Your brain on ketosis

May 29, 2020

When people switch to a ketogenic diet, this often brings many benefits. For example a ketogenic diet may aid the gut microbiome. There are some benefits however that remain underexposed, but for which there is increasing scientific evidence. In this article I want to show what benefits ketosis may have for your brain. I will give you a clue, it has something to do with mental sharpness and increased cognitive skills.

The brain is a complex organ and requires a lot of energy.¹ Although it only covers 2-3% of our body weight, it does require 20-23% of the body's total energy requirement. And while it is sometimes  claimed that the brain runs entirely on glucose, it is now difficult to deny that the brain can also run on ketones. After a few weeks of fat adaptation, this is approximately between 50 and 75% of the required energy. If the brain only used glucose, we would only be able to be without food for a few days. Without the ketones extracted from the fats in the liver, we would soon be unable to function. With this alternative fuel, the brain can go into a sort of glucose saving mode.²

And since ketones are burned through a different metabolic pathway from glucose, they also have other benefits, such as:

  • Ketones are a more efficient form of energy than sugar. Ketones and especially beta-hydroxybutyrate are more efficient per unit of oxygen. Particularly as the brain cell ages, it loses the efficiency of using glucose as a fuel.

  • Ketones increase the efficiency of mitochondria. Mitochondria are the small engines that the body runs on which provide energy for the cells in your body. In addition to increased efficiency, ketosis can cause more mitochondria to be produced and more energy in the form of ATP to be released to your brain cells, which is also known as mitochondrial biogenesis. It has been shown in rats, that ketones provide more Adenosine Tri Phospate (ATP - the energy carrier of the body) compared to pyruvate, the energy form of glucose.³
  • Ketones are a neuroprotective antioxidant. Several animal studies have shown that ketones act as an antioxidant, protecting brain cells from harmful reactive oxygen particles.⁴ In addition, ketones increase GABA signaling activity.⁵ GABA is the counterpart of glutamate, which we both need for cognitive performance. Glutamate provides the stimuli and GABA ensures relaxation. While glutamate is very important for neural communication, memory and learning ability, too much of it can also lead to neurodamage. Ketosis can help to balance this.
  • Ketones trigger the expression of neurotrophin. Neurotrophin is a protein that acts on specific neurons in the nervous system. It aids in the survival of existing neurons while supporting the growth and connection between new neurons. Ketones trigger the expression of neurotrophin leading to improvement of the performance of the hippocampus, cortex and basal ganglia. These areas are indispensable for learning, remembering and critical thinking.

Finally, more and more evidence is emerging that ketosis can provide support for neuro-related problems. For example, it is suggested that a large percentage of Alzheimer's cases are caused by too much insulin. Its pathology is showing signs increasingly similar to diabetes and insulin resistance, which is now also sometimes referred to as type 3 diabetes.⁶ Glucose uptake is also reduced in epilepsy and Parkinson's even before the cognitive decline is visible.⁷ In all these cases, a ketogenic diet can provide relief.⁸ A very low carbohydrate diet can lead to improvements in memory in the elderly with mild cognitive complaints, but also in the elderly without cognitive complaints.⁹ˈ¹⁰


Verbal memory improvements in the elderly

So whether you want to boost your brain or prevent neuro-related problems, the ketogenic diet is one of the best ways to do it. With the ketogenic diet you give your body and brain a more efficient energy source that reduces inflammation and neuronal damage while stimulating brain cell growth and function!

1. Cunnane, S.C., Courchesne‐Loyer, A., St‐Pierre, V., Vandenberghe, C., Pierotti, T., Fortier, M., Croteau, E. and Castellano, C.‐A. (2016), Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease. Ann. N.Y. Acad. Sci., 1367: 12-20. doi:10.1111/nyas.12999

2. LaManna, J. C., Salem, N., Puchowicz, M., Erokwu, B., Koppaka, S., Flask, C., & Lee, Z. (2009). Ketones suppress brain glucose consumption. Advances in experimental medicine and biology645, 301–306.

3. Maalouf, M., Sullivan, P. G., Davis, L., Kim, D. Y., & Rho, J. M. (2007). Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience145(1), 256–264.

4. Murray AJ, Knight NS, Cole MA, et al. Novel ketone diet enhances physical and cognitive performance. FASEB J. 2016;30(12):4021‐4032. doi:10.1096/fj.201600773R

5. Yudkoff M, Daikhin Y, Horyn O, Nissim I, Nissim I. Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia. 2008;49 Suppl 8(Suppl 8):73‐75. doi:10.1111/j.1528-1167.2008.01841.x

6. de la Monte, S. M., & Wands, J. R. (2008). Alzheimer's disease is type 3 diabetes-evidence reviewed. Journal of diabetes science and technology2(6), 1101–1113.

7. Cunnane, S., Nugent, S., Roy, M., Courchesne-Loyer, A., Croteau, E., Tremblay, S., Castellano, A., Pifferi, F., Bocti, C., Paquet, N., Begdouri, H., Bentourkia, M., Turcotte, E., Allard, M., Barberger-Gateau, P., Fulop, T., & Rapoport, S. I. (2011). Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition (Burbank, Los Angeles County, Calif.)27(1), 3–20.

8. Gasior, M., Rogawski, M. A., & Hartman, A. L. (2006). Neuroprotective and disease-modifying effects of the ketogenic diet. Behavioural pharmacology17(5-6), 431–439.

9. Krikorian R, Shidler MD, Dangelo K, Couch SC, Benoit SC, Clegg DJ. Dietary ketosis enhances memory in mild cognitive impairment. Neurobiol Aging. 2012;33(2):425.e19‐425.e4.25E27. doi:10.1016/j.neurobiolaging.2010.10.006

10. Ota M, Matsuo J, Ishida I, et al. Effect of a ketogenic meal on cognitive function in elderly adults: potential for cognitive enhancement. Psychopharmacology (Berl). 2016;233(21-22):3797‐3802. doi:10.1007/s00213-016-4414-7

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