Ketogenic Diet Therapy; Improving Outcome, Management and New Indications

Ketogenic diet therapy (KDT) for epilepsy is a high-fat (71-90 energy% (en%)), low-carbohydrate (5-19 energy%) diet with adequate amounts of protein that mimics the metabolic state of fasting without caloric restriction. Although KDT nowadays is seen as a well-established and effective treatment option in pharmacoresistant epilepsy in children, evaluation of clinical practice shows that its management and outcomes might be further improved. For some vulnerable groups of patients, the feasibility and safety of KDT application needs to be explored. There are new insights from studies with animals that carbohydrate restriction might influence growth of malignant tumors, especially tumor types (e.g. malignant brain tumors) that highly depend on glucose as energy source. The research presented in this thesis shows it is still not possible to predict successful outcome, that there is medication interfering efficacy of KDT, safe outpatient initiation of KDT is possible, consensus treatment guidelines for the vulnerable age group infants and one for parenteral application during complex medical situations. This thesis reports the application of KDT in new indications, during pregnancy of women with epilepsy and KDT as adjuvant to standard treatment of malignant brain tumors in both children and adults. The outcomes of the studies presented in this thesis confirm the potential and importance of KDT from a medical, social and economic perspective and have the potency to stimulate management decisions on making this non-pharmacological treatment option more widely available. The use of KDT as metabolic therapy in oncology is a new exciting area that needs further exploration

Ketogenic diet treatment in recurrent diffuse intrinsic pontine glioma in children: A safety and feasibility study

Background: The mean overall survival rate of children with diffuse intrinsic pontine glioma (DIPG) is 9–11 months, with current standard treatment with fractionated radiotherapy and adjuvant chemotherapy. So far, novel therapeutic strategies have not yet resulted in significantly better survival. The main source of energy for glioblastoma cells is glucose. Therefore, metabolic alterations induced by the use of the extremely carbohydrate-restricted ketogenic diet (KD) as adjuvant therapy are subject of interest in cancer research. Procedure: This study explores the safety and feasibility of the KD in children with recurrent DIPG and no remaining treatment options. Safety was defined as the number of adverse effects. Feasibility was defined as the number of patients who were able to use the KD for three months. Coping of patients and parents was measured with questionnaires. Results: Three of 14 children referred to our hospital between 2010 and 2015 were included. Two patients completed the study, and one died before the end of the study. Hospitalizations were needed for placing a nasogastric tube (n = 1) and epileptic seizures (n = 1). Adverse effects related to the diet were mild and transient. Parents were highly motivated during the study. Conclusion: Use of KD is safe and feasible, but the effect on survival has to be proven in a larger cohort of children who start the KD earlier after diagnosis, preferably as adjuvant therapy to fractionated radiotherapy

Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study

Background: High-grade glioma cells consume mainly glucose and cannot compensate for glucose restriction. Apoptosis may potentially occur under carbohydrate restriction by a ketogenic diet (KD). We explored the feasibility and safety of KD during standard treatment of chemoradiation in patients with glioblastoma multiforme. Methods: A full liquid KD induced ketosis within 2 weeks before start of chemoradiation. After 6 weeks, the KD was modified with solid foods and medium-chain-triglyceride emulsions and used for an additional 6 weeks while maintaining ketosis. During the total study period (14 weeks), feasibility, safety, coping (both patient and partner), quality of life (QoL), neurological functioning and impairment were measured. Overall survival was analyzed with actuarial estimates. Results: Eleven patients started the study protocol, nine reached ketosis and six (67%) completed the study. Severe adverse effects did not occur. The majority of coping scores ranged from 3 to 6 on a 10-point scale at all timepoints; QoL, neurological functioning, and impairment did not essentially change over time; overall survival ranged between 9.8 and 19.0 months. Conclusion: KD was feasible and safe as an adjuvant to standard chemoradiation treatment of glioblastoma multiforme. A supportive partner and intensive counseling were essential for coping. Future research should identify possible beneficial effects on overall survival. Clinical trial registration: Netherlands Trial Registry: NTR5167 (registration date 29-01-2015), http://www.trialregister.nl/trialreg/index.asp

Can we predict efficacy of the ketogenic diet in children with refractory epilepsy?

Background: The ketogenic diet (KID) can be effective in reducing seizures in children. Predictors of success have not been identified yet. Aims: To evaluate efficacy of KD treatment and to search for child- or diet-related factors that can predict its efficacy at 12 months follow-up. In addition we wish to determine the usefulness of a 3-month KD trial period. Methods: Single center retrospective study in a university paediatric hospital of children with refractory epilepsy in which the KD had been initiated. Patient and diet characteristics as well as seizure reduction data were obtained from medical records and parental review. Efficacy of the KD was defined as > 50% seizure reduction. Variables were evaluated in their relation to a successful treatment at three and 12 months after diet initiation. Results: During a 9.5-year period, the KD was initiated in 59 children with refractory epilepsy. Twenty-four children were still on the KD after 12 months, and 21 experienced >50% seizure reduction. Success of the KD at three months was significantly related to a successful response to KD treatment at 12 months (p <0.001). Conclusions: The KD can be an effective treatment in reducing seizures in children with refractory epilepsy. No significant relationships between variables and efficacy at 12 months were revealed. Children with a successful response at 3 months were significantly more likely to achieve success at 12 months of KD treatment. (C) 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved