Therapeutic Potential of the Ketogenic Diet following Brain Injury
7th January 2024
Written by JJ Wellock, Assistant Psychologist.
In the first blog we introduced what the Ketogenic diet is, how our brain uses ketones, its properties and challenges. In this part, we are going to discuss the therapeutic potential of the Ketogenic diet for those with brain injuries.
With any major dietary change, it is highly important that you seek medical advice first!
Brain injuries can be understood as occurring in two main stages: the ‘primary’ injury, when brain tissue is damaged through blunt force, open wound, or ‘shearing’ of brain axons. ‘Secondary’ damage occurs as a consequence of the brain’s response to injury, occurring over a period of hours to days. Examples of a secondary response include: inflammation; reduced blood flow/oxygen supply, and neurochemical changes leading to significant to tissue and cell death and causing neurological changes, including physical or cognitive impairment, over time.
With over a century of research, there is evidence to suggest that ketones have neuroprotective abilities, although this is still yet to be fully understood. What is known is that ketone bodies not only provide an alternative energy source when glucose is scarce, but can also influence the function of brain cells and thus modify the effects of injury.
Antioxidant and anti-convulsant properties
After a brain injury, unstable molecules called ‘free radicals’ accumulate due to a lack of antioxidants. This imbalance leads to oxidative stress that results in mitochondrial dysfunction, causing mental and physical fatigue, and damage to cells/tissue. Multiple studies have shown that ketones have antioxidant properties that can neutralise these ‘free radicals’, and therefore prevent further damage (Greco et al, 2016). The development of epilepsy may also be prevented through supplementary antioxidant therapies, decreasing seizure frequency by almost 50% (Dahlin et al, 2012; Mehvari et al, 2016; Shekh-ahmad et al, 2019).
Glutamate and GABA neurotransmitters play a huge role in brain communications and the balance is crucial for normal neuronal functioning. Glutamate is responsible for memory, learning, synaptic ‘plasticity’ and pain transmission. GABA counteracts glutamate and can prevent messages being transmitted, it is known for its calming effect on the nervous system and has anti-convulsant, anti-anxiety properties.
After a brain injury, a reduction of GABA producing skills causes glutamate levels to rise, generating excitotoxicity (Mattson, 2017). Ketones, however, are able to efficiently enhance synthesisation of GABA to counteract the imbalance, thus preventing toxicity and any further damage from secondary injury (Daikhin & Yudkoff, 1998; Yudkoff et al, 2008).
Epigenetic properties
Epigenetic refers to the way in which the environment and behaviours change how the body reads a DNA sequence. Things like diet, substance use, exercise, etc. can change how genes are read, causing them to switch “on” and “off”. Epigenetic alterations have been associated with inflammation that can lead to death or damage of brain cells; increasing the developmental risk of neurodegenerative diseases after brain injury, as well as some cancer types (Wong & Langley, 2016; Sagarkar et al, 2017; Duan et al, 2021). Studies have shown that a ketogenic diet is associated with positive epigenetic changes although the ‘mechanism’ is not fully understood (Davie, 2003; Ruan & Crawford, 2018; Ungaro et al, 2022). MicroRNAs (miRNAs), which control protein production and intracellular concentration, are able to easily cross the blood brain barrier and are essential to neuronal injury and repair. MiRNAs have now been identified as a potential biomarker of brain injuries by providing information on severity and recovery tracking (Croce, 2009; Atif & Hicks, 2019).
Despite the many benefits of the ketogenic diet outlined in research, it is not without its challenges. To learn more, check out the next and final part to this ketogenic series.
References:
Atif, H., & Hicks, S. D. (2019). A review of microRNA biomarkers in traumatic brain injury. Journal of experimental neuroscience, 13, 1179069519832286.
Croce, C. M. (2009). Causes and consequences of microRNA dysregulation in cancer. Nature reviews genetics, 10(10), 704-714.
Dahlin, M., Månsson, J. E., & Åmark, P. (2012). CSF levels of dopamine and serotonin, but not norepinephrine, metabolites are influenced by the ketogenic diet in children with epilepsy. Epilepsy research, 99(1-2), 132-138.
Daikhin, Y., & Yudkoff, M. (1998). Ketone bodies and brain glutamate and GABA metabolism. Developmental neuroscience, 20(4-5), 358-364.
Davie, J. R. (2003). Inhibition of histone deacetylase activity by butyrate. The Journal of nutrition, 133(7), 2485S-2493S.
Duan, K., Mayer, A. R., Shaff, N. A., Chen, J., Lin, D., Calhoun, V. D., & Liu, J. (2021). DNA methylation under the major depression pathway predicts pediatric quality of life four-month post-pediatric mild traumatic brain injury. Clinical epigenetics, 13, 1-17.
Greco, T., Glenn, T. C., Hovda, D. A., & Prins, M. L. (2016). Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity. Journal of Cerebral Blood Flow & Metabolism, 36(9), 1603-1613.
Hlady, R. A., & Robertson, K. D. (2016). Use of chromatin changes as biomarkers. In Chromatin Signaling and Diseases (pp. 403-421). Academic Press.
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Mattson, M. P. (2017). Excitotoxicity. Neurodegeneration, 37-45.
Mehvari, J., Motlagh, F. G., Najafi, M., Ghazvini, M. R. A., Naeini, A. A., & Zare, M. (2016). Effects of Vitamin E on seizure frequency, electroencephalogram findings, and oxidative stress status of refractory epileptic patients. Advanced biomedical research, 5.
Ruan, H. B., & Crawford, P. A. (2018). Ketone bodies as epigenetic modifiers. Current Opinion in Clinical Nutrition & Metabolic Care, 21(4), 260-266.
Sagarkar, S., Bhamburkar, T., Shelkar, G., Choudhary, A., Kokare, D. M., & Sakharkar, A. J. (2017). Minimal traumatic brain injury causes persistent changes in DNA methylation at BDNF gene promoters in rat amygdala: a possible role in anxiety-like behaviors. Neurobiology of Disease, 106, 101-109.
Shekh-Ahmad, T., Lieb, A., Kovac, S., Gola, L., Wigley, W. C., Abramov, A. Y., & Walker, M. C. (2019). Combination antioxidant therapy prevents epileptogenesis and modifies chronic epilepsy. Redox Biology, 26, 101278.
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Yudkoff, M., Daikhin, Y., Horyn, O., Nissim, I., & Nissim, I. (2008). Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia, 49, 73-75.