Efficacy of the Ketogenic Diet for the Treatment of Refractory Childhood Epilepsy: Cerebrospinal Fluid Neurotransmitters and Amino Acid Levels

Pediatr Neurol. 2015 Nov;53(5):422-6. doi: 10.1016/j.pediatrneurol.2015.07.013. Epub 2015 Aug 8.


Objective: The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet.

Methods: We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown.

Results: Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed.

Significance: The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not.

Keywords: amino acids; cerebrospinal fluid; children; ketogenic diet; neurotransmitters; refractory epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Amino Acids / cerebrospinal fluid*
  • Child, Preschool
  • Diet, Ketogenic*
  • Drug Resistant Epilepsy / cerebrospinal fluid*
  • Drug Resistant Epilepsy / diet therapy*
  • Drug Resistant Epilepsy / etiology
  • Epilepsies, Partial / cerebrospinal fluid
  • Epilepsies, Partial / diet therapy
  • Epilepsies, Partial / etiology
  • Humans
  • Neurotransmitter Agents / cerebrospinal fluid*
  • Seizures / cerebrospinal fluid
  • Seizures / diet therapy
  • Seizures / etiology
  • Treatment Outcome


  • Amino Acids
  • Neurotransmitter Agents