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Biomedical Research

The Ketogenic Diet and Epilepsy

The ketogenic diet, commonly referred to as “keto”, is an increasingly popular recent trend in the dieting world. However, new studies show that this diet doesn’t only help put off a few pounds; it can also be used to help epileptic patients and improve the trajectory of their condition.

Introduction

The ketogenic diet, commonly referred to as ‘keto,’ is an increasingly popular recent trend in the dieting world. While there are a variety of ketogenic diets, including the Atkins and  South Beach diet,  the principle idea behind keto is that you use fats and ketones in your body to provide energy, rather than carbohydrates and glucose.  

However, keto isn’t just a new practice that started in the past couple of years.  With the first records of this practice dating back to the time of Hippocrates, ketogenic diets and fasting have been used for many medicinal reasons besides weight loss such as helping to treat or reduce the symptoms of various conditions such as acne, polycystic ovary syndrome to even genetic disorders. 

Ketogenic diets have been studied extensively in people with epilepsy. They are often recommended for those who either fail to respond to anti-seizure medications or can’t tolerate their side effects and have been proven quite effective.

How Does the Ketogenic Diet Work?

Typically in standard diets, some carbohydrates burn up quickly and are packed with intense fuel that yields large bursts of energy.  The human body’s main energy store is through fats [1].  Proteins and fats burn slowly thus results in a constant stable release of energy.  This is beneficial as you would not experience any peaks or crashes in energy in comparison to carbohydrates by which glucose is released instantaneously in the body and not stored [1,2].  This is how ketosis also regulates blood glucose levels without complications. Involving complex carbs into your diet causes your body to heighten your blood sugar and as a result, produce insulin.  As high glucose levels are perceived as toxic by the body, insulin is released by the pancreas as negative feedback to decrease and regulate this.  When your body starts struggling to keep up, excess glucose is converted into fat, and insulin stores it in cells. Your body is capable of regulating your blood sugar on its own without help when you aren’t mainlining so much sucrose. Ketogenic diets avoid such problems.

Fat is essentially satiety. Consuming fat keeps you full and combines with low carbohydrate intake, allows the body to produce ketones [2,3].  In Glucose 1 transporter (Glut 1) deficiency and pyruvate dehydrogenase (PDH) deficiency ketones provide an alternative energy source to glucose [3].

As with any alterations to the body, the Ketogenic diet too has side effects whilst adjusting to the low-carb lifestyle.  Though for many the intended goal is weight loss, in other cases where the ketogenic diet is prescribed, side effects can include feeling weary with symptoms of influenza, also known as the Keto-Flu, constipation, or diarrhea, and high cholesterol.

The Ketogenic Diet for Epilepsy

Most often lifelong, epilepsy is a common condition that affects the brain and causes frequent seizures. Seizures that are resistant to standard medications remain a major clinical problem.

In severe epileptic patients, after 2-3 days of fasting from food, and even in some cases, water, there was severe seizure control observed.  These observations have been around for millennia. 

We don’t completely understand how the ketogenic diet works but there is some evidence that the brain needs energy from glucose to create a seizure. The ketogenic diet makes the body think that it’s in a state of starvation or fast [3].

Though having years of insight and trials, clinically, doctors do not assign patients keto from initial diagnosis of epilepsy; it is usually reserved for drug-resistant epilepsy.  This is due to the balance of the diet needing to be carefully worked out for each individual and because vitamins and other special supplements are needed. It is not advisable as a treatment option for some with some metabolic disorders or other neurological disorders.

The ketogenic diet was initially for children and currently in the UK, medically still is; this treatment is offered for children between 3 months to 16 years suffering from any type of epilepsy [2,4,5].  During infancy, the brain is much more efficient at extracting and utilizing ketone bodies from the blood due to the higher levels of ketone metabolizing enzymes and monocarboxylic acid transporters produced during this period [6-8]. 

In a review by Mcgill et al., four studies with 385 participants reported that more children achieved seizure freedom with a ketogenic diet than with control. Two small underpowered studies reported no events in adults with 141 participants reported no adults achieved seizure freedom; the analysis was underpowered [9].

There is limited evidence for how effective or tolerable the ketogenic diet is for adults but it has been highly proven to be effective for pediatric epilepsy. Some particular studies show that keto can be effective on the adult brain as it increases its levels of monocarboxylic acid transporters and ketone metabolizing enzymes rapidly during periods of stress such as ischemia, trauma, or low glucose as in the case of keto [8,10].  A review of 16 studies in adults with uncontrolled epilepsy found that ketogenic diets were well-tolerated long term and typically resulted in significantly fewer seizures or, in a minority of cases, complete freedom from seizures [8].

A study by Rho et al. suggests that adults may produce ketones at different levels in response to a ketogenic diet, possibly explaining the inconsistencies in findings on the effect of keto on the adult brain.  In addition, they also demonstrated variations between the production of ketones in rats and humans, which is a crucial consideration when running animal trials before implementing techniques and diets clinically [11].

Conclusion

The ketogenic diet is not just a trend for health gurus to lose weight.  It lessens the burden and potentially frees many, if not, millions of those suffering from drug-resistant seizures from epilepsy.  Though not much is known about epilepsy as a condition in itself, and the ketogenic diet heavily varying in effect amongst people of different ages, for centuries, techniques like fasting and keto have been observed to be helpful.  Though not as commonly prescribed or allocated to adults, it is an extremely effective technique on children, potentially improving their trajectory and progress of the condition.

Nara Ito, Youth Medical Journal 2020

References

[1] Wasserman, D. H. (2009). Four grams of glucose. American Journal of Physiology-Endocrinology and Metabolism, 296(1), E11-E21.

[2] Great Ormond Street Hospital for Children. (2011). Ketogenic diet. https://www.gosh.nhs.uk/medical-information/procedures-and-treatments/ketogenic-diet

[3] Laffel, L. (1999). Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes/metabolism research and reviews, 15(6), 412-426.

[4] Lambrechts, D. A., de Kinderen, R. J., Vles, J. S., de Louw, A. J., Aldenkamp, A. P., & Majoie, H. J. (2017). A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy. Acta neurologica Scandinavica, 135(2), 231–239. https://doi.org/10.1111/ane.12592

[5] Sharma, S., Goel, S., Jain, P., Agarwala, A., & Aneja, S. (2016). Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: A randomized controlled trial. Epilepsy research, 127, 152–159. https://doi.org/10.1016/j.eplepsyres.2016.09.002

[6] Sokoloff L. (1973). Metabolism of ketone bodies by the brain. Annual review of medicine, 24, 271–280. https://doi.org/10.1146/annurev.me.24.020173.001415

[7] Bilger, A., & Nehlig, A. (1992). Quantitative histochemical changes in enzymes involved in energy metabolism in the rat brain during postnatal development. II. Glucose-6-phosphate dehydrogenase and beta-hydroxybutyrate dehydrogenase. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 10(2), 143–152. https://doi.org/10.1016/0736-5748(92)90042-x

[8]McNally, M. A., & Hartman, A. L. (2012). Ketone bodies in epilepsy. Journal of neurochemistry, 121(1), 28–35. https://doi.org/10.1111/j.1471-4159.2012.07670.x

[9] Martin‐McGill, K. J., Jackson, C. F., Bresnahan, R., Levy, R. G., & Cooper, P. N. (2018). Ketogenic diets for drug‐resistant epilepsy. Cochrane Database of Systematic Reviews, (11). 

[10]Prins M. L. (2008). Cerebral metabolic adaptation and ketone metabolism after brain injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 28(1), 1–16. https://doi.org/10.1038/sj.jcbfm.9600543[11]Prins M. L. (2008). Cerebral metabolic adaptation and ketone metabolism after brain injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 28(1), 1–16. https://doi.org/10.1038/sj.jcbfm.9600543

By Nara Ito

Nara Ito is a student from London, England. She is interested in neurology, immunology, and genetics

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