Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

Int J Mol Sci. 2020 Nov 20;21(22):8767. doi: 10.3390/ijms21228767.


Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain's utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain's metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain's glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer's disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson's disease and cognitive benefits in patients with-or at risk of-Alzheimer's disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.

Keywords: SGLT-2 inhibitors; astrocytes; cerebral metabolism; cognition; ketogenic diet; ketone bodies; ketone supplements; neurodegeneration.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Alzheimer Disease / diet therapy
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / pathology
  • Diet, Ketogenic / methods
  • Fasting / physiology
  • Glucose / metabolism*
  • Glycolysis / drug effects
  • Humans
  • Ketone Bodies / metabolism*
  • Ketone Bodies / therapeutic use
  • Liver / drug effects
  • Liver / metabolism
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Neuroprotective Agents / therapeutic use
  • Parkinson Disease / diet therapy
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Rodentia


  • Ketone Bodies
  • Neuroprotective Agents
  • Adenosine Triphosphate
  • Glucose