Treating Concussions with Ketones

broken-brain

What is a Concussion?

Head injury, whether it is from a concussion or a severe traumatic brain injury, can have long term and serious consequences. Concussions are typically described as mild traumatic brain injury. Concussions are most commonly occur from sports related injuries, such as from being tackled in football, to hitting a soccer ball off of head, or falling off a bicycle. In the US, there is estimated between 1.6 to 3.8 million sports related concussions that occur every year. The rates for concussion are highest in pediatric and adolescent age ranges. Even though concussions often do not cause structural damage to the brain, they still can causes significant symptoms. Headaches are the most common symptom seen with a concussion, but other post concussion symptoms include problems sleeping, impaired memory, dizziness, balance problems, attention problems and depression. These symptoms can last from weeks to months and in some cases even longer. (Giza, 2014)

Concussions have come to the forefront of pubic awareness with the recently discovered disease, chronic traumatic encephalopathy, which was the topic of the movie ‘Concussion’. Chronic traumatic encephalopathy (CTE) is the neurodegenerative changes that occur in the brains of individuals who have sustain multiple concussions earlier in their lives. CTE results in long-term neurological symptoms including behavioral, cognitive and motor symptoms.   The behavioral symptoms include depression, mood swings, aggression and possibly suicide. The cognitive deficits can range from memory problems to dementia. The motor symptoms vary from parkinsonian tremors to ataxia and even possibly a motor neuron disease. (Jordan, 2014)

What is the treatment of concussion?

Currently, there is no medical treatment for concussion except supportive measures. Other than the prevention of concussion in the first place, there is no medical ways to prevent it from progressing into CTE.

What is the pathobiology of concussion?

The underlying pathobiology of concussion has been well described. The shaken brain causes a disruption of the cellular membranes. This then causes a release of chemicals; potassium to flow out of the cells and calcium to flow into the cells. This triggers a cortical spreading depression of the neurons, which then results in the release of glutamate from the cells. The brain needs energy, or ATP to reestablish a balance or homeostasis of these chemicals. ATP is produced in the mitochondria of the cell after the uptake of glucose thru the process of glycolysis.(Giza, 2014)

Immediately after the brain injury there is then a transient increase in glucose uptake, followed by a prolonged decreased in glucose uptake and decrease glycolysis. This impairment in glucose uptake and glycolysis results in an over decreased in ATP production. This time of energy crisis or metabolic dysfunction of the brain is variable, ranging from days to months, depending on severity of injury and age of the brain.(Prins, 2104) Other changes that are occurring in the brain during this time include; increased glutamate excitotoxic damage and increased free radical production. During this time of metabolic dysfunction the brain is felt to be more vulnerable to a second injury. (Giza, 2014)

Is there an alternate fuel source that can be used?

Ketones are the only known natural alternative of glucose that can be used for cerebral energy metabolism. The advantage of using ketones is that they produce ATP thru beta- oxidation not thru glycolysis. Thus ketones are able to bypass the glucose metabolic derangements that are seen associated with brain injuries. ATP supply is also increased from mitochondria biogenesis that is seen with ketones. (Streijger, 2016) In the injured brain, ATP stores have been to be restored after administration of a ketone, beta-hydroxybutyate. (Prins, 2004) Ketones may also benefit the injured brain by their antioxidant effect, ability to increase the antioxidant glutathione and reduce free radical production. (Gano, 2014) Ketones also have been shown to protect cells against glutamate-induced neurotoxicity. (Ziegler, 2003) Hence, using Ketones as an as alternate fuel source instead of glucose, as therapeutic treatment of head injury is appealing.

How does this translate clinically?

There have not been any trials, as of yet, in humans. In studies using adolescent rats, the ketogenic diet has been shown to improve outcomes both with cognitive and motor function, following traumatic brain injury.   When the rats are pretreated with ketogenic diet they were found to have 58% less cortical injury volumes and better neuronal preservation. (Streijger, 2016)

For maximum neuroprotective effects, it is best to be in a state of ketosis (a state where the body is producing ketones) prior to any brain injury. The next best is to start it as soon as possible after the injury. Typically, if you start a ketogenic diet, it may take a while, up to several days, before you will be in ketosis. Another option, which can be used either in place of, or in addition to a ketogenic diet, is to use a ketone supplement. This supplement will get your body in the state of ketosis in less than 60 minutes. This supplement is not currently FDA approved for the treatment of concussion or other diseases. However, the researchers, who are currently using this supplement in research studies for concussion and head injury, are very excited about its potential. They currently recommended it for anyone who plays contact sports and are discussing potential uses in college and profession sports.

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Bibliography

Gano, L. (2014). Ketogenic Diet, mitochondria, and neurological diesases. Journal Lipid Research, 55, 2211-2228.
Giza, C. C. (2014). An Introduction to Sports Concussions. Continuum Lifelong learning in Neurology, 20 (6), 1545-1551.
Jordan, B. (2014). Chronic Traumatic Encephalopathy and other long-term sequelae. Continuum, lifelong learning in Neurology, 20 (6)1588-1604.
Prins, M. (2004). Increased cerebral uptake and oxidation of exogenous BHB improves ATP following traumatice brain injury in adult rats. Journal of Neurochemistry, 90, 666-672.
Prins, M. M. (2014). The collective therapeutic potential of cerebralketone metabolism in traumatic brain injury. Journal of Lipid Research, 55, 2450-2457.
Streijger, F. (2016). Ketogenic Diet and Ketones for the Treatment of Traumatic Brain and Spinal Cord Injury. In S. Masino (Ed.), Ketogenic Diet and Metabolic Therapies (pp. 133-146). Oxford.
Ziegler, D. (2003). Ketogenic diet increases glutathion peroxidase activity in rat hippocampus. Neurochem Res, 28, 1793-1797.