[Rhonda]: What do you think of exogenous ketone esters?
Like, do you think that they’re safe?
Is that something that you know about or have thought about?
[Dr. Verdin]: Well, we’ve thought about it.
We are experimenting with them as well.
It is one of the central questions.
It’s most of the beneficial effect that we have seen have been with the ketogenic
diet.
Again, that’s very different from a high beta-hydroxybutyrate level.
And one of the remaining or at least the next step in this whole field is really to understand
what can we recapitulate with beta-hydroxybutyrate alone, and I think we’re working actively
on this and so are many other groups.
The ketogenic diet itself it’s important to realize is not an easy diet to live on.
You know, I don’t mean to be diminishing the merit…
Actually, I highlight the merit of people who are on a long-term ketogenic diet.
It takes a lot of discipline.
You basically cannot eat a significant amount of carbohydrates.
Many people who have been on this diet for a long time actually tout its benefits and
the fact that they feel very healthy and they feel very present.
There are a lot of brain effects linked to ketogenic diet.
Now, big question is what can we replicate just by administering BHB, beta-hydroxybutyrate,
alone.
[Rhonda]: Yeah.
I think that you’re absolutely right, you know, and not to mention that with a ketogenic
diet there’s also…
You know, some people can’t really do them.
You know, there are certain gene polymorphisms.
I know there’s one in the PPAR-alpha gene which is important for the whole process of
making ketone bodies and that people have that they actually can’t do that very well,
and so it can be sort of dangerous, and they can have inflammation.
Sort of the opposite profile will happen, you know, so it’s certainly something to
consider.
And then not to mention, like, you found in your paper that you just published this year…was
it last month?
[Dr. Verdin]: Yeah.
[Rhonda]: Yeah, last month.
That you found, you know, there were multiple changes going on.
I think there was a decrease in insulin, obviously, and IGF-1, and mTOR activity went down.
And then, you know, so that’s something you’re not gonna just get from beta-hydroxybutyrate.
Maybe, we don’t know.
I don’t…
[Dr. Verdin]: We don’t know.
I suspect, not for the mTOR part, but we compared the ketogenic diet to a high-fat diet which
was not ketogenic, which mice ate a large amount of fat and enough carbohydrate to suppress
ketogenesis.
And one of the biggest difference, I think, actually between these two was the activation
of PPAR-alpha.
And this is also very exciting, because that indicates that maybe a lot of the beneficial
effect that we see on the ketogenic diet come from PPAR-alpha activation.
We’ve been reading that literature.
There’s quite a bit of information there that really hasn’t been pursued as a next
direction to try to dissect these effects.
[Rhonda]: Because PPAR-alpha’s doing something to the mitochondria.
What’s the main…
[Dr. Verdin]: It’s a key enzyme of the fasting response, but it seems to be more highly activated
in response to the ketogenic diet than to a pure high-fat diet.
[Rhonda]: What about fasting, if you compare fasting to…
[Dr. Verdin]: It is activated.
We did not compare to fasting.
We compared it just high-fat to…but I think it just points to a new direction in which
we can start dissecting what is the role of PPAR-alpha in these responses.