Nutrients

24 pages, 7132 KB

Open AccessArticle

Early Oral Administration of D-Chiro-Inositol Reverses Hippocampal Insulin and Glutamate Signaling Deficits in the 3×Tg Humanized Mouse Model of Alzheimer’s Disease

by Beatriz Pacheco-Sánchez, Julia Verheul-Campos, Antonio Vargas, Rubén Tovar, Miguel Rodríguez-Pozo, Juan A. Navarro, Antonio J. López-Gambero, Elena Baixeras, Pedro J. Serrano-Castro, Juan Suárez, Carlos Sanjuan, Patricia Rivera and Fernando Rodríguez de Fonseca

Nutrients 2025, 17(18), 3024; https://doi.org/10.3390/nu17183024 (registering DOI) - 22 Sep 2025

Abstract

Background and Objective: Humanized models of Alzheimer’s disease (AD) provide valuable tools for investigating the mechanisms of this neurodegenerative disorder, the leading cause of dementia. These models enable the study of AD progression and the potential disease-modifying properties of drugs or dietary nutrients [...] Read more.

Background and Objective: Humanized models of Alzheimer’s disease (AD) provide valuable tools for investigating the mechanisms of this neurodegenerative disorder, the leading cause of dementia. These models enable the study of AD progression and the potential disease-modifying properties of drugs or dietary nutrients delivered through nutrition. Here, we examine molecular markers of metabolic and synaptic dysfunction in the hippocampus of 6-month-old 3×Tg-AD mice and assess whether a dietary insulin sensitizer can delay synaptic decline. Methods: First we characterized the molecular phenotype of 3×Tg-AD at 12 months using shotgun proteomics and phosphoproteomics to assess metabolic and synaptic changes in the hippocampus. Then, we characterized the effects of early daily oral D-chiro-inositol (DCI, Gyneos^®) for three months, starting at 3 months of age, to test restoration of insulin signaling and glutamatergic synaptic markers. To this end we evaluated a) insulin signaling pathway components (insulin receptor, IRS1, PI3K, AKT, GSK3β) at mRNA, protein, and phosphorylation levels, and b) the expression of glutamate receptors (mGluR5, GluR1, GluR2, NMDAR1, NMDAR2A, NMDAR2B). Sex effects were explored. Results: 12-month 3×Tg-AD mice exhibit metabolic and synaptic dysfunction in the hippocampus, with phosphoproteomic changes suggesting altered glutamatergic synapses. At 6 months, disruptions in insulin signaling were evident, including altered expression and phosphorylation of insulin pathway components, and changes in glutamate receptor subunits. Early DCI treatment largely reversed these alterations. Several effects showed sex dependency. Conclusions: Early insulin-sensitizing intervention via DCI can restore insulin signaling and counteract hippocampal synaptic impairments in this AD model, supporting the potential for nutrient-based strategies to delay synaptic decline. Sex differences underscore the need to tailor therapeutic approaches in modifying AD progression. Full article

(This article belongs to the Special Issue Dietary Supplement in Neurodegenerative Diseases: Nutritional Assessment)

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10 pages, 470 KB

Open AccessArticle

Nutritional Status Is Not a Predictor of Anaphylaxis Severity in a Pediatric Cohort: A Retrospective Analysis

by Izabela Kucharek, Krzysztof Przystał-Dyszyński, Aleksandra Godyńska, Maria Gregorczyk and Adam J. Sybilski

Nutrients 2025, 17(18), 3023; https://doi.org/10.3390/nu17183023 - 22 Sep 2025

Abstract

Background: Childhood obesity is a pro-inflammatory state associated with poorer outcomes in chronic allergic diseases, such as asthma, and in adults, it is a recognized risk factor for more severe anaphylaxis. However, whether this association extends to the pediatric population remains unclear. [...] Read more.

Background: Childhood obesity is a pro-inflammatory state associated with poorer outcomes in chronic allergic diseases, such as asthma, and in adults, it is a recognized risk factor for more severe anaphylaxis. However, whether this association extends to the pediatric population remains unclear. Objectives: The aim of this study was to assess the association between nutritional status, as measured by Body Mass Index (BMI), and anaphylaxis severity and presentation in a cohort of hospitalized children. Methods: We retrospectively assessed the association between BMI categories (underweight, normal weight, overweight, and obese) and the severity (WAO grading) and clinical presentation of anaphylaxis in 199 hospitalized children (0–18 years). Results: No statistically significant association was found between BMI categories and anaphylaxis severity (χ² = 7.06, p = 0.861). Severe reactions (WAO grades 4–5) were rare across BMI categories, occurring in 0% of underweight, 3.8% of normal-weight, 9.1% of overweight, and 7.7% of obese children. In regression analyses adjusting for age, sex, asthma, and atopic dermatitis, BMI was not an independent predictor of anaphylaxis severity, whether considered as a categorical or continuous variable (all odds ratios non-significant, 95% CIs crossing 1). Similarly, organ system involvement did not differ between BMI groups (all p > 0.05). Conclusions: In this pediatric cohort, contrary to findings in adults, we did not find nutritional status to be a predictor of anaphylaxis severity or presentation. This suggests obesity’s role as a risk factor may be age-dependent and that adult data should be extrapolated to children with caution. Full article

(This article belongs to the Special Issue Exploring the Role of Nutrition in Modulating Allergies and Allergic Reactions)

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14 pages, 1149 KB

Open AccessArticle

Feeding Models in Classical Phenylketonuria: Do They Make a Difference in Infant Sleep?

by Ezgi Burgaç, Ebru Çiçek Türköz, Adnan Barutçu, Fatma Derya Bulut, Deniz Kor, Tuğçe Kartal, Sema Uzunoğlu, Esra Kara, Burcu Köseci, İrem Kaplan, Nazlı Totik and Neslihan Onenli Mungan

Nutrients 2025, 17(18), 3022; https://doi.org/10.3390/nu17183022 - 22 Sep 2025

Abstract

Background: Phenylketonuria (PKU) is an inherited metabolic disorder that requires early diagnosis and strict phenylalanine (Phe)-restricted diet to prevent neurocognitive impairment. Various infant feeding models have been used to achieve optimal metabolic control during early life. The aim of this study was to [...] Read more.

Background: Phenylketonuria (PKU) is an inherited metabolic disorder that requires early diagnosis and strict phenylalanine (Phe)-restricted diet to prevent neurocognitive impairment. Various infant feeding models have been used to achieve optimal metabolic control during early life. The aim of this study was to compare two different feeding models for infants with classical PKU in terms of metabolic control, growth parameters, micronutrient status, the process of introducing complementary foods, and with a particular focus on sleep quality. Methods: In this prospective observational study, 26 infants with classical PKU were followed for 12 months. Patients were assigned to one of two feeding groups: Group-1 received breast milk and Phe-free formula in alternating feeds, while Group-2 received Phe-free formula followed by breastfeeding until satiety. Blood Phe, micronutrient levels and anthropometric measurements were recorded. Sleep quality was evaluated using the Brief Infant Sleep Questionnaire-Revised (BISQ-R). A structured set of parental questions was used to evaluate their experiences during the complementary feeding period. Results: No statistically significant differences were observed between the groups in terms of blood Phe levels, anthropometric measurements, serum levels of iron, ferritin, vitamin-B12, vitamin-D, and zinc. Complementary feeding tolerance were similar across the groups. The BISQ-R analysis revealed no significant differences between the groups. Conclusions: Both feeding models were equally effective in maintaining metabolic control, supporting normal growth, complementary feeding processes, and preserving sleep quality during infancy. These findings suggest that either approach can be adopted based on the preference of the caregiver and the practicality of the clinical setting. Full article

(This article belongs to the Section Pediatric Nutrition)

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14 pages, 620 KB

Open AccessArticle

Undernourished and Undertreated: The Role of Nutritional Care in Geriatric Hospital Outcomes

by Paolo Orlandoni, Nikolina Jukic Peladic, Mirko Di Rosa, Claudia Venturini and Fabrizia Lattanzio

Nutrients 2025, 17(18), 3021; https://doi.org/10.3390/nu17183021 - 22 Sep 2025

Abstract

Background: Malnutrition is highly prevalent in hospitalized older adults and is associated with adverse clinical outcomes. However, the extent to which nutritional care is systematically implemented and its relationship with outcomes remains unclear. Methods: We conducted a retrospective analysis of 4963 patients aged [...] Read more.

Background: Malnutrition is highly prevalent in hospitalized older adults and is associated with adverse clinical outcomes. However, the extent to which nutritional care is systematically implemented and its relationship with outcomes remains unclear. Methods: We conducted a retrospective analysis of 4963 patients aged ≥65 years who were admitted to the National Institute for Health and Scientific Research for the Elderly (IRCCS INRCA, Ancona, Italy) between 2012 and 2020 and received at least one nutritional consultation. We examined associations between timing and type of nutritional interventions, the Geriatric Nutritional Risk Index (GNRI), and clinical outcomes, including in-hospital mortality and length of hospital stay (LOS). We also analyzed the prevalence of different complications during Medical Nutritional Therapy (MNT). Results: Only 11% of hospitalized patients received a nutritional consultation. Among them, in-hospital mortality was 35.8%. The Geriatric Nutritional Risk Index was a significant predictor of mortality (HR 1.89; 95% CI: 1.55–2.31; p < 0.001) and inversely associated with LOS, reflecting a frail subset of patients with complex clinical conditions. The timing of nutritional consultation showed no significant association with mortality or LOS, possibly due to relatively prompt intervention (median 4 days). Enteral (EN) and parenteral nutrition (PN) were more frequently prescribed to non-survivors. Medical nutrition therapy-related complications were also more common in non-survivors (22.3% vs. 14%, p < 0.001). Artificial nutrition (AN) was not associated with increased mortality, but it was associated with prolonged hospital stays both in survivors and in non-survivors. Conclusions: Our findings highlight the limited use of nutritional consultations in hospitalized elderly patients despite the high prevalence of malnutrition and its prognostic relevance. The GNRI is a valuable tool for early risk stratification and clinical decision-making. Systematic screening and timely nutritional intervention, integrated with broader therapeutic goals, may improve care and optimize outcomes even in this vulnerable population. Full article

(This article belongs to the Section Geriatric Nutrition)

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26 pages, 677 KB

Open AccessSystematic Review

Systematic Review of the Effects of Plant-Based Foods on Metabolic Outcomes in Adults with MASLD and Comorbidities Such as Obesity, Metabolic Syndrome, and Type 2 Diabetes

by Joanna Michalina Jurek, Katarzyna Zablocka-Slowinska, Joanna Pieczynska, Helena Clavero Mestres and Teresa Auguet

Nutrients 2025, 17(18), 3020; https://doi.org/10.3390/nu17183020 - 22 Sep 2025

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent liver diseases, affecting up to 40% of adults and strongly associated with obesity and metabolic dysfunction. Despite the lack of approved pharmacological treatments, dietary interventions with plant-based foods, [...] Read more.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent liver diseases, affecting up to 40% of adults and strongly associated with obesity and metabolic dysfunction. Despite the lack of approved pharmacological treatments, dietary interventions with plant-based foods, including the Mediterranean diet (MED), rich in numerous bioactive compounds may offer benefits for metabolic health and hepatic function. However, the role of individual plant foods in MASLD management remains unclear. Objectives: This review investigates the effects of specific plant-based foods, consumed as part of the MED and Dietary Approaches to Stop Hypertension (DASHs) diet, on metabolic outcomes, including hepatic function, in MASLD patients alone or in combination with comorbidities such as obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). Methods: A systematic search was registered and conducted across nine databases to identify randomized controlled trials (RCTs) carried out in adults with MASLD and published between January 2020 and May 2025, following PRISMA guidelines. Results: Plant-based interventions including oranges, whole-grain products (WGPs), high-fiber buns (HFBs), beetroot juice (BJ), garlic, ginger, flaxseed, spirulina, rapeseed oil, sour tea, and green coffee extract (GCE) demonstrated mixed effects on metabolic and hepatic outcomes. GCE, flaxseed, and rapeseed oil improved anthropometric measures, while sour tea and ginger supported blood pressure control. WGPs, GCE, flaxseed, rapeseed oil, spirulina, ginger, and garlic were beneficial for glycemic regulation, whereas WGPs, HFBs, BJ, golden flaxseed, rapeseed oil, and garlic improved lipid profiles. Liver enzymes improved following consumption of WGPs, BJ, sour tea, flaxseed oil, and garlic, and hepatic steatosis was reduced after intake of oranges, WGPs, HFBs, BJ, flaxseed powder, rapeseed oil, and garlic powder. Conversely, a solely fruit-rich diet (FRD) had negative effects across all outcomes. Conclusions: Plant-based foods improved metabolic outcomes, with WGPs, HFBs, beetroot, oranges, sour tea, flaxseed oil, and garlic providing specific benefits for liver health. Further research is needed to validate these effects and ensure their safety in MASLD management. Full article

(This article belongs to the Special Issue Nutritional Interventions and Dietary Supplements in Chronic Diseases: Mechanisms and Therapeutic Potential)

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Graphical abstract

20 pages, 8819 KB

Open AccessArticle

Cholesterol-Lowering Mechanism of Lactobacillus Bile Salt Hydrolase Through Regulation of Bifidobacterium pseudolongum in the Gut Microbiota

by Yingying Liu, Weijia Kuang, Man Li, Zhihao Wang, Yanrong Liu, Menghuan Zhao, Hailin Huan and Yao Yang

Nutrients 2025, 17(18), 3019; https://doi.org/10.3390/nu17183019 - 22 Sep 2025

Abstract

Background: Cardiovascular diseases (CVDs) represent a major global health burden, and cholesterol reduction is a key strategy for their prevention and management. This study investigated the mechanism by which bile salt hydrolase (BSH) from Lactobacilli reduces cholesterol levels by modulating the growth of [...] Read more.

Background: Cardiovascular diseases (CVDs) represent a major global health burden, and cholesterol reduction is a key strategy for their prevention and management. This study investigated the mechanism by which bile salt hydrolase (BSH) from Lactobacilli reduces cholesterol levels by modulating the growth of Bifidobacterium pseudolongum. Methods: The BSH-recombinant strain YB334 was administered to high-cholesterol-diet mice, and the cholesterol-lowering function of the strain was evaluated by assessing serum cholesterol parameters, including total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Metagenomic sequencing was used to analyze the gut microbiota, leading to the screening and acquisition of the “responsive” strains affected by BSH. Subsequent investigations were conducted into their cholesterol-lowering effects and mechanisms of action. Results: Oral administration of the BSH-recombinant strain YB334 can effectively reduce serum cholesterol levels in hypercholesterolemic mice while simultaneously leading to a significant increase in the abundance of B. pseudolongum within the gut microbiota. In vitro experiments indicated that this increased abundance might be closely associated with the strain’s high tolerance to CA, the catalytic product of the BSH enzyme. The BPL-4 strain, obtained through screening, demonstrated cholesterol-lowering efficacy. Mechanistically, BPL-4 altered bile acid pool composition and modulated the farnesoid X receptor (FXR) signaling axis: it suppressed ileal FXR-fibroblast growth factor 15 (FGF15) expression, thereby de-repressing hepatic cholesterol 7α-hydroxylase (CYP7A1) and accelerating cholesterol catabolism into bile acids. Conclusions: This study provides the first evidence that BSH from lactobacilli can shape the signature gut microbiota by modulating bile acid metabolism via the FXR-CYP7A1 axis, thereby demonstrating a mechanism for its cholesterol-lowering effects. Full article

(This article belongs to the Special Issue Effect of Dietary Components on Gut Homeostasis and Microbiota)

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15 pages, 789 KB

Open AccessArticle

Education Level and Cardioprotective Dietary Patterns in Polish Post-MI Patients: A Cross-Sectional Study Using the KomPAN Tool

by Elżbieta Szczepańska, Barbara Janota, Karolina Janion, Krzysztof Biernacki and Oskar Kowalski

Nutrients 2025, 17(18), 3018; https://doi.org/10.3390/nu17183018 - 22 Sep 2025

Abstract

Background: Among patients who have experienced a myocardial infarction, adherence to the principles of healthy eating becomes particularly important. These behaviors may potentially depend on the level of education. Objectives: The aim of this study is to assess the relationship between the level [...] Read more.

Background: Among patients who have experienced a myocardial infarction, adherence to the principles of healthy eating becomes particularly important. These behaviors may potentially depend on the level of education. Objectives: The aim of this study is to assess the relationship between the level of education and dietary behaviors potentially beneficial to health among patients hospitalized due to a previous myocardial infarction. Methods: This study includes 164 patients of the Silesian Center for Heart Diseases in Zabrze (Poland). The research tool used was the KomPAN questionnaire for assessing dietary beliefs and habits. The analysis focused on the part of the questionnaire related to the consumption of products with potentially beneficial health effects. To assess diet quality and its association with educational level, the pro-Healthy Diet Index (pHDI) was used. Results: The participants consumed an average of 3.42 ± 0.81 meals per day, with individuals with higher education consuming more meals daily (3.85 ± 0.78). Daily consumption of vegetables and fruits was most common among patients with higher education (69.23% and 63.16%, respectively), followed by those with secondary (47.37% and 63.16%), vocational (37.93% and 40.74%), and primary education (33.33% and 33.33%). Statistically significant correlations were observed between education level and frequency of consumption of vegetables (rs = 0.25, p = 0.001), fruits (rs = 0.24, p = 0.003), legumes (rs = 0.21, p = 0.009), whole grain bread (rs = 0.23, p = 0.006), and coarse groats (rs = 0.24, p = 0.002). The dietary patterns of all study groups were characterized by a moderate level of pro-health features (pHDI among all study participants was 49.87 ± 12.40 points). However, a statistically significant correlation was found between education level and the pro-health diet index (rs = 0.24, p = 0.002), with this index increasing with higher education levels. Conclusions: Dietary behaviors with potentially beneficial health effects among patients hospitalized due to a myocardial infarction may be related to education level. A higher level of education in our study is associated with more favorable dietary choices compared to a lower level of education. Full article

(This article belongs to the Section Nutritional Epidemiology)

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17 pages, 734 KB

Open AccessArticle

Social Media Consumption and Risk of Addiction Associated with Adolescent Disordered Eating Behaviour: An Observational Analysis

by María Peréz-Jiménez, María del Mar Uclés-Torrente, Gema Esperanza Ruiz-Gamarra, Manuel Vaquero-Álvarez, Isabel Maria Blancas-Sánchez, Pilar Aparicio-Martínez and Manuel Vaquero-Abellán

Nutrients 2025, 17(18), 3017; https://doi.org/10.3390/nu17183017 - 21 Sep 2025

Abstract

Objectives: To examine the association between social media (SM) use and content exposure with the risk of developing eating disorders (EDs) among adolescents. Methods: A descriptive observational study was conducted using a structured questionnaire incorporating validated scales. The instrument assessed quantitative and qualitative [...] Read more.

Objectives: To examine the association between social media (SM) use and content exposure with the risk of developing eating disorders (EDs) among adolescents. Methods: A descriptive observational study was conducted using a structured questionnaire incorporating validated scales. The instrument assessed quantitative and qualitative variables related to eating habits, SM usage, self-esteem, and body image. The sample comprised students aged 12–17 years from a school in Córdoba, Spain. Results: A total of 115 students participated in the study. Among them, 43.5% were identified as being at risk of developing EDs. Of this subgroup, 54.0% were female, with male gender appearing as a protective factor against ED risk. A significant association was found between increased hours of SM use and higher ED risk, with an odds ratio (OR) of 5.54 (95% confidence interval [CI]: 2.03–14.33). Conclusions: The findings suggest that low self-esteem and negative body image are key factors associated with increased ED risk, and that SM may act as an amplifying influence. Preventive interventions should focus on enhancing self-esteem and fostering critical and conscious engagement with SM among adolescents to mitigate the development of eating disorders. Full article

(This article belongs to the Special Issue The Impact of Social Media on Eating Behavior)

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13 pages, 360 KB

Open AccessArticle

The Impact of Physical Education Attendance and Diet on Bone Mineralization in Adolescents

by Agata Przytula and Joanna Popiolek-Kalisz

Nutrients 2025, 17(18), 3016; https://doi.org/10.3390/nu17183016 - 20 Sep 2025

Abstract

Background: Bone mineralization can be influenced by physical activity and dietary factors; however, the relative contributions of these factors are not well defined. Physical activity in adolescents can be implemented with physical education (PE) classes and there is no reported data on [...] Read more.

Background: Bone mineralization can be influenced by physical activity and dietary factors; however, the relative contributions of these factors are not well defined. Physical activity in adolescents can be implemented with physical education (PE) classes and there is no reported data on their impact on bone mineralization. This study investigates the relationship between PE class attendance, dietary factors, and bone mineralization in adolescents. Methods: 57 adolescents (median age 17.00 [16.00–17.00] years) were enrolled in this study. Bone mineralization was assessed with bioelectrical impedance analysis (BIA) and dietary knowledge and selected foods intakes were assessed with a validated questionnaire. Results: PE attendance and dietary knowledge were positively associated with bone mineralization in the multivariate models (R² = 0.85, p < 0.001 for the best model, and R² = 0.81, p < 0.001 for the simplified model), and PE attendance was the dominant positive factor among the modifiable ones (B = 0.20, p = 0.02, and B = 0.25, p = 0.004, respectively). The impact of calcium sources intake was diminished when controlled for PE class attendance. Conclusions: PE attendance is one of the key factors of bone mineralization in adolescents. Our study showed that the role of calcium sources intake was diminished when acknowledging physical activity data, however dietary knowledge remained a significant predictor. Enhancing dietary knowledge and promoting physical activity are key targets for improving bone health. Full article

(This article belongs to the Special Issue Association between Nutrition, Diet Quality, Dietary Patterns, and Human Health and Diseases—2nd Edition)

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Graphical abstract

18 pages, 738 KB

Open AccessArticle

Predictors of Weight Reduction in a Multidisciplinary Community Program for Children with Overweight and Obesity: A Study from Emilia-Romagna, Italy

by Gianmarco Imperiali, Cecilia Acuti Martellucci, Marina Fridel, Giuseppe Diegoli, Maurizio Iaia, Giuliano Carrozzi, Petra Bechtold, Maria Elena Flacco and Lamberto Manzoli

Nutrients 2025, 17(18), 3015; https://doi.org/10.3390/nu17183015 - 20 Sep 2025

Abstract

Background: The worldwide prevalence of obesity in children and adolescents quadrupled in the past decades, becoming a public health priority. Following the recommendation by the Italian Minister of Health, the Emilia-Romagna Region started a community-based program aimed at reducing pediatric overweight through [...] Read more.

Background: The worldwide prevalence of obesity in children and adolescents quadrupled in the past decades, becoming a public health priority. Following the recommendation by the Italian Minister of Health, the Emilia-Romagna Region started a community-based program aimed at reducing pediatric overweight through children and family behavioral counseling on nutrition and physical activity. Methods: Children with excess weight, aged 2–17 years, and without severe diseases were visited five times by a multidisciplinary team, who provided dietary advice, exercise plans, and psychosocial support, according to Italian guidelines. The outcomes were the median pre–post change in Δ₃₀BMI (distance between children’s BMI and age- and sex-specific obesity threshold values) and the proportion of children who moved to a lower weight class. Logistic regression was used to identify potential predictors of weight improvement. Results: Up to March 2025, 1331 participants completed the follow-up. In total, 17.5% of the children showed an improvement in weight class, and 32.5% had a reduction of more than one unit of Δ₃₀BMI. The program was significantly and substantially more effective among the children with obesity at baseline (overweight vs. obese children adjusted odds ratio—aOR—of weight class improvement: 0.28; p < 0.001), older than eight years (9–11 years vs. 2–8 years children aOR: 1.41; p < 0.05), who adhered to breakfast recommendations (aOR: 1.60; p < 0.01) and had no obese parents (≥1 vs. 0 obese parents aOR: 0.62; p < 0.05). Conclusions: The multidisciplinary model was associated with an overall positive impact on the weight status of the enrolled children. Given the varying response, however, in order to maximize cost-effectiveness, future programs could be reserved for children with obesity, older than eight years. Further randomized research is needed to investigate the efficacy of this intervention in different settings and on late clinical endpoints. Full article

(This article belongs to the Section Pediatric Nutrition)

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15 pages, 652 KB

Open AccessArticle

Exploring the Anti-Inflammatory Potential of a Mediterranean-Style Ketogenic Diet in Women with Lipedema

by Małgorzata Jeziorek, Angelika Chachaj, Andrzej Szuba, Dorota Różańska and Anna Prescha

Nutrients 2025, 17(18), 3014; https://doi.org/10.3390/nu17183014 - 20 Sep 2025

Abstract

Background/Objectives: Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation and inflammation, predominantly affecting women. While recent evidence suggests a systemic pro-inflammatory state in lipedema, the role of diet in modulating inflammation remains underexplored. This study assessed the anti-inflammatory potential [...] Read more.

Background/Objectives: Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat accumulation and inflammation, predominantly affecting women. While recent evidence suggests a systemic pro-inflammatory state in lipedema, the role of diet in modulating inflammation remains underexplored. This study assessed the anti-inflammatory potential of a Mediterranean-style ketogenic diet and its effects after 7 months of adherence on systemic inflammation markers (CRP and IL-6) in women with lipedema (n = 24) and a control group with overweight/obesity (n = 24). Methods: The Dietary Inflammatory Index (DII) was used to characterize the inflammatory potential of the diet throughout the intervention. Dietary intake was analyzed pre- and post-intervention, and anthropometric, body composition, and biochemical parameters were measured. Results: Beyond its beneficial effects on body composition (significant reductions in body weight, fat, leg circumferences, and visceral fat), the intervention diet also demonstrated anti-inflammatory potential. In lipedema, baseline diet showed a pro-inflammatory DII profile (DII/day = 3.04), which was reduced by about 1.5 points after the intervention (p = 0.008). When expressed per 1000 kcal, the DII values were markedly lower for both baseline (DII = 0.22) and intervention diet (DII = ~0.01). Following the intervention diet, reduction in CRP (−0.39, p = 0.016) and IL-6 levels (−0.33, p = 0.034) in lipedema were observed. A significant positive association was observed between the intervention diet’s DII and CRP (r = 0.55, p = 0.005), and between the baseline diet’s DII and IL-6 (r = 0.50, p = 0.013) in lipedema group. Conclusions: These findings suggest that ketogenic diet rich in anti-inflammatory and antioxidant nutrients can reduce systemic inflammation in lipedema patients, independently of caloric restriction. Full article

(This article belongs to the Section Nutrition in Women)

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13 pages, 4733 KB

Open AccessArticle

Differential Associations of Vitamin D Metabolites with Adiposity and Muscle-Related Phenotypes in Korean Adults: Results from KNHANES 2022–2023

by Se-Hong Kim, Yuji Jeong, Seok-Won Son and Ha-Na Kim

Nutrients 2025, 17(18), 3013; https://doi.org/10.3390/nu17183013 - 20 Sep 2025

Abstract

Background: Body composition plays a crucial role in metabolic health, aging, and the development of various diseases. Vitamin D has been implicated in the regulation of muscle and adipose tissue function, but its relationship with body composition remains unclear. Objectives: This study aimed [...] Read more.

Background: Body composition plays a crucial role in metabolic health, aging, and the development of various diseases. Vitamin D has been implicated in the regulation of muscle and adipose tissue function, but its relationship with body composition remains unclear. Objectives: This study aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) concentration, its subspecies, and body composition parameters and related phenotypes in Korean adults aged ≥20 years. Methods: This cross-sectional study included 2612 eligible participants from the Korea National Health and Nutrition Examination Survey 2022–2023, and data on body composition parameters and serum 25(OH)D levels were analyzed. Serum 25(OH)D levels and subspecies were determined using liquid chromatography-tandem mass spectrometry. Body composition factors included anthropometric indices, muscle strength, and fat and muscle mass, which were assessed using bioelectrical impedance analysis. Results: After multivariable adjustment, serum concentrations of total 25(OH)D and 25(OH)D₃ were inversely associated with waist circumference, body mass index, and fat mass and positively associated with handgrip strength and lean mass, whereas serum 25(OH)D₂ and 3-epi-25(OH)D₃ levels showed no such associations. Higher 25(OH)D₂ concentrations were positively associated with low muscle strength and the prevalence of sarcopenia. Through non-linear analyses, U-shaped correlations were identified between total 25(OH)D and 25(OH)D₃ levels with low muscle mass, respectively, while a J-shaped correlation was observed between 25(OH)D₂ level and low muscle mass. Conclusions: Total 25(OH)D and 25(OH)D₃ levels were inversely associated with adiposity and positively associated with muscle strength and lean mass, whereas the 25(OH)D₂ level was linked to low muscle strength and sarcopenia. The U- and J-shaped associations with low muscle mass indicate the complex and differential roles of vitamin D subspecies, warranting further study. Full article

(This article belongs to the Section Micronutrients and Human Health)

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22 pages, 423 KB

Open AccessReview

Ultra-Processed Food Consumption and Systemic Inflammatory Biomarkers: A Scoping Review

by Jacopo Ciaffi, Luana Mancarella, Claudio Ripamonti, Veronica Brusi, Federica Pignatti, Lucia Lisi and Francesco Ursini

Nutrients 2025, 17(18), 3012; https://doi.org/10.3390/nu17183012 - 20 Sep 2025

Abstract

Background/Objectives: The consumption of ultra-processed foods (UPF) has increased worldwide and has been hypothesized to contribute to chronic diseases, including conditions characterized by inflammatory dysregulation. We conducted a scoping review to map the human evidence on the relationship between UPF consumption and systemic [...] Read more.

Background/Objectives: The consumption of ultra-processed foods (UPF) has increased worldwide and has been hypothesized to contribute to chronic diseases, including conditions characterized by inflammatory dysregulation. We conducted a scoping review to map the human evidence on the relationship between UPF consumption and systemic inflammatory biomarkers. Methods: We developed a search strategy combining terms for UPF with terms for circulating inflammatory biomarkers, including C-reactive protein (CRP/hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1), and leptin. Findings were synthesized separately for children/adolescents and adults. Results: A total of 24 studies were included. CRP/hs-CRP was assessed in 21; IL-6 in 9; TNF-α in 8; IL-1β in 5; leptin in 5; MCP-1 in 5; PAI-1 in 5; and IL-8 in 2. In children/adolescents, CRP/hs-CRP tended to be higher with greater UPF intake in large cohorts and in preterm infants, whereas smaller or clinically selected samples did not show an association. For other biomarkers, IL-6 generally did not vary with UPF, TNF-α and IL-1β showed no association across studies, and the two IL-8 analyses yielded mixed results. In adults, 11/17 analyses reported higher CRP/hs-CRP levels with greater UPF intake, 5/17 reported no association, and 1/17 reported an association limited to women. IL-6 was predominantly higher with greater UPF intake; TNF-α likewise tended to be higher with UPF across several settings; IL-1β showed no association; MCP-1 and PAI-1 provided limited, inconsistent signals; leptin results were mixed. Conclusions: Higher UPF consumption is frequently associated with elevated systemic inflammatory biomarkers—most consistently CRP/hs-CRP—across adults and selected pediatric contexts. Signals for IL-6 and TNF-α appear in specific populations, whereas IL-1β, MCP-1, PAI-1, and leptin show inconsistent patterns. Full article

(This article belongs to the Special Issue Mechanisms of Ultra-Processed Foods and Health Outcomes)

16 pages, 340 KB

Open AccessArticle

Time-Restricted Eating Without Exercise Enhances Anaerobic Power and Reduces Body Weight: A Randomized Crossover Trial in Untrained Adults

by Zifu Yu and Takeshi Ueda

Nutrients 2025, 17(18), 3011; https://doi.org/10.3390/nu17183011 - 20 Sep 2025

Abstract

Background: Time-restricted eating (TRE), a dietary strategy that confines daily food intake to specific time windows, has been shown in animal models to enhance physical performance even without exercise training. However, evidence in humans under non-exercise conditions remains limited. Objective: This [...] Read more.

Background: Time-restricted eating (TRE), a dietary strategy that confines daily food intake to specific time windows, has been shown in animal models to enhance physical performance even without exercise training. However, evidence in humans under non-exercise conditions remains limited. Objective: This study aimed to investigate the effects of early TRE (eTRE; 08:00–14:00) and delayed TRE (dTRE; 12:00–18:00) on body weight, aerobic endurance, and anaerobic power in untrained adults. Methods: In a randomized crossover trial, 28 healthy university students (mean age 23.47 ± 2.87 years; 16 women) completed two 4-week interventions, eTRE and dTRE, separated by a 2-week washout. Participants did not engage in any structured exercise during the intervention period. Body weight, aerobic endurance (cycling time to exhaustion at a fixed workload), and anaerobic power (peak power output during sprint cycling) were assessed after each phase. Results: Body weight significantly decreased after eTRE (−1.56 kg; 95% CI [−2.07, −1.05]; p < 0.001; Cohen’s

d_{z}

= 1.17) and dTRE (−0.61 kg; 95% CI [−1.12, −0.10]; p = 0.022; Cohen’s

d_{z}

= 0.55), with a greater reduction observed in eTRE compared to dTRE (−0.95 kg; 95% CI [−1.74, −0.16]; p = 0.020). Aerobic endurance showed no significant change across phases (all p > 0.05). Anaerobic power significantly improved after both eTRE (+21.25 W; 95% CI [12.03, 30.47]; p < 0.001; Cohen’s

d_{z}

= 1.10) and dTRE (+35.43 W; 95% CI [26.21, 44.65]; p < 0.001; Cohen’s

d_{z}

= 1.20), and the improvement was significantly greater in dTRE compared to eTRE (+14.18 W; 95% CI [1.79, 26.57]; p = 0.025; Cohen’s

d_{z}

= 0.54). Conclusions: Both early and delayed TRE independently led to weight loss and enhanced anaerobic power in the absence of an exercise intervention. eTRE was more effective for weight reduction, whereas dTRE produced greater improvements in anaerobic performance. Full article

(This article belongs to the Section Sports Nutrition)

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11 pages, 216 KB

Open AccessArticle

Dietary Inflammatory Index and Nutritional Status in Children with Inborn Errors of Metabolism on Protein-Restricted Diets

by Emine Aktaş, Betül Çiçek, Ilyas Okur, Asli İnci and Leyla Tümer

Nutrients 2025, 17(18), 3010; https://doi.org/10.3390/nu17183010 - 20 Sep 2025

Abstract

Background: The primary treatment for inborn errors of metabolism (IEM) involves restricted intake of natural protein. Inadequate diets can lead to an increased risk of inflammation and susceptibility to infections. The Dietary Inflammatory Index (DII) is used to estimate whether a diet [...] Read more.

Background: The primary treatment for inborn errors of metabolism (IEM) involves restricted intake of natural protein. Inadequate diets can lead to an increased risk of inflammation and susceptibility to infections. The Dietary Inflammatory Index (DII) is used to estimate whether a diet has anti-inflammatory or pro-inflammatory properties. This study aimed to investigate the relationship between the inflammatory index score of natural protein-restricted diets used in medical nutrition therapy for IEM intoxication, the anthropometric measurements and nutritional status of affected children. Method: The study included 20 patients (5 organic acidemia, 5 urea cycle disorders, 10 phenylketonuria) and 20 healthy children. Patients followed a natural protein-restricted diet, while the healthy control group maintained their usual dietary habits. Dietary records were collected for both groups, and the DII and macro-micronutrient intakes were calculated. Result: DII scores were similar between the patient and control groups. Anthropometric measurements did not differ significantly between the groups. However, carbohydrate and fat intakes were higher in the patient group compared to the control group (p < 0.05). Additionally, comparative analyses revealed that vitamin B1, C and E, iron, and magnesium intakes were higher in the patient group than in the control group. Conclusions: Children on a natural protein-restricted diet showed growth patterns comparable to their healthy peers. This study demonstrated that nutritional deficiencies can be prevented in amino acid metabolism disorders treated with a natural protein-restricted diet by carefully controlling nutrition with vitamin and mineral-fortified formulas. Full article

(This article belongs to the Section Pediatric Nutrition)

29 pages, 915 KB

Open AccessReview

Gut Microbiota and Food Allergy: A Review of Mechanisms and Microbiota-Targeted Interventions

by Roxana Cristina Mareș, Maria Oana Săsăran and Cristina Oana Mărginean

Nutrients 2025, 17(18), 3009; https://doi.org/10.3390/nu17183009 - 20 Sep 2025

Abstract

Background: Food allergies (FAs) have become a major public health concern worldwide, with rising prevalence particularly among children. Traditional genetic and allergen exposure models do not fully explain this increase, prompting growing interest in the role of the gut microbiota. Early-life microbial [...] Read more.

Background: Food allergies (FAs) have become a major public health concern worldwide, with rising prevalence particularly among children. Traditional genetic and allergen exposure models do not fully explain this increase, prompting growing interest in the role of the gut microbiota. Early-life microbial colonization is now recognized as a critical determinant of immune development, with disruptions in microbial balance implicated in allergic sensitization. Objective: This review aims to synthesize recent human studies investigating the relationship between gut microbiota composition and food allergies, with an emphasis on underlying mechanisms and the potential of microbiota-targeted interventions. Methods: A literature search was conducted, including eligible studies concerning gut microbiota and food allergy. A total of 31 studies met the inclusion criteria. Results: The findings indicate that early-life factors, including delivery mode, feeding practices, antibiotic exposure, and environmental microbial diversity, have a significant influence on gut microbial colonization. Allergic children consistently exhibit reduced microbial diversity and lower levels of beneficial taxa such as Bifidobacteria, Faecalibacteria, and Clostridia. Microbial dysbiosis is associated with enhanced type 2 immune responses, reduced regulatory T cell activity, and altered profiles of short-chain fatty acids. Dietary modulation through prebiotics, probiotics, and synbiotics has shown potential in restoring microbial balance and promoting immune tolerance, although with varying degrees of efficacy depending on the strains, formulas, and timing of intervention. Conclusions: The gut microbiota plays a central role in the pathogenesis and potential prevention of food allergies. Microbiota-targeted dietary strategies, particularly in early life, offer promising avenues for promoting immune tolerance. Full article

(This article belongs to the Special Issue Nutrition and Gut Microbiome in the Prevention of Food Allergy)

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17 pages, 869 KB

Open AccessArticle

A 12-Week Randomized Controlled Trial of Nutrition and Exercise Education with Dietary Supplementation for Sarcopenia Prevention in Korean Baby Boomers

by Eun-Hee Jang and Seungmin Lee

Nutrients 2025, 17(18), 3008; https://doi.org/10.3390/nu17183008 - 20 Sep 2025

Abstract

Background/Objectives: Sarcopenia is a major public health concern, and early preventive strategies in midlife are increasingly emphasized. The goal of this study was to evaluate the effectiveness of a 12-week lifestyle intervention that included nutrition education, exercise education, and dietary supplementation in [...] Read more.

Background/Objectives: Sarcopenia is a major public health concern, and early preventive strategies in midlife are increasingly emphasized. The goal of this study was to evaluate the effectiveness of a 12-week lifestyle intervention that included nutrition education, exercise education, and dietary supplementation in Korean baby boomers. Methods: This single-blind, randomized controlled trial included 42 Korean baby boomers born between 1955 and 1963. Participants were randomly assigned to one of three groups: (1) nutrition and exercise education plus dietary supplementation (DiExSp), (2) nutrition and exercise education only (DiEx), or (3) control. The intervention was delivered online, and the DiExSp group additionally received a daily supplement containing protein, vitamins, and minerals. Primary outcomes included dietary intake, body composition, physical function, and fasting blood biomarkers. Nonparametric tests and effect size calculations were performed using SAS version 9.4. Results: A total of 31 participants completed the study. The results showed significant increases in protein and micronutrient intake (p < 0.05), with large effect sizes in the DiExSp group. Handgrip strength showed improvement in both the DiExSp and DiEx groups (DiExSp: p = 0.027, r = 0.63; DiEx: p = 0.020, r = 0.73), while no changes were observed in other physical parameters. HbA1c levels showed a significant decrease in the DiExSp group compared to the control (p < 0.05, ε² = 0.01). No significant differences were observed for other biomarkers. Conclusions: A 12-week intervention combining dietary supplementation with education resulted in improved dietary intake, muscle strength, and glycemic control. However, most effects were confined to within-group changes. Between-group differences were minimal, and effect sizes were small. These findings provide preliminary evidence that lifestyle intervention strategies may contribute to sarcopenia prevention in midlife adults. Full article

(This article belongs to the Special Issue Nutrition and Exercise in the Prevention and Treatment of Chronic Diseases)

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16 pages, 11378 KB

Open AccessArticle

Manganese Deficiency Causes Testicular Developmental Disorders, Blood–Testis Barrier Damage, and Spermatogenesis Disruption via Nrf2-Mediated Oxidative Stress

by Dianyi Peng, Fuqing Feng, Heng Yin, Jianfei Zhao, Shanchuan Cao and Jingbo Liu

Nutrients 2025, 17(18), 3007; https://doi.org/10.3390/nu17183007 - 20 Sep 2025

Abstract

Background: Manganese (Mn) is a trace element essential for multiple physiological and biological processes. The testis plays a key role in male reproduction by producing sperm and synthesizing male hormones. This study investigates how Mn deficiency affects testicular development, spermatogenesis, and the [...] Read more.

Background: Manganese (Mn) is a trace element essential for multiple physiological and biological processes. The testis plays a key role in male reproduction by producing sperm and synthesizing male hormones. This study investigates how Mn deficiency affects testicular development, spermatogenesis, and the blood–testis barrier (BTB), and evaluates associated variations in oxidative stress to explore potential mechanisms. Methods: A Mn-deficient diet was used to induce Mn deficiency in mice, with MnCl₂ administered via intraperitoneal injection. Mn levels in testicular tissue were measured by atomic absorption spectrometry. Testis and sperm morphology were assessed by H.E. and sperm staining. BTB markers were analyzed using immunofluorescence, Western blot, and qPCR. Oxidative stress was evaluated biochemically. Nrf2 pathway changes were detected by qPCR and Western blot. Results: The results indicated that Mn deficiency dramatically decreased the testicular index, caused abnormal testicular tissue structure, and significantly decreased Johnsen’s score. At the same time, sperm density and motility were significantly reduced, and the sperm deformity rate was significantly increased. In addition, the BTB function was impaired, as indicated by the significantly down-regulated expression of tight junction proteins including Occludin, ZO-1, JAM-A, and Claudin-11. As the oxidative stress levels increased, the mRNA and protein expression levels of molecules (including Nrf2 and HO-1) related to the Nrf2 signaling pathway were significantly down-regulated, while its inhibitor Keap1 exhibited significantly up-regulated expression. Notably, after supplementing MnCl₂, all the above abnormal indicators were significantly improved. Conclusions: Mn deficiency can lead to testicular tissue damage, decreased sperm quality, and BTB dysfunction, and the potential mechanism is probably closely associated with the increase in the oxidative stress level mediated by the Nrf2 pathway. Full article

(This article belongs to the Special Issue A New Perspective: The Effect of Trace Elements on Human Health)

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25 pages, 8488 KB

Open AccessArticle

Identification of Amino Acids That Regulate Angiogenesis and Alter Pathogenesis of a Mouse Model of Choroidal Neovascularization

by Chenchen Li, Jiawen Wu, Yingke Zhao, Jing Zhu, Xinyu Zhu, Yan Chen and Jihong Wu

Nutrients 2025, 17(18), 3006; https://doi.org/10.3390/nu17183006 - 19 Sep 2025

Abstract

Background: Metabolic stress from amino acid (AA) insufficiency is increasingly linked to pathological angiogenesis, but specific essential AA (EAA) roles remain undefined. Neovascular age-related macular degeneration (AMD), a major cause of blindness driven by aberrant ocular neovascularization, has limited efficacy with current [...] Read more.

Background: Metabolic stress from amino acid (AA) insufficiency is increasingly linked to pathological angiogenesis, but specific essential AA (EAA) roles remain undefined. Neovascular age-related macular degeneration (AMD), a major cause of blindness driven by aberrant ocular neovascularization, has limited efficacy with current VEGFA-targeting therapies. We sought to identify specific EAAs that regulate pathological angiogenesis and dissect their mechanisms to propose new therapeutic strategies. Methods: Human retinal microvascular endothelial cells (HRMVECs) were used to identify angiogenesis-regulating amino acids through systematic EAA screening. The molecular mechanism was investigated using shRNA-mediated knockdown of key stress response regulators (HRI, PKR, PERK, GCN2) and ATF4. Angiogenesis was assessed via tubule formation and migration assays. Therapeutic potential was examined in a laser-induced choroidal neovascularization (CNV) mouse model, evaluated by fluorescein angiography and histomorphometry. Results: Deprivation of methionine, lysine, and threonine potently induced capillary-like tube formation (p < 0.01). Mechanistically, restriction of these three EAAs activated HRI and GCN2 kinases, converging on eIF2α phosphorylation to induce ATF4 and its target VEGFA. Dual, but not single, knockdown of HRI and GCN2 abolished eIF2α-ATF4 signaling and angiogenic responses. Restricting these EAAs exacerbated CNV area in mice. Conclusions: Our findings reveal a coordinated HRI/GCN2-ATF4-VEGFA axis linking EAA scarcity to vascular remodeling, establishing proof-of-concept for targeting this pathway in CNV. This work highlights the therapeutic potential of modulating specific AA availability or targeting the HRI/GCN2-ATF4 axis to treat CNV. Full article

(This article belongs to the Section Proteins and Amino Acids)

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