What the Godfather of IF Eats – Mark Mattson, Ph D – #634

So I think caffeine's good. I published an article in scientific American in 2015, and the whole take home message of the article was that many of the chemicals that are in fruits, vegetables, tea, coffee plants that are good for our health, the actual reason they're in the plants, the evolutionary reason, is that they are noxious agents, they're toxins. And, and caffeine's a good example. If you take pure caffeine and put it on your tongue, you wouldn't want to eat it. It's very bitter tasting. And caffeine is a natural pesticide produced by coffee beans and tea leaves. And if you take coffee beans or tea leaves and put them on your counter and put most any food next to it, and there's ants in your house, the ants will avoid the coffee beans and the tea and they'll go for the other things that don't have the bitter tasting chemicals. Bulletproof radio. A state of high performance.

You're listening to Bulletproof Radio with Dave Asprey. Today's cool fact of the day is that there are different ways to kickstart intermittent fasting. So it's easier for you if you don't know about intermittent fasting. This is something I wrote about in the Bulletproof Diet, something I've been doing for a very long time. And basically you eat the same amount of calories you were going to eat. You just eat them in a smaller eating window each day. Basically, you have just lunch and dinner, skip breakfast, or have just lunch and breakfast, skip dinner. It's pretty straightforward. You want to eat in about six or eight hours. So here are a few different options that are out there for you. There's one is fasting for 12 hours a day. And there's studies for each of these things. There's no one fasting for, for 16 hours. And interestingly, in that study, men fasted for 16 hours and women fasted for 14 hours. Because this is gonna sound really, really bad, but men and women are actually different biologically. I know that's shocking for some of us. However, fasting can be harder on women. And I've seen this over and over since I started the Bulletproof blog, where like, the rules are different. And there's a couple really popular posts about why intermittent fasting can be bad for women that I've written over. There's also fasting two days a week, which is called the 5:2 diet. There's alternate day fasting where you fast every other day or have limited calories every other day. There's one weekly 24 hour fast known as Eat, Stop, Eat. People just skip an occasional meal. And then there's this omad or the warrior diet, which is a 20 hour fasting window with a huge meal at night, steak and whatnot. And you could do the same thing with a huge meal in the morning if you really want to carry around steak, eggs and whatever else you're eating all day long. But that might have some circadian benefits. So bottom line is six hours or sorry, six meals a day so your body doesn't go into starvation mode. It is absolute bullshit and it is a way to feel crappy and probably stay fat. At least that's what happened to me on something like that. And that's not to say you couldn't do that sometimes, especially if you're working out a lot. But if you want to do that on a regular basis as a regular human being, you might not like the results of that. But the number of processed food snacks you eat may go up dramatically if you do that. Today's guest is the foremost scientific researcher on the topic of intermittent fasting. A guy that I'm really, really excited to talk with because there's so much academic research that goes back quite a while now about what intermittent fasting does. But it's one of these precious pieces of knowledge that hasn't entered our consciousness where it's sort of, it has been French knowledge and it's just now becoming something that not just biohackers do, but your mom might do. In fact, my mom does do it, and it makes a really big difference. So not only is today's guest a top expert on what intermittent fasting does for you, it he's also an expert on what it does for your brain. And he's one of the foremost researchers looking at cellular and molecular mechanisms of neurodegeneration, like Alzheimer's and Parkinson's. If you read my book Head Strong, I actually referenced some of his work in that book. I'm talking about Dr. Mark Matson, who's a professor of neuroscience at Johns Hopkins. Welcome to the show, Mark.

Thanks, Dave. I'm looking forward to talking to you. Followed your bulletproof website for a long time and when I can listen to your podcasts, which are always both informative and entertaining. So I'm looking forward to our discussion.

Wow. Well, thank you. I did not know that until we just got on you mentioned that. So I'm truly honored because, I mean, in addition to the intro I just gave you, I mean, you are chief of the laboratory of neuroscience at the National Institute on Aging. At least you were until you just retired last month. So in terms of the anti aging world that I live in, you're sort of a godfather of that. So the fact you've ever heard the show is epic. Thank you.

Yeah, well, you know, there's a big One of the big bottlenecks in getting science translated into the real world is communicating to the public. And there's many scientists that either avoid intentionally or just don't want to bother with taking the time to learn how to communicate with the general public. So, you know, outlets like yours, which really are evidence based and communicate things in a way people can understand, I think are value. So, you know, I do and these podcasts are easy to listen to. I can even be working on a manuscript while I've got a podcast in the background. So yeah, I do find time to listen.

Okay, that's really cool. I'm going to go there. There are not a lot of people here who can listen to one thing and write another thing. Have you always had that superpower?

I don't know if it's a soup. I think it started by, you know, I'm a NPR nerd, so I'll, I'll have. And I telework. I even when I was lab chief at nih, I used to telework one sometimes two days a week and I just have NPR on in the background and I'd kind of tune in and out. There's place certain points when one writes that you can kind of relax a little because you know what, you don't have to concentrate so much. And yeah, so I've learned to do that.

One of my buddies, real dynamic guy named Andrew, and I'm not going to drop his last name because I think he kind of likes to hide behind the curtains. But he's. I had dinner at his house and wrote about it in Game Changers and he knows who I'm talking about. Entrepreneur friend. He told me that years ago he started using Bluetooth headphones before they actually had the Bluetooth standard done. And he listened to audiobooks 24 hours a day, like all the nonfiction stuff just to learn things. And he just finally said after two years of it, my brain just started learning when I wasn't paying attention. But he had to stop worrying about losing something and just assume some of it's going in. And I haven't gotten to that level yet. But I have been able to listen to one thing and write on my latest book, but not the whole Time. Sometimes I would, but the load on my brain felt pretty high. Do you feel more loaded if you listen to a podcast and write a manuscript? I'm fascinated by this. I wasn't getting.

Well, no, so. So I'll, you know, I'll, I'll pause or turn off the volume on what I'm listening to. When I get to some where I have to really think for like 10, 20 minutes straight.

That's a neat little technique. I think most people listening are going, oh, my God, it's possible to write and listen anyway. That's a new skill for me. So. All right. You also talked about the difficulty of translating science from academia into public knowledge. And I think some of my scientist friends are a little bit frustrated. They're saying, I've spent my life doing all this crazy work, but no one knows about it. And so they're kind of feeling like, I did my part. But you've done something interesting in academia and for research, there's an index of productivity and citation impact. So your H index is over 200, which in academia means your super rockstar gold record label. And it's a pretty good number, and.

It'S based on your total career. So it also means I'm getting old.

Okay, that's a fair point. But you've been cited 150,000 times or your work has been cited. So you're, you're up there. Right. But at the same time, you have three and a half million TED views on your talk about intermittent fasting. So you've crossed, I'm going to call it crossing the chasm to butcher that term into. All right, you can now talk to the public about intermittent fasting and reach large numbers. And you've talked to the academic and nutrition and research and neuroscience world. What was the trick for you as a. I'm called a hardcore aging neuroscience guy, to cross over and talk to the public? Well.

Talking to friends and even students in the lab and trying to learn to explain things initially in a very easy way. And then it's by looking at their facial expressions, you can tell whether they're understanding it or not. And if they're not, back off and give some analogy or take a little different pathway to try to help them understand what I'm trying to convey. So I think it's just a matter of doing it.

Practice.

It's practice. Yeah.

Okay. And just something you set out to do. Was this a goal you set or it just emerged over time?

It just emerged, yeah.

Okay, cool.

Although. And I now that I'm retired from nia, so I'm kind of semi retired. I'm still gonna. I'm still involved with working with clinicians at Hopkins, doing trials of intermittent fasting in various patient populations. And I'm writing a book, finally. Two books, actually. The first is going to be kind of with an intermittent fasting theme and a historical perspective and a lot of hardcore science, hopefully explained in a way people can understand. And then the second book is going to be pure neuroscience, which is the one I'm really excited about. It's going to be something like thought patterns, how the brain understands and escapes reality.

Okay, that. That is going to be fascinating. In fact, when you write that book, I'll have you on. A big part of my understanding of the world is really. It's the challenge of not believing your own story so you can see what's really going on, including around food. Right. The story in your head is, if I don't have lunch, I'm going to die. And it's probably not really true.

We wouldn't be here, would we?

Exactly. But, man, it sure feels true at the time. And that's the challenge of fasting in a nutshell, is how do you feel good when you do that? Well, let's get in on fasting and just go in for people who. All right, we've heard about fasting. You have pictures of people in robes fasting for days on end and things like that. Talk to me about the difference between calorie restriction and actual fasting and what you've learned about that over the course of your career.

The differences have to do with the frequency of food intake. A typical human liver can store about 700 calories worth of glucose in the form of glycogen. And if you're just kind of moderate activity like we are now, it takes 10, 12 hours to use up those 700 calories. And then when those calories go, then you start using fats. The fatty acids are released, and those are the precursors of the ketones. And so it's possible to reduce your daily calorie intake. But eat, as you mentioned in your introduction, eat meals frequently. Every time you eat a meal, you replenish the glucose stores in your liver, and so your fats are never mobilized, your ketones never go up. So fasting, by definition, if you're in a fasted ketogenic state, that's a sufficient time period with not eating to be designated as fasting. If your ketones never go up, you haven't hit a fasting state.

Okay? What do you do? You've been studying this stuff for a long time. What, what do you do when you wake up in the morning? Like, what's a typical day for you? What's a typical week?

I never eat breakfast and I usually try to work out midnight, midday or early afternoon.

Yep.

I used to run a lot, do a lot of trail running and some knee osteoarthritis because I had a meniscus tear probably. But so now I'm mountain biking maybe two or three days a week. I'm on the trails on mountain bike. The other days I usually just do some walking or stationary bike, but I pretty much always do that before I eat around midday, early afternoon, and then I eat all my food within a, usually a six hour time window, sometimes five hours. So the rationale for exercising at the end of the fasting period is pretty simple. You get an extra boost in the ketogenic state. But there's also a number of, we call pathways or signaling mechanisms that are activated by exercise, both exercise and fasting, to get amplification of those pathways.

Is this MTOR you're talking about?

Well, yeah, that's one. So. And autophagy.

Ah, okay. Some of my favorite words. Can you define them for people who don't know what they are? MTOR and autophagy.

Okay. And this again relates to the notion of the metabolic switch from glucose to ketones. And what happens then. So when your glucose levels are high, normal, or particularly after eating a meal, there's a pathway called the MTOR pathway in cells that is activated and that pathway stimulates the uptake of the glucose. It also stimulates the uptake of amino acids from proteins in your diet. And then the cells increase their protein synthesis and they're in kind of a growth state. However, while they're in the growth state, they're also accumulating molecular garbage. So when cells are in a growth state and your glucose protein levels are up in your blood, it can help the cells grow. But if that stays chronically on, there's accumulation of molecules damaged by free radicals. Dysfunctional mitochondria.

Yeah.

Those damaged molecules are normally removed from the cells by a process called autophagy. It's the cell's garbage disposal.

In fact, we just had a recent interview on metabolic autophagy that was very well received. And it's a very important thing, like getting rid of the garbage. And you're saying that if you do an intermittent fast and then exercise at the end of it, you're going to turn up autophagy and you're going to turn up mtor, which allows you to take amino acids and put it into the cells or no, because those don't go at the same time. Right.

So no, they go. So the. During the fasting and exercise, MTOR pathway is inhibited. The cells go into a stress resistance mode and they're trying to conserve energy. Molecules, recycle proteins. So autophagy, it's a garbage disposal, but it's also a recycling bin.

So you can incinerate garbage to make energy.

To make energy, but also to break down damaged proteins, but then take the amino acids from those proteins that are not damaged and use them to make new proteins.

Okay. And you get this from fasting and exercise both.

And when you combine them, you get a further enhancement of the autophagy. Then when you eat and rest, then what happens is the cells have cleaned out the garbage. And then when you eat and rest, the MTOR pathway is active. The cells synthesize a lot of new proteins and they can grow, for example, to your muscle cells. When you exercise regularly, your muscle cells don't get bigger during the exercise, they get physically bigger during the rest period.

But so it's about recovery.

Right. But if you don't exercise, the cells never get signals that enhance their ability to grow when you do rest. So these cycles of metabolic challenge, recovery, challenge recovery, and the challenges being fasting and exercise and then eating and resting, sleeping is very important. Those intermittent challenges, we think can optimize health.

Here's another question, and you may have gone into this in some of your prodigious research. I would. I haven't read all of it. When I wrote the Bulletproof Diet, I was looking for things that would suppress MTOR so it would bound back more strongly. And the three things I found were certainly exercise. We just talked about fasting, which we talked about, but there was also studies on coffee and mtor. Have you looked at the effect of coffee on either autophagy or mtor?

We haven't, and it's a good question that I don't know the answer to. There's a lot of excitement from. It's actually a drug development standpoint in rapamycin, and I'm sure you've heard about that. Yes, but that's a little bit scary because you can inhibit MTOR too much, and if you inhibit it too much too long, that's not good either. So again, you know these cycles of. But as far as caffeine goes, my opinion is it's good for your cells, but probably not if you have caffeine levels high 24 7.

Yeah, that whole sleep thing.

I think what most people do then, you know, drinking coffee or tea in the morning while fasting is a good idea. Caffeine certainly boosts your alertness and enhances your cognition and your ketones.

Right. Kunaine's work at UC San Diego showed a ketone boost from it.

Yep.

Okay.

So I think caffeine's good. I published an article in scientific American in 2015, and the whole take home message of the article was that many of the chemicals that are in fruits, vegetables, tea, coffee plants that are good for our health, the actual reason they're in the plants, the evolutionary reason, is that they are noxious agents, they're toxins. And caffeine's a good example. If you take pure caffeine and put it on your tongue, you wouldn't want to eat it. It's very bitter tasting. And caffeine is a natural pesticide produced by a coffee beans and tea leaves. And if you take coffee beans or tea leaves and put them on your counter and put most any food next to it, and there's ants in your house, the ants will avoid the coffee beans and the tea, and they'll go for the other things that don't have the bitter tasting chemicals in them.

It's fascinating. Nicotine's that way too. I mean, caffeine and nicotine are two of the smartest drugs from nature that increase human cognitive performance and they both kill bugs, which doesn't mean they're bad for us, although nicotine in high doses from any mechanism is.

What's interesting here, Dave, is that some of those chemicals activate the exact same responses in cells that are activated by fasting and exercise.

Wow.

And one of those, one of those pathways, which I'm sure you're part of, is the NRF2.

Yes.

Pathway. It's. For example, there's a chemical, sulforaphane, that's present in high levels and broccoli, broccoli sprouts, green leafy vegetables and. But the key thing of this pathway is it's an antioxidant defense pathway. So when this NRF2 are pathway is activated by exercise, fasting some chemicals in plants, then cells boost their intrinsic antioxidant defenses and are more resistant to being damaged by free radicals. And this is really why the trials are like vitamin E, vitamin A, vitamin C, and a lot of different diseases, cancers, et cetera, pretty much uniformly failed. What you don't, you don't want to swap your cells continuously with these chemicals that scavenge the free radicals. Because then the pathways, such as the Interrupt 2 pathway, are never activated. Yeah, because they're activated.