Clinical Applications of Ketogenic Diet-Induced Ketosis in Neurodegenerative and Metabolism-Related Pathologies

: Metabolic-based therapies such as nutritional ketosis have been proven effective for seizure disorders and various acute and chronic neurological pathologies. In a healthy brain, glucose is the primary metabolic fuel for cells. However, neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), seizure disorders, and traumatic brain injury (TBI) are associated with impaired glucose transport and metabolism and with mitochondrial dysfunction leading to energy deficit. Therapeutic ketosis can be considered as a form of metabolic therapy by providing alternative energy substrates. In addition, ketosis leads to metabolic adaptations that improve brain metabolism, restore mitochondrial ATP production, decrease reactive oxygen species production, reduce inflammation, and increase the activity of neurotrophic factors. Moreover, the synaptic activity between neurons is also stabilized through the increase of Szent-Györgyi–Krebs cycle intermediates, antioxidant effects, increased GABA-to-glutamate ratio, and activation of ATP-sensitive potassium channels.