Ketogenic diet versus ketoacidosis: what determines the influence of ketone bodies on neurons?

• Published in: Neural regeneration research Vol. 13; no. 12; pp. 2060 - 2063
• Main Authors: Fedorovich, Sergei, Voronina, Polina, Waseem, Tatyana
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.12.2018; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Institute of Biophysics and Cell Engineering, Minsk, Belarus%Department of Pharmacology, University of Oxford, Oxford, UK; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Adenosine; Alcoholism; Alzheimer's disease; Carbohydrates; Diabetes; Diabetic ketoacidosis; Diet; DNA methylation; Energy; Enzymes; Epigenetics; Fatty acids; Gene expression; Glucose; Glycemic index; Glycogen; Hyperglycemia; Insulin; Liver; Metabolism; Metabolites; Mitochondria; Neurons; Proteins; Review; Starvation; β-hydroxybutirate; epilepsy; diabetes mellitus; alcoholism; metabolism; hydroxyl-carboxylic acid receptor; epigenetics; acidosis; epilepsy; hydroxyl-carboxylic acid receptor; alcoholism; acidosis; β-hydroxybutirate; diabetes mellitus; metabolism; epigenetics
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.241442

Glucose is the main energy substrate for neurons, however, at certain conditions, e.g. in starvation, these cells could also use ketone bodies. This approach is used in clinical conditions as the ketogenic diet. The ketogenic diet is actually a biochemical model of fasting. It includes replacing carbohydrates by fats in daily meal. Synthesis of ketone bodies β-hydroxubutirate, acetoacetate and acetone begins once glycogen stores have depleted in the liver. The ketogenic diet can be used to treat clinical conditions, primarily epilepsy. The mechanism of neuroprotective action of ketogenic diet is not very clear. It is shown that ketone bodies influence neurons at three different levels, namely, metabolic, signaling and epigenetic levels. Ketone bodies are not always neuroprotective. Sometimes they can be toxic for the brain. Ketoacidosis which is a very dangerous complication of diabetes mellitus or alcoholism can be taken as an example. The exact mechanism of how neuroprotective properties of ketone bodies reverse to neurotoxic is yet to be established.