This has been a question I have seen passed around for years and nobody seems to have a solid answer. Mostly they just say it is because you are adapted and you don’t need as much so you make less. I have seen one fairly plausible explanation in that the kidneys take up more ketones and retain more in the beginning.
I have never really liked either of those answers and finally, I think I have a very plausible mechanism.
In my last post I discussed the Krebs Cycle and how ketones are made when there is an excess of one of the precursors for it named AcetylCoA. Another thing that influences the amount of ketones is another intermediate of the Krebs Cycle called Oxaloacetate (OA).
We also discussed how OA is necessary in the process of making glucose out of non glucose metabolites known as gluconeogenesis (GNG). We learned that the body reserves alot of OA for this process because it is critical to maintaining glucose levels in the body. Like life or death critical. The liver will always keep it for GNG before letting the krebs cycle use it if it is low supply. So if there is alot of GNG happening it will deplete the levels of OA that is available for the krebs cycle to process AcetylCoA and this will result in higher ketone levels. This can be seen in people who do intense exercise with no available glycogen to supply the exercise. Like in a fasted state or even just in ketosis. The lack of available glucose from glycogen will cause a very high level of gluconeogenesis which will deplete the levels of oxaloacetate. If these folks check ketones shortly after their workout they can see very high levels. I have seen levels well above 8.0 mmol.
With this being said, when we first go keto there is a high rate of GNG happening as our body is still very used to using glucose as a fuel. So at this point we would be using much of the available OA to make glucose. This in turn would decrease the amount of krebs cycle activity and cause an elevated amount of ketones. As we adapt to the ketogenic diet our body slowly starts to need less and less glucose. The brain uses less as it gets used to using ketones and the muscles actually get used to using fatty acids directly. The muscles also develop a type of physiologically normal insulin resistance to keep them from using glucose that could be retained for the parts of the body that absolutely must use glucose like the red blood cells, some parts of the eye and some parts of the brain. As we adapt to use less and less glucose we will see a reduction in the level of GNG. With the reduced GNG we see less utilization of OA. This will leave more available for the krebs cycle which will better be able to empty the AcetylCoA pool. If we empty the AcetylCoA pool we end up with less ketone build up!
Boom. The longer you are adapted to keto and your body needs less glucose the less oaxaloacetate is used for making glucose and the more that is available to process AcetylCoA to energy directly rather than diverting to ketones.
Seems like a very plausible mechanism to me. Let me know what you think.
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