The first true report of using diet modification to treat
epilepsy was in 1911. Such modification required prolonged periods of fasting
and reported improvements in seizure episodes after only 2 to 3 days. This
began the proposition that an absence of macronutrients caused a change in
metabolism. Eventually, the macronutrient responsible for this metabolic shift
was discovered to be carbohydrates.1 Thus, solidifying the ketogenic
diet as an acceptable treatment for pharmacoresistant epilepsy. In 1938, the
ketogenic diet, also referred to as “keto”, fell from popularity due to the
discovery of phenytoin. With the strict adherence of the keto diet, this new
medication became the norm. However, with 30% of the epileptic population not
responding to pharmaceutical intervention, it was clear the ketogenic diet
needed to be reintroduced, but maybe with less-restrictive versions.2
The ketogenic diet (KD) is defined as a high fat,
low-carbohydrate, and moderate-protein diet with intentions to force the body
into a state of ketosis, meaning the breakdown of fat for energy (ATP), rather
than glucose. A classic KD calculation is 1 g protein/kg of body weight, 10 to
15 g carbohydrates/day, and the remaining calories from fat.1 Often
a ratio of 4:1 is prescribed, as a ratio of grams of fat to grams of
carbohydrates and proteins combined.3
There are several other varieties of the ketogenic diet,
perhaps making it more palatable for the patients and increasing adherence to
the diet. While each type has proven some level of positive effects on seizure
control, the most effective is still the classic ketogenic diet. The Medium
Chain Triglyceride Diet (MCT) allows for larger amounts of protein and
carbohydrates, allowing for a more flexible meal plan.4
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Source: https://www.raps.org/regulatory-focus™/news-articles/2017/10/intractable-epilepsy-and-the-value-of-formulated-ketogenic-diet-products
The ketogenic diet has several proposed mechanisms of action
often involving alterations in current body status. As previously mentioned,
this diet alters energy metabolism. As less carbohydrates are consumed, the
supply of glucose in the body decreases. Subsequently, this decreases
glycolysis which has been found to play a role in seizure reduction. Due to adequate
energy intake by way of fat, gluconeogenesis is prevented which increases
beta-oxidation and ketone bodies.1,4 These ketone bodies then become
the main source of energy for the body. Alterations in neurotransmitters are
another potential mechanism for how seizure activity is reduced, similar to how
antiepileptic drugs work. Ketone bodies have been found to inhibit g-aminobutyric acid
receptor-induced seizures by decreasing the amount of glutamate converted to
aspartate. They also block neuronal uptake of glutamate.1Furthermore,
ketone bodies have been found to reduce reactive oxygen species (ROS) and
inflammation that results from seizure activity, helping to mend the effects
brought on by an epileptic brain.
The MCT diet has a specific fatty acid that is the most
important piece in its efficacy. Medium-chain triglyceride oil is made up of
two major fatty acids: N-octanoic acid and n-decanoic acid. Decanoic acid
readily crosses the blood-brain barrier through diffusion and
mediated-transport via a medium-chain fatty acid transporter, which
coincidentally is the same transporter that mediates brain uptake of the
antiseizure drug, valproic acid.4 Once inside the brain, decanoic
acid blocks excitatory synaptic currents and causes a non-competitive inhibition
of AMPA receptors, which are a basis for seizure activity.4
The reported rates of seizure freedom reach as high as 55%
in a classic KD 4:1 diet after three months and reported rates of seizure
reduction are up to 85% in exact same circumstances. Of course, there are some
adverse effects within the vast amount of studies relating to the ketogenic
diet. Most notably are short-term gastrointestinal-related issues and increased
cholesterol.3 But given the incredible results, these unfavorable
effects seem trivial. Even if the ketogenic diet is deemed outdated, it cannot
be ignored how large of a stepping-stone it has been for science to curing
seizure episodes and epilepsy. By following the mechanisms of action of the
ketogenic diet, we better understand seizures and possibly accept the idea that
food can in fact be medicine.
2. Chen F, He X, Luan G and Li T. Role of
DNA Methylation and Adenosine in Ketogenic Diet for Pharmacoresistant Epilepsy:
Focus on Epileptogenesis and Associated Comorbidities. (2019) Front. Neurol.
10(119) doi: 10.3389/fneur.2019.00119.1.
3. Martin-McGill KJ, Jackson CF,
Besnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy.
(2018) Cochrane Database of Systematic Reviews. 11. doi:
10.1002/14651858.CD001903.pub4.
4. Rogawski M. A fatty acid in the MCT ketogenic diet for
epilepsy treatment blocks AMPA receptors. (2016) Brain. 139(2), 306–309. https://doi.org/10.1093/brain/awv369
By Alivia Larkin, A Master’s in Medical Sciences Student, University of Kentucky
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Great work! This is very informative. I have also read research that claims the ketogenic diet beneficially changes the composition and function of microbiota in the gut to reduce epilepsy symptoms via the gut-brain axis. The method of action through which gut microbiota can influence seizure activity is yet to be elucidated, and the human cohorts for studies investigating the potential effects of microbiota diversity on epilepsy are limited, both in number and statistical power. There is sound evidence that the ketogenic diet causes changes within the gut microbiota, which in turn affects neurological symptoms such as depression, anxiety and cognition. The few studies on ketogenic diet and epilepsy highlights the potential of several different genera and species found within the gut to play a role in seizure symptoms, such as a decrease in Bifidobacteria, Escherichia rectale and Dialister, and an increase in relative abundance of Bacteroides. E. Coli relative abundance increases and is proposed to have a role in keto diet therapy. Bacteria involved in fiber consumption become less abundant and this is actually a concern for patients being treated with the keto diet. So far, there is not enough evidence to conclusively determine a role of the gut-brain axis in ketogenic diet therapy for epileptic patients, but research shows promise that the composition of gut microbiota could indeed have a significant effect on seizure symptoms, as well as other wide-ranging implications in many disease models.
ReplyDeleteIt is interesting to see that there are other modes of treatment for diseases like epilepsy. We all hear that diet and exercise are the main things that are lacking in the average population of America and by changing intake values in certain groups of foods can have life changing benefits long term. You also have to be careful when being put on these diets long term since it is literally changing your bodies composition overtime, this is why it works great with epileptic patients but be very detrimental to patients with Parkinsonism type diseases and Alzheimer. That is why everything should be kept in moderation for it to serve its desired purpose in aiding the pathology driving the progression of these neurological conditions. It is also good to see in my opinion that there are alternative treatments that dont require the use of harmful drugs that overtime can cause chronic stress and other potential deadly side effects.
ReplyDeleteThis comment has been removed by the author.
ReplyDeleteI found this blog very interesting, as I had never heard of implementing a keto diet to treat epilepsy. Your mention of fasting improving seizure episodes made me think of another popular diet, intermittent fasting, which involves shortening a person's daily eating window. Having a smaller eating window helps push the body to pull energy from fat when food is not available, essentially putting the body into a period of ketosis. After some research, I found an article that explained that intermittent fasting and the keto diet can reduce seizure episodes for different reasons, and combining the diets could be even more beneficial for epileptic pediatric patients and perhaps offset some of the disadvantages of adopting just the keto diet. Again, it is very interesting how diet can play a significant role in medical disorders.
ReplyDeleteThis blog entry has given new insight on how the ketogenic diet has helped with epileptic patient and seizure control. I have read some articles on how a keto diet has been beneficial for many people with epilepsy. This blog gives good information and explains that specifically the MCT diet has had some positive effect on reducing seizure activity. However, in some studies it seems that the ketogenic diet may not be a clear indications to anti-seizure efficacy.
ReplyDeleteThe paper by Simeone et al, summarize the finding of how anti-seizure and neuroprotective properties of ketone bodies. It seems that the mechanism for how anti-seizure effects of high-fat ketogenic diet has not been clearly understood. It may be that ketone bodies alone or in combination may have some mechanistic ability in helping with anti-seizure effects.1 As you explain in the paper that the MCT diet seems to help in oxidation and thus help with reduction in seizure activity. However, it seems that these ketone bodies may not be the key mediators because studies have looked at the ketone bodies produced by the liver having an anti-seizure effect.1 Most studies do clinical observation that examines blood ketone levels, specifically at β-hydroxybutyrate. This β-hydroxybutyrate, ketone body does not have a good enough correlation with seizure control.1
In recent studies ketone bodies have been studied extensively, but there has not been any clear evidence that shows the ability of β-hydroxybutyrate to exert anti-seizure effects. More studies need to examine how β-hydroxybutyrate has any effect in the brain and in turn related to seizure control. However, it appears that local ketone levels at neuronal or synaptic levels are good reflection of helping with seizure control.1 Further studies, need to find clear evidence that shows a better correlation with how ketogenic diets and anti-seizure efficacy are.
Thus, it would not be a accurate statement to say that ketogenic diet will help with controlling seizures in epileptic patients. It would require more experiments and understanding of how these ketone bodies correlate to anti-seizure activity. There needs to be some corroboration between the role of ketone bodies and clinical settings to find a firm correlation.
1. Simeone, Timothy A., Simeone, Kristina A., Stafstrom, Carl E., and Rho, Jong M. "Do Ketone Bodies Mediate the Anti-seizure Effects of the Ketogenic Diet?" Neuropharmacology 133 (2018): 233-41. Web.
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ReplyDeleteThis is a very interesting topic. Your post is insightful, and informative! I have encountered additional information on studies following the Modified Atkins Diet (MAD) that relates to treatment of drug resistant epilepsy. MAD aims to provide increased flexibility and palatability and contains around 65% fat, 25% protein, and 10% carbohydrate, while showing positive results in children and adults. A recent meta-analysis performed using 70 studies concluded that the MAD and classical KD do not differ in reduction of seizure frequency at month 3 and month 6, with ≥50% and ≥90% reductions, respectively (Rezaei et al., 2017). A retrospective study showed >50% of seizure reduction in 65% of the 10 children who remained on the diet for up to 6 months, and 20% of them were seizure-free (Park et al., 2018). Treatment with MAD was shown to be more effective in seizure control when the MAD was started with lower carbohydrate limits (Kossoff et al., 2010). The efficacy of the MAD is also proven for the treatment of drug-resistant epilepsy in adults and adolescents. In a recent meta-analysis, eight studies were identified that used the MAD in adult patients with refractory epilepsy, aged between 15 and 86 years, with treatment times ranging from 3 to 36 months. In these studies, the proportion of patients who showed >50% seizure reduction ranged from 20 to 70% and the rate of seizure freedom ranged from 7 to 30%. The rate of abandonment of the diet varied between 12.5 and 82% of the patients (Liu et al., 2018). Overall, the MAD has shown to be well tolerated for children and adults when compared to classical KD; though some typical side effects such as gastrointestinal complaints, dyslipidemia have been reported. Beneficial effects have also been reported, such as mood improvement, and weight loss. The data from these meta-analyses are hopeful, however they suggest there is great variability in the etiology and possible treatment of epilepsy.
ReplyDeleteD'Andrea Meira, Isabella et al. “Ketogenic Diet and Epilepsy: What We Know So Far.” Frontiers in neuroscience vol. 13 5. 29 Jan. 2019, doi:10.3389/fnins.2019.00005
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ReplyDeleteYour blog entry was incredibly interesting! I would have never guessed that implementing a change in diet could help treat seizures in epilepsy patients. I am familiar with epileptic drugs because I have been diagnosed with chronic migraines. In small doses, epileptic drugs are commonly used to prevent migraines. I am prescribed a drug known as Keppra (an antiepileptic). I am on a very low dose and this medication has been the only thing that has worked for preventing my severe migraines. I have not noticed any major side effects associated with this medication; however, I know that epileptic drugs tend to have a laundry list of possible side effects. It is interesting to know that there are different courses of treatment outside of medical management for patients with epilepsy. I love the idea of using our food intake and diet as a medication on its own. You did a great job of explaining the physiologic details of how this works in the body.
ReplyDeleteVery interesting topic and great post! I have been fascinated with the ketogenic diet recently as it is regaining mainstream popularity. The data certainly suggests that the keto-diet is immensely beneficial for those with epilepsy, and it seems to be an excellent proponent to an idea that I also support - which is finding ways to treat disease through dietary and other lifestyle changes primarily, and using pharmacological interventions only when absolutely needed.
ReplyDeleteThe ketogenic diet is very popular in the fitness community today as well. I have seen countless anecdotal accounts of incredible success in weight loss and athletic performance from those who have adopted the "keto-lifestyle." Personally, my own diet tends to be mostly ketogenic and I have noticed that it has made a positive difference in not only my body composition but also my mental health.
In addition to neurological disease - as you mentioned - the keto diet also proves to be very efficacious in treating psychiatric disorders as well. For example, a study from the University of Edinburgh just earlier this year (Campbell, 2019) demonstrated the diet was significantly beneficial with regards to emotional regulation and mood stabilization in patients with bipolar disorder. A majority of subjects presented with fewer depressive episodes, improved energy, improved clarity of thought and speech, and weight loss.
It's remarkable that a simple dietary change can have such profound effects as a medical intervention. In the future I expect to see more research suggesting that a ketogenic type of diet may be the universal standard for a healthy human diet in general.
Campbell, IH et al. "Ketosis and Bipolar Disorder: Controlled Analytic Study of Online Reports." BJPsych Open 2019 July 4; 5(4): 58. doi: 10.1192/bjo.2019.49.
Great job Alivia, I was very interested and surprised by the benefits of the Ketogenic diet. Fad diets are a constant topic of interest among many. However, I believe that the ketogenic diet may actually be tapping into a way on transforming health, by allowing the body to receive nutrients it needs, while removing those negatives effects we see when eating highly processed foods. It seems the more we learn about the ketogenic diet, the more we learn about its immense ability to benefit brain disorders across a wide spectrum of issues. Great job relating your nutritional science background into clinical aspect, as many of us have not had the opportunity to deeply understand these connections.
ReplyDeletehttps://www.healthline.com/nutrition/low-carb-ketogenic-diet-brain
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ReplyDeleteSuch an insightful post Alivia, I especially loved your opener! I really enjoy the idea of employing diet to intervene in medical conditions when it is possible. I feel this gives the patient a stronger feeling of control over their own health care. This allots the patient a change they can personally see themselves making in comparison to just remembering to take a pill. Also making a lifestyle change such as this would show to them they are capable of such large lifestyle changes and may motivate them to better themselves in other ways such as exercising. I also find the linkage of the microbiota to so many conditions like epilepsy, liver disease, diabetes, arteriosclerosis, obesity, IBD and many more to be extremely interesting. It is not something I have thought of when considering the etiology of disease however when brought into the light, it only makes sense. In medical sciences, homeostasis is everything and one's microbiota is apart of their homeostasis. It makes me curious how many more conditions that the microbiota is in some way involved and if we shouldn't be looking at it for more conditions than we currently do.
ReplyDeleteWang, Baohong, et al. “The Human Microbiota in Health and Disease.” Engineering, Elsevier, 28 Mar. 2017, https://www.sciencedirect.com/science/article/pii/S2095809917301492.
Jen Eccleston
ReplyDeleteIt fascinates me how simple lifestyle modifications may be so life altering. Research has tried to formulate various medications to curb the epilepsy and yet mere diet adjustment showed drastic results. Before reading your blog, I did not consider diet modification as a method for managing epilepsy even though it has been considered since the early 1900s. I would be curious, however, to see how different KD ratios affect different people with regards to seizure reduction. A comparative diet is the Low Glycemic Index Diet that uses a ratio of 6:1 (fats: carbs/proteins). In this diet they focus on carbohydrates that have a low glycemic index, thus causing a slower rise in glucose levels. This, too, produces a small increase in ketones in the body, and has an efficacy that compares to the ketogenic diet. And though these diet modifications seem simple, I can also see how they can be difficult for people to implement and remain consistent with to allow for sufficient results.
Meira, Isabella D’Andrea, et al. “Ketogenic Diet and Epilepsy: What We Know So Far.” Frontiers in Neuroscience, vol. 13, 2019, doi:10.3389/fnins.2019.00005.
ReplyDeleteThe ketogenic diet has been helpful to so many people. Although it is a big lifestyle change for the patients and their families, it's awesome that some forms of seizures/epilepsy can be prevented without medications that usually have side effects. The ketogenic diet seems to only have positive side effects such as weight loss and increased energy which leads me to believe that this diet could be beneficial for other disease such as cardiovascular disease, diabetes (espeically type 2), and many others.
A very well-written blog. I liked the explanation on how a keto diet works on the chemistry-level. I was unaware that there were options available within the keto diet. At least this allows for some scope of flexibility. And as you mentioned, the diet does have its “unfavorable effects”, and I have heard that some of those happen to be quite painful. A friend of mine has been on a keto diet for about 3-4 months now and she told me she initially had severe leg cramps at nighttime, a lot of fatigue, and extreme hunger. However, I agree that it is still a better option for a person with epilepsy.
ReplyDeleteI looked at the deep brain simulation therapy that would help a person suffering from epilepsy that cannot take medications for it either. It also has disadvantages to it like the keto diet. It is not able to stop the seizures, but it does reduce them. There is not an exact percentage provided for the effectiveness of this therapy. According the Epilepsy Society, it might take up to 2 years for this therapy to take effect on an individual. So, it is truly a serious concern for these type of epilepsy patients and before your blog, I was honestly unaware of this issue. Thank you for researching on this!
“Deep Brain Stimulation.” Epilepsy Society, 5 Feb. 2018, www.epilepsysociety.org.uk/deep-brain-stimulation#.Xb6Oiy-ZMWo.
Great post, Alivia! We often jump to the most aggressive forms of treatment so it is interesting to hear about other forms of treatment especially for ailments like epilepsy. I think recently there has been a lot of emphasis on diet and exercise so this is not surprising; I am glad that more research is being done in this field. I used to think that advancements in medical technology was solely responsible for the rising incidence of disease but maybe there is something else to blame as well. We can't control our genes or events in our lives that can predispose us to diseases but maybe we can control them with something as simple as lifestyle changes. It is good to provide people with alternatives because drugs can have severe and deadly side effects. That being said, I hope this is not taken completely out of context because more and more people are relying on natural forms of treatment as opposed to consulting with physicians and developing a treatment plan together. Epilepsy can be fatal, so while I think this is a wonderful alternative, I worry about people who may not seek a physician or medical professional's advice first.
ReplyDeleteAlivia, this was a really good introduction! You effectively grabbed my attention by describing an incredibly scary situation that many people are faced with on a daily basis. There has been a dramatic increase in the number of epileptic patients in the United States over the past decade. In 2010 roughly 2.3 million Americans had been diagnosed with epilepsy, that number jumped to over 3.5 million Americans just seven years later in 2017. With such a large growing portion of the population affected by seizures, I agree that needs to be done. I did not realize that so many epileptics (1/3) suffer from seizures that cannot be controlled by pharmaceutical agents, that must be severely debilitating and place an enormous strain on their quality of life. I was surprised because I have heard so many people raving about going on the “keto diet” and I assumed that it was another fad diet for weight loss, but instead it could offer some real clinical benefits. I am curious that if the ketogenic diet is suitable to prevent seizures in epileptic patients why would it not be used as the first line of treatment? Modifying a patient’s diet seems like a better alternative than automatically resorting to drugs for treatment.
ReplyDeleteThis made me do a little more research on the ketogenic diet and I found that many physicians warn patients on this diet, that they may suffer nutritional deficiency since they are primarily consuming fats. Even patients adhering to the MCT diet will not get enough vitamins, minerals, and fibers that they would normally get from a diet including fruit, vegetables, and whole grains. This depletion of nutrients also causes many people to experience what is known as the “keto flu” which causes them to feel sick and drowsy. I am not sure that this diet would be a safe alternative especially for patients that are very young or elderly. Although epilepsy is the most common childhood neurologic disorder, I do not think this would be a safe diet for children because I feel it would have many adverse effects on their growth, immunity, and overall health. I am also curious if this diet has been tested in patients experiencing a certain class of epileptic seizures or all classes. Different classifications of seizures affect different areas of the brain and I would think that this diet would not be able to prevent all types of seizures. For instance, a simple partial seizure is classified as a focal seizure without impaired consciousness. Patients suffering from simple partial seizures are the ones who experience an aura (subjective sensation prior to seizure). If the temporal lobe is affected by the simple partial seizure, then the patient experiences déjà vu, fear, and distortions of time. On the other hand, if the parietal lobe is affected the patient will experience contralateral arm sensory symptoms and if the occipital lobe is affected then there will be contralateral visual symptoms. I am also curious if this diet would be beneficial to patients with seizures caused by genetic or by structural defects. Overall, I agree that food can be just as effective as pharmaceutical agents when treating patients.
Niamh Costello
Northwestern Medicine, Ring, D., & Maganti, D. (n.d.). Pros and Cons of the Ketogenic Diet: Northwestern Medicine. https://www.nm.org/healthbeat/healthy-tips/nutrition/pros-and-cons-of-ketogenic-diet.
Mathias, Sally B. MD (2018). Clinical Approach to Epilepsy - I. ANA780: Special Topic in Neurobiology. University of Kentucky, Lexington.
Hey Alivia, this was a very informative blog. I personally had never heard of using the ketogenic diet to confront and treat epilepsy, however it seems to be quite effective. This must truly be helpful to those that are struggling to avoid and decrease seizures. Seizure conditions must be both scary and frustrating especially after years of failure to respond to drugs.
ReplyDeleteAfter doing some more research I found that the ketogenic diet has even more benefits than just epilepsy, mostly in regards to quick and sustained weight loss. Due to the decreased carbohydrate consumption the body is trained, in a sense, to be more metabolically active in fat burning. As such, some studies have recommended the ketogenic diet for treating such diseases such as diabetes, hypertension, and heart disease that are both lifestyle and diet linked.
I have to wonder now if the ketogenic diet should be recommended for a much wider range of people with varying metabolic conditions and chronic illnesses to improve overall health. In the process of getting treatment for my own chronic illness my physicians recommended me to switch to the ketogenic diet which I adhered to for several years. In that time, it was actually quite difficult to eat unhealthy foods because the definitions of the diet simply do not allow it. As such it was necessary to eat many more fruits and vegetables to supplement and replace the carbohydrates that I cut out, especially since the consumption of protein is held relatively constant. It became very easy for me to lose weight and my overall health improved dramatically prior to getting my chronic condition under control.
Great work with the blog entry! I have a friend who was following a ketogenic diet, so it is very interesting to see how the diet actually effects the body on a deeper level. It is fascinating that there this form of treatment can take many different forms, primarily depending on the needs of the patient. These multifaceted treatment options are very important for to be able to give the patient the best opportunity to improve their quality of life. As you mentioned, ketogeneic diets can seem outdated. Despite this, it can still be utilized to great effect in many cases throughout the population. This blog post has shown how something as simple as altering your diet can have great effects on so many medical conditions and that is very fascinating.
ReplyDeleteThis is a very timely entry as more people are rediscovering keto in the mainstream and others are searching for non-medication alternatives to treat various disorders. I found this paper on the autoimmune protocol (AIP) diet, which is a 6-week elimination diet designed to decrease inflammation, like that associated with Crohn’s disease (CD) and ulcerative colitis (UC). This diet was evaluated as an adjunct to existing therapies. All the participants who stayed on the diet achieved clinical remission of their symptoms by the week 6 of the study, and many of the patients also had marked endoscopic improvement. This study was very small, and some participants had to drop out due to inability to stick to the diet, but it seems like this could be a valid piece of the treatment for UC and CD. I think we need to continue our studies for diets as therapy to help more naturally and sustainably treat a variety of diseases.
ReplyDeleteKonijeti, G. G., Kim, N. M., Lewis, J. D., Groven, S., Chandrasekaran, A., Grandhe, S., … Torkamani, A. (2017, November). Efficacy of the Autoimmune Protocol Diet for Inflammatory Bowel Disease. Retrieved October 14, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647120/.
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ReplyDeleteGreat post! I always find keto related topics very interesting ever since my father decided it’s been the best thing to his health since bottled water. Epilepsy is a crippling disease and it’s great that patients can find relief in something like a diet change. However, it makes me curious about the relationship these patients share or develop with diabetes and insulin resistance. We recently learned in our Biochemistry class that the ketogenic diet is not extremely sustainable for the body past 3 months. It has been found that seizure activity and diabetes have a strong association to begin with. A study done in 2016 reported that individuals admitted to a medical center with drug resistant epilepsy showed a rate of T1D that was double that of the overall prevalence. However, it was also found that using the diet in patients with T1D had great neuro benefits for the patients that could help to prevent seizure activity and increase brain neuron abilities. Obviously, there are many questions about the consequences and benefits of the diet and it will be interesting to see where the research goes with the increasing popularity of this diet again!
ReplyDeleteKalra, S., Unnikrishnan, A. G., & Gupta, Y. (2016). Epileptogenicity of diabetes and antiepileptogenicity of ketogenic states: Clarity or confusion? Indian Journal of Endocrinology & Metabolism, 20(5), 583–585. https://doi-org.ezproxy.uky.edu/10.4103/2230-8210.190520