Search Results (650)

Ketones are metabolites primarily produced by the liver and are utilized by various organs outside of the liver. Recent advances have demonstrated that ketones serve not only as alternative energy sources but also as signaling molecules. Research indicates that ketones can influence cancer development and metastasis, cardiac metabolic and structural remodeling, physical performance, vascular function, inflammation, and the aging process. Emerging evidence from preclinical and early-phase clinical studies suggests that strategies such as ketone salts, ketone esters, and the ketogenic diet may offer therapeutic benefits for conditions like heart failure, acute cardiac injury, diabetic cardiomyopathy, vascular complications, atherosclerosis, hypertension, and aortic aneurysm. This literature review updates the current understanding of ketone metabolism and its contributions to cardiovascular health and diseases. We highlight the underlying molecular mechanism with post-translational modification known as β-hydroxybutyrylation, which affects the fate and function of target proteins. Additionally, we discuss the therapeutic challenges associated with ketone therapy, the potential of using ketone levels as biomarkers for cardiovascular diseases, as well as gender- and age-specific differences in ketone treatment. Finally, we explore future research directions and what is needed to translate these new insights into cardiovascular medicine. Full article

Background/Objectives: Intermittent fasting and ketogenic dietary approaches are increasingly investigated for their potential metabolic benefits in obesity. However, their long-term neuroendocrine effects—particularly those involving Orexin-A, a peptide implicated in energy regulation—remain poorly understood. The objective of this study was to compare the long-term metabolic, inflammatory, and orexinergic responses to different dietary strategies in adults with obesity. Methods: In this 12-month randomized, three-arm trial, 30 adults with obesity (BMI ≥ 30 kg/m²) were randomly assigned (1:1:1) to a hypocaloric ketogenic diet (KD), a 16:8 time-restricted eating regimen (TRF16:8), or a 5:2 intermittent fasting protocol (ADF5:2). Anthropometric parameters, body composition, fasting glucose, lipid profile, inflammatory cytokines (CRP, IL-6, TNF-α, IL-10), and plasma Orexin-A levels were assessed at baseline and every 3 months. Dietary adherence was monitored through structured logs and monthly assessments. Statistical analyses included repeated-measures models with sensitivity analyses adjusted for age and sex. Results: All participants completed the intervention. The ketogenic diet produced the largest sustained reductions in BMI, fat mass, fasting glucose, and total cholesterol over 12 months. TRF16:8 elicited more rapid early metabolic improvements and showed the most consistent longitudinal increase in Orexin-A levels. The ADF5:2 protocol resulted in moderate improvements across outcomes. In all groups, increases in Orexin-A were associated with markers of improved metabolic flexibility and reduced inflammation; however, mediation analyses were exploratory and non-causal. Between-group differences remained significant for fat mass, glucose, and Orexin-A trajectories after correction for multiple comparisons. Conclusions: The ketogenic diet was associated with the most pronounced long-term metabolic improvements, whereas 16:8 time-restricted eating yielded faster early responses and the most stable enhancement in Orexin-A levels. These findings indicate distinct metabolic and neuroendocrine adaptation profiles across dietary strategies. Given the small sample size, results should be interpreted cautiously, and larger trials are warranted to clarify the role of Orexin-A as a potential biomarker of dietary response in obesity. Full article

Background: Metabolic syndrome (MetS) is a multifactorial condition characterized by insulin resistance, dyslipidemia, hypertension, and central obesity, and is strongly influenced by lifestyle factors. Growing evidence highlights the gut microbiota as a key mediator linking diet and physical exercise to cardiometabolic health. Objective: This narrative review aims to qualitatively synthesize current evidence on the effects of physical exercise and major dietary patterns including the Mediterranean diet (MedDiet), Dietary Approaches to Stop Hypertension (DASH), and ketogenic/very-low-calorie ketogenic diets (KD/VLCKD) on gut microbiota composition and function, and their implications for metabolic health in MetS. Methods: A qualitative narrative synthesis of experimental, observational, and interventional human and animal studies was performed. The reviewed literature examined associations between structured physical exercise or dietary interventions and changes in gut microbiota diversity, key bacterial taxa, microbial metabolites, and cardiometabolic outcomes. Considerable heterogeneity across studies was noted, including differences in populations, intervention duration and intensity, dietary composition, and microbiota assessment methodologies. Results: Across human interventional studies, moderate-intensity physical exercise was most consistently associated with increased gut microbial diversity and enrichment of short-chain fatty acid (SCFA)-producing taxa, contributing to improved insulin sensitivity and reduced inflammation. MedDiet and DASH were generally linked to favorable microbiota profiles, including increased abundance of Faecalibacterium prausnitzii, Akkermansia muciniphila, and Bifidobacterium, alongside reductions in pro-inflammatory metabolites such as lipopolysaccharides and trimethylamine N-oxide. In contrast, KD and VLCKD were associated with rapid weight loss and glycemic improvements but frequently accompanied by reductions in SCFA-producing bacteria, depletion of Bifidobacterium, and markers of impaired gut barrier integrity, raising concerns regarding long-term microbiota resilience. Conclusions: Lifestyle-based interventions exert diet- and exercise-specific effects on the gut microbiota–metabolism axis. While MedDiet, DASH, and regular moderate physical activity appear to promote sustainable microbiota-mediated cardiometabolic benefits, ketogenic approaches require careful personalization, limited duration, and medical supervision. These findings support the integration of dietary quality, exercise prescription, and individual microbiota responsiveness into translational lifestyle strategies for MetS prevention and management. Full article

Background: Pharmacotherapy is the therapeutic mainstay in epilepsy, but in about 30% of patients, the epilepsy is pharmacoresistant. A ketogenic diet (KD) is an alternative therapeutic option. The mechanisms underlying the anti-seizure effect of KD are not fully understood. An enhanced energy metabolism may have a protective effect; C8 and C10 fatty acids were previously shown to activate mitochondrial function in vitro. In the present study, we investigated whether ß-hydroxybutyrate (HOB), C8, C10 or a combination of C8 and C10 fatty acids, which all increase under KD, could activate mitochondrial respiratory chain enzymes in murine hippocampal neurons (HT22). Methods: Cells were incubated for one week in the presence of the different metabolites. Respiratory chain enzyme activities as well as citrate synthase as a mitochondrial marker enzyme were determined spectrophotometrically in these cells. We observed that enzyme activities of complexes I and III, II and III, and IV (cytochrome c-oxidase) and V (ATP synthase) significantly increased in response to incubation with C8 and C10 fatty acids and a combination of both. Results: This activation of the respiratory chain enzymes was not inferior to an incubation with HOB, the key metabolite in KD. The activity of the mitochondrial marker enzyme citrate synthase increased under incubation with the fatty acids, showing that the mitochondrial content increased. Conclusions: In murine hippocampal cells, C8, C10 and combined C8 and C10 fatty acids led to variable increases in activities of mitochondrial respiratory chain enzymes and citrate synthase. This indicates that both C8 and C10 fatty acids may be important for the antiepileptic effect of KD, as they enhance energy production. Full article

Cystinosis is a rare lysosomal storage disorder characterized by defective cystine transport and progressive multi-organ damage, with the kidney being the primary site of pathology. In addition to the traditional perspective on lysosomal dysfunction, recent studies have demonstrated that cystinosis exerts a substantial impact on cellular energy metabolism, with a particular emphasis on oxidative pathways. Mitochondria, the central hub of ATP production, exhibit structural abnormalities, impaired oxidative phosphorylation, and increased reactive oxygen species. These factors contribute to proximal tubular cell failure and systemic complications. This review highlights the critical role of energy metabolism in cystinosis and supports the emerging idea of organelle communication. A mounting body of evidence points to a robust functional and physical association between lysosomes and mitochondria, facilitated by membrane contact sites, vesicular trafficking, and signaling networks that modulate nutrient sensing, autophagy, and redox balance. Disruption of these interactions in cystinosis leads to defective mitophagy, accumulation of damaged mitochondria, and exacerbation of oxidative stress, creating a vicious cycle of energy failure and cellular injury. A comprehensive understanding of these mechanisms has the potential to reveal novel therapeutic avenues that extend beyond the scope of cysteamine, encompassing strategies that target mitochondrial health, enhance autophagy, and restore lysosome–mitochondria communication. Full article

Background: Standard ketogenic diets (KD) and fish oil have established efficacy for drug-resistant epilepsy (DRE), but adherence and variability remain challenging. Objective: The objective of this study is to provide the first systematic evaluation of clinical evidence for emerging dietary interventions for epilepsy—specifically those other than standard KD and fish oil—and to rigorously evaluate their effectiveness and certainty of evidence to address the current gap in dietary management literature. Unlike prior reviews focused on standard KD or carbohydrate-modified versions, this study is the first to synthesize evidence for “non-standard” interventions—including olive oil-based KDs, probiotics, and restrictive gluten/glutamate-free diets—which are typically excluded from traditional dietary meta-analyses. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Web of Science, Cochrane, and Google Scholar up to March 2025. Randomized Controlled Trials (RCTs) and Non-Randomized Studies of Interventions (NRSIs) were included, with quality assessed using RoB 2 and ROBINS-I tools. Results: Eight studies (total n = 675) were identified, comprising 2 RCTs and 6 NRSIs. These included olive oil-based KDs (n = 1), probiotic/synbiotic supplementation (n = 2), medium-chain triglyceride (MCT) additions (n = 2), and gluten-free (n = 1) or glutamate-free (n = 1) diets. Evidence quality is generally low, with 75% of studies at high risk of bias. Preliminary responder rates reached 83.1% in uncontrolled olive oil-based KD studies, whereas the only RCT evaluating a low-glutamate diet showed no significant seizure reduction (p = 0.57). Conclusion: Evidence for emerging dietary interventions beyond standard KD is nascent and of low certainty. Interpretation: While preliminary signals exist for olive oil-based KDs and probiotics, current data are insufficient for clinical recommendation; this review identifies these as promising exploratory targets requiring validation through rigorous, blinded RCTs. Full article

This narrative review explores the impact of diet and physical exercise both as a risk factor of central nervous system inflammatory diseases, but more importantly as potential adjunctive disease modifiers in Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorders (NMOSD), and Myelin Oligodendrocyte Glycoprotein (MOG) antibody-associated disease (MOGAD). The majority of evidence relies on MS preclinical and clinical studies, but preclinical studies also support the benefit of lifestyle intervention in NMOSD and MOGAD. In MS, adherence to healthy diets (particularly Mediterranean and MIND diets) could lead to a milder disease course with reduced relapse rates, while structured exercise from early disease stages promotes neuroprotection by upregulating neurotrophic factors and preserving brain volume, possibly impacting disease progression. The ketogenic diet and intermittent caloric restriction also showed promising results. Physical activity, including both aerobic training and resistance training, emerges as a potential disease-modifying strategy by promoting neuroprotection, reducing inflammation, and supporting functional and cognitive outcomes, particularly when implemented early in the disease course. A synergistic approach alongside disease-modifying treatments (DMTs) would further positively modulate core pathological processes. Evidence for NMOSD and MOGAD warrants further investigation. We highlight that integrating personalized lifestyle strategies would be beneficial from the early stages. However, future large-scale, standardized trials are required to fully confirm the neuroprotective potential of diet and exercise across the entire spectrum of CNS disorders. Full article

Background/Objectives: The over 100-year-old practice of using ketogenic diet (KD) in the treatment of epilepsy has consolidated its position as an effective therapeutic tool. The available publications suggest a significant influence of KD on gut microbiome and metabolome and, on the other hand, a correlation between microbiome and metabolome changes and the course of epilepsy. The conclusion is therefore justified that KD can exert a therapeutic effect in epilepsy through the mechanism of gut microbiome and metabolome modulation. Methods:This article is a narrative review aimed at a comprehensive analysis of the literature to gather existing evidence on the relationship between ketogenic diet, its antiepileptic effects and modulation of gut microbiome and metabolome. Results: It has been demonstrated that a ketogenic diet exerts a significant effect on intestinal bacteria and their metabolites, among other actions, increasing the Bacteroides to Firmicutes (B/F) ratio, alleviating dysbiosis, reducing the inflammatory condition in the gut and whole body, increasing the number of specific strains associated with antiepileptic effect, mediating the production of neurotransmitters (GABA, serotonin), exerting influence on the dopaminergic system, on a number of metabolic pathways, on inhibition of genotoxicity and production of short-chain fatty acids (SCFA) in the intestine. Conclusions: Further studies are needed, since the effect of KD on gut microbiome and metabolome modulation in the treatment of epilepsy is an extremely promising and trendsetting direction of research. Full article

Introduction: Refractory Status Epilepsy Syndrome is a heterogeneous group of diseases associated with status epilepsy. Literature and definition have been conflicting and confusing in terms of their nomenclatures. New-onset refractory status epilepticus (NORSE) is a syndrome characterized by new onset refractory seizures in a previously health child. Febrile infection-related epilepsy syndrome (FIRES) is a similar syndrome now considered a variant of NORSE and is defined as a febrile event taking place between twenty-four hours and two weeks prior to the commencement of refractory status epilepticus. An autoimmune or inflammatory etiology is often implied in both conditions because infection is rarely identified. Aim: This review provides an update on hypotheses, etiology, pathophysiology, clinical features, diagnosis, laboratory evaluation, treatment, and perspectives for NORSE/FIRES. Methods: A PubMed Clinical Queries search is performed using keywords of NORSE and FIRES, on human subjects up to May 2025. All reviews, systematic reviews, case series and case reports were included. Results: Seizures are typically recalcitrant in NORSE/FIRES. Treatments include anti-seizure medications (ASM), ketogenic diet, immunotherapy (intravenous immunoglobulin ± plasmapheresis ± corticosteroid). The prognosis is usually poor. Most children would suffer refractory epilepsy and associated cognitive impairment if they survived. Guidelines and new consensus on NORSE/FIRES terminology have aided clinicians in managing status epilepticus in a previously healthy child that occurs ± a minor febrile episode. When an autoimmune or paraneoplastic condition is subsequently identified, the condition will be named accordingly. Conclusions: NORSE and FIRES are similar conditions except that vagus nerve stimulation appears to be more efficacious in NORSE than FIRES. We propose to define these heterogeneous and confusing conditions as “NOSES” as a two-criteria syndrome: New Onset + Status Epilepticus Syndrome, lasting for over 24 h despite the use of two standard ASM. Autoimmune, paraneoplastic and infectious encephalitis are specific diagnoses of NOSES with etiology subsequently identified. Full article

Cancer remains a leading global cause of morbidity and mortality. Modifiable lifestyle factors, including avoidance of tobacco use and excessive ultraviolet radiation, healthy dietary patterns, regular physical activity, and weight management, play key roles in prevention and care. This narrative review synthesizes evidence on lifestyle-based interventions influencing cancer risk, treatment tolerance, and survivorship. A literature search was conducted in PubMed and Scopus, supplemented by manual screening via Google Scholar. The time frame (2001–2025) was selected to reflect evidence produced within the modern era of molecular oncology and contemporary lifestyle medicine research. Eligible publications addressed carcinogen exposure (tobacco, alcohol, ultraviolet radiation), diet and nutritional strategies, physical activity, sedentary behavior, obesity, metabolic health, complementary therapies, and cancer outcomes. Evidence indicates that reducing exposure to tobacco and ultraviolet radiation remains central to cancer prevention. Adherence to predominantly plant-based diets, regular physical activity, and maintenance of healthy body weight are consistently associated with lower incidence of several cancers, including breast, colorectal, and liver cancer. Nutritional strategies such as caloric restriction, ketogenic diets, and fasting-mimicking diets show promise in improving treatment efficacy and quality of life. Complementary and mind–body therapies may alleviate treatment-related symptoms, although high-quality evidence on long-term safety and effectiveness is limited. Integrating lifestyle medicine into oncology offers a cost-effective, sustainable strategy to reduce cancer burden and enhance survivorship. Comprehensive programs combining carcinogen avoidance, dietary regulation, structured exercise, and effective radiation risk mitigation may extend healthspan, improve treatment tolerance, and help prevent recurrence. Full article

Background and Objectives: Infantile spasms (ISs), or West syndrome (WS), represent an early-onset epileptic encephalopathy in which diverse structural, genetic, metabolic, infectious, and neurocutaneous conditions converge on a shared pattern of hypsarrhythmia, clustered spasms, and later developmental impairment. Growing use of genomic diagnostics has revealed that variants in STXBP1, KCNQ2, GRIN2A, GRIN2B, and TSC-related genes are more common than previously recognized and can be linked to partially actionable pathways. This review aimed to synthesize current evidence on the multifactorial etiology, network-based pathogenesis, and evolving targeted therapies for ISs, with particular attention to TSC-related forms. Materials and Methods: A structured narrative review was undertaken of publications from 1990 to 2025 in PubMed, Scopus, Web of Science, and Embase using terms related to ISs, WS, genetics, mTOR, ACTH, vigabatrin, ketogenic diet, and precision therapies. Authoritative guidance from ILAE and AAN was incorporated. Clinical, molecular, and therapeutic data were grouped under etiological, pathogenetic, and management domains. Results: Structural causes remained the largest group, but combined genetic, genetic–structural, and metabolic etiologies accounted for about one third of contemporary cohorts. Early network disruption involving cortex, thalamus, basal ganglia, and brainstem, together with imbalances in NGF, BDNF, and IGF-1, explained why distinct primary insults produce a uniform electroclinical phenotype. Early treatment with ACTH or high dose prednisolone, with or without vigabatrin, was consistently associated with higher electroclinical remission and better developmental outcome. Everolimus and related mTOR inhibitors showed benefit in TSC-associated ISs, while agents directed at NMDA receptors or KCNQ channels are emerging for genotype defined subgroups. Conclusions: ISs should be approached as a heterogeneous but mechanistically convergent disorder in which rapid diagnosis, parallel genetic testing, and early disease modifying therapy improve prognosis. Integration of molecular profiling with standardized outcome monitoring is likely to move management from symptomatic seizure control to pathway-specific intervention. Full article

Introduction: Nutrition plays a fundamental role in sports performance by influencing energy availability, recovery, and training adaptation. In recent years, different dietary strategies have gained popularity among athletes, although the evidence supporting their efficacy is inconsistent. Objective: This consensus document, developed under the auspices of the Spanish Society of Nutrition, aims to provide a critical overview of the most relevant nutritional strategies currently used in sports and to offer evidence-based practical recommendations for both professional and recreational athletes, coaches, and health professionals. Methods: A narrative review was conducted following standardized scientific procedures by a multidisciplinary panel of experts. The analyzed strategies included high-carbohydrate, low-carbohydrate, ketogenic, intermittent fasting, plant-based, Paleolithic, and carbohydrate periodization diets. Each strategy was assessed based on its physiological rationale, evidence of performance in endurance, strength/power, sprint, aesthetic, weight category, and team sports, practical applications, and potential risks. Results: The available evidence shows that no single dietary strategy can be universally recommended for all athletes. High carbohydrate availability remains the most consistent approach for sustaining performance in endurance and high-intensity efforts. Low-carbohydrate and ketogenic diets enhance fat oxidation but often compromise exercise economy at competitive intensity levels. Intermittent fasting may improve body composition and metabolic health; however, it requires careful adaptation. Well-planned plant-based diets can support performance, although attention to certain nutrients (e.g., B12, iron, and omega-3) is essential. Paleolithic diets improve metabolic parameters but show limited direct evidence of athletic performance. Carbohydrate periodization is a promising tool for combining metabolic adaptations with competitive demands. Conclusions: Nutritional strategies should be individualized according to the athlete’s sport, training phase, and personal context. Professional guidance is crucial for minimizing risks and optimizing benefits. Further well-designed, long-term studies on athletes are needed to resolve the current controversies. Full article

The ketogenic diet (KD) is a metabolic intervention characterized by high fat and very low carbohydrate intake, showing significant metabolic, neuroprotective, and therapeutic effects. However, its efficacy varies widely due to individual genetic and epigenetic factors. This review synthesizes current knowledge of genes most strongly associated with KD response, including polymorphisms in FTO, APOA2, PPAR, SCN1A, KCNQ2, STXBP1, CDKL5, the MODY gene group, and SLC2A1, which shape outcomes across lipid metabolism, energy expenditure, inflammation, and neurotransmission. Epigenomic modifications induced by a KD, such as changes in DNA methylation and histone acetylation involving BDNF, SLC12A5, KLF14, and others, modulate functional metabolic and neurological effects. Sex and age further modulate KD effects through distinct patterns of gene activation and hormonal interactions. These variables together impact metabolic and neurological outcomes and are critical for developing personalized nutrition and disease management strategies. Based on the reviewed evidence, genetic and epigenetic profiling can help identify patients who are likely to benefit from a KD (e.g., GLUT1DS, PDH deficiency) and those in whom a KD may be ineffective or harmful (e.g., SCOT or SLC2A1-independent defects). The review concludes that genetic and epigenetic profiling is recommended for personalized dietary interventions. Full article

Background/Objectives: Dietary patterns play a crucial role in musculoskeletal health; however, the effects of different diets on bone mineral density (BMD), fracture risk, and bone metabolism remain inconsistent across studies. This systematic review and meta-analysis aimed to evaluate the impact of Mediterranean, calorie restriction, high-protein, low-carbohydrate, and ketogenic diets on skeletal outcomes in adults. Methods: A comprehensive search of PubMed/MEDLINE, CENTRAL, and Web of Science was conducted for studies published between January 2000 and June 2025. Eligible randomised controlled trials (RCTs) and cohort studies involving adults (≥18 years) and reporting outcomes related to BMD, fractures, bone turnover markers, and vitamin D or calcium status were included. Risk of bias was assessed using the Cochrane’s Risk of Bias tool for RCTs and the Joanna Briggs Institute checklist for observational studies. Random-effects meta-analyses were performed for outcomes reported by ≥3 comparable studies, presenting standardised mean differences (SMDs) for BMD and hazard ratios (HRs) for fractures. Results: Thirty studies met inclusion criteria, comprising 14 RCTs and 16 observational studies with over 500,000 participants. Pooled analyses showed no significant differences in BMD at the femoral neck (SMD = 0.12, 95% CI −0.80 to 1.04), lumbar spine (SMD = 0.04, 95% CI: −1.12 to 1.03), total hip (SMD = −0.07, 95% CI −0.36 to 0.21), or whole body (SMD = 0.03, 95% CI −0.07 to 0.14) across diet categories. However, adherence to a Mediterranean diet was associated with a significantly reduced hazard of hip and overall fractures (pooled HR = 0.95, 95% CI 0.93–0.96). Calorie restriction consistently increased bone resorption markers, whereas Mediterranean and high-protein diets showed neutral or modestly favourable effects. Vitamin D and calcium status were minimally affected across interventions. Conclusions: While dietary patterns exert diverse effects on skeletal health, consistent evidence supports Mediterranean-style diets as protective against fractures. Calorie restriction may elevate bone turnover, whereas ketogenic and high-protein diets show mixed effects on bone. However, across all analyses, high heterogeneity was observed. Further high-quality RCTs are warranted to clarify these relationships and inform dietary guidance for bone health. Full article