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When More is Less: The Surprising Link Between Blood Sugar and Brain Performance

The brain has a continuously high energy demand, for which it primarily relies on glucose. If ketones are present in the bloodstream, they serve as essential energy substrates for the brain as well.

Unlike other organs that can also use fatty acids for energy, the brain has unique restrictions due to the "blood-brain barrier." This barrier acts like a precise filter between the bloodstream and the brain's fluid, mainly protecting the brain from harmful pathogens.

While fatty acids can't pass through, glucose and ketones have active transport mechanisms to enter the brain. Due to the high energy demands and relative lack of local energy storage, the central nervous system continuously relies upon blood-brain barrier expression of transporters for the delivery of glucose and ketones to the brain.

And while the brain uses glucose for energy, does this mean that higher blood glucose levels lead to more energy and better mental performance?

In short, No.

Studies have shown that vascular endothelial cells exposed to high glucose levels downregulate the rate of glucose transport by reducing glucose transporter protein expression. Meaning: the higher glucose levels in the blood rise, the less glucose is transported into the brain, preventing cell damage from high glucose.

So, this is, on the one hand, a protective mechanism from damage through high glucose levels. On the other hand, it leads to an important question: Could, in some people, chronic hyperglycemia, and therefore chronic down-regulation of glucose transporters, play a role in cognitive decline, Alzheimer’s disease, and neurodegeneration?

Put your thoughts in the comments!


Leão, L. L., Tangen, G., Barca, M. L., Engedal, K., Santos, S. H. S., Machado, F. S. M., de Paula, A. M. B., & Monteiro-Junior, R. S. (2020). Does hyperglycemia downregulate glucose transporters in the brain? Medical Hypotheses, 139, 109614.


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