#1701 - Dr. Rhonda Patrick

**Joe Rogan** (0:04)
The Joe Rogan Experience.
What's happening, Rhonda? Very good to see you.

**Rhonda Patrick** (0:16)
Good to see you. It's been a year.

**Joe Rogan** (0:18)
It has been. It's been quite a while.

**Rhonda Patrick** (0:20)
Yeah.

**Joe Rogan** (0:20)
And you were just telling me that you were 13 days into keto.

**Rhonda Patrick** (0:24)
I am.

**Joe Rogan** (0:25)
How you feeling?

**Rhonda Patrick** (0:26)
Well, let's start off with, why did I even want to do keto? Why now? I mean, this has been, how many years? It's been trendy. It's been lots of benefits. And it's like, why did I start trying it out now?
Well, I've noticed that when I am in a fasted state, so when I'm in ketosis, when I'm burning fatty acids and making keto bodies and using them as energy, I'm on top of my mental game. So I've been doing, when I have any sort of podcast interviews I'm doing, or whatever, I'm always trying to do them fasted, like I'm fasted right now.
And so I thought to myself, is this something that could be mimicked by a ketogenic diet? It's very noticeable for me, where I can stay focused, I have more endurance, so I don't crap out a couple hours.

**Joe Rogan** (1:21)
More mental endurance.

**Rhonda Patrick** (1:22)
Mental endurance, sorry, yeah, more mental endurance.
So I decided to try it out, and I recently had a neuroscientist on the podcast, Dr. Mark Mattson, have you heard of him? He's legendary, he's probably one of the most cited neuroscientists, but he's most well known for his intermittent fasting studies, like the 5-2 intermittent fasting stuff came out of his lab. He's also the father of hormesis, and why humans adapted to be in a stressful environment and how all these stress response pathways that happen as a response to that are beneficial. But anyways, so he was talking about when you're in a fasted state, when you haven't eaten, how your nervous system has evolved to become more focused, more alert, and that's adaptive because if you can't find food, you have to be alert in order to eat or else you'll die.
So he's talking about one of the main things that happens is this metabolic switch, is what he calls. So you do switch from burning glucose as a source of energy to basically fatty acids are immobilized from your adipose tissue and go to your liver and you start to oxidize them and use them from energy and then you make something called ketone bodies as a byproduct, beta hydroxybutyrate, acetoacetate. And most people think about these, well, this is an alternative source of energy across the blood brain barrier. It is easily used by neurons and other cells as well, but it's actually an energetically favorable source of energy. So, it actually requires energy to use glucose as energy, to make energy from glucose, requires energy. But beta hydroxybutyrate, that doesn't happen, like it goes into the mitochondria and it's used without that energy requirement. So you can imagine-

**Joe Rogan** (3:21)
Can you explain how that works? You use energy to use glucose?

**Rhonda Patrick** (3:25)
Yeah, so glucose gets broken down into something called pyruvate. And pyruvate, so it takes energy to do that. And then pyruvate has to be transported into the mitochondria through an active transport mechanism. And that requires energy to do that. Once pyruvate gets into the mitochondria, it's then used through what's called the TCA cycle to make energy.
So beta hydroxybutyrate gets converted into acetyl-CoA, and beta hydroxybutyrate can just go in without this active transport mechanism. So you're not requiring that energy to transport it in. Does that make sense? Because you're making energy, but you're not using as much energy to make that energy. So that's kind of like what most people are thinking about as this sort of metabolic switch that happens. And you can imagine most people never do that. I typically, I do a lot of time-restricted eating where I'll eat my food anywhere between eight to ten hours, and then I'm fasting anywhere between like 14 to 16 hours a day. And in order to actually go into this metabolic switch, you have to deplete all of your glycogen levels in your liver and muscle.
And that usually takes anywhere between 13 to 36 hours, depending on the person's carbohydrate intake, on their physical activity. And so, you know, most people never get that metabolic switch. Most people are just constantly burning using glucose. And then when you're doing that, any fat that you're taking in gets stored as triglycerides and adipose tissue. So they're always in this like fat storage state instead of a fat burning state, right? And so, because most people are eating three meals a day and plus snacks, you just you never get there. So with the, you know, my, you know, anywhere between 14 to 16 hours, so what I typically was doing, I'd noticed that like I was really mentally sharp. And so as I extended that out a little bit, it was like really clear to me that like not eating was like good for my brain in terms of like, like I felt smarter, I felt like I could focus more. It was noticeable, like a nootropic effect, right? And so one of the other things that's probably less well known about beta hydroxybutyrate, which is one of the major circulating ketones you do make when you're in ketosis, is that it is actually a signaling molecule. And this was shown by Dr. Eric Verdin. He runs the Buck Institute for Aging in Nevada, California.