Dominic D’Agostino – KD Epilepsy Mechanisms

Because the ketogenic diet works when medicines fail, it appears that the diet’s mechanisms of action are different than those of anti-epileptic drugs. AEDs work by targeting neurons, and altering the chemical signals they produce. While the Ketogenic Diet shows efficacy in a spectrum of epilepsy syndromes, specific AEDs are only effective if the drug is matched to the condition which is subjective at best. AEDs are known to carry harsh adverse effects, the most common of which are dizziness, drowsiness, and mental slowing, while less common though more severe side effects include weight gain, metabolic acidosis, liver damage, colitis, and behavioral disorders.

The Ketogenic Diet, on the other hand, has broad sweeping effects on the way in which the body produces and uses energy. This translates to a reduction in neuronal excitability, and, thus, not only reduces or eliminate seizures by at least 50% in half of the people who try it, but it can actually prevent them from reoccurring. It can be a cure. Since the metabolic shift is not site specific and takes place throughout the brain, the diet can be applied to several epilepsy syndromes. Though the exact mechanisms of action are still being studied, the metabolic theory as well as serum ketones continue to be the most highly supported and studied. The metabolic theory postulates that the seizure control is realized through the restoration of the brain’s natural metabolic state through pathways including enhanced mitochondrial energy metabolism and increased availability of energy to the brain. The diet has also been shown to exert neuroprotective antioxidant effects by reducing reactive oxygen species (ROS) production in mitochondria. Moreover, a reduction in glucose levels in the blood, excitatory neurotransmitters in the brain, and inflammation body-wide may support the anti-seizure effect of the diet.

Researchers have also shown that the ketone bodies, beta hydroxybuterate and acetoacetate, might be the cause for the anti-seizure effects. One such paradigm supporting this theory is the fact that seizure control can be lost by consuming carbohydrates, and, thus, falling out of ketosis. Another phenomenon supporting this claim is that blood or serum ketone levels have a strong, negative correlation with seizure activity.

Though ketosis is a natural metabolic state, there can be transition effects, such as “keto flu”, a temporary state when your body converts from burning carbohydrates as its main source of fuel to using fat as its primary energy source. Symptoms can include headache, fatigue, constipation, dehydration, bad breath, and irritability, and generally lasts between 2 days to 2 weeks. In addition, the most common adverse effects of the diet used on a long term basis are kidney stones and constipation. Both can be treated prophylacticlally. We advise that all patients seek medical guidance and supervision prior to attempting a Ketogenic Diet.

In 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the Ketogenic Diet. The consensus statement was subsequently endorsed by the Practice Committee of the Child Neurology Society, paving the way for broad use of the Ketogenic Diet to treat epilepsy. Among the committee’s conclusions were:

“The KD should be strongly considered in a child who has failed two to three anticonvulsant therapies, regardless of age or gender, and particularly in those with symptomatic generalized epilepsies. It can be considered the treatment of choice for two distinct disorders of brain metabolism, GLUT-1 deficiency syndrome and PDHD. In the particular epilepsy syndromes of Dravet syndrome, infantile spasms, myoclonic-astatic epilepsy, tuberous sclerosis complex, the KD could be offered earlier.”

Clinical Guidelines For Ketogenic Therapies

Pediatric: Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group

Adult: Coming Soon!

Supportive Research

The Ketogenic Diet and the associated modified diets are also established in the treatment of epilepsy and in the following syndromes and conditions:

  • Angelman Syndrome (1) (2)
  • Complex 1 mitochondrial disorders (3)
  • Glucose Transporter Protein 1 (Glut-1) Deficiency Syndrome (4)
  • Febrile Infection-Related Epilepsy Syndrome (FIRES) (5) (6)
  • Formula-fed (solely) children or infants (7)
  • Infantile Spasms (8)
  • Myoclonic-Astatic Epilepsy (Doose syndrome) (9)
  • Ohtahara Syndrome (10)
  • Pyruvate Dehydrogenase Deficiency (PDHD) (11)
  • Severe Myoclonic Epilepsy of Infancy (Dravet’s Syndrome) (12)
  • Super-refractory status epilepticus (13) (14) (15)
  • Tuberous Sclerosis Complex (16)(17)
  • Adolescents and adults with epilepsy (18)
  • Juvenile Myoclonic Epilepsy (19)
  • Lafora Body Disease (20)
  • Lennox Gastaut Syndrome (21)
  • Rett Syndrome (22)
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