Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study.

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.

What are the minimum requirements for ketogenic diet services in resource-limited regions? Recommendations from the International League Against Epilepsy Task Force for Dietary Therapy.

Despite the increasing use of dietary therapies for children and adults with refractory epilepsy, the availability of these treatments in developing countries with limited resources remains suboptimal. One possible contributory factor may be the costs. There is often reported a significant perceived need for a large ketogenic diet team, supplements, laboratory studies, and follow-up visits to provide this treatment. The 2009 Epilepsia Consensus Statement described ideal requirements for a ketogenic diet center, but in some situations this is not feasible. As a result, the International League Against Epilepsy (ILAE) Task Force on Dietary Therapy was asked to convene and provide practical, cost-effective recommendations for new ketogenic diet centers in resource-limited regions of the world.

International Recommendations for the Management of Adults Treated With Ketogenic Diet Therapies.

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.

Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report.

BACKGROUND: Chronic anorexia nervosa is a tragic disease with no known effective pharmacological or behavioral treatment. We report the case of a 29 year-old woman who struggled with severe and enduring anorexia nervosa for 15 years, and experienced a complete recovery following a novel treatment of adopting a ketogenic diet followed by ketamine infusions. Her remission has persisted for over 6 months. CASE PRESENTATION: At age 14.5, the patient embarked on an effort to "eat healthy." She quickly lost control of the dieting, developed associated compulsions and obsessions about food, body dissatisfaction, emotional lability, and lost nearly 13.6 kilograms (30 pounds). She was hospitalized for 6 weeks, and while she regained some weight, she did not attain full weight restoration. For 15 years, she continued to eat in a restrictive manner, exercise compulsively, and have intermittent periods of alcohol dependence. Nevertheless, she always hoped to get well, and at age 29, she began a novel treatment for anorexia nervosa. CONCLUSIONS: This is the first report of a ketogenic diet used specifically for the treatment of anorexia nervosa, followed by a short series of titrated IV ketamine infusions leading to complete remission of severe and enduring anorexia nervosa, with weight restoration, and sustained cessation of cognitive and behavioral symptoms, for 6 months. Although these treatments were used sequentially the relationship between these modalities, and possible synergy, is unclear, and deserves further study. Complete and sustained remission of chronic anorexia nervosa is quite rare, and the novel use of a ketogenic diet and IV ketamine treatment in this potentially lethal condition suggests avenues for further research, and hope for patients and their families.

Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group.

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.

Dietary intervention for canine epilepsy: Two case reports.

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.

Yield of laboratory testing in pediatric ketogenic diet patients: Critical assessment of abnormal results and impact on clinical care.

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.

KetoCalculator: a web-based calculator for the ketogenic diet.

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).

Long-term management of the ketogenic diet: seizure monitoring, nutrition, and supplementation.

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.

An overview of the ketogenic diet for pediatric epilepsy.

Epilepsy is the most common serious neurological condition in the world, with an estimated prevalence of 1% of the population. The highest incidence occurs in childhood and in the elderly, with lower levels in early adulthood. Traditional epilepsy management includes pharmacological treatment, epilepsy surgery, and vagal nerve stimulation. Despite these therapies, 25% of children continue to have uncontrolled seizures. The ketogenic diet (KD), which has been in use since 1921, is a treatment option for many of these children. A meta-analysis of 19 studies with a combined sample of 1084 pediatric patients was completed in 1998 by Blue Cross Blue Shield. Estimates of the overall efficacy of the KD in controlling seizures were reported as follows: 16% became seizure free, 32% had a >90% reduction in seizures, and 56% had a >50% reduction. The KD is high in fat, moderate in protein, and low in carbohydrates. This combination of energy results in a sustained ketosis that somehow serves to abate seizures through an unknown mechanism. Strict adherence to the diet is required for it to be effective. Newer, more liberal versions of the KDs have been recently introduced and are being studied in children and adults. Administration of all of these metabolically adjusted diets must be medically managed as there can be adverse effects. The focus of this review is on the pediatric application of the KD.

Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group.

Ketogenic dietary therapies (KDTs) are established, effective nonpharmacologic treatments for intractable childhood epilepsy. For many years KDTs were implemented differently throughout the world due to lack of consistent protocols. In 2009, an expert consensus guideline for the management of children on KDT was published, focusing on topics of patient selection, pre-KDT counseling and evaluation, diet choice and attributes, implementation, supplementation, follow-up, side events, and KDT discontinuation. It has been helpful in outlining a state-of-the-art protocol, standardizing KDT for multicenter clinical trials, and identifying areas of controversy and uncertainty for future research. Now one decade later, the organizers and authors of this guideline present a revised version with additional authors, in order to include recent research, especially regarding other dietary treatments, clarifying indications for use, side effects during initiation and ongoing use, value of supplements, and methods of KDT discontinuation. In addition, authors completed a survey of their institution's practices, which was compared to responses from the original consensus survey, to show trends in management over the last 10 years.

Toward a cancer-specific diet.

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.

The ketogenic diet for the treatment of pediatric status epilepticus.

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.

An update on diets in clinical practice.

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.

Ketogenic diets: an update for child neurologists.

The ketogenic diet, modified Atkins diet, and low-glycemic-index treatment have all emerged over the past decade as important therapeutic options for children with intractable epilepsy. Whereas only a decade ago the ketogenic diet was seen as an "alternative'' treatment of last resort, it has become more frequently used throughout the world. The past year alone 2 randomized and controlled trials of the ketogenic diet were published, as well as the use of the ketogenic diet for new-onset epilepsy (infantile spasms), and a 26-member international consensus statement guiding optimal clinical management. There has been an equally dramatic increase of interest into mechanisms of action using various experimental models. Researchers are also highly interested in using diets for neurologic disorders other than epilepsy, including autism and brain tumors. This review will update child neurologists on the recent advances in the use of ketogenic diets.