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Quick Summary tl;dr
Again, as noted from the International Ketogenic Diet Study group, there is a recommendation to strongly consider the use of the ketogenic diet in patients of any age who have failed up to three medications.
It can be stated that the use of the ketogenic diet is a proven therapy option for the use in children given the strong clinical data.
Although the data is limited in adults, for those with drug resistant epilepsy, this could be a very good treatment of choice. The major barrier is to establish a ketogenic approach that will result in good compliance.
Whilst we can see that the diet does appear to offer significant anticonvulsant for those with refractory epilepsy, more work is needed to truly understand the exact mechanism of action that is at play. Having this then means that more and better therapeutic modalities could be developed in the future.
What is Epilepsy?
Epilepsy is a chronic neurological disorder that is associated with a disruption in the normal electrical activity within the brain. The main symptom of this abnormal brain activity results in repeated seizures, which can range from brief lapses to severe and prolonged convulsions.
Epilepsy is a variable condition that can differ in its impact from person to person. There are over 40 different types of seizures that people can experience. The classification of seizures is based on how much of the brain is affected:
- Partial (or focal) seizures= affects a small part of the brain
- Generalised seizures= where most or all the brain is affected
Epilepsy is classed as one of the most common neurological diseases as it affects 50 million people worldwide, occurring at any age.
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What Causes Epilepsy?
There exist several causes of epilepsy including genetic, environmental and physiological factors. All of which modify neuronal function or cause functional changes within the brain.
The most common form of epilepsy, which affects 6 out of 10 people, is known as idiopathic epilepsy. The exact cause for this type of epilepsy remains unknown, with genetic factors appearing to be key. The presence of a family history is known to enhance an individual’s risk for developing epilepsy (1).
For all other types of epilepsy that exists, the cause is believed to be secondary to an environmental or physiological factor. The term epileptogenesis is what is given to describe the development of the state of epilepsy ( 2). Such causes include:
- Brain damage
- Severe Head Injury
- Stroke
- An infection in the brain i.e. meningitis
- Brain tumours
- Certain genetic syndromes
Is There a Cure for Epilepsy?
At present, there is currently no known cure for epilepsy. However, there does exist some very effective medications known as Anti-Epileptic Drugs (AEDs). It is estimated that around 70% of individuals with epilepsy can control their condition with these drugs.
There does exist a group of the population with epilepsy that do not respond well to AEDs and are believed to have drug resistant epilepsy. Otherwise known as intractable or refractory epilepsy. In the case of these individuals, other forms of treatment need to be sought.
The History of the Ketogenic Diet (KD) for Use in Epilepsy
The use of the ketogenic diet to treat epilepsy dates as far back as Hippocrates time. The major way to induce ketosis at that time was using fasting or starvation. Since then, modern reports put the use of the KD in treating childhood epilepsy starting in the 1920s ( 3).
It was within this time that discoveries were made to show that the same level of ketosis could be induced with carbohydrate restriction and higher levels of fat intake (4).
How Can the Ketogenic Diet Help Patients with Epilepsy?
Although the KD is an established treatment option in the major epilepsy centres around the world, the exact mechanism of its action is still not fully understood.
Over the past 2 decades, the understanding into the mechanism has begun to grow. Proposed mechanisms of action for the anticonvulsant effects of the ketogenic diet are believed to be due to:
- The state of ketosis
- A reduction in glucose levels
- A rise in fatty acids
- Enhanced bioenergetic reserves
It is believed that the ketone bodies produced with the ketogenic diet provide the anticonvulsant effects as well as reducing neuronal excitability in the brain ( 5). However, the exact link between ketone bodies and the anticonvulsant efficacy of the ketogenic diet is not fully understood.
Another hypothesis for the role of ketone bodies in the anticonvulsant activity is due to their impact on certain neurotransmitters. Namely it is thought that the ketone bodies influence the main excitatory and inhibitory neurotransmitters, GABA and glutamate ( 6).
Are Higher Ketone Levels Better for Seizure Control?
The level of ketones doesn’t always appear to correlate with seizure control. For example, people demonstrating just a mild ketosis level (0.5-1mmol/L) could have just as good seizure control as those with a higher ketone level (4-6mmol/L).
Although the optimal ketone body level has not been classified, it is known that infusion of glucose does cause the return of seizures as quickly as one hour ( 7).
It appears that as well as the state of ketosis and the neuroprotective role that ketone bodies generally display, the lower glucose levels, as well as other circulating fatty acids i.e. PUFAs also contribute to the anti-seizure effect ( 8)
The Effect of the Ketogenic Diet in Children
The use of the ketogenic diet has most extensively been used in children for those with refractory epilepsy. There now exist several studies, which confirm a response rate of approximately 50% in children with refractory epilepsy. In 2008, the first randomised controlled trial was undertaken to look at the specific efficacy of the ketogenic diet in children compared to a control ( 9).
The study collected data from 54 children on the KD and 49 on the control group. The results showed that after 3 months, 38% of children in the ketogenic group had greater than 50% seizure reduction compared to just 6% in the control group.
The same research group went on to conduct another similar study which this time reported data at 3, 6 and 12-month time points. At 12 months, they reported similar improvements in seizure control confirming that the KD for use in refractory epilepsy in children is an acceptable treatment of choice ( 10).
In 2009, the first blinded, crossover design study was carried out in children ( 11). This type of design meant that both the physicians and the parents of the children didn’t know what group they belonged to i.e. the ketogenic or the control group.
Both groups consumed the ketogenic diet but one group was given a solution of saccharin (a sweetener not known to stop ketosis) or a solution of glucose (known to inhibit ketosis). A trend towards improved seizures in the saccharin group was reported.
The International Ketogenic Diet Study Group, which consists of 26 neurologists and dietitians, has deemed the KD an effective nonpharmacologic treatment for intractable epilepsy ( 12).
The Effect of the Ketogenic Diet in Adults
Unlike in children, the use of the KD in adults has been a lot more limited. The main reason is there is a perceived lack of tolerability and compliance in adults. As such, there remains very few well designed or randomised controlled trials within adults following a ketogenic diet.
A meta-analysis study carried out in 2014, looked to summarise the main studies that have been conducted in adults. A total of 12 studies were identified which included data on 270 patients. Three different types of the ketogenic diet were looked at (the classical, other forms of ketogenic and the Modified Atkins).
It was reported that better compliance came with that of the Modified Atkins Approach (56% vs 45%). However, better seizure control was noted with the classical ketogenic approach in comparison to the Modified Atkins approach (42% vs 34%) ( 13).
It has been found that for those adults (with drug resistant epilepsy) who comply with the diet, around 30% report 50% or more reduction in seizures (14).
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