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Therapeutic Ketosis and Exogenous Ketones: Main applications and clinical updates

Raffaele Pilla

It has been recently shown that nutritional ketosis is effective against seizure disorders and various acute/chronic neurological disorders. Physiologically, glucose is the primary metabolic fuel for cells. However, many neurodegenerative disorders have been associated with impaired glucose transport/metabolism and with mitochondrial dysfunction, such as Alzheimer’s/Parkinson’s disease, general seizure disorders, and traumatic brain injury. Ketone bodies and tricarboxylic acid cycle intermediates represent alternative fuels for the brain andcan bypass the rate-limiting steps associated with impaired neuronal glucose metabolism. Therefore, therapeutic ketosis can be considered as a metabolic therapy by providing alternative energy substratesThe Ketogenic Diet (KD) represents a well-known therapeutic option for refractory epilepsy, although mechanisms regulating its anticonvulsant effects still remain partially unknown. Human brain derives over 60% of its energy from ketones when glucose availability is limited. After prolonged periods of fasting or during a Ketogenic Diet, the whole body utilizes energy obtained from free fatty acids (FFAs) released from adipose tissue. However, the brain is not capable to obtain significant energy from FFAs, thus hepatic ketogenesis converts them into ketone bodies: β-hydroxybutyrate (BHB) and acetoacetate (AcAc), while a percentage of AcAc spontaneously decarboxylates to acetone. Recent perspectives about the Ketogenic diet potentials and neuroprotective properties strongly support its experimental and clinical application in a wide plethora of different neurological diseases.