On the mechanisms of brain protection by ketones.

The interest to ketones remains high for almost a century because they are produced during the ketogenic diet, which is famous for many beneficial health effects. Notwithstanding its high clinical efficacy for treatment of drug-resistant childhood epilepsy, how exactly it worked, remained poorly understood. It's been known for a long time that early in life (as well as on a high-fat, low carbohydrate diet), glucose alone cannot meet the brain's energy needs and other energy carrying chemicals should take part. What's not been know, was how basic brain traits changed depending on available fuels.

Researchers studied how naturally occurring ketones influenced activity of brain cells during development. They showed that a shortage of ketones caused pathological changes in brain cells resulting in abnormal behavior of GABA, the principal brain chemical helping to resist hyperactivity. It was repeatedly reported earlier that, normally working as a "break pedal", GABA did not do the job in the immature brain and acted as a "gas pedal" instead. To imagine the devastating consequences, picture a car having two gas pedals and no brakes.

To make things worse, the energy deficit during hyperactivity is usually combined with increased energy demands thus starting a vicious circle -- demands/deficit/demands -- a well known feature of many neurodegenerative diseases including Alzheimer's, Parkinson's, epilepsy, encephalopathies, dementia, or multiple sclerosis. For many of them, the ketogenic diet was shown to be of a significant help. In the new article, the French and UK researchers offered an explanation. When there was enough of ketone bodies, GABA displayed its natural "break" properties and parameters of brain cells were also normal -- as it happens in real life, in real animals and babies.

Researchers suggest that sufficient supply of appropriate brain fuels can break the vicious circle and prevent brain's hyper-excitation. They now look into other natural energy substrates possibly having greater potential as a "diet in a bottle" than the costly ketones while being as efficient as the overly-stringent ketogenic diet.

Source: J Neurochem. 2009 Aug;110(4):1330-8. Epub 2009 Jun 22.
GABA action in immature neocortical neurons directly depends on the availability of ketone bodies. Rheims S, Holmgren CD, Chazal G, Mulder J, Harkany T, Zilberter T, Zilberter Y.