BHB is produced through a process known as ketogenesis (“the origin of ketones”).
When our body is in a fasted or glucose-depleted state (and muscle and liver glycogen are also low), insulin levels fall. Low insulin levels allow the process of lipolysis to occur, which means that fat cells begin to release free fatty acids out of our internal stores. These fatty acids are then sent to the liver and broken down into a molecule known as acetyl-coenzyme A (acetyl-CoA).
In the liver, acetyl-CoA goes through a process of steps that eventually leads to the production of the ketone body acetoacetate (AcAc) .
An enzyme known as BHB-dehydrogenase converts AcAc into BHB. Once BHB is produced, specialized transporters then shuttle it out of the liver and into our circulation, where it’s used as a fuel. Using BHB for energy essentially involves a process that is a reversal of ketone production—acetyl-CoA is produced from BHB breakdown and then used to create ATP.
How exactly does BHB move around? It’s transported out of the liver through a transporter known as the monocarboxylate transporter (MCT)—not to be confused with MCT oil (short for medium-chain triglyceride oil).
In the brain, BHB uses the MCT transporter to cross the blood-brain barrier.
Molecules of BHB also dissolve very easily in water and blood, making it super efficient at circulating through the body. This might be one reason why we have more BHB than AcAc.
It may be an evolutionary advantage that our brains use BHB instead of its precursor, fatty acids. Using fatty acids for energy in the brain could lead to problems such as 1) causing a hypoxic (oxygen-poor) environment for neurons due to the greater amount of oxygen needed for the oxidation of fatty acids 2) oxidation of fatty acids increases production of the oxygen free radical superoxide, which can cause damage to the brain and 3) oxidation of fatty acids is a “slow” process meaning the brain wouldn’t have the energy it would need to make quick decisions that could dictate life or death.
This process is pretty intricate and fine-tuned. But it’s completely natural, something our bodies have evolved to do. But besides “starvation,” how else can we increase BHB in our blood?
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