Nutrients doi: 10.3390/nu18223791

Authors: Shotaro Nakashima Koji Yamatsu

Background/Objectives: Proper adherence to dietary guidelines and regular physical activity (PA) are important for chronic disease prevention. However, the prevalence of adherence to the protein-fat-carbohydrate (PFC) balance guidelines and its association with PA among Japanese adults remain unclear. This study examined adherence to the PFC-balance guidelines and its association with PA among Japanese adults living in Saga Prefecture. Methods: This cross-sectional study included 2545 randomly selected Japanese adults living in Saga Prefecture. Dietary intake was assessed using the Brief-type self-administered Diet History Questionnaire (BDHQ), and PA was assessed using the Japanese version of the International Physical Activity Questionnaire Short Form (IPAQ-SF). Modified Poisson regression analyses were performed with adjustment for sociodemographic factors. Results: Only 135 participants (5.3%) achieved full adherence to the PFC-balance guidelines. Adherence rates for protein (PRT), fat (FAT), and carbohydrate (CHO) were 36.8%, 27.1%, and 27.5%, respectively. PA guideline adherence was positively associated with CHO guideline target. No significant association was observed with full adherence to the PFC-balance guidelines. Moderate-to-vigorous physical activity and vigorous-intensity PA was significantly associated with PRT guideline target. Conclusions: Full adherence to the PFC balance guidelines may be difficult to achieve. Adherence to the PA guideline was positively associated with adherence to the CHO target, while moderate-to-vigorous PA and vigorous-intensity PA were positively associated with adherence to the PRT target. These associations differed by PA measure and intensity.

Nutrients doi: 10.3390/nu18223790

Authors: Mohammad Idreesh Khan

The C-reactive protein-to-albumin ratio (CAR) is a readily available composite biomarker reflecting systemic inflammatory activity and changes in circulating albumin, but its nutritional interpretation and clinical utility remain incompletely defined. This narrative review critically examines the biological basis, nutritional and functional relevance, clinical evidence, comparative performance, methodological limitations, and potential precision-nutrition role of CAR. PubMed/MEDLINE, Embase, Scopus, and Web of Science Core Collection were searched from database inception through 20 August 2026, supplemented by citation tracking and relevant consensus and methodological literature. Across diverse clinical populations, higher CAR has generally been associated with adverse outcomes, while nutrition- and function-focused studies link elevated CAR with nutritional risk, frailty, sarcopenia, and impaired physical performance. Reported discrimination for nutrition- and function-related outcomes has been context dependent, with selected area under curve (AUCs) ranging from 0.619 to 0.814. Current evidence does not establish CAR as consistently superior to CRP, albumin, or established inflammatory and nutrition-related indices. Interpretation is further limited by heterogeneity in assay and calculation conventions, sampling time, organ dysfunction, fluid status, study-derived cut-offs, and limited external validation. CAR should therefore be regarded as an inflammation-associated marker of nutritional and physiological vulnerability rather than a diagnostic marker of malnutrition. Future research should prioritize standardized measurement, prospective construct validation, longitudinal and multicentre validation, incremental and clinical-utility evaluation, and randomized assessment of CAR-by-intervention effects before precision-nutrition treatment selection is considered.

Nutrients doi: 10.3390/nu18223789

Authors: Yabin Zhou Jin Hua

Exogenous dietary microRNAs, commonly referred to as xenomiRs, have been proposed to survive digestion, enter animal tissues, and regulate host gene expression, with plant-derived miRNAs representing one of the most debated sources. This review critically evaluates evidence for plant-derived xenomiR stability, uptake, and tissue accumulation in mammals, with particular emphasis on differential detection patterns between gastrointestinal and systemic compartments. This review also examines proposed mechanisms of gastrointestinal uptake and retention and considers their potential relevance to local gastrointestinal physiology. Current evidence indicates that some plant miRNAs can persist through digestion, although survival varies substantially by miRNA species, food matrix, and experimental protocol. Detection in gastrointestinal contents or feces supports persistence but does not establish cellular internalization, cytosolic delivery, or sequence-specific gene regulation. Studies provide the strongest in vivo support for SIDT1-mediated gastric uptake under acidic conditions, while intestinal uptake remains less well defined and may involve endocytic routes, vesicle-associated delivery, and cell-type-specific interactions. Overall, these findings motivate a gut-local hypothesis, but gastrointestinal detection does not establish cellular uptake or local gene regulation. Direct evidence linking ordinary dietary exposure to functionally available intracellular miRNAs and sequence-specific target regulation remains limited in both gastrointestinal and systemic tissues.

Nutrients doi: 10.3390/nu18223788

Authors: Katherine J. Ball Maria Woloshynowych Ihab Tewfik

Background: Fashion models are widely assumed to eat very little, yet their own dietary intake has rarely been measured. Most research regarding this occupational group has examined the effects of images of thin models on the body image of the wider public rather than on the nutritional health of the models themselves. Objective: This exploratory study measured the anthropometric status, energy intake and macronutrient and micronutrient intake of professional female and male fashion models working through agencies in the four principal fashion capitals (New York, London, Milan and Paris) and used the findings to design a preliminary tailored nutrition intervention framework. Methods: Eleven models (8 female, mean age 25.8 years; 3 male, mean age 32.7 years) completed a three-day self-reported food diary and had height and weight measured and basal metabolic rate estimated by bioelectrical impedance. Diaries were analysed in Nutritics, with energy requirements estimated from basal metabolic rate and a low physical activity level (1.49). Results: Female models had a mean body mass index (BMI) of 18.34 kg/m2 and male models 22.29 kg/m2. Both groups consumed fewer calories than their estimated requirement (female mean intake 1616 kcal/day compared with an estimated requirement of 2047 kcal/day; male mean intake 2222 kcal/day against 3172 kcal/day), yet both consumed more than the reported national average and met most micronutrient reference values. Mean intakes of calcium, iron, selenium and vitamin D fell below UK reference nutrient intakes in one or both groups, and female vitamin E intake was below the European adequate intake; without biochemical measures, these indicate a risk of inadequate intake rather than confirmed deficiency. Based on these apparent shortfalls and the occupational constraints described by the cohort, a Tailored Nutritional Care (TNC) cookbook and educational guideline were developed, offering 53 recipes across four dietary patterns (vegan, vegetarian, omnivore, and low-FODMAP) and the four fashion capitals. Conclusions: These findings come from 11 models, rely on three days of self-reported intake and on estimated requirements, and cannot be generalised to fashion models as a whole. The intervention is preliminary: its feasibility, acceptability, safety and effectiveness have not yet been tested.

Nutrients doi: 10.3390/nu18223787

Authors: Wanli Zang Jiarong Wu Qiuxia Zhang

Background/Objectives: Evidence on subsequent dietary changes associated with leisure-time exercise participation patterns remains limited. We examined these associations among Chinese adults. Methods: We used two China Health and Nutrition Survey sequences (T0–T1–T2): 2004–2006–2009 and 2006–2009–2011. Linear regression examined associations between reported T0–T1 participation patterns and T1-to-T2 changes in energy intake and protein density (co-primary outcomes) and absolute protein intake, adjusting for T0 and T1 dietary levels and covariates and accounting for repeated observations and community clustering. Holm correction was applied within comparison families. Results: The analysis included 6279 adults contributing 10,016 observations. Compared with reporting no leisure-time exercise at either assessment, reporting exercise only at T1 or at both assessments was associated with adjusted between-group differences in protein density change of 1.30 (95% confidence interval [CI], 0.59 to 2.00) and 2.09 (95% CI, 0.70 to 3.48) g/1000 kcal, respectively (Holm-adjusted p = 0.002 and 0.017). Corresponding adjusted differences in absolute protein intake change were 0.66 (95% CI, −1.53 to 2.84) and 4.28 (95% CI, 1.20 to 7.36) g/day (Holm-adjusted p = 1.000 and 0.020); statistical support for the latter varied across sensitivity analyses. The energy omnibus test was significant (Holm-adjusted p = 0.044), but individual energy contrasts were not significant after correction. Direct comparisons between these participation groups were not significant for any of the three outcomes after correction. Conclusions: Compared with nonparticipation at both assessments, reported participation only at T1 or at both assessments was associated with modestly greater subsequent protein density changes. Interpretation should consider both protein density and absolute protein intake.

Nutrients doi: 10.3390/nu18223786

Authors: Maya Taha Tanzina Ferdous Riya Claire Shen James H. Segars Md Soriful Islam

Oxidative stress, inflammation, metabolic dysregulation, and altered extracellular matrix (ECM) remodeling are involved in reproductive physiology and contribute to the pathophysiology of several gynecological disorders. Strawberry (Fragaria × ananassa) is a widely consumed fruit rich in bioactive compounds, including anthocyanins, ellagitannins, flavonols, phenolic acids, and vitamin C. Strawberries and their bioactive compounds have demonstrated a range of biological activities in experimental studies, including antioxidant, anti-inflammatory, and antifibrotic effects, suggesting potential benefits for reproductive health and selected gynecological conditions. This narrative review summarizes current evidence regarding the potential roles of strawberries and their bioactive compounds in female reproductive health and related diseases. Potential benefits for fertility, oocyte health, ovarian aging, and menopause are biologically plausible but remain supported primarily by preclinical studies and indirect clinical evidence rather than human studies directly evaluating reproductive outcomes. Preclinical studies of uterine fibroids have shown that strawberry extracts reduce fibroid cell viability and glycolysis, promote apoptosis, and modulate ECM-related pathways. A small randomized pilot trial reported reduced menstrual pain following fresh strawberry consumption in women with primary dysmenorrhea. Experimental studies further suggest antiproliferative and proapoptotic effects of strawberry-derived preparations in models of breast, ovarian, and cervical cancers, although evidence of clinical efficacy is lacking. Overall, strawberries represent a dietary source of bioactive compounds with potential relevance to women’s reproductive health and selected gynecological diseases, but further mechanistic and clinical studies are needed to establish their potential preventive or therapeutic benefits.

Nutrients doi: 10.3390/nu18223785

Authors: Wentao Gu Zhenhua Niu Qisijing Liu Haitao Wang Miao Yu Meiying Xu Xuemeng Ji Dancai Fan Jin Wang Yanrong Zhao Shuo Wang

Background: Activity-related knee discomfort is common in endurance-trained adults. Multi-ingredient supplements targeting complementary biological pathways may support knee comfort and load tolerance in this population, but controlled evidence is limited. Methods: In this randomized, double-blind, placebo- and active-comparator-controlled pilot trial, 60 endurance-trained adults (20 per group) with activity-related knee discomfort received for 12 weeks either a multi-ingredient formula (undenatured type II collagen, curcumin phytosome, and enzymatically hydrolyzed bone powder; Group A), glucosamine hydrochloride plus chondroitin sulfate (Group B), or placebo (Group C). Assessments of functional and patient-reported outcomes were conducted at baseline, week 6, week 12, and 24 h after a post-intervention half-marathon challenge. Outcome measures covered functional pain tolerance, patient-reported pain symptoms, exploratory biomarkers of cartilage turnover, inflammation, and oxidative stress. Results: Group-by-time interactions were significant for SLSD repetitions to pain levels 2 and 5 and for VAS (all p < 0.0001). At week 12, Group A exceeded placebo for the SLSD repetitions to pain level 5 (mean difference 30.5 repetitions; 95% CI 8.7 to 52.3; p = 0.0201), for SLSD repetitions to pain level 2 (21.4; 8.8 to 34.1; p = 0.0037), and for VAS (−1.6; −2.6 to −0.7; p = 0.0030), whereas Group B differed from placebo for SLSD pain level 2 and VAS but not for the SLSD pain level 5. No direct comparison between Groups A and B was statistically significant (all adjusted p > 0.05). After the half-marathon, only Groups B and C showed significant within-group declines in ROM relative to baseline (p = 0.0262 and p = 0.0147), whereas Group A did not (p > 0.99), although between-group ROM contrasts were not significant. Biomarker changes were exploratory, and no between-group biomarker difference reached significance. Conclusions: In this pilot trial, 12 weeks of multi-ingredient supplementation improved pain-limited knee load tolerance and self-reported knee pain relative to placebo in endurance-trained adults. These results require confirmation in a larger trial.

Nutrients doi: 10.3390/nu18223784

Authors: Montserrat Argemí Relat Sergio Abanades Ismael San Mauro Jordi Esquirol Caussa Núria Capdevila Menac

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) involves insulin resistance, altered iron homeostasis, and oxidative stress. We explored changes in hepatic steatosis and cardiometabolic parameters following targeted micronutritional supplementation. Methods: In this prospective, single-centre, open-label, single-arm pilot study, 15 adults with ultrasound-confirmed grade II–III hepatic steatosis and metabolic dysfunction received two micronutrient formulations for four months, without a new weight-loss programme. The prespecified primary efficacy target was a ≥10% reduction in mean Fatty Liver Index (FLI). Secondary outcomes included ultrasound steatosis severity, metabolic and biochemical parameters, quality of life, and safety. Results: The primary efficacy target was not achieved: mean FLI decreased from 59.18 to 56.63 (−4.3%; p = 0.256). Exploratory analyses showed a shift towards lower ultrasound-defined steatosis grades (nominal p = 0.010), with 13 of 15 participants improving and none worsening. Fasting glucose, insulin, homocysteine (−23%), and ferritin decreased, and transferrin saturation increased (nominal p ≤ 0.033), whereas BMI did not change. No serious adverse events occurred. Conclusions: Although the primary endpoint was not met, the exploratory within-participant changes in ultrasound-defined steatosis and selected cardiometabolic biomarkers warrant randomised controlled trials with quantitative hepatic fat assessment.

Nutrients doi: 10.3390/nu18223783

Authors: Ersilia Troiano Martina Tosi Fabrizia Lisso Taira Monge Maurizio Fadda Elena Carrano Vincenzo Bosco Giulia Cairella Nicola Veronese Laura Rossi Elisa Mazza

Background/Objectives: Nutrition research is expanding, yet translating evidence into routine care, public health, and policy remains challenging. Implementation science (IS) offers approaches to identify barriers and support the uptake of evidence-based interventions, but its application in nutrition and dietetics remains fragmented. This narrative review examines the application of IS across four areas: research, clinical practice, primary care and population health, and health systems and policy. Methods: Non-systematic searches of PubMed/MEDLINE and Scopus focused primarily on publications from 2015 to 2026, with earlier foundational papers considered where relevant. Twenty publications were selected purposively for a qualitative synthesis of implementation determinants, strategies, frameworks and reported outcomes. Results: The literature identifies barriers at professional, organizational and system levels, including limited implementation skills, insufficient resources and challenges in adapting interventions to local contexts. Frameworks and theories such as CFIR, NPT and RE-AIM serve distinct purposes in assessing implementation determinants, understanding how practices become embedded and evaluating implementation outcomes. Evidence from reviews and individual studies suggests that implementation strategies may support the integration of nutrition care into clinical practice. However, the evidence base is heterogeneous and includes a substantial proportion of conceptual publications, with limited empirical evaluation across diverse settings. Examples from community programs and health systems illustrate the potential value of context assessment, stakeholder engagement and iterative adaptation. Evidence on long-term sustainability, equity and the implementation of precision nutrition remains limited. Conclusions: IS provides an approach to studying and supporting the integration of evidence into nutrition and dietetics practice. Strengthening implementation training, organizational support and context-sensitive evaluation may help improve the adoption and sustainability of interventions. Further research should assess patient and population outcomes, equity and scalability.

Nutrients doi: 10.3390/nu18223782

Authors: Ghaith M. Al-Taani Aseel O. Rataan Mariam Alameri Alaa Al-Tarawneh Amal S. Albawaana Islam A. Berdaweel Afaf Khasawneh Alaa A. A. Aljabali Ameera M Bataineh Sireen Abdul Rhaim Shilbayeh

Background: Anemia is a universal health problem, especially among children. It affects a country’s development and economic prospects. Understanding its prevalence and associated factors in Jordan is necessary before implementing targeted interventions. Aim: To determine the prevalence of anemia and associated factors among children aged 6 months to 5 years in Jordan using the 2023 Demographic and Health Survey (DHS) data. Methods: We conducted a secondary analysis of the 2023 Jordan DHS database. We defined anemia according to WHO age-specific hemoglobin levels. Chi-square and t-tests were used in univariable analysis. We used logistic regression to assess the independent effects of variables on anemia status. Results: Of 8831 children, 33.6% had anemia; prevalence among children aged 2–5 years was 30.4%, compared with 40.5% among those aged 6 months to 2 years. Independent factors associated with anemia included lower mother’s highest education attainment, a higher number of children in the household, geographical location, and mothers with anemia. Inversely associated factors included older child age and baby formula consumption. Children who consumed fortified foods and nutritional products had lower incidence rates. Differences were observed by geolocation, including among Arab nationals other than Jordanians, by wealth index, and by maternal anemia. Conclusions: Anemia is a public health problem in Jordan. Differences exist at the socioeconomic, maternal, and nutritional levels. The results revealed factors associated with anemia and highlighted the need for interventions to address maternal anemia and improve access to fortified foods.

Nutrients doi: 10.3390/nu18223781

Authors: Melania Melis Gianfranca Carta Silvia Deligia Monica Cabboi Claudia Manca Elisabetta Murru Sebastiano Banni Iole Tomassini Barbarossa

Background/Objectives: Taste sensitivity has been associated with body mass index (BMI) independently of dietary intake, suggesting that taste-related pathways may influence metabolic health beyond food consumption. However, the mechanisms underlying these associations remain unclear. We investigated relationships among taste-related and metabolically relevant single nucleotide polymorphisms (SNPs), body composition, red blood cell (RBC) total lipids, fatty acids (FAs), and lipid mediators to identify potential associations between taste perception and metabolic phenotype. Methods: Body composition, RBC total lipids, FAs, and N-acylethanolamines (NAEs) were assessed in 52 healthy subjects genotyped for selected SNPs in taste-related genes (TAS1R2, TAS1R3, GNAT3, CD36), and genes involved in nutrient-sensing NAE metabolism (FGF21, FAAH and PPARα). The associations were evaluated using explanatory univariate analyses and regression models. Results: Carriers of the GNAT3 rs7792845 CC genotype showed a lower mean fat-free mass percentage and higher RBC total lipids than carriers of the CT genotype. CD36 rs1761667 and rs1984112 were associated with NAE lipid mediators and rs1761667 with RBC total lipids, with AA genotype carriers showing higher mean values. Regression analyses identified GNAT3 rs7792845, FGF21 rs838133, and taste-sensitivity scores associated with body composition, accounting for 41.5% of the variance, and CD36 rs1761667 and rs1984112 associated with lipid and NAE values, accounting for up to 38.1% of the variance. FAAH rs324420 and TAS1R2 rs35874116 were involved in RBG lipid and NAE models. The specific lipid species underlying these associations remain unknown. Conclusions: These findings suggest that sensory- and nutrient-sensing pathways might contribute to interindividual variability in metabolic phenotypes.

Nutrients doi: 10.3390/nu18223780

Authors: Marta Pelczyńska Szymon Starosta Stanisław Pogonowski Emilia Adamczak Michał Rodziak Paweł Bogdański Małgorzata Moszak

Metabolic syndrome (MetS), with obesity as its primary pathogenic driver, is a major public health concern and a leading risk factor for type 2 diabetes (T2D) and cardiovascular disease. Increasing evidence highlights the critical role of the microbiota-gut-brain axis (MGBA) in the pathogenesis of these disorders through its regulation of energy homeostasis, metabolic function, and immune responses. This review summarizes current evidence on the mechanisms by which disturbances in MGBA signaling contribute to the development and progression of MetS. Gut microbiome dysbiosis may increase intestinal permeability, facilitating the translocation of bacterial lipopolysaccharide into the systemic circulation. This process may contribute to metabolic endotoxemia and chronic low-grade inflammation, potentially promoting insulin resistance, adipose tissue dysfunction, and metabolic impairment. In addition, alterations in microbiome composition and function influence the secretion of gut-derived hormones, vagal signaling, hypothalamic–pituitary–adrenal axis activity and bile acid metabolism, ultimately disrupting appetite regulation, glucose homeostasis, lipid metabolism and blood pressure control. Preclinical studies and limited clinical evidence suggest that gut microbiota-targeted interventions, including prebiotics and probiotics, may improve selected metabolic parameters. However, evidence demonstrating sustained clinical benefits or reductions in cardiometabolic events in patients with MetS remains insufficient. Although the MGBA represents a potential therapeutic target, further well-designed randomized controlled trials with predefined metabolic outcomes, direct assessment of microbial function, and adequate follow-up are needed to establish the clinical efficacy and long-term safety of microbiota-targeted interventions, including fecal microbiota transplantation (FMT).

Nutrients doi: 10.3390/nu18223779

Authors: Emilio Ros Sheila López-Ruiz Aleix Sala-Vila Montserrat Cofán Mercè Serra-Mir Irene Roth Mònica Domènech Sujatha Rajaram Joan Sabaté Dolores Corella Gemma Chiva-Blanch

Background and Objectives: Walnuts have recognized health benefits but are fat-rich, raising the concern that regular consumption might increase adiposity. We investigated whether long-term walnut consumption is associated with changes in body composition. Subjects and Methods: The Walnuts And Healthy Aging (WAHA) study is a 2-year, two-center (Barcelona, Spain; Loma Linda, California), randomized controlled trial designed to assess the effects of walnuts on age-related health outcomes. Healthy older adults (63–79 years) were assigned to either a walnut-supplemented diet (15% daily energy) or a control diet (no walnuts). Changes in body weight, BMI, and total fat and fat-free mass, measured by dual-energy X-ray absorptiometry, were pre-specified endpoints. Other body composition variables were secondary endpoints. Changes in circulating leptin and adiponectin and effect modification by obesity-linked variants at the FTO and APOE gene loci were exploratory outcomes. Results: We included 326 participants (220 women) from the Barcelona node. After 2 years, total and android fat mass increased, whereas gynoid fat mass and fat-free mass decreased irrespective of sex and group allocation. There were no effects of walnut vs. control diets on any endpoints, except for a small increase of the android/gynoid ratio in women. On the walnut but not the control diet, men with the CC genotype for the FTO-rs1861868 C > T polymorphism disclosed adverse body composition changes compared to T-allele carriers. However, sample size was small. Effects did not vary by APOE genotype. Conclusions: Two-year walnut consumption had little effect on body composition in older adults. Genetic variability at FTO may modulate the response. The results support the overall harmlessness of walnuts regarding adiposity.

Nutrients doi: 10.3390/nu18223778

Authors: Shuwei Luo Yukun Cheng Jing Sun Jia Xie Kaining Liu Hankun Mao Jianjun Deng Haixia Yang

Background/Objectives: Gallic acid (GA) is a dietary phenolic acid with antioxidant and anti-inflammatory activity, but its poor stability may limit its health-promoting benefits. Plant-derived extracellular vesicles (EVs) are naturally occurring nanostructures that have emerged as potential carriers for dietary bioactive compounds. However, whether tissue origin affects their capacity to load GA and functional performance remains unclear. Methods: Exosome-like nanoparticles (ELNs) with characteristics similar to EVs were isolated from grape skin (GS) and grape pulp (GP) by differential ultracentrifugation and loaded with GA using ultrasound-assisted technology. GA loading efficiency and stability under thermal, ultraviolet (UV), and simulated gastrointestinal conditions were evaluated. The protective effects of GA-loaded ELNs against oxidative stress and inflammatory damage were assessed in RAW264.7 macrophages. Results: At an ELN protein-to-GA mass ratio of 2:1, GS ELNs exhibited a higher GA loading efficiency than GP ELNs (86.06 ± 2.23% vs. 5.25 ± 2.93%) and achieved a GA loading content of 1721.28 ± 44.50 µg/mg. This difference may be associated with the lipid composition of ELNs. Compared with free GA, GA-loaded ELNs exhibited greater stability under thermal, UV, and simulated gastrointestinal conditions. In addition, GA-loaded ELNs also provided protection against oxidative stress and inflammatory damage in RAW264.7 cells. Conclusions: These results provide preliminary evidence that tissue origin influences the functional properties of ELNs, including their loading capacity and ability to enhance the stability of bioactive compounds. In addition, GA-loaded ELNs exhibit antioxidant and anti-inflammatory activities, suggesting their potential nutritional and health benefits.

Nutrients doi: 10.3390/nu18223777

Authors: Maciej Rybiński Emilia Gospodarska Ranjini Ghosh Dastidar Moray J. Campbell Carsten Carlberg

Background/Objectives: Individuals differ in their molecular response to vitamin D3 supplementation. We investigated variation in acute chromatin accessibility changes in peripheral blood mononuclear cells (PBMCs), which predominantly comprise lymphocytes and monocytes, and their relationship with gene expression and baseline accessibility. Methods: Paired ATAC-seq and RNA-seq profiles were analyzed in 38 healthy VitDPAS participants before (Day 0) and 24 h after (Day 1) a body-weight-adjusted vitamin D3 bolus of 1000 IU/kg. Exploratory k-means clustering used region-level Day 1–Day 0 differences in normalized ATAC-seq signal across 23,244 consensus regions, standardized separately for each region across participants. Chromatin-state annotations, transcription factor motifs and previously mapped vitamin D receptor (VDR)-binding sites were examined. Results: Clustering identified accessibility-increase (n = 13), mixed (n = 18) and accessibility-decrease (n = 7) groups. Within-group analyses identified two, zero and three differentially accessible regions, respectively, at false discovery rate (FDR) < 0.05. Nominal significance and signal-abundance filtering yielded 620 candidate regions. RNA-seq identified 74, eight and zero differentially expressed genes in the respective groups at FDR < 0.05, with immune-related pathway enrichment in the accessibility-increase group. Accessibility gains frequently coincided with reduced expression at selected RNA-seq-significant loci. Lower baseline accessibility was associated with subsequent increases, although mathematical coupling, regression to the mean and library signal-to-background variation limit interpretation. Conclusions: Normalized PBMC chromatin accessibility changes following vitamin D3 supplementation varied among participants. The association between baseline accessibility and subsequent change remains descriptive and does not establish predictive value. Controlled, longitudinal and cell-type-resolved studies are needed to distinguish biological responses from compositional and technical variation.

Nutrients doi: 10.3390/nu18223776

Authors: Naiara Ribeiro Almeida Marco Antônio Ferreira Santos José Raimundo Fernandes Michele Andrade de Brito Keveenrick Ferreira Costa Dany Alexis Sobarzo Soto Diego Valenzuela Pérez Esteban Aedo-Muñoz Felipe J. Aidar Lindsei Brabec Mota Barreto Otávio Toledo Nóbrega Ciro José Brito

Background: Creatine supplementation is widely used to enhance physical performance, but its effects across health and performance outcomes remain uncertain. Objective: To synthesise evidence from systematic reviews and meta-analyses on creatine supplementation, evaluating methodological quality, certainty of evidence, and primary-study overlap. Methods: An umbrella review was conducted according to the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement and registered in PROSPERO (CRD420261501087). PubMed, Scopus, and Web of Science were searched for systematic reviews with quantitative meta-analyses published during the preceding 20 years. Methodological quality was assessed using AMSTAR-2, and primary-study overlap using the Corrected Covered Area (CCA). Results: Forty-five systematic reviews were included, and the evidence was organised into seven thematic domains. Most reviews examined healthy, physically active, or athletic populations, whereas clinical cohorts (e.g., chronic obstructive pulmonary disease, heart failure, chronic kidney disease, depression, or metabolic disease) were represented in approximately one fifth of the reviews, mainly in mixed samples of healthy and clinical participants. Creatine supplementation showed favourable effects on selected measures of muscular strength, power, lean mass, and physical function, with more consistent findings when combined with resistance training. Cognitive findings suggested improvements in selected measures of memory, attention, and processing speed, whereas evidence for endurance, recovery, inflammation, and mental health outcomes remained mixed or outcome-specific. Serum creatinine increased, but Cr-EDTA-measured GFR and urinary kidney-injury markers showed no significant changes; evidence regarding long-term renal safety remains limited. No review achieved high AMSTAR-2 confidence, and nearly half were rated critically low. Primary-study overlap was slight (global CCA: 3.49%), although 395 unique studies accounted for 1001 study–review inclusions, indicating that concordance across reviews does not necessarily represent independent replication. Conclusions: Creatine supplementation appears to provide outcome-specific benefits, particularly for selected measures of strength, power, lean mass, and physical function. However, these findings are tempered by the absence of high-confidence reviews and substantial reuse of primary studies across syntheses. Interpretation should therefore account for methodological limitations, population and outcome variability, and primary-study overlap.

Nutrients doi: 10.3390/nu18223775

Authors: Shirley Wing Yan Poon Jessica R. Biesiekierski David Jia Wei Wang Robyn Mary Brown Priya Sumithran

Background/Objectives: The objective of this study was to evaluate the feasibility, acceptability, weight loss response, safety and preliminary clinical outcomes of a pragmatic 8-week food-based very-low-energy intervention in adults with obesity. Methods: In this prospective, single-arm study, 10 adults eligible for very-low-energy diet (VLED) therapy completed an 8-week food-based intervention targeting approximately 800 kcal/day with an accepted intake range up to 1000 kcal/day. Participants planned, purchased and prepared all foods, supported by dietary self-monitoring and fortnightly dietitian consultations. The primary feasibility outcomes were acceptability and weight loss response. The secondary outcomes included recruitment, retention and engagement. The exploratory outcomes included anthropometric measures, blood pressure, nutritional and biochemical markers, dietary quality, nutritional adequacy and adverse events. Results: All participants completed the intervention. Nine of 10 (90%) Food Acceptability Questionnaire (FAQ) scores met their prespecified item-level acceptability thresholds, while 90% (95%CI 55.5 to 99.7%) of participants achieved ≥5% weight loss. Mean weight loss was 10.8%. Attendance at study visits was 100% (95% CI 69.2 to 100%). Participants completed 93 ± 13% of expected food diary days with mean daily energy intakes of 842 ± 70 kcal/day. Statistically significant improvements were observed in anthropometric measures, blood pressure, total and LDL cholesterol and dietary quality. No clinically concerning changes in micronutrient or safety parameters were observed. Adverse events were predominantly mild to moderate. Conclusions: This pragmatic 8-week food-based very-low-energy intervention demonstrated encouraging feasibility outcomes, although challenges associated with eating out warrant further attention. Further evaluation in larger controlled trials is needed to assess its comparative effectiveness relative to traditional meal replacement VLEDs and longer-term outcomes.

Nutrients doi: 10.3390/nu18223774

Authors: Dominika Pietrasik Dominik Szwajgier Ewa Baranowska-Wójcik

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most commonly diagnosed neurodevelopmental disorders, occurring in both children and adults, with its etiology and clinical presentation being multifactorial. Despite significant progress in diagnostics and treatment, available therapeutic strategies—particularly pharmacotherapy—are characterized by limited efficacy in some patients and the risk of numerous adverse effects. In recent years, natural bioactive compounds capable of modulating monoaminergic neurotransmission are gaining increasing interest; one of the mechanisms is the inhibition of the activity of monoamine oxidases (MAO-A and MAO-B), key enzymes involved in the metabolism of selected neurotransmitters. This paper provides a narrative review of the current state of knowledge on ADHD, covering its clinical characteristics, diagnostic process, currently used therapeutic methods, and the role of MAO enzymes in the regulation of central nervous system functions. Particular attention is devoted to natural MAO inhibitors, with an emphasis on plant-derived compounds. Due to the fact that the extraction and analysis of bioactive substances from flower petals remains a poorly explored area, this can be a significant research topic for developing new, potentially safer and better tolerated alternatives or adjuncts to conventional drugs used in ADHD therapy.

Nutrients doi: 10.3390/nu18223773

Authors: Antonios Siargkas Antigoni Tranidou Themistoklis Dagklis Ioannis Tsakiridis

Among the exposures relevant to pregnancy, maternal diet stands out as one of the few that can be modified and one of the most difficult to investigate rigorously [...]

Nutrients doi: 10.3390/nu18223772

Authors: Károly Szili Csilla Dézsi Viktor Gulyás-Oldal Anikó Gál Ekaterine Paschali Csaba Busznyák Sándor Nagy

Background/Objectives: Obesity in adolescent girls is associated with metabolic and reproductive changes that can persist into adult life. Methods: This review examines nutrition therapy and glucagon-like peptide-1 (GLP-1) receptor agonist pharmacotherapy in girls aged 8–18 years. PubMed/MEDLINE, Scopus and OpenAlex were searched; one author selected the studies and extracted the data. Each outcome is classified as demonstrated in adolescent trials, extrapolated from adults, mechanistic, unknown or an expert proposal. Results: In adolescents aged 12 to <18 years, semaglutide and liraglutide increased the proportion achieving a 5% reduction in body weight or body mass index compared with placebo, and semaglutide improved insulin resistance; a Cochrane review rates the anthropometric benefit of paediatric pharmacotherapy as low-certainty. Effects on androgen excess and menstrual function have been shown only in adults and cannot be separated from weight loss; pubertal timing, lean mass and bone accrual have not been studied as outcomes in randomised trials. Conclusions: Small trials in adolescents and young women with polycystic ovary syndrome suggest that dietary or lifestyle treatment with weight loss can improve menstrual regularity, whereas effects on androgens are inconsistent. Nutritional protection of lean mass, bone and micronutrient status during drug-induced weight loss is untested; we present it, with a stepped-care framework, as an expert proposal.

Nutrients doi: 10.3390/nu18223771

Authors: Juliana F. W. Cohen Nan Dou Leah E. Chapman Mary Curnutte Salima Taylor Marlene B. Schwartz Lindsey Turner Erin R. Hager

Background/Objectives: School-based nutrition policy, systems, and environmental (PSE) strategies have the potential to improve children’s nutrition and reduce the risk of obesity. This umbrella review synthesized evidence from systematic reviews examining school-based PSE strategies and their associations with nutrition- and weight-related outcomes among school-aged children in the United States. Methods: PubMed was searched for systematic reviews and meta-analyses (2010–2026). Screening and extraction were conducted in duplicate. Methodological quality was assessed using an adapted AMSTAR 2. The review was registered (PROSPERO-2026 CRD420261387630). Results: Eighteen systematic reviews were included. PSE strategies examined included: breakfast after the bell (BATB), school nutrition policies, local food initiatives, cafeteria environment changes, and universal free school meals (UFSM). Consistent evidence supported positive associations with meal participation for BATB, food environment policies, and UFSM. Evidence also suggested improvements in school meal consumption and/or diet quality with BATB, food environment policies, local food initiatives, and some cafeteria environment changes. Few studies examined food security or weight-related outcomes. Research among subpopulations was generally limited, with the strongest evidence for BATB and food environment policies improving meal participation and nutrition outcomes among students from lower-income households. Four out of the eighteen reviews were of high or moderate quality based on the adapted AMSTAR rating. Conclusions: Multiple school-based nutrition PSE strategies were associated with positive associations regarding school meal participation and consumption, but more research is needed to examine food security or weight-based outcomes. Future research should prioritize strong study designs and objective measures, as well as evaluate impacts on subpopulations at greatest risk for adverse health outcomes. Finally, multicomponent PSE strategies with sufficient dose and duration should be implemented to maximize effectiveness.

Nutrients doi: 10.3390/nu18223770

Authors: Barbara Pala Mariagrazia Piscione Francesco Cribari Walter Vignaroli Paola Gualtieri Giada La Placa Dario Gaudio Giuseppe Merra Gianluca Iacobellis Laura Di Renzo

Epicardial adipose tissue (EAT) is an active endocrine and paracrine organ involved in coronary artery disease, atrial fibrillation (AF), and heart failure with preserved ejection fraction (HFpEF). Beyond its role as a risk marker, EAT is increasingly investigated as a potentially modifiable target, and exploratory, low-certainty evidence suggests that its response to intervention is only partly explained by weight loss. This narrative review addresses two core themes: the pathophysiology of EAT as a distinct, regionally heterogeneous adipose organ; and the effects of nutrition and physical exercise—particularly the Mediterranean diet, caloric restriction, structured training, and bariatric surgery—on EAT quantity and inflammatory quality. Pharmacological data are summarized only as a complementary comparator. Multimodality imaging—echocardiography, cardiac computed tomography (cCT), and cardiac magnetic resonance (CMR)—is discussed as the means by which EAT is measured, and minimum standards for its assessment are proposed. Finally, we outline a hypothesis-generating framework for incorporating EAT assessment into lifestyle-based cardiovascular prevention. This framework has not been validated, and whether reducing EAT improves cardiovascular outcomes independently of weight loss and other risk factors remains unknown; EAT should currently be regarded as a modifiable biomarker rather than an established therapeutic target.

Nutrients doi: 10.3390/nu18223769

Authors: James Chmiel Anna Krajewska-Pędzik Donata Kurpas

Introduction: Acute caffeine may modify laboratory-evoked pain, but its relevance to clinical analgesia is uncertain. We systematically reviewed controlled experiments of caffeine administered alone in healthy humans, distinguishing pain intensity, threshold, tolerance, and induced hypoalgesia. Methods: Six databases were searched through 1 September 2026 using PRISMA 2020 methods. Nine experiments (216 analyzed participants) were included; five (130 participants) supplied pain-intensity contrasts for an exploratory REML random-effects meta-analysis with Hartung–Knapp confidence intervals. Results: The pooled effect was uncertain (Hedges’ g = 0.61, 95% CI −0.33 to 1.54; p = 0.146; I2 = 89.0%). Exclusion of the influential graph-derived cold-immersion estimate reduced g to 0.16 (95% CI −0.22 to 0.53; I2 = 24.7%). Pain threshold, tolerance, and induced hypoalgesia were not combined with pain intensity. Protocol differences could be described but not tested as reliable moderators. Adverse-event ascertainment varied substantially. Conclusions: The available evidence does not establish a consistent generalized hypoalgesic effect of caffeine alone. It can inform standardization of experimental pain research, but cannot justify caffeine treatment for clinical pain.

Nutrients doi: 10.3390/nu18223768

Authors: Piraorn Suvanbenjakule Nusrat Akber Pepijn Schreinemachers Nattawirot Mahayot

Background: As the 24-h economy expands, an increasing share of the global workforce engages in nighttime work. Most previous studies have documented adverse effects among healthcare workers and in high-income countries. Evidence in low-income earners in low- and middle-income countries is limited. This study analyzed the association between night shift work and the diets of convenience store workers in Bangkok, Thailand, focusing on fruit and vegetable intake. Methods: The study used a within-person repeated-measures design with questionnaires administered to 100 convenience store workers in Bangkok during their regular daytime and nighttime shifts. The Diet Quality Questionnaire (DQQ) was used and relied on self-reported food intake over the past 24 h. Data were analyzed using a paired t-test and panel regression. Predictors included food sources and personal domains of the food environment. Results: Mean fruit and vegetable intake was 198 g per day, half the amount recommended by the World Health Organization. There was no statistically significant difference in combined fruit and vegetable intake between days with a day shift and days with a night shift for both the panel logistic regression (p = 0.184) and the paired t-test analysis (p = 0.156). However, diet diversity (MD = 0.40, SEMD = 0.16, p < 0.05) and the non-communicable disease (NCD)-Protect score (MD = 0.61, SEMD = 0.17, p < 0.01) statistically differed across shifts. Night shifts were associated with lower diet diversity (B = −0.41, p < 0.01) and reduced NCD-Protect (B = −0.63, p < 0.001). The number of convenience store visits was significantly associated with NCD-Protect (B = −0.45, p < 0.01). Conclusions: Night shift workers generally have low fruit and vegetable intake. Night shift work is negatively associated with dietary diversity and intake of protective foods. There is a need for employer and policy measures to protect shift workers’ health regardless of work hours.

Nutrients doi: 10.3390/nu18223767

Authors: Meng Xiao Xianbin Ding Liling Chen Xiaojun Tang Yanqi Hu Hao Mu Yao Liu Hongbo Qi Dianjianyi Sun

Background: Social, behavioural, and environmental determinants of cardiovascular disease (CVD) frequently co-occur, but their joint associations are poorly understood. We examined whether social vulnerability and habitual numbing–spicy food consumption modified the association between pre-baseline residential humid heat and CVD. Methods: The Chongqing sub-cohort of the China Multi-Ethnic Cohort enrolled 23,308 adults aged 30–79 years in 2018–2019 and followed them through September 2025. The incidence analysis included 21,734 individuals and 641 CVD events. The mortality analysis included 22,923 individuals and 82 CVD deaths. Median follow-up was 6.84 years (145,349 and 154,559 person-years, respectively). Social vulnerability was measured using a 16-item psychosocial risk score (PsRS). Diet was classified into four categories for the incidence analysis and as any versus no numbing–spicy consumption for the mortality analysis. Humid-heat exposure was characterised by total humid-heat days, heatwave frequency, and longest heatwave duration, derived from daily Heat Index values in the three complete years before baseline. Cox models estimated the main associations and tested two-way and three-way interactions. For each heat metric, 36 exposure combinations were defined by 3 PsRS groups × 4 dietary categories × 3 heat-exposure groups in the incidence analysis. Results: Consumption of both numbing and spicy foods was associated with lower CVD incidence (HR 0.75, 95% confidence interval [CI] 0.61–0.93). The three-way interaction for heatwave frequency was statistically significant before (p = 0.0433) but not after (p = 0.1299) Holm adjustment across the three heat metrics. No corresponding interaction was detected for total HTH days (p = 0.8514) or longest heatwave duration (p = 0.4190). In exploratory analyses, high social vulnerability was associated with CVD mortality (HR range 2.73–2.78, all p < 0.05). Neither diet nor humid heat showed a statistically significant association with CVD mortality. Conclusions: The three-way interaction involving heatwave frequency, social vulnerability, and diet was exploratory and did not remain statistically significant after correction for multiple testing. These findings warrant replication. The dietary associations should not be interpreted as evidence of a causal protective effect.

Nutrients doi: 10.3390/nu18223766

Authors: Alisa Weiland Sabrina Eichhorn Phil Weiland Bea Klos Norbert Schäffeler Stephan Zipfel Isabelle Mack

Background/Objective: Dietary energy density (ED; kcal/g) influences energy intake and is central to obesity prevention. Little is known about how children understand energy density and apply the knowledge in decision-making contexts. This study examines classification accuracy, structured error patterns, and decision-making during a serious game intervention: a cognitive decision-process analysis of how children apply the concept of dietary ED, using serious gameplay data as behavioral readout. Methods: Gameplay data from a cluster-randomized controlled trial were analyzed. Children aged 9–11 years (n = 82) participated in a serious game intervention targeting energy density of foods (tasks with and without time pressure), beverage sugar content, and overall meal composition. Analyses focused on first-attempt responses to assess spontaneous application of the dietary ED concept. In-game decision patterns were used to assess children’s ability to classify foods by ED, estimate sugar content in beverages, and adapt food choices across repeated gameplay sessions. Results: Children understand ED. Misclassifications occurred predominantly between adjacent ED categories, with medium-ED (1.5–2.5 kcal/g) foods posing the greatest challenge. Classification accuracy was highest for fruits, vegetables, and high-energy sweets, while cereals and dairy products showed greater variability. Under time pressure, accuracy remained largely stable, with modestly longer decision times for nutritionally similar item pairs. Sugar content in fruit-based beverages was underestimated. Over repeated gameplay sessions, children increasingly selected lower-energy-density foods, reflecting a shift toward more energy-density-appropriate choices. Conclusions: The findings suggest that children acquire a transferable decision principle rather than memorizing isolated food properties. Teaching transferable nutritional concepts rather than isolated food facts may promote lasting improvements in nutritional literacy and support early obesity prevention.

Nutrients doi: 10.3390/nu18223765

Authors: Sang-Jae Lee Sondor Ganbat So Young Kim Ji Hyeong Chae Eun Ju Ye Jung wook Kim Mi Hwa Park

Background/Objectives: Fatigue results from prolonged physical exertion and is characterized by declining physical performance. This study assessed anti-fatigue potential of an allithiamine garlic complex (AGC) in a mouse model of forced swimming-induced fatigue. Methods: Male ICR mice were assigned to five groups (n = 8 per group)—sedentary control (normal control), forced swimming test control (FST-C), FST + AGC at 100 mg/kg (AGC100), FST + AGC at 500 mg/kg (AGC500), and FST + red ginseng at 500 mg/kg (positive control, PC). Fatigue was induced by forced swimming (15 min/day) for 1 week, after which the treatments were administered orally once daily for 7 days. On days 0 and 7, weight-loaded FSTs (5% of body weight) were conducted to measure immobility time, and mice were euthanized on day 7 for biochemical analysis (serum, liver, and gastrocnemius muscle). Results: On day 7, both AGC doses significantly reduced immobility time compared with the FST-C group, and immobility time in the AGC500 group did not differ significantly from that in the PC group. AGC significantly reduced serum lactate, free fatty acids, and ammonia levels, whereas decreases in lactate dehydrogenase, creatine kinase, and blood urea nitrogen were not statistically significant. AGC increased glycogen content in the liver and skeletal muscle. AGC upregulated the protein expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the skeletal muscle, suggesting an association with AMPK/SIRT1/PGC-1α signaling. AGC treatment reduced malondialdehyde levels and increased superoxide dismutase activity relative to the FST-C group. Conclusions: Collectively, these findings demonstrated that AGC enhances exercise endurance and alleviates fatigue by activating the AMPK/PGC-1α signaling pathway, indicating its potential as a functional ingredient for mitigating high-intensity exercise-induced fatigue.

Nutrients doi: 10.3390/nu18223762

Authors: Cuiyu Yang Tu Hong Jiamin Xu Xinhui Wang Lixia Bi Jiandong Shen Rui Feng

Background: Low birthweight (LBW) remains a major global public health challenge, with long-term consequences for neonatal survival and chronic disease risk. Maternal exposure to ambient ozone (O3) has been implicated in fetal growth restriction, but evidence remains inconsistent. Methods: We conducted a retrospective cohort study of 14,381 term singleton live births in Zhejiang Province, East China, during the COVID-19 lockdown and quarantine period. Maternal O3 exposure during each trimester and the entire pregnancy was estimated using data from nearest atmospheric monitoring stations, with refined time-activity patterns accounting for home and workplace locations. Results: In multivariable linear regression adjusted for the pre-specified covariates, maternal O3 exposure averaged over the entire pregnancy was inversely associated with birthweight (pooled estimate across sex- and residence-stratified models: β = −2.1 g per μg/m3, 95% CI: −3.6 to −0.5; stratum-specific β ranged from −2.24 to −0.92). An interquartile range (IQR) of approximately 10–15 μg/m3 in entire-pregnancy O3 exposure increase was associated with an estimated birthweight reduction of about 20–33 g; the range reflected the combination of stratum-specific β estimates and stratum-specific IQRs. The explained variance was small as indicated by R2, showing that O3 was not a powerful individual-level predictor of birthweight; the precisely estimated β nonetheless reflected a systematic shift in the population distribution of birthweight. Conclusions: Maternal O3 exposure during pregnancy was associated with reduced birthweight in a sex- and window-specific manner. The third trimester was more stronger association period for female fetuses, whereas cumulative exposure across mid-to-whole pregnancy was more critical for males. Maternal nutritional intake is a plausible modifiable factor that may attenuate susceptibility, but the present study did not measure diet, food insecurity, or psychological stress. Future studies should incorporate dietary assessment and biomarkers to test this hypothesis.

Nutrients doi: 10.3390/nu18223764

Authors: Ghadeer S. Aljuraiban Tagreed A. Mazi Madhawi M. Aldhwayan Sara Al-Musharaf

Background/Objectives: Excess sodium and inadequate potassium are interrelated dietary determinants of blood pressure (BP). Evidence on concurrent intake, food-group patterns, and BP in Saudi adults remains limited. We aimed to characterize sodium and potassium intakes and the sodium-to-potassium (Na:K) ratio, associated food-group patterns, and BP across tertiles. Methods: This cross-sectional secondary analysis included 1041 Saudi adults recruited in 2021–2023. Intakes were estimated from two nonconsecutive multiple-pass 24 h recalls; food-group densities were expressed as g/1000 kcal. BP was measured using a standardized protocol, and the mean of three readings was analyzed. Models adjusted for age, sex, total energy, body mass index, smoking status, and family history of hypertension examined BP across Na:K tertiles and food-group density associations. Results: In this cohort, 96.7% reported sodium intake ≥2000 mg/day, 86.1% potassium intake <3510 mg/day, and 82.9% had both. Geometric mean sodium intake was 4750 mg/day (95% CI 4600–4900), and potassium intake was 2330 mg/day (2270–2390). Adjusted systolic BP was 2.28 mmHg and diastolic BP 2.10 mmHg higher in the highest versus lowest tertile. A higher ratio was associated with greater densities of breads and grains, soft drinks, animal-protein foods, and fast food, and lower densities of fruit, vegetables, dairy, plant-protein foods, fats and oils, and juice and fruit drinks. Fruit showed the strongest inverse association (standardized β = −0.31, 95% CI −0.39 to −0.24). Conclusions: Excessive sodium and inadequate potassium commonly coexisted in our cohort. A higher Na:K ratio was associated with higher systolic and diastolic BP and a broader dietary pattern. These findings support reducing sodium and promoting potassium-rich foods, although the cross-sectional design precludes causal inference.

Nutrients doi: 10.3390/nu18223763

Authors: Fang Liu Xiaole Zhang Dongfang Guan Zexian Wang He Sun Lin Ding

Background: Malvidin-3-O-glucoside (MV), a grape/berry anthocyanin, is metabolized in the gut to syringic acid (SA), gallic acid (GA), and pyrogallol. Despite reported antioxidative and anti-inflammatory activities, cell-specific actions in immune cells and enterocytes remain incompletely defined. Methods: We profiled human THP-1 monocytes, macrophages, and C2BBe1 enterocytes exposed to MV and metabolites using untargeted metabolomics. Functional readouts included cytokine/chemokine secretion, pathway enrichment, and lipid mediators with the endocannabinoid network. Benjamini–Hochberg false discovery rate (FDR) correction was applied; multivariate analyses were used in an exploratory capacity. Results: MV increased IL1B and IL8 in monocytes/macrophages while inhibiting CXCL10, CXCL11, and CXCL13; MV plus dimethyl fumarate suppressed CXCL10. In enterocytes, MV and its metabolic products altered focal adhesion–related pathways and histamine and were associated with changes in endocannabinoid-linked metabolites, such as N-arachidonoyl glycine and stearoyl ethanolamide; these observations derive from untargeted profiling without receptor, enzyme, or targeted validation. Conclusions: MV exerts cell type-dependent immunomodulatory effects, enhancing select cytokines while suppressing key chemokines. In enterocytes, MV is associated with transcriptional and metabolomic changes affecting focal adhesion pathways and endocannabinoid-related metabolites. These findings are hypothesis-generating and derived from in vitro models; receptor-level assays, orthogonal validation, and in vivo studies are required before inferring physiological modulation.

Nutrients doi: 10.3390/nu18223761

Authors: Jennifer Mytych Kamil Kubas Justyna Widłak-Kargul Anna Koziorowska Marek Koziorowski

Background/Objectives: Obesity is a major chronic disease associated with increased cardiometabolic risk. Multi-ingredient nutritional interventions combining bioactive compounds have been proposed as a strategy to modulate energy balance through complementary metabolic pathways. This study evaluated the effects of a multi-ingredient Formulation on body weight gain and selected metabolic parameters in leptin-deficient B6.V-Lep^ob/ob mice maintained on a high-fat diet. Methods: Male B6.V-Lep^ob/ob mice were treated for 8 weeks with either a multi-ingredient Formulation, L-carnitine tartrate, or Vehicle. Body weight was monitored throughout the study. At study end, plasma biochemical parameters, hepatic glycogen content, organ weights, hematological indices, and circulating growth differentiation factor-15 (GDF-15) concentrations were assessed. Results: Formulation significantly reduced body weight gain compared with both Vehicle and L-carnitine-treated mice. Liver weight was significantly lower in the Formulation group than in Vehicle-treated animals. Hepatic glycogen content and plasma bilirubin concentrations were reduced in both active treatment groups, whereas plasma glucose concentrations were increased. No marked differences were observed in plasma transaminases. Circulating GDF-15 concentrations were significantly higher in the Formulation group compared with Vehicle-treated mice. Conclusions: The tested multi-ingredient Formulation attenuated body weight gain in obese leptin-deficient mice and was associated with lower liver weight, altered carbohydrate-related metabolic parameters, and increased circulating GDF-15 concentrations. These findings support the potential of multi-component nutritional interventions to modulate obesity-related metabolic outcomes and identify elevated circulating GDF-15 as a biomarker warranting further investigation.

Nutrients doi: 10.3390/nu18223760

Authors: Tianshuo Zhang Dongsheng Jia Huiyi Zhang Guangzhao Zhou Jie Liu Jiatian Gu Xiaotang Ding Man Wang Ding Zhao

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disorder with limited effective pharmacological treatments. Ziziphus jujuba Mill. leaves (ZJL) contain multiple bioactive compounds, but their effects on MASLD and underlying mechanisms remain unclear. Methods: The chemical constituents of ethanolic ZJL extract were characterized using UHPLC-Q-Orbitrap MS. A high-fat diet (HFD)-induced MASLD mouse model was used to evaluate its protective effects. Serum biochemical parameters, liver histopathology, and inflammatory indicators were assessed. Gut microbiota and hepatic metabolic alterations were investigated using 16S rDNA sequencing and untargeted metabolomics, respectively. Potential microbiota–metabolite associations and key regulatory targets were further explored by correlation analysis, molecular docking, and qRT-PCR. Results: Fifty-five compounds were identified in ZJL, mainly flavonoids, organic acids, and triterpenoids. ZJL treatment significantly reduced HFD-induced body weight gain, dyslipidemia, hyperglycemia, hepatic injury, inflammation, and lipid accumulation. ZJL also partially restored gut microbial homeostasis, particularly by decreasing the abundances of Blautia and Dorea. Metabolomic analysis indicated that glycerophospholipid metabolism was the major affected pathway, together with fatty acid biosynthesis and cytochrome P450-related metabolism. Microbial alterations were closely associated with lipid-related metabolites. Moreover, ZJL downregulated key genes, including Pla2g2a, Fasn, and Cyp2e1. Conclusions: ZJL alleviated HFD-induced MASLD, accompanied by coordinated alterations in gut microbiota composition, hepatic metabolism, and lipid-related gene expression, suggesting that these changes may contribute to its protective effects.

Nutrients doi: 10.3390/nu18223759

Authors: Shengzhe Xu Shaoqing Zhang Jiayu Xu

Amid the worsening environmental crisis, sustainable dietary patterns have become central to reconciling human nutrition with planetary health. Plant-based diets are among the most widely recognized sustainable dietary patterns; when well planned, they are associated with a lower risk of type 2 diabetes, cardiovascular disease, and certain cancers. In 2019, the EAT-Lancet Commission proposed the Planetary Health Diet (PHD), a flexible plant-forward pattern that retains defined, modest amounts of animal-source foods while keeping food production within planetary boundaries. Neither approach is without limitations. Restrictive plant-based diets can be low in vitamin B12, long-chain omega-3 fatty acids, iron, and iodine unless fortified foods or supplements are used, whereas the PHD may still fall short of calcium, iron, and zinc for some populations. Both also raise concerns about affordability, cultural acceptability, and regional adaptation. Moreover, their benefits are context-dependent and rest largely on observational evidence that cannot establish causation. Therefore, this narrative review compares the nutritional adequacy, chronic disease outcomes, and environmental impacts of plant-based diets and the PHD, focusing on the conditions under which each meets nutrient requirements. In summary, we conclude that both offer promising but not unequivocally superior pathways for reconciling human nutrition with planetary health, provided nutrient adequacy is ensured.

Nutrients doi: 10.3390/nu18223757

Authors: Jingke Liu Chao Fang Haixia Yang Daidi Fan Jianjun Deng

Background: Pancreatic cancer (PC) remains one of the most lethal malignancies because of its highly immunosuppressive tumor microenvironment and profound resistance to current therapies. Increasing evidence suggests that pyroptosis, a pro-inflammatory form of programmed cell death, may provide a promising strategy for enhancing anti-tumor immunity and improving therapeutic responsiveness. Ginsenoside Compound K (CK), a major bioactive intestinal metabolite of Panax ginseng, exhibits diverse pharmacological and anti-tumor activities. However, whether its anti-PC effects involve the induction of tumor cell pyroptosis remains unclear. Methods: The anti-tumor effects and underlying mechanisms of CK were investigated in Panc02 tumor-bearing mice and BxPC-3 pancreatic cancer cells. Tumor growth, systemic toxicity, pyroptosis-related events, reactive oxygen species (ROS) production and the involvement of the HAPLN1–TNFα/NF-κB signaling pathway were evaluated. Pharmacological inhibition of ROS and caspase-1 was employed to verify the mechanism of CK-induced pyroptosis. Results: CK significantly suppressed tumor growth without causing apparent systemic toxicity and induced characteristic pyroptotic changes, including caspase-1 activation, enhanced lactate dehydrogenase release, and disruption of mitochondrial membrane potential. Mechanistically, CK promoted intracellular ROS accumulation and activated the HAPLN1–TNFα/NF-κB axis, leading to NLRP3 inflammasome activation and subsequent cleavage of caspase-1 and gasdermin D (GSDMD). And either ROS scavenging or caspase-1 inhibition markedly attenuated CK-induced pyroptosis. Conclusions: CK exerts potent anti-pancreatic cancer activity by promoting ROS/NLRP3-dependent pyroptosis and is associated with HAPLN1-related inflammatory signaling, supporting its further development as a therapeutic candidate for pancreatic cancer.

Nutrients doi: 10.3390/nu18223758

Authors: Natalia Veronica Alaniz-Salinas Hassan Vatanparast Jessica Lieffers Daniel Fuller Rachel Engler-Stringer

Background/Objectives: Universal school food programs may reshape lunch composition by changing foods available at school and lunch sources. We assessed whether food-group and processing-level composition changed differently in intervention and control schools following implementation of a universal school lunch program. Methods: Four elementary schools in Saskatoon, Saskatchewan, Canada, were included; two implemented a universal free lunch program and two served as controls. Lunch consumption was measured in May–June 2021 and May–June 2023 using photography-assisted weighed plate waste. Foods were classified using Canada’s Food Guide and NOVA. Outcomes were expressed as grams and percentage of total quantified lunch grams and analyzed using an equal-school-weighted difference-in-differences approach. Results: The analysis included 980 student-period observations. Total quantified lunch grams declined in both groups, with a smaller reduction in intervention schools (DiD = 32.62 g). Vegetable and fruit intake declined less in intervention schools (DiD = 3.52 g), although proportional change did not favour intervention schools (DiD = −3.75 percentage points). Whole-grain foods declined more in intervention schools in grams (DiD = −18.71 g) and proportional contribution (DiD = −8.07 percentage points), a pattern consistent across sensitivity analyses. Ultra-processed foods declined in both groups, with little differential proportional change (DiD = −0.17 percentage points). Conclusions: Implementation was not accompanied by consistent differential improvements in lunch composition. Whole-grain foods showed the most consistent between-group pattern, whereas reductions in ultra-processed foods possibly reflected broader changes across schools. These findings highlight the importance of distinguishing the foods available through school food programs from those students actually consume.

Nutrients doi: 10.3390/nu18223756

Authors: Leonardo Musto Juan Francisco Merino-Torres Dario Mercatante Maria Teresa Rodríguez-Estrada Amparo Alegría Guadalupe Garcia-Llatas

Objective: To evaluate the effects of plant sterol (PS) supplementation on inflammation, endothelial dysfunction and oxidative stress in subjects with overweight/class I–III obesity and mild hypercholesterolemia. Methods: Randomized, double-blind, placebo-controlled, crossover trial. Twenty-three subjects received 2 g/day of PS or placebo for 8 weeks, separated by a 6-week wash-out. LDL-cholesterol (LDL-C) was the primary outcome of the trial; all other parameters, which are the main focus of this article, were secondary and exploratory outcomes. Results: PS supplementation increased serum β-sitosterol (+1.21 µg/mL [95% CI 0.70, 1.72]) and its cholesterol-normalized ratio (+0.60 µmol/mmol [0.35, 0.85]), the only outcomes that retained significance after false discovery rate (FDR) correction. Campesterol showed a nominal increase (+0.72 µg/mL [0.10, 1.35]) that did not retain significance after FDR correction, whereas cholesterol synthesis markers (desmosterol and lathosterol) showed no statistically significant treatment effect. No statistically significant treatment effect was detected on LDL-C (−3.19 mg/dL [−15.91, 9.53]) or total cholesterol (−1.79 mg/dL [−14.39, 10.81]). No inflammatory, endothelial dysfunction or oxidative stress biomarker showed a statistically significant treatment effect after FDR correction, VCAM-1 being the only parameter with a nominal treatment effect (+59.08 ng/mL [7.14, 111.02]). Cholesterol-normalized ratios of four cholesterol oxidation products (COPs) decreased within the PS arm but not versus placebo. Inverse Pearson correlations of PS absorption markers with IL-1β, IL-12p70 and ICAM-1 (r = −0.56 to −0.49) were not reproduced by Spearman analysis and did not retain significance after FDR correction. No clear correlation was found between serum PS and oxidative stress markers. Conclusions: PS supplementation increased circulating β-sitosterol concentrations, but no statistically significant effects were detected on LDL-C or the measured inflammatory, endothelial dysfunction, or oxidative stress biomarkers. Larger studies are needed to clarify the effects of PS supplementation on these outcomes.

Nutrients doi: 10.3390/nu18223754

Authors: Sofoklis Stavros Anastasios Potiris Athanasios Zikopoulos Nikolaos Machairiotis Stefanos Dafopoulos Nikolaos Kathopoulis Efthalia Moustakli Eirini Drakaki Ioannis Arkoulis Ismini Anagnostaki Konstantinos Dafopoulos

Background/Objectives: Nutritional exposures may influence female reproductive health through metabolic and epigenetic pathways, including DNA methylation, chromatin regulation, and non-coding RNAs. However, evidence for direct nutritional–epigenetic mediation of reproductive outcomes remains heterogeneous. This narrative review examines the evidence linking nutrition, epigenetic regulation, and female reproductive health across developmental programming, adult reproductive function, pregnancy, reproductive disorders, and reproductive aging. Methods: A comprehensive literature search was performed in PubMed/MEDLINE, Scopus, and Web of Science to identify experimental, epidemiological, and clinical studies examining relationships among nutrition, metabolic status, epigenetic regulation, and female reproductive health. Evidence from molecular, animal, and human studies was critically synthesized, distinguishing epigenetic associations from evidence of mechanistic mediation. Results: Nutritional and metabolic exposures are associated with epigenetic pathways involved in ovarian and endometrial function, placental development, and reproductive aging. Experimental evidence supports nutrition-responsive epigenetic regulation, but evidence for epigenetic mediation of reproductive outcomes remains limited in humans. Similar limitations apply to major reproductive disorders and pregnancy complications. Conclusions: Nutritional epigenetics provides a biologically plausible framework linking diet, metabolism, and female reproductive health, but nutritional–epigenetic associations should not be interpreted as evidence of mediation without temporal and functional validation. Longitudinal and interventional studies integrating nutritional exposures with tissue-specific epigenomics and reproductive outcomes are needed before epigenetically informed biomarkers or personalized nutritional strategies can be translated into clinical practice.

Nutrients doi: 10.3390/nu18223751

Authors: Gianna Zhi-Yang Lai Gebretsadkan Gebremedhin Gebretsadik Noya Yue Zhu Yueying Yao Sin Li Zhi-Hui Lu Kwok Tai Chui Justina Yat Wa Liu Jean Woo Kenneth Ka-Hei Lo

Objectives: To examine the cross-sectional and prospective associations of dietary magnesium (Mg), including different food sources, with sarcopenia and its components in older adults. The study used data from the Mr. OS and Ms. OS cohorts, which recruited 4000 community-dwelling older adults in Hong Kong. A total of 3142 participants with complete data at baseline and the 4-year follow-up were included in the analysis. Methods: Dietary intake was evaluated using a validated food frequency questionnaire, and Mg intake was classified into quartiles (Q1–Q4). Sarcopenic status was assessed at baseline and 4-year follow-up. Multivariable logistic and linear regression models were used to examine the associations between Mg (both total and by food source) and sarcopenia and its components, with analyses stratified by sex and adjusted for covariates such as dietary energy, protein intake, sociodemographic factors, lifestyle habits, and medical history. Results: Higher Mg intake was associated with better physical performance. In men, moderate Mg intake was associated with lower odds of incident sarcopenia at 4 years (Q2: OR = 0.57, 95% CI: 0.33–0.97). Mg from fruits and legumes was associated with better physical function and a lower risk of sarcopenia, whereas animal-derived Mg sources, such as poultry, exhibited inconsistent associations. In the prospective analysis, egg-derived Mg was associated with lower sarcopenia odds only in Q3 (OR = 0.63, 95% CI: 0.42–0.95), with this association observed in men but not women. Conclusions and Implications: Higher dietary Mg intake, particularly from plant-based foods, was more consistently associated with better physical function than with sarcopenia risk in older adults. These findings support the role of Mg-rich foods in healthy aging.

Nutrients doi: 10.3390/nu18223753

Authors: Nathan I. Wood Heran Essayas Eileen Lee Max Goldstein Amy Ralph Emma Popowitz Wendy Zhang Danielle Sanders Kathleen O’Connor Duffany

Background/Objectives: Poor dietary quality contributes substantially to the global burden of chronic disease. Culinary medicine (CM) integrates culinary arts with nutrition science through hands-on education. The Yale New Haven Health Teaching Kitchen offers free patient classes using a flexible adaptation of the Health meets Food curriculum. Patients complete an introductory class and then choose the number, order, and pacing of subsequent classes. This study evaluated the acceptability and perceived benefits of the CM programming during its first year. Methods: This retrospective, cross-sectional evaluation surveyed patients who attended at least one class between October 2023 and October 2024. A voluntary electronic survey assessed perceived changes in attitudes and dietary behaviors, barriers addressed, and acceptability. Responses were summarized descriptively; exploratory Kruskal–Wallis tests assessed differences across age groups. Results: Of 293 invited patients, 120 responded (41%). Respondents reported greater comfort cooking healthy foods (82%; 95% CI, 74–87%), greater enjoyment eating healthy foods (83%; 75–89%), increased awareness of diet’s impact on health (96%; 91–98%), more frequent home cooking (68%; 59–76%), and increased consumption of fiber-containing foods (81%; 73–87%). No statistically significant differences were observed across age groups. Overall, 98% reported at least one barrier to healthy eating was addressed. Among these respondents, the most common barriers addressed involved nutrition knowledge (73%), grocery shopping (69%), and meal planning (68%). Ninety-five percent would attend another class (95% CI, 90–98%). Open-ended feedback described increased culinary confidence and perceived dietary and health improvements. Conclusions: Respondents reported high acceptability and perceived benefits from a flexible, patient-centered CM program. These findings support further evaluation of teaching kitchen education as a complement to clinical nutrition counseling. Further prospective studies incorporating objective clinical outcomes are warranted.

Nutrients doi: 10.3390/nu18223755

Authors: Mengxue Yang Irwin K. Cheah Zhaoyu Li Kaisy Xinhong Ye Jiuyu Guo Luwen Cao Na Li Wei Zhang Tih-Shih Lee Long Lu Andrea B. Maier Chen Chen Lei Feng

Background: Cognitive impairment poses significant challenges to aging populations globally. Mushrooms, the primary dietary source of ergothioneine (ET), have been associated with cognitive health, but the specific roles of ET and its metabolite S-methyl-ergothioneine (S-ET) remain unclear. Objectives: This study intends to extend previous work on mushroom intake and cognition by simultaneously examining mushroom consumption, plasma ET, and plasma S-ET, and by exploring the independent associations and potential mediation or moderation roles of ET and S-ET in relation to cognitive impairment. Methods: Cross-sectional data from 499 older adults (67 ± 8 years, 75.35% female) from the “Diet and Healthy Ageing Study” (DaHA) in Singapore were analyzed. Cognitive impairment (CI) was defined as Modified Mini-Mental State Examination (MMSE) score < 27. Plasma ET and S-ET concentrations were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Associations were examined using logistic regression, with exploratory mediation and moderation analyses. Results: Mushroom consumption >2 servings/week was associated with lower odds of CI (OR = 0.421, 95% CI: 0.180–0.986). Higher plasma ET levels were also independently associated with lower CI odds. Exploratory moderation analyses suggested that the inverse association between mushroom intake and CI was more evident among individuals with higher ET or S-ET levels (Mushroom × ET interaction: β = −0.008, p = 0.007; Mushroom × S-ET interaction: β = −0.079, p < 0.05). No evidence of exploratory mediation was observed for either ET or S-ET. Conclusions: Higher mushroom intake and plasma ET levels were associated with lower odds of cognitive impairment. Exploratory analyses suggested that the mushroom–cognition association may vary according to ET and S-ET status. The findings on mushroom and ET/S-ET interaction and the lack of a mediating role in our cohort are preliminary and hypothesis-generating and require validation in future longitudinal and intervention studies.

Nutrients doi: 10.3390/nu18223752

Authors: Ming-Ti Lv Chun-Xu Li Huan Tu Mei Han Han-Ting Zhang

Alcohol use disorder (AUD) is a major cause of cognitive impairment, yet the molecular mechanisms underlying alcoholic dementia remain unclear. Epigallocatechin gallate (EGCG), the major catechin in green tea, has shown neuroprotective potential, but its targets in alcoholic dementia are undefined. This study aimed to explore disease-associated candidate molecular markers and potential EGCG-related targets in alcoholic dementia through integrated bioinformatics, machine learning, molecular docking, and experimental analyses. Differentially expressed genes (DEGs) from GEO datasets GSE5281 and GSE62699 were subjected to functional enrichment, protein–protein interaction (PPI) network analysis, and machine learning-based feature selection. Exploratory receiver operating characteristic (ROC) analysis, immune infiltration analysis, molecular docking, and experimental assays were subsequently performed. We identified 60 overlapping DEGs enriched in synaptic signaling, postsynaptic structure, GABA-A receptor activity, and cytokine receptor activity. IL-1R1 and ID3 were identified as candidate genes associated with immune infiltration, and both were upregulated in the hippocampus of ethanol-exposed mice. These findings highlight IL1R1 and ID3 as exploratory candidate genes and provide a preliminary basis for further investigation of EGCG in the context of alcohol-associated cognitive impairment.

Nutrients doi: 10.3390/nu18223750

Authors: Dilek Güneş İlknur Hacıoğlu Vehibe Berber Suzin Tatonyan Aylin Yetim Şahin Meryem Karaca Asuman Gedikbaşı Fatmahan Atalar Mübeccel Demirkol Gülden Gökçay Mehmet Cihan Balcı

Background: Phenylketonuria (PKU) requires lifelong phenylalanine (Phe) restriction, potentially affecting dietary inflammatory potential. We investigated the relationships between the Dietary Inflammatory Index (DII), circulating cytokines, and metabolic parameters in adolescents with PKU. Methods: This case–control study enrolled 61 adolescents with PKU (aged 10–18 years) and 61 healthy age- and sex-matched controls. DII scores were calculated from three-day dietary records using 22 available dietary parameters. Anthropometric measurements, bioelectrical impedance analysis, biochemical markers, blood Phe concentrations, and pro-inflammatory and anti-inflammatory cytokines (GM-CSF, IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13) were assessed. IL-4 was excluded from analysis because of analytical concerns. Between-group cytokine comparisons were evaluated using Bonferroni correction, and within-group correlation analyses and exploratory multivariable regression analyses were performed. Results: DII scores were significantly lower in the PKU group than in controls (−1.83 ± 1.35 vs. 0.71 ± 1.39; p < 0.001), with negative scores in 93.4% of adolescents with PKU. GM-CSF, TNF-α, IL-1β, and IL-12 (p70) concentrations were nominally higher in PKU (unadjusted p = 0.006–0.023; r = 0.206–0.247), but none remained significant after Bonferroni correction (threshold p < 0.00417). In exploratory adjusted regression analyses, DII was not significantly associated with the four selected cytokines, whereas the study group showed a nominal association with TNF-α (p = 0.007). Within-group analyses showed no significant correlations between DII scores and GM-CSF, TNF-α, IL-1β, or IL-12 (p70) concentrations in either group. Conclusions: Adolescents with PKU exhibited more anti-inflammatory dietary scores than healthy controls, but cytokine differences did not withstand correction for multiple comparisons. These exploratory findings warrant confirmation in larger studies.

Nutrients doi: 10.3390/nu18223749

Authors: Ihsan Shawki Akili Madeline Orlowski Jake Grenon Alanna Sherman Catherine Young Whitney Barbour Cree Pacher R. Chris Skinner

Purpose: Excessive alcohol intake is detrimental to liver health, but the differential impacts of types of alcohol on hepatic health remain understudied. Beer, wine, and liquor are the most common alcohols consumed worldwide, with each varying substantially in alcohol content and chemical profile, and given their popularity, an understanding of alcohol types and general liver health is needed. Search Methods: As such, we conducted a comprehensive narrative review focusing on pre-clinical and clinical studies on alcohol type and liver health by searching major research databases (PubMed, Google Scholar, Cochrane Library) for key terms associated with our topic and utilizing snowballing between August 2025 and September 2026. Search Results: Our search strategy yielded 301 total articles, of which 74 were included in the pre-clinical and clinical sections of this study, with 277 articles excluded. Discussion: Overconsumption of alcohol is detrimental to the liver regardless of type. Although some research indicates low and moderate red wine consumption is less deleterious, caution must be applied due to a variety of confounding factors. Liquor was found to be harmful to the liver across pre-clinical and clinical studies, while beer’s impact was largely negative albeit varied based on many factors. Several gaps emerged, including a lack of studies on differing types of liquors, non-red wines, beers, and hard seltzers, as well as pre-clinical experiments in females. This review highlights that all alcoholic beverages may not uniformly impact the liver, and that more research is needed to determine how different alcohol types impact liver health.

Nutrients doi: 10.3390/nu18223748

Authors: Alessia Mariano Anna Scotto d’Abusco

Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide, currently affecting approximately 8–10% of the global population aged over 60 [...]

Nutrients doi: 10.3390/nu18223747

Authors: Xinhao Cai Yang Xiao Yumeng Sun Shiyin Zhang Yang Li Ying-Hua Jin

Background: The immune system protects the body against invasion by external pathogens and is fundamental to survival; appropriately enhancing immunity enables organisms to maintain health more effectively. Li-Ginseng Powder (LGP) is a specifically processed ginseng product with reported natural killer (NK) cell activating effects in tumor-bearing animals; however, its immunostimulatory effects and underlying mechanisms in healthy animals remain largely unclear. Methods: Female BALB/c mice were used to investigate the effect of LGP on immune function. A network pharmacology method was employed to explore the possible mechanism of its immunomodulatory effects. Results: LGP enhances the adaptive and innate immune functions of mice, including enhancing the body’s antibody response, improving the proliferation activity and cytotoxic ability of T cells and NK-like cells, and increasing the phagocytic ability of macrophages. LGP did not significantly change the differentiation subtypes of T cells in the body. In addition, LGP rapidly regulates the inflammatory response through positive and negative feedback mechanisms by regulating the secretion of inflammatory cytokines, thereby maintaining the homeostasis of the immune microenvironment. Network pharmacology analysis predicted the potential involvement of the phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt) and mitogen-activated protein kinase (MAPK) signaling pathways in the immunomodulatory effects of LGP. Conclusions: LGP enhances both adaptive and innate immune functions in mice and may therefore show considerable potential as a dietary supplement for supporting immune function.

Nutrients doi: 10.3390/nu18223746

Authors: Xin-Wen Zhang Hui Song Lei Yu Jia-Qi He Kai Xu Rui Ma Lang Lang

Autoimmune diseases are markedly heterogeneous in pathogenesis, target-organ injury, clinical state, and treatment context, while partial immunometabolic convergence and recurring nutrition-related phenotypes may occur in specific disease states. This narrative review synthesizes human evidence identified through a structured literature search to examine the clinical roles of medical nutrition therapy (MNT), patient stratification, and clinical implementation. The clearest disease-directed applications include a gluten-free diet for celiac disease and nutritional induction therapy for low-risk pediatric luminal Crohn’s disease, with separate evidence for cyclic exclusive enteral nutrition (EEN) as maintenance after EEN-induced remission. Adjunctive MNT addresses specific symptoms, nutritional or functional phenotypes, and comorbidity burden alongside standard treatment; supportive MNT prioritizes nutritional adequacy and physiological safety when organ dysfunction constrains intake or nutrient handling. Shared phenotypes provide common domains for cross-disease assessment and generate hypotheses for patient stratification; intervention selection must also account for disease state, nutritional phenotype, organ function, and background treatment. Candidate multi-omics biomarkers may help predict differential treatment responses, but their predictive performance and clinical utility for intervention selection remain to be validated. Future research should prospectively test patient–intervention matching and document actual intervention exposure alongside clinical outcomes, safety, and feasibility, with reassessment as disease state and treatment context change.

Nutrients doi: 10.3390/nu18223744

Authors: Pei-Ju Li Yau-Jiunn Lee Hui-Chun Hsu

Diabetes care increasingly relies on continuous glucose monitoring (CGM), automated insulin delivery, connected devices, digital nutrition tools, and artificial intelligence (AI). However, data connectivity does not ensure timely, accountable clinical action. Building on World Health Organization digital health principles and established diabetes care models, we propose the Digital Diabetes Care Ecosystem (DDCE), a conceptual implementation framework centered on clinical orchestration. Its distinctive contribution is an auditable signal-to-action accountability pathway comprising seven elements: signal identification and provenance, risk stratification, assigned professional responsibility, defined response intervals, permitted actions and automation boundaries, escalation procedures, and outcome reassessment. DDCE extends existing digital diabetes ecosystems and the Chronic Care Model by specifying how digital signals may be translated into coordinated, time-bounded, and reviewable care. Medical nutrition therapy is a core application, integrating CGM and dietary data with dietitian-led assessment, personalized nutrition interventions, and critical appraisal of AI-generated dietary recommendations. Diabetes self-management education and support (DSMES), guided by the seven self-care behaviors of the Association of Diabetes Care & Education Specialists (ADCES7), links professional interventions to patient-centered self-management and measurable behavioral outcomes. Four testable propositions address data integration, signal-to-action performance, human–AI safety, and continuous learning. The proposed framework requires prospective validation, with outcomes extending beyond glycated hemoglobin and algorithmic accuracy to include timeliness, therapeutic inertia, dietary and self-management behaviors, safety, clinician workload, equity, and cost.

Nutrients doi: 10.3390/nu18223745

Authors: Muneerah Abdullah Alali Amal Bakr Shori

Introduction. Almond milk is among the most purchased plant-based alternatives to bovine milk and can be fermented with kefir grains, but the resulting beverage has been studied only in terms of its own properties and its effect on the gut microbiota has not been examined. Aims. This study characterized kefir produced from almond milk and examined whether it is associated with differences in the intestinal microbial community in mice. Materials and methods. Kefir grains were inoculated into commercial almond milk at 2%, 3% and 4% (w/v) and fermented at 25 °C for 22 h, and pH, titratable acidity and microbial counts on five culture media were followed over 14 days of refrigerated storage at 4 °C, with sensory evaluation on the first day of storage. The 3% product was then given by daily gavage to male C57BL/6 mice for 21 days alongside plain almond milk and an untreated control, with the fecal microbiota assessed by culture-based enumeration and the colonic luminal contents characterized by 16S rRNA gene sequencing. Results. Fermentation lowered the pH of the almond milk from 7.78 to between 4.74 and 5.27 at day 0 according to the grain concentration (p < 0.001), with titratable acidity rising in parallel (p = 0.009). Mean viable counts stayed at or above 8.00 log10 CFU/mL on four culture media throughout 14 days of refrigerated storage, and neither the counts nor the sensory scores differed between the three concentrations (p > 0.05), apart from texture, which was rated higher as the grain concentration rose (p = 0.005). In mice, fecal lactic acid bacteria were most abundant in the kefir group (p < 0.001); after adjustment for the counts recorded on day 0 the difference from the plain almond milk group remained significant (p = 0.002) while that from the untreated control did not (p = 0.071). In the colonic luminal contents, alpha diversity did not differ among groups (p > 0.05), whereas beta-diversity analysis suggested differences in community composition (PERMANOVA on Bray–Curtis distances, p = 0.004). Bacillota predominated over Bacteroidota only in the kefir group, while Lactobacillus represented 13.0% of the community compared with 4.8% and 5.8% in the almond milk and control groups, respectively. LEfSe further identified Lactobacillus as a discriminating taxon in the kefir group in this exploratory analysis. Conclusion. These findings indicate an association between almond milk kefir consumption and differences in the composition of the colonic luminal microbiota in mice, while alpha diversity remained unchanged.

Nutrients doi: 10.3390/nu18223743

Authors: Paul Florian Dragos Alexandru Bogdan Ilies Zbigniew Jastrzębski Marius Alin Marinau Maria Skalska Sorin Dacian Buhas Joanna Jastrzębska Mirela Stef

Background: Vitamin D insufficiency is common among indoor athletes, but supplementation effects on performance remain uncertain. This randomized, double-blind, placebo-controlled study examined eight-week vitamin D3 supplementation in 20 female national level (second-division) handball players during the competitive season. Methods: Participants were randomized within pairs matched for baseline serum 25-hydroxyvitamin D [25(OH)D] to receive vitamin D3 (5000 IU/day; n = 10) or placebo (n = 10). Serum 25(OH)D, parathyroid hormone, calcium, phosphorus, 10 m and 30 m sprint times, 20 m shuttle-run distance, Wingate peak power, and total work were assessed before and after supplementation. Exploratory between-group comparisons of change used Holm adjustment across nine outcomes. Results: Serum 25(OH)D increased from 26.70 ± 11.12 to 42.96 ± 16.20 ng/mL with supplementation and from 27.05 ± 8.01 to 29.65 ± 7.67 ng/mL with placebo. The between-group difference in change was 13.66 ng/mL (95% confidence interval: 7.32–20.00; Holm-adjusted p = 0.002). No other outcome showed a significant time-by-group interaction after adjustment. Confidence intervals for all between-group performance contrasts included zero. Conclusions: Vitamin D3 supplementation improved vitamin D status, but a supplementation-specific performance benefit was not established. Given the small sample and imprecise estimates, these findings do not establish equivalence or exclude meaningful performance effects.

Nutrients doi: 10.3390/nu18223742

Authors: Wenjing Hu Xiaonan Guo Ruizhen Hou Yuchen Jiang Yuxing Zhao Linjie Wang Hongbo Yang Huijuan Zhu Hui Pan Fengying Gong

Background: Hydroxysafflor yellow A (HSYA) is the main active monomer of safflower yellow (SY), an adjunct for cardiovascular/cerebrovascular diseases. Our previous studies demonstrated that SY/HSYA improved non-alcoholic fatty liver disease (NAFLD) in obese mice; however, the precise mechanisms remain unclear. This study aimed to investigate the molecular targets and mechanisms by which HSYA ameliorates NAFLD. Methods: Male C57BL/6J mice were fed a high-fat diet for 8 weeks to induce diet-induced obesity (DIO), followed by HSYA treatment (100 mg/kg/d) for 8 weeks and antibiotic or non-antibiotic treatment for another 5 weeks. Body weight, OGTT, IPITT, liver histology, liver transcriptomics, and fecal metagenomics were assessed. In vitro, HepG2 cells were treated with 400 μM of palmitic acid (PA) to induce steatosis, followed by HSYA treatment and/or cluster of differentiation 36 (CD36) overexpression. Results: HSYA significantly reduced body weight and fat mass and improved glucose metabolism in DIO mice. HSYA also alleviated hepatic steatosis, which was partly abolished by antibiotic treatment, indicating partial dependence on gut microbiota. Metagenomics revealed that HSYA increased the abundance of Akkermansia muciniphila, which negatively correlated with NAFLD scores. HSYA significantly downregulated CD36 and its upstream signal transducer and activator of transcription 1 (STAT1) protein expression in liver tissue by 59.5% and 35.4%, respectively. Similarly, HSYA reduced CD36 and phospho-STAT1 expression in PA-treated HepG2 cells, and these effects were abolished by CD36 overexpression. Conclusions: HSYA improved NAFLD by remodeling gut microbiota and by inhibiting the STAT1/CD36 pathway, thereby reducing fatty acid uptake in hepatocytes.

Nutrients doi: 10.3390/nu18223741

Authors: Cristian Marco-Alacid Andres Leon Fierro

Creatine is an established ergogenic aid, but its benefits beyond its effects in muscles remain uncertain. This critical narrative review examines cognitive, neurological, psychiatric, metabolic, vascular, skeletal, inflammatory, and rehabilitation outcomes. Targeted searches and citation tracing included publications available on 30 October 2026. We distinguished effects without prescribed exercise, incremental benefits within a common programme, interaction, intervention packages, and mediation. Small studies under sleep loss or hypoxia reported selected cognitive signals; findings in rested adults were inconsistent and benefits in the neurodegenerative conditions examined remained unestablished. Psychiatric findings remained heterogeneous and did not establish clinically important average efficacy. A potentially clinically important glycated haemoglobin reduction in one small exercise-add-on trial in type 2 diabetes remains unreplicated and at a high risk of bias. Vascular findings concerned short-term surrogates; bone-density outcomes were largely null, chronic anti-inflammatory efficacy unestablished, and rehabilitation findings inconsistent. Creatine modestly increased lean mass during resistance training, but downstream clinical mediation was unproven. Sparse evidence on randomised creatine-by-exercise interaction and mediation limits causal attribution without invalidating incremental effects estimated in suitable two-arm trials. Heterogeneous regimens preclude a generalisable dose recommendation. Clinical interpretation should remain indication-specific, prioritising the replication of relevant effects and testing interactions or mediations when those are the research questions.

Nutrients doi: 10.3390/nu18223740

Authors: Kseniya V. Vybornaya Inna Yu. Tarmaeva Dmitry B. Nikityuk

Background/Objectives: Body mass index does not distinguish between the fat and lean components of body mass and may therefore misclassify the nutritional status of athletes. This study aimed to assess the nutritional status of male combat athletes by a combined method based on body mass index and fat mass percentage and to compare their somatotype with population data of the Russian Federation. Methods: In this cross-sectional screening study, anthropometry and bioelectrical impedance analysis were performed in 122 male combat athletes aged 14–43 years; the Heath–Carter somatotype was calculated with bioimpedance equations. Trend tests, logistic regression and non-parametric tests with Holm correction were applied. Results: According to body mass index, 34.4% of the athletes were overweight, and 10.7% were obese, whereas only 13.9% had increased fat mass. Among overweight athletes, 76.2% had a muscular body type. In the older age groups, the muscular type was more frequent (odds ratio 1.67 per 5 years; p = 0.002) and the gracile type less frequent (odds ratio 0.56; p = 0.002). The mean somatotype was ecto-mesomorphic (2.2–5.2–3.2) at 14–17.9 years and endo-mesomorphic (4.8–6.6–1.1) at 36–43 years. Conclusions: The combined assessment of body mass index and fat mass percentage against age-specific population data may serve as a simple screening tool to identify combat athletes who require an in-depth assessment of diet and energy expenditure; it does not replace a comprehensive nutritional assessment.

Nutrients doi: 10.3390/nu18223739

Authors: Zhaoming Cao Ziyuan Wang Daizhao Tian Yinchao Ma Can Zhu Xin Li Yaning Fu Huan Chen Hongwei Hou Ming Chu

Background/Objectives: Diabetes-associated cognitive dysfunction (DACD) remains difficult to treat, and improved peripheral metabolism does not necessarily restore cognition. We investigated solanesol, a plant-derived long-chain polyisoprenoid alcohol, in a high-fat-diet (HFD) mouse model. Methods: Male C57BL/6 mice received an HFD for 24 weeks, followed by 6 weeks of solanesol (10, 20 or 30 mg/kg/day) or rosiglitazone (20 mg/kg/day). Metabolic indices, Morris water maze and novel object recognition performance, hippocampal and ileal morphology, hippocampal transcriptomics, faecal metagenomics and untargeted metabolomics were assessed. Results: HFD feeding induced obesity, hyperglycaemia, hyperinsulinaemia, insulin resistance and impaired spatial and recognition memory. Rosiglitazone improved insulin sensitivity without a detectable cognitive benefit. Solanesol reduced HOMA-IR at all tested doses; reductions in body weight and fasting glucose were observed at the highest dose (SNL-30). Cognitive responses differed by endpoint and were most consistent at the medium and high doses. SNL-30 was associated with a qualitative improvement in hippocampal and ileal morphology, increased hippocampal Apoc3 and Pon1 expression and changes in the gut microbiota and faecal metabolome. Faecal microbial and metabolite profiles covaried. Conclusions: Solanesol improved metabolic and selected cognitive outcomes in HFD-fed mice, with the broadest response at the highest tested dose. Solanesol is a candidate for further preclinical study in DACD.

Nutrients doi: 10.3390/nu18223738

Authors: Anna Olasińska-Wiśniewska Tomasz Urbanowicz Weronika Gościniak Anetta Hanć Wojciech Seniuk Kevser Gülcihan Balcı Dagmara Tritt Filip Waśniewski Rafał Górniak Krzysztof Błaszyk

Background: Trace elements are essential for cardiovascular physiology, and their systemic imbalance has been linked to cardiovascular diseases and pharmacological therapies. However, the relationship between amiodarone therapy and whole-blood elemental profiles in patients with atrial fibrillation (AF) remains unclear. Objectives: This exploratory study evaluated whole-blood elemental concentrations in AF patients with and without amiodarone treatment. Methods: This single-center observational study included 51 AF patients (32 males, 62.8%; median (Q1–Q3) age of 71 (60–76) years) referred for catheter ablation. Whole-blood concentrations of 12 elements were compared in the amiodarone (n =18) and non-amiodarone (n = 33) subgroups. A subgroup analysis restricted to patients with predefined comorbidities was performed. Results: After correction for multiple comparisons, patients receiving amiodarone had higher copper and cobalt concentrations and lower rubidium concentrations (q = 0.01, 0.02, and 0.04, respectively). Amiodarone use remained associated with higher copper concentration after multivariable adjustment (B = 86.3 µg/L, 95% CI 25.3–147.3; p = 0.007), with a similar bootstrap estimate. Adjusted associations for cobalt and rubidium were not statistically significant in the full sample. Among patients with predefined comorbidities, the differences in copper, cobalt, and lead remained significant after correction. Conclusions: Amiodarone use was associated with higher whole-blood copper concentrations after adjustment for selected demographic and clinical characteristics. This association may partly reflect underlying cardiovascular disease burden, although the contributions of disease characteristics and treatment exposure remain uncertain. These findings are hypothesis-generating and do not establish causality.

Nutrients doi: 10.3390/nu18223737

Authors: Rosa Helena Ramos Paula-Vieira Nycole Vieira Ramos Gomes Anamei Silva-Reis Meiry Souza Moura-Maia Naiara Nadia Moreira-Silva Raianne Veiga Celestino Fernanda Rodrigues Monteiro Gustavo Paixão-Santos Yanesko Fernandes Bella Andre Luis Lacerda Bachi Claudio Ricardo Frison Andreas Hoheisel Eleni Papakonstantinou Daiana Stolz Viviane Soares Rodolfo P. Vieira

Background: Caloric deficiency may adversely affect respiratory and immune function in older adults, but its association with pulmonary function, respiratory muscle strength, and pulmonary immunoregulatory mediators remains poorly understood. Methods: In this cross-sectional observational study, community-dwelling older adults were classified according to habitual energy intake relative to estimated energy requirements as normocaloric or hypocaloric. Pulmonary function, handgrip strength, maximal inspiratory and expiratory pressures (MIP and MEP), 1-min sit-to-stand (STS) performance, and systemic and pulmonary concentrations of IL-6, TNF-α, IL-10, and Klotho were assessed. Associations between energy adequacy and study outcomes were additionally investigated. Results: Participants with hypocaloric intake exhibited lower FVC (92.23 ± 14.66 vs. 101.32 ± 19.41% predicted; p = 0.012) and FEV1 (87.31 ± 18.09 vs. 102.93 ± 21.82% predicted; p = 0.002), while FEV1/FVC and expiratory flows were preserved. Handgrip strength (p < 0.001), MIP (p = 0.013), MEP (p = 0.038), and 1-min STS performance (p < 0.001) were also lower. Plasma IL-10 (p = 0.002) and Klotho (p = 0.012), and exhaled breath condensate IL-10 (p = 0.010) and Klotho (p = 0.003), were lower in the hypocaloric group, whereas IL-6 and TNF-α did not differ. Energy adequacy was positively associated with FVC, FEV1, functional capacity, and systemic and pulmonary IL-10 and Klotho. Conclusions: Hypocaloric dietary intake was associated with reduced pulmonary function, respiratory and peripheral muscle strength, functional capacity, and lower systemic and pulmonary IL-10 and Klotho in older adults, without concomitant elevations in IL-6 or TNF-α.

Nutrients doi: 10.3390/nu18223736

Authors: Kai Takedani Masakazu Notsu Shinichiro Ishihara Yuta Takagaki Sabrina Haque Nesyana Nurmadilla Salman Ahmad Ying Zhang Sho Maejima Kentaro Matsuzaki Hiroko Kishi Keizo Kanasaki

Background/Objectives: Circulating erythritol has been linked to cardiometabolic disorders, but its association with renal function decline remains unclear. We investigated this association in patients with type 2 diabetes and examined the effects of erythritol on interleukin-6 (IL-6) secretion from tubular cells. Methods: This retrospective study included 217 patients with baseline estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2. Plasma erythritol and IL-6 concentrations were measured. Renal outcomes were defined as an annual change in eGFR < −2.5 mL/min/1.73 m2 and an eGFR reduction > 30%. Multivariable logistic regression analyses were performed. Human renal proximal tubular epithelial cells (RPTECs) were treated with erythritol for 24 h. Results: Median follow-up was 50 months. Plasma erythritol concentrations were positively correlated with cardio-ankle vascular index, total plaque score, and plasma IL-6 concentrations, and inversely correlated with baseline eGFR. Among 196 patients with eGFR ≥ 60 mL/min/1.73 m2, higher erythritol concentrations were independently associated with Criterion 1 after adjustment for age, sex, body mass index, eGFR, and urinary albumin-to-creatinine ratio. Erythritol increased IL-6 secretion from RPTECs at 1 and 10 μmol/L. Conclusions: Plasma erythritol may serve as a functional biomarker and risk marker for subsequent renal function decline in patients with type 2 diabetes and relatively preserved kidney function. Its association with plasma IL-6 concentrations and its effects on RPTEC IL-6 secretion suggest a potential link between erythritol and renal tubular inflammation.

Nutrients doi: 10.3390/nu18223735

Authors: Haejin Kwon Jiyoung Mun Min-Seok Oh Yoonhee Park Yongju Kim Seong-Ju Han Hong-Kyu Kim Seung-Hyun Oh Jae-Young Kim Kwang-Won Lee Hyun-Mee Park

Background/Objectives: Dietary γ-aminobutyric acid (GABA) is a food-derived bioactive compound with potential metabolic benefits. However, its effects on hepatic protein networks and lipid droplet (LD) organization under high-fat diet (HFD)-induced steatosis remain incompletely understood. This study investigated the hepatic responses to dietary GABA supplementation in mice with HFD-induced hepatic steatosis. Methods: Male C57BL/6J mice with HFD-induced hepatic steatosis supplemented GABA orally at 180 mg/kg/day for 5 weeks. Hepatic responses were evaluated using label-free quantitative proteomics and scanning electron microscopy (SEM)-based analysis of LD morphology and spatial organization. Differentially expressed proteins (DEPs; adjusted p < 0.1, |log2FC| > 1) and protein–protein interaction networks were analyzed to characterize functional pathways and protein modules associated with GABA supplementation. Results: Proteomic profiling identified 108 DEPs (38 upregulated, 70 downregulated), indicating changes in protein networks related to proteostasis, lipid metabolism, and immune- and stress-responsive processes. Protein–protein interaction analysis identified a hub module enriched in ubiquitin-dependent protein quality control components, including ubiquilin-1 (UBQLN1) and ubiquitin carboxyl-terminal hydrolase L3 (UCHL3), which showed reduced abundance following GABA supplementation. GABA also increased the abundance of LD-associated proteins, including perilipin-5 (PLIN5) and glycerol-3-phosphate acyltransferase 4 (GPAT4), while changes were also observed in immune- and stress-responsive proteins, including poly(ADP-ribose) polymerase family member 9 (PARP9). SEM revealed remodeling of hepatic LD architecture in HFD with GABA-supplemented mice compared with HFD mice, with reduced mean LD area (593.30 vs. 1267.24 μm2, p = 0.012), decreased nearest-neighbor distance (32.69 vs. 46.95 μm, p = 0.015), and increased perimeter-to-area ratio (0.17 vs. 0.12, p < 0.001). Total hepatic lipid content and body weight were not significantly altered. Conclusions: Dietary GABA supplementation was associated with remodeling of hepatic LD architecture and changes in protein networks related to proteostasis, lipid metabolism, and immune- and stress-responsive pathways, without reducing total hepatic lipid burden.

Nutrients doi: 10.3390/nu18223734

Authors: Irina Naskinova Mikhail Kolev Meglena Lazarova Hristo Kalinov Velin Klisurov

Background: Dietary pattern–mortality studies usually report one estimate from a single 24-hour recall, without asking what share of the variance in the resulting pattern score is between-person rather than within-person variation. Methods: We pooled ten National Health and Nutrition Examination Survey (NHANES) cycles (1999–2018) linked to the 2019 Mortality File, derived nutrient-density patterns from 26 harmonized nutrients by non-negative matrix factorization, and modeled cause-specific mortality with survey-weighted Fine–Gray subdistribution hazards. Results: The cohort comprised 47,257 adults and 7629 deaths over a median of 9.2 years. No reconstruction-error elbow appeared at any rank from k = 2 to 8, so the two retained components are reported as macronutrient-dominant axes, one fat-dominant and one carbohydrate-dominant, not as discovered food-based patterns. Between-person variation accounted for 31.6% and 35.2% of the variance of a single observed day’s score. After Holm–Bonferroni correction no pattern–mortality contrast reached significance. The strongest, the fat axis against other-cause mortality, gave a hazard ratio of 0.92 (95% CI: 0.82–1.04, padj = 1.000). Regression calibration against a second-day recall moved that estimate away from the null (0.80, 95% CI: 0.57–1.10) while widening its interval, quantifying the attenuation a single recall imposes. Conclusions: The reliability coefficients and calibration factors are reusable by other single-recall NHANES analyses.

Nutrients doi: 10.3390/nu18223733

Authors: Alain K. Koyama Anu Pejavara Julie L. Self

Background/Objectives: High intake of added sugars is associated with adverse health outcomes. Recent studies have not evaluated added sugars intake by nutrition label use, which could provide insight into their effectiveness. We examined added sugars intake by frequency of nutrition label usage in a nationally representative sample of children and adults. Methods: We studied 9416 children and adults from the 2017–March 2020 National Health and Nutrition Examination Survey, a nationally representative sample of the noninstitutionalized civilian US population. Frequency of nutrition label use (frequent vs. infrequent) was self-reported by adults and reported by adult proxies for children < 16 years. Added sugars intake was measured from two 24 h dietary recalls and analyzed as daily intake of added sugars in grams and percent of daily calories from added sugars. Results: Among adults in a cross-sectional study, added sugars intake was significantly associated with nutrition label use for percent of daily calories from added sugars (frequent use: 11.7 [95% CI: 11.2, 12.2]) vs. infrequent use: 17.5 [95% CI: 16.4, 18.5], respectively) and added sugars intake in grams (frequent use: 61.7 [95% CI: 59.2–64.1] vs. infrequent use: 104.4 [95% CI: 97.0–111.9). Significant differences were observed for children for both percent of daily calories from added sugars (frequent use: 13.9 [95% CI: 13.2, 14.6]; infrequent: 16.1 [95% CI: 14.7, 17.5]) and added sugars intake in grams (frequent: 64.5 [95% CI: 61.8, 67.2]; infrequent: 79.0 [95% CI: 71.9, 86.0]). Conclusions: Findings highlight the potential role of nutrition labels in reducing added sugars intake among children and adults.

Nutrients doi: 10.3390/nu18223731

Authors: Gizem Altundal Fatma Yuce Yusuf Emre Altundal Cansu Esen Sibel Biren

Background/Objectives: It is unclear whether patients with degenerative temporomandibular disorders (TMD) eat a poorer diet or simply eat differently. We examined whether diet quality and jaw functional limitation were associated with the severity of cone-beam computed tomography (CBCT)-assessed condylar degeneration. Methods: One hundred adults with TMD (60 with and 40 without CBCT-confirmed degeneration) completed the MEDAS-14, the JFLS-20, a food-frequency questionnaire and an investigator-developed questionnaire on avoidance, texture and weight change. Results: MEDAS-14 scores neither differed between groups (5.62 ± 1.43 vs. 6.15 ± 1.70; p = 0.087) nor correlated with erosion severity (ρ = −0.09), whereas JFLS-20 scores were higher in the degenerative group and correlated with erosion severity overall (ρ = 0.42; both p < 0.001), but not within the degenerative group. Degenerative patients avoided more items, also after adjusting for pain diagnoses, and less often preferred foods of any consistency; chewing-gum avoidance was more frequent (30.0% vs. 5.0%; p = 0.002), and weight loss was self-reported by 28.3% vs. 2.5% (p < 0.001). Conclusions: Degenerative TMD was associated with food avoidance and masticatory limitation, whereas Mediterranean diet adherence did not differ significantly; nutrient intake was not measured. Dietary assessment may need to address how food is eaten, not only what.

Nutrients doi: 10.3390/nu18223732

Authors: Tim T. Lambers Amit Oberai Adam D. Shandling Joshua M. Edgar Jozelyn V. Pablo Andy Teng Antti E. Seppo Xiaowu Liang Angela Yee Kirsi M. Järvinen Joseph J. Campo

Background/Objectives: Human milk supports neonatal protection and immune maturation through a diverse repertoire of immunoglobulins. Antigen recognition profiling has shown geographic and interindividual variation in human milk IgA and IgG responses to global pathogens. In bovine milk, studies indicate that bovine immunoglobulins can recognize and inhibit human pathogens, but comprehensive antigen recognition profiles are lacking. Furthermore, bovine immunoglobulins are susceptible to heat-induced denaturation during milk processing and infant formula production. Therefore, this study compared antigen recognition patterns of human milk and bovine milk, and explored patterns of immunoglobulin-rich bovine milk ingredients (milk fat globule membrane-enriched whey and native whey protein concentrate) and bovine milk-based infant formulae. Methods: Antigen recognition patterns were determined using multipathogen protein microarrays containing 644 full-length or fragmented proteins representing a diverse set of pathogens relevant to human health. Results: Human milk IgA and IgG recognized the highest levels and breadth of pathogen antigens, while infant formulae recognized the least, although all bovine samples had antibodies against a subset of pathogens associated with common pediatric infections. Bovine milk-based ingredients were more similar in antigen recognition profiles to raw bovine milk, as was an infant formula that was gently processed. Conclusions: Human milk provides the highest levels and diversity of specific IgA and IgG antibodies to numerous pathogen antigens, unmatched by infant formulae, which highlights the unique capacity of breastfeeding in providing protection against a wide array of infections in infancy. The use of bovine milk ingredients rich in immunoglobulins and gentle processing may result in formulae that are closer in antibody composition to raw bovine milk than regular infant formulae. The clinical and public health relevance of the pool of antibodies in these bovine milk products in protecting infants from pediatric infections remains to be studied.

Nutrients doi: 10.3390/nu18223730

Authors: Anne Daly Sharon Evans Alex Pinto Catherine Ashmore Srividya Sreekantam Anita MacDonald

Introduction: Liver transplantation is an established therapeutic option for selected inborn errors of metabolism (IEM), providing metabolic stabilisation and reducing disease-related morbidity. However, the nutritional and growth outcomes of children undergoing transplantation for IEM remain poorly characterised. We retrospectively evaluated 24 years of nutritional and clinical outcomes following liver transplantation in children with propionic acidemia (PA), methylmalonic acidemia (MMA), glycogen storage disease type 1a/b (GSD1a/b), and urea cycle disorders (UCDs). Methods: Clinical and nutritional data were retrospectively extracted from hospital records. Of 58 children with IEM who underwent liver transplantation, 46 survived (79%). Survivors included children with PA/MMA (n = 13; PA, n = 4/10; MMA, n = 0/3), neonatal-(n = 9/10) and late-onset UCDs (n = 7/8), GSD1a/b (n = 9/9), tyrosinemia type I (n = 14/14), and maple syrup urine disease (n = 3/4). Detailed nutritional analyses were conducted in 27 surviving children, excluding those with tyrosinemia (n = 14), maple syrup urine disease (n = 3), and two children with PA. Data included age at diagnosis and transplantation, post-transplant follow-up, hospital admissions, anthropometric measures, nutritional support, energy and protein intake, micronutrient intake, and nutritional biochemistry where available. Pre- and post-transplant nutritional intake was assessed against reference nutrient intake (RNI) and estimated average requirement (EAR). Results: Overall survival was lowest in MMA (0%) and PA (40%) compared with 100% in GSD1a/b, 90% in late-onset UCDs, and 88% in neonatal-onset UCDs. PA and neonatal-onset UCDs were typically diagnosed within the first 5 days of life, whereas median age at diagnosis was 21 months for late-onset UCDs and 3 months for GSD1a/b. Median age at transplantation ranged from 2.2 years in neonatal-onset UCDs to 4.9 years in late-onset UCDs, with a median of 12 years (5–24 years) post-transplant follow-up. Before transplantation, 21/27 children (78%) required gastrostomy or nasogastric tube feeding. Hospital admissions statistically significantly decreased across all diagnostic groups; the incident rate ratio (IRR) was 0.32 for GSD, 0.04 for PA, 0.12 for neonatal and 0.48 for late-onset UCDs. Despite this reduction in disease-related morbidity, growth did not improve. Weight and height z-scores declined or remained unchanged across all diagnostic groups, with significant deterioration in height in children with PA (p < 0.0289) and GSD (p < 0.0002). Before transplantation, median energy intake was 72 kcal/kg/day (96% of EAR) and protein intake was 1.2 g/kg/day (120% of RNI). The median time for discontinuation of tube feeding was 18 months after transplantation, although three children, one each with PA, GSD1b, and late-onset UCD, remained dependent on enteral feeding. Conclusions: In this single-centre retrospective cohort, liver transplantation was associated with reduced hospital admission frequency, but improvements in linear growth were not consistently observed. Interpretation is limited by small diagnostic subgroups, missing post-transplant dietary data, differences in follow-up and changes in clinical practice across the study period. These findings support prospective evaluation of structured nutritional and growth surveillance after transplantation, including multidisciplinary assessment before withdrawal of enteral feeding.

Nutrients doi: 10.3390/nu18223729

Authors: Zhihan Yang Xiao Zhang Yujia He Jielan Mi Kun Yue Jing Liu Liqiong Song Yuanming Huang Zhihong Ren

Background: The global prevalence of hyperuricemia (HUA) has increased worldwide, and probiotics are considered an adjunctive treatment with fewer side effects. However, the effective strains and underlying mechanisms are not well understood. Objective: This study aimed to investigate the role of Lacticaseibacillus paracasei SUB12 (SUB12) in alleviating HUA and elucidate its potential molecular mechanisms. Methods: In this study, a HUA mouse model was established using potassium oxonate and adenine to evaluate the uric acid-lowering effect of SUB12. High-throughput metabolomics and 16S rRNA sequencing were used to identify key metabolites and altered microbiota. Results: Oral administration of SUB12 significantly reduced serum UA level, hepatic xanthine oxidase (XOD) activity, and renal inflammation and altered uric acid transport-related proteins. Sequencing analysis suggested that SUB12 not only had the capacity of consuming succinate but also reduced the abundance of succinate-producing Prevotellamassilia. Succinate supplementation significantly promoted XOD activity through the succinate receptor 1 (SUCNR1)/hypoxia-inducible factor 1-alpha (HIF-1α) axis. Conclusions: Our findings reveal that SUB12 attenuates hyperuricemia by down-regulating succinate, which promotes XOD activity and uric acid production through the SUCNR1/HIF-1α/XOD axis.

Nutrients doi: 10.3390/nu18223728

Authors: Marina Toscano de Oliveira Mateus Kawata Salgaço Victoria Mesa Flávia Aparecida Resende Manoela de Araújo Gonçalves Maria Antonella Costa Marcheti Fischer Maria Luísa Souza Marques Adilson Sartoratto Victor Hugo Nascimento Breno Vilas Boas Raimundo Katia Sivieri

Background: Gut microbiota alterations have been implicated in Autism Spectrum Disorder (ASD), but the effects of cannabinoid-based interventions on microbial metabolism remain unclear. This study evaluated the effects of a standardized Cannabis sativa extract on microbial composition and metabolism, epithelial barrier integrity, and inflammatory responses using an in vitro colonic fermentation model. Methods: Fecal samples from 10 children with ASD and 10 neurotypical controls were pooled within groups to generate one ASD-derived (ASD group) and one neurotypical inoculum (NT-group). Each inoculum underwent 48 h anaerobic fermentation in three independent vessels per condition with 0.02, 0.10, or 0.50 mg/mL extract. Cytotoxicity was assessed in Caco-2 cells, microbial composition by 16S rRNA gene sequencing, and ammonia and short-chain fatty acids in both groups. Barrier integrity and inflammatory responses were evaluated only with ASD-derived fermentation supernatants in a Caco-2/THP-1 co-culture model. Results: The extract showed low cytotoxicity in Caco-2 cells across the concentrations evaluated. In the ASD group, treatment was associated with lower ammonia and acetate and higher butyrate concentrations, while propionate remained unchanged. Alpha and beta diversity were largely preserved, and epithelial barrier integrity was not significantly altered. Supernatants from the 0.50 mg/mL condition were associated with lower TNF-α concentrations, whereas IL-6, IL-8, and IL-10 did not differ among conditions. Conclusions: The standardized Cannabis sativa extract modulated microbial metabolism, reducing ammonia production and, in ASD microbiota, increasing butyrate while decreasing acetate, without major changes in microbial diversity. The highest concentration also reduced TNF-α production in the Caco-2/THP-1 model, with no significant effects on barrier integrity or other cytokines. These exploratory findings suggest a potential effect of the extract on microbial metabolic and inflammatory responses and should be considered hypothesis-generating.

Nutrients doi: 10.3390/nu18223727

Authors: Beatriz Pacheco-Sánchez Claire Lensen Antonio J. López-Gambero Pablo Rubio Juan Suárez Carlos Sanjuan Pedro J. Serrano-Castro Antonia Serrano Fernando Rodríguez de Fonseca Patricia Rivera

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of dementia worldwide. Among the mechanisms implicated in AD progression, brain insulin resistance has been associated with impaired synaptic function and cognitive decline. In this context, inositols have emerged as promising neuroprotective compounds, and previous studies have reported beneficial effects of early D-chiro-inositol (DCI) administration in the 3×Tg mouse model. This exploratory study aimed to evaluate whether chronic oral DCI administration initiated at an advanced stage can modulate hippocampal neuronal density, synaptic markers and signaling pathways associated with insulin resistance in aged 3×Tg mice. Methods: Male and female wild-type and 3×Tg mice received DCI in drinking water (approximately 200 mg/kg/day) from 9 to 12 months of age. Neuronal density was assessed by unbiased counting of NeuN-positive cells (cells/mm2), and hippocampal protein expression was analyzed by Western blot, including markers related to insulin signaling, Tau phosphorylation, glutamatergic and endocannabinoid pathways, neuroinflammation and synaptic integrity. Sex effects were formally evaluated by three-way ANOVA (sex × genotype × treatment). Results: 3×Tg mice showed a lower neuronal density in the dentate gyrus–CA3 circuit, females displayed lower neuronal densities than males, and synaptophysin (males) and PSD95 (females) were reduced in 3×Tg mice. DCI increased neuronal density in the CA1 region of 3×Tg females but did not restore the neuronal deficit in the dentate gyrus–CA3 circuit or the synaptic markers. Compared with wild-type mice, 12-month-old 3×Tg animals displayed limited alterations in hippocampal signaling proteins, and DCI induced only sparse, often sex-dependent changes that neither normalized insulin signaling nor reduced Tau phosphorylation. Conclusions: Late-onset administration of DCI had limited effects on hippocampal alterations in aged 3×Tg mice. Although treatment ages were not directly compared, these findings contrast with previous results in which DCI treatment initiated at 3 months of age proved effective, and support the hypothesis that the therapeutic window for DCI narrows as pathology progresses. The sex-dependent differences observed further highlight the importance of considering sex as a biological variable in the design of therapeutic studies.

Nutrients doi: 10.3390/nu18223726

Authors: Lilian de Jonge

The dietary habits of students are critical factors influencing their overall health, cognitive development, and academic performance [...]

Nutrients doi: 10.3390/nu18223725

Authors: Yilin Li Shujun Huang Benhua Zeng Xiang Fang Hong Wei Zhenlin Liao Yonghong Zhou

Background: With the rising prevalence of obesity and its cardiometabolic complications, there is increasing demand for safe and affordable dietary approaches that can counteract excessive adiposity and related metabolic dysfunction. Resistant starch (RS), which bypasses digestion in the upper gastrointestinal tract and is subsequently fermented by colonic bacteria, has emerged as a bioactive food component with reported benefits for glucose homeostasis, lipid profiles, and intestinal health. Methods: Here, we assessed whether green banana powder rich in RS2, incorporated into a high-fat diet at calculated RS contents of 5%, 10%, or 15% (w/w), could mitigate metabolic disturbances in C57BL/6J mice over an 8-week feeding period. Results: Relative to the high-fat diet alone, supplementation with the RS-rich banana powder produced dose-related improvements in body-weight trajectory, fasting glycemia and hyperinsulinemia, circulating TC/TG/LDL-C, glucose clearance (OGTT), and histologic features of hepatic lipid accumulation and adipocyte enlargement; the 15% dose most closely approximated the normal-diet phenotype. Fecal 16S rRNA profiling showed that community composition differed significantly among groups (ANOSIM R = 0.404, p = 0.001). Conclusions: Collectively, these data indicate that the RS-rich banana powder ameliorates several high-fat-diet-induced metabolic derangements in parallel with measurable shifts in gut microbial ecology, supporting its further evaluation as a candidate functional food ingredient for obesity prevention.

Nutrients doi: 10.3390/nu18223724

Authors: Maryam Zibaee Payal Sangani Ahudiya Ochuru William S. Harris Mitchell S. Fineman Richard B. Rosen Pinakin Gunvant Davey

Background/Objectives: Diabetic retinopathy (DR) is a leading cause of vision loss worldwide, and its pathology is driven by chronic hyperglycemia, elevated oxidative stress, inflammation, and microvascular dysfunction. Polyunsaturated fatty acids (PUFAs), particularly omega-3 and omega-6 fatty acids, influence inflammatory and angiogenic pathways, but their role in DR prevention and progression remains uncertain. This integrative review synthesizes current evidence on the effects of PUFAs in DR. Methods: A comprehensive literature search was conducted and eligible studies included human cell culture, animal model, observational, Mendelian randomization, and interventional studies. A total of 44 studies meeting inclusion criteria were systematically analyzed and categorized by study design. Results: Human trials with whole-diet/complex supplements suggest that higher intake or circulating levels of omega-3 PUFAs, particularly docosahexaenoic acid (DHA), are associated with reduced risk and severity of DR. A Mediterranean diet enriched with omega-3 sources demonstrated consistent protective associations. However, randomized controlled trials using isolated omega-3 supplementation reported mixed findings, with some showing no significant effect on disease progression (e.g., ASCEND). Mechanistic studies indeed support biological plausibility, demonstrating that omega-3 PUFAs reduce oxidative stress, inhibit inflammatory signaling, and modulate angiogenesis by attenuating vascular endothelial growth factor activity. Emerging evidence also suggests the potential protective role of certain omega-6 fatty acids, though findings remain heterogeneous. Conclusions: PUFAs, particularly omega-3 fatty acids, may play a protective role in DR through anti-inflammatory, antioxidant, and anti-angiogenic mechanisms. These outcomes appear influenced by dietary context, dosage, and disease stage, highlighting the need for additional long-term, well-designed studies.

Nutrients doi: 10.3390/nu18223723

Authors: Wasima Oualla-Bachiri Ana M Lago-Sampedro Sergio Valdés Flores Martín-Reyes Sara García Serrano Gabriel Olveira Inmaculada González-Molero Araceli Pineda Cantero Alfonso Calle-Pascual Elías Delgado Luis Castaño Inés Urrutia Josep Franch-Nadal Felipe Javier Chaves Núria Amigó Montserrat Guardiola Josep Ribalta Eduardo García-Fuentes Gemma Rojo-Martínez Eva García-Escobar Viyey Doulatram-Gamgaram

Background/Objectives: Standard lipid profiling only partially captures the atherogenic risk conferred by lipoprotein heterogeneity. We investigated the association between olive oil consumption and both the standard lipid profile and the advanced lipoprotein subclass profile in a Spanish population-based cohort. Methods: In this cross-sectional analysis of the Di@bet.es study (n = 3123 after exclusions), 98 participants who reported never using olive oil were matched 1:1 by propensity score (nearest neighbor, caliper 0.2 SD; age, sex, BMI, sweets and carbohydrate intake, waist and hip circumference, physical activity, alcohol, and smoking) to 98 participants who always or usually used olive oil. Lipoprotein subclasses were quantified by 1H-NMR spectroscopy (Liposcale®). Groups were compared using Student’s t-test or the Mann–Whitney U test; p-values were adjusted with the Benjamini–Hochberg procedure. Results: Olive oil users had a lower concentration of medium VLDL particles (−28%; p = 0.002; adjusted p = 0.024). Total VLDL-P, VLDL-TG, total triglycerides, and HDL TG/C were nominally lower and HDL-c higher (p = 0.035–0.049), but none remained significant after adjustment (adjusted p ≥ 0.112). The derived TG/HDL-c ratio, a single unadjusted comparison, was also lower (p = 0.022). No differences in total cholesterol, LDL-c, or LDL and HDL particle number were found. Conclusions: Olive oil use was associated with a lower concentration of medium VLDL particles, without differences in LDL-c. Given the cross-sectional design and small matched sample, these exploratory findings do not establish causality or support clinical use of NMR profiling.

Nutrients doi: 10.3390/nu18223722

Authors: Varshini Kumar Chiao-Ming Chen Dang Hien Ngan Nguyen Shih-Ping Lin Chien-Tien Su Theivasigamani Parthasarathi Sing-Chung Li

Background/Objectives: Plant-based dietary patterns and culinary–medicinal mushrooms may reduce inflammation and cardiometabolic risk but have not been reviewed together. This systematic review assessed their effects on inflammatory and cardiometabolic outcomes and whether proposed mechanisms were directly measured. Methods: PubMed/MEDLINE, Scopus, Embase, and Web of Science were searched (PROSPERO CRD420261503833). Fifty-five human studies (28 intervention and 27 observational) were included and synthesized narratively owing to heterogeneity. Risk of bias was assessed using RoB 2, ROBINS-I, and the Newcastle–Ottawa Scale. Results: Randomized trials supported modest reductions in body weight and LDL-C with vegan and vegetarian diets, whereas effects on CRP and other inflammatory markers were inconsistent. Observational studies consistently associated higher plant-based diet quality with lower CRP, insulin resistance, and type 2 diabetes risk, whereas less healthful plant-based patterns showed opposite associations. Mushroom studies were small and preparation-specific, with mixed findings; a large cohort found no association with incident cardiovascular disease or diabetes. Direct human evidence for the proposed mechanisms was limited, and none was shown to mediate clinical outcomes. Most randomized trials had some risk-of-bias concerns. Conclusions: Healthful plant-based dietary patterns are of interest for cardiometabolic prevention, with benefits depending on diet quality rather than a plant-based label. Evidence for culinary–medicinal mushrooms is insufficient to support recommendations, and proposed mechanisms remain unproven.

Nutrients doi: 10.3390/nu18223721

Authors: Miori Tanaka Norichika Akamatsu Hisako Takahashi Keita Ito Yoshifumi Kimira Toshihiro Suzuki Hirofumi Inoue Nobuyuki Takahashi Mariko Uehara

Background/Objectives: Obesity is associated with increased bone marrow fat content and saturation, which contribute to enhanced osteoclastogenesis and bone loss. Although saturated, monounsaturated, and polyunsaturated fatty acids (FAs) have been reported to differentially affect bone metabolism, their comparative effects and the underlying mechanisms remain unclear. This study compared the effects of palmitic acid (PA), oleic acid (OA), α-linolenic acid (ALA), and linoleic acid (LA) on osteoclastogenesis in vitro and examined the effects of PA-, OA-, and LA-enriched diets on bone metabolism. Methods: Receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL)-stimulated RAW264.7 macrophages were treated with PA, OA, ALA, or LA. The number of osteoclasts, tartrate-resistant acid phosphatase (TRAP) activity, osteoclastic gene and protein expression, NF-κB signaling, reactive oxygen species (ROS)-related fluorescence, and antioxidant-related gene expression were evaluated. The involvement of toll-like receptor 4 (TLR4) signaling was examined using TAK-242. Male C57BL/6J mice were fed high-fat high-sucrose diets enriched with PA, OA, or LA for 8 weeks, and bone mineral density (BMD), plasma bone turnover markers, and osteoclast-related gene expression were assessed. Results: PA enhanced RANKL-induced osteoclastogenesis and NF-κB transcriptional activity, which were partially attenuated by TAK-242. ALA and LA attenuated PA-enhanced osteoclastogenesis and oxidative stress-related responses. Mice fed a PA-enriched diet exhibited lower BMD and higher plasma free fatty acid levels and bone turnover markers. Conclusions: PA promotes RANKL-induced osteoclastogenesis, which can be alleviated by ALA and LA in vitro. These findings suggest that different FAs exert distinct effects on osteoclastogenesis and that dietary FA composition may influence bone metabolism.

Nutrients doi: 10.3390/nu18223720

Authors: Jerzy Kruk Renata Szymańska Beatrycze Nowicka Michał Gabruk

Although vitamin K (VK) was discovered decades ago and its fundamental function in humans as a cofactor required for γ-carboxylation of VK-dependent proteins is recognized, significant progress in the research on this lipid-soluble vitamin has been made only recently. For example, the molecular structure of γ-glutamyl carboxylase (GGCX) from humans has been resolved, as well as that of the cyanobacterial vitamin K epoxide reductase (VKOR) homologue, thereby providing structural information for all enzymes of the VK epoxide cycle that are engaged in carboxylation of VK-dependent γ-carboxyglutamic acid (Gla) proteins. These proteins are responsible for the best-known functions of VK in blood clotting and the prevention of osteoporosis, as well as vascular calcification. Moreover, it has recently been shown that all organisms, from bacteria to mammals and higher plants, share common, phylogenetically related VKOR-type enzymes engaged in the formation of disulfide bridges in various target proteins. The intriguing function of UBIAD1 prenyltransferase is presented and discussed, suggesting a specific role for MK-4 in humans, although such a function has not yet been identified. The nutritional aspects of VK are described, along with numerous reports of its positive effects, mostly unresolved at the molecular level, such as those related to cellular signaling, regulation of gene expression or the prevention of many diseases.

Nutrients doi: 10.3390/nu18223719

Authors: Meda-Ada Bugi Raluca Asproniu Giorgiana-Flavia Brad Niculina Mang Delia-Maria Nicoară Alexandra-Cristina Scutca Diana-Georgiana Basaca Laura Grațiela Olariu Andrei-Ioan Munteanu Andra Romana Țenț Andrei Păun Alexandra Diana Cheleș Iulius Jugănaru

Background/Objectives: Food neophobia, the reluctance to try unfamiliar foods, may restrict dietary variety and complicate the dietary treatment of pediatric obesity. We described caregiver-reported food neophobia in children and adolescents with obesity recruited from the Pediatric Endocrinology and Obesity Outpatient Service of the “Louis Țurcanu” Emergency Clinical Hospital for Children, Timișoara, a tertiary referral center serving Western Romania, and examined its association with adherence to standardized dietary recommendations. Methods: In this cross-sectional study, caregivers of 90 children and adolescents (2–18 years) completed the 10-item Romanian Food Neophobia Scale (FNS) and rated adherence three months after the recommendations had been given. Associations were tested with non-parametric tests (Holm-adjusted) and logistic regression, with penalized, ordinal and multiple-imputation sensitivity analyses. Results: The mean FNS score was 37.0 ± 9.6 (median 39.0); internal consistency was moderate (α = 0.68). FNS was inversely correlated with adherence (ρ = −0.334; p = 0.002; n = 83). Each 10-point FNS increase was associated with higher odds of poor adherence after adjustment for age, sex and residence (OR 4.26; 95% CI 1.72–10.55; n = 81), with consistent estimates in Firth-penalized (OR 3.62), ordinal and multiple-imputation (OR 3.95; n = 90) analyses and after adjustment for parental education. FNS was not associated with sex or BMI-for-age z-score; exploratory associations with rural residence and paternal education did not survive correction for multiple testing. Conclusions: Caregiver-reported food neophobia was associated with poorer caregiver-reported adherence to dietary recommendations. Because of the cross-sectional design and the shared informant, whether assessing neophobia can improve dietary treatment requires prospective validation.

Nutrients doi: 10.3390/nu18213718

Authors: Pedro Vieira Gonçalo Ferreira Filipa Carvalho Carolina Ferreira André Alves Pedro Gomes Tânia Martins-Marques Tânia Ribeiro Pedro Castro Mónica Zuzarte Henrique Girão Manuela Pintado Lígia Salgueiro Flávio Reis Sofia Viana

Background/Objectives: “Low-fat” claims are defined by a fat threshold, with no requirements regarding the nutrients replacing fat. Reformulation often relies on refined starches and free sugars at the expense of dietary fiber. Thus, a low-fat (LF) product is not necessarily of good carbohydrate quality, a dimension that macronutrient-based classification fails to capture. Whether LF-derived poor carbohydrate quality is associated with organ-specific alterations across the gut–liver–kidney axis remains unknown. Methods: Male Wistar rats were fed for 24 weeks a purified LF diet, its ingredient-matched purified high-fat, high-sucrose counterpart (HF), or a whole-grain Chow reference of similar energy density. Carbohydrate quality was assessed using the carbohydrate-to-dietary fiber-to-free sugars ratio. Body weight and adiposity, glucose homeostasis, gut fermentation, and hepatic and renal functional and structural parameters were evaluated. Results: Only Chow met the 10:1:1 carbohydrate quality criterion. At a caloric intake that did not exceed that of Chow, LF feeding was associated with increased body weight, adipocyte hypertrophy, impaired glucose tolerance and postprandial hyperinsulinemia. Fecal short-chain fatty acids (SCFAs) and branched SCFAs declined, consistent with a reduction in colonic fermentative output. Chronic LF exposure was additionally associated with hepatic and renal lipid accumulation, normoglycemic glycosuria, and podocyte structural alterations. Conclusions: A purified low-fat diet was associated with the same spectrum of gut, liver and kidney alterations as its high-fat counterpart, without excess caloric intake. These findings support an important role for nutrient sources and carbohydrate quality in shaping metabolic health beyond dietary fat content or caloric load alone.

Nutrients doi: 10.3390/nu18213717

Authors: Carol Kotliar Rocío Martínez Vivot Cristian Beltramo Ezequiel Huguet Alfredo Lozada Laura Montecchiesi Leopoldo Marcon Sebastián Eduardo Obregón

Background: Omega-3 fatty acids exert anti-inflammatory and hemodynamic effects; however, their concurrent effects in patients receiving treatment for hypertension and dyslipidemia remain incompletely characterized. Objective: To evaluate the effects of 12 weeks of supplementation with pharmaceutical-grade omega-3 fatty acids on inflammatory biomarkers, central and brachial blood pressure including office and 24 h ambulatory measurements, and vascular function in this population. Methods: In this exploratory, randomized, double-blind, placebo-controlled pilot trial, 100 adults received omega-3 ethyl esters at a capsule dose of 2 g/day or a matching placebo for 12 weeks, in addition to stable usual pharmacological treatment. Treatment effects were estimated using linear mixed-effects models. p-values were nominal, and 95% confidence intervals were not adjusted for multiplicity. Results: Compared with placebo, omega-3 supplementation was associated with greater reductions in the neutrophil-to-lymphocyte ratio (NLR; −0.43; 95% CI, −0.73 to −0.13; p = 0.005), ferritin (−47.32 ng/mL; 95% CI, −77.55 to −17.08; p = 0.003), daytime systolic blood pressure (−6.52 mmHg; 95% CI, −10.66 to −2.39; p = 0.002), nighttime diastolic blood pressure (−5.55 mmHg; 95% CI, −9.87 to −1.22; p = 0.013), central systolic blood pressure (−6.71 mmHg; 95% CI, −12.22 to −1.20; p = 0.019), and estimated pulse wave velocity (−0.77 m/s; 95% CI, −1.19 to −0.36; p < 0.001). Conclusions: The trial identified exploratory signals involving NLR, ferritin, selected ambulatory blood-pressure measures, central systolic blood pressure, and algorithm-derived ePWV. Multiplicity, limited sample size, and incomplete outcome availability preclude confirmatory interpretation. Independent replication in larger, prospectively registered trials with clearly specified endpoints and reproducible sample-size calculations is required.

Nutrients doi: 10.3390/nu18213716

Authors: David Rodríguez-García Marta Gómez-Sánchez Elena Navarro-Matías Silvia Arroyo-Romero Alicia Navarro-Cáceres Nuria Suárez-Moreno Andrea Domínguez-Martín Manuel A. Gómez-Marcos David Arjol Leticia Gómez-Sánchez BioICOPER Investigators Group BioICOPER Investigators Group

Background/Objectives: The relationship between macronutrient intake and the clinical manifestations of long COVID-19 remains poorly understood. This study examined these associations in adults from the BioICOPER cohort. Methods: This cross-sectional study included 290 adults with long COVID-19 from the BioICOPER cohort who had complete seven-day dietary records collected using the EVIDENT application. Twelve clinical outcomes were assessed using linear regression with robust standard errors, ordinal logistic regression for frailty, and multinomial logistic regression for dyspnea. Model 1 examined eight exposures (total energy and seven nutrient intake variables), adjusting for age and sex. Model 2 examined seven exposures expressed as energy percentages or fiber density, additionally adjusting for total energy intake. Benjamini–Hochberg correction was applied separately to the 96 and 84 tests, respectively. Results: In Model 1, higher intakes of total fat (odds ratio [OR]: 0.983; 95% confidence interval [CI]: 0.974–0.992), saturated fatty acids (OR: 0.956; 95% CI: 0.932–0.981), and monounsaturated fatty acids (OR: 0.967; 95% CI: 0.948–0.987), per additional g/day, were associated with lower odds of being in a higher frailty category (q: 0.034, 0.034, and 0.038, respectively). No primary association in Model 2 remained significant after correction for multiple testing. Exploratory analyses identified quadratic relationships between the energy percentages from protein and polyunsaturated fatty acids and Montreal Cognitive Assessment (MoCA) scores (q = 0.0163 and 0.0111, respectively). Conclusions: Absolute intakes of certain fats were inversely associated with frailty, whereas the primary analyses of energy-adjusted dietary composition showed no significant associations after correction for multiple testing. These findings do not support recommending a specific macronutrient distribution. The exploratory cognitive findings require replication in longitudinal studies.

Nutrients doi: 10.3390/nu18213715

Authors: Euler Ribeiro-Filho Verônica Farina Azzolin Vitória Farina Azzolin Ednea Aguiar Maia-Ribeiro Suziani da Cruz Madson do Nascimento João Batista Xavier Moraes Josiel do Nascimento Amazonas Alan Diego da Conceição Santos Maria Eduarda Chelotti Débora Filipetto Pulcinelli Fernanda Barbisan Ivana Beatrice Mânica da Cruz

Background: Plant-derived bioactive compounds are increasingly investigated as modulators of cellular processes associated with healthy aging. Uncaria tomentosa is traditionally consumed as a botanical preparation, but the effects of its aqueous stem-bark extract on keratinocyte repair-related responses remain insufficiently characterized. Methods: The extract was examined using colorimetric assays, DPPH radical scavenging, and untargeted LC-HRMS/MS with molecular networking and in silico class prediction. Cell viability, membrane integrity, extracellular NDUFS7, superoxide, nitric oxide-related products, and cell-cycle distribution were assessed at 1–100 µg/mL. Scratch closure, cytomorphology, IL-1β, and TNF-α were evaluated at 1, 3, and 10 µg/mL. Results: The aqueous extract contained phenolic compounds, flavonoids, tannins, and alkaloids and exhibited DPPH-scavenging activity. LC-HRMS/MS supported a diverse profile including flavonoid glycosides, caffeoylquinic acids, procyanidins, iridoids, and putative triterpenoid glycosides. The extract preserved viability and membrane integrity and did not produce marked basal redox imbalance or increased extracellular NDUFS7. It moderately redistributed cell-cycle phases without a classical arrest pattern. Scratch closure increased at 6 and 24 h. IL-1β decreased at 1 and 3 µg/mL, whereas TNF-α remained broadly stable. Conclusions: The aqueous extract enhanced keratinocyte monolayer closure and selectively modulated inflammatory and redox-metabolic responses relevant to inflammaging. Cellular senescence and the senescence-associated secretory phenotype were not directly demonstrated.

Nutrients doi: 10.3390/nu18213713

Authors: Agnieszka Dombrowska-Pali Agnieszka Chrustek Dorota Olszewska-Słonina Maciej W. Socha

Background: Thyroid disorders and diabetes are among the most common endocrine and metabolic conditions affecting pregnant women. It is important to note that adequate serum thyroid hormone levels are essential for proper lactation. Diabetes, in turn, is associated with delayed lactogenesis, especially in cases of poor glycemic control. It should be emphasized that breastfeeding is globally recognized as the safest and most effective method of feeding infants. Human milk has a variable nutritional composition in distinct phases: colostrum, transitional milk, and mature milk. Methods: The present observational cross-sectional study included 208 breastfeeding women between 3 and 12 months postpartum: 79 women with hypothyroidism, 53 women with type 2 diabetes, and 76 healthy controls. An analysis was conducted on a sample of human milk to determine its basic nutritional composition, cortisol concentration, and antioxidant status. This analysis utilized DPPH and FRAP assays, which are methods employed to assess the antioxidant capacity of a sample. The basic composition of human milk was analyzed using the MIRIS HMATM analyzer (Uppsala, Sweden). Cortisol levels were determined using an immunoenzymatic method. Results: In unadjusted analyses, milk fat content was higher in women with hypothyroidism and lower in women with type 2 diabetes compared with the control group. However, these differences were no longer statistically significant after adjustment for maternal and clinical covariates in multiple regression analyses. A lower reduction in the DPPH radical was shown in the milk of women with type 2 diabetes (13.8%) and in the milk of women with hypothyroidism (29%) compared to the control group. In the group of women with type 2 diabetes, cortisol levels positively correlated with the protein content and caloric content of milk. It was also noted that BMI in this group was significantly associated with the caloric content of human milk. Conclusions: These findings demonstrate differences in selected characteristics of human milk among the studied groups; however, their clinical relevance for infant health cannot be determined from the present study, as infant growth, body composition, and developmental outcomes were not assessed. Further prospective studies incorporating infant outcomes are needed to determine the clinical significance of these observations.

Nutrients doi: 10.3390/nu18213714

Authors: Aleksandra Purkiewicz Renata Pietrzak-Fiećko

Algae are a promising source of biologically active compounds with potential significance for human health and modern food technology. Their diverse chemical composition includes, among other things, proteins and peptides, polyunsaturated fatty acids, polysaccharides, carotenoids, chlorophylls, polyphenols, vitamins, and minerals. The aim of this review is to provide a comprehensive characterization of the bioactive potential of algae and to analyze their health-promoting properties and potential applications in the production of functional foods. Particular attention was paid to compounds that have been shown in studies to exhibit antioxidant, anti-inflammatory, and antihypertensive effects, as well as those that potentially support normal glucose metabolism and have anticancer properties. The importance of selected algal components in protecting cells from oxidative stress and modulating metabolic processes was also discussed. From a food technology perspective, the possibilities for using algal biomass and components isolated from it as functional additives, natural colorants, texturizers, and sources of nutrients were presented. The potential of algae as an alternative source of protein and lipids in response to the growing demand for sustainable food raw materials was also considered. At the same time, limitations related to the bioavailability of bioactive compounds, variability in chemical composition, the presence of potential contaminants, and the need to standardize methods were highlighted. An analysis of the available data indicates that algae may be a valuable raw material for the development of functional foods; however, fully realizing their potential requires further in vivo studies and clinical trials to confirm their efficacy and safety.

Nutrients doi: 10.3390/nu18213712

Authors: Seiya Masukane Suguru Fujita Ayano Ueda Fumihiko Hakuno Koichi Ito Yuki Kawashima-Sonoyama Takeshi Taketani

Background/Objectives: Food avoidance may compromise nutrient intake and growth in children with food allergy; however, its association with plasma amino acid profiles remains poorly understood. We aimed to examine dietary restriction status for hen’s egg, cow’s milk, and wheat in relation to plasma amino acids, growth, and insulin-like growth factor I. Methods: This single-center cross-sectional study included 80 children aged < 10 years. Dietary restriction status, defined based on the amount of each food medically permitted for routine daily consumption, was dichotomized as complete avoidance/minimal intake or partial/unrestricted intake. Plasma amino acids were available for 79 participants. Multivariable models included all three foods, with Benjamini–Hochberg correction. Results: No broad reduction in plasma amino acid concentrations was evident across dietary restriction categories, although several food-specific associations were observed. Less restrictive cow’s milk status was nominally associated with higher height standard deviation score (SDS) and lower aspartic acid concentration. Less restrictive wheat status was associated with lower weight SDS after multiple-testing correction (q = 0.046), although the complete avoidance/minimal intake group comprised only three participants. Among children with a cow’s milk allergy, threonine concentration was 34.2% lower in the partial/unrestricted group than in the complete avoidance/minimal intake group (q = 0.002). The minimum essential amino acid z-score was inversely associated with weight SDS and body mass index SDS (q = 0.023 for both). No association with the overall 20-amino-acid profile remained significant after multiple-testing correction. Conclusions: Dietary restriction status was not accompanied by a broad or uniform reduction in circulating amino acids. Instead, the observed pattern suggested selective rather than generalized differences, warranting confirmation in longitudinal studies with quantitative dietary assessments.

Nutrients doi: 10.3390/nu18213711

Authors: Jiří Vejmelka Martina Kollerová Ivana Pražanová Khanh Ha Pham Magdalena Trusinová Pavel Kohout

Background/Objectives: Simple anthropometry may complement nutritional assessment in irritable bowel syndrome (IBS). We examined the associations of arm anthropometry and handgrip strength (HGS) with bioelectrical impedance analysis (BIA) parameters. Methods: This cross-sectional baseline analysis included 55 adults with IBS-D or IBS-M for valid non-adiposity measurements; 54 contributed valid paired body-fat estimates, and 54 had valid dominant-hand HGS. Results: MUAMC correlated with BIA-derived skeletal muscle mass within men (Spearman’s ρ = 0.748) and women (ρ = 0.673). After adjustment for sex, age, height and body weight, the MUAMC association was attenuated (β = 0.0337 kg/mm, 95% CI 0.0059–0.0616; p = 0.0187). MUAMC was correlated with phase angle in the pooled sample (ρ = 0.806), but sex-related differences were exploratory. In a sensitivity model using the impedance index, the association was not significant after further adjustment for body weight (β = 0.0670, 95% CI −0.0087 to 0.1427; p = 0.0816). HGS correlated with BIA-derived skeletal muscle mass before adjustment (ρ = 0.769; n = 54), whereas an adjusted association was not established. BIA- and skinfold-derived body-fat estimates were correlated but showed proportional bias, limiting interchangeability. Conclusions: MUAMC is associated with BIA-derived muscle-related parameters, but mathematical coupling, body size and the absence of a criterion method limit causal and validation claims. Findings from this exploratory single-centre analysis require independent confirmation.

Nutrients doi: 10.3390/nu18213710

Authors: Huimin Ben Yuqian Hua Zixuan Ping Shouxin Peng Yuxuan Tan Xiuli Zhao Zhihao Xie Xiaoxia Liu Wei Liang

Background: HIV-infected individuals with compromised immune function are particularly vulnerable to atmospheric particulate matter (PM). While Vitamin D is known to modulate inflammation and immune function, its effect on PM-induced immune impairment in HIV-infected individuals remains unclear. Methods: This randomized, double-blind, placebo-controlled trial in Wuhan, China, investigated Vitamin D’s protective effects. In total, 80 participants received daily Vitamin D or a placebo and were followed up every 28 days across four visits. PM exposure was assessed 72 h before each follow-up, with immune cell counts, immunomodulatory factors, and whole-genome DNA methylation profiles measured. Linear mixed-effects models were used to assess the association between PM exposure and cell counts, and to identify CpG sites associated with Vitamin D. Mediating models further evaluated the role of these CpG sites in linking Vitamin D intervention to cytokine changes. Results: From March to July, 2023, 75 participants received 271 follow-ups. Vitamin D supplementation significantly attenuated the negative associations between PM exposure and CD4+T cell and CD19+B cell counts. Compared with the placebo group, the estimated PM-associated changes in CD4+T cell counts differed by 3.37%, 2.21%, and 1.96% per 10 µg/m3 increase in PM1, PM2.5, and PM10 concentrations, respectively, while the corresponding differences for CD19+B cell counts were 4.71%, 2.98%, and 2.65%, respectively. Significant methylation changes were observed at 173 CpG sites related to Vitamin D. Of these, 25 sites—including cg27066321 (PEX14), cg08500112 (PDE4D), and cg25882580 (CACNG6)—were identified as potential mediators of the effects of vitamin D supplementation on TLR4, IL-6, and TNF-α levels, with mediation proportions ranging from 27.98% to 78.78%. Conclusions: Vitamin D supplementation may attenuate PM-associated immune alterations in people living with HIV, with DNA methylation potentially contributing to the underlying mechanisms.

Nutrients doi: 10.3390/nu18213709

Authors: Ana Ilić Ivana Rumbak Ružica Brečić Martina Bituh

Background/Objectives: Although investments are being made in school meals worldwide, their quality remains problematic due to financial, knowledge-related, or logistical factors. The aim of this study was to examine the nutritional adequacy of school meals in Zagreb (Croatia) and to determine whether the energy adequacy differs depending on selected environmental factors such as school location and neighborhood poverty rate, type of meal service system, staffing, menu planning, and participation in school-based nutrition initiatives and programs. Methods: The study was conducted in 14 primary schools in the city of Zagreb during the 2016/2017 and 2017/2018 school years. A total of 2469 daily menus were collected (2379 breakfasts, 2376 lunches, and 2103 snacks). Menus and information on environmental factors were obtained through on-site audits, direct dialogs with staff, and school curricula. The energy and macronutrient content of school meals was analyzed using Prehrana software version 1.0 and evaluated according to national guidelines. Results: The energy and macronutrient content varied greatly among schools. In 75% of schools, the average energy and macronutrient content of breakfasts exceeded 110% of recommendations, while 70% of schools averaged less than 90% of recommendations for energy and macronutrients in lunches. Considering energy and macronutrient content, three breakfasts, 38 lunches, and one snack met all four recommendations. Among the school-level environmental factors observed, the proportion of energy-adequate meals differed significantly by kitchen type, number of on-site-prepared meals, and neighborhood poverty for lunches, as well as school garden presence for breakfasts. Conclusions: The findings reveal differences in the nutritional adequacy of school meals across primary schools in Zagreb and may help guide future improvements in school food system guidelines and practices.

Nutrients doi: 10.3390/nu18213708

Authors: Grzegorz Bartosz Izabela Sadowska-Bartosz

Ergothioneine (ET) is an exogenous thiol antioxidant present mainly in mushrooms and, in smaller amounts, in various other food products as well. Numerous beneficial health effects of ET have been reported, suggesting that ET is a vitamin-like compound. Evidence that ET prevents and inhibits the development of neurodegenerative diseases, especially Alzheimer’s disease and Parkinson’s disease, has been accumulated based on studies of cellular and animal models, as well as epidemiologic and interventional studies in humans. The mechanism of the neuroprotective action of ET remains to be elucidated. Apart from the direct antioxidant effect, ET was found to stimulate an endogenous antioxidant defense through the activation of Nrf2 signaling while also affecting other signaling pathways. The accumulating literature data suggest that an ET-rich diet could be recommended for the prevention of neurodegeneration in the general population, but such a recommendation, though noteworthy, is not yet adequately supported by the limited human intervention data, and further studies are needed.

Nutrients doi: 10.3390/nu18213707

Authors: Anna Rogala Renata Nestorowicz

Background/Objectives: Consumers often hold positive attitudes towards sustainable food, but this rarely translates into behaviour, as everyday food decisions are shaped by routines, constraints and situations. Research on food-related mobile applications has focused mainly on their functions or persuasive power, with less attention to whether their content matches the conditions under which consumers decide. We conceptualise such applications as decision-support environments and examine how their content could be tailored to behavioural readiness to change. Methods: We combined the Transtheoretical Model (stages of change, SOC) and the COM-B model. Three quantitative studies among Polish consumers examined food literacy, decisional balance, values, well-being and use of mobile applications. Results: We found non-linear differences across stages in motivational profiles and values, with health as the most consistent motivator. Readiness was not linearly related to well-being or engagement with digital tools: consumers at the earliest stage did not report the lowest well-being, and some consumers willing to use sustainability-oriented applications were unaware that such applications existed. Conclusions: Standardised, persuasive approaches are, therefore, of limited use. We propose the SOC–COM-B framework as a conceptual and decision-support design approach for organising application content according to behavioural readiness. It is a basis for prospective testing and informs developers of nutrition-related applications.

Nutrients doi: 10.3390/nu18213706

Authors: Lucian-Ioan Cristun Otilia Mărginean Iulius Jugănaru Raluca-Nicoleta Vasilescu Niculina Mang Andrei-Ioan Munteanu Delia-Maria Nicoară Meda Ada Bugi Andrei Păun Alexandra-Diana Cheleș Laura Cristina Rusu

Childhood diet may shape immune and inflammatory trajectories through interacting metabolic, microbial, and developmental pathways, but the long-term human evidence remains heterogeneous. This scoping review mapped longitudinal studies examining dietary exposures from birth to 18 years in relation to subsequent immune, inflammatory, allergic, autoimmune, gastrointestinal, immunometabolic, hepatic, neurocognitive, and endocrine–immunometabolic outcomes. The review was conducted in accordance with Joanna Briggs Institute guidance and reported according to PRISMA-ScR principles. A total of 403 studies were included. Evidence was concentrated in infancy and early childhood and predominantly addressed allergic and atopic outcomes; evidence on other immunological outcomes and on middle childhood and adolescence was more limited. Thirty studies provided relatively direct immunometabolic evidence, 149 contributed mechanistically indirect evidence, and 224 primarily reported longitudinal clinical diet–outcome associations. The principal mechanistic axes involved allergic sensitization and immune tolerance, lipid and fatty-acid metabolism, micronutrient and antioxidant pathways, cytokine signaling, gut microbiome and metabolite pathways, and human-milk-derived bioactive signals. Dietary diversity and overall diet quality intersected with several of these pathways. Associations were frequently context-dependent, varying according to developmental timing, host susceptibility, genetic background, immune state, and feeding context. Mechanistic interpretation rests on convergence across complementary studies rather than on complete pathways demonstrated within individual cohorts. Overall, the evidence is compatible with a proposed life-course nutritional immunology framework in which childhood diet acts as a dynamic developmental exposure interacting with microbial, metabolic, and immune processes; however, this framework derives mainly from early-life exposures and allergic and atopic outcomes, and the persistence of effects beyond early childhood remains insufficiently demonstrated. Limitations include restriction to English-language publications, marked methodological heterogeneity, residual confounding, and the absence of a formal risk-of-bias assessment.

Nutrients doi: 10.3390/nu18213704

Authors: Agnieszka I. Mazur-Bialy

Postpartum bowel symptoms are often attributed to tissue injury, pelvic-floor trauma, or abdominal diastasis. Structural measures do not capture task-specific diaphragm–abdominal-wall–pelvic-floor function. This critical narrative review proposes an abdominopelvic-to-gut model for a susceptible postpartum subgroup. PubMed/MEDLINE, Scopus, and Web of Science were searched till 8 August 2026; 40 reports were included (12 Core; 28 Supporting). All 34 primary reports among the 40 retained received preliminary design-specific appraisal. Route A connects pressure–outlet dysfunction with inefficient evacuation, retention, and possible transit delay. Its relatively closer support comes from non-postpartum physiological studies and selected postpartum anorectal and symptom outcomes, without demonstrating stabilization-mediated transit change after childbirth. Route B links respiratory mechanics to bowel displacement, accommodation, and possible pressure-dependent fluid transport; its postpartum bowel effects remain hypothetical. Transit and stool residence may connect mechanics with microbial metabolism, while diet and lactation can modify or independently generate intestinal changes. The contribution is an integrated, falsifiable framework, not validation of the full causal chain. Functional, bowel, and nutritional measurements must be synchronized to test its links.

Nutrients doi: 10.3390/nu18213705

Authors: Pablo Lozano-Martínez Rosana Urdániz Borque Gema González Fernández Clara Fernández Rivera Alba Gil-Pascual Carlota Losfablos de Castro José Antonio Gimeno Orna Julia Ocón Bretón

Background/Objectives: Cancer cachexia is linked to poor oncological outcomes. The Cachexia Index (CXI) and the CRP–triglyceride–glucose index (CTI), composite markers of body composition, nutrition, and inflammation, have emerged as prognostic tools, but their value in hospitalized cancer patients remains unexplored. We evaluated their association with short- and long-term outcomes in this population. Methods: This retrospective, observational study included 139 hospitalized patients with active cancer by a Nutrition Unit during 2023. Nutritional status was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria; body composition was quantified by computed tomography (CT) imaging at L3 level. Primary outcomes were in-hospital mortality, intensive care unit (ICU) admission due to clinical deterioration, hospital readmission, and overall survival. Each index was analyzed as a continuous variable, in quartiles, by the median, and at an exploratory ROC-derived cut-off, using logistic and Cox regression. Results: CXI at its ROC-derived cut-off (<9.03; AUC 0.69) was associated with in-hospital mortality (OR 3.91; 95% CI 1.22–12.52; p = 0.022) and overall survival (HR 1.75; 95% CI 1.04–2.95; p = 0.035), unlike its continuous, quartile, and median forms. CTI at its cut-off (≥6.71; AUC 0.704) remained associated with ICU admission after adjustment for surgery and age (OR 5.52; 95% CI 1.64–18.54; p = 0.006) or surgery and myosteatosis (OR 4.94; 95% CI 1.48–16.47; p = 0.009), but not with survival. Conclusions: CXI and CTI show complementary, threshold-dependent prognostic value: CXI identifies in-hospital and long-term mortality risk, and CTI, more consistently than CXI, identifies ICU admission risk due to clinical deterioration. These exploratory findings need prospective, multicenter validation.

Nutrients doi: 10.3390/nu18213703

Authors: Sithembiso S. Msibi Kidist Woldehawariat Nguyet Trinh MinJae Lee Lihchyun Joseph Su

Background: Metabolic dysfunction has been linked to prostate cancer (PCa) development and progression. This study sought to assess whether metabolic risk factors influence PCa death or simply reflect overall mortality risk among men with PCa. Methods: We analyzed data from 1497 men enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Pre-diagnosis dietary and metabolic factors were summarized into a standardized metabolic health-related (MHD) index reflecting higher intake of added sugars, glycemic load, saturated fat, and sodium intake, and lower intake of fiber, fruit, vegetable, and whole grain. Adjusting for demographic, clinical and lifestyle factors, we used multinomial logistic regression to examine associations between the metabolic index and outcomes: PCa death, non-PCa death, and alive at follow-up. Results: Among 1497 men, 95 and 311 died from PCa and non-PCa causes, respectively, and 1091 were alive at follow-up. The MHD index differed across mortality-status groups (p < 0.001) and was higher among men with aggressive PCa (p < 0.001) but did not differ significantly by race (p = 0.187). In adjusted multinomial logistic models, higher MHD index, which represents a less favorable metabolic health–related dietary profile, was significantly associated with increased odds of PCa-specific death adjusted odds ratio [aOR] = 1.38 (95% CI, 1.10–1.73; p = 0.006), but not non-PCa death [aOR] = 1.03 (95% CI, 0.89–1.19; p = 0.687). Conclusions: Less favorable pre-diagnosis metabolic health–related dietary profiles were significantly associated with PCa-specific mortality but not non-PCa mortality, suggesting a potentially distinct role of dietary pattern in PCa progression. The association was not observed for non-PCa death and was attenuated after adjustment for anthropometric and tumor characteristics. These findings support further investigation of overall dietary-metabolic profiles as potentially relevant factors in PCa-specific mortality.

Nutrients doi: 10.3390/nu18213702

Authors: Pedro Hidalgo-Lopezosa Patricia Ruz-Cea Laura Moreno-Domínguez Laetitia Emmanuelle Crosse Cristina Quirós-Córdoba Rubén García-Fernández Pablo Jesús López-Soto Inmaculada Ortiz-Esquinas

Background/Objectives: There is international consensus that breastfeeding is the best form of nutrition for newborns. Many studies demonstrate the effectiveness of educational interventions in maintaining exclusive breastfeeding up to 6 months. The aim was to assess the effectiveness of an educational and support intervention in breastfeeding by a lead midwife on the postnatal ward. Methods: A retrospective quasi-experimental pre-post study complemented by a supplementary descriptive survey was conducted at a tertiary hospital in southern Spain with women (N = 136) who expressed a desire to breastfeed their babies. An institutional intervention, consisting of the support provided by a midwife employed exclusively to offer support with breastfeeding for a period of two months, was carried out. An inferential analysis was performed using the corresponding statistics. A multiple logistic regression analysis was performed to identify potential confounding variables and determine factors associated with the dependent variable of exclusive breastfeeding at 6 months. In addition, a brief institutional survey was conducted among these women after the first 6 months postpartum as a complementary component to the quantitative analysis. Data were obtained from hospital records and from the survey. Results: Exclusive breastfeeding at discharge and at two months postpartum was higher in the intervention group than in the control group. The need for supplementary feeding and phototherapy among infants was lower in the intervention group. A higher level of satisfaction with the support received regarding breastfeeding was also observed among mothers in the intervention group (95.7% vs. 63%; p < 0.001). However, we did not detect a between-group difference in exclusive breastfeeding at six months. Conclusions: Availability of support from a breastfeeding specialist midwife in hospital and in the weeks following birth can assist women to exclusively breastfeeding and supports to improve maternal satisfaction.

Nutrients doi: 10.3390/nu18213700

Authors: Anna Vedani Maria Jose Habib Erica DellaBianca Lucia Rogledi Nicola Lamberti Giacomo Fontana Carola Ricci Giulia Mattavelli

Background/Objectives: Food waste contributes to environmental, social, economic, and nutritional losses. In this context, school canteens represent a key setting for shaping sustainable and healthy early dietary behaviors. This pilot study aimed to evaluate the implementation of a combined digital meal-planning and educational intervention and to explore changes in plate waste, food-related responses, and perceived inclusivity and involvement. Methods: An uncontrolled pre-post pilot study in one preschool and one primary school in a single municipality was conducted. The intervention combined a digital lunch-planning tool, enabling menu and portion selection, with educational workshops on food and sustainability. Plate waste was weighed during two menu-matched weeks, one before and one after implementation. Parent and child questionnaires assessing dietary habits, emotional responses to food and food waste images, perceived inclusivity and involvement, and well-being were recorded. Results: Of 159 enrolled pupils, 155 registered on the platform and 152 used it at least once. Overall, 82.3% of meals were pre-planned through the platform. Questionnaires were completed at baseline by 93 participants and at follow-up by 60, with 48 participating at both time points. Exploratory analyses identified differences over time in some emotional-response ratings and higher parent-rated inclusivity and involvement at follow-up. Across the two observation weeks, measured plate waste decreased from 0.066 to 0.038 kg per meal attendance, an observed reduction of 42.1%. As portion sizes could be reduced or omitted, lower discarded quantities could be related to both increased food consumption and/or reduction in the amount of food prepared. Conclusions: High platform uptake supports the operational feasibility of implementing this combined programme in the participating schools. The observed differences are exploratory: the uncontrolled design, brief waste-measurement periods, and questionnaire attrition preclude causal attribution. Controlled studies with repeated measurements and longer follow-up are needed to evaluate effectiveness and transferability.

Nutrients doi: 10.3390/nu18213701

Authors: Agnieszka Rudzka Ondřej Patloka Marcin Kruk Magdalena Płecha Marek Zborowski Tomasz Królikowski Michał Oczkowski Danuta Kołożyn-Krajewska Marcelina Karbowiak Wioletta Mosiej Renata Barczyńska-Felusiak Dorota Zielińska

Background: The transfer of human intestinal microbiota from in vivo to in vitro conditions alters its structure. This transition may trigger functional changes in the microbial community, such as its ability to produce short-chain fatty acids (SCFAs) and lactate. Methods: This study evaluated SCFAs and lactate profiles in the dynamic simulator and in the feces of a human volunteer who donated a sample for the inoculation of the system. Changes in SCFA and lactate levels were monitored over a 28-day dietary intervention and a parallel 14-day probiotic supplementation. Results: Microbial and dietary variation were not significant predictors of variability in SCFA and lactate profiles. In contrast, culturing environment and probiotic intervention exerted significant effects on SCFAs and lactate. The probiotic intervention appeared to influence SCFA and lactate profiles under in vitro conditions, whereas no similar effect was observed in vivo. Furthermore, the abundance of individual microbial genera was mostly weakly correlated with SCFA and lactate levels, and the direction of these correlations was inconsistent across two microbiota culturing environments. Conclusions: Our findings suggest that structural changes in the microbiota during its transfer from in vivo to in vitro conditions are accompanied by alterations in microbial functions, such as SCFA and lactate levels or response to interventions. However, these responses align with data from other human studies, supporting the ability of dynamic in vitro models to simulate key functions of the intestinal microbiota. Further optimization is required to accurately model personalized microbiota responses.

Nutrients doi: 10.3390/nu18213699

Authors: Laura Gil-Caselles

Background/Objectives: Olive-derived foods and bioactive compounds are increasingly investigated in sports nutrition, but their effects on exercise outcomes remain unclear. This systematic review evaluated randomized controlled evidence on olive-derived nutritional interventions in humans. Methods: MEDLINE/PubMed, Scopus, Web of Science Core Collection, SPORTDiscus, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) were searched from inception to 30 September 2026. Randomized controlled trials of orally administered olive-derived interventions in healthy participants undergoing exercise, training, or physical-function assessment were included. Risk of bias was assessed using the revised Cochrane Risk of Bias tool for randomized trials (RoB 2), with two assessments rated as low risk and eight as having some concerns, and findings were synthesized without meta-analysis because of substantial heterogeneity. Results: Eleven reports representing 10 independent trials evaluated chemically distinct interventions: extra virgin olive oil, hydroxytyrosol-rich olive-fruit-water preparations, oleuropein-rich olive-leaf extracts, and maslinic acid. In specific exercise settings, maslinic acid was associated with lower perceived fatigue or muscle soreness, while selected muscle-related outcomes differed in trials involving older adults. Other preparations yielded heterogeneous physiological, metabolic, or fatigue-related findings, without consistent improvements in objective exercise performance. Conclusions: The available evidence does not establish a common ergogenic effect across olive-derived products. Any potential benefit must be interpreted in relation to the specific formulation, dose, population, exercise context, and outcome assessed. Independent confirmation is required before practical recommendations can be established.

Nutrients doi: 10.3390/nu18213698

Authors: Debra Jones Paul Clarkson Anthony Gilfillan Jeff Burns Sorrel Burden

Background/Objectives: Food insecurity (FI) is an increasing concern in the UK. Early Help (EH) provided by social services, based on strengths-based conversations with families, can address wider social and economic needs experienced by families living with FI. This study aimed to describe needs identified through EH assessments among families attending foodbanks, the proportion of recorded needs met, and stakeholder experiences. Methods: A mixed-methods study was undertaken using 30 months of routinely collected social services data. Regression modelling examined associations between needs identified at the start of EH and the proportion documented as met at the end of support. Semi-structured interviews explored stakeholder experiences using Framework Analysis. Results: Records were available for 385 families comprising 1840 individuals (1108 children; 732 adults). Thirty-five categories of need were recorded, with 2646 needs identified (mean 6.9, standard deviation [SD] 3.2 per family). Of these, 2505 (95%) were documented as met, and 301/385 (78%) families had all identified needs recorded as met. In the primary quasi-binomial regression analysis (n = 378), longer duration of EH involvement was associated with a higher proportion of initially identified needs recorded as met (β = 0.139, p = 0.017). Area-level deprivation was also associated with the outcome (β = −0.179, p = 0.049), whereas household size was not (p = 0.249). The positive association with duration was supported by a Gaussian sensitivity analysis (p = 0.003). Interviews (n = 23) identified three overarching themes: systemic and structural drivers of FI; lived experiences and service engagement; and visions for improvement. Conclusions: Participants described practical and emotional support gained from EH. Families attending foodbanks had multiple needs across diverse domains and most needs were documented as met following EH involvement. However, the study design does not establish that EH caused these outcomes.

Nutrients doi: 10.3390/nu18213697

Authors: Thu Trang La Jennell Jia Ying Koh Wen Wei Ang Jing Xuan Ng Karishma Chandramohan Amudha Jessie Jun Min Lim Diana-Lyn Baptiste Mei Hui Liu Asim Shabbir Roger Foo Su Lin Lim Kee Yuan Ngiam Han Shi Jocelyn Chew

Background/Objectives: Excess adiposity is associated with abnormal postprandial glucose responses (PPGRs), and controlled studies show that one meal can influence the PPGR of the next. Whether this carry-over occurs in everyday eating is unclear. We examined whether the timing, composition, and PPGR of the preceding meal were associated with the subsequent PPGR. Methods: This observational secondary analysis included 55 Southeast Asian adults with excess body weight and 342 within-day consecutive eating-occasion pairs recorded using a smartphone app and continuous glucose monitoring. Participant fixed-effects linear regression examined 12 preceding-meal characteristics, including intermeal interval (IMI), glycemic load, total sugar, protein, and saturated fat. The outcome was the log-transformed positive incremental area under the glucose curve ln(1 + positive 0–120 min iAUC after the subsequent meal. Each characteristic was examined separately per within-person standard deviation (SD), adjusting for current-meal characteristics, premeal glucose, and temporal factors. Confidence intervals and p values used 2000 participant-cluster bootstrap resamples; Benjamini–Hochberg q values addressed the 12 tests. Results: Higher preceding-meal protein was associated with lower iAUC (−13.9%; 95% confidence interval (CI), −23.1 to −4.2; p = 0.008; q = 0.032), whereas total sugar was associated with higher iAUC (+29.6%; 95% CI, +16.9 to +45.2; p = 0.001; q = 0.006). A 1 SD (1.9 h) longer IMI was associated with 29.1% higher iAUC (95% CI, 15.0 to 48.8; p = 0.001; q = 0.006). The saturated-fat estimate was uncertain (+14.8%; 95% CI, −0.8 to +35.2; p = 0.066; q = 0.198). Conclusions: Preceding-meal sugar, IMI and protein were associated with subsequent glucose responses. Protein was sensitive to additional macronutrient adjustment; saturated fat remained uncertain. Incomplete metabolic and dietary information limits causal interpretation.

Nutrients doi: 10.3390/nu18213695

Authors: Chieh-Ju Lu Chi-Lun Tsai Kuo-Pin Wang

Background: Caffeine mouth rinse (Caf-MR) has been investigated as a non-ingestive strategy that may influence cognitive performance and psychological responses. However, evidence in trained individuals remains limited, and psychological responses have not been comprehensively synthesized. This systematic review evaluated the effects of Caf-MR on cognitive performance and psychological responses in trained individuals. Methods: Six electronic databases were searched through 24 September 2026 for randomized controlled studies comparing Caf-MR with a non-caffeinated placebo or control. Reference lists of relevant reviews and eligible studies were also screened. Owing to heterogeneity in protocols and outcomes, findings were synthesized qualitatively. Results: Ten studies were included; five assessed cognitive outcomes and six psychological responses, with one study contributing to both domains. Cognitive findings were heterogeneous, with improvements observed in selected reaction-time measures and Stroop interference time, as well as fewer errors during a sport-specific cognitive–motor task, while other reaction-time and accuracy outcomes showed no clear benefit. Among psychological studies, only one reported a Caf-MR-specific increase in felt arousal, with no consistent effects on mood, motivation, mental effort, mental fatigue, or enjoyment. Methodological quality ranged from fair to good, and all studies had some concerns regarding overall risk of bias. Conclusions: Overall, despite improvements in selected cognitive outcomes, current evidence remains insufficient to establish consistent cognitive or psychological benefits of Caf-MR in trained individuals. Future research should prioritize assessing blinding effectiveness, comparing Caf-MR protocols under standardized experimental conditions, and using comparable outcome measures to clarify potential differences across tasks and contexts.

Nutrients doi: 10.3390/nu18213696

Authors: Gianluigi Oggionni Giuseppina Bernardelli Mara Malacarne Francesco Capria Michele Galiano Marcello Marchese Stefano Cribellati Daniela Lucini

Background/Objectives: Stress is one of the main concerns of the working population in Western countries, as it is associated with reduced well-being and performance, as well as the adoption of an unhealthy lifestyle. Nevertheless, scientific findings indicate that lifestyle improvements, particularly healthy nutrition and increased physical activity, are a pivotal tool for managing stress and improving well-being. This study aimed to verify, in a large cohort of employees, whether overall and individual lifestyle categories might be associated with different stress perceptions (primary outcome). Methods: In this cross-sectional study, 3380 employees from several Italian companies voluntarily completed an anonymous questionnaire on lifestyle. Five lifestyle components for which validated cut-offs are available in the literature (nutrition, physical activity, smoking, sleep, and body mass index [BMI]) were used to define lifestyle categories both individually and through a combined lifestyle score (overall lifestyle score [OLS]). Results: We observed that OLS healthier lifestyle categories are characterized by a progressive reduction in stress perception, which remains significant after adjustment for sex, age and job role (p < 0.001, ηp2 = 0.022). Moreover, they also showed lower fatigue and somatic symptom scores and better perceived health, sleep quality, and work performance. For individual lifestyle components, nutrition (p < 0.001; ηp2 = 0.011), physical activity (p < 0.001; ηp2 = 0.018), and sleep duration (p < 0.001; ηp2 = 0.015) were associated with stress perception, whereas findings for BMI and smoking were less consistent. Conclusions: Healthier dietary habits, higher physical activity volume, and a more favourable overall lifestyle profile were associated with lower self-reported stress in this population.

Nutrients doi: 10.3390/nu18213694

Authors: Courtney L. Millar Alyssa B. Dufour Alex Wolfe Jasmin Kuo Douglas P. Kiel Lewis A. Lipsitz

Background/Objectives: Several dietary interventions of blueberry intake have been performed for a wide variety of clinical outcomes (e.g., cardiovascular, bone), but none have been conducted in older adults with mild depressive symptoms and low activity. Such individuals may represent a unique group who may be in particular need of a lifestyle change, but lack the motivation to engage in an intervention. Thus, our goal was to test the feasibility of a dietary intervention in which older adults with mild depressive symptoms and low activity were randomly assigned to consume 48 g of freeze-dried blueberry or placebo powder each day for 3 months. Methods: Individuals were recruited by various methods (e.g., targeted web-based advertisements, flyers, etc.). Our primary assessment of feasibility was retention rate (e.g., the percentage of individuals that completed the intervention out of the total randomized); however, other metrics like recruitment rate, safety, and compliance were also evaluated. We pre-specified that the study would be considered feasible if 80% of the individuals that were randomized to the intervention completed the study. Results: Our study found that 76% (95%CI: 59–93; n = 22 out of 29) of the individuals randomized to the intervention went on to complete the intervention, which is close to, but does not satisfy our pre-specified feasibility threshold. Among individuals that completed the study, compliance with the study powder over the 3 months was relatively high (≥87% in both groups). There were no serious adverse events, and only 10 adverse events that occurred similarly across groups (n = 6 in placebo, n = 4 in blueberry). Conclusions: Together, our data provides evidence that a dietary intervention supplementing a relatively high dose of blueberry powder in a unique population of older adults is possible and adherence was high among those that completed the intervention.

Nutrients doi: 10.3390/nu18213693

Authors: Enrico Polati Marco Anderloni Leonardo Gottin Katia Donadello Lorenzo Peluso Alvise Martini Luca Polati Vincenzo Di Maria Libera Villagrossi Alex Patton Filomena Puntillo Gabriele Finco Giovanna Del Balzo Vittorio Schweiger

Background/Objectives: Long-term treatment options for fibromyalgia syndrome (FMS) remain limited and there is a lack of real-world data on the extended use of nutraceutical formulations containing palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC). This study describes a cohort treated for 12 months with a fixed multicomponent formulation containing PEA and ALC, followed by an additional visit three months post-treatment. Methods: This retrospective, uncontrolled single-cohort study involved 150 consecutive adults diagnosed with fibromyalgia syndrome (FMS). Participants received a fixed oral formulation comprising palmitoylethanolamide (PEA) 600 mg, acetyl-L-carnitine (ALC) 500 mg, Boswellia serrata 100 mg, vitamin B6 and vitamin E, administered twice daily as an adjunct to stable background therapy. Pain levels were assessed using the Visual Analogue Scale (VAS), and the impact of the disease was evaluated with the revised Fibromyalgia Impact Questionnaire (FIQR) over a period of up to 15 months. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) for up to 6 months. Missing data were addressed through various methods, including a mixed model, last observation carried forward, delta-adjusted and baseline-carried-forward scenarios, as well as non-responder imputation. Results: Sixty-four patients completed the 12-month course, 45 discontinued (36 for perceived lack of efficacy) and 41 were lost to follow-up. Estimated mean VAS fell from 76.3 to 52.3 at 12 months and FIQR from 73.6 to 56.1; under the worst-case assumption that every non-completer returned to baseline, the mean 12-month change in VAS was −13.0 points (95% CI −15.9 to −10.2). At 6 months, 78.1% of completers reached the FIQR minimal clinically important difference and 59.4% the IMMPACT 30% pain threshold, corresponding to 37.3% and 28.7% of all 150 patients with non-responder imputation; only 20.3% of completers (10.0% of all patients) improved by ≥3 PSQI points. Recorded adverse events occurred in 10.0% of patients. Retention at 12 months was 60.6% (42.7% if patients lost to follow-up were counted as discontinuations). In completers, pain and FIQR three months after the end of treatment were within one point of the 12-month values. Conclusions: In this uncontrolled cohort, 12 months of add-on treatment with a multicomponent formulation containing PEA and ALC was associated with reductions in pain and disease impact, whereas sleep outcomes changed minimally. However, attrition was substantial and partially response-dependent; therefore, the observed changes cannot be attributed to the formulation or its individual components. These descriptive findings support the need for a controlled trial with a duration of at least 12 months.

Nutrients doi: 10.3390/nu18213690

Authors: Petra Platz Márk Szakály Kinga Lili Balogh Péter Huszka

Background/Objectives: Eating behaviour patterns are fundamental determinants of chronic disease risk and public health. Hungary faces among the highest rates of obesity, cardiovascular disease, and diet-related mortality in Europe. Despite this, population-level consumer profiling based on validated multi-scale instruments remains limited. This study used nationally representative samples to assess eating motivations, health and taste attitudes, and eating styles among Hungarian adults, and grouped adults into consumer segments for each measure. Methods: Two independent nationally representative cross-sectional surveys were conducted: (1) eating attitudes (TFEQ-R21) and health/taste attitude scales (HTAS) were assessed in 2021 (n = 1000); (2) eating motivations (TEMS) were assessed in late 2019 (n = 1000). Exploratory factor analysis (EFA) was applied to each instrument, and confirmatory factor analysis (CFA) to the TFEQ-R21 and to both HTAS subscales. Consumer segmentation was performed using hierarchical and K-means cluster analysis. Sociodemographic differences across segments were explored via chi-square tests and one-way analysis of variance (ANOVA). The perceived palatability and healthiness of functional food categories were examined across TFEQ-R21 segments. Results: The TEMS yielded eight eating motivation factors and five consumer segments: Traditional Simplifiers (17.9%), Frugal Social and Emotional Eaters (19.9%), Balanced Self-Rewarders (27.5%), Health-Conscious (18.3%), and Indifferent (16.4%). The HTAS health subscale produced four clusters, with Health-Conscious Metropolitans (19.8%) as the primary functional food target. The HTAS taste subscale identified taste-oriented consumers (26.9%) alongside three further groups. The TFEQ-R21 confirmed a three-factor eating attitude structure (emotional eating, uncontrolled eating, cognitive restriction; explained variance 57.2%) and yielded five behavioural clusters. Controlled Dieters represented 20.6% of the sample; the other TFEQ-R21 segments showed average, uncontrolled, or emotionally driven eating profiles. Perceived palatability and healthiness of functional foods differed across TFEQ-R21 segments (one-way ANOVA, unadjusted p < 0.05 in six of ten categories for palatability and eight of ten for healthiness), and Controlled Dieters gave the highest mean rating in eight of ten categories on each measure. Conclusions: The parallel application of three validated eating behaviour scales describes eating attitudes, motivations and consumer segments among Hungarian adults. Habitual, taste-oriented and average-profile segments were common, and each instrument also yielded a smaller health-oriented segment (about 18–21%). These cross-sectional findings on attitudes and self-reported motivations may inform segment-specific communication, which should be tested in future intervention studies.