The ketogenic diet, also known as the traditional ketogenic diet and modified Atkin’s diet, is an important and validated dietary approach to controlling intractable epilepsy that focuses on a high-fat, protein, and low-carb diet. Yet despite its success in cases of drug-resistant epilepsy, the mechanism behind its effectiveness is still not well understood.
Several hypotheses are based on the difference in cell metabolism between standard and fat-based KD, while other hypotheses focus on increased production of adenosine triphosphate.
“There is an ion channel in the membrane of neurons which makes membrane less excitable; a potassium channel which is activated specifically by adenosine triphosphate (ATP). The more ATP is generated, the more this channel is active and the less excitable the neuron becomes,” said Pavel Klein, MD, of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, Maryland. “It has also been shown that ketone bodies also act directly to reduce the release of glutamate, the main excitatory neurotransmitter. When less glutamate is released by a neuron, neighboring neurons are excited less and less prone to generate a seizure.”
Diet Efficacy in Adults and Children
Data on the efficacy of KD and the modified Atkin’s diet (MAD) in children and adults are similar.1 “Approximately one-third of adults with epilepsy that does not respond to medications may have a 50% seizure frequency reduction. Five to 10% of these adults may have a dramatic response, with greater than or equal to 90% seizure frequency reduction. This is similar to the response seen in children,” said Klein.
However, the main difference between children and adults is persistence of the effect of KD after discontinuing the diet. In a small proportion of children who become seizure free on the diet, the seizures do not recur even after the diet is stopped. In adults, this has not been seen so far.
KD is also known to be effective in a number of rare childhood epilepsies, including Dravet syndrome and Lennox-Gastaut syndrome. A recent study found KD equally as effective as various antiepileptic drugs as compared with vagus nerve stimulation.2 In addition, Klein said KD is the specific treatment for glucose transporter 1 deficiency, a very rare form of intractable epilepsy in children.
Determining Outcomes of the Ketogenic Diet
Determining who will respond well to KD is a topic still ripe for research. Researchers have previously explored the use of electroencephalogram, but results from a recent study were not statistically signifigant.3 Other studies have explored a patient’s preference for certain foods, but neither have been very effective strategies to determine the success of KD.
In a recent study, Eric H. Kossoff, MD, of Johns Hopkins Children’s Center in Baltimore, Maryland, and colleagues found that children with epilepsy preferred fat and avoided carbohydrates when presented with a choice between two types of foods.4
“However, we did not find a clear correlation between how much they preferred fat and how well they later did with either the KD or MAD. There was a slight hint that those with seizure freedom with the KD or MAD were those with the highest fat preference, but it wasn’t statistically significant overall,” said Kossoff. “Although interesting, the idea of fat preference being a screening test for going on the KD or MAD doesn’t appear to be valid. However, tt also tells us that if a child does not prefer fat, it does not mean they shouldn’t go on the KD or MAD.”
While KD and MAD have demonstrated efficacy in reducing the extent and degree of seizures in epileptic patients, the dietary approaches have been tied to risk of adverse events in both adults and children, although most are treatable and are nearly all preventable. Adverse effects include constipation, low blood sugar, and gastrointestinal reflux.5,6 Other side effects, such as kidney stones and high cholesterol, can often be improved with supplements or dietary changes.1 These also tend to improve over the long term. Kossoff and colleagues found that both total cholesterol and LDL cholesterol normalized within a year of treatment after initial increases during the first three months of MAD.5
Similar trends in adverse events have been noted in children. One key concern is the high risk of osteoporosis, which reaches as high as 20% in KD cases. Along with osteoporosis come growth issues. “Children on the classic KD do often grow slightly slower than children not on the diet. When the diet stops, there is ‘catch-up’ growth, usually to normal,” said Kossoff.
Success in the Long Term
In terms of seizure recurrence among children, the risk of seizures returning in those who are seizure free and stop the diet is 15 to 20%, according to Kossoff. In children who experience less frequent seizures, but are not seizure free, about one-third will have some worsening of seizures when the diet is stopped, though this is sometimes transient.
Overall, the benefits of KD and MAD appear to outweigh the risk of long-term adverse events, providing an immeasurable boost to quality of life that cannot be accomplished with antiepileptic drugs.
Beth Gilbert is a freelance health and science writer. She has an undergraduate degree in chemical engineering from Lehigh University and a Master’s in biomedical engineering from Columbia University. This article was medically reviewed by Pat F. Bass III, MD, MS, MPH.
- Klein P et al. Dietary treatment in adults with refractory epilepsy: a review. Neurology. 2014; 83(21): 1978-85.
- Dressler A et al. Efficacy and tolerability of the ketogenic diet in Dravet syndrome – Comparison with various standard antiepileptic drug regimen. Epilepsy Research. 2015;109: 81-89.
- Walker I, et al. Predictors of ketogenic diet efficacy in children based on the electrogencephalogram (EEG). Journal of Child Neurology. 2014.
- Amari A, et al. Exploring the relationship between preferences for high fat foods and efficacy of the ketogenic and modified Atkins diets among children with seizure disorder. Seizure. 2015; 25: 173-177.
- Cervenka MC, et al. The impact of the modified Atkins diet on lipid profiles in adults with epilepsy. Nutritional Neuroscience. 2014.
- Berqvist C A.G. Long-term monitoring of ketogenic diet: Dos and Don’ts. Epilepsy Research. 2012; 100: 261-266.