scholarly journals Therapeutic Use of the Ketogenic Diet in Refractory Epilepsy: What We Know and What Still Needs to Be Learned

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2616
Author(s):  
Iwona Maria Zarnowska

Ketogenic diet (KD) has been used to treat epilepsy for 100 years. It is a high-fat, low-carbohydrate, and sufficient-protein-for-growth diet that mimics the metabolic changes occurring during starvation. Except for classic KD, its modified counterparts, including modified Atkins diet and low-glycemic-index treatment, have gained grounds to increase palatability and adherence. Strong evidence exists that the KD offers protection against seizures in difficult-to-treat epilepsy and possesses long-lasting anti-epileptic activity, improving long-term disease outcome. The KD can also provide symptomatic and disease-modifying activity in a wide range of neurodegenerative diseases. In an era of highly available new anti-seizure medications (ASMs), the challenge of refractory epilepsy has still not been solved. This metabolic therapy is increasingly considered due to unique mechanisms and turns out to be a powerful tool in the hands of a skillful team. Despite decades of extensive research to explain the mechanism of its efficacy, the precise mechanism of action is to date still largely unknown. The key feature of this successful diet is the fact that energy is derived largely from fat but not from carbohydrates. Consequently, fundamental change occurs regarding the method of energy production that causes alterations in numerous biochemical pathways, thus restoring energetic and metabolic homeostasis of the brain. There are barriers during the use of this special and individualized therapy in many clinical settings worldwide. The aim of this review is to revisit the current state of the art of therapeutic application of KD in refractory epilepsy.

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1809 ◽  
Author(s):  
Jana Wells ◽  
Arun Swaminathan ◽  
Jenna Paseka ◽  
Corrine Hanson

Epilepsy in the pediatric and adolescent populations is a devastating condition where individuals are prone to recurrent epileptic seizures or changes in behavior or movement that is the direct result of a primary change in the electrical activity in the brain. Although many children with epilepsy will have seizures controlled with antiseizure medications (ASMs), a large percentage of patients are refractory to drug therapy and may consider initiating a ketogenic diet. The term Ketogenic Diet or Ketogenic Diet Therapy (KDT) refers to any diet therapy in which dietary composition results in a ketogenic state of human metabolism. Currently, there are 4 major Ketogenic diet therapies—the classic ketogenic diet (cKD), the modified Atkins diet (MAD), the medium chain triglyceride ketogenic diet (MCTKD) and the low glycemic index treatment (LGIT). The compositions of the 4 main KDTs differ and limited evidence to distinguish the efficacy among different diets currently exists. Although it is apparent that more randomized controlled trials (RCTs) and long-term studies are needed to evaluate efficacy, side effects and individual response to the diet, it is imperative to study and understand the metabolic profiles of patients with epilepsy in order to isolate which dietary restrictions are necessary to maximize clinical benefit.


2016 ◽  
Vol 74 (10) ◽  
pp. 842-848 ◽  
Author(s):  
Letícia Pereira de Brito Sampaio

ABSTRACT The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients. This review summarizes the history of the KD and the principles and efficacy of the classic ketogenic diet, medium-chain triglyceride(s) (MCT) ketogenic diet, modified Atkins diet, and low glycemic index treatment.


Author(s):  
Suvasini Sharma

The Ketogenic Diet (KD) is a high fat, low carbohydrate and restricted protein diet which has been used for the treatment of drug resistant epilepsy in children. It is considered the treatment of choice for refractory nonsurgical epilepsy in children. However, despite this being a very useful and relatively simple treatment, children from developing countries have not been able to benefit as much as their counterparts in more privileged settings. In this article, the challenges faced by pediatric neurologists and parents who wish to use the diet in children with refractory epilepsy are discussed, and also the simple low cost innovations which can be used to overcome these challenges are suggested. The evolution from the use of the classic ketogenic diet to the flexible use of the modified Atkins diet in low resource settings will be discussed.


2019 ◽  
Vol 6 (4) ◽  
pp. 1773
Author(s):  
Bella Kurnia

Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet (KD) is a nonpharmacologic treatment that has been used for refractory epilepsy since 1921. The KD is a high-fat, low-carbohydrate, and restricted protein diet, which is calculated and weighed for each individual patient. The goal of the KD treatment is to bring the brain into a state of ketosis to control seizures. Many studies have shown that ketogenic diet was very useful in controlling refractory epilepsy.


2015 ◽  
Vol 22 (4) ◽  
pp. 389-394 ◽  
Author(s):  
Arrigo F. G. Cicero ◽  
Maddalena Benelli ◽  
Marco Brancaleoni ◽  
Giuseppe Dainelli ◽  
Desiré Merlini ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Aryadi Arsyad ◽  
Irfan Idris ◽  
Andi A. Rasyid ◽  
Rezky A. Usman ◽  
Kiki R. Faradillah ◽  
...  

Background. Ketogenic diet has been used as supportive therapy in a range of conditions including epilepsy, diabetes mellitus, and cancer. Objective. This study aimed to investigate the effects of long-term consumption of ketogenic diet on blood gas, hematological profiles, organ functions, and superoxide dismutase level in a rat model. Materials and Methods. Fifteen male Wistar rats were divided into control (n = 8) and ketogenic (n = 7) groups. Controls received standard diet contained 52.20% of carbohydrates, 7.00% fat, and 15.25% protein; meanwhile, the ketogenic group received a high-fat-low-carbohydrate diet which contained 5.66% of carbohydrate, 86.19% fat, and 8.15% protein. All rats were caged individually and received 30g of either standard or high-fat-low-carbohydrate pellets. The experiment was carried out for 60 days before the blood samples were taken and analyzed to obtain blood gas, cell counts, organ biomarkers, and plasma antioxidant superoxide dismutase (SOD) levels. Results. The rats subjected to ketogenic diet experienced a marked decrease in body weight, blood sugar, and increased blood ketones (p<0.05). The average blood pH was 7.36 ± 0.02 and base excess was −5.57 ± 2.39 mOsm/L, which were significantly lower than controls (p<0.05). Hematological analysis showed significantly lower erythrocyte, hemoglobin, and hematocrit levels. No significant changes were found in alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels, indicating normal liver and kidney functions. Nevertheless, plasma SOD level significantly reduced with ketogenic diet. Conclusion. Long-term ketogenic diet induces metabolic acidosis, anemia, and reduced antioxidant enzyme level in rats following 60 days of consuming high-fat-low-carbohydrate diet.


2020 ◽  
Vol 11 ◽  
Author(s):  
Wanghuan Dun ◽  
Tongtong Fan ◽  
Qiming Wang ◽  
Ke Wang ◽  
Jing Yang ◽  
...  

Empathy refers to the ability to understand someone else's emotions and fluctuates with the current state in healthy individuals. However, little is known about the neural network of empathy in clinical populations at different pain states. The current study aimed to examine the effects of long-term pain on empathy-related networks and whether empathy varied at different pain states by studying primary dysmenorrhea (PDM) patients. Multivariate partial least squares was employed in 46 PDM women and 46 healthy controls (HC) during periovulatory, luteal, and menstruation phases. We identified neural networks associated with different aspects of empathy in both groups. Part of the obtained empathy-related network in PDM exhibited a similar activity compared with HC, including the right anterior insula and other regions, whereas others have an opposite activity in PDM, including the inferior frontal gyrus and right inferior parietal lobule. These results indicated an abnormal regulation to empathy in PDM. Furthermore, there was no difference in empathy association patterns in PDM between the pain and pain-free states. This study suggested that long-term pain experience may lead to an abnormal function of the brain network for empathy processing that did not vary with the pain or pain-free state across the menstrual cycle.


2014 ◽  
Vol 94 (1) ◽  
pp. 81-140 ◽  
Author(s):  
Emmanuel Bourinet ◽  
Christophe Altier ◽  
Michael E. Hildebrand ◽  
Tuan Trang ◽  
Michael W. Salter ◽  
...  

The detection and processing of painful stimuli in afferent sensory neurons is critically dependent on a wide range of different types of voltage- and ligand-gated ion channels, including sodium, calcium, and TRP channels, to name a few. The functions of these channels include the detection of mechanical and chemical insults, the generation of action potentials and regulation of neuronal firing patterns, the initiation of neurotransmitter release at dorsal horn synapses, and the ensuing activation of spinal cord neurons that project to pain centers in the brain. Long-term changes in ion channel expression and function are thought to contribute to chronic pain states. Many of the channels involved in the afferent pain pathway are permeable to calcium ions, suggesting a role in cell signaling beyond the mere generation of electrical activity. In this article, we provide a broad overview of different calcium-permeable ion channels in the afferent pain pathway and their role in pain pathophysiology.


2011 ◽  
Vol 300 (6) ◽  
pp. G956-G967 ◽  
Author(s):  
Joel R. Garbow ◽  
Jason M. Doherty ◽  
Rebecca C. Schugar ◽  
Sarah Travers ◽  
Mary L. Weber ◽  
...  

Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis.


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