Search

Studies suggest that ketogenic diets (KD) may improve memory in mouse models of aging and Alzheimer's disease (AD). This study determined whether a continuous or intermittent KD (IKD) enhanced cognitive behavior in the TgF344-AD rat model of AD. At 6 months-old, TgF344-AD and wild-type (WT) littermates were placed on a control (CD), KD, or IKD (morning CD and afternoon KD) provided as two meals per day for 2 or 6 months. Cognitive and motor behavior and circulating β-hydroxybutyrate (BHB), AD biomarkers and blood lipids were assessed. Animals on a KD diet had elevated circulating BHB, with IKD levels intermediate to CD and KD. TgF344-AD rats displayed impaired spatial learning memory in the Barnes maze at 8 and 12 months of age and impaired motor coordination at 12 months of age. Neither KD nor IKD improved performance compared to CD. At 12 months of age, TgF344-AD animals had elevated blood lipids. IKD reduced lipids to WT levels with KD further reducing cholesterol below WT levels. This study shows that at 8 or 12 months of age, KD or IKD intervention did not improve measures of cognitive or motor behavior in TgF344-AD rats; however, both IKD and KD positively impacted circulating lipids.

Endurance exercise can disturb intestinal epithelial integrity, leading to increased systemic indicators of cell injury, hyperpermeability, and pathogenic translocation. However, the interaction between exercise, diet, and gastrointestinal disturbance still warrants exploration. This study examined whether a 6-day dietary intervention influenced perturbations to intestinal epithelial disruption in response to a 25-km race walk. Twenty-eight male race walkers adhered to a high carbohydrate (CHO)/energy diet (65% CHO, energy availability = 40 kcal·kg FFM−1·day−1) for 6 days prior to a Baseline 25-km race walk. Athletes were then split into three subgroups: high CHO/energy diet (n = 10); low-CHO, high-fat diet (LCHF: n = 8; <50 g/day CHO, energy availability = 40 kcal·kg FFM−1·day−1); and low energy availability (n = 10; 65% CHO, energy availability = 15 kcal·kg FFM−1·day−1) for a further 6-day dietary intervention period prior to a second 25-km race walk (Adaptation). During both trials, venous blood was collected pre-, post-, and 1 hr postexercise and analyzed for markers of intestinal epithelial disruption. Intestinal fatty acid-binding protein concentration was significantly higher (twofold increase) in response to exercise during Adaptation compared to Baseline in the LCHF group (p =.001). Similar findings were observed for soluble CD14 (p <.001) and lipopolysaccharide-binding protein (p =.003), where postexercise concentrations were higher (53% and 36%, respectively) during Adaptation than Baseline in LCHF. No differences in high CHO/energy diet or low energy availability were apparent for any blood markers assessed (p >.05). A short-term LCHF diet increased intestinal epithelial cell injury in response to a 25-km race walk. No effect of low energy availability on gastrointestinal injury or symptoms was observed. [ABSTRACT FROM AUTHOR]

• High-fat, low-carbohydrate ketogenic diet (KD) normalized amount and bandwidth of USVs in asocial BTBR mice. • KD improved USV temporal structure more effectively in juvenile than adult BTBR mice. • BTBR showed a different USV call type profile than age-matched C57BL/6J control mice. • BTBR mice seemed to exert a much simpler syllabic structure than C57BL/6J mice. • KD normalized call type usage more effectively in juvenile than in adult BTBR mice. Deficits in social communication and language development are a hallmark of autism spectrum disorder currently with no effective approaches to reduce the negative impact. Interventional studies using animal models have been very limited in demonstrating improved vocal communication. Autism has been proposed to involve metabolic dysregulation. Ketogenic diet (KD) is a metabolism-based therapy for medically intractable epilepsy, and its applications in other neurological conditions have been increasingly tested. However, how KD would affect vocal communication has not been explored. The BTBR mouse strain is widely used to model asocial phenotypes. They display robust and pronounced deficits in vocalization during social interaction, and have metabolic changes implicated in autism. We investigated the effects of KD on ultrasonic vocalizations (USVs) in juvenile and adult BTBR mice during male–female social encounters. After a brief treatment with KD, the number, spectral bandwidth, and much of the temporal structure of USVs were robustly closer to control levels in both juvenile and adult BTBR mice. Composition of call categories and transitioning between individual call subtypes were more effectively altered to more closely align with the control group in juvenile BTBR mice. Together, our data provide further support to the hypothesis that metabolism-based dietary intervention could modify disease expression, including core symptoms, in autism. Future studies should tease apart the molecular mechanisms of KD's effects on vocalization. [ABSTRACT FROM AUTHOR]

Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer's disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches. [ABSTRACT FROM AUTHOR]

Aim: To investigate the clinical characteristics of non‐epileptic seizures due to transient brain dysfunction caused by energy deficiency after prolonged fasting or exercise in individuals with glucose transporter type 1 deficiency syndrome (Glut1DS), and then elucidate further the seizure features to distinguish non‐epileptic seizures from epileptic seizures. Method: This retrospective case–control study included 57 non‐epileptic seizures and 23 epileptic seizures (control group) in 14 individuals (11 males, three females; aged 5–44 years, median = 20 years) with Glut1DS, all with a heterozygous pathogenic SLC2A1 mutation. Results: Non‐epileptic seizures were classified as paroxysmal altered consciousness (n = 8), movement disorders (n = 35) (eye‐head movements, ataxia, spasticity, weakness, involuntary movement), dysaesthesia (n = 8), and vomiting (n = 6) at the peak ages at onset of 5 to 10 years. Ketogenic diet therapy was effective in 33 of 43 (77%) non‐epileptic seizures. Providing supplementary food before high‐impact exercise or during attacks prevented or mitigated non‐epileptic seizures in some individuals. Glut1DS‐associated non‐epileptic seizures are fundamentally situation‐related seizures with specific provoking and ameliorating factors. Non‐epileptic seizures can be distinguished from epileptic seizures by the absence of complete consciousness loss and rapid postictal recovery despite prolonged seizures. Interpretation: Non‐epileptic seizures are not well recognized but require different therapeutic approaches compared to epileptic seizures. Awareness of the differentiation of non‐epileptic seizures from epileptic seizures is essential when performing preventive or therapeutic decision‐making for acute exacerbation seizures. What this paper adds: Non‐epileptic seizures are invariably situation‐related seizures.Non‐epileptic seizures were classified as altered consciousness, movement disorders, dysaesthesia, and vomiting.Non‐epileptic seizures were characterized by the absence of complete consciousness loss and were accompanied by rapid recovery.Non‐epileptic seizures can occur simultaneously or consecutively with another.Supplementary food can be effective in preventing the development of sustained exercise‐induced movement disorders. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is an effective treatment for epilepsy. In recent years, studies have shown favorable efficacy of KD in epilepsy from genetic disorders. In this study, we propose an approach to KD in monogenic epilepsy: we evaluate the utility of categorizing genetic variants based on rational associations with the known mechanisms of KD. Patients with monogenic epilepsy treated with KD were reviewed. The genetic etiologies were categorized into five groups: (1) conditions causing cellular energy impairment, (2) GABA-pathies, (3) mToR-pathies, (4) ion channelopathies, and (5) no known mechanisms associated with KD mechanisms. Treatment response was defined as a median reduction in seizure frequency of greater than 50%. Of 35 patients, 24 (69%) were responders at three months. Based on categories, Group 1 had the highest response rate with seven of seven (100%), followed by Group 2, six of seven (86%), and Group 3, two of three (67%). Patients in Groups 4 and 5 had poorer responses with three of seven (43%) and four of 11 (36%) response rates, respectively (P < 0.01). Median percentage of seizure reduction showed Group 1 with the highest reduction of 97.5%, Group 2 at 94%, and Groups 3, 4, and 5 at 62.5%, 30%, and 40%, respectively (P = 0.036). Our findings show a favorable response to KD in patients with monogenic epilepsy (69% at three months) with the highest response in patients with conditions involving cellular energy impairment and GABA-pathies. The KD, therefore, should be considered early in patients with monogenic epilepsy, especially those involving genes associated with cellular energy impairment or GABA-pathies. [ABSTRACT FROM AUTHOR]

The ketogenic diet or exogenous supplementation with 3-hydroxybutyrate (3HB) is progressively gaining recognition as a valuable therapeutic or health intervention strategy. However, the effects of 3HB on cancers have been inconsistent in previous studies. This study aimed to comprehensively investigate the causal effects of circulating 3HB levels on 120 cancer phenotypes, and explore the 3HB mediation effect between liver fat accumulation and cancers. Univariate Mendelian randomization (UVMR) was used in this study to investigate the causal impact of circulating 3HB levels on cancers. We conducted meta-analyses for 3HB-cancer associations sourced from different exposure data. In multivariate MR(MVMR), the body mass index, alcohol frequency and diabetes were included as covariates to investigate the independent effect of 3HB on cancer risk. Additionally, utilizing mediation MR analysis, we checked the potential mediating role of 3HB in the association between liver fat and cancer. Integrating findings from UVMR and MVMR, we observed that elevated circulating 3HB levels were associated with reduced risk of developing diffuse large B-cell lymphoma(DLBCL) (OR[95%CI] = 0.28[0.14–0.57] p = 3.92e-04), biliary malignancies (OR[95%CI] = 0.30[0.15–0.60], p = 7.67e-04), hepatocellular carcinoma(HCC) (OR[95%CI] = 0.25[0.09–0.71], p = 9.33e-03), primary lymphoid and hematopoietic malignancies (OR[95%CI] = 0.76[0.58–0.99], p = 0.045). Further UVMR analysis revealed that an increase in the percent liver fat was associated with reduced 3HB levels (Beta[95%CI] = -0.073[-0.122∼-0.024], p = 0.0034) and enhanced susceptibility to HCC (OR[95%CI] = 13.9[9.76–19.79], p = 3.14e-48), biliary malignancies (OR[95%CI] = 4.04[3.22–5.07], p = 1.64e-33), nasopharyngeal cancer (OR[95%CI] = 3.26[1.10–9.67], p = 0.03), and primary lymphoid and hematopoietic malignancies (OR[95%CI] = 1.27[1.13–1.44], p = 1.04e-4). Furthermore, 3HB fully mediated the effect of liver fat on susceptibility to DLBCL (OR[95%CI] = 1.076[1.01–1.15], p = 0.034). Circulating 3HB is associated with a reduced susceptibility to developing DLBCL, HCC, biliary malignancies, and primary lymphoid and hematopoietic malignancies. The impaired ketogenesis induced by metabolic-dysfunction associated fatty liver disease (MAFLD) contributes to risk of DLBCL. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is a popular option for managing body weight, though its influence on glucose and lipid metabolism was still inconclusive. Gut microbiota is modulated by dietary pattens and has been associated with the changes of metabolic homeostasis induced by KD. Here, we found that two types of KDs, KD1 (8.8% carbohydrate, 73.4% fat, 17.9% protein, 5.7 kcal/g) and KD2 (0.4% carbohydrate, 93.2% fat, 6.4% protein, 6.7 kcal/g), induced changes of gut microbiota and its metabolites, contributing to glucose intolerance but not lipid accumulation in mice. Following a 2-week intervention with KDs, mice fed on KD1 displayed symptoms related to obesity, whereas KD2-fed mice exhibited a decrease in body weight but had severe hepatic lipid accumulation and abnormal fatty acid metabolism, while both KDs led to significant glucose intolerance. Compared to the mice fed on a standard chow diet, the conventional mice fed on both KD1 and KD2 had significant shifted gut microbiota, lower levels of short chain fatty acids (SCFAs) and composition alteration of cecal bile acids. By using an antibiotic cocktail (ABX) to deplete most of the gut microbiota in mice, we found the disturbances induced by KDs in lipid metabolism were similar in the ABX-treated mice to their conventional companions, but the disturbances in glucose metabolism were absent in the ABX-treated mice. In conclusion, these findings suggest that ketogenic diets disrupted glucose and lipid metabolism, at least in mice, and highlight the gut microbial culprits associated with KD induced glucose intolerance rather than lipid accumulation. [ABSTRACT FROM AUTHOR]

The article discusses a case of hypercalcaemia in a 16-year-old male with a complex medical history, including trisomy 21 and intractable epilepsy, who was on a ketogenic diet. The hypercalcaemia was managed with various treatments, including denosumab and bisphosphonates, before ultimately ceasing the ketogenic diet, which led to the normalization of calcium levels. The article highlights the challenges of managing hypercalcaemia in patients on a ketogenic diet and emphasizes the importance of monitoring serum calcium levels and renal function in such cases. [Extracted from the article]

Background: Considering differences in body composition and inflammatory status between sexes, as well as recent recommendations advocating for personalized dietary approaches, this study aimed to explore how sex influences weight loss, changes in body composition, and inflammatory status in subjects with grade I and II obesity undergoing a 45-day of the Very Low-Energy Ketogenic Therapy (VLEKT). Methods: Participants (21 premenopausal females and 21 males), included in the study adhered to the 45-day of the VLEKT and underwent assessments of anthropometric parameters (weight, height, body mass index—BMI –, and waist circumference), body composition via bioelectrical impedance analysis, and inflammatory status measured by high sensitivity C-reactive protein (hs-CRP) levels at baseline and post-intervention. Results: At baseline, premenopausal females and males did not differ in BMI (p = 0.100) and hs-CRP levels (p = 0.948). Males demonstrated overall larger benefits than premenopausal females from the VLEKT in terms of weight loss (Δ% = − 11.63 ± 1.76 vs − 8.95 ± 1.65 kg, p < 0.001), fat mass (Δ% = − 30.84 ± 12.00 vs -21.36 ± 4.65 kg, p = 0.002), and hs-CRP levels (Δ% = − 41.42 ± 21.35 vs − 22.38 ± 17.30 mg/L, p = 0.003). Of interest, in males phase angle values are statistically improved compared to female (Δ% = 17.11 ± 9.00 vs 7.05 ± 3.30°, p < 0.001). Conclusion: These findings underscore the importance of considering sex-specific responses in personalized obesity treatment strategies, particularly dietary interventions like VLEKTs. [ABSTRACT FROM AUTHOR]

ABSTRACT This study investigates diet quality across four popular dietary patterns: Ketogenic Diet, Low‐Carbohydrate Healthy‐Fat, Vegetarian, and Vegan, employing the NOVA and Human Interference Scoring System (HISS) classification systems. Utilizing a modified Food Frequency Questionnaire (FFQ) and analyzing 168 participants' dietary habits, the research identifies notable differences in dietary quality among the dietary patterns. While all groups reported lower consumption of UPFs than the general population, plant‐based diets demonstrated higher UPF consumption than ketogenic and low carbohydrate diets. The study reveals that both NOVA and HISS effectively identify UPFs, with significant differences observed at various processing levels, except for UPFs where both systems showed similarity. This research contributes to the detailed understanding of diet quality within popular dietary patterns, highlighting the importance of considering food processing in dietary choices and the need for ongoing research to further elucidate the health implications of different types of UPFs. [ABSTRACT FROM AUTHOR]

The article from eLife explores the impact of ketogenic diets on brain development, focusing on the role of PTEN mutations in neurodevelopmental disorders. Researchers found that exposure to ketone bodies early in development can mitigate neurological impairments in a nematode model with PTEN defects. The study sheds light on the link between PTEN, the balance of inhibitory and excitatory activity, and the potential neuroprotective effects of ketogenic diets, offering insights into human nervous system biology and conditions like autism spectrum disorder. [Extracted from the article]

Lysine β‐hydroxybutyrylation (Kbhb) is a post‐translational modification that has recently been found to regulate protein functions. However, whether and how protein Kbhb modification participates in Alzheimer's disease (AD) remains unknown. Herein, we carried out 4D label‐free β‐hydroxybutylation quantitative proteomics using brain samples of 8‐month‐old and 2‐month‐old APP/PS1 AD model mice and wild‐type (WT) controls. We identified a series of tricarboxylic acid (TCA) cycle‐associated enzymes including citrate synthase (CS) and succinate‐CoA ligase subunit alpha (SUCLG1), whose Kbhb modifications were decreased in APP/PS1 mice at pathological stages. Sodium β‐hydroxybutyrate (Na‐β‐OHB) treatment markedly increased Kbhb modifications of CS and SUCLG1 and their enzymatic activities, leading to elevated ATP production. We further found that Kbhb modifications at lysine 393 site in CS and at lysine 81 site in SUCLG1 were crucial for their enzymatic activities. Finally, we found that β‐OHB levels were decreased in the brain of APP/PS1 mice at pathological stages. While ketogenic diet not only significantly increased β‐OHB levels, Kbhb modifications and enzymatic activities of CS and SUCLG1, and ATP production, but also dramatically attenuated β‐amyloid plaque pathologies and microgliosis in APP/PS1 mice. Together, our findings indicate the importance of protein Kbhb modification for maintaining normal TCA cycle and ATP production and provide a novel molecular mechanism underlying the beneficial effects of ketogenic diet on energy metabolism and AD intervention. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Despite growing interest in the potential use of exogenous ketones for the treatment of epilepsy, their impact on seizures and the gut microbiome and mycobiome remain unclear.Here, we examined the effects of both oral gavage and subcutaneous (SC) injection of a ketone ester (KE) in spontaneously epileptic Kcna1‐null (KO) mice that model seminal aspects of human temporal lobe epilepsy. Electroencephalographic recordings and biochemical analyses were performed in KE‐treated KO mice. Fecal microbial and fungal communities were profiled to determine whether the antiseizure activity of KE involves changes in the gut microbiome.We found that exogenous KE administration by SC injection was more effective than oral gavage in terms of rendering antiseizure effects while generating similar degrees of ketonemia. However, reductions in mean daily seizure counts were accompanied by overall alterations in the fecal bacterial microbiome. Either oral or SC injection imposed a greater impact on the microbiome in male than female mice. In males, oral KE decreased Bacteroidota phylum and genera of Ligilactobacillus and Muribaculaceae, whereas SC injection decreased Bacteroides, Lactobacillus, and Lachnospiraceae. The fecal mycobiome was affected by KE injection to a greater degree than by oral gavage, and more in females than in males, as reflected by an increase in Ascomycota and Saccharomyces. Correlation analysis between microbiome and seizure counts revealed that in mice receiving KE injection, the seizure count was positively correlated with an amplicon sequencing variant of Lactobacillus (Spearman rho = .64, p = .03) and tended toward a negative correlation with Saccharomyces (Spearman rho = −.57, p = .057).Our findings demonstrate that exogenous ketone administration alone can induce antiseizure effects equally via different routes of administration, and that they induce differential shifts in both the bacterial microbiome and mycobiome. [ABSTRACT FROM AUTHOR]

While the macronutrient content of a ketogenic diet specifically utilized for childhood epilepsy is clearly defined in the literature, variations among other ketogenic diets exhibit substantial heterogeneity. Furthermore, studies utilizing ketogenic diets contain several confounders with notable impacts on outcomes, thereby rendering both their findings and those of the meta-analyses less reliable. The objective of this meta-epidemiological assessment was to scrutinize existing clinical trials that investigated the effects of ketogenic diets on patients with obesity and diabetes, thereby determining the feasibility of conducting a meta-analysis. The Ovid Medline, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases were searched from 1946 to 24 September 2024. Of the studies reviewed, none met the predefined inclusion criteria. However, seven articles met these criteria very closely. In the future, studies investigating the effects of ketogenic diets containing significant confounding factors should adopt a single definition of a ketogenic diet. Additionally, accurate measurement of actual macronutrient and caloric intake, along with regularly monitored nutritional ketosis, will be essential to highlight the true effects of a ketogenic diet. [ABSTRACT FROM AUTHOR]

Background: Due to the increasing prevalence of obesity and type 2 diabetes, effective dietary recommendations are needed. Previously, we developed the low-insulin method: by avoiding insulinogenic, i.e., insulin-release-triggering foods, insulin secretion becomes reduced, lipolysis is stimulated, and energy production is shifted to ketosis with excess ketone bodies exhaled in the form of acetone. Now, we investigate how quickly stable ketosis (defined as fasting breath acetone concentration ≥ 7.0 ppm) is achieved, whether and for how long a carbohydrate meal inhibits ketosis, and whether the responses differ in healthy adults with different insulin levels. Methods: An oral glucose tolerance test was conducted, and body composition and fasting insulin were determined at the beginning and end of the 14-day study. Participants (n = 10) followed a ketogenic diet and performed continuous glucose monitoring. Ketosis levels were determined by measuring breath acetone concentrations. On day 8, two white bread rolls with jam (72 g carbohydrates) were consumed for breakfast. Results: After seven days, all participants achieved stable ketosis (defined as fasting breath acetone concentration ≥ 7.0 ppm), which dropped from 8.2 to 5.7 ppm (p = 0.0014) after the carbohydrate meal. It took five days to achieve stable ketosis again. The stratification of participants into tertiles according to their fasting insulin levels demonstrated that individuals with low fasting insulin levels achieved stable ketosis again after two days and those with medium insulin levels after five days, while those with high baseline values did not reach stable ketosis by the end of the study. Conclusions: By carbohydrate restriction, stable ketosis can be achieved within one week. However, a single carbohydrate meal inhibits ketosis for several days. This effect is pronounced in individuals with elevated fasting insulin levels. [ABSTRACT FROM AUTHOR]

Background/Objectives: Elevating ketone levels with therapeutic nutritional ketosis can help to metabolically manage disease processes associated with epilepsy, diabetes, obesity, cancer, and neurodegenerative disease. Nutritional ketosis can be achieved with various dieting strategies such as the classical ketogenic diet, the modified Atkins diet, caloric restriction, periodic fasting, or the consumption of exogenous ketogenic supplements such as medium-chain triglycerides (MCTs). However, these various strategies can be unpleasant and difficult to follow, so that achieving and sustaining nutritional ketosis can be a major challenge. Thus, investigators continue to explore the science and applications of exogenous ketone supplementation as a means to further augment the therapeutic efficacy of this metabolic therapy. Methods: Here, we describe a structurally new synthetic triglyceride, glycerol tri-acetoacetate (Gly-3AcAc), that we prepared from glycerol and an acetoacetate precursor that produces hyperketonemia in the therapeutic range (2–3 mM) when administered to mice under both fasting and non-fasting conditions. Animal studies were undertaken to evaluate the potential effects of eliciting a ketogenic response systemically. Acute effects (24 h or less) were determined in male VM/Dk mice in both fasted and unfasted dietary states. Results: Concentration levels of β-hydroxybutyrate in blood were elevated (βHB; 2–3 mM) under both conditions. Levels of glucose were reduced only in the fasted state. No detrimental side effects were observed. Conclusions: Pending further study, this novel compound could potentially add to the repertoire of methods for inducing therapeutic nutritional ketosis. [ABSTRACT FROM AUTHOR]

Introduction: The application of ketogenic dietary interventions to mental health treatments is increasingly acknowledged within medical and psychiatric fields, yet its exploration in clinical psychology remains limited. This article discusses the potential implications of ketogenic diets, traditionally utilized for neurological disorders, within broader mental health practices. Methods: This article presents a perspective based on existing ketogenic diet research on historical use, biological mechanisms, and therapeutic benefits. It examines the potential application of these diets in mental health treatment and their relevance to clinical psychology research and practice. Results: The review informs psychologists of the therapeutic benefits of ketogenic diets and introduces to the psychology literature the underlying biological mechanisms involved, such as modulation of neurotransmitters, reduction of inflammation, and stabilization of brain energy metabolism, demonstrating their potential relevance to biopsychosocial practice in clinical psychology. Conclusion: By considering metabolic therapies, clinical psychologists can broaden their scope of biopsychosocial clinical psychology practice. This integration provides a care model that incorporates knowledge of the ketogenic diet as a treatment option in psychiatric care. The article emphasizes the need for further research and training for clinical psychologists to support the effective implementation of this metabolic psychiatry intervention. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder that significantly impacts patients' quality of life. Recent evidence has highlighted a complex relationship between the gut microbiota (GM) and PD. Understanding this relationship is crucial for potentially targeting GM in PD treatment and expanding therapeutic options. This study aimed to comprehensively analyze the global landscape, trends, and research focus on GM and PD using bibliometric analysis. Utilizing publications from the Web of Science Core Collection (WsSCC), bibliometric tools such as the R package 'Bibliometrix,' VOS viewer, and CiteSpace software were employed to assess parameters like yearly publications, countries/regions, institutions, and authors. Research trends and hotspots were identified through keyword analysis. The results revealed 1,161 articles published between 2013-2023, with China leading in publications (n=352, 30.31% of total), while the United States had a higher influence (Hindex= 58). The University of California System was the top institution in terms of publications (n=35), with the National Natural Science Foundation of China funding the most projects (n=172). Keshavarzian A and Sampson TR were the authors with the highest publication and co-citation counts, respectively. The International Journal of Molecular Sciences had the most articles published (n=48). Keyword analysis identified parkinson's disease, gut microbiota, shortchain fatty acids, inflammation, and probiotics as main research topics. Biomarkers, ketogenic diet, and NF-κB were recent research hotspots and trends (2021-2023). The current study conducts an objective and comprehensive analysis of these publications, identifying trends and hotspots in the field of research. The findings offer valuable insights to scholars globally and in-vestigate potential therapeutic strategies for Parkinson's Disease. [ABSTRACT FROM AUTHOR]

Objective: To identify key factors influencing the therapeutic efficacy of the ketogenic diet (KD) for children with drug‐resistant epilepsy and elucidate their interconnected relationships to optimize clinical practice. Methods: Participants were selected from children receiving KD treatment at West Second University Hospital of Sichuan University from September 2015 to October 2023. Clinical factors pre‐KD and post‐KD (at the third month) were analyzed systematically using an analytical framework. Descriptive analyses, univariate analyses, and multivariate regression analyses were performed for the entire cohort and subgroups of genetic and non‐genetic (i.e., structural and unknown) etiologies. Thereby, the most significant predictors were identified for each relevant dependent variable. Path analysis diagrams were used for visual representation. Results: Of 156 patients, genetic etiology was prevalent (38.5%). In the genetic subgroup, channelopathies predicted lower baseline seizure frequency and increased chance of seizure freedom with KD. Frequent seizures and complex history of anti‐seizure medications (ASMs) predicted severe baseline psychomotor abnormalities. Younger age at KD initiation benefited psychomotor improvement. In the non‐genetic subgroup, lower baseline seizure frequency increased the likelihood of seizure freedom post‐KD. Concurrent use of multiple ASMs helped achieve ≥50% seizure reduction. Boys were more likely to experience psychomotor improvement. A significant correlation was found between ≥50% seizure reduction and psychomotor improvement in both subgroups. Delayed KD initiation (longer epilepsy duration at KD start) was related to a greater number of ASMs used, infrequent seizures, and older age at epilepsy onset. In addition, patients with channelopathies had delayed initiation of KD. Significance: Children with genetic epilepsy display more pronounced characteristics of epileptic encephalopathy. Early KD intervention is crucial for channelopathies, notably SCN1A variants. For other drug‐resistant epilepsy cases, KD alongside diverse ASMs may improve seizure control and developmental outcomes. However, the patient population benefiting most from early KD tends to start the treatment later, urging a re‐evaluation of KD decision‐making paradigms. [ABSTRACT FROM AUTHOR]

Purpose: Ketogenic diets are proposed as a therapeutic approach for type 1 and type 2 diabetes due to their low glucose intake. However, their potential effects on the immune system need investigation. This study aims to explore how glucose concentration and beta-hydroxybutyrate (BHB) impact T cell phenotype, metabolism, and function, with a focus on systemic inflammatory response (T2D) and autoimmunity (T1D). Methods: T cells from healthy donors were cultured in vitro under varying glucose concentrations with or without BHB. Flow cytometry was employed to analyze changes in T cell phenotype, while proliferation was evaluated through a CFSE dilution assay. Additionally, we used a novel flow cytometry method allowing a direct assessment of T cell metabolism. Results: Culturing T cells in low glucose concentrations revealed their dependency on glucose metabolism, leading to reduced proliferation rates, overexpression of exhaustion markers and increased susceptibility to Treg suppression and the influence of immune-modulating drugs such as rapamycin, FK506, and MMF. Notably, T cells cultured in low glucose concentrations increased the expression of BDH1 to utilize BHB as an alternative fuel source. Finally, the addition of BHB to the culture effectively rescued T cell impairments caused by insufficient glucose levels. Conclusions: T cells display limited capacity to adapt to low glucose levels, resulting in profound functional impairment. However, T cell functions can be efficiently recovered by the presence of 2mM BHB. [ABSTRACT FROM AUTHOR]

Background: Low-carbohydrate diets (LCD) are popular for weight loss but lack evidence about micronutrient sufficiency in real-life use. This study assessed the intake and biochemical status of selected micronutrients in people voluntarily following LCDs. Methods: A cross-sectional study was conducted (2018-20) among 98 adults recruited as self-reporting either LCD (n = 49) or diets not restricting carbohydrates (controls; n = 49). Diets were assessed using the 130-item EPIC-Norfolk food-frequency questionnaire. Red-blood-cell thiamine diphosphate (TDP) was measured for thiamine status using HPLC. Plasma magnesium, zinc, copper, and selenium were measured using inductively coupled plasma mass spectrometry. Between-group biomarker comparisons were conducted using ANCOVA and adjusted for age, sex, body mass index (BMI), and diabetes status. Results: LCD-followers (26% male, median age 36 years, median BMI 24.2 kg/m2) reported adhering to LCDs for a median duration of 9 months (IQR 4–36). The most followed LCD type was 'their own variations of LCD' (30%), followed by ketogenic (23%), 'palaeolithic' (15%), and Atkins diets (8%). Among controls, 41% were male (median age 27 years, median BMI 23 kg/m2). Median macronutrient intakes for LCD vs control groups were carbohydrate 16%Energy (E) vs. 50%E; protein 25%E vs. 19%E; and fat 55%E vs 34%E (saturated fat 18%E vs. 11%E). Two-thirds of LCD followers (32/49) and half of the controls (24/49) reported some use of dietary supplements (p = 0.19). Among LCD-followers, assessing from food data only, 21 (43%) failed to meet the reference nutrient intake (RNI) for thiamine (vs.14% controls, p = 0.002). When thiamine from supplementation (single- or multivitamin) was included, there appeared to be no difference in thiamine intake between groups. Still, red-blood-cell TDP was lower in LCD-followers than controls (407 ± 91 vs. 633 ± 234 ng/gHb, p < 0.001). Three LCD-followers were thiamine-deficient (RBC thiamine < 275 ng/gHb) vs. one control. There were no significant differences in dietary intakes or plasma concentrations of magnesium, zinc, copper, and selenium between groups. Conclusions: Following LCDs is associated with lower thiamine intake and TDP status than diets without carbohydrate restriction, incompletely corrected by supplement use. These data, coupled with a lack of RCT evidence on body weight control, do not support recommending LCDs for weight management without appropriate guidance and diet supplementation. [ABSTRACT FROM AUTHOR]

Simple Summary: Exogenous ketone esters (KEs) are compounds that elevate blood ketones without dietary restriction and they show promise as anti-cancer agents. This study examined the effects of an exogenous ketone ester-supplemented (eKET) diet in mouse models of metastatic breast and kidney cancers. Our eKET diet slowed tumor growth and reduced metastatic spread to the lungs in both cancer types. The mechanisms behind these effects differed: the eKET diet downregulated genes involved in Wnt and TGFβ signaling in mammary cancers, whereas it downregulated genes related to hypoxia and DNA damage repair in tumor-bearing kidneys. The diet was safe for use overall but was associated with some negative physiological effects in mice with renal cancer. Thus, eKET diets could be an effective addition to current cancer treatments, but additional work is needed to fully understand their limitations. Background/Objectives: Ketone esters (KEs) exhibit promise as anti-cancer agents but their impact on spontaneous metastases remains poorly understood. Although consumption of a ketogenic diet (KD) that is low in carbohydrates and high in fats can lead to KE production in vivo, the restrictive composition of KDs may diminish adherence in cancer patients. Methods: We investigated the effects of an exogenous ketone ester-supplemented (eKET), carbohydrate-replete diet on tumor growth, metastasis, and underlying mechanisms in orthotopic models of metastatic breast (4T1-Luc) and renal (Renca-Luc) carcinomas. Mice were randomized to diet after tumor challenge. Results: Administration of KEs did not alter tumor cell growth in vitro. However, in mice, our eKET diet increased circulating β-hydroxybutyrate and inhibited primary tumor growth and lung metastasis in both models. Body composition analysis illustrated the overall safety of eKET diet use, although it was associated with a loss of fat mass in mice with renal tumors. Immunogenetic profiling revealed divergent intratumoral eKET-related changes by tumor type. In mammary tumors, Wnt and TGFβ pathways were downregulated, whereas in renal tumors, genes related to hypoxia and DNA damage repair were downregulated. Conclusions: Thus, our eKET diet exerts potent antitumor and antimetastatic effects in both breast and renal cancer models, albeit with different modes of action and physiologic effects. Its potential as an adjuvant dietary approach for patients with diverse cancer types should be explored further. [ABSTRACT FROM AUTHOR]

Here we describe a pediatric patient with febrile infection–related epilepsy syndrome with a good functional and neurologic outcome after treatment with early and aggressive cytokine-directed immunomodulatory therapy and a seizure management strategy that intentionally avoided a barbiturate coma. A 5-year-old previously healthy male presented with staring, behavioral arrest, and encephalopathy evolving to super-refractory status epilepticus. He had had onset of fever 5 days prior. He was treated with early and aggressive immunomodulatory therapy targeted to his evolving cytokine profile. He was also treated with the ketogenic diet, antiseizure medications, and continuous anesthetic infusions. Pentobarbital was purposely avoided. Now, 2½ years later, he attends mainstream school, has attention-deficit hyperactivity disorder (ADHD), mild neurocognitive impairment, and well-controlled epilepsy. By using cytokine-directed immunotherapy and avoiding a barbiturate coma, we were able to successfully treat a pediatric patient with febrile infection-related epilepsy syndrome and achieve a good outcome. [ABSTRACT FROM AUTHOR]

Background: Ketogenic diet is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with the most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of ketogenic diet, usually with long-term use. However, there are limited data to implicate ketogenic diet in acute liver toxicity. Methods and results: We analyzed all patients who underwent elective inpatient ketogenic diet initiation at our institution from June 2019 to June 2022. Of the 25 patients reviewed, we found 6 patients who showed acute, asymptomatic changes in liver function tests during initiation, in both hepatocellular and cholestatic patterns. Two patients stopped the ketogenic diet acutely and 3 patients continued ketogenic diet with changes in medications and/or addition of choline—all patients had improvement and normalization of liver function tests in the short term. One patient had acute normalization of chronically elevated liver function tests on ketogenic diet initiation. Conclusion: Ketogenic diet can cause acute changes in liver function tests during initiation of ketogenic diet, with both hepatocellular and cholestatic patterns, with and without the concurrent use of hepatotoxic medications. In most patients, ketogenic diet can be continued successfully by making changes to medications or addition of choline. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To develop your knowledge of rare epilepsy syndromes • To enhance your understanding of the association between epilepsy and learning disability • To contribute towards revalidation as part of your 35 hours of CPD (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers). Epilepsy is more prevalent in people with learning disabilities than in the general population and there are a number of rare epilepsy syndromes closely associated with learning disability. These syndromes are challenging to manage, notably because seizures are often refractory, the risk of status epilepticus is high and comorbidities are usually present. People with a rare epilepsy syndrome need high levels of specialist support throughout their lives. Such syndromes are rare, but professionals who care for people with learning disabilities are likely to encounter them at some point in their career. Improved knowledge and understanding of rare epilepsy syndromes can assist learning disability nurses to provide adequate information, care and support to service users, family members and paid carers as well as to other healthcare professionals. This article explains the association between epilepsy and learning disability, describes rare epilepsy syndromes and explores the goals of treatment, additional treatment options and challenges of management. [ABSTRACT FROM AUTHOR]

Objectives: Mood disorders are trending to be among the leading causes of years lived with disability. Despite multiple treatment options, around 30% patients with major depressive disorder (MDD) develop treatment resistant depression (TRD) and fail to respond to current pharmacological therapies. This study aimed to explore the potential benefits of nutritional treatment strategies, along with their molecular mechanisms of action, focusing especially on low-carbohydrate diet (LCHD), ketogenic diet (KD) and other strategies based on carbohydrates intake reduction. Methods: A comprehensive literature review was conducted to determine the impact of LCHD on alleviating depressive symptoms in patients with MDD, along with an explanation of its mode of action. Results: The study revealed significant impact of nutritional interventions based on restriction in carbohydrate intake such as LCHD, KD or sugar-sweetened beverages (SSB) exclusion on anxiety or depression symptoms reduction, mood improvement and lower risk of cognitive impairment or depression. The efficacy of these approaches is further substantiated by their underlying molecular mechanisms, mainly brain-derived neurotrophic factor (BDNF) which is a potential key target of sugar restriction diets in terms of neuroplasticity. Discussion: Healthcare professionals may consider implementing LCHD strategies for MDD and TRD patients to modify the disease process, maintain euthymia, and prevent depressive episode relapses. Ranging from the exclusion of SSB to the adherence to rigorous LCHD regimens, these nutritional approaches are safe, straightforward to implement, and may confer benefits for well-being and relapse prevention in this specific patient population. [ABSTRACT FROM AUTHOR]

A ketogenic diet (KD) can induce weight loss and improve glycemic regulation, potentially reducing the risk of type 2 diabetes development. To elucidate the underlying mechanisms behind these beneficial effects of a KD, we investigated the impact of a KD on organ-specific insulin sensitivity (IS) in skeletal muscle, liver, and adipose tissue. We hypothesized that a KD would increase IS in skeletal muscle. The study included 11 individuals with obesity who underwent a randomized, crossover trial with two 3-week interventions: 1) a KD and 2) a standard diet. Skeletal muscle IS was quantified as the increase in glucose disposal during a hyperinsulinemic-euglycemic clamp (HEC). Hepatic IS and adipose tissue IS were quantified as the relative suppression of endogenous glucose production (EGP) and the relative suppression of palmitate flux during the HEC. The KD led to a 2.2-kg weight loss and increased insulin-stimulated glucose disposal, whereas the relative suppression of EGP during the HEC was similar. In addition, the KD decreased insulin-mediated suppression of lipolysis. In conclusion, a KD increased skeletal muscle IS in individuals with obesity. Article Highlights: It remains unclear whether the glucose-lowering effect of a ketogenic diet is due to increased glucose disposal in skeletal muscle or due to an increased insulin-mediated suppression of endogenous glucose production. We investigated how the ketogenic diet affects organ-specific insulin sensitivity. A 3-week ketogenic diet increased insulin-mediated glucose disposal with no change in insulin-mediated suppression of endogenous glucose production. In addition, a decreased insulin-mediated suppression of lipolysis was observed. A 3-week ketogenic diet increases skeletal muscle insulin sensitivity in individuals with obesity. [ABSTRACT FROM AUTHOR]

Objectives The present study was designed to study the efficacy of sequential dietary therapy with a modified Atkins diet (mAD) followed by low glycemic index treatment (LGIT) in treating drug-resistant epilepsy in children. Methods This interventional study was conducted from February 2021 to February 2022 among children aged 6 months to 5 years who had failed to respond to more than two conventional and correctly chosen antiseizure medications. The primary endpoint was the proportion of good responders, that is, children with more than 50% seizure reduction. Secondary outcome measures were the proportion of children with seizure freedom, > 90% seizure reduction, and the nature of parent-reported adverse events. Results A total of 45 children were recruited for the study, with 6 children being lost to follow-up at 12 weeks. At 12 weeks, 30 of 39 (76.9%) children were good responders with more than 50% seizure reduction. Of these 30 children, 11 (24.4%) had more than 90% seizure reduction, with 9 (20%) achieving complete spasm freedom. Constipation was the most common side effect of the diet among the enrolled subjects. Conclusion Clinicians can consider sequential dietary therapy with a mAD in the first month followed by LGIT in the next 2 months for treating children who could not tolerate mAD beyond 1 month. [ABSTRACT FROM AUTHOR]

The very-low calorie ketogenic diet (VLCKD) is recommended as an effective dietary approach for the management of obesity. This study investigated changes in circulating biomarkers of redox homeostasis induced by a multiphase VLCKD in obese individuals. A total of 40 obese subjects were prescribed a multiphasic VLCKD for eleven weeks. Anthropometric measurements, body composition parameters, calorimetric measures, and standard laboratory markers of glucose and lipid metabolism were evaluated at baseline (T 0) and at the end of the dietary intervention (T 1). Additionally, circulating markers of oxidative damage and antioxidant status were analyzed in serum and erythrocytes. Compared to T 0 , at T 1 the multiphase VLCKD induced significant weight loss and reduction of waist circumference, with beneficial effects on body composition parameters and the glucose/lipid biochemical profile. Moreover, a decrease in serum markers of oxidative damage was reported at T 1 , while no changes in serum markers of antioxidant status and in erythrocyte redox markers were observed. In addition, a significant association was found between variations in anthropometric measurements, body composition, glucose metabolism parameters, and changes in circulating markers of oxidative damage. Regression models showed that variation in lipofuscin was significant predictor of changes in body mass index, fat mass, visceral adiposity, and insulin sensitivity. In conclusion, this study demonstrated that the multiphase VLCKD improves serum redox balance by reducing markers of oxidative damage in obese individuals, highlighting the interplay between adiposity, glucose metabolism, and redox homeostasis in the pathogenesis of obesity. Furthermore, these data provide a rationale for future investigations aimed at testing serum lipofuscin as a reliable redox marker in obesity. [Display omitted] • Multiphase very-low calorie ketogenic diet (VLCKD) is promising for obesity • Multiphase VLCKD induces beneficial changes in serum markers of redox balance • Serum parameters of oxidative damage are reduced by multiphase VLCKD • Multiphase VLCKD-induced redox changes associate with weight and fat mass loss • Serum lipofuscin may be suggested as a reliable biomarker in obesity [ABSTRACT FROM AUTHOR]

A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated. [ABSTRACT FROM AUTHOR]

Background: Lipedema is a frequently misdiagnosed condition in women, often mistaken for obesity, which significantly deteriorates both quality of life and physical health. Recognizing the necessity for holistic treatment strategies, research has increasingly supported the integration of specific dietary approaches, particularly ketogenic diets focusing on low-carbohydrate and high-fat intake. Objectives: to evaluate the impact of ketogenic diets on women with lipedema through a systematic review and meta-analysis. Methods: A systematic review and meta-analysis were conducted by reviewing published, peer-reviewed studies addressing the implications of a low-carbohydrate, high-fat (LCHF) ketogenic diet in managing lipedema following comprehensive scrutiny of digital medical databases, such as PubMed, PubMed Central, Science Direct, and the Web of Science. This research was governed by specified parameters, including an established search string composed of search terms and an eligibility criterion (PICO) as denoted by the principal authors. Statistical analysis was carried out using RevMan 5.4.1 software with the Newcastle–Ottawa Scale utilized for quality appraisal of the included studies. Results: Seven studies reporting statistical outcomes were included in the systematic review and meta-analysis following a rigorous quality appraisal and data identification process. Three hundred and twenty-nine female participants were diagnosed with lipedema and treated using a low-carbohydrate, high-fat diet. Data analysis identified the high-fat diet with a mean study duration of 15.85 weeks. Mean Differences (MDs) on changes pre- and post-intervention showed significant reductions in BMI and total body weight [4.23 (95% CI 2.49, 5.97) p < 0.00001 and 7.94 (95% CI 5.45, 10.43) p < 0.00001 for BMI and body weight, respectively]. Other anthropometric measurements, such as changes in waist/hip circumferences and waist/hip ratios, showed a significant reduction in these parameters, with an MD of 8.05 (95% CI 4.66, 11.44) p < 0.00001 and an MD of 6.67 (95% CI 3.35, 9.99) p < 0.0001 for changes in waist and hip circumferences from baseline, respectively. Lastly, changes in pain sensitivity were statistically significant post-intervention [MD 1.12 (95% CI, 0.44, 1.79) p = 0.001]. All studies scored fair on the Newcastle–Ottawa Scale. Conclusions: despite the limited studies and low number of study participants, the review observed a significant reduction in anthropometric and body composition metrics, indicating a potentially beneficial association between LCHF ketogenic diets and lipedema management. [ABSTRACT FROM AUTHOR]

Background/Objectives: Obesity is a major risk factor for knee osteoarthritis (OA), and weight loss is crucial for its management. This pilot study explores the effects of a Very Low-Calorie Ketogenic Diet (VLCKD) in women with obesity and symptomatic knee OA. Methods: Women with symptomatic knee OA and obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, were eligible for the VLCKD protocol. The intervention included a ketogenic phase from baseline (T0) to the 8th week (T8), followed by a progressive reintroduction of carbohydrates over the next 12 weeks, ending at the 20th week (T20). Body mass index (BMI), the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, the EuroQol 5D (EQ-5D), and the 36-item Short Form Health Survey (SF-36) were assessed at all time points. Generalized estimating equations were used to analyze the association between BMI and patient-reported outcomes across the study period. Results: Twenty participants started the study, but four discontinued the intervention, with two of these being due to adverse effects. The mean age of the 16 patients who completed the 20-week program was 57.3 ± 5.5 years, and their mean BMI was 40.0 ± 4.8 kg/m2. The mean BMI significantly decreased to 37.5 ± 4.5 at T4, 36.3 ± 4.6 at T8, and 34.8 ± 4.8 at T20 (all p < 0.001 compared to baseline). The total WOMAC score improved from a mean of 43.6 ± 16.9 at T0 to 30.2 ± 12.8 at T4 (p = 0.005) and further to 24.7 ± 10.6 at T8 (p = 0.001) and to 24.8 ± 15.9 at T20 (p = 0.005). The reduction in BMI was significantly correlated with the improvements in WOMAC, EQ-5D, and SF-36 over time. No major adverse effects were observed. Conclusions: A 20-week VLCKD in women with obesity and knee OA significantly reduced their weight and improved their outcomes, warranting further research. This trial is registered with number NCT05848544 on ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

Background: Drug-resistant epilepsy (DRE) impacts a significant portion, onethird, of individuals diagnosed with epilepsy. In such cases, exploring nonpharmacological interventions are crucial, with the ketogenic diet (KD) standing out as a valuable option. KD, a high-fat and low-carb dietary approach with roots dating back to the 1920s for managing DRE, triggers the formation of ketone bodies and modifies biochemistry to aid in seizure control. Recent studies have increasingly supported the efficacy of KD in addressing DRE, showcasing positive outcomes. Furthermore, while more research is needed, limited data suggests that KD May also be beneficial for specific genetic epilepsy syndromes (GESs). Objective: This study aimed to assess the short-term efficacy of KD among pediatric patients diagnosed with GESs. Materials and methods: This is a multi-center retrospective analysis of pediatric patients with GESs diagnosed using next-generation sequencing. The enrolled patients followed the keto-clinic protocol, and the KD efficacy was evaluated at 3, 6, and 12-month intervals based on seizure control and compliance. The collection instrument included demographic, baseline, and prognostic data. The collected data was coded and analyzed promptly. Results: We enrolled a cohort of 77 patients with a mean current age of 7.94 ± 3.83 years. The mean age of seizure onset was 15.5 months. Notably, patients experienced seizures at a younger age tended to have less positive response to diet. Overall, 55 patients responded favorably to the diet (71.4%) while 22 patients (28.6%) showed no improvement. Patients with genetic etiology showed a significantly more favorable responses to the dietary intervention. Patients with Lennox-Gastaut syndrome showed the most significant improvement (14/15) followed by patients with Dravet syndrome (6/8), and West syndrome (3/4). The number of used anti-seizure medications also played a significant role in determining their response to the diet. While some patients experienced mild adverse events, the most common being constipation, these occurrences were not serious enough to necessitate discontinuation of the diet. Conclusion: The study revealed a high improvement rate in seizure control, especially among younger patients and those with later seizure onset. The success of dietary treatment hinges greatly on early intervention and the patient's age. Certain genetic mutations responded favorably to the KD, while efficacy varied among various genetic profiles. [ABSTRACT FROM AUTHOR]

Background: Frailty is a geriatric syndrome characterized by chronic inflammation and metabolic insufficiency that creates vulnerability to poor outcomes with aging. We hypothesize that interventions which target common underlying mechanism of aging could ameliorate frailty. Ketone bodies are metabolites produced during fasting or on a ketogenic diet that have pleiotropic effects on inflammatory and metabolic aging pathways in laboratory animal models. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. Our long-term goal is to examine if KEs modulate aging biology mechanisms and clinical outcomes relevant to frailty in older adults. Objectives: The primary objective of this randomized, placebo-controlled, double-blinded, parallel-group, pilot trial is to determine tolerability of 12-weeks of KE ingestion in a broad population of older adults (≥ 65 years). Secondary outcomes include safety and acute blood ketone kinetics. Exploratory outcomes include physical function, cognitive function, quality of life, aging biomarkers and inflammatory measures. Methods: Community-dwelling adults who are independent in activities of daily living, with no unstable acute medical conditions (n = 30) will be recruited. The study intervention is a KE or a taste, appearance, and calorie matched placebo beverage. Initially, acute 4-hour ketone kinetics after 12.5g or 25g of KE consumption will be assessed. After collection of baseline safety, functional, and biological measurements, subjects will randomly be allocated to consume KE 25g or placebo once daily for 12-weeks. Questionnaires will assess tolerability daily for 2-weeks, and then via phone interview at bi-monthly intervals. Safety assessments will be repeated at week 4. All measures will be repeated at week 12. Conclusion: This study will evaluate feasibility, tolerability, and safety of KE consumption in older adults and provide exploratory data across a range of aging-related endpoints. This data will inform design of larger trials to rigorously test KE effects on aging mechanisms and clinical outcomes relevant to frailty. [ABSTRACT FROM AUTHOR]

Epilepsy, a complex neurological condition marked by recurring seizures, is increasingly recognized for its intricate relationship with mitochondria, the cellular powerhouses responsible for energy production and calcium regulation. This review offers an in-depth examination of the interplay between epilepsy, mitochondrial function, and aging. Many factors might account for the correlation between epilepsy and aging. Mitochondria, integral to cellular energy dynamics and neuronal excitability, perform a critical role in the pathophysiology of epilepsy. The mechanisms linking epilepsy and mitochondria are multifaceted, involving mitochondrial dysfunction, reactive oxygen species (ROS), and mitochondrial dynamics. Mitochondrial dysfunction can trigger seizures by compromising ATP production, increasing glutamate release, and altering ion channel function. ROS, natural byproducts of mitochondrial respiration, contribute to oxidative stress and neuroinflammation, critical factors in epileptogenesis. Mitochondrial dynamics govern fusion and fission processes, influence seizure threshold and calcium buffering, and impact seizure propagation. Energy demands during seizures highlight the critical role of mitochondrial ATP generation in maintaining neuronal membrane potential. Mitochondrial calcium handling dynamically modulates neuronal excitability, affecting synaptic transmission and action potential generation. Dysregulated mitochondrial calcium handling is a hallmark of epilepsy, contributing to excitotoxicity. Epigenetic modifications in epilepsy influence mitochondrial function through histone modifications, DNA methylation, and non-coding RNA expression. Potential therapeutic avenues targeting mitochondria in epilepsy include mitochondria-targeted antioxidants, ketogenic diets, and metabolic therapies. The review concludes by outlining future directions in epilepsy research, emphasizing integrative approaches, advancements in mitochondrial research, and ethical considerations. Mitochondria emerge as central players in the complex narrative of epilepsy, offering profound insights and therapeutic potential for this challenging neurological disorder. [ABSTRACT FROM AUTHOR]

Neonatal intensive care unit (NICU), particularly in treating developmental and epileptic encephalopathy (DEE) and metabolic epilepsy (ME), requires a deep understanding of their complex etiologies and treatment responses. After excluding treatable cases such as infectious or autoimmune encephalitis, our focus shifted to a more challenging subgroup of 59 patients for in-depth genetic analysis using exome sequencing (ES). The ES analysis identified 40 genetic abnormalities, significantly including de novo variants. Notably, we found structural variation as duplications in regions 2q24.3, including SCN1A and SCN2A were observed in 7 cases. These genetic variants, impacting ion channels, glucose transport, transcription regulation, and kinases, play a crucial role in determining medication efficacy. More than one-third (34.2%) of patients with DEE had an unfavorable response to anti-seizure medications (ASMs) in the chronic phase. However, since the ketogenic supplementary diet showed a positive effect, more than three-quarters (80%) of these drug-resistant patients improved during a 3-month follow-up. In contrast, the ME had a lower adverse reaction rate of 9.1% (2/22) to specialized medications, yet there were 5 fatalities and 10 cases with unidentified genetic etiologies. This study suggests the potential of categorizing drug-resistant variants and that a ketogenic diet could be beneficial in managing DEE and ME. It also opens new perspectives on the mechanisms of the ketogenic diet on the discovered genetic variants. [ABSTRACT FROM AUTHOR]

Polycystic kidney disease (PKD) includes autosomal dominant (ADPKD) and autosomal recessive (ARPKD) forms, both of which are primary genetic causes of kidney disease in adults and children. ADPKD is the most common hereditary kidney disease, with a prevalence of 329 cases per million in Europe. This condition accounts for 5–15% of end-stage chronic kidney disease (ESKD) cases, and in developed countries such as Poland, 8–10% of all dialysis patients have ESKD due to ADPKD. The disease is caused by mutations in the PKD1 and PKD2 genes, with PKD1 mutations responsible for 85% of cases, leading to a more aggressive disease course. Recent research suggests that ADPKD involves a metabolic defect contributing to cystic epithelial proliferation and cyst growth. Aim: This review explores the interplay between metabolism, obesity, and ADPKD, discussing dietary and pharmacological strategies that target these metabolic abnormalities to slow disease progression. Conclusion: Metabolic reprogramming therapies, including GLP-1 analogs and dual agonists of GIP/GLP-1 or glucagon/GLP-1 receptors, show promise, though further research is needed to understand their potential in ADPKD treatment fully. [ABSTRACT FROM AUTHOR]

Objectives: Heart failure (HF) is a global health concern with rising incidence and poor prognosis. While the essential role of nutritional and dietary strategies in HF patients is acknowledged in the existing scientific guidelines and clinical practice, there are no comprehensive nutritional recommendations for optimal dietary management of HF. Methods: In this review, we discuss results from recent studies on the obesity paradox and the effects of calorie restriction and weight loss, intermittent fasting, the Western diet, the Mediterranean diet, the ketogenic diet, and the DASH diet on HF progression. Results: Many of these strategies remain under clinical and basic investigation for their safety and efficacy, and there is considerable heterogeneity in the observed response, presumably because of heterogeneity in the pathogenesis of different types of HF. In addition, while specific aspects of cardiac metabolism, such as changes in ketone body utilization, might underlie the effects of certain dietary strategies on the heart, there is a critical divide between supplement strategies (i.e., with ketones) and dietary strategies that impact ketogenesis. Conclusion: This review aims to highlight this gap by exploring emerging evidence supporting the importance of personalized dietary strategies in preventing progression and improving outcomes in the context of HF. [ABSTRACT FROM AUTHOR]

This study examined the effect of a low-carbohydrate diet (LCD) and a low-carbohydrate ketogenic diet (LCKD) on diabetic retinopathy in high-fat diet-induced diabetes mellitus in rats and studied the mechanisms of action. Rats were divided into four groups: the Control group, which was fed a normal diet for 16 weeks; the HFD group, which was fed a high-fat diet (HFD) for the first 8 weeks and then switched to a normal diet for 8 weeks; the HFD+LCD group, fed a HFD for 8 weeks followed by an LCD for 8 weeks, and the HFD+LCKD group, which was fed a HFD for 8 weeks followed by an LCKD for 8 more weeks. Both the LCD and the LCKD effectively reduced the final body and total fat weights and decreased fasting serum levels of glucose, insulin, hemoglobin A1 (HbA1C), triglycerides, cholesterol, and LDL-c. They also reduced the levels of malondialdehyde (MDA), tumor necrosis factor-α, vascular endothelial factor, caspapse-3, and bax. In the HFD rats, we found increased serum levels of β-Hydroxybutyrate and upregulated expression of Bcl2, glutathione, superoxide dismutase, and hemeoxygenase-1. Moreover, the LCD and LCKD significantly reduced mRNA levels of Kelch-like ECH-associated protein 1 (Keap1) and enhanced mRNA and nuclear concentrations of nuclear factor erythroid factor 2 (Nrf2). All these effects were associated with improved layers of the retina in the HFD − LCD and HFD + LCKD rats but not in HFD animals. The impact of the LCKD was always more profound on all measured parameters and on improving the structure of the retina compared to the LCD. In conclusion, the LCKD is superior to the LCD in preventing diabetic retinopathy in HFD-fed rats. Mechanistically, our results suggest that the hypoglycemic and hypolipidemic conditions and the Nrf2-dependent antioxidant and anti-inflammatory effects may be involved in the preventative effects of the LCD and LCKD. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsDiscussionSome anti-seizure medications (ASMs) are known to induce liver enzymes and impact lipid values that include total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglyceride (TG). In addition, use of ketogenic diet therapies, including the modified Atkins diet (MAD), has also influenced lipids. Here, we explored the combined impact of enzyme inducing ASMs (EIASMs) and MAD on lipid values in adults with epilepsy.Diet-naïve adults with epilepsy who began MAD were divided into three groups based on ASM use: EIASMs, non-EIASMs, and those on no ASMs. Demographic information, epilepsy-specific clinical history, anthropometrics and lipid values were obtained through retrospective chart review at baseline and after a minimum of 12 months of MAD use.Forty-two adults on MAD had baseline and follow up 12-month lipid outcomes. There was a significant increase in median levels of TC, LDL, non-HDL, and HDL after 12 months of MAD use. There was no change in median levels of TG. When separated according to ASM category, adults on non-EIASMs showed significant elevations in TC, HDL, and LDL after 12 months of MAD use. In contrast, adults on EIASMs only showed a significant increase in HDL after 12 months of MAD use.The increase in atherogenic cholesterol levels observed after 12 months of MAD use was most pronounced in adults with epilepsy on non-EIASMs and not observed in adults with epilepsy on EIASMs despite a higher proportion of abnormal cholesterol levels at baseline in those on EIASMs. [ABSTRACT FROM AUTHOR]

Medium chain fatty acids are commonly consumed as part of diets for endurance sports and as medical treatment in ketogenic diets where these diets regulate energy metabolism and increase adenosine levels. However, the role of the equilibrative nucleoside transporter 1 (ENT1), which is responsible for adenosine transport across membranes in this process, is not well understood. Here, we investigate ENT1 activity in controlling the effects of two dietary medium chain fatty acids (decanoic and octanoic acid), employing the tractable model system Dictyostelium. We show that genetic ablation of three ENT1 orthologues unexpectedly improves cell proliferation specifically following decanoic acid treatment. This effect is not caused by increased adenosine levels triggered by both fatty acids in the presence of ENT1 activity. Instead, we show that decanoic acid increases expression of energy-related genes relevant for fatty acid β-oxidation, and that pharmacological inhibition of ENT1 activity leads to an enhanced effect of decanoic acid to increase expression of tricarboxylicacid cycle and oxidative phosphorylation components. Importantly, similar transcriptional changes have been shown in the rat hippocampus during ketogenic diet treatment. We validated these changes by showing enhanced mitochondria load and reduced lipid droplets. Thus, our data show that ENT1 regulates the medium chain fatty acid-induced increase in cellular adenosine levels and the decanoic acid-induced expression of important metabolic enzymes in energy provision, identifying a key role for ENT1 proteins in metabolic effects of medium chain fatty acids. [ABSTRACT FROM AUTHOR]

Copyright of Medicina (Buenos Aires) is the property of Medicina (Buenos Aires) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The very low-calorie ketogenic diet (VLCKD), characterized by a marked energy restriction that induces rapid weight loss, has recently been proposed as a valid nutritional strategy for managing obesity. VLCKD is commonly considered dangerous for the kidneys due to the misconception that it is high in protein, beyond the risk of electrolyte imbalances and an increase in diuresis. We report a case of safe and effective weight loss induced by VLCKD in a 43-year-old Caucasian woman with a recent episode of acute kidney injury on advanced chronic kidney disease. Surprisingly, we observed that after the diet-induced weight loss, not only did renal function not worsen, but proteinuria also improved. The principal value of this case report is its singular demonstration of impressive weight loss induced by VLCKD in a complex obese patient that was apparently not accompanied by the development of serious adverse sequelae. [ABSTRACT FROM AUTHOR]

The prevention and treatment of cardiovascular diseases have always been a focus of attention in related fields. This paper discusses the application and mechanism of exogenous and endogenous supplementation with β-hydroxybutyrate in the prevention and treatment of cardiovascular diseases such as myocardial ischemia, myocardial infarction, diabetic cardiomyopathy, hypertension, myocardial inflammation, hypertrophic cardiomyopathy and heart failure. Exogenous β-hydroxybutyrate supplementation can quickly and directly provide substitute energy for the heart and thus prevent and treat heart injury. The comprehensive effect of exogenous β-hydroxybutyrate supplementation is significantly better than that of endogenous β-hydroxybutyrate. Endogenous fatty acid, obtained through a ketogenic diet, needs to be oxidized to β-hydroxybutyrate in vivo for energy supply, which is greatly influenced by glucose and lipid metabolism under the conditions of the basic disease itself. At present, ketogenic diet is not recommended for use in the prevention and treatment of myocardial ischemia or myocardial infarction, and in the treatment of diabetic cardiomyopathy or hypertension. [ABSTRACT FROM AUTHOR]

Recent scientific research has shown that the ketogenic diet may have potential benefits in a variety of medical fields, which has led to the diet receiving a substantial amount of attention. Clinical and experimental research on brain tumors has shown that the ketogenic diet has a satisfactory safety profile. This safety profile has been established in a variety of applications, including the management of obesity and the treatment of drug-resistant epileptic cases. However, in human studies, the impact of ketogenic therapy on the growth of tumors and the life expectancy of patients has not provided results that are well characterized. Consequently, our purpose is to improve the comprehension of these features by succinctly presenting the developments and conclusions that have been gained from the most recent study that pertains to this non-pharmacological technique. According to the findings of our study, patients with brain tumors who stick to a ketogenic diet are more likely to experience improved survival rates. However, it is required to conduct additional research on humans in order to more accurately define the anti-tumor efficiency of this diet as well as the underlying processes that support the therapeutic effects of this dieting regimen. [ABSTRACT FROM AUTHOR]

Deranged gut microbiota can release increased levels of uremic toxins leading to exacerbated kidney injury. In diabetic kidney disease (DKD), phenyl sulfate (PS) derived from tyrosine catabolism by gut microbiota has been demonstrated to be both an early diagnostic marker and a therapeutic target. In this perspective article, we summarize PS generation pathways and recent findings on PS and kidney injury in DKD. Increasing evidence has shown that the underlying mechanisms of PS-induced kidney injury mainly involve oxidative stress, redox imbalance, and mitochondrial dysfunction, which all may be targeted to attenuate PS-induced kidney injury. For future research directions, we think that a deeper understanding of the pathogenic role of PS in kidney injury using a variety of diabetic animal models should be investigated. Moreover, we also suggest beneficial approaches that could be used to mitigate the deleterious effect of PS on the kidney. These approaches include caloric restriction, tyrosine restriction, and administration of ketogenic drugs, ketogenic diets or natural products; all of which should be conducted under obese and diabetic conditions. [ABSTRACT FROM AUTHOR]

Opioids are commonly prescribed to patients with chronic pain. Chronic opioid usage comes with a slew of serious side effects, including opioid-induced hyperalgesia (OIH). The patients with long-term opioid treatment experience paradoxical increases in nociceptive hypersensitivity, namely, OIH. Currently, treatment options for OIH are extremely lacking. In this study, we show that the ketogenic diet recovers the abnormal pain behavior caused by chronic morphine treatment in male mice, and we further show that the therapeutic effect of the ketogenic diet is mediated through gut microbiome. Our 16S rRNA sequencing demonstrates that chronic morphine treatment causes changes in mouse gut microbiota, specifically a decrease in short-chain fatty acids-producing bacteria, and the sequencing data also show that the ketogenic diet rescues those bacteria in the mouse gut. More importantly, we show that supplementation with short-chain fatty acids (butyrate, propionate, and acetate) can delay the onset of OIH, indicating that short-chain fatty acids play a direct role in the development of OIH. Our findings suggest that gut microbiome could be targeted to treat OIH, and the ketogenic diet can be used as a complementary approach for pain relief in patients with chronic opioid treatment. We only used male mice in this study, and thus, our findings cannot be generalized to both sexes. [ABSTRACT FROM AUTHOR]