TY - JOUR

T1 - Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

AU - Jensen, Nicole Jacqueline

AU - Wodschow, Helena Zander

AU - Nilsson, Malin

AU - Rungby, Jørgen

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Adenosine Triphosphate/biosynthesis

KW - Alzheimer Disease/diet therapy

KW - Animals

KW - Brain/drug effects

KW - Diet, Ketogenic/methods

KW - Fasting/physiology

KW - Glucose/metabolism

KW - Glycolysis/drug effects

KW - Humans

KW - Ketone Bodies/metabolism

KW - Liver/drug effects

KW - Neuroglia/drug effects

KW - Neurons/drug effects

KW - Neuroprotective Agents/therapeutic use

KW - Parkinson Disease/diet therapy

KW - Rodentia

U2 - 10.3390/ijms21228767

DO - 10.3390/ijms21228767

M3 - Review

C2 - 33233502

VL - 21

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 22

M1 - 8767

ER -