What is the ketogenic diet?

A ketogenic diet is a style of food intake that promotes the production of ketone bodies from fatty acids. It was first developed by Wilder¹ in 1921 in an effort to sustain the epilepsy-alleviating effects of fasting that Geyelin² had reported.  Today, randomized controlled trials^3,4 and meta-analyses^5,6 have shown that the ketogenic diet is an effective alternative treatment for pediatric epilepsy, and it is recommended as a possible second-line treatment in clinical guidelines.⁷ Although the diet is effective, the mechanism underlying this efficacy is not well-understood.⁸  Recently, the benefits of the ketogenic diet as a weight loss⁹ or anti-cancer^10-13 therapy have been studied, but these results are too preliminary to make any firm conclusions.

Ketone bodies are an alternative energy source for certain tissues of the body when glucose levels are very low.^11,14,15 For example, key regions of the human brain can metabolize ketone bodies during periods of prolonged fasting.^16,17  During these times of metabolic stress, glucose and insulin levels fall. The body compensates by generating glucose from amino acids, a process termed gluconeogenesis, and metabolizing fatty acids to produce ketone bodies.¹⁴  A ketogenic diet is a dietary plan that restricts carbohydrate and protein intake in order to mimic the fasting state and encourage ketone formation.^11,18

In its original conception, the ketogenic diet is a dramatic change from the normal Western-style diet.  It mandates a protein intake of ≤ 1 g of protein per kilogram of bodyweight, ≤ 15 g of carbohydrates per day (the exact number is dependent on basal metabolic rate), and enough fat to make up the rest of the calorie expenditure.¹⁹ Practically, this composition was interpreted as a ratio ranging from 5:1 to 2:1 of ketogenic-to-antiketogenic macromolecules (ketogenic being fats and antiketogenic being the sum of proteins and carbohydrates) with the higher ratios having stronger ketogenic effects but the lower ratios being better tolerated. The goal of the treatment in epilepsy is to find the minimal ratio that protects against seizures and ensures compliance.  The degree of ketosis is often monitored by measuring acetone and acetoacetate in the urine or β-hydroxybutyrate in the serum.²⁰  A concentration of 80 – 160 mg/dL in urine ^18,21, and 2 – 4 mM in the serum^22,23 is considered the minimum for anticonvulsant effects. The clinical interpretation of the ketogenic diet is in contrast to those described in popular online diet websites and magazines.  These sites often interpret the ketogenic diet as one with 70 – 80% of the calories from fat, 5 – 10% from carb, and 10 – 20% from protein.^24-26 This type of diet has roughly a 2:1 ketogenic ratio where only 70% of the daily calories come from fat. ^21,27  It is important to note that this type of diet is not backed by clinical studies, and will not completely suppress insulin production.

There are several alternative forms of the ketogenic diet.  The first is known as the medium chain triglyceride ketogenic diet (MCTKD) in which the diet is tailored to include more medium chain triglycerides than is found in the classic ketogenic diet.²⁸  Medium chain triglycerides yield more ketones per kilocalorie consumed than long chain triglycerides because the medium chain fatty acids bypass the regulation of carnitine palmitoyl transferase to directly enter the mitochondria.²⁹ As such, the MCTKD requires less carbohydrate restriction. A typical MCTKD breakdown would be 15% of daily energy coming from carbohydrates, 10% from protein, 30% from long chain fatty acids and 40 – 45% from medium chain triglycerides usually given as an oil supplement.¹⁸ A randomized trial of 125 children ages 6 – 12 comparing the tolerability and anti-seizure effect of MCTKD to the classic ketogenic diet showed no significant difference in mean percentage of baseline seizures after 12 months (p>0.05) or tolerability.³⁰ Another form of the ketogenic diet is the modified Atkins diet (MAD), which has a 0.9:1 ketogenic ratio.³¹ It is often better tolerated than the classical form because it imposes less severe protein and carbohydrate restrictions.  The Atkins diet itself is also sometimes considered a very mild form of a ketogenic diet – one that does not restrict protein intake.³² Lastly, there is the low glycemic index treatment (LGIT), which prescribes 40 – 60 g of carbohydrates per day, but only those with a glycemic index <50. Around 60% of the daily energy intake should come from fat and around 30% from protein.^18,33,34

^References

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2. Geyelin H. Fasting as a method for treating epilepsy. M Rec. 1921;99:2.
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5. Rezaei S, Abdurahman AA, Saghazadeh A, Badv RS, Mahmoudi M. Short-term and long-term efficacy of classical ketogenic diet and modified Atkins diet in children and adolescents with epilepsy: A systematic review and meta-analysis. Nutri Neurosci. 2017:1-18.
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