The Ketogenic Diet: An Anticonvulsant

Though the ketogenic diet is primarily in the news as a means of weight loss, it has carved a useful niche in the treatment of child and adolescent epilepsy.


Epilepsy is a common neurological disorder arising from recurrent, excessive activation of the neurons in the brain that causes the characteristic seizures of the condition. It carries significant impacts across socio-economic, health and well-being domains. As such, effective seizure control is all the more important [1].


In modern day treatment protocols, anticonvulsant drugs are the first-line treatments, and are generally quite useful at preventing and/or decreasing seizure frequency. However, there are very few non-pharmaceutical treatments for epilepsy that are actually effective, and surprisingly, dietary therapy is chief among them. Traditionally, the ketogenic diet is used to treat epilepsy in children and adolescents and, more recently, adults. All versions of the diet - classical and modified - are of a high-fat and low-carbohydrate content [1]. The ketogenic diet is used to treat many epilepsy disorders as it is an alternative to pharmaceutical treatment for those with drug-resistant epilepsy or in individuals who suffer significant adverse effects from these antiepileptic drugs.


There are records of utilising fasting to treat epilepsy from as far back as the times of ‘The Father of Medicine’, Hippocrates. The first scientific article supporting fasting as a means of epilepsy treatment was published in the 20th Century by a couple of French physicians - G. Guelpa and A. Marie [2]. It was around the 1920s that doctors came to note that it was diets with high-fat and low-carbohydrate content that had patients presenting with fewer seizures. On these low-carbohydrate diets, the decrease in blood glucose levels causes the production of ketone bodies (known as ketogenesis) so the body can continue to function by relying on ketones for producing energy [3]. Eventually, owing to this metabolic process when on the diet, the name ‘Ketogenic Diet’ came to be. Therefore, while the term has been around for 100 years, the diet itself has existed for a lot longer [2]! There are, however, fewer studies investigating ketogenic diet on treatment in adult epilepsy patients.


It is unclear as to how these changes in body chemistry have resulted in the beneficial effects seen with the ketogenic diet. A pilot study published this year (2021) looked at the cerebrospinal fluid (CSF) as it was determined to be more relevant to the ketogenic diet effects in epilepsy. In the CSF samples taken, lipids and their metabolites were shown to have increased from baseline (before being on the ketogenic diet) to treatment (during the diet), as seen in Figure 1. The changes seen in carbohydrates were more varied - glucose decreased in those who responded to treatment, but some other carbohydrates increased. These increases in certain carbohydrates, like sorbose, were especially seen amongst those who did not see improvement in seizure control from the diet [3]. Unsurprisingly, there were great increases in ketone bodies and its fellow metabolites. The study raised the interesting question of whether these metabolic differences observed could explain why some subjects responded to the diet and observed a decrease in seizures, whilst others did not [3].



Figure 1: Changes in CSF levels of ketone bodies (γ-hydroxybutyrate and acetoacetate) increase significantly, and glucose decreases with ketogenic diet. Note that those with an optimal response to the diet saw greater changes. * and † correspond to thresholds of p-value (** p<0.01, *** p<0.001 compared to pre-KD; † p<0.05, ††p<0.01, †††p<0.001 compared to optimal responder during KD). [3].



Whilst many benefits are found for the treatment of epilepsy via the ketogenic diet, it is generally recommended as a last resort for individuals with drug-resistant epilepsy [4]. These recommendations are based on the cost-effectiveness and limitations the diet presents. Compliance with the diet is generally quite difficult, especially so in the long term, which might result in poor treatment outcomes, not only for the individual but perhaps on a larger societal scale in terms of cost-effectiveness [4].


Though the ketogenic diet is primarily in the news for its purported benefits in weight loss, it seems to have carved a useful niche in epilepsy treatment. Its promising potential warrants further research to figure out exactly how it leads to these benefits, which could one day lead to more targeted interventions to help patients suffering from treatment-resistant epilepsies.



References:

[1] Kaul N, Nicolo JP, O’Brien TJ, Kwan P. Practical considerations of dietary therapies for epilepsy in adults. Acta Epileptologica. 2021 Dec;3(1):1-7.


[2] Sampaio LP. Ketogenic Diet for Epilepsy Treatment. Arquivos de Neuro-Psiquiatria. 2016 Oct;74(10):842-8.


[3] Masino SA, Ruskin DN, Freedgood NR, Lindefeldt M, Dahlin M. Differential ketogenic diet-induced shift in CSF lipid/carbohydrate metabolome of pediatric epilepsy patients with optimal vs. no anticonvulsant response: a pilot study. Nutrition & Metabolism. 2021 Dec;18(1):1-1.


[4] De Kinderen RJ, Lambrechts DA, Wijnen BF, Postulart D, Aldenkamp AP, Majoie MH, Evers SM. An economic evaluation of the ketogenic diet versus care as usual in children and adolescents with intractable epilepsy: an interim analysis. Epilepsia. 2016 Jan;57(1):41-50.


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