Nutrients

12 pages, 745 KB

Open AccessArticle

Effects of Pomegranate Extract on IGF-1 Levels and Telomere Length in Older Adults (55–70 Years): Findings from a Randomised Double-Blinded Controlled Trial

by Grace Farhat, Jhama Malla, Liam Hanson, Jay Vadher and Emad A. S. Al-Dujaili

Nutrients 2025, 17(18), 2974; https://doi.org/10.3390/nu17182974 (registering DOI) - 16 Sep 2025

Abstract

Background: Emerging evidence suggests that polyphenols may contribute to the attenuation of telomere attrition and the upregulation of insulin-like growth factor 1 (IGF-1), primarily in animal and cell studies, and to a lesser extent in humans. Pomegranate extract, known for its high [...] Read more.

Background: Emerging evidence suggests that polyphenols may contribute to the attenuation of telomere attrition and the upregulation of insulin-like growth factor 1 (IGF-1), primarily in animal and cell studies, and to a lesser extent in humans. Pomegranate extract, known for its high antioxidant capacity, has shown promise in preventing telomere shortening and enhancing IGF-1 levels, but evidence in humans is lacking. Objective: To investigate the effects of pomegranate extract on telomere length and serum IGF-1 levels in older adults aged 55–70 years. Methods: Participants took part in a two-arm double-blind parallel trial, receiving either placebo capsules (maltodextrin) or pomegranate extract (740 mg) daily for 12 weeks. At baseline, week 6 and week 12, anthropometric measurements, blood pressure readings and blood samples were collected. Telomere length and serum IGF-1 levels were assessed. Results: A total of 72 participants completed the study. Analysis showed a significant effect of treatment and time on IGF-1 ((F_2,136 = 3.43, p = 0.04), with levels significantly increasing in the pomegranate extract group at week 12. No significant effects on telomere length were noted. Weight status, physical activity, age, gender and energy intake did not impact the outcomes. Conclusions: Pomegranate extract significantly increased IGF-1 levels and could exert a positive role on vascular ageing. Further research is needed to replicate these findings and confirm its long-term benefits. Extended studies are required to elucidate its potential to counteract telomere shortening. Full article

(This article belongs to the Special Issue The Role of Bioactive Compounds in Human Health and Diseases (3rd Edition))

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20 pages, 536 KB

Open AccessSystematic Review

A Systematic Review Evaluating the Impact of Fibre Supplementation on Gut Health and Other Clinical Outcomes in Adults with Haematological Malignancies During Haematopoietic Stem Cell Transplantation

by Fiona McCullough, Janice Cheung and Laura J. Miller

Nutrients 2025, 17(18), 2973; https://doi.org/10.3390/nu17182973 (registering DOI) - 16 Sep 2025

Abstract

Background: Gut health is often disrupted in adults with haematological malignancies (HMs) receiving chemotherapy and haematopoietic stem cell transplantation (HCT). Microbial diversity is reduced, and both infection risk and inflammation increased. The role of dietary fibre in enhancing gut health, immune regulation, reducing [...] Read more.

Background: Gut health is often disrupted in adults with haematological malignancies (HMs) receiving chemotherapy and haematopoietic stem cell transplantation (HCT). Microbial diversity is reduced, and both infection risk and inflammation increased. The role of dietary fibre in enhancing gut health, immune regulation, reducing complications, and improving clinical outcomes for people with HMs shows promise but the extent of their role remains unclear. Objectives: This systematic review evaluated the role of dietary fibre supplementation in adults with HMs undergoing HCT on gut health, immune function, and gastrointestinal health. This included assessment of differences between fibre types. Methods: A systematic search of PubMed and EMBASE was conducted following PRISMA guidelines, independently by two reviewers. Study quality was assessed using the Newcastle–Ottawa scale (NOS). Results: Of the 5023 studies after de-duplication, 63 remained after abstract and title screening, 59 studies were full-text screened, 56 studies were excluded due to language (n = 6), wrong intervention (n = 25), wrong population (n = 4), or reporting on unrelated outcomes (n = 21), and 3 studies met all inclusion criteria. Interventions included fructooligosaccharides (FOS), resistant starch (RS), and a glutamine, fibre, and oligosaccharide (GFO) prebiotic blend. Despite heterogeneity in measured outcomes, positive impacts on gut health, immune function, and gastrointestinal health were shown. Conclusions: Fibre supplementation represents a promising adjunctive strategy to improve clinical outcomes in adults with HMs undergoing HCT, by improving microbial diversity, increasing short-chain fatty acid (SCFA) production, and reducing incidence of acute GVHD. Further research is needed to establish specific recommendations for fibre in the nutritional management of patients with HM. Full article

(This article belongs to the Special Issue Diet, Gut Health, and Clinical Nutrition)

38 pages, 2046 KB

Open AccessReview

Effects of Diet and Exercise on Mitochondrial Health in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Role of Ceramides

by Jonas M. McCaffrey and Jamal A. Ibdah

Nutrients 2025, 17(18), 2972; https://doi.org/10.3390/nu17182972 (registering DOI) - 16 Sep 2025

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) impacts nearly a quarter of the world’s population and encompasses a range of disease states, from simple steatosis to more advanced stages like metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and cirrhosis. A key driver of disease progression is [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) impacts nearly a quarter of the world’s population and encompasses a range of disease states, from simple steatosis to more advanced stages like metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and cirrhosis. A key driver of disease progression is mitochondrial dysfunction, characterized by impaired fatty acid oxidation and an overall decline in mitochondrial health. Emerging evidence has implicated ceramides—bioactive sphingolipids that serve roles in apoptotic pathways and as signals of nutrient excess—as important contributors to this dysfunction. Ceramide accumulation within mitochondria mirrors impairments seen in MASLD, specifically elevations in oxidative stress, disrupted fatty acid oxidation, and impaired mitochondrial dynamics. Ceramides may serve as an important molecular link between nutrient overload and mitochondrial dysfunction in the pathogenesis of MASLD. Given the limited availability of effective pharmacologic therapies for MASLD, lifestyle interventions like dietary modification and physical activity remain the cornerstone of disease management worldwide. In this review, we provide an overview of the current understanding of the role of ceramides in mediating the effects of diet and exercise on MASLD through their influence on mitochondrial health. Full article

(This article belongs to the Special Issue Exercise, Diet, and Mitochondria)

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22 pages, 745 KB

Open AccessArticle

A Standardised Exercise Protocol to Induce Oxidative Stress in Humans: Validation with a Dietary Polyphenol Intervention

by Oiva V. Kamati, Laura Bragagna, Dirk J. Bester, Karl-Heinz Wagner, Vera Stürmer, Markus Gassner, Lina Maqboul, Roan Louw, Sacha West, Simeon Davies and Jeanine L. Marnewick

Nutrients 2025, 17(18), 2971; https://doi.org/10.3390/nu17182971 - 16 Sep 2025

Abstract

Background: Generating oxidative stress in a predictable and controllable way without the risk of causing harm is important for enabling the safe validation of interventions such as dietary polyphenols and ensuring ethical standards in human studies, while also advancing mechanisms involved in the [...] Read more.

Background: Generating oxidative stress in a predictable and controllable way without the risk of causing harm is important for enabling the safe validation of interventions such as dietary polyphenols and ensuring ethical standards in human studies, while also advancing mechanisms involved in the induced oxidative stress. Although, many experimental animal and in vitro models have been developed to conduct oxidative stress-based research, to date, very few reliable human models are available. Objective: This study’s main objective was to establish a standardised exercise model to induce oxidative stress in a repeatable and controllable manner and was tested with dietary polyphenols. Method: We applied a single blinded, randomised, cross-over, placebo-controlled trial with adult (25.95 ± 6.25 years) males (N = 40) where the induction of oxidative stress was achieved by an incremental aerobic exercise activity followed by a maximal anaerobic activity until exhaustion. To assess the model, rooibos polyphenolics was used as one of the interventions, while markers of safety and oxidative stress were measured on various occasions during the trial period. Results: The exercise regime reliably and repeatably induced oxidative stress, evidenced by increased levels of oxidative damage markers, i.e., oxidised glutathione (p = 0.003), malondialdehyde (p = 0.004), and a Comet assay tail moment (p < 0.05), while unconjugated bilirubin (p = 0.002) and the ferric reducing antioxidant potential (p < 0.001) increased over the study period, in the male study participants, irrespective of the oral intervention. Conclusions: This model showed an exercise regime that could be adapted to induce oxidative stress in a reliable and repeatable fashion without risk of causing harm. This study also demonstrated that a dietary polyphenolic intervention with rooibos did not complicate the onset of oxidative stress. Full article

(This article belongs to the Section Sports Nutrition)

19 pages, 1036 KB

Open AccessReview

A Scoping Review of Contextual and Individual Factors for Hospital-Acquired Malnutrition Development in Adult Hospital Inpatients: Guiding a Proactive Preventative Approach

by Vivien Hui In Cheung and Ching Shan Wan

Nutrients 2025, 17(18), 2970; https://doi.org/10.3390/nu17182970 - 16 Sep 2025

Abstract

Background: Preventing nutritional decline during hospitalisation is imperative in reducing the development of complications such as malnutrition and pressure injuries. However, existing malnutrition screening and assessment tools employ a reactive rather than proactive approach, using predictors to identify inpatients who are already malnourished [...] Read more.

Background: Preventing nutritional decline during hospitalisation is imperative in reducing the development of complications such as malnutrition and pressure injuries. However, existing malnutrition screening and assessment tools employ a reactive rather than proactive approach, using predictors to identify inpatients who are already malnourished instead of those at risk of developing hospital-acquired malnutrition. Therefore, this review aimed to identify key contextual and individual factors contributing to nutritional deterioration and their interrelatedness, and to inform strategies for preventing hospital-acquired malnutrition. Methods: A scoping review of five databases (Medline, CINAHL, Embase, All EBM Reviews and PsycINFO) up to June 2024 was conducted to include English-language studies that reported statistically significant risk factors for changes in nutritional status during hospitalisation. A directed acyclic graphing method was used to visualise the interlinkage between contextual and individual risk factors identified. PRISMA Extension for Scoping Reviews was followed in reporting. Results: Of 8215 retrieved abstracts, 51 studies were included. Four contextual (ward type; food service satisfaction; medical-related mealtime interruption; nutrition care collaboration) and four individual factors (nutritional status prior admission; hospital length of stay; multimorbidity; disease acuity) were found to significantly predict nutritional decline during hospitalisation and were closely interrelated. Conclusions: More contextual risk factors are modifiable, suggesting a need for organisational strategies to optimise collaborative nutrition care and improve patient satisfaction with hospital food services to promote early nutritional intervention, particularly within the first three days of admission and for inpatients with multimorbidity, high disease acuity, or pre-existing malnourishment. Full article

(This article belongs to the Special Issue The Role of Nutrition in Wound Care, Prevention and Healing: From Acute Trauma to Chronic Conditions)

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36 pages, 3212 KB

Open AccessReview

The Ketogenic Diet Through a Metabolomic Lens: Biochemical Pathways, Therapeutic Applications, and Analytical Challenges

by Katarzyna Idzikowska, Paulina Gątarek, Anna Gajda, Piotr Safiński, Lukasz Przyslo and Joanna Kałużna-Czaplińska

Nutrients 2025, 17(18), 2969; https://doi.org/10.3390/nu17182969 - 16 Sep 2025

Abstract

Background: The ketogenic diet (KD), a high-fat and low-carbohydrate dietary approach, has been used therapeutically in drug-resistant epilepsy and other neurological and metabolic disorders. Recent interest has shifted toward understanding its broader metabolic effects through metabolomics. This review aims to summarize current knowledge [...] Read more.

Background: The ketogenic diet (KD), a high-fat and low-carbohydrate dietary approach, has been used therapeutically in drug-resistant epilepsy and other neurological and metabolic disorders. Recent interest has shifted toward understanding its broader metabolic effects through metabolomics. This review aims to summarize current knowledge on the biochemical mechanisms and therapeutic implications of the KD, with a particular focus on metabolomic profiling and neurological health. Methods: This narrative review synthesizes findings from the last five years of metabolomic studies investigating the biochemical consequences of the KD and its variants, including the classical KD, modified Atkins diet (MAD), medium-chain triglyceride diet (MCT), and low glycemic index treatment (LGIT). The review integrates data on analytical techniques, such as liquid chromatography–mass spectrometry (LC-MS) and gas chromatography–mass spectrometry (GC-MS), and evaluates alterations in key metabolic pathways. Results: The KD significantly modulates energy metabolism, shifting adenosine triphosphate (ATP) production from glycolysis to fatty acid oxidation and ketone body utilization. It affects mitochondrial function, one-carbon metabolism, redox balance, neurotransmitter regulation, and gut–brain axis signaling. Metabolomic profiling has identified β-hydroxybutyrate (βHB) as a key regulatory metabolite influencing mitochondrial respiration. Long-term KD use may impact renal and hepatic function, necessitating clinical caution and individualized nutritional monitoring. Conclusions: Metabolomic analysis provides critical insights into the multifaceted effects of the KD, supporting its role as a targeted metabolic therapy in neurological diseases. However, potential risks linked to prolonged ketosis warrant further investigation. Future studies should focus on personalized applications and long-term safety profiles of KD variants across patient populations. Full article

(This article belongs to the Special Issue Neurological Disorders: Diets and Nutrition)

4 pages, 138 KB

Open AccessEditorial

Public Health, Nutritional Behavior, and Nutritional Status: An Editorial Synthesis and Roadmap for Precision Nutrition

by Sabina Lachowicz-Wiśniewska and Agata Kotowska

Nutrients 2025, 17(18), 2968; https://doi.org/10.3390/nu17182968 - 16 Sep 2025

Abstract

In the face of growing lifestyle-related health concerns across many populations—such as obesity and poor diet—understanding the determinants of these behaviors is crucial for designing effective public health strategies [...] Full article

(This article belongs to the Special Issue Public Health, Nutritional Behavior and Nutritional Status—2nd Edition)

17 pages, 3157 KB

Open AccessArticle

Immunomodulatory Effects of Lactobacillus brevis NES-428 in a Hyperthyroidism Mouse Model: Potential Applications for Graves’ Disease

by Min-Gyu Lee, Dong-Hyun Lee, Suzie Kang, Jongho Koh and Cheol-Won Yun

Nutrients 2025, 17(18), 2967; https://doi.org/10.3390/nu17182967 - 16 Sep 2025

Abstract

Background: Safe, microbiome-based interventions for autoimmune hyperthyroidism are lacking. We isolated the lactic acid bacterium NES-428 from kimchi and previously demonstrated that it shares 99% 16S-rRNA identity with Lactobacillus brevis reference strains, confirming NES-428 as a novel strain. Here we evaluated its immunomodulatory [...] Read more.

Background: Safe, microbiome-based interventions for autoimmune hyperthyroidism are lacking. We isolated the lactic acid bacterium NES-428 from kimchi and previously demonstrated that it shares 99% 16S-rRNA identity with Lactobacillus brevis reference strains, confirming NES-428 as a novel strain. Here we evaluated its immunomodulatory and anti-thyroid activity in cellular and murine models. Methods: Jurkat T cells (5 × 10⁶) were incubated with heat-killed NES-428 for 24 h and subsequently stimulated with phorbol 12-myristate 13-acetate/ionomycin (50 ng mL⁻¹/1 µg mL⁻¹) for 6 h; cytokine transcripts were quantified by qRT-PCR. Hyperthyroidism was induced in female BALB/c mice by three intramuscular injections of adenovirus-encoding human TSH receptor (Ad-TSHR). Mice received a daily oral dose of NES-428 (1 × 10⁹ CFU) for 15 weeks. Serum thyroxine (T₄) levels, splenocyte cytokine secretion, and thyroid histopathology were assessed. Statistical analyses employed one-way ANOVA with Tukey post hoc or log-rank tests (α = 0.05). Results: NES-428 pre-conditioning of Jurkat cells significantly down-regulated IL-2 and IFN-γ transcripts (−48% and –43%, respectively; p < 0.01) compared with stimulated controls while modestly increasing IL-4 (+26%). In Ad-TSHR mice, daily NES-428 reduced mean serum T₄ from 11.2 ± 2.1 to 5.8 ± 1.4 µg dL⁻¹ (p < 0.001), restored body weight gain, and normalized follicular architecture relative to untreated hyperthyroid animals. NES-428 supplementation also lowered splenocyte IFN-γ secretion by 58% and raised IL-4 by 41% (p < 0.05). Conclusions: The kimchi-derived strain NES-428 attenuates Th1-skewed cytokine responses and ameliorates experimental hyperthyroidism in vivo. These findings support further investigation of NES-428 as a probiotic candidate for immune modulation in Graves’ disease. Full article

(This article belongs to the Section Prebiotics and Probiotics)

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21 pages, 892 KB

Open AccessArticle

Dietary Modifications in IBS Leads to Reduced Symptoms, Weight, and Lipid Levels: Two Randomized Clinical Trials

by Bodil Roth and Bodil Ohlsson

Nutrients 2025, 17(18), 2966; https://doi.org/10.3390/nu17182966 - 16 Sep 2025

Abstract

Background/Objectives: Irritable bowel syndrome (IBS) is presented with both gastrointestinal and extraintestinal symptoms. In addition, overweight/obesity and metabolic syndrome is prevalent in IBS. Dietary interventions with a low content of fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) or a starch- and [...] Read more.

Background/Objectives: Irritable bowel syndrome (IBS) is presented with both gastrointestinal and extraintestinal symptoms. In addition, overweight/obesity and metabolic syndrome is prevalent in IBS. Dietary interventions with a low content of fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) or a starch- and sucrose-reduced diet (SSRD) efficiently reduce symptoms and weight. Our hypothesis was that not only nutrition composition but also weight reduction is of importance for symptom relief. The aim was to merge two randomized trials and examine symptoms, weight, nutrition intake, and lipid levels at baseline and during nutritional intervention. Methods: One study with 105 IBS patients randomized to either an SSRD (n = 80) or control diet (n = 25) and one study with 155 IBS patients randomized to an SSRD (n = 77) or low FODMAP (n = 78) were merged. Symptom and food questionnaires were analyzed together with weight/body mass index (BMI) and lipid levels. Results: Patients had moderate or severe IBS at baseline, and half of them were overweight/obese. Energy intake was reduced by both diets, with the most pronounced carbohydrate reduction after the SSRD. The cholesterol levels were highest in the second cohort, possibly due to the higher fat and lower starch intake. About 25% had high-density lipoprotein below reference levels. Gastrointestinal and extraintestinal symptoms, as well as weight/BMI, were reduced by the SSRD and low FODMAP, but not in the control group. The SSRD in the second cohort and low FODMAP rendered lower levels of total cholesterol, low-density lipoprotein, and non-high-density lipoprotein levels. Weight/BMI were more often associated with lipid levels and symptoms than nutrient composition at baseline, and weight/BMI reductions correlated with carbohydrate reduction and were associated with a reduction in gastrointestinal and extraintestinal symptoms. Conclusions: Not only food components, but also overweight/obesity may be of importance for the development and severity of IBS and related symptoms. Full article

(This article belongs to the Special Issue Hot Topics in Clinical Nutrition (3rd Edition))

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18 pages, 1702 KB

Open AccessArticle

Effects of Cistanche deserticola Y.C. Ma Supplementation on Muscle Strength and Recovery: A Randomized Controlled Trial

by Biaoxu Tao, Weihao Lian, Rongrong Min, Xiaoyu Zhang, Liqi Chen, Sun Hao, Ze Li, Chengzhe Ma, Haojie Zhang and Chang Liu

Nutrients 2025, 17(18), 2965; https://doi.org/10.3390/nu17182965 - 16 Sep 2025

Abstract

Objective: This study aimed to evaluate the effects of Cistanche deserticola Y.C. Ma (CD) supplementation on muscle strength and recovery in individuals with and without resistance training experience. Methods: A randomized, double-blind, placebo-controlled trial was conducted with 48 male participants, including 24 resistance-trained [...] Read more.

Objective: This study aimed to evaluate the effects of Cistanche deserticola Y.C. Ma (CD) supplementation on muscle strength and recovery in individuals with and without resistance training experience. Methods: A randomized, double-blind, placebo-controlled trial was conducted with 48 male participants, including 24 resistance-trained and 24 untrained individuals. Participants were stratified by training status and randomly assigned to either the CD or placebo (PLAC) group. All subjects completed a standardized resistance training program three times per week for eight weeks. The CD group received 5 g of CD extract twice daily, while the PLAC group consumed a matched placebo. Assessments included one-repetition maximum (1RM) for bench press and squat, maximal voluntary isometric contraction (MVIC), and repetitions to failure (RTF). Blood biomarkers including serum testosterone, cortisol, C-reactive protein (CRP), and creatine kinase (CK) were also measured. Results: No significant differences in dietary energy intake or macro-nutrient composition were observed based on two 5-day dietary records collected before baseline testing and at the end of the intervention. Among untrained individuals, the CD group showed significantly greater improvements in 1RM bench press and squat compared with the PLAC group (p < 0.05), with MVIC and RTF also significantly increased (p < 0.01). Serum cortisol levels were reduced (p < 0.05), and significant improvements were observed in testosterone, CRP, and CK (p < 0.01). In trained individuals, CD supplementation led to significant increases in 1RM squat and MVIC (p < 0.05), along with improvements in testosterone and cortisol levels (p < 0.05) and marked reductions in CRP and CK (p < 0.01). Conclusions: Daily supplementation with 5 g of CD extract for eight consecutive weeks significantly enhanced muscle strength and endurance in males with different training backgrounds and facilitated post-exercise recovery by modulating hormonal responses and reducing stress levels and inflammation. These findings provide experimental evidence supporting the application of CD in sports nutrition. Full article

(This article belongs to the Special Issue Bioactive Compounds and Functional Foods in Human Health—2nd Edition)

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40 pages, 3508 KB

Open AccessReview

Iron: More than Meets the Eye

by Ethan R. Naquin, Richa Garg, William J. Chen, Eshani Karmakar, Amogh Prasad, Saicharan Mandadi, Kiran Depala, Jyotsna S. Gopianand and Jaya P. Gnana-Prakasam

Nutrients 2025, 17(18), 2964; https://doi.org/10.3390/nu17182964 - 16 Sep 2025

Abstract

Iron is an essential micronutrient integral to ocular physiology, supporting biochemical processes such as mitochondrial respiration, DNA synthesis and phototransduction. Disruptions in systemic or local iron homeostasis, whether due to overload or deficiency, have been increasingly implicated in the pathogenesis of a broad [...] Read more.

Iron is an essential micronutrient integral to ocular physiology, supporting biochemical processes such as mitochondrial respiration, DNA synthesis and phototransduction. Disruptions in systemic or local iron homeostasis, whether due to overload or deficiency, have been increasingly implicated in the pathogenesis of a broad range of anterior and posterior segment ocular disorders. Iron deficiency may compromise retinal bioenergetics, impair cellular repair, and increase susceptibility to oxidative stress, while iron overload facilitates the generation of reactive oxygen species, contributing to lipid peroxidation, mitochondrial dysfunction, and ferroptosis. Dysregulated iron metabolism has been associated with several ocular pathologies, including age-related macular degeneration, diabetic retinopathy, glaucoma, retinal detachment, cataracts, and anemic retinopathy. The eye possesses specialized iron regulatory mechanisms involving proteins such as transferrin, ferritin, ferroportin, and hepcidin that govern iron transport, storage, and export across ocular barriers. Aberrations in these pathways are now recognized as contributing factors in disease progression. This narrative review explores the complex dual role of iron overload and deficiency in ocular diseases. It highlights the molecular mechanisms underlying iron-mediated pathologies in both the posterior and anterior segments of the eye, along with the clinical manifestations of iron imbalance. Current therapeutic approaches are discussed, including oral and parenteral iron supplementation for deficiency and emerging chelation-based or antioxidant strategies to address iron overload, while highlighting their limitations. Key challenges remain in developing targeted ocular delivery systems that optimize bioavailability and minimize systemic toxicity. Hence, maintaining iron homeostasis is critical for visual function, and further research is needed to refine therapeutic interventions and clarify the mechanistic role of iron in ocular health and disease. Full article

(This article belongs to the Special Issue Iron Homeostasis in Chronic Diseases)

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13 pages, 530 KB

Open AccessArticle

Influence of Adherence to the Mediterranean Diet on Vascular Health and Healthy Aging in Women: Assessment Using CAVI

by Inés Llamas-Ramos, Rocío Llamas-Ramos, María Cortés Rodríguez, Emiliano Rodríguez-Sánchez, Manuel A. Gómez-Marcos, Marta Gómez-Sánchez and Leticia Gómez-Sánchez

Nutrients 2025, 17(18), 2963; https://doi.org/10.3390/nu17182963 - 16 Sep 2025

Abstract

Background: Vascular aging, characterized by a progressive increase in arterial stiffness, is associated with an increased risk of cardiovascular disease. The Mediterranean diet (MD) has been shown to have protective effects on cardiovascular health, but its relationship with vascular aging, as assessed by [...] Read more.

Background: Vascular aging, characterized by a progressive increase in arterial stiffness, is associated with an increased risk of cardiovascular disease. The Mediterranean diet (MD) has been shown to have protective effects on cardiovascular health, but its relationship with vascular aging, as assessed by the Cardio-Ankle Vascular Index (CAVI), is not yet well established. Objective: To analyze the association between adherence to the MD and vascular aging estimated with CAVI in a sample of Spanish women with no history of previous cardiovascular disease. Methods: A cross-sectional study was conducted in 1468 women (aged 30–80 years), classified into three categories according to CAVI: healthy vascular aging (HVA), normal (NVA), and early (EVA). Adherence to the MD was assessed using the MEDAS questionnaire validated in Spain. ANOVA and chi-square tests were used to compare baseline characteristics, and multinomial logistic regression was used to analyze the association between MD adherence and vascular aging status, adjusting for age, sex, and drug treatment. Results: The CAVI increased progressively with age (p < 0.001) and was associated with higher blood pressure, dyslipidemia, hyperglycemia, and diabetes mellitus. Adherence to the MD was significantly higher in groups with lower arterial stiffness (p < 0.001). In the multivariate analysis, greater adherence to MD was associated with a higher probability of healthy vascular aging compared to NVA (OR: 1.872; 95% CI: 1.366–2.566; p < 0.001) and EVA (OR: 1.738; 95% CI: 1.363–2.218; p < 0.001). Conclusions: Greater adherence to the MD is associated with a healthier vascular aging profile. Promoting this dietary pattern may be an effective strategy for preventing arterial stiffness and reducing the cardiovascular risk associated with aging. Full article

(This article belongs to the Special Issue Nutritional Strategies for Promoting Arterial Health and Cardiovascular Prevention)

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18 pages, 1586 KB

Open AccessArticle

The Effects of Essential Amino Acid Supplementation on Hippocampal Neurotrophin, Dopaminergic and Serotonergic Changes in an Overtraining Mouse Model

by Lior Binman, Tavor Ben-Zeev, Asher Harris, Chagai Levi, Inbal Weissman, David D. Church, Arny A. Ferrando and Jay R. Hoffman

Nutrients 2025, 17(18), 2957; https://doi.org/10.3390/nu17182957 - 16 Sep 2025

Abstract

Background/Objectives: This study examined the efficacy of essential amino acid (EAA) supplementation on changes in behavior and hippocampal neurotrophin, dopaminergic and serotonergic markers to a volume overload stress resembling an overtraining syndrome. Methods: Thirty-two 3-month-old male C57Bl/6J mice were randomized into [...] Read more.

Background/Objectives: This study examined the efficacy of essential amino acid (EAA) supplementation on changes in behavior and hippocampal neurotrophin, dopaminergic and serotonergic markers to a volume overload stress resembling an overtraining syndrome. Methods: Thirty-two 3-month-old male C57Bl/6J mice were randomized into four groups: Resistance training (RT), resistance training with overtraining (RTO), resistance training with overtraining and EAA (RTOEAA), or control. Mice in RTOEAA received EAA supplementation (1.5 g·kg·day⁻¹), while the other groups received a sham treatment. A 5-week resistance training protocol was employed. Training volume was increased two-fold during the final two weeks for RTO and RTOEAA to cause the OTS. EAA intervention for RTOEAA occurred during the OTS. Results: A significant decline in the maximum resistance carrying load in RTO compared to RT (p = 0.002) and RTOEAA (p = 0.029) confirmed that the animals in that group were overtrained. Significantly greater average latency times for RTO compared to RT (p = 0.009) and C (p = 0.05) indicated that the OTS caused spatial memory deficits in animals that were not supplemented. These latter changes may have been related to the significant declines in brain derived neurotrophic (BDNF) expression and elevations in dopamine 1 receptor (D1R) expressions. Increased resiliency for RTOEAA may have been related to the effect of EAA on stimulating significant increases in the expression of hippocampal tyrosine receptor kinase B (TrkB) and serotonin receptors (5-HT1A). Conclusions: EAA supplementation during a resistance model of overtraining appeared to provide increased resiliency to OTS by maintaining neurotrophin expression and enhancing serotonergic adaptation. Full article

(This article belongs to the Section Sports Nutrition)

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22 pages, 7591 KB

Open AccessArticle

Exercise-Induced Changes in Enterohepatic Communication Are Linked to Liver Steatosis Resolution

by Yong Zou, Jie Xia, Sen Zhang, Yingjie Guo, Weina Liu and Zhengtang Qi

Nutrients 2025, 17(18), 2962; https://doi.org/10.3390/nu17182962 - 15 Sep 2025

Abstract

Background/Objectives: This study aimed to investigate the effects of long-term aerobic exercise on high-fat diet (HFD)-induced hepatic steatosis and its underlying enterohepatic communication mechanisms. Methods: C57BL/6J mice were divided into four groups: normal-diet with sedentary (ND-SED), normal-diet with exercise (ND-EXE), HFD [...] Read more.

Background/Objectives: This study aimed to investigate the effects of long-term aerobic exercise on high-fat diet (HFD)-induced hepatic steatosis and its underlying enterohepatic communication mechanisms. Methods: C57BL/6J mice were divided into four groups: normal-diet with sedentary (ND-SED), normal-diet with exercise (ND-EXE), HFD with sedentary (HFD-SED), and HFD with exercise (HFD-EXE). After 16 weeks of HFD feeding, ND-EXE and HFD-EXE groups underwent an 8-week aerobic exercise intervention. Hepatic lipid accumulation was assessed via histology and triglyceride (TG) quantification. Liver function and glucose tolerance were evaluated. Gut microbiota composition (16S rRNA sequencing), hepatic bile acid profiles (LC-MS metabolomics), and gene expression were analyzed. Results: HFD induced hepatic steatosis, glucose intolerance, and liver injury in mice, all of which were ameliorated by exercise. Compared to HFD-SED mice, which exhibited impaired gut microbiota diversity, exercise restored key genera such as Faecalibaculum, and Turicibacter. Functional analysis revealed that exercise modulated microbiota shifts in lipid metabolism and secondary bile acid biosynthesis. HFD-EXE mice displayed altered hepatic bile acid composition, characterized by increased tauroursodeoxycholic acid (TUDCA) and reduced taurohyodeoxycholic acid (THDCA). Notably, TUDCA levels correlated with Turicibacter abundance, while deoxycholic acid (DCA) was associated with Faecalibaculum, independent of precursor availability. Exercise also suppressed hepatic endoplasmic reticulum (ER) stress and downregulated lipogenic genes via the inositol-requiring enzyme 1 alpha (IRE1α)- spliced X-box binding protein 1 (Xbp1s) pathway, while concurrently activating farnesoid X receptor (FXR) signaling to enhance fatty acid oxidation through the FXR-short heterodimer partner (SHP) related to hepatic secondary bile acid abundance change. Conclusions: The beneficial effect of long-term aerobic exercise on high-fat diet-induced hepatic steatosis in mice is potentially mediated through structural changes in the gut microbiota, which influence the abundance of hepatic secondary bile acids (TUDCA, DCA) and subsequently regulate the expression of genes involved in lipid metabolism. Full article

(This article belongs to the Special Issue Effects of Exercise and Diet on Health)

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19 pages, 2381 KB

Open AccessArticle

The Longitudinal Influence of Parent–Grandparent Coparenting Relationships on Preschoolers’ Eating Behaviors in Chinese Urban Families: The Mediating Roles of Caregivers’ Feeding Behaviors

by Zhihui Zhao, Fangge Qu, Ruxing Wu, Xiaoxue Wei, Xinyi Song, Chenjun Wu, Jian Wang, Wenzhe Hua and Daqiao Zhu

Nutrients 2025, 17(18), 2961; https://doi.org/10.3390/nu17182961 - 15 Sep 2025

Abstract

Background: The early development of children’s eating behaviors is a complex process shaped by dynamic interactions within the family system. While extensive research has focused on parental feeding practices as a primary predictor of children’s eating behaviors, the role of intergenerational coparenting dynamics [...] Read more.

Background: The early development of children’s eating behaviors is a complex process shaped by dynamic interactions within the family system. While extensive research has focused on parental feeding practices as a primary predictor of children’s eating behaviors, the role of intergenerational coparenting dynamics (especially with involved grandparents) is less studied. This study aimed to examines how primary caregivers’ feeding behaviors mediate the relationship between parent–grandparent coparenting dynamics and children’s eating behaviors. Methods: We conducted a longitudinal study among 343 stem families with preschool children. The cross-lagged analysis was applied to examine: the mechanism of parent–grandparent coparenting relationships on preschool children’s eating behaviors and the bidirectional relationship between feeding behaviors and eating behaviors. Results: Our results revealed that coparenting agreement significantly and negatively predicted satiety responsiveness through the mediating role of parental encouragement of healthy eating (β = −0.012, 95% CI [−0.022, −0.001]). Similarly, coparenting support had a significant negatively indirect effect on satiety responsiveness, also partially mediated by parental encouragement of healthy eating (β = −0.012, 95% CI [−0.023, −0.002]). The association between coparenting undermining and satiety responsiveness was mediated by parental encouragement healthy eating (β = −0.612, 95% CI [−0.796, −0.429]). Mutual predictive relationships were observed between preschool children’s satiety responsiveness and parental encouragement of healthy eating (p < 0.05). Conclusions: The study results highlighted the critical role of parent–grandparent coparenting relationships as indirect predictors of preschoolers’ eating behavior through mediator of parental feeding behaviors. Importantly, healthcare providers may be able to offer anticipatory guidance or relevant healthy eating resources to parents and grandparents, who should be recognized as important stakeholders in promoting healthy eating among children. Full article

(This article belongs to the Section Pediatric Nutrition)

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49 pages, 1358 KB

Open AccessPerspective

Is There a Future Without Gluten Restrictions for Celiac Patients? Update on Current Treatments

by Marina Girbal-González and Francisco J. Pérez-Cano

Nutrients 2025, 17(18), 2960; https://doi.org/10.3390/nu17182960 - 15 Sep 2025

Abstract

Celiac disease (CeD) is a chronic autoimmune enteropathy triggered by dietary gluten in genetically predisposed individuals. Along with other disorders such as non-celiac gluten/wheat sensitivity and gluten allergy, adherence to a strict gluten-free diet (GFD) is required as the only effective treatment for [...] Read more.

Celiac disease (CeD) is a chronic autoimmune enteropathy triggered by dietary gluten in genetically predisposed individuals. Along with other disorders such as non-celiac gluten/wheat sensitivity and gluten allergy, adherence to a strict gluten-free diet (GFD) is required as the only effective treatment for CeD. To this end, and partially due to the burdensome nature and limited efficacy in some patients of a GFD, significant research into alternative therapies has been catalyzed. This review gives a perspective on current and emerging treatment strategies targeting different aspects of CeD pathogenesis. These include gluten-degrading enzymes (e.g., AN-PEP, Latiglutenase, Zamaglutenase), gluten-sequestering agents (e.g., AGY-010, BL-7010), modulators of intestinal permeability (e.g., Larazotide acetate, IMU-856), immune-modulating agents (e.g., ZED1227, AMG 714, EQ102), and strategies for immune tolerization (e.g., TAK-101, KAN-101, Nexvax2). Newer approaches are also targeting probiotics to modulate the gut microbiota (e.g., VSL#3, Lactobacillus plantarum HEAL9), nutraceuticals (e.g., polyphenols, vitamins), or food modifications to remove the gluten from naturally gluten-containing foodstuffs (e.g., gluten transamidation, Gluten Friendly™ technology). Despite encouraging results in preclinical and clinical trials, no treatment has yet been conclusively proven to serve as an effective alternative to the GFD. Continued research is essential to validate efficacy, optimize dosing, and ensure safety in broader patient populations. Here, we provide a comprehensive overview of the therapeutic landscape for CeD, analyze the main strengths and limitations of each treatment and highlight promising directions for future management of CeD, altogether evidencing the urgent need to develop effective alternatives for these patients. Full article

(This article belongs to the Section Nutritional Immunology)

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31 pages, 2087 KB

Open AccessArticle

Synbiotic Supplementation with Probiotics and Omega-3 Fatty Acids Enhances Upper-Body Muscle Strength in Elite Swimmers: Evidence for Gut–Muscle Axis Modulation During Race-Pace Training

by Babak Imanian, Mohammad Hemmatinafar, Ideh Maymandinejad, Mohammad Reza Binazade, Ralf Jäger, Zeinab Jahan, Kimia Naseri, Rasoul Rezaei and Katsuhiko Suzuki

Nutrients 2025, 17(18), 2959; https://doi.org/10.3390/nu17182959 - 15 Sep 2025

Abstract

Background: The gut–muscle axis is believed to influence training adaptations through microbiota-derived signals and the regulation of inflammation, but evidence in elite swimmers is limited and mixed. This study aims to determine whether synbiotic supplementation (probiotics + omega-3) combined with ultra-short race-pace training [...] Read more.

Background: The gut–muscle axis is believed to influence training adaptations through microbiota-derived signals and the regulation of inflammation, but evidence in elite swimmers is limited and mixed. This study aims to determine whether synbiotic supplementation (probiotics + omega-3) combined with ultra-short race-pace training (USRPT) improves sprint-related upper-body strength. Methods: In a randomized, double-blind, 8-week trial of male elite sprint freestyle swimmers, participants completed USRPT and were allocated to either synbiotic supplementation or its single-component arms (probiotic or omega-3) or placebo. Primary outcomes indexed dynamic/explosive strength (isokinetic shoulder torque and power at 180°/s, rate of force development, time-to-peak torque); secondary outcomes included maximal strength (MVIC; 60°/s) and field/strength-endurance tests (dead-hang, handgrip, medicine-ball throw). Analyses reported p-values with effect sizes. Results: The synbiotic group showed greater improvements in high-velocity, sprint-relevant measures versus comparators—higher 180°/s torque and power, increased rate of force development, and shorter time-to-peak torque (Time × Group p < 0.05 across domains; effects in the medium–large range). Changes in handgrip and medicine-ball throw were small and not different between groups (p > 0.05). Conclusions: Synbiotic supplementation concurrent with USRPT preferentially enhances dynamic (explosive) upper-body strength in elite sprint swimmers, whereas non-stroke-embedded field tests show limited added value. Any reference to gut–muscle-axis modulation is hypothesis-generating, as stool sequencing and metabolite profiling were not performed. Larger, sex-inclusive trials incorporating in-water, stroke-embedded assessments and microbiome/metabolomic profiling are warranted. Full article

(This article belongs to the Special Issue The Role of Nutritional Intake and Supplements in Improving Athletic Performance)

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14 pages, 1892 KB

Open AccessArticle

In Vitro Suppression Effects of Ephedra przewalskii Stapf-Derived Natural Compounds on SARS-CoV-2

by Xiaolan Zhu, Abeer Mohamed Abdelfattah Elsayed, Masaki Kakimoto, Sachiko Sugimoto, Takemasa Sakaguchi and Keiko Ogawa-Ochiai

Nutrients 2025, 17(18), 2958; https://doi.org/10.3390/nu17182958 - 15 Sep 2025

Abstract

Background: Ephedra przewalskii Stapf stems are a traditional Mongolian medicine commonly used to treat infectious diseases. Previous in vitro experiments have shown that the extract powder derived from its stems possesses antiviral activity. However, the active compounds responsible for this activity in E. [...] Read more.

Background: Ephedra przewalskii Stapf stems are a traditional Mongolian medicine commonly used to treat infectious diseases. Previous in vitro experiments have shown that the extract powder derived from its stems possesses antiviral activity. However, the active compounds responsible for this activity in E. przewalskii Stapf have not yet been identified or evaluated. This study aimed to identify the active components in E. przewalskii that exhibit antiviral effects against SARS-CoV-2 in vitro and validate their antiviral activity. Methods: E. przewalskii stem extracts were subjected to high-performance liquid chromatography with varying methanol ratios in the mobile phase to obtain fractions with different polarities. Antiviral activity was assessed by infecting VeroE6/TMPRSS2 cells with the SARS-CoV-2 Delta strain and treating them with the obtained fractions. Infectious titers were measured using the 50% tissue culture infective dose (TCID₅₀) method, and half-maximal inhibitory concentration (IC₅₀) values were calculated for each fraction. The active components in the two fractions with the highest antiviral activity were identified and structurally characterized by nuclear magnetic resonance analysis. The antiviral activity of these compounds was confirmed by adding them to SARS-CoV-2-infected cells and measuring their infectious titers using the TCID₅₀ method. The IC₅₀ values were also calculated. Viral-particle inactivation assays were conducted by mixing the extracts with SARS-CoV-2 and measuring infectious titers. Results: (−)-Catechin, (+)-epigallocatechin-(2α→O→7,4α→8)-(−)-epicatechin, and ent-epicatechin-(4α→8;2α→O→7)-catechin were isolated from E. przewalskii. These compounds exhibited significant antiviral activity against SARS-CoV-2 but demonstrated minimal direct virucidal effects. Conclusion: (−)-Catechin, (+)-epigallocatechin-(2α→O→7,4α→8)-(−)-epicatechin, and ent-epicatechin-(4α→8;2α→O→7)-catechin exhibit antiviral activity against SARS-CoV-2 in infected cells. Full article

(This article belongs to the Special Issue Plant Extracts in the Prevention and Treatment of Chronic Disease)

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31 pages, 1203 KB

Open AccessReview

Vitamins, Vascular Health and Disease

by George Ayoub

Nutrients 2025, 17(18), 2955; https://doi.org/10.3390/nu17182955 - 15 Sep 2025

Abstract

Vascular health relies on the proper function of endothelial cells, which regulate vascular tone, blood fluidity, and barrier integrity. Endothelial dysfunction, often aggravated by inadequate vitamin absorption, contributes to a spectrum of clinical disorders, including cardiovascular disease, cerebrovascular disease, peripheral artery disease, age-related [...] Read more.

Vascular health relies on the proper function of endothelial cells, which regulate vascular tone, blood fluidity, and barrier integrity. Endothelial dysfunction, often aggravated by inadequate vitamin absorption, contributes to a spectrum of clinical disorders, including cardiovascular disease, cerebrovascular disease, peripheral artery disease, age-related macular degeneration, lymphedema, and chronic venous insufficiency. B-group vitamins (especially folate, or vitamin B9), along with vitamins B12, B6, C, D, and E, are essential in maintaining endothelial function, supporting DNA synthesis, regulating methylation, enhancing cellular repair, mitigating oxidative stress and inflammatory signaling, and curtailing vascular damage. Folate is noted for its central function in one-carbon metabolism and in converting homocysteine to methionine, thereby reducing vascular toxicity. We cover natural dietary sources of folate, synthetic folic acid, and the biologically active forms 5-methyl-(6S)-tetrahydrofolate (L-5-MTHF, L-methylfolate) and 5-formyl-(6S)-tetrahydrofolate (levoleucovorin). Therapeutic strategies to address vascular health and prevent hyperhomocysteinemia in order to preclude follow-on disorders include targeted vitamin supplementation, dietary improvements to ensure a sufficient intake of bioavailable nutrient forms, and, in certain clinical contexts, the use of active L-methylfolate or levoleucovorin (a drug product) to bypass metabolic conversion issues. These evidence-based interventions aim to restore endothelial homeostasis, slow disease progression, and improve patient outcomes across a variety of disorders linked to poor vascular health. Full article

(This article belongs to the Special Issue Nutritional Approaches in Autism and Related Disorders)

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