Desirée Victoria-Montesinos

Context: Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition in children and adolescents, yet the comparative effectiveness of dietary strategies remains unclear. Objective: To compare the effects of different dietary interventions on liver enzymes and metabolic outcomes in children and adolescents with MASLD using a frequentist network meta-analysis (NMA) of randomized clinical trials (RCTs). Data Sources: The MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched from inception to December 2, 2024. Reference lists of relevant systematic reviews were also screened. Data Extraction: Eligible studies were RCTs including participants aged 2-19 years with MASLD and that compared dietary interventions and reported liver-related outcomes. Primary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) levels. Secondary outcomes included body mass index (BMI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and lipid profile. Two reviewers independently extracted study and outcome data, with discrepancies resolved by a third reviewer. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2.0. Data Analysis: Eleven RCTs (n = 668; n = 22 intervention arms) were included. Random-effects NMA was performed using restricted maximum likelihood estimation, and treatment rankings were assessed using P scores. Pairwise analyses showed that low-fat diets significantly reduced ALT and AST levels compared with usual diets. In the NMA, no dietary pattern significantly outperformed others for improved liver enzyme values, although low-fat diets ranked as the intervention with the highest probability to be effective in improving ALT (71.5%), AST (74.1%), and GGT (77.3%) levels. Low-carbohydrate diets ranked highest for improving BMI (84.5%), HOMA-IR (84.5%), low-density lipoprotein cholesterol (71.4%), high-density lipoprotein cholesterol (67.4%), and total cholesterol (96.3%) values, whereas moderate diets ranked highest for improving triglyceride values (72.2%). Conclusions: Low-fat diets ranked highest for liver enzyme outcomes, whereas low-carbohydrate and moderate dietary patterns ranked highest for several metabolic outcomes. However, the low to very low certainty of evidence warrants cautious interpretation and confirmation in larger, methodologically homogeneous trials. Systematic Review Registration: PROSPERO (International Prospective Register of Systematic Reviews) registration no. CRD42024614131

Neurodegenerative diseases arise from interacting oxidative, inflammatory, mitochondrial, and proteostatic disturbances. Hydroxytyrosol (HT), an olive phenol, has been proposed as a multitarget neuroprotective compound. This narrative review integrates HT chemistry, parent/metabolite pharmacokinetics, blood–brain barrier (BBB) evidence, mechanisms, disorder-specific models, and human studies. Direct HT evidence is strongest for nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) activation and experimental modulation of α-synuclein; support for AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), mitochondrial protection, nuclear factor-kappa B (NF-κB)-related inflammation, and amyloid-β (Aβ) is predominantly preclinical, whereas tau, autophagic flux, and ubiquitin–proteasome effects remain preliminary. Oral HT is rapidly absorbed but extensively conjugated, and no study has quantified parent HT or its major metabolites in the human brain or cerebrospinal fluid after oral supplementation. Isolated-HT trials show systemic antioxidant or anti-inflammatory biomarker effects, while cognitive findings derive mainly from phenolic-rich olive matrices and cannot be assigned to HT alone. No disease-modifying efficacy has been established for isolated HT in Alzheimer’s disease (AD), Parkinson’s disease (PD), or related disorders. HT is therefore a mechanistically plausible candidate, but human brain exposure, dose–response, and efficacy require adequately powered disease-specific trials.

Diabetic retinopathy, diabetic kidney disease, and diabetic peripheral neuropathy remain major causes of visual loss, kidney failure, pain, disability, and reduced quality of life despite improvements in glycemic and cardiovascular risk management. Oxidative stress, mitochondrial dysfunction, iron dyshomeostasis, lipid peroxidation, and sterile inflammation are shared features of these complications and converge on regulated cell-death programs. Ferroptosis is driven by iron-dependent phospholipid peroxidation when glutathione peroxidase 4 and complementary antioxidant systems are insufficient, whereas pyroptosis is an inflammatory lytic process executed by gasdermins after activation of inflammasome-associated or other inflammatory caspases. Nuclear factor erythroid 2-related factor 2 (NRF2) connects these pathways by regulating glutathione synthesis, lipid peroxide detoxification, iron handling, mitochondrial homeostasis, and redox-sensitive inflammatory signaling. Dietary polyphenols may influence this network through electrophilic or kinase-dependent NRF2 activation, preservation of the SLC7A11-glutathione-GPX4 axis, modulation of iron and lipid metabolism, and inhibition of NF-kappaB, TXNIP, NLRP3, caspase-1, and gasdermin signaling. This integrative review critically examines mechanistic, preclinical, and human evidence for these effects in the diabetic retina, kidney, and peripheral nerve. The strongest direct preclinical evidence currently concerns corilagin, resveratrol, isoquercetin, quercetin, epigallocatechin gallate, punicalagin, and selected anthocyanin-rich or phenolic extracts. Human studies suggest possible benefits for albuminuria, retinal edema, endothelial function, and neuropathic outcomes, but they rarely measure ferroptosis- or pyroptosis-specific biomarkers and their results are heterogeneous. The proposed ferroptosis–pyroptosis–NRF2 network should therefore be viewed as a biologically plausible integrative framework rather than a clinically validated linear pathway. Future trials require chemically characterized interventions, exposure biomarkers, tissue-relevant pharmacokinetics, prespecified regulated-cell-death panels, and clinically meaningful microvascular endpoints.

Introduction: Nutrition knowledge and the ability to translate it into appropriate food and hydration choices are important for health, development, recovery, and performance in young athletes. However, evidence on nutrition interventions in youth team-sport settings remains dispersed across sports, educational formats, and outcome domains. This systematic review aimed to synthesize evidence on nutrition education, hydration education, dietary counseling, digital tools, controlled dietary modification, and multicomponent interventions in child, adolescent, and late-adolescent development settings. Methods: The review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261441507). PubMed/MEDLINE, Scopus, Web of Science Core Collection, SPORTDiscus/EBSCO, and Cochrane CENTRAL were searched from inception to 3 July 2026. Two reviewers independently screened reports, extracted data, and assessed risk of bias using RoB 2 or ROBINS-I. Because of substantial heterogeneity in interventions and outcomes, findings were synthesized narratively. Results: Database searches identified 419 records. After duplicate removal and screening, 46 full-text reports were assessed, 19 were excluded, and 27 unique studies were included. Soccer/football predominated, with additional evidence from volleyball, basketball, handball, baseball, hockey, American football, and mixed-sport settings. Nutrition and sports nutrition knowledge showed the most consistent favorable changes. Findings for dietary intake, diet quality, body composition, biochemical markers, and performance were mixed. Hydration interventions showed clearer short-term improvements when education was combined with practical cues, improved fluid access, feedback, or individualized prescriptions. Discussion: Nutrition interventions in youth team-sport and related development settings may support knowledge acquisition and selected hydration behaviors, but their effects on dietary behavior and physiological outcomes remain uncertain. Confidence in the evidence is limited by small samples, short follow-up periods, heterogeneous measures, reliance on self-report, incomplete fidelity reporting, and risk-of-bias concerns. Future trials should use validated age-appropriate measures, objective outcomes, longer follow-up, prespecified analyses, and implementation strategies involving athletes, families, coaches, schools, and clubs. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261441507 , CRD420261441507.

Background/Objectives: Automated insulin delivery (AID) systems have improved the management of type 1 diabetes (T1D), but exercise and nutrition remain challenging because they rapidly alter glucose flux, substrate oxidation, hepatic glucose output, insulin requirements, and fuel availability. This narrative review aimed to synthesize current evidence on the interaction between AID systems, physical activity, and nutritional strategies from a metabolism-oriented perspective. Methods: A narrative bibliographic approach was used to integrate evidence from clinical trials, observational studies, technical studies, consensus statements, and reviews involving people with T1D across different life stages, including pediatric, adolescent, adult, and pregnancy-related contexts, when available. The review focused on AID systems, exercise physiology, nutritional strategies, meal announcement, bolus adjustment, dual-hormone systems, metabolic biomarkers, and emerging metabolomic approaches. Results: AID systems generally improve time in range and reduce hypoglycemia across several user groups, although most exercise- and nutrition-specific evidence comes from adult and pediatric/adolescent cohorts rather than pregnancy-specific exercise studies. Exercise-related glucose responses remain highly dependent on user input, exercise modality, insulin on board, meal timing, and metabolic state. Planned exercise announcement, prandial bolus reduction before postprandial activity, and individualized carbohydrate intake remain key strategies. Biomarkers such as lactate, ketone bodies, non-esterified fatty acids, and counter-regulatory hormones may help explain interindividual variability and support future personalization. Conclusions: Nutrition and exercise management in AID users should be interpreted as a dynamic metabolic interface among exogenous insulin, endogenous counter-regulation, substrate availability, and algorithmic control. Emerging approaches, including activity sensors, adaptive algorithms, dual-hormone systems, digital twins, and metabolomics-informed personalization, may improve safety and reduce user burden, but several remain exploratory and require further validation in diverse free-living conditions.

Background/Objectives: Curcumin has been proposed as a nutritional strategy to support exercise recovery through antioxidant and anti-inflammatory actions. However, trials differ in sport context, training status, supplementation timing, dose, formulation, and methodological control. This systematic review evaluated its effects on recovery outcomes in active individuals and athletes, with particular attention to the applicability of the evidence to real-world sport settings. Methods: PubMed, Scopus, Web of Science, SPORTDiscus, and Cochrane Library/CENTRAL were searched from 2012 to June 2026. Randomized double-blind placebo-controlled trials were eligible when they evaluated oral curcumin, curcuminoids, Curcuma-derived preparations with a specified curcumin dose, or curcumin combined only with bioavailability enhancers. Studies using artificial muscle-damage protocols, clinical populations, non-randomized designs, or combined bioactive interventions were excluded. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale, supplemented by a Cochrane Risk of Bias 2 (RoB 2) assessment and a Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty-of-evidence evaluation. Owing to heterogeneity, findings were synthesized narratively by outcome domain, supplementation timing, formulation type, exercise context, and training status. Results: Fifteen trials were included. Favorable effects were reported in 6/7 studies assessing oxidative stress, 4/6 assessing muscle damage, 3/8 assessing inflammation, 3/7 assessing subjective recovery, soreness, or fatigue, and 4/8 assessing physical or athletic performance. However, effects varied substantially according to population, exercise context, biomarker selection, timing of assessment, and formulation type. The certainty of evidence was low for oxidative stress and very low for muscle damage, inflammation, subjective recovery/soreness/fatigue, and performance. Conclusions: Curcumin supplementation may support selected aspects of exercise recovery, particularly oxidative stress responses. However, these findings should be interpreted cautiously because the evidence derives mostly from small trials with heterogeneous populations, exercise protocols, supplementation regimens, formulations, biomarkers, and assessment time points. Evidence for muscle damage, inflammation, subjective recovery, fatigue, and performance remains inconsistent, and further well-controlled trials in trained and high-performance athletes are needed before practical recommendations can be established.

To evaluate the efficacy and safety of gut microbiota-modulating interventions in children and adolescents with type 1 diabetes. A systematic review and meta-analysis was conducted according to PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and CENTRAL were searched from inception to 28 February 2026 for randomised controlled trials of oral probiotics, prebiotics, or synbiotics in participants aged ≤ 19 years with type 1 diabetes. Primary outcomes were glycated haemoglobin, fasting blood glucose, total daily insulin dose, and C-peptide. Immune-inflammatory, microbiota-related, intestinal permeability, and safety outcomes were narratively synthesised. Twelve randomised controlled trials involving 808 paediatric participants were included. Interventions varied in formulation, dose, and duration. Pooled analyses showed significant reductions in glycated haemoglobin and fasting blood glucose, whereas no significant effects were found for total daily insulin dose or C-peptide. Immune-inflammatory, microbiota-related, and intestinal permeability outcomes suggested possible benefits, but reporting was inconsistent and quantitative pooling was not feasible. Overall, the evidence was limited by substantial clinical and methodological heterogeneity. Conclusion: Gut microbiota-modulating interventions may improve glycaemic control in children and adolescents with type 1 diabetes, particularly glycated haemoglobin and fasting blood glucose. However, current evidence is insufficient to support any specific formulation, dose, or duration, and larger well-designed paediatric trials are still needed. What is Known: • Gut microbiota-modulating interventions are biologically plausible adjunctive strategies in paediatric type 1 diabetes. • Earlier paediatric reviews included few randomised trials and reported inconsistent glycaemic findings. What is New: • This updated review included 12 randomised controlled trials involving 808 children and adolescents. • It adds a structured synthesis of immune-inflammatory, microbiota/barrier, metabolite-related and safety outcomes beyond glycaemic endpoints.

We thank the authors of the Comment for their careful reading of our article and for raising important interpretative and methodological considerations

1. Alopecia is a prevalent condition frequently associated with diminished quality of life and increased psychological distress (1,2). Its pathology is broadly categorized into scarring (permanent)...

Cardiovascular disease is a leading cause of global morbidity and mortality, and processed meat consumption has been consistently associated with adverse cardiometabolic outcomes in observational studies. However, processed meat products differ substantially in composition and processing methods, and traditional dry-cured ham presents distinct nutritional and biochemical characteristics. This systematic review and meta-analysis aimed to synthesize evidence from human intervention studies evaluating the effects of dry-cured ham consumption on cardiometabolic and vascular health in adults. A comprehensive search of major databases identified eligible randomized and non-randomized intervention studies. Five trials were included in the qualitative synthesis, and meta-analyses were performed for blood pressure, lipid profile, and fasting blood glucose outcomes when sufficient data were available. The pooled analyses indicated a small but statistically significant reduction in diastolic blood pressure and total cholesterol associated with dry-cured ham consumption, whereas no significant effects were observed for systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, or fasting blood glucose. Substantial heterogeneity was present across most outcomes. Overall, the available intervention evidence suggests that dry-cured ham consumption at doses ranging from 40 to 120 g/day does not appear to adversely affect conventional cardiometabolic risk markers in adults. Nevertheless, the limited number and short duration of trials warrant cautious interpretation.