Ketone bodies in exercise, health and disease: Metabolic mechanisms, pathophysiology, and therapeutic implications

Ketone bodies (KBs) are alternative metabolic fuels predominantly produced in the liver during periods of carbohydrate restriction, prolonged fasting, or ketogenic dietary intake. Beyond energy metabolism, KBs exert pleiotropic effects by modulating cellular signaling pathways, oxidative stress, and...

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Main Authors: Yin Li, Qingyi Liu, Zhihao Jia, Bin Guo
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-06-01
Series:Advanced Exercise and Health Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950273X25000293
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author Yin Li
Qingyi Liu
Zhihao Jia
Bin Guo
author_facet Yin Li
Qingyi Liu
Zhihao Jia
Bin Guo
author_sort Yin Li
collection DOAJ
description Ketone bodies (KBs) are alternative metabolic fuels predominantly produced in the liver during periods of carbohydrate restriction, prolonged fasting, or ketogenic dietary intake. Beyond energy metabolism, KBs exert pleiotropic effects by modulating cellular signaling pathways, oxidative stress, and epigenetic regulation. Recent advances have underscored the importance of ketone bodies in exercise physiology and muscle function. Excessive or impaired ketone handling underlies diabetic ketoacidosis and contributes to the pathogenesis of selected neurodegenerative, cardiovascular and neoplastic disorders. Therapeutically, ketogenic diet (KD) and exogenous ketone supplementation are being explored for their potential in treating metabolic disorders, neurodegeneration, and even malignancies. This review provides a comprehensive synthesis of the latest scientific insights into KB classification, metabolic regulation, pathophysiological roles in disease, and their emerging therapeutic applications. We critically examine recent findings on KB metabolism and discuss the mechanistic underpinnings that define their physiological and pathological relevance.
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publisher KeAi Communications Co., Ltd.
record_format Article
series Advanced Exercise and Health Science
spelling doaj-art-65701fedf4d945dea2475a071e8ebf7c2025-08-20T03:28:06ZengKeAi Communications Co., Ltd.Advanced Exercise and Health Science2950-273X2025-06-0122839310.1016/j.aehs.2025.05.004Ketone bodies in exercise, health and disease: Metabolic mechanisms, pathophysiology, and therapeutic implicationsYin Li0Qingyi Liu1Zhihao Jia2Bin Guo3Cambridge-Suda Genomic Resource Center, Suzhou Medical College, Soochow University, Suzhou, China; School of life science, Suzhou Medical College, Soochow University, Suzhou, ChinaCambridge-Suda Genomic Resource Center, Suzhou Medical College, Soochow University, Suzhou, China; School of life science, Suzhou Medical College, Soochow University, Suzhou, ChinaCambridge-Suda Genomic Resource Center, Suzhou Medical College, Soochow University, Suzhou, China; Correspondence to: Suzhou Medical College, Soochow University, 199 Ren'ai Rouad, Suzhou 215123, China.Wisdom Lake Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, China; Corresponding author.Ketone bodies (KBs) are alternative metabolic fuels predominantly produced in the liver during periods of carbohydrate restriction, prolonged fasting, or ketogenic dietary intake. Beyond energy metabolism, KBs exert pleiotropic effects by modulating cellular signaling pathways, oxidative stress, and epigenetic regulation. Recent advances have underscored the importance of ketone bodies in exercise physiology and muscle function. Excessive or impaired ketone handling underlies diabetic ketoacidosis and contributes to the pathogenesis of selected neurodegenerative, cardiovascular and neoplastic disorders. Therapeutically, ketogenic diet (KD) and exogenous ketone supplementation are being explored for their potential in treating metabolic disorders, neurodegeneration, and even malignancies. This review provides a comprehensive synthesis of the latest scientific insights into KB classification, metabolic regulation, pathophysiological roles in disease, and their emerging therapeutic applications. We critically examine recent findings on KB metabolism and discuss the mechanistic underpinnings that define their physiological and pathological relevance.http://www.sciencedirect.com/science/article/pii/S2950273X25000293Ketone bodiesEnergy metabolismExercise physiologyNeurodegenerationKetogenic dietTherapeutic ketones
spellingShingle Yin Li
Qingyi Liu
Zhihao Jia
Bin Guo
Ketone bodies in exercise, health and disease: Metabolic mechanisms, pathophysiology, and therapeutic implications
Advanced Exercise and Health Science
Ketone bodies
Energy metabolism
Exercise physiology
Neurodegeneration
Ketogenic diet
Therapeutic ketones
title Ketone bodies in exercise, health and disease: Metabolic mechanisms, pathophysiology, and therapeutic implications
title_full Ketone bodies in exercise, health and disease: Metabolic mechanisms, pathophysiology, and therapeutic implications
title_fullStr Ketone bodies in exercise, health and disease: Metabolic mechanisms, pathophysiology, and therapeutic implications
title_full_unstemmed Ketone bodies in exercise, health and disease: Metabolic mechanisms, pathophysiology, and therapeutic implications
title_short Ketone bodies in exercise, health and disease: Metabolic mechanisms, pathophysiology, and therapeutic implications
title_sort ketone bodies in exercise health and disease metabolic mechanisms pathophysiology and therapeutic implications
topic Ketone bodies
Energy metabolism
Exercise physiology
Neurodegeneration
Ketogenic diet
Therapeutic ketones
url http://www.sciencedirect.com/science/article/pii/S2950273X25000293
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AT qingyiliu ketonebodiesinexercisehealthanddiseasemetabolicmechanismspathophysiologyandtherapeuticimplications
AT zhihaojia ketonebodiesinexercisehealthanddiseasemetabolicmechanismspathophysiologyandtherapeuticimplications
AT binguo ketonebodiesinexercisehealthanddiseasemetabolicmechanismspathophysiologyandtherapeuticimplications