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Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with a universally lethal prognosis despite maximal standard therapies. Here, we present a consensus treatment protocol based on the metabolic requirements of GBM cells for the two major fermentable fuels: glucose and glutamine. Glucose is a source of carbon and ATP synthesis for tumor growth through glycolysis, while glutamine provides nitrogen, carbon, and ATP synthesis through glutaminolysis. As no tumor can grow without anabolic substrates or energy, the simultaneous targeting of glycolysis and glutaminolysis is expected to reduce the proliferation of most if not all GBM cells. Ketogenic metabolic therapy (KMT) leverages diet-drug combinations that inhibit glycolysis, glutaminolysis, and growth signaling while shifting energy metabolism to therapeutic ketosis. The glucose-ketone index (GKI) is a standardized biomarker for assessing biological compliance, ideally via real-time monitoring. KMT aims to increase substrate competition and normalize the tumor microenvironment through GKI-adjusted ketogenic diets, calorie restriction, and fasting, while also targeting glycolytic and glutaminolytic flux using specific metabolic inhibitors. Non-fermentable fuels, such as ketone bodies, fatty acids, or lactate, are comparatively less efficient in supporting the long-term bioenergetic and biosynthetic demands of cancer cell proliferation. The proposed strategy may be implemented as a synergistic metabolic priming baseline in GBM as well as other tumors driven by glycolysis and glutaminolysis, regardless of their residual mitochondrial function. Suggested best practices are provided to guide future KMT research in metabolic oncology, offering a shared, evidence-driven framework for observational and interventional studies., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: A.P. is an owner of Poff Medical Consulting and Communications, LLC, which performs consulting and public speaking services related to ketogenic metabolic therapy. A.P. is a scientific advisor to Pruvit Ventures, LLC, which sells exogenous ketone products. A.P. is an owner of Metabolic Health Initiative, LLC which is a medical education company in the field of metabolic health and metabolism-based therapies. A.P. is an inventor on and receives royalties from the following patent: “Targeting Cancer with Metabolic Therapy and Hyperbaric Oxygen” (Patent Number: 9801903). D.P.D. is an inventor of patents on the use of exogenous ketones, advisor for Levels Health, and co-owner of Ketone Technologies LLC, which does consulting and public speaking events. C.E.C. receives royalties from books, consulting, and lectures on nutrition and exercise, and serves on the scientific advisory board of Simply Good Foods/Atkins. M.K. is employed by Dietary Therapies LLC. The other authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Anorexia nervosa (AN) is a severe psychiatric disorder, and shape and weight concerns are often chronic despite weight normalization. No specific treatments exist for those preoccupations that interfere with recovery and trigger relapse. A case study using a ketogenic diet followed by ketamine infusions led to sustained remission in one patient with chronic AN. Here we conducted an open-label trial to test whether this response could be replicated., Methods: Five adults weight recovered from AN but with persistent eating disorder thoughts and behaviors adopted a therapeutic ketogenic diet (TKD) aimed at maintaining weight. After sustaining nutritional ketosis, participants received six ketamine infusions and were followed over 6 months., Results: All participants completed the study protocol without significant adverse effects. Two participants maintained TKD for 8 weeks prior to ketamine infusions due to good behavioral response and remained on TKD. Three participants received TKD for 4 weeks prior to and during ketamine, then tapered off after the final infusion. The group showed significant improvements on the Clinical Impairment Assessment (p = 0.008), Eating Disorder Examination Questionnaire (EDEQ) Global score (p = 0.006), EDEQ-Eating Concerns (p = 0.005), EDEQ-Shape Concerns (p = 0.016), EDEQ-Weight Concerns (p = 0.032), Eating Disorders Recovery Questionnaire (EDRQ) Acceptance of Self and Body (0.027) and EDRQ-Social and Emotional Connection (p = 0.001). Weight remained stable, except for one participant who relapsed 4 months after treatment and off TKD., Conclusion: This novel treatment appears to be safe and effective for adults with chronic AN-related psychopathology. The results from this open trial support that there are specific neurobiological underpinnings of AN that can be normalized using TKD and ketamine., Level of Evidence: Level IV, multiple time series with intervention., (© 2022. The Author(s).)

Objective: To evaluate current clinical practices and evidence-based literature to establish preliminary recommendations for the management of adults using ketogenic diet therapies (KDTs)., Methods: A 12-topic survey was distributed to international experts on KDTs in adults consisting of neurologists and dietitians at medical institutions providing KDTs to adults with epilepsy and other neurologic disorders. Panel survey responses were tabulated by the authors to determine the common and disparate practices between institutions and to compare these practices in adults with KDT recommendations in children and the medical literature. Recommendations are based on a combination of clinical evidence and expert opinion regarding management of KDTs., Results: Surveys were obtained from 20 medical institutions with >2,000 adult patients treated with KDTs for epilepsy or other neurologic disorders. Common side effects reported are similar to those observed in children, and recommendations for management are comparable with important distinctions, which are emphasized. Institutions differ with regard to recommended biochemical assessment, screening, monitoring, and concern for long-term side effects, and further investigation is warranted to determine the optimal clinical management. Differences also exist between screening and monitoring practices among adult and pediatric providers., Conclusions: KDTs may be safe and effective in treating adults with drug-resistant epilepsy, and there is emerging evidence supporting the use in other adult neurologic disorders and general medical conditions as well. Therefore, expert recommendations to guide optimal care are critical as well as further evidence-based investigation., (© 2021 American Academy of Neurology.)

Epilepsy is a common neurologic disorder in humans and domesticated canines. In both species the etiology is diverse and complex, and even with medication a significant portion of the population does not experience sufficient seizure control and/or has unacceptable side effects. Humans often try alternatives such as dietary therapy or brain surgery, but in dogs, brain surgery is rarely an option and, despite potential benefits, there are no standard recommendations for a dietary approach. Herein we describe 2 retrospective case studies detailing the effects of homemade diets prepared for dogs with uncontrolled epileptic seizures and/or toxic side effects of medication. Basic recipes are provided for each formula-a high-fat "ketogenic" diet and a partial "whole food" diet. Carbohydrate content was reduced or controlled, and in one case this was proven to be essential for seizure control: ingesting carbohydrates would reverse the benefits of the diet and precipitate a seizure. Both dogs experienced fewer seizures and side effects when eating these modified diets compared to when they were administered antiepileptic drugs, including complete cessation of seizures for extended periods. Practical advantages and success of these homemade dietary interventions highlight the potential for diet-based metabolic therapy as a treatment option for seizures not only in humans but also in dogs., Competing Interests: 7Author Beth Zupec‐Kania is the sole proprietor of Ketogenic Therapies, LLC. The remaining authors have no conflicts of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Objectives: To retrospectively assess the incidence of high beta hydroxybutyrate, low bicarbonate (BIC), high acyl carnitine, low selenium, low magnesium, low zinc, low phosphorus, in a cohort of supplemented patients treated with the ketogenic diet (KD) for medically intractable epilepsy. To analyze effect of age, duration of exposure to KD, type of KD, and route of KD intake on lab abnormalities. To analyze the incidence of clinically actionable results, resulting in medical interventions based on abnormal results and to analyze costs of testing., Methods: Retrospective chart review and statistical analysis. Association between abnormal values (binary) and categorical variables was tested with Chi-square/Fisher's exact test. Associations between abnormal values (binary) and continuous variables were analyzed with logistic regression. Statistical analyses were performed in SAS 9.4., Results: We included 91 patients with average duration on diet of 46.73 months (IQR 18.8-75.5 months). Most patients were on the classic KD (81 KD- 59% on 4:1 ratio, 10 modified Atkins diet). 74% were orally fed and 70% completed lab visits to the 12-month mark. There was no significant association between abnormal laboratory parameters and duration of exposure, type of diet, route of administration. Younger children were more likely to have low BIC, high acyl carnitine. Older children were more likely to have low phosphorus. Less than 15% of patients reported clinical changes to suggest dietary deficiency in vitamins/ minerals and in < 11% of cases was an actionable laboratory parameter found., Significance: Our study is the first to document the real-life incidence of selected tests being abnormal when following consensus guidelines on lab testing. Elimination of tests with low yield will result in cost savings of up to $USD 185 per visit. Low phosphorus is frequently found in patients on KD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background & Aims: It is widely acknowledged that the energy metabolism of cancer cells mainly relies on anaerobic glycolysis and this has prompted many researchers to try to reduce the malignant cells growth of experimental tumours through a programme of calorie restriction. Recently this approach has been proposed also to cancer patients. In the meantime it was demonstrated that the effects of calorie restriction on tumour growth are mediated through the toxic effect of ketone bodies on cancer cells which have a defective mitochondrial function, while these substrates are well-utilized by the normal cells., Methods: This review analyzes the main available data regarding the tumour growth in patients undergoing a period of starvation or of normal/artificial nutrition as well as the recent approach through special normocaloric ketogenic diets which are well utilized by cancer patients while may be unfavourable for cancer cells., Results: Despite the paucity of data it appears that modulation of tumour growth by the calorie restriction/nutritional support is unlikekly in humans for several reasons: the different tumour cells growth rate and different tumour/host carcass ratio and duration of treatment, between tumour-bearing animals and patients., Conclusion: There is a large consensus in literature that maintaining a normal body weight and preserving the lean body mass through an adequate nutrition is beneficial in cancer patients. The nutritional approach through a ketogenic diet which may be toxic for the cancer cells while is well utilized and tolerated by the patient seems promising in a next future., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Refractory status epilepticus carries a high risk of morbidity and mortality for children. Traditional treatment of status epilepticus consists of multiple anticonvulsant drugs and, if needed, induction of a medical coma. The ketogenic diet has been used for intractable epilepsy for many years. The purpose of this article is to report a case series of five patients with refractory status epilepticus successfully managed with the ketogenic diet., Methods: A summary of pediatric patients with refractory status epilepticus treated with diet was performed., Conclusions: Ketogenic diet therapy should be considered as a treatment option in pediatric patients with refractory status epilepticus., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Ketogenic diet therapies involve a collaborative healthcare team and therefore are typically offered in tertiary care centers. Centers that utilize these therapies with frequency gain valuable experience and become skilled in their practice. This chapter is a summary from the presentations of 5 practitioners including a nurse, pharmacist, and 3 dietitians who shared their expertise during the clinical session of the 2012 International Symposium.

The classic ketogenic diet (KD) is a mathematically calculated diet with specific daily goals of fat, protein, and carbohydrate. Precise quantities of foods are then derived from these values which result in meal plans for the individual patient. The algebraic algorithm to determine a single meal requires approximately 35 calculations. This process is time consuming given that each individual requires many meals for variety and satisfaction. Computer applications can process multiple calculations in seconds. In 1997, a program was designed by this author with LifeTime Computing, a computer software company. This program was rebuilt into digital format in 2002, given the title KetoCalculator, and made available to registered dietitians on the World Wide Web (Zupec-Kania, 2002).

The ketogenic diet (KD) is a medical nutrition therapy (MNT) for the treatment of epilepsy. As such, it can affect the outcome of an individual's health and chronic medical condition. The components of MNT which have been established by the American Dietetic Association as core guidelines for nutrition care include a diet history, assessment, diet therapy and a follow-up plan of care (American Dietetic Assoc 2002). We have utilized these guidelines in designing our approach to KD therapy in our pediatric population. Many of the practices described here have been adopted from our practical experience.