Open Future HealthBrain Research - Ketone Use

It's been known for 500 years that if epileptic people were maintained on short rations (semi-starvation) that their seizures were infrequent or might stop altogether. 100 years ago it was discovered that if carbohydrates were removed from the diet the same effect on the seizures occurred without starvation.

It now known that a ketogenic diet, produces ketones that the brain can use for energy, conserving glucose. This might be particularly important in any brain condition where glucose metabolism is compromised.

Three Brain Diseases of Interest

Alzheimer's Disease

An early sigh of Alzheimer's disease is a decline in blood glucose metabolism. Any inhibition of glucose has a profound effect on brain function.

The brain is unable to use fatty-acids, but is very capable of running on ketone bodies, acetoacetate, ß-hydroxybutyrate, and acetone, that the liver makes from fatty acids, in the absence of insulin.

The mitochondria in the brain seem to much more efficient when ketones are the fuel. Ketone produce energy with less oxygen demand, and they burn more cleanly, producing little or no reactive oxygen species (ROS). It's thought that the ability to oxidize co-enzyme Q and reduce NADP+ may be the reason.

ATP hydrolysis produces increased energy if ketones are available.

In a culture based on human Alzheimer's disease cells, ketones were effective in reducing apoptosis.

It's thought that for clinical purposes ß-hydroxybutyrate level in the blood should be at 2-5 mmol. That can be achieved by diet alone, but the researchers look forward to when synthetic esters or polymers of ß-hydroxybutyrate might be taken orally.

Parkinson's Disease

Parkinson's disease is a neurological disease characterized by nerve damage and cell death. Brain structures called substantis nigra contain dopaminergic neurons, that produce the neurotransmitter called dopamine.

When dopaminergic neurons are damaged they produce much less dopamine, and eventually they die, leaving "tangles" of proteins called Lewy bodies.

There is evidence that mitochondrial dysfunction, causes oxidative stress. Dopamine oxidation creates oxidative stress which inflames and damages the dopaminergic cells.

Several investigators have demonstrated that the ketogenic diet can relieve some of the symptoms of Parkinson's disease. It's thought that the use of ketones can bypass the dysfunctional mitochondria. Also that there is less mitochondrial respiratory damage reducing the number of free radicle's and ROS created.

In a small study, 5 out of 7 on a ketogenic diet showed improved ratings on a standard Parkinson's rating test.

Symptoms of Parkinson's disease include motor disorders such as tremors, slowed movements, stiffness, slumped posture, and impaired coordination and balance. Non-motor symptoms also occur, such as loss of smell sense, inability to sleep deeply, bladder and bowel issues, fatigue, confusion, memory loss and mood disorders.

In a culture based on human Parkinson's disease cells, ketones were effective in reducing apoptosis.

Stroke Rehabilitation

It's plausible that neuroprotection of ß-hydroxybutyrate improves the ability of neurons to resist metabolic challenges, there may be other actions in addition to antioxidant and anti-inflammatory effects.

The idea of a ketogenic pill for stroke victims is attractive and in future may be available.

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