Ketones as a treatment for seizures

The treatment of recurrent seizures (epilepsy) thru the use of dietary changes, specifically starvation, has been reported since Biblical times. The metabolic benefits of starvation are due to the shift to fat metabolism resulting in ketone body production. Since the ketogenic diet has the same metabolic effects of starvation, it has been used for the treatment of epilepsy first by Dr. Russell M. Wilder from Mayo Clinic, in the 1920s. Dr. Wilder observed a reduction of seizures by 50%. (Keene, 2006)

The diet fell out of favor as anti-seizure medications were developed. Since 1994 there has been a renewed interest in the ketogenic diet after the publicity of a young boy named Charlie who was treated very successfully with the ketogenic diet. He remains seizure free today off medications despite now being off the ketogenic diet.

The anti-epileptic effects of the ketogenic diet have been well studied. It is most commonly used kids with medically intractable seizures. A meta-analysis of the studies that have been preformed since 1990 was published in Pediatric Neurology in 2006. This study found 15.6% of the children who were treated with ketogenic diet for 6 months became seizure free and a third had greater than 50% reduction of seizures. Of significance, is that these patients were intractable, meaning they continued to have frequent seizures despite being on multiple antiepileptic medications before starting the diet.(Keene, 2006) The ketogenic diet is has been shown to be effective for all types of seizure disorders both in kids and adults. What is amazing is that some of the patients treated with ketogenic diet can actually maintain a significant reduction in seizures frequency or remain seizure free even after discontinuing the diet. (Baranano, 2008)

The difficultly with this this treatment is not whether the ketogenic diet works but keeping people compliant with it. It is a very rigid diet composed of eating very high fats (as high as 80- 90% fats) and very low carbohydrates (5%). This requires detailed meal planning, prepping, and weighing of foods. If this is not maintained, such that amount of carbohydrates are increased even a slight amount (such as by eating an half of a banana), they will be kicked out of ketosis. Thus losing the anti-epileptic benefits of the ketones until they get back into ketosis, which may take several days.

The anti-epileptic effect of the ketogenic diet is believed to be from the ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) that are produced by the body when on ketogenic diet. Thus the next question is, if giving the ketones exogenously, as an oral ketone supplement, would it have the same benefits as the ketogenic diet? The simple answer to this question is yes.

There have been 3 studies using different animal models of seizures. They have all shown that the use of exogenously given ketone bodies has an anti-epileptic effect. One study looked at preventing grand-mal seizures induced by central nervous system oxygen toxicity. (D’Agostino, 2013) Another looked at rats treated with a pro-convulsant agent PTZ. (Viggiano, 2015) The third study used a mouse model that represents human temporal lobe epilepsy. Importantly, this study also documented that the administration of ketone bodies has a direct positive effect, independent of the hypoglycemia. (Kim, 2015)

The mechanisms underlying the anticonvulsant effects of ketone bodies are not completely clear. Research indicates multiple possible mechanisms including thru the neuro-protective properties of ketones. Ketone bodies also have been shown to decrease the release of the excitatory neurotransmitter glutamate and increase the inhibitory neurotransmitter GABA. Others potential benefits include increasing intracellular ATP levels, decreasing reactive oxygen species, and improvement of mitochondrial function.

For more information of the ketogenic diet check out my other blog posts including potential benefits in Alzheimer’s dementia. For more information on a commercially available exogenous ketone supplement click this link.

Please, if you do want to use the ketogenic diet for treatment of your epilepsy make sure you are under medical supervision and do not stop or alter your anti-epileptic medication without approval of your Neurologist.

Bibliography

Baranano, K. W. (2008). The Ketogenic Diet: Uses in Epilepsy and Other Neurologic Illness. Current Treatment Options Neurology , 10 (6), 410-419.

D’Agostino, D. E. (2013). Theraputic ketosis with ketone esters delays central nervous oxygen toxicity seizures in rats. Am J Physiol Regul Integr Comp Physiol , 304, R829-R836.

Keene, D. (2006). A Systemic Review of the USe of the Ketogenic Diet in Childhood Epilepsy. Pediatruc Neurology (35), 1-5.

Kim, D. Y. (2015). Ketone Bodies Mediate Antiseizure Effects through Mitochondrial Permeability Transition. Annuals of Neurology (78), 77-87.

Stafstrom, C. E. (2012). The ketogenic diet as a treatment paradigm for diverse neurological disorders. Frontiers in Pharmacology , 3, 1-8.

Viggiano, A. D. (2015). Anticonvulsant properties of an oral ketone ester in a pentylenetetrazole-model of seizure. Brain Research , 50-54.

 

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