Ketogenic diet (KD) therapy is effective for refractory epilepsy but significantly impacts carbohydrate and lipid metabolism. We previously encountered a patient who developed diabetes during KD; metabolic abnormalities were undetected by conventional criteria for diabetes, suggesting standard criteria are inapplicable. This study aimed to establish specialized metabolic reference ranges for patients on KD. We retrospectively analyzed laboratory data from 18 pediatric patients with refractory epilepsy treated with KD. Geometric means and reference ranges (mean ± 2SD) were calculated using mixed-effects models to account for repeated measures. Before KD, geometric means (reference ranges) were: random plasma glucose (RPG), 96.7 (79.1-118.3) mg/dL; HbA1c (NGSP), 4.76% (4.22-5.36); HbA1c (IFCC), 29 (23-35) mmol/mol; total cholesterol (T-Cho), 159.1 (98.8-256.5) mg/dL; and triglycerides (TG), 107.3 (41.4-277.8) mg/dL. During KD, values were: RPG, 77.6 (59.8-100.6) mg/dL; HbA1c (NGSP), 4.09% (3.58-4.69); HbA1c (IFCC), 21 (16-28) mmol/mol; T-Cho, 184.5 (113.3-300.7) mg/dL; and TG, 155.5 (48.2-501.7) mg/dL. Multiple mixed-effects models showed that KD significantly lowered HbA1c and RPG but increased T-Cho, HDL-Cho, TG, and free fatty acids. Changes in LDL-Cho were not statistically significant. KD therapy significantly lowers HbA1c and RPG while increasing lipid profiles. Consequently, impaired glucose tolerance may be masked by "normal" values if conventional criteria are used. To avoid delayed diagnosis, patients on KD should be evaluated using specialized reference ranges specific to their dietary therapy. The online version contains supplementary material available at 10.1007/s13340-026-00906-5.

Ketogenic diet modulates AMPK-mTOR pathway in breast cancer.

Ketogenic diet attenuates late gestational sleep deprivation-induced aggression in adult offspring mice.

SLC6A1-Related Neurodevelopmental Disorder: A Scoping Review of Clinical Features and Emerging Therapeutic Strategies.

Emerging evidence suggests dietary interventions regulate inflammatory signaling through gut microbiome modulation, yet their therapeutic potential in radiation-induced intestinal injury (RIII) remains underexplored. This study demonstrates that ketogenic diet (KD), a high-fat and low-carbohydrate dietary regimen, exerts protective effects against RIII through dual mechanisms involving microbial regulation and inflammatory pathway inhibition. Using high-salt diet (HSD) as a dietary control, KD significantly attenuated intestinal inflammation by downregulating pro-inflammatory cytokines while enhancing barrier integrity through tight junction protein upregulation in radiation-exposed murine model. 16S rDNA sequencing showed KD enriched Akkermansia and reduced Enterobacteriaceae, whereas HSD exhibited inverse patterns. Mechanistically, RNA sequencing revealed that KD uniquely suppressed the JAK2/STAT3 pathway in RIII mice. In vitro studies demonstrated that β-hydroxybutyrate, a key ketone metabolite, effectively suppressed RORγt expression and subsequent downregulation of IL-17A gene transcription via the inhibition of JAK2/STAT3 pathway, thus mitigate inflammatory damage. Fecal microbiota transplantation validated that KD-modified microbiome directly inhibited JAK2/STAT3 signaling activation, as well as the downregulation of RORγt and IL-17A. These findings establish KD as a promising dietary strategy mitigate acute RIII through synergistic modulation of gut microbiota and inflammatory signaling, providing novel insights into nutritional approaches targeting microbial-host crosstalk in radiation injury.

The progression of various devastating metabolic syndromes like diabetes, metabolic dysfunction-associated fatty liver disease (MAFLD), obesity, etc., is due to the inappropriate lifestyle with respect to the consumption of high-fat and high glycemic index (GI) products. The epidemiological data revealed that the prevalence of metabolic disorders is increasing gradually and will create a global burden. According to reports, the global prevalence of MAFLD in people with Type 2 diabetes mellitus (T2DM) is between 50% and 75%, with 12.5%–87.5% in India. The culprit dietary components, which have a high GI (potatoes, rice, high-sugar beverages, candies and pastries, white bread, etc.), and high-fat diet products (trans fatty acids, sucrose, fructose, high cholesterol, etc.), act significantly in the pathogenesis underlying liver-related complications and further trigger the other secondary metabolic complications. These inappropriate dietary interventions lead to alteration of different pathways like fibroblast growth factor 10 (FGF10), AMP-activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK) pathways, etc., which directly trigger the other secondary pathways leading to diabetes-associated MAFLD and liver-related complications. There are numerous dietary interventions (Vitamin D-rich diet, soy isoflavones, ketogenic diet, unsaturated fatty acid diet, low-carbohydrate diet, green leafy vegetables, etc.), which may improve the various molecular pathways and help in normalizing the pathological state of liver-compromised subjects. In the present review, the new dietary interventions are discussed, which help in managing the diabetes-associated metabolic disorders.

The ketogenic diet (KD) is widely used in disease management and healthy populations, but its long-term physiological safety remains unclear. While KD protects against kidney injury in models, its effects on healthy renal tissue are poorly understood. Two-sample Mendelian randomization (MR) analyzed causality between serum 3-hydroxybutyrate (BHB) and renal injury. Mice underwent 3-month KD, short-term BHB gavage, or time-restricted feeding (tRF). Renal histology, fibrosis, and partial epithelial-mesenchymal transition (pEMT) were assessed. RNA sequencing identified pathways, validated in HK-2 cells. Genetically elevated serum BHB was causally linked to higher renal injury risk. In healthy mice, long-term KD induced renal interstitial fibrosis and maladaptive repair of renal tubular epithelial cells (TECs), characterized by partial EMT, while short-term BHB gavage or tRF reproduced early pro-fibrotic changes (partial EMT and increased fibronectin/collagen I expression) without establishing overt fibrosis. In contrast, in mice with unilateral ischemia-reperfusion injury (UIRI), both BHB and tRF reduced renal damage, renal interstitial collagen deposition and maladaptive repair of TECs. Mechanically, KD upregulated Wnt8b and Junb in healthy kidneys, and BHB treatment promoted β-catenin nuclear translocation in a Wnt8b-dependent manner. Knockdown of Wnt8b or Junb suppressed BHB-induced partial EMT in HK-2 cells. Notably, BHB oppositely regulated Wnt8b in injured kidneys, where it attenuated injury-driven Wnt8b elevation. Ketosis exhibits a dichotomous renal role: promoting fibrosis through Wnt8b/Junb mediated partial EMT in healthy tissue, while protecting against injury-induced fibrosis. These findings emphasize the context-dependence of KD and caution against its long-term use in healthy individuals.

Redox coupling of lactate and β-hydroxybutyrate: An inter-organ circuit linking metabolic flexibility, mitochondrial adaptation, and disease.

Ketogenic diets (KDs) modulate brain function, but how their fatty acid composition impacts behavior remains poorly understood. Male Wistar rats were fed a control diet (CD, n = 6), a classic ketogenic diet (CKD, n = 6) rich in saturated fatty acids (SAFAs), or a modified ketogenic diet (MKD, n = 6) enriched with polyunsaturated fatty acids (PUFAs) and DHA. After 100days, both KDs induced similar ketosis and increased brain glucose metabolism (1⁸F-FDG PET/CT), while reducing some cerebral pro-inflammatory cytokines (IL-1β, IL-6) and oxidized LDL. Notably, the CKD group exhibited an anxiety-like phenotype in the Elevated Plus Maze versus controls, significantly reducing open arm entries [1.58(0.60) vs. 5.08(1.03); p = 0.025], increasing closed arm time [3.33min(0.22) vs. 1.70min(0.19); p = 0.001], and elevating the Anxiety Index [0.92(0.04) vs. 0.70(0.07); p = 0.048], which correlated with SAFA incorporation in the frontal lobe. In contrast, the MKD group did not induce this anxiety-like effect, maintaining behavioral parameters comparable to the CD group, while showing an intense incorporation of omega-3 fatty acids and DHA in the hippocampus. These findings demonstrate that the behavioral divergence between KDs occurred despite shared reductions in the specific neuroinflammatory and oxidative markers evaluated. Overall, our results suggest that the dietary fatty acid profile, rather than the magnitude of systemic ketosis level, plays a critical role in modulating behavioral outcomes under ketogenic conditions.

Epilepsy syndromes are clinically defined by their specific set of features, including seizure types, age at onset, electroencephalographic patterns, and prognosis. For example, autosomal-dominant lateral temporal lobe epilepsy (ADLTE) is a well-recognized epilepsy syndrome associated with heterozygous leucine-rich glioma inactivated-1 (LGI1) gene variants. Relatedly, developmental and epileptic encephalopathies (DEEs) are a diverse group of severe, childhood-onset epilepsy syndromes associated with developmental impairments. While DEEs are often associated with a genetic etiology, ADLTE does not usually present as a DEE spectrum. A 7-month-old girl, born to consanguineous parents, developed drug-resistant epilepsy from the neonatal period. She had recurrent multifocal seizures, progressing to refractory status epilepticus despite multiple antiseizure medications and ketogenic diet. She also had profound global developmental delay, suggestive of a DEE. Whole-exome sequencing revealed a homozygous pathogenic variant (c.1438C>T p.Gln480Ter) in the LGI1 gene. Both unaffected parents and 2 other affected family members were found to carry the variant in the heterozygous state. This homozygous variant was predicted to cause our patient's aggressive epilepsy phenotype because heterozygous carriers typically exhibit only benign, pharmacoresponsive seizures. The patient succumbed to aspiration pneumonitis and septic shock at 7 months of age. This case, along with supporting data from animal models, suggests a critical role for LGI1 in neurodevelopment and seizure control. In addition to highlighting the severe consequences of homozygous LGI1 loss of function, it underscores the importance of genetic counseling. Especially among consanguineous families, the potential for worsening phenotype with homozygosity should be discussed.

Methionine-supplemented longevity diet increases growth hormone, GLP-1, and FGF21; reduces frailty; and promotes healthspan.

Ketogenic diet therapy in pyruvate dehydrogenase deficiency: Global clinical practice from literature and survey data.

Myelin alterations, tightly linked to axonal degeneration, are common in neurodegenerative diseases, including multiple sclerosis (MS). However, the metabolic mechanisms that sustain white matter integrity remain elusive. Monocarboxylates are important energy fuels, but their role in myelinating oligodendrocyte function remains unclear. Here, we show that myelinating oligodendrocytes express high affinity monocarboxylate transporter 2 (MCT2), which is downregulated in progressive MS. While deletion of MCT2 in the mouse spinal white matter using oligodendrotropic AAV injection does not affect oligodendrocyte survival, it downregulates lipid synthesis-associated enzymes and increases inflammation, leading to a failure of myelin maintenance. These changes, not evidenced in AAV-control mice that only show mild inflammation, are accompanied by axonal upregulation of lactate dehydrogenase A and injury, effects alleviated by ketogenic diet. Therefore, our findings show that oligodendroglial MCT2 regulates myelin maintenance and axonal support under mild inflammation. This appears disrupted in progressive MS but might be compensated for by specific metabolic therapies to preserve white matter integrity.

Critical illness leads to profound metabolic, neuroendocrine and immune disorders that affect the prognosis of patients treated in intensive care units (ICUs). The ketogenic diet, a high-fat and low-carbohydrate eating model, is gaining increasing importance as a potential metabolic intervention in the ICU. Preliminary data suggest that the ketogenic diet (KD) may support the control of seizures in a super-refractive epileptic state (SRSE), stabilize glycemia, reduce insulin demand, and modulate the immune response in sepsis. The aim of this review was to present a synthetic presentation of the current state of knowledge regarding use of the KD in intensive care patients. The review was carried out in accordance with the guidelines of the Joanna Briggs Institute and PRISMA-ScR. PubMed, Scopus, EBSCO, Web of Science, Google Scholar and Cochrane Library databases were searched (10-19 April 2026) using the Population-Concept-Context model. Full-text observational studies, randomized trials and reviews of the use of KDs in ICU patients were included. Data extraction was performed independently by two reviewers. Of the 42 publications identified, seven studies were included in the analysis. The KD was feasible and safe in both critically ill adults and children. In SRSE, most patients achieved stable ketosis within a few days, which often allowed for reduction or discontinuation of anesthetics. In sepsis, the KD led to glycemic stabilization, reduced insulin demand and reduced immune deregulation; in one study, "after day 4, none of the patients in the KD group required insulin treatment." The KD also showed beneficial effects on cellular bioenergetics and mitochondrial function. The safety profile was acceptable and adverse reactions were manageable with appropriate monitoring. The KD represents a promising, non-pharmacological metabolic intervention in intensive care, particularly in the treatment of SRSE and in the stabilization of glucose metabolism in sepsis and other critical conditions. Despite the growing number of positive clinical observations, the available evidence remains limited due to small samples, heterogeneous protocols, and a lack of randomized trials. Further, well-designed prospective studies are needed to determine optimal KD implementation protocols and identify the patient populations that benefit most.

Effect of the ketogenic diet on absence seizures in rats with genetic absence epilepsy.

Diet is a priority to the kidney community, with increasing interest in whether a ketogenic diet can slow autosomal dominant polycystic kidney disease (ADPKD) progression. People with ADPKD have unique nutritional requirements that need to be considered when designing a ketogenic diet for this population. The nutritional adequacy of an ADPKD ketogenic diet needs to be evaluated prior to testing in a clinical trial. The current paper describes the (i) development of an ADPKD-Keto meal plan, in addition to modified PKD-Keto diets targeting the risk of nephrolithiasis and hyperkalemia, (ii) nutritional adequacy of these diets compared to a reference chronic kidney disease (CKD) diet, and (iii) cost-analysis of PKD-Keto meal plans and CKD reference meal plans. Dietary guidelines for ADPKD, CKD and general healthy eating were used to develop ketogenic meal plans for people living with ADPKD. All meal plans were analyzed for energy, macronutrient and micronutrient content, and results were compared to dietary intake targets. Caloric and macronutrient targets were achieved, with total carbohydrate, total fat and protein meeting 10%, 75% and 15% of total caloric intake, respectively across PKD-Keto meal plans. Micronutrients were mostly adequate in all meal plans except for iodine in the PKD-Keto meal plans; iron for females aged 19-50; and zinc for males. PKD-Keto diet meal plans were slightly higher in cost, however there was no difference based on socioeconomic area. A well-planned ketogenic diet tailored for ADPKD can be nutritionally adequate with supplementation of iodine, iron and zinc to be considered if the diet is to be used for an extended period.

Cancer cells require large quantities of glucose to ensure sufficient ATP production through glycolysis, and the liver may facilitate this glucose supply. A high-fat low-carbohydrate ketogenic diet (KD) could represent a strategy to reduce tumor growth. However, the molecular effects of carbohydrate restriction mediated by the KD and its hepatic impact remain poorly understood. To address this question, 6-week-old FVB/N-Tg(MMTV-PyVT)634Mul/J mice, which develop spontaneous mammary tumors, were fed a standard chow diet (SD group) or a KD diet (KD group) until reaching the age of 12 weeks. The effects of carbohydrate restriction were assessed by plasma analyses, as well as histological staining, RT-qPCR and Western Blotting in tumors and liver. We found that carbohydrate restriction reduced tumor growth by 46% and was associated with decreased expression of pro-tumorigenic factors (Ang2, Hgf, Mki67). Moreover, a decrease of metabolic enzymes (Pfk, Bdh1, Scot1) highlighted the lack of metabolic flexibility of the tumor cells and underscored their strong dependency on glucose. Conversely, the liver exhibited a strong adaptive response with enhanced ketogenesis and gluconeogenesis, evidenced by elevated blood glucose and upregulation of Pepck, Foxo1, and CREB. A high-fat, low-carbohydrate diet exerts a dual metabolic effect: it suppresses tumor progression through local metabolic reprogramming but simultaneously enhances hepatic glucose production. This highlights the pivotal role of systemic glucose availability in tumorigenesis and underscores the need to consider liver metabolism when designing dietary interventions for cancer therapy.

Ketogenic diet as a metabolic vehicle enhancing the therapeutic efficacy of mebendazole and devimistat in juvenile syngeneic high-grade glioma.

Febrile infection-related epilepsy syndrome (FIRES) mainly affects previously healthy children and adolescents, often leading to severe neurological impairment and long-term sequelae such as drug-resistant epilepsy and cognitive dysfunction. Based on two pediatric FIRES cases, combined with international and domestic guidelines as well as clinical experience, this paper highlights therapeutic strategies and escalation pathways tailored to different inflammatory phases in the acute and chronic stages. Incorporating continuous electroencephalogram monitoring and cerebrospinal fluid inflammatory cytokine profile changes, a phase-specific treatment approach is systematically described, centered on the rapid termination of status epilepticus, targeted cytokine immunotherapy, and multidisciplinary collaborative support, and the active use of tocilizumab, anakinra, and the ketogenic diet is emphasized, to provide practical guidance for clinicians in managing FIRES.

This study assessed changes in body composition and 24-h energy metabolism at 6 and 12 months after initiation of a 1-month very low-calorie ketogenic diet (VLCKD) in women with obesity. Seventeen women with obesity who completed a 1-month VLCKD underwent a 4-week transition phase with carbohydrate reintroduction, followed by a hypocaloric balanced diet. Assessments of body composition by dual-energy X-ray absorptiometry (DXA) and 24-h energy expenditure (24hEE) by a whole-room indirect calorimeter were performed. Following the initial 7% weight loss, body weight further decreased at 6 months (-3.9%, p < 0.05), primarily driven by a significant decrease in fat mass (-10%, p < 0.05). From 6 to 12 months, three participants continued to lose weight, whereas most remained stable or partially regained. Lean soft tissue, decreased during the VLCKD phase, remained stable throughout follow-up. Both 24hEE and 24-h sleeping metabolic rateexhibited a progressive trend toward increase. Minute-by-minute 24hEE trajectories revealed a significant increase in metabolic rate from 1 to 6 months (p < 0.001). The metabolic adaptation observed after 1 month of VLCKD was no longer detectable at either 6 or 12 months. These findings provide novel insight into the physiological adaptations following VLCKD, supporting its role in supervised weight loss programs for selected patients. ClinicalTrials.gov identifier: NCT07418281.