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Ketogenic Diet: Can It Cure Epilepsy?

Introduction to the Ketogenic Diet

Assessment 9 – Anti-seizure medication is the standard therapy for patients with epilepsy as discussed in an earlier blog ( Assessment 6 – Epilepsy Medication – Need to Know Information). Despite the availability of over 20 some anti-seizure drugs, approximately 30-35% of patients with epilepsy gain no benefit from these medications.  These patients are considered to have resistant epilepsy.  Options for resistant epilepsy are few.  However, one such option is the ketogenic diet.  This blog will describe the ketogenic diet, its effect on seizures and its limitations.

Background

The composition and efficacy of the ketogenic diet was published close to 100 years ago in a paper by Peterman (1928).  It is named the classic ketogenic diet (CKD) to distinguish it from the more recently developed variations of this diet.  In many respects, the CKD is similar to starvation/fasting diets in vogue to treat epilepsy some 2000 years ago. 

Classic Ketogenic Diet (CKD)

Components of the Classic Ketogenic Diet

CKD is a diet that is very high in fats and very low in carbohydrates and proteins.  Adherence to the CKD requires consumption (as a percentage of daily calories) of 80-90% fats, 6-8% protein and 3-4% carbohydrates.  The dietary goal of the CKD is to convert normal metabolism driven by the use of sugars for energy to one driven by the use of fats for energy.  The result is a decline in blood levels of sugar and insulin and an elevation in blood levels of fats and their metabolic products, termed ketone bodies.  Ketone bodies (e.g. hydroxybutyrate, acetoacetate and acetone) are fats readily utilized by the brain.  Although poorly understood, the outcome is seizure suppression.

Modified Ketogenic Diets

As you can imagine, the CKD with its incredibly high fat content requirement is unappealing and to some quite unpalatable.  Patients that do not immediately respond to the diet, readily give up on it.  Generally after 2 years, only 30% of patients remain on the diet.  Hence, over the years, scientists developed modifications of the CKD. 

The established variations are a) modified Atkins Diet (MAD), b) the low glycemic index treatment (LGIT), and c) the medium chain triglyceride diet (MCTD).  Compared to CKD, these modified diets permit a significant reduction in consumption of fats and allow an increase in protein and carbohydrate consumption.  Specifically, the percentage of calories from fat is reduced to 60% or less. Protein is increased to 10-25 %. Similarly, carbohydrates is increased to 10-19%.  Although not studied as extensively as the CKD, these diets are more palatable. So far, the results of studies to date indicate that efficacy is close to that shown with the CKD.

Actual Dietary Benefits – Seizure Reduction

Children/Adolescents with Resistant Epilepsy  

Since 1928, as reviewed by Wells et al., (2020)  results of many studies (observational trials, randomized clinical trials and meta-analyses) show that adherence to the ketogenic diet significantly decreases seizure frequency in children and adolescents with resistant epilepsy.  In particular, from 2008 to 2017, 7 randomized clinical trials tested the efficacy of CKD or one of its variants.  The trials differed in number of patients (48-145), age of participants (1-18 years) and duration (3- 16 months).  Nevertheless, patients consuming ketogenic diets compared to those on a normal diet experienced significant reductions in seizure frequency.  Depending on the trial, 38% to 100% of patients on ketogenic diets experienced greater than a 50% reduction in seizure frequency.  Additionally, a smaller number  of patients became seizure free.

Adult Patients with Resistant Epilepsy  

There are few studies on the use of ketogenic diets in adult patients with resistant epilepsy.  A summary analysis of several small clinical trials with adults (18-86 yrs) with drug resistant epilepsy, concluded that CKD was efficacious in adults.  In particular, 53%  of patients experienced greater than 50% reduction in seizure frequency. Thirteen percent of patients were seizure free on the diet.  There is a need for confirmation with larger trials.

Mechanism of Seizure Reduction

There is no convincing evidence as to how an increase in ketone bodies serves to suppress seizures and in some cases to cure epilepsy.  Study results in animals suggest that ketone metabolism unlike sugar metabolism promotes

a) anti-inflammatory activity and neuronal protection and repair,

b) suppresses production of mediators that excite nerves and enhances production of mediators that inhibit abnormal nerve activity,

c) influences gut bacteria to produce effective brain relevant compounds, and changes brain metabolism to optimize function of favorable nerve genes. 

 At present, there is no evidence in man that these pathways predominate during adherence to ketogenic diets.

Adverse Effects Of the Ketogenic Diet

Appearance of adverse effects is one reason patients discontinue the ketogenic diet.  To be fair, this is not the only reason. Lack of efficacy and poor palatability of the diet are generally more important. Not surprisingly, a series of gastrointestinal-related changes are the main complaints with consumption of ketogenic diets.  Specific adverse effects include constipation, diarrhea, abdominal pain, gastroesophageal reflux, and hunger.  Other adverse effects, not as common occur with long term use (greater than one year). They are kidney stones, reduction of bone mineral content, and abnormal blood lipid profile e.g. elevation of triglycerides/low density lipoprotein (LDL) and decrease in high density lipoprotein (HDL).  However, abnormal blood lipids did not result in cardiovascular disease.  As expected, modified CKDs e.g. diets noted above, result in fewer and less severe adverse effects. Hence patients achieve greater tolerance and adherence

Summary

Ketogenic diets remain an option for patients of all ages with resistant epilepsy.  For those responding to these diets, seizure frequency declined by half or more and some patients become seizure free.  Compared to the classic ketogenic diet, the modified diets encourage greater adherence. Patients experience fewer adverse effects and efficacy is nearly equal to the classic diet.  Considering these observations, it seems incredibly important for scientists to determine exactly how ketogenic diets work to suppress seizures.

Reference used for this blog are available on request and found on pubmed.com.