Transcript The ketogenic diet

I.
high-fat, adequate-protein, low-carbohydrate diet .
II.
The diet forces the body to burn fats rather than carbohydrates.
III.
The original therapeutic diet provides just enough protein for body growth and
repair, and sufficient calories to maintain the correct weight for age and height.
This classic ketogenic diet contains a 4:1 ratio by weight of fat to combined
protein and carbohydrate. This is achieved by excluding high-carbohydrate
foods.
IV.
the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass
into the brain and replace glucose as an energy source.
V.
A typical ketogenic diet meal
I.
30 % of patients become seizure free. 60 % of patients
experience significant benefit.
II.
The onset of seizure control is typically slow, probably reflecting
the induction of the transporters and enzymes required for
effective utilization of ketone bodies by the brain.
III.
In contrast, seizure protection is lost quite quickly when the
ketogenic diet is “broken” by a supply of sugar by having a
candy bar), seizure protection is lost in the course of tens of
minutes.
IV.
V.
broad anticonvulsant effects, as it is able to control seizures of many different
types. In this way it is a more effective anticonvulsant therapy than any of the
currently available antiepileptic drugs
Ketogenic diet is used as a second line treatment for refractory epilepsy (
don’t respond to 2-3 different anticonvulsants).
Kennedy A R et al. Am J Physiol Endocrinol
Metab 2007;292:E1724-E1739
I. Augmentation of ketone bodies production
II. The metabolic changes associated with
decreased glucose oxidation
I.
the10 mM concentration of acetoacetate directly dialyzed into the
rat brain was considerably higher than the effective concentrations
required for inhibition of VGLUT2
II.
organotypic hippocampal slice cultures chronically exposed to
BHB were not protected from pharmacologically induced
epileptiform activity.
III. acetoacetate rapidly breaks down to acetone or is converted to
BHB, so it remains to be shown whether acetoacetate levels in the
brain during dietary therapy are sufficient to inhibit VGLUT2
chronically
1.
2.
Adenosine is a well established and powerful
anticonvulsant
deletion of A1Rs and increased adenosine
clearance by elevated adenosine kinase (ADK)
both cause spontaneous intrahippocampal
electrographic seizures and increase the brain’s
susceptibility to injury
I. K channels (KATP channels) Best-
known for their role in controlling
insulin secretion from pancreatic cells
II. KATP channels are also widely
expressed in central neurons.
I.
A protein with dual functions in apoptosis and glucose metabolism.
II.
BAD modifications (by phosphorylation) that reduce glucose metabolism
produce a marked increase in the activity of metabolically sensitive KATP
channels in neurons.
III.
phosphorylation is required for mitochondrial metabolism of glucose.
IV.
Seizure resistance of knockout BAD mice is reversed by genetic ablation of the
KATP channel.
 glutamate cysteine ligase – the rate limiting enzyme of glutathione production
 Reduced COA is an indicator of the mitochondrial redox status
 lipoic acid - a thiol antioxidant.