Ketogenic diet in epilepsy

The ketogenic diet (KD) was formally introduced into practice in the 1920s - developed by a faith healer to help children with epilepsy (1)

• however the origins of ketogenic medicine may date back to ancient Greece (2)
  

Ketogenic diet (KD) in epilepsy

• seizures have been reported to cease on absolute fasting, and early studies suggested that a diet high in fat and low in carbohydrate would produce similar conditions to fasting; the anticonvulsant effect was attributed to the production of ketones
• ketogenic diet was introduced as a treatment for epilepsy in the 1920s, but its use waned with the introduction of phenytoin and other antiepileptic drugs (4)
• currently used mainly for children who continue to have seizures despite treatment with antiepileptic drugs
  • more recently there has been interest in less restrictive KDs including the modified Atkins diet (MAD) and the use of these diets has extended into adult practice
  • KD is used in various forms including classic KD, medium-chain triglyceride (MCT) diet, long-chain triglyceride (LCT) diet, modified Atkins diet (MAD) and low glycemic index diet (LGIT)
    • has shown to decrease seizure frequency by about 40%-50% from baseline in selected groups of patients and has a prolonged beneficial effect even after its discontinuation (5)
• a systematic review concluded (6)
  • randomised controlled trials discussed in this review show promising results for the use of KDs in epilepsy - however, the limited number of studies, small sample sizes and a sole paediatric population resulted in a poor overall quality of evidence
  • adverse effects within all of the studies and for all KD variations, such as short-term gastrointestinal-related disturbances, to longer-term cardiovascular complications. Attrition rates remained a problem with all KDs and across all studies, reasons for this being lack of observed efficacy and dietary tolerance
  • other more palatable but related diets, such as the MAD ketogenic diet, may have a similar effect on seizure control as classical KD but this assumption requires more investigation
  • for people who have medically intractable epilepsy or people who are not suitable for surgical intervention, a KD remains a valid option

Notes:

• KD is a high-fat, low-carbohydrate diet induces ketone body production in the liver through fat metabolism
  • the goal is to mimic a starvation state without depriving the body of necessary calories to sustain growth and development
  • ketone bodies acetoacetate and -hydroxybutyrate then enter the bloodstream and are taken up by organs including the brain where they are further metabolized in mitochondria to generate energy for cells within the nervous system
  • ketone body acetone, produced by spontaneous decarboxylation of acetoacetate, is rapidly eliminated through the lungs and urine
    
    
• classic KD is typically composed of a macronutrient ratio of 4:1 (4 g of fat to every 1 g of protein plus carbohydrates combined) - so shifting the predominant caloric source from carbohydrate to fat
  • lower ratios of 3:1, 2:1, or 1:1 (referred to as a modified ketogenic diet) can be used depending on age, individual tolerability, level of ketosis and protein requirements
  • more 'relaxed' variants have been developed, including the modified Atkins diet (MAD), the low glycemic index treatment (LGIT) and the ketogenic diet combined with medium chain triglyceride oil (MCT)
    • MAD typically employs a net 10-20 g/day carbohydrate limit which is roughly equivalent to a ratio of 1-2:1 of fat to protein plus carbohydrates
    • LGIT recommends 40-60 g daily of carbohydrates with the selection of foods with glycemic indices <50 and approximately 60% of dietary energy derived from fat and 20-30% from protein
    • MCT variant KD uses medium-chain fatty acids provided in coconut and/or palm kernel oil as a diet supplement and allows for greater carbohydrate and protein intake than even a lower-ratio classic KD, which can improve compliance

Reference:

• Walczyk T, Wick JY.The Ketogenic Diet: Making a Comeback.Consult Pharm. 2017 Jul 1;32(7):388-396.
• Hippocrates. On the Sacred Disease. Available online: http://classics.mit.edu/Hippocrates/sacred.html
• Ketogenic diets in the treatment of epilepsy.Drug Ther Bull. 2012 Jun;50(6):66-8.
• Agarwal N et al. Ketogenic diet: Predictors of seizure control. SAGE Open Med. 2017 Jun
• Martin K et al. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. 2016 Feb 9;2:CD001903