Epilepsy is a widely known disorder that is characterized by
episodes of seizures. This disorder can either be inherited or be developed through
life due to traumatic brain injuries. Epilepsy is caused by a change in the way
neuronal messages fire. These neuronal messages are transmitted by electrical
impulses called the Action Potential. Usually, the action potential reaches
peak depolarization (+30 mv), followed by repolarization, and then returns to
the resting state. With epilepsy, there
is either too much excitatory transmission, or not enough inhibitory transmission
(Engelborghs et al., 2000). When either of these occur, they result in prolonged
depolarization with continuous bursts of action potentials, which leads to
hyperexcitability, resulting in a seizure.
The usual treatment for epilepsy is antiepileptic drugs
(AED). AEDs have multiple modes of action that include membrane stabilizers,
which include sodium and potassium channel blockers/inhibitors, decreasing neurotransmitter
release, or GABAmimetics which alter the effects of GABA (Howard et al., 2011).
There are constantly new AEDs being created, but despite advancements, “approximately
30% of children who develop epilepsy still experience uncontrolled seizures or
intolerable side effects from AEDs.” (Sampaio, 2016). This has led to the use
of alternative methods, one of them being the newly popularized Ketogenic diet
(KD).
The KD includes a low-carbohydrate high-fat diet, in
addition to a fair amount of meat for protein. It has become a mainstream dieting
fad because of the fast results and lack of calorie counting. But alternatively,
it can be used as a treatment for epilepsy. More specifically, the KD treatment
for people who have not had success with AEDs. It is used when a patient has
had no success and has a failed response to three different AEDs in the case of
children and around five different AEDs for adults (Sampaio, 2016).
The KD has been used for centuries to treat epilepsy, but
they didn’t truly understand the reason as to why it worked until the 1900’s,
and even so, only theories exist to explain the phenomenon. There are two theories
as to why the KD can be used as an alternative treatment for epilepsy. One of
them involves glucose metabolism and how the KD greatly decreasing their
glucose intake. Glucose produces the rapidly available energy that allows for
seizure activity, so patients on the KD have low glucose energy levels. This causes
the brain to use ketone bodies for energy instead which slows the energy
availability, ultimately reducing seizure activity (D’Andrea et al., 2019). More
recent studies have been exploring alterations of the KD such at the modified
Atkins diet (MAD) which is a low glycemic index diet. Overall, these new
modified KDs have shown great results in many cases, and if applied correctly, are
a great alternative treatment for epilepsy.
D'Andrea Meira, I., Romão, T. T., Pires do Prado, H. J.,
Krüger, L. T., Pires, M., & da Conceição, P. O. (2019). Ketogenic Diet and
Epilepsy: What We Know So Far. Frontiers in neuroscience, 13, 5.
https://doi.org/10.3389/fnins.2019.00005
Engelborghs,
S., D'Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of
epilepsy. Acta neurologica Belgica, 100(4), 201–213.
Howard, P., Twycross, R., Shuster, J., Mihalyo, M., Rémi,
J., & Wilcock, A. (2011). Anti-epileptic Drugs. Journal of Pain and Symptom
Management, 42(5), 788–804. https://doi.org/10.1016/j.jpainsymman.2011.10.007
Sampaio, L. P. (2016). Ketogenic diet for epilepsy
treatment. Arquivos De
Neuro-Psiquiatria, 74(10), 842–848. https://doi.org/10.1590/0004-282x20160116
So, I was able to find some recent research that corroborates your argument. In this specific article, “The Ketogenic and Modified Atkins Diet Therapy for Children with Refractory Epilepsy of Genetic Etiology,” the researchers were able to conclude that “the ketogenic diet is an effective treatment modality in children with refractory epilepsy of genetic etiology” (Jagadish et al., 2019). After multiple readings, however, I was unable to ascertain any specific parameters for what constitutes a “ketogenic diet” or a “modified Atkin’s diet.” This was strange to me, as the proportion of macronutrients alone can vary widely while still being defined as ketogenic, or rather there is immense variability within that single term. I am curious, then, if the anti-convulsant effects of the ketogenic and modified Atkin’s diet can be altered through manipulation of macronutrient ratios and their individual constituents (i.e. saturated fat versus unsaturated fat).
ReplyDeleteJagadish S, Payne ET, Wong-Kisiel L, Nickels KC, Eckert S, Wirrell EC. The Ketogenic and Modified Atkins Diet Therapy for Children with Refractory Epilepsy of Genetic Etiology. Pediatr Neurol. 2019 May; 94:32-37. doi: 10.1016/j.pediatrneurol.2018.12.012. Epub 2018 Dec 29. PMID: 30803845.
Hi Lixlia! I enjoyed reading your post about how the ketogenic diet can be used as an alternative treatment for epilepsy. I worked with a pharmacist who was on the ketogenic diet and she recommended I read the book, “The Diabetes Code: Prevent and Reverse Type 2 Diabetes Naturally,” by Dr. Jason Fung. I did not get around to reading it, however, she explained the book essentially discusses, that the ketogenic diet along with intermittent fasting has been used as a way to treat type 2 diabetes and to reverse it. I found an article where Hussain et. al (2012) conducted a study to understand the effect of the low-calorie diet (LCD) versus low-carbohydrate ketogenic diet (LCKD). For the study, they recruited three hundred and sixty-three overweight and obese patients (and 102 of them had type 2 diabetes) for a 24-week diet intervention trial. The study found that both the LCD and LCKD had beneficial effects on changes in weight, body mass index, changes in waist circumference, blood glucose level, glycosylated hemoglobin, etc. However, interestingly, subjects who were on the LCKD showed results that the changes were more significant. It was also found that the dosage of anti-diabetic medications was decreased to half while some were discontinued in the subjects of the LCKD group. However, Hussain et. al (2012) also mentioned diabetic patients on the LCKD should be under strict medical supervision due to the LCKD potentially lowering the blood glucose levels to a dangerous level. Nevertheless, this study proposes that the ketogenic diet improves glycemic control and that this diet could potentially be used as an alternative treatment for other health conditions as well, such as type 2 diabetes.
ReplyDeleteReferences:
Hussain, T. A., Mathew, T. C., Dashti, A. A., Asfar, S., Al-Zaid, N., & Dashti, H. M. (2012).
Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition (Burbank, Los Angeles County, Calif.), 28(10), 1016–1021. https://doi.org/10.1016/j.nut.2012.01.016
Hi Lix,
ReplyDeleteA lot of the refractory epilepsy patients I saw at Children’s for research were either on or had tried the keto diet before, and it’s a bit of a mixed bag. Like most epilepsy drugs, some patients respond well to it, and others not so much. Like you said, the underlying biological mechanism for how the keto diet works (and even how epilepsy works) isn’t entirely understood, so it’s difficult to know when exactly this treatment is indicated.
I don’t think you mentioned this in your post, but another interesting theory that I have seen is that the ketogenic diet allows for more efficient conversion of glutamate to glutamine, which is a substrate for the inhibitory neurotransmitter, GABA. So basically it could have a dual effect by clearing glutamate from synapses and enhancing GABA release (Yudkoff et al., 2008). In reality, it’s probably a combination of all of these theories, so we may never be able to point to just one mechanism.
References:
Yudkoff, M., Daikhin, Y., Horyn, O., Nissim, I., & Nissim, I. (2008). Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia, 49, 73–75. https://doi.org/10.1111/j.1528-1167.2008.01841.x