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.
Traumatic Brain Injury
It's been shown with rats, that after and induced brain injury, rats on a ketogenic diet are troubled less by the injury and recover better after the injury. This is especially true of young rats. Much higher energy levels were reported.
The problem is that to get into ketosis for a human is a process taking 5 to 14 days, perhaps longer. If ketones are easier fuel for the brain to use, we need the effect immediately after the injury to limit the brain damage as much as possible.
There is research into the production of ketone esters, which will produce blood ketones in 15 minutes. This research is aimed at navy divers who are liable to pass-out at extreme depths with no warning, but if they are running on ketones they are protected.
Unfortunately the esters are unpleasant to take.
Epilepsy
A ketogenic diet has been used to treat epilepsy since the 1920's. There is often long term benefit from a period in ketosis and the epilepsy never returns.
The ketogenic diet has been especially useful in treating children, and in forms of epilepsy that are resistant to drug therapy.
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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.
