Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

• Published in: Journal of nutrition and metabolism Vol. 2018; no. 2018; pp. 1 - 27
• Main Authors: Miller, Vincent J., Volek, Jeff S., Villamena, Frederick A.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; John Wiley & Sons, Inc; Wiley
• Subjects: 3-hydroxybutyric acid; Adaptations; antioxidant activity; Antioxidants; Biosynthesis; Cancer; Carbohydrates; Cardiovascular disease; cardiovascular diseases; chronic diseases; Chronic illnesses; Convulsions & seizures; Development and progression; Diabetes; Diabetes mellitus; Diet; Diseases; Electron transport; Energy resources; Epilepsy; Etiology; exercise; fasting; Health; High fat diet; human health; Ketogenesis; ketogenic diet; ketosis; Kinases; Low carbohydrate diet; Metabolism; Microbiota; Mitochondria; Mitochondrial DNA; Musculoskeletal system; neoplasms; Neurodegenerative diseases; Nutrient deficiency; Nutrition research; Oxidative stress; Physiological aspects; Physiology; Prebiotics; Proteins; Reactive oxygen species; Review; Rodents; Signal transduction; Type 2 diabetes; Weight control; United States > US
• ISSN: 2090-0724; 2090-0732; 2090-0732
• DOI: 10.1155/2018/5157645

Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS) and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β-hydroxybutyrate (BHB), which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations.