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BACKGROUND: Increases in low-density lipoprotein cholesterol (LDL-C) can occur on carbohydrate restricted ketogenic diets. Lean metabolically healthy individuals with a low triglyceride-to-high-density lipoprotein cholesterol ratio appear particularly susceptible, giving rise to the novel lean mass hyper-responder (LMHR) phenotype. OBJECTIVES: The purpose of the study was to assess coronary plaque burden in LMHR and near-LMHR individuals with LDL-C ≥190 mg/dL (ketogenic diet [KETO]) compared to matched controls with lower LDL-C from the Miami Heart (MiHeart) cohort. METHODS: There were 80 KETO individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL, high-density lipoprotein cholesterol ≥60 mg/dL, and triglyceride levels ≤80 mg/dL, without familial hypercholesterolemia, matched 1:1 with MiHeart subjects for age, gender, race, hyperlipidemia, hypertension, and smoking status. Coronary artery calcium and coronary computed tomography angiography (CCTA) were used to compare coronary plaque between groups and correlate LDL-C to plaque levels. RESULTS: The matched mean age was 55.5 years, with a mean LDL-C of 272 (maximum LDL-C of 591) mg/dl and a mean 4.7-year duration on a KETO. There was no significant difference in coronary plaque burden in the KETO group as compared to MiHeart controls (mean LDL 123 mg/dL): coronary artery calcium score (median 0 [IQR: 0-56]) vs (1 [IQR: 0-49]) (P = 0.520) CCTA total plaque score (0 [IQR: 0-2] vs [IQR: 0-4]) (P = 0.357). There was also no correlation between LDL-C level and CCTA coronary plaque. CONCLUSIONS: Coronary plaque in metabolically healthy individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL on KETO for a mean of 4.7 years is not greater than a matched cohort with 149 mg/dL lower average LDL-C. There is no association between LDL-C and plaque burden in either cohort. (Diet-induced Elevations in LDL-C and Progression of Atherosclerosis [Keto-CTA]; NCT057333255).

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.

Tay-Sachs disease is a rare lysosomal storage disorder caused by β-Hexosaminidase A enzyme deficiency causing abnormal GM2 ganglioside accumulation in the central nervous system. GM2 accumulation triggers chronic neuroinflammation due to neurodegeneration-based astrogliosis and macrophage activity with the increased expression level of Ccl2 in the cortex of a recently generated Tay-Sachs disease mouse model Hexa-/-Neu3-/-. Propagermanium blocks the neuroinflammatory response induced by Ccl2, which is highly expressed in astrocytes and microglia. The ketogenic diet has broad potential usage in neurological disorders, but the knowledge of the impact on Tay-Sach disease is limited. This study aimed to display the effect of combining the ketogenic diet and propagermanium treatment on chronic neuroinflammation in the Tay-Sachs disease mouse model. Hexa-/-Neu3-/- mice were placed into the following groups: (i) standard diet, (ii) ketogenic diet, (iii) standard diet with propagermanium, and (iv) ketogenic diet with propagermanium. RT-PCR and immunohistochemistry analyzed neuroinflammation markers. Behavioral analyses were also applied to assess phenotypic improvement. Notably, the expression levels of neuroinflammation-related genes were reduced in the cortex of 140-day-old Hexa-/-Neu3-/- mice compared to β-Hexosaminidase A deficient mice (Hexa-/-) after combined treatment. Immunohistochemical analysis displayed correlated results with the RT-PCR. Our data suggest the potential to implement combined treatment to reduce chronic inflammation in Tay-Sachs and other lysosomal storage diseases. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a leading cause of disability worldwide. While traditional pharmacological treatments are effective for many cases, a significant proportion of patients do not achieve full remission or experience side effects. Nutritional interventions hold promise as an alternative or adjunctive approach, especially for treatment-resistant depression. This review examines the potential role of nutrition in managing MDD through addressing biological deficits and modulating pathways relevant to its pathophysiology. Specifically, it explores the ketogenic diet and gut microbiome modulation through various methods, including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Numerous studies link dietary inadequacies to increased MDD risk and deficiencies in nutrients like omega-3 s, vitamins D and B, magnesium, and zinc. These deficiencies impact neurotransmitters, inflammation, and other biological factors in MDD. The gut-brain axis also regulates mood, stress response, and immunity, and disruptions are implicated in MDD. While medications aid acute symptoms, nutritional strategies may improve long-term outcomes by preventing relapse and promoting sustained remission. This comprehensive review aims to provide insights into nutrition's multifaceted relationship with MDD and its potential for developing more effective integrated treatment approaches. [ABSTRACT FROM AUTHOR]

Epilepsy stands out as one of the most prevalent chronic neurological conditions affecting companion animals. Recent research has increasingly focused on exploring the role of gut microbiota in influencing neurological conditions, like epilepsy. This influence stems from the bidirectional communication pathways between gut bacteria and the brain, which involve metabolic, neural, immunological, and endocrine mechanisms. In fact, a balanced and stable gut microbiota is essential to maintaining normal gut physiology and ensuring appropriate signaling along the gut–brain axis. Conversely, dysbiosis can have detrimental effects on gut physiology and may contribute to the development or exacerbation of neurological conditions, including epilepsy. Considering these findings, this review article aims to deepen the understanding of the mechanisms underlying the microbiota–gut–brain connection in the context of canine idiopathic epilepsy. Moreover, this review presents recent data on innovative gut-related therapeutic strategies for canine idiopathic epilepsy treatment. [ABSTRACT FROM AUTHOR]

The use of a ketogenic diet (KD) in glioma is currently tested as an adjuvant treatment in standard chemotherapy regimens. The metabolic shift induced by the KD leads to the generation of ketone bodies that can influence glioma cells and the surrounding microenvironment, but the mechanisms have not yet been fully elucidated. Here, we investigated the potential involvement of glial cells as mediators of the KD-induced effects on tumor growth and survival rate in glioma-bearing mice. Specifically, we describe that exposing glioma-bearing mice to a KD or to β-hydroxybutyrate (β-HB), one of the main KD metabolic products, reduced glioma growth in vivo, induced a pro-inflammatory phenotype in astrocytes and increased functional glutamate transporters. Moreover, we described increased intracellular basal Ca2+ levels in GL261 glioma cells treated with β-HB or co-cultured with astrocytes. These data suggest that pro-inflammatory astrocytes triggered by β-HB can be beneficial in counteracting glioma proliferation and neuronal excitotoxicity, thus protecting brain parenchyma. [ABSTRACT FROM AUTHOR]

Objective: To assess the anti-seizure efficacy and safety of a C10-enriched medium-chain triglyceride (MCT) ketogenic diet (KD) compared with the classic KD in pediatric patients with refractory epilepsy. Methods: This 16-week, open-label, randomized, controlled, crossover pilot study was conducted at Severance Children's Hospital, Seoul, South Korea, between August 2022 and September 2023. Fifteen pediatric patients with refractory epilepsy were enrolled and received classic KD and C10-enriched KD for 8 weeks each. The study compared seizure reduction rate, tolerability, and safety of the two diets. Results: Fifteen patients were enrolled. Patients were divided into 2 groups depending on the type of KD initiated. Ten patients completed the trial. Initial treatment with the C10-enriched KD resulted in seizure reduction in all five patients, with two becoming seizure-free. Initial treatment with classic KD was effective in two out of five patients. Upon crossover, those initially on C10-enriched KD maintained their seizure reduction, while patients initially on the classic KD showed additional seizure reduction when switched to C10-enriched KD. Adverse effects included transient hypoglycemia, metabolic acidosis, hypercalciuria, and gastrointestinal symptoms, all of which were manageable. Discussion: The C10-enriched KD demonstrated comparable efficacy and tolerability to the classic KD, offering a promising option for patients with refractory epilepsy who do not respond adequately to the classic KD alone. This study, the first to directly compare a C10-enriched KD with a classic KD, highlights the potential synergistic effects of decanoic acid. [ABSTRACT FROM AUTHOR]

Background: The ketogenic diet (KD) therapy is a primary treatment for drug-resistant epilepsy, and beta-hydroxybutyrate (BHB) is the main ketone produced during KD. However, the pattern of increase in BHB levels is not well understood, and the reference range for BHB need to be defined. The aim of this study was to evaluate the BHB levels in the first three months, especially one week, after KD initiation, and to explore the physiological reference range for BHB. Methods: In our study, a fasting initiation strategy was used for the majority of patients (252/300, 84%) who underwent fasting for 24–48 h, the rest fasted for at least 12 h. The concentration of blood BHB was measured four times a day during the first week, at one month and three months. Seizure frequency was recorded at one week, one month and three months. Responders were defined as those with a seizure reduction 50% or more compared to baseline. BHB levels were compared between responders and non-responders. The BHB levels of responders were used to calculate the reference range. Results: A total of 300 patients were recruited, of whom 172 (57%) had accessible BHB data. BHB levels rapidly rose to 2.0 mmol/L at 19 h, peaked at 4.2 mmol/L at 43 h of therapy, and stabilized by three months. The reference range for BHB was 1.1 to 4.9 mmol/L. Conclusions: BHB levels increased rapidly following fasting, reaching the peak at day 2, stabilizing from the end of the first week through three months. The lower reference limit for BHB to ensure KD efficacy should be set at 1.1 mmol/L. [ABSTRACT FROM AUTHOR]

Drug addiction is a chronic and potentially deadly disease that is considered a global health problem and describes the alteration of brain function by psychostimulant drugs through changes in the reward system. However, there is still no ideal strategy for the management of drug addiction. Previous studies have suggested that microglia are involved in events associated with neuroplasticity and memory, which are also related to drug addiction. Many studies have shown that psychoactive substances may act directly on immune cells, altering their function and inducing the production of various inflammatory mediators. In recent years, a ketogenic diet (KD) was shown to have therapeutic benefits as a dietary therapy for a variety of neurological disorders. With respect to drug addiction, studies have shown that a KD can alleviate glucose metabolism disorders caused by alcohol use disorders by increasing ketone metabolism, thereby reducing withdrawal symptoms. This finding indicates the potential of a KD as a treatment for drug addiction, since a KD may promote the transition of microglia to a predominantly anti-inflammatory state through several mechanisms. Here, we discuss recent research showing that a KD plays a variety of roles in controlling microglia-mediated inflammation, opening new treatment avenues to treat drug addiction. This succinct analysis offers evidence of the enormous potential of a KD to treat drug addiction through the inhibition of microglial activation. [ABSTRACT FROM AUTHOR]

With increasing attention to diabetes remission, various special dietary patterns have been found to be effective in achieving diabetes remission. The effect of a single dietary pattern on lowering blood glucose is clear, but studies on the synergistic effects of different dietary patterns are limited. This article describes the types of intermittent fasting and ketogenic diets, potential mechanisms, contraindications of combination diets, recommendations for combination diets, and their health outcomes. This paper aims to illustrate the evidence for intermittent fasting combined with a ketogenic diet on outcomes of diabetes remission and effect on blood glucose control. Knowledge of these findings can help doctors and patients determine dietary patterns for achieving diabetes remission and understanding their application. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is a very low-carbohydrate, high-fat diet that reduces glucose catabolism and enhances β-oxidation and ketogenesis. While research in female rodents is limited, research in male rodents suggests that ketogenic interventions initiated at midlife may slow age-related cognitive decline, as well as preserve muscle mass and physical function later in life. This study aimed to investigate the effects of a KD on global metabolic changes in middle-aged females to inform potential mechanisms behind the anti-aging effects of this diet in an understudied sex. Targeted 1H-NMR metabolomics was conducted on serum, the liver, the kidney, and the gastrocnemius muscle, as well as the cortex and the hippocampal brain regions in 16-month-old female mice after a 2-month KD. Analysis of the serum and liver metabolome revealed that the 2-month KD resulted in increased concentrations of fatty acid catabolism metabolites, as well as system-wide elevations in ketones, consistent with the ketogenic phenotype. Metabolites involved in the glucose-alanine cycle were altered in the gastrocnemius muscle, serum and the liver. Other tissue-specific alterations were detected, including distinct effects on hepatic and renal one-carbon metabolism, as well as region specific differences in metabolism across hippocampal and cortical parts of the brain. Alterations to hippocampal metabolites involved in myelinogenesis could relate to the potential beneficial effects of a KD on memory. [ABSTRACT FROM AUTHOR]

Background/Objectives: Prurigo pigmentosa (PP) is a rare inflammatory dermatosis characterized by recurrent pruritic eruptions resolving with reticulated hyperpigmentation. Initially described in young Asian women, PP is increasingly reported worldwide, often linked to ketosis-inducing factors such as low-carbohydrate diets. This report documents the first case of PP in a Romanian patient and highlights the importance of recognizing the condition in diverse populations. Methods: We describe a 16-year-old girl with a six-month history of pruritic eruptions on the neck, trunk, shoulders, and thighs. A detailed clinical assessment was conducted, including dietary history, physical examination, laboratory evaluation of urinary ketones, and skin biopsy for histopathological analysis. Results: Clinical examination revealed erythematous papules and plaques with peripheral pustules and post-inflammatory hyperpigmentation. Substantial weight loss and elevated urinary ketone levels suggested dietary-induced ketosis from a strict low-carbohydrate diet. Histopathological findings confirmed the diagnosis of PP. The patient's skin lesions resolved following carbohydrate reintroduction and doxycycline therapy. Conclusions: This case highlights the association between ketosis and PP, emphasizing the importance of thorough dietary history-taking and histopathological confirmation for accurate diagnosis. As ketogenic diets become more popular globally, heightened awareness of PP is essential to ensure timely diagnosis and effective management. [ABSTRACT FROM AUTHOR]

Background: To date, there is no effective cure for the highly malignant brain tumor glioblastoma (GBM). GBM is the most common, aggressive central nervous system tumor (CNS). It commonly originates in glial cells such as microglia, oligodendroglia, astrocytes, or subpopulations of cancer stem cells (CSCs). Glucose plays an important role in the, which energy metabolism of normal and cancer cells, but cancer cells exhibit an increased demand for glucose is required for their differentiation and proliferation. The main aim of this study is to explore the anti-cancer efficacy of the ketogenic diet against GBM. Also, this research focuses on the identification of the catalytic action of zinc in epigenetic modulators such as oxyresveratrol and ensures the combinatorial effect in the treatment of GBM. Method: In this study, we have evaluated various parameters to understand the therapeutic efficacy of the treatment groups through in vivo experiments against aggressive brain tumors. Intracerebroventricular experiments were performed to induce the tumor in the animals and estimate the tumor burden and proliferative index. Followed by the Morris water maze, an open field test, and rota rod was performed to evaluate the memory and motor coordination. To understand the glucose, and ketone level modification before and after treatment, the level of glucose and ketone was analyzed. Moreover, the zinc level is assessed using flame atomic absorption spectroscopy. Results: The results suggested that the ketogenic diet has an anti-cancer efficacy against C6-induced GBM cell lines. Also, it exerts a synergistic effect with the epigenetic modulator, oxyresveratrol, and zinc against GBM cell lines. Moreover, the treatment groups improved memory and motor coordination and modified the glucose and ketone levels to reduce the tumor burden and Ki-67 proliferative index. Conclusion: This study revealed the therapeutic effect of the ketogenic diet along with its combination such as oxyresveratrol and zinc against the C6-induced GBM in the Wistar rats. Also, it improved memory and motor coordination and reduced tumor growth. It also modified the glucose and ketone levels in the tumor-induced animal and supported to diminish the tumor burden. [ABSTRACT FROM AUTHOR]

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Background and aims: To investigate the feasibility, safety and effectiveness of the ketogenic diet (KD) for super-refractory status epilepticus (SRSE) in the intensive care unit (ICU). Methods: We conducted a prospective investigation on patients with SRSE treated with the KD. The primary outcome measures were ketosis development as a biomarker of feasibility and resolution of SRSE as effectiveness. KD-related side effects were also investigated. Results: Twelve patients (9 females and 3 males) with SRSE, with a median age of 34 years [range 16–69, interquartile range (IQR) 18–52], were treated with a KD. The median duration of SRSE prior to KD treatment was 21 days (range 4–46). SRSE resolved in 75% (9/12) of patients at a median of 3 days (range 1–18) after KD initiation. Among the nine KD responders, all were successfully weaned off anesthetic agents at a median of 16 days (range 4–32) after KD initiation, and all were also successfully weaned off ventilator. Side effects varied, and included gastrointestinal intolerances, malnutrition and metabolic abnormalities, electrolyte disturbance, and acute weight loss, although most of them could be corrected. No patient died due to KD, and neurofunctions continued to improve under KD therapy. Conclusion: The KD may be feasible and effective for the treatment of SRSE in the ICU. Moreover, it is relatively safe. However, there are numerous adverse events that can be corrected under close monitoring. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder is a serious mental illness, which requires new strategies for prevention and management. Recent evidence suggests that a ketogenic diet may be an effective intervention. This research aimed to explore the feasibility and acceptability of a ketogenic diet intervention for bipolar disorder, fidelity to its behavioural components and the experiences of the participants and research clinicians involved. Methods: A mixed-methods process evaluation was conducted. Semi-structured telephone interviews were carried out with 15 participants 1–2 months after completing a 6–8 week modified ketogenic diet intervention, and 4 research clinicians from the study team following the completion of data collection. Data were thematically analysed. Fidelity checklists completed by research dietitians were analysed using descriptive count and percentage statistics. Findings are reported post-hoc, following the analysis and publication of the main pilot study findings. Reporting was guided by the COREQ checklist. Results: Five themes were identified in the qualitative data: (1) 'Encouraging entry and supporting exit' (e.g. recognising and managing participants' varied motives and expectations, including around weight loss and symptom alleviation); (2) 'Challenging but potentially transformational,' which reflects that while it can be difficult to initiate and maintain a ketogenic diet day-to-day, many participants perceived physical and psychological benefits (e.g. significant weight loss, mood stability and enhanced ability to focus); (3) 'Intervention facilitators,' including a range of behavioural (e.g. goal setting), social (e.g. family and dietitians) and technological (e.g. apps for monitoring) support mechanisms; (4) 'Intervention barriers' (e.g. dietary preferences, concerns about the diet and its impact, the testing burden and capacity of the delivery team); and (5) 'The wider context' (e.g. the cost of living and sociocultural expectations) was a crucial factor explaining differential experiences. Overall, descriptive analyses indicated moderate-to-good fidelity to the behaviour change components of the study. Conclusion: We provide novel insight into the experiences of people living with bipolar disorder initiating and following a ketogenic diet, as well as those of research clinicians who support the intervention. Future trials may benefit from increased clinical research capacity, better-defined entry and exit routes, additional interpersonal support, and greater understanding of how social and societal factors impact participation. Trial registration: Study registration number: ISRCTN61613198 (02/03/22). [ABSTRACT FROM AUTHOR]

The gut microbiome modulates the anti-seizure effects of the ketogenic diet, but how specific dietary formulations differentially modify the gut microbiome in ways that impact seizure outcome is poorly understood. We find that medical ketogenic infant formulas vary in macronutrient ratio, fat source, and fiber content and differentially promote resistance to 6-Hz seizures in mice. Dietary fiber, rather than fat ratio or source, drives substantial metagenomic shifts in a model human infant microbial community. Addition of fiber to a fiber-deficient ketogenic formula restores seizure resistance, and supplementing protective formulas with excess fiber potentiates seizure resistance. By screening 13 fiber sources and types, we identify metagenomic responses in the model community that correspond with increased seizure resistance. Supplementing with seizure-protective fibers enriches microbial genes related to queuosine biosynthesis and preQ0 biosynthesis and decreases genes related to sucrose degradation and TCA cycle, which are also seen in seizure-protected mice that are fed fiber-containing ketogenic formulas. This study reveals that different formulations of ketogenic diets, and dietary fiber content in particular, differentially impact seizure outcome in mice, likely by modifying the gut microbiome. Understanding interactions between diet, microbiome, and host susceptibility to seizures could inform novel microbiome-guided approaches to treat refractory epilepsy. Here, the authors show that different formulations of medical ketogenic diets, and dietary fiber content in particular, differentially impact seizure outcome in mice, via modifying the gut microbiome and microbial pathways associated with fiber-mediated seizure protection. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction, alongside repetitive behaviors, and atypical sensory-motor patterns. The growing prevalence of ASD has driven substantial advancements in research aimed at understanding its etiology, preventing its onset, and mitigating its impact. This ongoing effort necessitates continuous updates to the body of knowledge and the identification of previously unexplored factors. The present study addresses this need by examining the roles of nutrition, oxidative stress, and trace elements in the pathophysiology of ASD. In this review, an overview is provided of the key dietary recommendations for individuals with ASD, including gluten-free and casein-free (GFCF) diets, ketogenic diets (KDs), and other nutritional interventions. Furthermore, it explores the involvement of oxidative stress in ASD and highlights the significance of trace elements in maintaining neuropsychiatric health. The impact of these factors on molecular and cellular mechanisms was discussed, alongside therapeutic strategies and their efficacy in managing ASD. [ABSTRACT FROM AUTHOR]