Advances in Ketogenic Diet Therapies in Pediatric Epilepsy: A Systematic Review.

Objective: To review the effects of the ketogenic diet on epilepsy in children and adolescents.Data Sources: A literature search was conducted in PubMed with no publication date or language restrictions based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. Keywords used included children, adolescent, ketogenic diet, epilepsy, and seizure.Study Selection: After excluding articles that did not meet the inclusion criteria, such as missing variables of study, adult population, and nonrandomized clinical trials, a total of 12 studies were included in the final review.Data Extraction: Data on study design, duration, sample size, population, and type of intervention were collected using a standard template.Results: The ketogenic diet and its modified versions were noted to have beneficial effects in reduction of seizure frequency and severity, with manageable adverse effects such as gastrointestinal disturbances, dehydration, dyslipidemia, hyperuricemia, infection, and metabolic acidosis.Conclusions: Depending on patient compliance and comorbidities, all variations of the ketogenic diet were found to be helpful for seizure treatment, whether as an additive or an alternative treatment option, for children and adolescents with epilepsy.Prim Care Companion CNS Disord 2024;26(3):23r03661. Author affiliations are listed at the end of this article.

Metagenomic and metabolomic analysis showing the adverse risk-benefit trade-off of the ketogenic diet.

BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity. METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents. RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity. CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.

An open-label, randomized controlled trial to assess a ketogenic diet in critically ill patients with sepsis.

Patients with sepsis experience metabolic and immunologic dysfunction that may be amplified by standard carbohydrate-based nutrition. A ketogenic diet (KD) may offer an immunologically advantageous alternative, although clinical evidence is limited. We conducted a single-center, open-label, randomized controlled trial to assess whether a KD could induce stable ketosis in critically ill patients with sepsis. Secondary outcomes included assessment of feasibility and safety of KD, as well as explorative analysis of clinical and immunological characteristics. Forty critically ill adults were randomized to either a ketogenic or standard high-carbohydrate diet. Stable ketosis was achieved in all KD patients, with significant increases in ß-hydroxybutyrate levels compared with controls [mean difference 1.4 milimoles per liter; 95% confidence interval (CI): 1.0 to 1.8; P < 0.001). No major adverse events or harmful metabolic side effects (acidosis, dysglycemia, or dyslipidemia) were observed. After day 4, none of the patients in the KD group required insulin treatment, whereas in the control group, insulin dependency ranged between 35% and 60% (P = 0.009). There were no differences in 30-day survival, but ventilation-free [incidence rate ratio (IRR) 1.7; 95% CI: 1.5 to 2.1; P < 0.001], vasopressor-free (IRR 1.7; 95% CI: 1.5 to 2.0; P < 0.001), dialysis-free (IRR 1.5; 95% CI: 1.3 to 1.8; P < 0.001), and intensive care unit-free days (IRR 1.7; 95% CI: 1.4 to 2.1; P < 0.001) were higher in the ketogenic group. Next-generation sequencing of CD4+/CD8+ T cells and protein analyses showed reduced immune dysregulation, with decreased gene expression of T-cell activation and signaling markers and lower pro-inflammatory cytokine secretion. This trial demonstrated the safe induction of a stable ketogenic state in sepsis, warranting larger trials to investigate potential benefits in sepsis-related organ dysfunction.

Effects of a Ketogenic Diet on Body Composition in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial.

This study investigates the effects of a ketogenic low-carbohydrate high-fat (LCHF) diet on body composition in healthy, young, normal-weight women. With the increasing interest in ketogenic diets for their various health benefits, this research aims to understand their impact on body composition, focusing on women who are often underrepresented in such studies. Conducting a randomized controlled feeding trial with a crossover design, this study compares a ketogenic LCHF diet to a Swedish National Food Agency (NFA)-recommended control diet over four weeks. Seventeen healthy, young, normal-weight women adhered strictly to the provided diets, with ketosis confirmed through blood ß-hydroxybutyrate concentrations. Dual-energy X-ray absorptiometry (DXA) was utilized for precise body composition measurements. To avoid bias, all statistical analyses were performed blind. The findings reveal that the ketogenic LCHF diet led to a significant reduction in both lean mass (-1.45 kg 95% CI: [-1.90;-1.00]; p < 0.001) and fat mass (-0.66 kg 95% CI: [-1.00;-0.32]; p < 0.001) compared to the control diet, despite similar energy intake and physical activity levels. This study concludes that while the ketogenic LCHF diet is effective for weight loss, it disproportionately reduces lean mass over fat mass, suggesting the need for concurrent strength training to mitigate muscle loss in women following this diet.

The Liver Circadian Metabolic Homeostasis Influence by Combining Ketogenic Diet with Exercise.

The ketogenic diet (KD) and regular exercise (EX) are both capable of orchestrating circadian metabolism homeostasis during losing weight. However, the combined effects of these two factors on circadian metabolism remain poorly understood. To determine if the combined treatment yields a superimposed physiological phenotype, we measured weight loss, white adipose, the respiratory exchange ratio (RER), heat production, and activity parameters in individual and combined treatment groups. Surprisingly, none of these metrics displayed a cumulative effect when administered in the combined treatment approach. Additionally, we investigated the impact of combination therapy on molecular homeostasis through using high-throughput liver transcriptomic approaches. The results revealed that individual and combined treatments can reprogram the circadian rhythm; yet, the combined group exhibited a minimum quantity of cyclic transcript genes. Noteworthy, the amplitude of 24 h circadian expression genes was not significantly increased in the combination treatment, indicating that the combined approach has non-overlapping effects on maintenance peripheral metabolism homeostasis. This may be due to the liver requiring less ketogenic and gluconeogenic potential during metabolic processes. This research suggests that combined treatment may have adverse effects on the body's homeostasis and provide crucial insights for the homeostatic health of athletes or individuals who wish to lose weight.

A Multi-Omics Approach to Disclose Metabolic Pathways Impacting Intestinal Permeability in Obese Patients Undergoing Very Low Calorie Ketogenic Diet.

A very low calorie ketogenic diet (VLCKD) impacts host metabolism in people marked by an excess of visceral adiposity, and it affects the microbiota composition in terms of taxa presence and relative abundances. As a matter of fact, there is little available literature dealing with microbiota differences in obese patients marked by altered intestinal permeability. With the aim of inspecting consortium members and their related metabolic pathways, we inspected the microbial community profile, together with the set of volatile organic compounds (VOCs) from untargeted fecal and urine metabolomics, in a cohort made of obese patients, stratified based on both normal and altered intestinal permeability, before and after VLCKD administration. Based on the taxa relative abundances, we predicted microbiota-derived metabolic pathways whose variations were explained in light of our cohort symptom picture. A totally different number of statistically significant pathways marked samples with altered permeability, reflecting an important shift in microbiota taxa. A combined analysis of taxa, metabolic pathways, and metabolomic compounds delineates a set of markers that is useful in describing obesity dysfunctions and comorbidities.

Anticancer restrictive diets and the risk of psychological distress: Review and perspectives.

INTRODUCTION: The most studied anticancer restrictive diets include fasting, fasting-mimicking diets (FMDs) and ketogenic diets (KDs). Besides the current lack of established clinical benefit and the significant risk of malnutrition and micronutrient deficiencies, dietary restrictions in cancer patients might have relevant psychological effects. MATERIALS AND METHODS: We reviewed the randomized and non-randomized controlled clinical trials (CCTs) reporting data on the psychological impact of fasting, FMDs and KDs in cancer patients. We excluded trials on restrictive diets performed for weight reduction in obese or overweight patients, studies on dietary restrictions lasting less than 24 h, and studies on fasting related to cultural or religious beliefs. RESULTS: Three CCTs on fasting or FMDs and eight CCTs on KDs in cancer patients were included. In terms of diet-related distress, emotional, social, and family well-being, none of these studies showed a detrimental impact of fasting, FMDs and KDs. However, clinical trials specifically assessing the psychological aspects in the long term are lacking. CONCLUSIONS AND PERSPECTIVES: In the absence of a conclusive evidence on the clinical benefits of restrictive diets, which carry significant risks especially if unsupervised, further studies are needed to clarify their psychological impact in cancer patients. Multidisciplinary approaches including psychological evaluations should be used to ameliorate patient selection for clinical trials, identify early distress symptoms, and increase patient compliance to dietary recommendations.

Ketogenic diet therapy leads to antiseizure medication reduction in children and adults with drug-resistant epilepsy.

AIMS: This study aimed to evaluate the safety of reducing or withdrawing anti-seizure medications (ASMs) in a cohort comprising both adults and children with drug-resistant epilepsy (DRE) undergoing ketogenic diet therapy (KDT). METHODS: We conducted a comprehensive analysis of clinical profiles in adults and children with DRE who had adhered to KDT for at least 6 months. Successful withdrawal or reduction of an ASM was defined as discontinuation or dose reduction without subsequent resumption or increase and without initiation of any new ASM throughout the entire follow-up period. Changes in the ASM load were calculated specifically for adult patients. RESULTS: The study enrolled 56 participants (34 children and 22 adults) with DRE, with 64.3% achieving successful withdrawal of at least one ASM. The probability of ASM withdrawal remained consistent for children (64.7%) versus adults (63.6%), as well as for responders (62.5%) versus non-responders (68.8%), and it was not associated with other clinical factors. Early ASM reduction (including withdrawal) after diet initiation occurred in 15 patients (26.8%), with treatment outcomes comparable to those of the remaining participants. Among the 22 adults, the mean values of ASM load reduced by 24.5%, with a similar magnitude observed for responders (24.2%) versus non-responders (25.1%). In addition, adults tend to have a slower elevation in serum ketone levels compared to children. CONCLUSION: This study demonstrates the safe achievability of ASM withdrawal through KDT in most patients with DRE, irrespective of age or seizure frequency reduction.

Metabolic Effects of Ketogenic Diets: Exploring Whole-Body Metabolism in Connection with Adipose Tissue and Other Metabolic Organs.

The ketogenic diet (KD) is characterized by minimal carbohydrate, moderate protein, and high fat intake, leading to ketosis. It is recognized for its efficiency in weight loss, metabolic health improvement, and various therapeutic interventions. The KD enhances glucose and lipid metabolism, reducing triglycerides and total cholesterol while increasing high-density lipoprotein levels and alleviating dyslipidemia. It significantly influences adipose tissue hormones, key contributors to systemic metabolism. Brown adipose tissue, essential for thermogenesis and lipid combustion, encounters modified UCP1 levels due to dietary factors, including the KD. UCP1 generates heat by uncoupling electron transport during ATP synthesis. Browning of the white adipose tissue elevates UCP1 levels in both white and brown adipose tissues, a phenomenon encouraged by the KD. Ketone oxidation depletes intermediates in the Krebs cycle, requiring anaplerotic substances, including glucose, glycogen, or amino acids, for metabolic efficiency. Methylation is essential in adipogenesis and the body's dietary responses, with DNA methylation of several genes linked to weight loss and ketosis. The KD stimulates FGF21, influencing metabolic stability via the UCP1 pathways. The KD induces a reduction in muscle mass, potentially involving anti-lipolytic effects and attenuating proteolysis in skeletal muscles. Additionally, the KD contributes to neuroprotection, possesses anti-inflammatory properties, and alters epigenetics. This review encapsulates the metabolic effects and signaling induced by the KD in adipose tissue and major metabolic organs.

Investigating the Effectiveness of a Carb-Free Oloproteic Diet in Fibromyalgia Treatment.

Fibromyalgia (FM), a chronic disease with a high incidence in women, poses a significant challenge for diagnosis and treatment, especially due to the absence of specific biomarkers and the multifaceted nature of its symptoms, which range from neuromuscular pain to mood disorders and intestinal dysbiosis. While diagnosis currently relies on rheumatological clinical evaluations and treatment options mainly focus on symptom management, FM seems to have possible links with systemic metabolic dysfunctions with a common inflammatory root. In this context, a new therapeutic avenue emerges: could a therapeutic nutritional approach be the missing piece of the puzzle? Indeed, diet therapies employed particularly for metabolic syndromes proved recently to be efficacious for correcting systemic dysmetabolism and a high number of chronic inflammation conditions. In particular, the very-low-calorie ketogenic diet (VLCKD) demonstrated therapeutic benefits in many disorders. In the present study, we aimed to investigate the specific effects of two dietary interventions, namely the oloproteic VLCKD and the low-glycemic insulinemic (LOGI) diet, on two groups of female FM patients (FM1 and FM2) over a 45-day period. Utilizing clinical and laboratory tests, as well as non-invasive NMR metabolomic analysis of serum, urine, and saliva samples, we sought to uncover how these dietary regimens impact the metabolic dysfunctions associated with FM.

Simplification of Dietary Treatment in Pharmacoresistant Epilepsy: Impact of C8 and C10 Fatty Acids on Sirtuins of Neuronal Cells In Vitro.

Pharmacotherapy is the therapeutic mainstay in epilepsy; however, in about 30% of patients, epileptic seizures are drug-resistant. A ketogenic diet (KD) is an alternative therapeutic option. The mechanisms underlying the anti-seizure effect of a KD are not fully understood. Epileptic seizures lead to an increased energy demand of neurons. An improvement in energy provisions may have a protective effect. C8 and C10 fatty acids have been previously shown to activate mitochondrial function in vitro. This could involve sirtuins (SIRTs) as regulatory elements of energy metabolism. The aim of the present study was to investigate whether ß-hydroxybutyrate (ßHB), C8 fatty acids, C10 fatty acids, or a combination of C8 and C10 (250/250 µM) fatty acids, which all increase under a KD, could up-regulate SIRT1, -3, -4, and -5 in HT22 hippocampal murine neurons in vitro. Cells were incubated for 1 week in the presence of these metabolites. The sirtuins were measured at the enzyme (fluorometrically), protein (Western blot), and gene expression (PCR) levels. In hippocampal cells, the C8, C10, and C8 and C10 incubations led to increases in the sirtuin levels, which were not inferior to a ßHB incubation as the 'gold standard'. This may indicate that both C8 and C10 fatty acids are important for the antiepileptic effect of a KD. A KD may be replaced by nutritional supplements of C8 and C10 fatty acids, which could facilitate the diet.

Do Popular Diets Impact Fertility?

Infertility affects 15% of the population in developed countries, and its prevalence is increasing. Fertility can be influenced by different factors. Although key factors like maternal age cannot be changed, there is growing evidence that other modifiable factors, such as diet, can have an impact on fertility. Diet has become increasingly important in recent years for a number of reasons: the new trend toward a healthy lifestyle, the higher prevalence of certain digestive disorders, a lack of time that leads people to consume more prepared and processed food, and personal choice to not eat meat, among others. To meet these needs, several diets have recently become popular, such as the Mediterranean diet, known as the gold standard of health; the DASH diet, known for preventing hypertension; the Western diet, characterized by processed food; the ketogenic diet, characterized by low carbohydrate intake; and the vegetarian diet, which is the choice for people who do not eat meat or animal by-products. Diets present a unique composition characterized by the presence or absence of specific nutrients, which have also been associated with male and female fertility individually. This review assesses the impact of these diets and of macro- and micronutrients on both female and male fertility.

The Assessment of the Efficacy, Safety, and Challenges of Ketogenic Diet Therapy in Children with Epilepsy: The First Experience of a Single Center.

Background and Objectives: Ketogenic diet therapy (KDT) has been used as a non-pharmacological treatment for childhood refractory epilepsy. Its efficacy and safety have been described in numerous studies and reviews. However, there have been fewer studies evaluating the challenges experienced by patients and their family members when starting KDT. When implementing a new treatment method, challenges arise for both the healthcare professionals and patients, making it important to summarize the initial results and compare them with the experiences of other centers. To analyze and evaluate the efficacy and safety of KDT in children with epilepsy, as well as to consider the challenges faced by their parents/caregivers. Materials and Methods: A retrospective analysis of patients' data (N = 30) and an analysis of the completed questionnaires of the parents/caregivers (N = 22) occurred. Results: In the study group, 66.7% of the patients had a >50% decrease in seizure frequency, and 2/3 of them had a >90% decrease in seizure frequency or were seizure-free, which enabled reducing the anti-seizure medications in 36.4% of the patients, as well as reducing the hospital visits. Cognitive improvement and better alertness were subjectively reported by 59.1% of the parents/caregivers. No dangerous long-term adverse effects of KDT have been observed in the study group. The patients with generalized epilepsy experienced significantly more adverse events. Most of the adverse effects of KDT were related to the digestive system, but usually they were temporary and controllable. The challenges of the parents/caregivers were mostly related to social life issues and financial difficulties; the medical-related challenges were minimal. Conclusions: KDT is an effective and safe treatment option for children with drug-resistant epilepsy, and the challenges faced by families are resolvable. In order to ensure effective KDT, a multidisciplinary team is required. This would ensure smooth and comprehensive care and the timely resolution of emerging problems. The cooperation of the families undergoing KDT is also important, enabling them to share their experiences.

International society of sports nutrition position stand: ketogenic diets.

POSITION STATEMENT: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the use of a ketogenic diet in healthy exercising adults, with a focus on exercise performance and body composition. However, this review does not address the use of exogenous ketone supplements. The following points summarize the position of the ISSN.1. A ketogenic diet induces a state of nutritional ketosis, which is generally defined as serum ketone levels above 0.5 mM. While many factors can impact what amount of daily carbohydrate intake will result in these levels, a broad guideline is a daily dietary carbohydrate intake of less than 50 grams per day.2. Nutritional ketosis achieved through carbohydrate restriction and a high dietary fat intake is not intrinsically harmful and should not be confused with ketoacidosis, a life-threatening condition most commonly seen in clinical populations and metabolic dysregulation.3. A ketogenic diet has largely neutral or detrimental effects on athletic performance compared to a diet higher in carbohydrates and lower in fat, despite achieving significantly elevated levels of fat oxidation during exercise (~1.5 g/min).4. The endurance effects of a ketogenic diet may be influenced by both training status and duration of the dietary intervention, but further research is necessary to elucidate these possibilities. All studies involving elite athletes showed a performance decrement from a ketogenic diet, all lasting six weeks or less. Of the two studies lasting more than six weeks, only one reported a statistically significant benefit of a ketogenic diet.5. A ketogenic diet tends to have similar effects on maximal strength or strength gains from a resistance training program compared to a diet higher in carbohydrates. However, a minority of studies show superior effects of non-ketogenic comparators.6. When compared to a diet higher in carbohydrates and lower in fat, a ketogenic diet may cause greater losses in body weight, fat mass, and fat-free mass, but may also heighten losses of lean tissue. However, this is likely due to differences in calorie and protein intake, as well as shifts in fluid balance.7. There is insufficient evidence to determine if a ketogenic diet affects males and females differently. However, there is a strong mechanistic basis for sex differences to exist in response to a ketogenic diet.

Imaging brain glucose metabolism in vivo reveals propionate as a major anaplerotic substrate in pyruvate dehydrogenase deficiency.

A vexing problem in mitochondrial medicine is our limited capacity to evaluate the extent of brain disease in vivo. This limitation has hindered our understanding of the mechanisms that underlie the imaging phenotype in the brain of patients with mitochondrial diseases and our capacity to identify new biomarkers and therapeutic targets. Using comprehensive imaging, we analyzed the metabolic network that drives the brain structural and metabolic features of a mouse model of pyruvate dehydrogenase deficiency (PDHD). As the disease progressed in this animal, in vivo brain glucose uptake and glycolysis increased. Propionate served as a major anaplerotic substrate, predominantly metabolized by glial cells. A combination of propionate and a ketogenic diet extended lifespan, improved neuropathology, and ameliorated motor deficits in these animals. Together, intermediary metabolism is quite distinct in the PDHD brain-it plays a key role in the imaging phenotype, and it may uncover new treatments for this condition.

Sex-dependent effects of carbohydrate source and quantity on caspase-1 activity in the mouse central nervous system.

BACKGROUND: Mounting evidence links glucose intolerance and diabetes as aspects of metabolic dysregulation that are associated with an increased risk of developing dementia. Inflammation and inflammasome activation have emerged as a potential link between these disparate pathologies. As diet is a key factor in both the development of metabolic disorders and inflammation, we hypothesize that long term changes in dietary factors can influence nervous system function by regulating inflammasome activity and that this phenotype would be sex-dependent, as sex hormones are known to regulate metabolism and immune processes. METHODS: 5-week-old male and female transgenic mice expressing a caspase-1 bioluminescent reporter underwent cranial window surgeries and were fed control (65% complex carbohydrates, 15% fat), high glycemic index (65% carbohydrates from sucrose, 15% fat), or ketogenic (1% complex carbohydrates, 79% fat) diet from 6 to 26 weeks of age. Glucose regulation was assessed with a glucose tolerance test following a 4-h morning fast. Bioluminescence in the brain was quantified using IVIS in vivo imaging. Blood cytokine levels were measured using cytokine bead array. 16S ribosomal RNA gene amplicon sequencing of mouse feces was performed to assess alterations in the gut microbiome. Behavior associated with these dietary changes was also evaluated. RESULTS: The ketogenic diet caused weight gain and glucose intolerance in both male and female mice. In male mice, the high glycemic diet led to increased caspase-1 biosensor activation over the course of the study, while in females the ketogenic diet drove an increase in biosensor activation compared to their respective controls. These changes correlated with an increase in inflammatory cytokines present in the serum of test mice and the emergence of anxiety-like behavior. The microbiome composition differed significantly between diets; however no significant link between diet, glucose tolerance, or caspase-1 signal was established. CONCLUSIONS: Our findings suggest that diet composition, specifically the source and quantity of carbohydrates, has sex-specific effects on inflammasome activation in the central nervous system and behavior. This phenotype manifested as increased anxiety in male mice, and future studies are needed to determine if this phenotype is linked to alterations in microbiome composition.

Efficacy and tolerability of classical and polyunsaturated fatty acids ketogenic diet in controlling paediatric refractory epilepsy - A randomized study.

OBJECTIVES: To measure and compare the efficacy and tolerability of a classical ketogenic diet (CKD) and a polyunsaturated fatty acids ketogenic diet (PUFAKD) in managing childhood refractory epilepsy. Efficacy was assessed by measuring the change in seizure frequency at 3, 6, 9, and 12 months within and between groups. The percentage reduction in seizures at <50 %, 50-90 %, >90 %, and 100 % was also measured. Tolerability was assessed and compared by recording adverse events - vomiting, nausea, lethargy, and constipation. METHODS: 52 children, aged 2-10 years, were randomized, 25 in the CKD group and 27 in the PUFAKD group. Fat: carbohydrate + protein ratio of 2.2:1-4:1 was maintained in both diets; the PUFAKD group only used unsaturated fats with an omega 3: omega 6 ratio of 1:2.8. Ketone levels were measured using keto-dipsticks, with 4+ and 4++ (80-160 mg/dL) being the most optimal values. RESULTS: A significant decrease (p=0.001) in seizures was observed (n=52), with no significant difference (p=0.537) between the two groups. The mean seizure reduction was 71.1 %, with no significant difference (p=0.488) in both groups. The mean compliance rate was 78.3 % (n=52). A statistically significant linear trend existed between a higher compliance rate and a greater reduction in seizures (p = 0.042, Z=4.039) among all children (n=52). Nausea (p=0.033) and vomiting (p=0.014) occurred more in PUFAKD than in CKD. CONCLUSION: No significant difference was seen in seizure reduction between the two groups. Compliance correlates with a greater seizure reduction. Despite similar seizure reduction rates, the novel PUFAKD exhibited poorer compliance and more pronounced adverse effects compared to CKD. CKD remained a superior choice over the novel PUFAKD in the management of paediatric refractory epilepsy. More controlled trials with varying PUFA compositions are recommended for long-term evaluations.

ChREBP plays a pivotal role in the nutrient-mediated regulation of metabolic gene expression in brown adipose tissue.

AIMS: Carbohydrate-responsive element-binding protein (ChREBP) is a transcription factor that regulates several metabolic genes, including the lipogenic enzymes necessary for the metabolic conversion of carbohydrates into lipids. Although the crucial role of ChREBP in the liver, the primary site of de novo lipogenesis, has been studied, its functional role in adipose tissues, particularly brown adipose tissue (BAT), remains unclear. In this study, we investigated the role of ChREBP in BAT under conditions of a high-carbohydrate diet (HCD) and ketogenic diet (KD), represented by extremely low carbohydrate intake. MAIN METHODS: Using an adeno-associated virus and Cas9 knock-in mice, we rapidly generated Chrebp brown adipocyte-specific knock-out (B-KO) mice, bypassing the necessity for prolonged breeding by using the Cre-Lox system. KEY FINDINGS: We demonstrated that ChREBP is essential for glucose metabolism and lipogenic gene expression in BAT under HCD conditions in Chrebp B-KO mice. After nutrient intake, Chrebp B-KO attenuated the KD-induced expression of several inflammatory genes in BAT. SIGNIFICANCE: Our results indicated that ChREBP, a nutrient-sensing regulator, is indispensable for expressing a diverse range of metabolic genes in BAT.

Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signaling pathway in aging mice.

Aging compromises brain function leading to cognitive decline. A cyclic ketogenic diet (KD) improves memory in aged mice after long-term administration; however, short-term effects later in life and the molecular mechanisms that govern such changes remain unclear. Here, we explore the impact of a short-term KD treatment starting at elderly stage on brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings reveal that KD improves working memory and hippocampal LTP. Furthermore, the synaptosome proteome of aged mice fed a KD long-term evidence changes predominantly at the presynaptic compartment associated to the protein kinase A (PKA) signaling pathway. These findings were corroborated in vivo by western blot analysis, with high BDNF abundance and PKA substrate phosphorylation. Overall, we show that a KD modifies brain function even when it is administered later in life and recapitulates molecular features of long-term administration, including the PKA signaling pathway, thus promoting synaptic plasticity at advanced age.