Ketone Body, 3-Hydroxybutyrate: Minor Metabolite - Major Medical Manifestations

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 9; pp. 2884 - 2892
• Main Author: Moller, Niels
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.09.2020; Copyright Oxford University Press
• Subjects: 3-Hydroxybutyric Acid - chemistry; 3-Hydroxybutyric Acid - metabolism; 3-Hydroxybutyric Acid - physiology; Acetone; Amino acids; Angiogenesis; Animals; Arteriosclerosis; Blood flow; Cancer; Carboxylic acids; Cardiac patients; Cardiovascular System - metabolism; Central Nervous System - metabolism; Central Nervous System - physiology; Convulsions & seizures; Dementia; Dementia disorders; Dextrose; Diabetes; Diabetes mellitus; Diabetes Mellitus - metabolism; Diabetes Mellitus - pathology; Diabetic ketoacidosis; Diabetics; Dietary restrictions; Enzymes; Epilepsy; Exercise - physiology; Fasting - physiology; Fatty acids; Glucagon; Glucose; Growth hormones; Heart diseases; Heart failure; Histone deacetylase; Humans; Hypoglycemia; Inflammasomes; Inflammation; Inflammation - metabolism; Inflammation - pathology; Insulin; Ketoacidosis; Ketone Bodies - chemistry; Ketone Bodies - metabolism; Ketone Bodies - physiology; Ketones; Lipolysis; Longevity - physiology; Medical research; Medicine, Experimental; Metabolic Networks and Pathways - physiology; Metabolic syndrome; Metabolic Syndrome - metabolism; Metabolic Syndrome - pathology; Metabolites; Nervous system; Nervous system diseases; Neurological diseases; Oxidative stress; Patients; Proteins; Seizures; Seizures (Medicine); Type 2 diabetes
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa370

Abstract Ketone bodies – 3-hydroxybutyrate (3-OHB), acetoacetate, and acetone – are ancient, evolutionarily preserved, small fuel substrates, which uniquely can substitute and alternate with glucose under conditions of fuel and food deficiency. Once canonized as a noxious, toxic pathogen leading to ketoacidosis in patients with diabetes, it is now becoming increasingly clear that 3-OHB possesses a large number of beneficial, life-preserving effects in the fields of clinical science and medicine. 3-OHB, the most prominent ketone body, binds to specific hydroxyl-carboxylic acid receptors and inhibits histone deacetylase enzymes, free fatty acid receptors, and the NOD-like receptor protein 3 inflammasome, tentatively inhibiting lipolysis, inflammation, oxidative stress, cancer growth, angiogenesis, and atherosclerosis, and perhaps contributing to the increased longevity associated with exercise and caloric restriction. Clinically ketone bodies/ketogenic diets have for a long time been used to reduce the incidence of seizures in epilepsy and may have a role in the treatment of other neurological diseases such as dementia. 3-OHB also acts to preserve muscle protein during systemic inflammation and is an important component of the metabolic defense against insulin-induced hypoglycemia. Most recently, a number of studies have reported that 3-OHB dramatically increases myocardial blood flow and cardiac output in control subjects and patients with heart failure. At the moment, scientific interest in ketone bodies, in particular 3-OHB, is in a hectic transit and, hopefully, future, much needed, controlled clinical studies will reveal and determine to which extent the diverse biological manifestations of 3-OHB should be introduced medically.