Ketogenic Brain Fueling refers to the metabolic state where the central nervous system predominantly utilizes ketone bodies—specifically beta-hydroxybutyrate (BHB) and acetoacetate—as its primary energy substrate instead of glucose. This physiological shift occurs during periods of carbohydrate restriction or fasting, offering a highly efficient, alternative fuel source for neurons and glia. Optimizing this fueling state is clinically explored for its neuroprotective and cognitive-enhancing benefits.
Origin
This concept originates from metabolic biochemistry and neuroendocrinology, drawing on the historical clinical use of the ketogenic diet for managing certain neurological conditions. The term highlights the brain’s metabolic plasticity, its ability to switch fuel sources, which was initially recognized in the study of starvation and later applied to therapeutic diets. “Ketogenic” refers to the generation of ketones, and “fueling” denotes the energetic utilization by the brain.
Mechanism
The core mechanism involves the hepatic production of ketone bodies from fatty acid oxidation when insulin levels are low and glucagon is high. These ketones cross the blood-brain barrier via monocarboxylate transporters and are then metabolized by neurons into acetyl-CoA, which enters the Krebs cycle for ATP generation. Ketone metabolism is considered energetically more efficient than glucose and may also exert signaling effects, such as inhibiting histone deacetylases, which can modulate gene expression and enhance mitochondrial biogenesis.
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