PURA syndrome is a congenital developmental disorder caused by de novo mutations in the PURA gene, which encodes a DNA/RNA-binding protein essential for transcriptional and translational regulation. We present the case of an 11-year-old patient with a de novo frameshift variant in the PURA gene, identified through whole exome sequencing (WES). In addition to the classical PURA deficiency phenotype, our patient exhibited pronounced sialorrhea and seizures, which were effectively treated with the ketogenic diet (KD). Our integrative approach, combining a literature review and bioinformatics data, has led to the first documented clinical case showing improvement in both sialorrhea and seizures with KD treatment, a phenomenon not previously reported. Although a direct relationship between the de novo PURA mutation and the KD was not established, we identified a novel frameshift deletion associated with a new clinical phenotype.

UNASSIGNED: There is little data that describe the use of ketogenic metabolic therapy to achieve full remission of major depression and generalized anxiety disorder in clinical practice. We present a retrospective case series of three adults with major depression and generalized anxiety disorder with complex comorbidity, treated with personalized ketogenic metabolic therapy, who achieved complete remission of major depression and generalized anxiety disorder and improvements in flourishing, self-compassion, and metabolic health.
UNASSIGNED: Three adults, ages 32-36, with major depression, generalized anxiety, other anxiety disorders, and comorbid psychiatric conditions were treated for 12-16 weeks with personalized whole food animal-based ketogenic metabolic therapy (1.5:1 ratio) in a specialized metabolic psychiatry practice. Interventions included twice-weekly visits with an experienced ketogenic registered dietitian; daily photo journaling and capillary blood BHB/glucose/GKI monitoring; virtual groups; family/friends support; nature walks and talks several times per week, and community building. Successful adoption of the ketogenic diet was defined as the achievement and maintenance of capillary BHB ≥ 0.8 mmol/L and GKI < 6. Remission was assessed by GAD-7 and PHQ-9, and quality of life was assessed subjectively and with validated scales for flourishing and self-compassion. Metabolic health was assessed by laboratories/biometric measures.
UNASSIGNED: Two patients achieved remission of major depression (PHQ-9 ≤ 4) and generalized anxiety (GAD-7 ≤ 4) within 7 weeks of therapeutic nutritional ketosis; one required 12 weeks. Anxiety responded and remitted more quickly than major depression. Flourishing and self-compassion increased steadily. Patients lost 10.9 to 14.8% of their initial body weight within 12 weeks and improved metabolically; one achieved optimal metabolic health.
UNASSIGNED: Complete remission of major depression and generalized anxiety disorder occurred within 7-12 weeks of therapeutic nutritional ketosis during treatment with a personalized animal-based ketogenic diet (ratio 1.5:1) in adults with complex comorbid depression and anxiety engaged in a specialized metabolic psychiatry program.

The Ketogenic Diet (KD) is a dietary regimen that is low in carbohydrates, high in fats, and contains adequate protein. It is designed to mimic the metabolic state of fasting. This diet triggers the production of ketone bodies through a process known as ketosis. The primary objective of KD is to induce and sustain ketosis, which has been associated with numerous health benefits. Recent research has uncovered promising therapeutic potential for KD in the treatment of various diseases. This includes evidence of its effectiveness as a dietary strategy for managing intractable epilepsy, a form of epilepsy that is resistant to medication. We are currently assessing the efficacy and safety of KD through laboratory and clinical studies. This review focuses on the anti-inflammatory properties of the KD and its potential benefits for neurological disorders and the gut-brain axis. We also explore the existing literature on the potential effects of KD on cardiac health. Our aim is to provide a comprehensive overview of the current knowledge in these areas. Given the encouraging preliminary evidence of its therapeutic effects and the growing understanding of its mechanisms of action, randomized controlled trials are warranted to further explore the rationale behind the clinical use of KD. These trials will ultimately enhance our understanding of how KD functions and its potential benefits for various health conditions. We hope that our research will contribute to the body of knowledge in this field and provide valuable insights for future studies.

Bone health encompasses not only bone mineral density but also bone architecture and mechanical properties that can impact bone strength. While specific dietary interventions have been proposed to treat various diseases such as obesity and diabetes, their effects on bone health remain unclear. The aim of this review is to examine literature published in the past decade, summarize the effects of currently popular diets on bone health, elucidate underlying mechanisms, and provide solutions to neutralize the side effects. The diets discussed in this review include a ketogenic diet (KD), a Mediterranean diet (MD), caloric restriction (CR), a high-protein diet (HP), and intermittent fasting (IF). Although detrimental effects on bone health have been noticed in the KD and CR diets, it is still controversial, while the MD and HP diets have shown protective effects, and the effects of IF diets are still uncertain. The mechanism of these effects and the attenuation methods have gained attention and have been discussed in recent years: the KD diet interrupts energy balance and calcium metabolism, which reduces bone quality. Ginsenoside-Rb2, metformin, and simvastatin have been shown to attenuate bone loss during KD. The CR diet influences energy imbalance, glucocorticoid levels, and adipose tissue, causing bone loss. Adequate vitamin D and calcium supplementation and exercise training can attenuate these effects. The olive oil in the MD may be an effective component that protects bone health. HP diets also have components that protect bone health, but their mechanism requires further investigation. In IF, animal studies have shown detrimental effects on bone health, while human studies have not. Therefore, the effects of diets on bone health vary accordingly.

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UNASSIGNED: Research in animal models on cerebral metabolism after brain injury highlights the potential benefits of ketosis in reducing secondary brain injury, but studies in humans are lacking.
UNASSIGNED: This study aimed to examine if a 6-week ketogenic diet intervention with added medium-chain triglycerides (MCT) was feasible in adult patients with acquired brain injury in the subacute phase, whether ketosis could be achieved and maintained, and to what extent serious adverse reactions, adverse reactions, serious adverse events, and adverse events occured.
UNASSIGNED: Patients ≥18 years of age diagnosed with subacute acquired brain injury and an expectation of hospitalisation ≥6 weeks were included in the intervention group. Patients not included in the intervention group were included in a standard care reference group. The intervention consisted of a ketogenic diet supplemented with MCT to obtain a plasma concentration of β-hydroxybutyrate (BHB) ≥0.5 mmol/L. Patients who were enterally fed were given KetoCal® 2.5:1 LQ MCT Multi Fiber (Nutricia A/S, Allerød, Denmark), supplemented with Liquigen® (Nutricia A/S, Allerød, Denmark). Patients consuming oral nutrition were given KetoCal® 2.5:1 LQ MCT Multi Fiber supplemented with Liquigen®, in addition to ketogenic meals.
UNASSIGNED: During a 13-week inclusion period, 12 of 13 eligible patients (92% [95% CI: 67% to 99%]) were included in the intervention group, and 17 of 18 excluded patients (94% [95% CI: 74% to 99%]) were included in the reference group. Eight patients (67%) completed the 6-week intervention. It took a median of 1 day to achieve ketosis from starting a 100% MCT ketogenic diet, and it was maintained for 97% of the intervention period after ketosis was obtained. There were no serious adverse reactions to the MCT ketogenic diet, and patients experienced adverse reactions not considered serious in 9.5% of days with the intervention. The MCT ketogenic diet was accepted by patients on all intervention days, and in the two patients transitioning from enteral feeding to oral intake, there were no complications related to transitioning.
UNASSIGNED: Intervention with MCT ketogenic diet is feasible and tolerated for 6 weeks in hospitalised adult patients with subacute acquired brain injury. Randomised controlled trials are needed to assess the benefits and harms of the MCT ketogenic diet and the effect on patients\' recovery.Clinical trial registration: ClinicalTrials.gov, identifier [NCT04308577].

Repetitive motor behaviors are associated with several neurodevelopmental disorders including autism spectrum disorder. Non-invasive environmental interventions that can ameliorate repetitive behavior and be introduced in early development could benefit many. In Experiment 1, we characterized the development of repetitive circling in mice reared in standard and enriched environments. Environmental enrichment was associated with reduced repetitive behavior. In Experiment 2, two weekly injections of an A2A adenosine receptor agonist reduced repetitive behavior in mice fed a ketogenic diet. Together, these two approaches modified the environment and reduced repetitive behavior with potential implications for increased functioning of the indirect basal ganglia pathway.

Neurodegenerative diseases are a large class of neurological disorders characterized by progressive dysfunction and death of neurones. Examples include Alzheimer\'s disease, Parkinson\'s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Aging is the primary risk factor for neurodegeneration; individuals over 65 are more likely to suffer from a neurodegenerative disease, with prevalence increasing with age. As the population ages, the social and economic burden caused by these diseases will increase. Therefore, new therapies that address both aging and neurodegeneration are imperative. Ketogenic diets (KDs) are low carbohydrate, high-fat diets developed initially as an alternative treatment for epilepsy. The classic ketogenic diet provides energy via long-chain fatty acids (LCFAs); naturally occurring medium chain fatty acids (MCFAs), on the other hand, are the main components of the medium-chain triglyceride (MCT) ketogenic diet. MCT-based diets are more efficient at generating the ketone bodies that are used as a secondary energy source for neurones and astrocytes. However, ketone levels alone do not closely correlate with improved clinical symptoms. Recent findings suggest an alternative mode of action for the MCFAs, e.g., via improving mitochondrial biogenesis and glutamate receptor inhibition. MCFAs have been linked to the treatment of both aging and neurodegenerative disease via their effects on metabolism. Through action on multiple disease-related pathways, MCFAs are emerging as compounds with notable potential to promote healthy aging and ameliorate neurodegeneration. MCFAs have been shown to stimulate autophagy and restore mitochondrial function, which are found to be disrupted in aging and neurodegeneration. This review aims to provide insight into the metabolic benefits of MCFAs in neurodegenerative disease and healthy aging. We will discuss the use of MCFAs to combat dysregulation of autophagy and mitochondrial function in the context of \"normal\" aging, Parkinson\'s disease, amyotrophic lateral sclerosis and Alzheimer\'s disease.

Currently, there is considerable interest in ketone metabolism owing to the benefits for human health. Conventionally, strict dietary restrictions on carbohydrates are required to increase plasma ketone levels, while supplementation with D-β-hydroxybutyric acid (D-BHB) can easily increase plasma ketone levels. We hypothesized that a daily intake of D-BHB could promote weight loss, especially through fat reduction. Herein, D-BHB (OKETOATM) was produced via a proprietary fermentation process from sugar. In this randomized, double-blind, placebo-controlled study, we assessed the safety and fat-reduction effects after 12 wk of daily ingestion of D-BHB (2.9 g) in 22 healthy Japanese adults and 22 control participants. Blood samples were collected pre- and post-treatment. Blood chemistry, anthropometric variables, and the body composition of the participants were investigated. Data analysis revealed that visceral fat at 12 wk significantly decreased by 9.0 cm2 (p=0.037), as evidenced by analysis of covariance. Blood parameters and body condition showed no significant differences between the two groups, and the participants reported no adverse effects or discomfort. Furthermore, data were analyzed by regrouping the participants. After removing one suspicious diabetes participant, all others showed significant decreases in visceral fat, body weight, BMI, and fat weight. Additionally, those aged under 50 y old had significantly decreased abdominal circumference and body fat percentage, in addition to visceral fat, body weight, BMI, and fat weight. Overall, our findings indicate that daily D-BHB intake may reduce body fat without dieting or exercise intervention. This study was registered with the UMIN Clinical Trials Registry as UMIN000045322.

In exercise science, the crossover effect denotes that fat oxidation is the primary fuel at rest and during low-intensity exercise with a shift towards an increased reliance on carbohydrate oxidation at moderate to high exercise intensities. This model makes four predictions: First, >50% of energy comes from carbohydrate oxidation at ≥60% of maximum oxygen consumption (VO2max), termed the crossover point. Second, each individual has a maximum fat oxidation capacity (FATMAX) at an exercise intensity lower than the crossover point. FATMAX values are typically 0.3-0.6 g/min. Third, fat oxidation is minimized during exercise ≥85%VO2max, making carbohydrates the predominant energetic substrate during high-intensity exercise, especially at >85%VO2max. Fourth, high-carbohydrate low-fat (HCLF) diets will produce superior exercise performances via maximizing pre-exercise storage of this predominant exercise substrate. In a series of recent publications evaluating the metabolic and performance effects of low-carbohydrate high-fat (LCHF/ketogenic) diet adaptations during exercise of different intensities, we provide findings that challenge this model and these four predictions. First, we show that adaptation to the LCHF diet shifts the crossover point to a higher %VO2max (>80%VO2max) than previously reported. Second, substantially higher FATMAX values (>1.5 g/min) can be measured in athletes adapted to the LCHF diet. Third, endurance athletes exercising at >85%VO2max, whilst performing 6 × 800 m running intervals, measured the highest rates of fat oxidation yet reported in humans. Peak fat oxidation rates measured at 86.4 ± 6.2%VO2max were 1.58 ± 0.33 g/min with 30% of subjects achieving >1.85 g/min. These studies challenge the prevailing doctrine that carbohydrates are the predominant oxidized fuel during high-intensity exercise. We recently found that 30% of middle-aged competitive athletes presented with pre-diabetic glycemic values while on an HCLF diet, which was reversed on LCHF. We speculate that these rapid changes between diet, insulin, glucose homeostasis, and fat oxidation might be linked by diet-induced changes in mitochondrial function and insulin action. Together, we demonstrate evidence that challenges the current crossover concept and demonstrate evidence that a LCHF diet may also reverse features of pre-diabetes and future metabolic disease risk, demonstrating the impact of dietary choice has extended beyond physical performance even in athletic populations.