• [Mike]: You talked about ketones a bit in that last answer. So let's move on to a question about ketones from Austin. "Will consumption of exogenous ketones disrupt a fasting state? And I know that there's been a lot of work in producing ketone supplements. So that's the question I think is, will that disrupt the fat? "

• [Dr. Patrick]: It's certainly a question that I've had myself. I've actually tried a beta-hydroxybutyrate, ester. So beta-hydroxybutyrate is the major circulating ketone body that's generated when your body starts to go into ketogenesis. A lot of things do happen when you're fasting and that's one of them. So basically, it takes anywhere between, you know, 12 to 36 hours for your liver to deplete the glycogen. And once that's depleted, what ends up happening is you immobilize fatty acids from your adipose tissue. They go to the liver and they're actually used to make ketone bodies. So you're oxidizing the fatty acids now using them to make ketone bodies like beta-hydroxybutyrate. Those ketone bodies can then be used as an alternative energy source themselves.

• [Mike]: Which is incredible. I mean, just on that point, the fact that, you know, the analog I've heard is, you know, you basically turning your body from a, you know, burning gas to diesel. It's like a completely different fuel glucose to ketones. It's amazing that our bodies can even do that. And in some ways, you know, it's a preferred fuel for different organs in our bodies, right?

• [Dr. Patrick]: It seems as though it might be. It certainly seems to be metabolically efficient. You know, so it takes less energy to use a ketone body compared to glucose. So it's energetically favorable in that sense, which is nice.

• [Mike]: Sound like it doesn't really interrupt a fast and sort of part of the natural...

• [Dr. Patrick]: Well, so let me, so I'll let me continue. So that was the natural phenomena I was explaining you, right?

• [Mike]: Okay. Got it. Got it.

• [Dr. Patrick]: Now, what ends up happening, so there's been about five clinical studies that I've read that have... They're most clinical studies with exogenous ketone esters .

• [Mike]: And just for the audience, exogenes meaning not produced in the body. You're taking it externally.

• [Dr. Patrick]: Exactly. You're taking a like a supplemental form of it. Yeah. Thanks for clarifying that. So the exogenous ketone esters that are taken, basically, a lot of the studies that have been done have been looking in the context of like athletic performance. But they also look at other metabolic parameters, which is interesting because that's kind of where you can find some of this data, if you look carefully. And within these five studies, there have been, it seems to be that what's been shown is that the exogenous consuming, for example, the exogenous beta-hydroxybutyrate, the supplemental beta-hydroxybutyrate ester, it ends up, it increases the blood levels of beta-hydroxybutyrate pretty high.

But it also seems to decrease circulating free fatty acids, which suggests you're not immobilizing fatty acids from your adipose tissue to be used to make your own, which means you may not be getting the benefit of what you would call a fat loss. Right. And that's a regulatory loop that occurs in the body. So it, you know, when your beta-hydroxybutyrate levels get high enough, you know, your body says, "Okay, we don't need to make any more of these." So it stops the immobilizing, what's called lipolysis, the cutting of the fatty acids from the adipose tissue, right?

• [Mike]: Interesting.

• [Dr. Patrick]: So your body's stopping you from making too much, right? So that does seem to happen. But then again, the exogenous ketone esters don't last for that long. And if you're exercising or doing physical activity, it's dose-dependent. So the more active you are, the quicker you use up those ketone bodies.

• [Mike]: Yeah. It's interesting because you know, I know that when I'm practicing fasting, which gets my ketones way up, and then I'm doing a ketogenic diet, which does the same thing. And then, I go for a big workout, I'll come back and measure my ketone bodies and they're way down. And I guess it's because I've been using my ketones for during the workout.

• [Dr. Patrick]: For energy. Yeah, exactly what happens. So that's kind of my one caveat that I would be aware of with consuming the beta-hydroxybutyrate supplemental esters or salts if you want. But salts don't work that well.

A good point is that they've also been shown consuming the exogenous beta-hydroxybutyrate has been shown in humans to prevent the use of amino acids from muscle. So it stops. And which also is, you know, makes sense during a prolonged fast, your body has mechanisms at play that help prevent you from, you know, using muscle, using proteins and amino acids from your muscle as energy. And one of those is that, you know, the ketone bodies prevents that from happening.

So that's a good thing. But so there's a trade-off, potentially. And again, this is something that, you know, I don't know how much of a difference it makes, but it's something to keep in mind.

• [Mike]: Yeah. And if you're an athlete and you're needing fuel, maybe you're a better candidate than someone that's just looking for purely metabolic body-based ketone production. And that's a maybe, but it's a factor.