Emma Craig Ketogenic Diets and Epilepsy The world of nutrition is constantly growing in both popularity and research

in todays society. More and more people are starting to realize just how important food is and how much it can affect the human body. Scientists are turning to food as a source of disease prevention and treatment, not just a foundation of fuel for the human body. The right types of food offer carbohydrates, fats, proteins, antioxidants, vitamins, minerals and water; all of which can be used to keep the body healthy and inhibit potential illnesses. When disease strikes, these micronutrients and macronutrients have a different responsibility: to fight the disease when medication is not an option or no longer works. One disease in specific, epilepsy, affects 65 million people worldwide, of this 300,000 are children, and of these 300,000 children, 90,000 cannot be adequately treated (Epilepsy Foundation, 2012). In the extreme cases of children, doctors have turned to a high fat, low-carbohydrate ketogenic diet, which produces ketones, in addition to medicine in hopes to control the epilepsy. Epilepsy in children is a disease characterized by recurrent seizures. Seizures occur when there is a disturbance in brain function. This disturbance happens when a group of nerve cells in the brain send abnormal and excessive brain signals. Brain signals are produced by action potentials. Generally, an action potential is triggered, and travels through motor neurons to an effector. This effector could be an organ or a muscle group. If the nerves are firing rapidly, going to all different effectors, rapid movements or involuntary actions will occur. There is more than one classification of what a seizure actually is. These classifications range from: atonic, which results in loss of muscle control to status epilepticus, a non-stop seizure generally requiring hospitals care. Seizures can last between a few seconds to a few minutes. In most cases, it is not

Craig 2 known what causes epilepsy. This being said oxygen deprivation at birth, brain infections, brain or head injury, stroke, brain tumors and certain genetic disorders are known to cause epilepsy (Center for Disease Control, 2012). A ketogenic diet is a non-invasive treatment for extreme cases of epilepsy that requires a certain amount of each macronutrient that is usually not recommended to the general public. A ketogenic diet is based on the idea that with enough fat, adequate protein, and little carbohydrates (generally a 4:1 ratio with respect to carbohydrate and protein combined), the body will set into ketosis and produce ketones. This mimics the idea of a starving state, which was used to treat seizures many years ago. Acetoacetate, beta-hydroxybutyrate, and acetone are the three main ketones produced by mitochondrial fatty acid oxidation. Acetly Co-A is synthesized into the three ketone bodies. These ketone bodies are then used as a source of fuel for the brain and body, instead of the usual glucose. The entrance of ketones into the brain occurs with the help of the bloodbrain barrier monocarboxylic transporter (MCT-1) (Hartman, Stafstrom 2012). There is no exact mechanism known for how exactly these ketones work in helping to prevent seizures, although there are several hypotheses. A variety of theories have been tested on how exactly ketones can help epilepsy. It has been proposed that acetone is responsible for the anticonvulsant effect of the ketogenic diet, based on studies done on mice injected with acetone. Acetone has this capability by preventing seizures induced by pentylentetrazol and AY-9944. Unfortunately, the ketogenic diet is not capable of doing so. Unlike using solely acetone, the ketogenic diet when used on mice, did not prevent against the pentylentetrazol seizures. This negates ideas that acetone is the sole ketone body responsible for the anticonvulsatory effects, but does not mean it is not contributory (Hartman, Gasior, Vining, Rogawski 2007). Another theory proposed to explain the effects of

Craig 3 the ketogenic diet focuses on -aminobutyric acid, also known as GABA. GABA is an inhibitory neurotransmitter that in some cases has shown to be higher in the cerebrospinal fluid of patients on the ketogenic diet. This could suggest ketones help increase the levels of GABA, which then prevent the number of seizures experienced by the patient. The exact specifics of how this occurs are unknown (Hartman, Stafstrom 2012). Another theory deals with KATP channels. KATP channels have hyperpolarizing abilities and deal with cellular metabolism. In the presence of the ketone beta-hydroxybutyrate, KATP inward-rectifying openings were increased. This showed increased neural inhibition, which can decrease seizure effects. Further research needs to be done on this topic in order to be proven as well (McNally, Hartman, 2012). As clearly portrayed, the exact mechanisms of how ketogenic diets and ketosis works are unknown. It could be a variety of different theories that may work alone or work together. Whether it is the GABA neurotransmitter or the KATP channels, the ketogenic diet is becoming more successful and is growing in the field of dietetics and medical research. Scientists, doctors and nutritionists will continue to do research until the reasoning is known; in hopes that one-day epilepsy can be treated completely.

Craig 4 References Epilepsy Foundation (n.d.). Retrieved from http://www.epilepsyfoundation.org/aboutepilepsy/treatment/ketogenicdiet/index.cfm Hartman, A., Gasior, M., Vining, E., & Rogawski, M. (2007). The neuropharmacology of the ketogenic diet.Pediatric Neurology, 36(5), 281-292. Hartman, A., & Stafstrom, C. (2013). Harnessing the power of metabolism for seizure prevention: focus on dietary treatments. Epilepsy & Behavior: E&B, 26(3), 266-272. doi:10.1016/j.yebeh.2012.09.011. McNally, M., & Hartman, A. (2012). Ketone bodies in epilepsy. Journal Of Neurochemistry, 121(1), 28-35. doi:10.1111/j.1471-4159.2012.07670. National Center for Chronic Disease Prevention and Health Promotion , D. O. P. H. (n.d.). Retrieved from http://www.cdc.gov/epilepsy/