We know the enzyme that we use to turn D-betahydroxybutyrate into Acetoacetate so we can use it for energy only works on the D- isoform and not the L- one. Although we do know that Acetoacetate is non-chiral … as in it has no mirror twin so if there is a way to get L-betahydroxybutyrate to Acetoacetate then our problems are solved.
The only experimental test that I am aware of to test what we do with the L- isoform was the tracer studies of Henri Brunengraber, who made a few micrograms of L-betahydroxybutyrate that was tagged with a radioactive isotopes, and gave it to a mouse. Some of the tagged carbon appeared in the exhalation of the mouse indicating that some of the L-betahydroxybutyrate had somehow made it into the respiration process. As I understand it the actual pathway that it took to get there is still unknown.
The questions I have are;
Why not all of it? What happened to the molecules that didn’t end up being used for energy. I assume that the mechanism for mice is the same as for humans … but I don’t plan on being the guinea pig if that assumption is in error. How much of a caloric amount (enough betahydroxybutyrate to be considered a minor energy source) would end up making it into respiration. We don’t know the pathway … is it competing for transports and enzymes with some other critical molecule? Would a caloric amount cause a back up of some other critical process … as yet unknown? How about a caloric amount for a fraction of an animals lifetime? That would be a different order of magnitude than a few micrograms “once off”.
I may be unnecessarily alarmist about this but one of my concerns is that this part of a cellular machinery, it’s energy production, is subject to derangements from seemingly minor changes … like making not enough of critical enzymes that then cause major systemic diseases for the organism - like Diabetes, or Parkinsons, or a host of horrible diseases.
If we couldn’t isolate the right isoform, and assuming it was essential to cure some diseases then that would be a trade-off that well informed individuals would have to make. But we CAN make isolated D-betahydroxybutyrate, it’s just expensive.
People aren’t being told by the manufacturers of the racemic mix of DL-betahydroxybutyrate of the concerns. They are just labeled as GRAS (generally recognized as safe) by the FDA without much evidence … other than the fact we appear NOT to have killed anyone with it in the few years that it’s been readily available on the market. I would hope the manufacturers might pay for that actual research … but this is not a question that anyone appears to want to know the answer to. Besides some of the manufacturers of ketone salts were involved in making illegal anabolic agents for athletes around the turn of the century and at least one did time for the Balco scandal. That kind of thing makes my Spidey sense tingle.
As a podcaster I regularly get offered free ketones. Often the first email is “So what flavour do you want” … and my response is “what science do you have that indicates benefit for weight loss or treatment of type 2 diabetes” … and I usually don’t get a second email.
If I had an elderly relative with a degenerative disease that could be treated with exogenous ketones, I might relent because if there is a problem that shows up after 30 years of using a caloric amount of them … well that wouldn’t impact a geriatric with a 10 year anticipated horizon. Also a product taken like medicine that does not require dietary compliance may be an easier solution for a geriatric especially if they are in a geriatric facility where the diet is pretty woeful.
On the other hand a young person who is capable of making all the ketones they want by just not eating carbs, who just wants to have the ketones AND eat carbs … well that would in my opinion be a silly use of exogenous ketones, and potentially a dangerous one.
I could also be completely wrong about all this.