The ketogenic diet has been initiated to treat a number for medical conditions. It is probably most well known for its beneficial effects for diseases of the nervous system.
The ketogenic diet (KD) was first prescribed as a treatment for epilepsy in the early 1900s, prior to the development of antiepileptic drugs. Even with numerous medication options today, KD is still used to help treat refractory cases of epilepsy. Several mechanism of action have been proposed: 1) the ketone bodies themselves are neuroprotective 2) increased mitochondrial metabolism and ATP generation in the brain stabilizes neuronal ion gradients and increases the production of the inhibitory mediator adenosine 3) increased GABA synthesis causes increased neurotransmitter inhibition 4) Decanoic acid (a medium chain triglyceride) acts as an antagonist of AMPA receptors (Interestingly, decanoic acid probably crosses the blood brain barrier using a medium-chain fatty acid transporter, the same transporter used by the anti-seizure drug Valproic acid, also a medium chain fatty acid!). One recent report looked at multiple studies on the KD and seizures and reported rates of seizure freedom up to 55%, and rates of seizure reduction up to 85%.
Although most well-studied for its effects on seizures, the KD is now being prescribed for a variety of other neurological diseases including Alzheimer’s Disease, Parkinson’s Disease, migraine and cluster headaches.
In Alzheimer’s Disease (AD) abnormal mitochondrial structure and function lead to decreased brain glucose utilization. When given a choice between glucose and ketone bodies for energy, neurons preferentially choose ketones. Although glucose utilization in the brain decreases with age (and to a greater degree in AD), utilization of ketone bodies does not. Several studies have shown modest improvements in cognitive performance testing after being fed a KD.
Regarding Parkinson’s Disease, theory exists that both neuroinflammation and oxidative stress play roles in the develop of the disease. Activated microglial cells in the brain release inflammatory mediators, like IL-6 and TNF-a, as well as reactive oxygen species. A KD (specifically, the ketone body B-hydroxybutyrate) has been shown to have help inhibit the activation of microglial cells (and thus the release of proinflammatory mediators) and dampen the negative effects of H2O2 (hydrogen peroxide).
Ketogenic diet has also been reported to help treat refractory migraine headaches and chronic daily headaches. Additionally, recent research has shown that a very low carbohydrate diet can also help alleviate the awful symptoms of cluster headache. Although the exact mechanism(s) for why the ketogenic diet works for some headache sufferers is still a mystery, there are several theories pertaining to its effects on neuronal ATP production, modulation of neuronal excitation, and neurotransmitter synthesis.
I believe that we are just scratching the surface of what the KD can do for a wide variety of neurological diseases. In addition to the neurological conditions discussed above, there is mounting evidence for KD and a possible role in treating traumatic brain injury, multiple sclerosis, and amyotrophic lateral sclerosis as well.
Di Lorenzo, Cherubino, et al. "efficacy of Modified atkins Ketogenic Diet in chronic cluster headache: an Open-label, single-arm, clinical Trial." Frontiers in neurology 9 (2018): 64.
Farkas, M. K., et al. "EHMTI-0336. Metabolic diet therapy in the prophylactic treatment of migraine headache in adolescents by using ketogenic diet." The journal of headache and pain. Vol. 15. No. S1. Springer Milan, 2014.
Maggioni, Ferdinando, Monica Margoni, and Giorgio Zanchin. "Ketogenic diet in migraine treatment: a brief but ancient history." Cephalalgia-International Journal of Headache 31.10 (2011): 1150.
Shaafi, Sheyda, et al. "Modulatory role of ketogenic diet on neuroinflammation; a possible drug naïve strategy to treatment of Parkinson's disease." Advances in Biosciences & Clinical Medicine 3.4 (2015): 43.