClinicalTrials.gov identifier: NCT04216251.
Does consuming ascorbate-rich fruits and fruit juices with meals improve iron bioavailability? A systematic review and meta-analysis of interventions.
Nyakundi PN, Nemeth LG, Galgalo DA … +5 more , Limungi GM, Nyabuti FM, Otieno K, Czina L, Lohner S
Am J Clin Nutr · 2026 Jun · PMID 42349680 · Publisher ↗
BACKGROUND: This systematic review summarizes the effect of whole ascorbate-rich fruits on iron bioavailability parameters among females (15-74 years) and children. METHODS: A systematic review and meta-analysis of inter...
BACKGROUND: This systematic review summarizes the effect of whole ascorbate-rich fruits on iron bioavailability parameters among females (15-74 years) and children. METHODS: A systematic review and meta-analysis of interventions was performed, where randomized controlled trials (RCTs) and controlled clinical trials were considered, with main outcomes being iron absorption (percentage uptake) and serum ferritin. The protocol was registered in PROSPERO (CRD42024615527). Searches were conducted in December 2024 and updated in March 2026 in Scopus, Ovid Medline, ClinicalTrials.gov, Cochrane CENTRAL, and WHO ICTRP. Two independent reviewers screened titles/abstracts, full texts, extracted data, and assessed risk of bias and GRADE certainty; conflicts were resolved by discussion to consensus. RESULTS: After screening 2594 unique records, 15 RCTs (n = 1381; 806 interventions, 575 controls) met inclusion criteria. Including ascorbate-rich fruits in meals had a positive impact on: serum ferritin (7 trials, n = 762; MD = 9.39 μg/L; p <0.001; moderate certainty), hemoglobin (12 trials, n=1141; MD = 1.34 g/L; p = 0.01; moderate certainty), serum transferrin receptor (6 studies; MD = -0.37 mg/L; p <0.001; high certainty), and iron balance (1 trial; MD = 2.4; low certainty). A negative effect on body iron stores was observed (2 studies; MD = -0.29 mg/kg; p = 0.32; high certainty). No impact on iron absorption (3 studies; MD=3.36%; p =0.07, low certainty), plasma ferritin (4 studies; MD = -0.11 μg/L, p = 0.82; high certainty) or plasma transferrin receptor (3 studies; MD=1.53 mg/L; very low certainty). CONCLUSION: Consuming ascorbate-rich fruits or juices with meals probably increases serum ferritin and hemoglobin concentrations, and slightly reduces serum transferrin receptors but shows little to no effect on iron absorption, plasma ferritin or body iron stores.
Short- and long-term effects of semaglutide 2.4 mg on energy intake, appetite, and food reward: a 60-week, double-blind randomized controlled trial.
Tronieri JS, Allison KC, DeRouen K … +6 more , Amaro A, Collins KG, Roy A, Watts S, Ananna T, Wadden TA
Am J Clin Nutr · 2026 Jun · PMID 42323166 · Publisher ↗
BACKGROUND: Studies of ≤20 wk have demonstrated reductions in energy intake, appetite, and food reward with semaglutide that may drive initial weight loss. These brief studies could not assess whether semaglutide has lon...
BACKGROUND: Studies of ≤20 wk have demonstrated reductions in energy intake, appetite, and food reward with semaglutide that may drive initial weight loss. These brief studies could not assess whether semaglutide has long-term effects on eating that support the maintenance of lost weight. OBJECTIVES: The goal of the present study was to compare short- and long-term energy intake, appetite, and food reward with semaglutide 2.4 mg to placebo. METHODS: This 60-wk, double-blind trial randomly assigned 120 adults with overweight/obesity in a 3:2 ratio to semaglutide 2.4 mg or placebo. In laboratory assessments at weeks 0, 20, 40, and 60, participants rated their appetite when fasting and for 4 h after a standardized breakfast. Energy intake was measured during an ad libitum lunch. Measures of food reward included the Power of Food Scale. Missing data were estimated using jump-to-reference multiple imputation, and analyses of covariance compared the groups in change at each assessment, controlling for baseline. RESULTS: The semaglutide group had significantly larger reductions from baseline in ad libitum energy intake relative to placebo at weeks 20, 40, and 60, consuming a mean ± standard error of 291.9 ± 64.4, 240.2 ± 87.8, and 269.5 ± 83.6 kcal less, respectively. At week 20, semaglutide-treated participants had significantly greater increases from baseline in appetite suppression after the standardized breakfast [mean difference (MD) = 2197 ± 823] and greater reductions in past-week hunger (MD = -17.4 ± 4.8) and food preoccupation (MD = -14.9 ± 4.5). However, the groups did not differ significantly in appetite outcomes at weeks 40 or 60. The semaglutide group had greater reductions in responsiveness to food at weeks 20 and 40 (MD = -0.4 ± 0.2 and -0.6 ± 0.2, respectively). CONCLUSIONS: In conclusion, semaglutide 2.4 mg continued to help participants consume fewer calories at 20, 40, and 60 wk of treatment, even though some subjective benefits declined. These findings suggest that reduced energy intake is a central mechanism by which semaglutide both induces and maintains weight loss. This study is registered at clinicaltrials.gov as NCT05548647.
Cardiovascular disease risk under low-fat, Mediterranean, and American Heart Association diets: a target trial emulation in United States adults.
Li Y, Stern D, Martínez-González MA … +6 more , Yang S, Chavarro JE, Manson JE, Rimm EB, Platt RW, Chiu YH
Am J Clin Nutr · 2026 Jun · PMID 42323165 · Publisher ↗
BACKGROUND: The Mediterranean diet reduces cardiovascular disease (CVD) risk in European populations, but its long-term effectiveness in United States adults, particularly relative to the American Heart Association (AHA)...
BACKGROUND: The Mediterranean diet reduces cardiovascular disease (CVD) risk in European populations, but its long-term effectiveness in United States adults, particularly relative to the American Heart Association (AHA)-2020 dietary goals, remains uncertain. OBJECTIVES: We compared 20-y CVD risk in United States adults under sustained adherence to a low-fat diet, a Mediterranean diet, and the food-based AHA-2020 dietary goals. METHODS: We emulated a target trial using data from the Nurses' Health Study and Health Professionals Follow-up Study among 12,197 United States adults aged 55 to 80 y with diabetes or ≥3 major CVD risk factor. Diet was assessed every 4 y via validated food frequency questionnaires. The primary outcome was CVD, defined as nonfatal myocardial infarction, coronary revascularization, stroke, and CVD death, confirmed by medical records. We applied the parametric g-formula to estimate 20-y CVD risk under each dietary strategy. RESULTS: Over 20 y, 3469 CVD cases occurred (1451 men and 2018 women). Pooled absolute risks of CVD were 35.9% (95% CI: 33.1%, 38.5%) under the low-fat diet, 28.2% (95% CI: 25.8%, 31.4%) under the Mediterranean diet, and 31.2% (95% CI: 29.1%, 33.4%) under the AHA-2020 dietary goals. Compared with the low-fat diet, estimated risk ratios were 0.79 (95% CI: 0.70, 0.91) for the Mediterranean diet and 0.87 (95% CI: 0.79, 0.96) for the AHA-2020 dietary goals. In a general population not selected for age, diabetes, or CVD risk factors, the corresponding risk ratios were 0.90 (95% CI: 0.84, 0.95) and 0.94 (95% CI: 0.90, 0.99), respectively. CONCLUSIONS: Sustained adherence to the Mediterranean diet and the AHA-2020 dietary goals have a lower 20-y risk of CVD than a low-fat diet in United States adults.
Brain and physiological responses to flavored waters with different sweeteners: a randomized crossover study in healthy young adults.
Smeets PA, Veit R, Oosterink E … +4 more , Meijboom S, Risso D, Preissl H, Kullmann S
Am J Clin Nutr · 2026 Jun · PMID 42323164 · Publisher ↗
BACKGROUND: Drinks with low-no-calorie sweeteners (LNCSs) do not contribute to energy intake but still provide a hedonic experience through sweetness. LNCS can have differential effects on brain areas involved in food in...
BACKGROUND: Drinks with low-no-calorie sweeteners (LNCSs) do not contribute to energy intake but still provide a hedonic experience through sweetness. LNCS can have differential effects on brain areas involved in food intake and reward compared with sugars. OBJECTIVES: This study determined changes in brain activity and the effect on physiological markers following the ingestion of flavored waters sweetened with the sugar sucrose or LNCS. METHODS: Thirty healthy individuals participated in a randomized crossover study with 6 treatments. Participants were scanned after an overnight fast using magnetic resonance imaging, including arterial spin labeling to measure cerebral blood flow (CBF), before and after ingestion of 500-mL drinks: water, or equisweet flavored waters with 25 g sucrose, sucralose, stevia extract, allulose+stevia extract, or monk fruit extract. CBF was measured at baseline and 5 and 30 min; gastric content volume was measured at baseline and 25 and 45 min. Serum insulin and glucose were measured, and participants rated their appetite and thirst throughout each visit. Data were analyzed with linear mixed models. RESULTS: Primary: Hypothalamus CBF was not differentially affected by any of the drinks. In the ventral tegmental area (midbrain), treatment effects differed, with lower ΔCBF after sucrose than water, sucralose and monk fruit drink ingestion at 30 min (difference: ∼8% ± 3%; all P < 0.05). Exploratory whole-brain analyses showed increased CBF after consumption for allulose+stevia (amygdala) and stevia (putamen) compared with sucrose (P < 0.05). Despite its low energy content, allulose+stevia delayed gastric emptying similar to sucrose, whereas only sucrose increased glucose and insulin concentrations. CONCLUSIONS: Although flavored waters with LNCS mostly elicit similar neural and gastrointestinal responses as water, they have some distinct effects on the brain compared with 25 g of sucrose, particularly in reward-related brain areas. Further exploration of the neural and physiological effects of allulose and stevia and dose-dependent investigations are warranted. This study was registered at clinicaltrials.gov as NCT05575687 (https://clinicaltrials.gov/study/NCT05575687).
Nutritional anemia is associated with increased risk of severe COPD exacerbations: a prospective cohort study.
Dehondt V, Kint N, Vanfleteren LE … +1 more , Lahousse L
Am J Clin Nutr · 2026 Jun · PMID 42323163 · Publisher ↗
BACKGROUND: Anemia prevalence in chronic obstructive pulmonary disease (COPD) varies widely across studies, and data on anemia subtypes and their association with mortality or COPD exacerbation readmission are limited. O...
BACKGROUND: Anemia prevalence in chronic obstructive pulmonary disease (COPD) varies widely across studies, and data on anemia subtypes and their association with mortality or COPD exacerbation readmission are limited. OBJECTIVES: We aimed to investigate anemia subtypes and their association with mortality and readmission for acute exacerbation of COPD (AECOPD) in patients hospitalized for AECOPD. METHODS: In this prospective observational cohort study, patients with COPD aged ≥45 y hospitalized for severe exacerbations in a Belgian nationwide database were included. Cox regression models investigated associations between anemia (or its subtypes) and (postdischarge) mortality and AECOPD readmission, adjusted for age, sex, socioeconomic status, smoking, weight, and age-adjusted Charlson Comorbidity Index. Inverse probability of treatment weighting examined the association between anemia treatment and mortality across anemia subtypes. RESULTS: Among 32,152 patients with COPD discharged from the hospital, 5956 (18.5%) had anemia. Nutritional anemia was most frequent (49.3%), followed by anemia of chronic disease (ACD; 31.3%). Anemia was associated with a 30% higher postdischarge mortality risk [adjusted hazard ratio (aHR): 1.30, 95% confidence interval (CI): 1.23, 1.37], and 8% higher readmission risk (aHR:1.08, 95% CI: 1.03, 1.14). Patients with hematologic anemia had the highest postdischarge mortality risk (aHR: 1.75, 95% CI: 1.54, 1.99), followed by nutritional anemia (aHR: 1.29, 95% CI: 1.20, 1.39). Only nutritional anemia was associated with increased readmission risk (aHR: 1.18, 95% CI: 1.10, 1.25). Treatment effects differed by anemia subtype, with iron, vitamin B12, and erythroid-stimulating agent (ESA) associated with lower postdischarge mortality in nutritional anemia; folic acid and iron in hematologic anemia; and ESA and iron in ACD. CONCLUSIONS: Nutritional anemia is the predominant subtype in hospitalized patients with AECOPD, and its increased readmission risk calls closer attention to iron deficiency in patients with COPD. All subtypes of anemia are associated with higher postdischarge mortality risk, but targeted treatment may reduce mortality risk and represents a potential strategy to improve outcomes.
Human-milk vitamin B-3 (niacin and vitamer) concentrations: secondary analysis of a randomized, placebo-controlled trial of maternal nicotinamide supplementation in rural Tanzania.
DeBoer MD, McDermid JM, Hampel D … +9 more , Shahab-Ferdows S, Mazzoni G, Peerson JM, Elwood SE, Scharf RJ, Jatosh S, Platts-Mills JA, Mduma E, Allen LH
Am J Clin Nutr · 2026 Jun · PMID 42309304 · Publisher ↗
BACKGROUND: The risk of vitamin B-3 (niacin) deficiency is increased if maize is consumed without improving bioavailability during food preparation and with limited consumption of niacin-rich foods. OBJECTIVES: We assess...
BACKGROUND: The risk of vitamin B-3 (niacin) deficiency is increased if maize is consumed without improving bioavailability during food preparation and with limited consumption of niacin-rich foods. OBJECTIVES: We assessed human-milk vitamin B-3 concentrations and their relationship to child outcomes as a secondary analysis of a randomized controlled trial of nicotinamide supplementation to lactating mothers in rural Tanzania. METHODS: The Early Life Interventions for Childhood Growth and Development in Tanzania study, conducted in Haydom, Tanzania, randomly assigned lactating females to supplemental nicotinamide (250 mg/d compared with placebo) from study entry (infant age <2 wk) until 6 mo. Among 1173 mother/child dyads, human-milk nicotinamide and B3 vitamer concentrations at lactation months 1 and 5 were compared with international reference limits (fifth and 95th percentile) from the recent Mothers, Infants and Lactation Quality study, and child anthropometry and cognitive development [Malawi Developmental Assessment Tool (MDAT)] relationships were assessed. RESULTS: The proportion of human-milk total vitamin B-3 concentrations below the lower reference limit increased over time in both those without and with nicotinamide supplementation (2.9% compared with 0.5% ≤0.720 mg/L at 1 mo; 28.8% compared with 9.9% ≤0.549 mg/L at 5 mo). Maternal nicotinamide supplementation was associated with many participants having human-milk total vitamin B-3 concentrations exceeding the upper reference limit (72.9% ≥3.284 mg/L at 1 mo; 50.7% ≥2.760 mg/L at 5 mo), and a sustained higher median concentration with supplementation compared with placebo (by 291% at month 1 and 281% at month 5). No associations were observed between human-milk total vitamin B-3 or vitamer concentrations and child weight, height, or head circumference ≤18 mo or with MDAT scores at 18 mo. CONCLUSIONS: Without maternal nicotinamide supplementation, lactating females had a greater prevalence of human-milk total vitamin B-3 concentrations below the fifth percentile reference limit. Although supplementation was associated with greater total vitamin B-3 and vitamer concentrations, there was no association between human-milk vitamin B-3 and child growth or development outcomes ≤18 mo. This study was registered at clinicaltrials.gov as NCT03268902.
Association between BMI-discordances in cardiometabolic biomarkers and risk of incident heart failure: a prospective cohort study.
Zhang S, Borné Y, Huang T … +2 more , Ma L, Qi L
Am J Clin Nutr · 2026 Jun · PMID 42309303 · Publisher ↗
BACKGROUND: Obesity is a major risk factor for heart failure (HF). However, individuals with similar body mass index (BMI), the main diagnostic measure of obesity, exhibit considerable heterogeneity in developing HF. OBJ...
BACKGROUND: Obesity is a major risk factor for heart failure (HF). However, individuals with similar body mass index (BMI), the main diagnostic measure of obesity, exhibit considerable heterogeneity in developing HF. OBJECTIVES: This study aimed to investigate the association between metabolically discordant subgroups characterized by cardiometabolic biomarkers deviated from those predicted by BMI and risk of incident HF. METHODS: Data from 394,198 participants in the United Kingdom Biobank were analyzed. A data-driven cluster approach was used to classify BMI subgroups according to cardiometabolic biomarker profiles. Incident HF during the follow-up was ascertained using the International Classification of Diseases, Tenth Revision codes. Cox proportional hazards models were applied to assess the association of the subclassified BMI with HF risk. RESULTS: Over a median follow-up of 12.3 y, 5176 (2.94%) males and 3602 (1.65%) females developed the first incidence of HF. Compared with participants in BMI-concordant subgroups, individuals with C-reactive protein or blood glucose deviating from the expected risk based on their BMI showed a higher risk of HF. The fully adjusted hazard ratios (95% confidence intervals) for HF in relation to discordant inflammatory state and discordant hyperglycemic status were 1.59 (1.40, 1.80) and 1.39 (1.22, 1.60) in males and 2.03 (1.77, 2.34) and 1.80 (1.53, 2.12) in females, respectively. In contrast, individuals with discordantly high blood pressure (only in females) or adverse blood lipid levels demonstrated a lower risk of HF than those in BMI-concordant subgroups. No significant association with HF was observed for discordant liver transaminase subgroups. CONCLUSIONS: Metabolically distinct BMI subgroups exhibit varying risks of HF, suggesting that subclassifying BMI based on cardiometabolic biomarkers may facilitate the precision prevention of HF.
Physical inactivity as an upstream driver of metabolic dysfunction: a perspective.
Miller TA
Am J Clin Nutr · 2026 Jun · PMID 42309302 · Publisher ↗
Obesity and metabolic dysfunction are often discussed as though they are interchangeable, yet contemporary frameworks increasingly distinguish excess adiposity, a heterogeneous risk state, from clinical disease character...
Obesity and metabolic dysfunction are often discussed as though they are interchangeable, yet contemporary frameworks increasingly distinguish excess adiposity, a heterogeneous risk state, from clinical disease characterized by physiological impairment. At the same time, current evidence on sedentary physiology indicates that low physical activity and prolonged sedentary behavior directly affect insulin sensitivity, glucose handling, vascular function, and metabolic regulation, even before major changes in body mass occur. This perspective argues that physical inactivity deserves greater attention as an upstream contributor to metabolic dysfunction. The central claim is not that diet is unimportant, nor that physical inactivity explains all variation in adiposity, but that low habitual movement may reduce metabolic capacity and thereby increase vulnerability to dietary burden, ectopic lipid deposition, and cardiometabolic disease. Descriptive long-term United States trends in obesity prevalence, caloric availability, occupational physical activity, and diagnosed diabetes are considered historical context, not causal evidence. These patterns support the need for models that distinguish adiposity from metabolic disease while also considering how population-wide reductions in routine movement may have altered metabolic vulnerability. This interpretation is consistent with experimental inactivity models and longitudinal evidence suggesting dynamic relationships among sedentary behavior, physical activity, and fat mass over time. Recent doubly labeled water analyses caution against overly simplistic claims that modern obesity can be explained solely by lower total daily energy expenditure. Rather than weakening the case for inactivity, these findings suggest that movement pattern, muscular loading, sedentary accumulation, and energy flux may matter in ways not captured by total energy expenditure alone. Physical inactivity should therefore be treated not as a secondary modifier but as a major upstream contributor to metabolic dysfunction, interacting with diet, adipose biology, and genetic susceptibility.
Rethinking the impact of dietary sodium and potassium on blood pressure to advance public health.
Fukagawa NK, Welling PA, Johnson J … +3 more , Reimers K, Lee SY, Zecca P
Am J Clin Nutr · 2026 Jun · PMID 42288189 · Publisher ↗
Public health guidelines emphasize sodium reduction as the key nutrient-focused dietary strategy to reduce hypertension and cardiovascular disease risk. However, successful reduction in sodium intake remains a significan...
Public health guidelines emphasize sodium reduction as the key nutrient-focused dietary strategy to reduce hypertension and cardiovascular disease risk. However, successful reduction in sodium intake remains a significant challenge because of the prevalent preference for salt taste as well as the complexity of multiple interacting factors such as different dietary habits, food production, and biological/cultural variability in consumers. Although the role of potassium in blood pressure (BP) management has been acknowledged, the evidence for potassium's effect on BP has not been as strong as that for sodium, but this is changing. New understanding of the critical role inadequate potassium intake plays in the etiology of hypertension indicates that the nutrient-based public health strategy should now include increased potassium intake as a partner with sodium reduction. Although it is evident that a comprehensive strategy combining education, consumer engagement, technological innovation, and culturally relevant interventions is essential to improving cardiovascular health, we propose that dietary impact will be greater if we embrace a paradigm shift from the singular focus on sodium reduction to include increasing potassium intake. This article reviews the basis for current intake recommendations for sodium and potassium, the strategies for sodium reduction and potassium enhancement, challenges for implementation, and future directions for research and policy to accelerate public health progress at a time of rapid changes in the food supply and consumer choices.
Corrigendum to "Effects of Mediterranean diet or Mindfulness-Based Stress Reduction during pregnancy on maternal gut and vaginal microbiota: a subanalysis of the Improving Mothers for a better PrenAtal Care Trial BarCeloNa (IMPACT BCN) trial." [Am J Clin Nutr. 2025 Oct;122(4):1121-1133. doi: 10.1016/j.ajcnut.2025.07.030. Epub 2025 Aug 5. PMID: 40759394; PMCID: PMC12674037.].
Selma-Royo M, Crispi F, Castro-Barquero S … +18 more , Casas I, Larroya M, Genero M, Paules C, Benitez L, Youssef L, Pascal R, Encabo N, Nakaki A, Martín-Asuero A, Oller-Guzmàn MT, Arranz A, Vieta E, Casas R, Estruch R, Gratacos E, Collado MC, Crovetto F
Am J Clin Nutr · 2026 Jun · PMID 42276149 · Publisher ↗
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Interpreting ultraprocessed food trial evidence: evidentiary limits, reporting practices, and policy relevance.
Louie JCY
Am J Clin Nutr · 2026 Jun · PMID 42269970 · Publisher ↗
Ultraprocessed foods (UPFs) have become a central topic in nutrition science, with extensive observational research linking higher intake to adverse health outcomes. More recent randomized controlled trials have been pre...
Ultraprocessed foods (UPFs) have become a central topic in nutrition science, with extensive observational research linking higher intake to adverse health outcomes. More recent randomized controlled trials have been presented as strengthening causal claims, yet closer examination reveals a pattern of interpretation that extends beyond what the data support. This perspective reviews 4 trials that directly compared ultraprocessed diets with minimally processed diets, examining both their findings and how those findings have been represented in scientific commentary. Across all studies, the comparison group limited the ability to isolate processing as the causal factor, as multiple dietary features differed simultaneously. Reporting consistently emphasized findings aligning with expectations of harm while downplaying neutral or contradictory evidence, including favorable clinical markers and higher adherence in some ultraprocessed conditions. Methodological limitations were also underrepresented in secondary interpretations. The current experimental evidence therefore requires cautious interpretation. Specifically, 4 actionable recommendations follow from this analysis: 1) future trials should match intervention arms on nutrient composition so that processing effects can be disaggregated from nutritional quality effects; 2) adherence and dropout rates should be reported as primary, not secondary, outcomes; 3) terms such as "excess consumption" and "overeating" should be reserved for conditions of positive energy balance and weight gain; and 4) the heterogeneity within NOVA Group 4 warrants subcategory analyses rather than class-wide causal claims. Without these changes, the evidentiary basis for UPF policy risks overstating certainty and misdirecting intervention targets.
Circulating palmitoleic acid is associated with cerebral glucose metabolism in healthy middle-aged individuals: results from the Progression of Early Subclinical Atherosclerosis prospective cohort study.
Sala-Vila A, Tristão-Pereira C, Lázaro I … +12 more , Shekari M, Fernández-Pena A, Monereo-Sánchez J, Garcia-Lunar I, Perez-Herreras C, Moro MA, Garcia-Alvarez A, Sanchez-Gonzalez J, Gispert JD, Ibanez B, Fuster V, Cortes-Canteli M
Am J Clin Nutr · 2026 Jun · PMID 42269969 · Publisher ↗
BACKGROUND: Excess energy intake upregulates de novo lipogenesis (DNL). Circulating palmitoleic acid (POA) is an objective DNL biomarker associated with higher cardiovascular risk, which has been linked to cerebral hypom...
BACKGROUND: Excess energy intake upregulates de novo lipogenesis (DNL). Circulating palmitoleic acid (POA) is an objective DNL biomarker associated with higher cardiovascular risk, which has been linked to cerebral hypometabolism. Whether POA also relates to altered cerebral glucose metabolism in midlife remains unknown. OBJECTIVES: This study aimed to examine cross-sectional and longitudinal associations between circulating POA (predictor) and cerebral glucose hypometabolism (outcome), a neuroimaging marker linked to increased risk of subsequent cognitive decline. METHODS: We studied 461 middle-aged [median age, 51 (47-54) y] individuals with subclinical atherosclerosis from the Progression of Early Subclinical Atherosclerosis (PESA) study, a longitudinal observational cohort of asymptomatic individuals (NCT01410318). Red blood cell (RBC) POA was quantified by gas chromatography in blood samples collected at 2 visits of PESA participants who had undergone longitudinal cerebral F-fluorodeoxyglucose (FDG) positron emission tomography (4.9 y of follow-up time). Dietary data were derived from a validated food-frequency questionnaire. Associations were assessed using region-of-interest and voxelwise multiple regression models as well as mediation analysis. RESULTS: Cross-sectionally, higher RBC POA was associated with widespread lower FDG uptake across the brain [β = -0.119 (95% confidence interval: -0.206, -0.032), P = 0.007], even after adjusting for cardiovascular risk. Longitudinally, participants with sustained high RBC POA exhibited a 65% greater decline in cerebral FDG uptake compared with those with sustained low POA [β = -0.403 (-0.744, -0.063), P = 0.021], particularly in frontal and parietal regions. RBC POA concentrations were higher among individuals adhering to the predefined "Social-Business" dietary pattern and were significantly associated with increased alcohol intake. Furthermore, the association between alcohol intake and subsequent precuneus hypometabolism was partially mediated by RBC POA concentrations. CONCLUSIONS: RBC POA, a marker of DNL, is associated with cerebral glucose hypometabolism, supporting that healthy dietary habits in midlife are key to preserving brain health. This trial was registered at clinicaltrials.gov as NCT01410318.
Effects of 12-month probiotic supplementation on bone mineral density and bone turnover markers in early postmenopausal females: A double-blind randomized controlled trial.
Resciniti S, Dacaya P, Yim K … +6 more , Esmaili T, Vinh A, Galvão HB, Ghasem-Zadeh A, Biesiekierski JR, Moschonis G
Am J Clin Nutr · 2026 Jun · PMID 42264450 · Publisher ↗
BACKGROUND: Early postmenopausal females experience rapid bone loss, and modulation of the gut-bone axis has been proposed as a preventive strategy. However, the role of probiotics relative to established lifestyle facto...
BACKGROUND: Early postmenopausal females experience rapid bone loss, and modulation of the gut-bone axis has been proposed as a preventive strategy. However, the role of probiotics relative to established lifestyle factors such as nutrition and physical activity remains unclear. OBJECTIVES: To evaluate whether 12 mo of supplementation with a lactobacilli-based probiotic attenuates bone loss in early postmenopausal females. METHODS: In this double-blind, randomized, placebo-controlled trial, 114 females 1 to 8 y postmenopause were allocated to a daily probiotic (Lactiplantibacillus plantarum DSM15312, DSM15313, and Lacticaseibacillus paracasei DSM13434) or placebo. The primary outcome was change in distal tibia total volumetric bone mineral density (BMD) assessed by high-resolution peripheral quantitative computed tomography. Secondary outcomes included additional high-resolution peripheral quantitative computed tomography parameters, areal BMD by dual-energy X-ray absorptiometry, and circulating biomarkers. Intention-to-treat analyses were conducted using linear mixed-effects models, adjusted for baseline covariates; secondary outcomes were corrected for multiple comparisons. RESULTS: A total of 114 participants were randomly assigned, and all available data were included in the analyses. Baseline characteristics were broadly comparable. Over 12 mo, both groups experienced modest declines in bone density. The primary analysis showed a modest but statistically significant greater decline in distal tibia total volumetric BMD in the probiotic group compared with placebo (-3.7 mg HA/cm; 95% confidence interval: -6.9, -0.4 mg HA/cm; P = 0.027). Similar trends were observed at other peripheral sites, but most secondary outcomes were not significant after multiple testing correction. No treatment effects were observed for bone turnover, calciotropic, or inflammatory markers. CONCLUSIONS: In early postmenopausal females, 12-mo supplementation with a lactobacilli-based probiotic did not attenuate bone loss and was associated with a small but statistically significant greater reduction at the primary site. These findings do not support this probiotic formulation as a standalone intervention for skeletal preservation. This trial was registered at the Australian and New Zealand Clinical Trials Registry as ACTRN12621000810819.
Integrated community case management plus compared with outpatient therapeutic programs: a quasi-experimental study among children with severe acute malnutrition in Jowhar, Somalia.
Bollemeijer I, Majer J, Ndung'u NM … +6 more , Ahmed ZD, Mohamud AE, Gulled GA, Verhoef H, Melse-Boonstra A, King S
Am J Clin Nutr · 2026 Jun · PMID 42264153 · Publisher ↗
BACKGROUND: WHO guidelines endorse treatment of severe acute malnutrition (SAM) by community health workers as an alternative to facility-based care, but supportive evidence for this shift is low. OBJECTIVES: Among Somal...
BACKGROUND: WHO guidelines endorse treatment of severe acute malnutrition (SAM) by community health workers as an alternative to facility-based care, but supportive evidence for this shift is low. OBJECTIVES: Among Somali children with uncomplicated SAM, we compared recovery between facility-based outpatient therapeutic programs (OTP) and integrated community case management (iCCM+), examining weight change, length of stay, discharge anthropometry, and overall anthropometric change. METHODS: In a quasi-experimental study (3 January-19 May, 2024), children with uncomplicated SAM [weight-for-height Z-scores (WHZ) < -3 SD and/or mid-upper arm circumference (MUAC) ≤115 mm] were enrolled for treatment in OTP (2 sites, 638 children) or iCCM+ (8 villages, 545 children). During weekly follow-up visits, children received nutritional assessments, ready-to-use therapeutic food, and routine medications until discharge (MUAC >115mm; WHZ > -3SD). Weight change and time-to-recovery were analyzed using generalized linear mixed-effects models and Cox proportional hazards models, respectively. To adjust for baseline differences in observed covariates, we used inverse probability weighting based on propensity scores. RESULTS: At enrolment, OTP children had more severe anthropometric deficits than their peers in the iCCM+ group (WHZ<-3SD: 48% compared with 42%, P = 0.04; MUAC ≤110 mm: 34% compared with 18%, P < 0.001). Recovery proportions were similar between groups (iCCM+: 89%; OTP: 91%). In adjusted analyses, no difference was observed in weight change over time. The iCCM+ group had a shorter median length of stay (by 7 d) and faster time-to-recovery (adjusted hazard ratio: 3.32, 95% CI: 2.70, 4.09). CONCLUSIONS: Treatment outcomes were similar between approaches; iCCM+ enabled earlier identification and shorter length of stays, suggesting improved efficacy and reduced burden on caregivers and health systems. It shows promise for expanding SAM treatment in settings with limited OTP access.
Enteral iron dose effect on iron storage, intestinal barrier, and gut microbiome in preterm infants: a randomized clinical trial.
Gibbons JA, Nelson RM, Dabrowski CN … +13 more , Narkhede A, Szalacha LA, Kneusel ML, Maru JS, Huszar MR, Hoang LK, Schiavo V, Eddins AC, Georgieff MK, Neu J, Donovan SM, Groer MW, Ho TT
Am J Clin Nutr · 2026 Jun · PMID 42264152 · Publisher ↗
BACKGROUND: Preterm infants routinely receive enteral iron supplementation to support growth, replace phlebotomy losses, and prevent iron deficiency. However, concerns regarding potential harms, including those on the gu...
BACKGROUND: Preterm infants routinely receive enteral iron supplementation to support growth, replace phlebotomy losses, and prevent iron deficiency. However, concerns regarding potential harms, including those on the gut microbiome, have contributed to recommendations for lower dosing. OBJECTIVES: This study aimed to compare the effects of 2 enteral iron doses on gut health in very-low-birth-weight preterm infants. We hypothesized that higher iron dose would increase abundances of pathogenic bacteria, intestinal inflammation, and barrier dysfunction. METHODS: This randomized, double-blind clinical trial assigned preterm infants born <1500 g to receive either the recommended dose, 2 mg/kg/d, or a higher dose of 6 mg/kg/d of total enteral iron. The primary outcome was the fecal microbiome after 2 wk on iron, assessed by metagenomic sequencing. Secondary outcomes included biomarkers of intestinal inflammation and barrier function (fecal calprotectin, urinary claudin-3, and urinary intestinal fatty acid-binding protein). Iron status, adverse events, and auditory brainstem response latencies at 36 wk postmenstrual age were also evaluated. RESULTS: Among 151 randomly assigned infants who received study iron (77 low dose; 74 high dose), bacterial diversity, individual taxa, virulence potential, bacterial overgrowth, and iron-related functional genes were not significantly different between the treatment groups. In the subgroup analysis of singletons, treatment groups demonstrated significant differences in temporal shifts in overall bacterial community structure. Infants receiving 2 mg/kg/d had higher posttreatment urinary claudin-3 concentrations, indicating possible differences in intestinal permeability, and a higher prevalence of iron deficiency than those receiving 6 mg/kg/d. Other biomarkers, clinical outcomes, adverse events, and auditory latencies did not differ between groups. CONCLUSIONS: Enteral iron supplementation at 6 mg/kg/d was associated with improved iron status and lower intestinal barrier dysfunction, without evidence of harms on gut microbiome compared with the recommended 2 mg/kg/d dose. These findings do not support concerns regarding gut microbiome disruption as a justification for lower iron dosing in preterm infants. This trial was registered at clinicaltrials.gov as NCT04497012.
Low folate status and related polymorphisms are associated with lower sperm quality in healthy males: The Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters (Led-Fertyl) cross-sectional study.
Eigbefoh-Addeh A, Salas-Huetos A, Ramos-Rodríguez C … +7 more , Santos-Calderón LA, Agarwal R, Salas-Salvadó J, Babio N, McCann A, Ueland PM, Murphy MM
Am J Clin Nutr · 2026 Jun · PMID 42250605 · Publisher ↗
BACKGROUND: Folate-mediated one-carbon metabolism is essential for deoxyribonucleic acid synthesis, methylation, and genomic integrity during spermatogenesis. OBJECTIVES: To study the associations between the status of f...
BACKGROUND: Folate-mediated one-carbon metabolism is essential for deoxyribonucleic acid synthesis, methylation, and genomic integrity during spermatogenesis. OBJECTIVES: To study the associations between the status of folate, cobalamin, homocysteine, single nucleotide polymorphisms (SNPs) affecting folate-mediated one-carbon metabolism, and sperm quality. METHODS: In this cross-sectional study, 197 healthy males (18‒40 y) were recruited between 2021 and 2023. Plasma folate, red blood cell folate (RBCF), plasma cobalamin, total homocysteine, and SNPs affecting folate and cobalamin status were determined. Sperm quality parameters were assessed by World Health Organization 2010 criteria. Associations between B-vitamin status, genetic polymorphisms, and sperm quality parameters were assessed using multivariable linear and logistic regression analysis. RESULTS: Median (25th and 75th percentiles) plasma folate was 14.2 (11.0, 17.8) nmol/L, and RBCF was 678.2 (582.3, 785.0) nmol/L. Deficiency, plasma folate <7 nmol/L and RBCF (<340 nmol/L), occurred in 4.6% [95% confidence interval (CI): 2.4%, 8.5%] and 2.6% (95% CI: 1.1%, 5.8%) of participants, respectively. Lowest compared with highest tertile plasma folate (<11.9 nmol/L compared with ≥17.0 nmol/L) and RBCF (<625.0 nmol/L compared with ≥742.1 nmo/L) were associated with lower sperm count [B = ‒0.428, standard error (SE): 0.196 and B = ‒0.459, SE: 0.183, respectively] and higher odds of altered seminogram [odds ratio: (OR): 3.367; 95% CI: 1.379, 8.220 and OR: 2.305; 95% CI: 1.002, 5.306, respectively]. Median (25th and 75th percentiles) plasma cobalamin was 239.1 (203.0, 282.3) pmol/L and plasma total homocysteine was 9.6 (7.8, 11.5) μmol/L. Cobalamin deficiency (<148 pmol/L) and plasma total homocysteine >15 μmol/L were observed in 1.5% (95% CI: 0.5%, 4.4%) and 5.6% (95% CI: 3.1%, 9.7%) of participants, respectively. Neither was associated with sperm quality parameters. The MTHFD1 1958AA compared with GG genotype was associated with reduced progressive motility (B = ‒7.732%, SE: 3.782), and higher odds of altered seminogram (OR: 4.388; 95% CI: 1.407, 13.687). CONCLUSIONS: Low folate status is negatively associated with sperm quality. The MTHFD1 1958AA genotype may be negatively associated with sperm quality.
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