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 performed since 1990 was published in Pediatric Neurology in 2006. This study found 15.6% of the children who were treated with the 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 difficulty with this treatment is not whether the ketogenic diet works but keeping people compliant with it. The ketogenic diet is a very rigid diet composed of eating very high fats (as high as 70-80% 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 a 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 and acetoacetate) which are produced by the body when on the 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?

There have been several studies using animal models of seizures which studied the potential anti-seizure effect of ketone bodies given as a supplement.  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) A third study used a mouse model that represents human temporal lobe epilepsy. These studies all showed that the administration of ketone bodies as a supplement all had direct anti-seizure effects, independently to changes in diet.(Kim, 2015)

The mechanisms underlying the anticonvulsant effects of ketone bodies are not completely clear. Research indicates multiple possible mechanisms including thru the neuroprotective 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 about the ketogenic diet check out my other blog posts including potential benefits for 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 the 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). Therapeutic 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. Pediatric Neurology (35), 1-5.

Kim, D. Y. (2015). Ketone Bodies Mediate Antiseizure Effects through Mitochondrial Permeability Transition. Annals 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.

 

The medical information on this site is provided as an information resource only. This information does not create any patient-physician relationship, and should not be used as a substitute for professional diagnosis and treatment.

*These statements have not been evaluated by the Food and Drug Administration.  These products are not intended to are not intended to diagnose prevent treat or cure any disease.