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Bulletproof radio at state of high performance, you're listening to bulletproof radio with Dave asprey. Today's guest is the foremost scientific researcher on the topic of intermittent fasting 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. He's also an exponent 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 headstrong, I actually referenced some of his work in that
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 podcast which are always both informative and entertaining. So I'm looking forward to our discussion. Well, let's let's get
in on on fasting.
And just go in for people who are and we've heard about fasting you have pictures of you know 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 the typical human liver can store about 700 calories worth of
Not in the form of glycogen and if you're just kind of moderate activity or like we are now it takes 1012 hours to use up those 700 calories. And then when those calories go, then you start using fats the fatty acid 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 mobilize your ketones never go up so fast Thing by definition if you're in a fasted ketogenic 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? It's a difficult 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 had 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.
around midday early afternoon and then I eat all my food within a usually a six hour time window sometimes five hours so that 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 that get amplification of those Pathways.
Is this employer you're
talking about?
Well, yeah, that's one so and on top of G.
Okay, some of my favorite word's. Can you define them for people who don't know what they are in Turin
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 it
Activated and that pathway stimulates the uptake of the glucose that also stimulates the uptake of amino acids from from proteins in your diet, and then the cells increase their protein synthesis and they're in kind of a growth State. However,
Well, they're in the growth state. They're also accumulating molecular garbage. Mmm. So when cells are in a growth State and your your glucose protein levels are up in your blood that can help the cells grow. But if that stays chronically on there's accumulation of
Molecules damage by free radicals dysfunctional mitochondria. Yeah, those those damage molecules are normally removed from the cells by a process called autophagy. It's the cells garbage
disposal. And 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 fasting
And then exercise at the end of it you're going to turn up otology 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 the same time.
Right? So now that they going up so the during the fasting and exercise mtor pathway is inhibited the cells the cells go into a stress resistance mode.
And they're trying to conserve energy molecules recycle proteins. So topology. 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 do 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
fast.
And exercise both and when you combine them you get a further enhancement of the autopsy G then 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, the 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 it's about
recovery right buddy.
You if you don't exercise the cells never get signals that enhance their ability to grow when you do rest.
So right so they cycles of metabolic challenge recovery challenge recovery and the challenges being fasting and exercise and then eating and resting sleeping is very important those finnerman challenges. We think can optimize health. 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 health the actual reason they're in the plants The evolutionary reason is that they are noxious agents their toxins, right 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's very bitter tasting and it caffeine is a natural pesticide.
Aside 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 in
it. It's fascinating nicotine's that way too and I mean caffeine and nicotine are
Two of the smartest drugs from nature that increase human cognitive performance and they are both kill bugs, which doesn't mean they're bad for us both on nicotine in high doses from it now, but
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 have heard of is the Nrf2 s a re pathway. It's for example, there's a chemical sulforaphane that's president high levels and broccoli and we sprouts green leafy vegetables and but the key thing of this
Pathway is it's an antioxidant defense pathway. So when this Nrf2 a re 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 this is really
why the trials are like vitamin D vitamin A vitamin C and a lot of different diseases cancers Etc. Pretty much uniformly failed.
What you don't you don't want to swap your cells continuously with these chemicals that scavenged in the free radicals because then the pathways such as they enter up to pathway or never activated. Yeah, because they're activated by the stress of the fasting the exerciser that can
there are lots of studies on mice done with water only fasting and so there are people others say, oh well, they just had Waters you.
You only have water but all this stuff. I know even like traditional Chinese medicine they at least had tea or coffee or you know pine bark tea or whatever the heck depending on where you're from. So I always say look we're in fasting have your coffee have your tea, you know, enjoy your life. But the purest like, oh, you know, we don't know what it does to your gut bacteria. Where are you on the spectrum of you should only do what the mice did versus have a fun.
I think it's actually a good idea at least from the standpoint of the
In to drink tea or coffee during a founder and yeah, yeah.
All right, and you'd be fine with an herbal tea as well then. Yeah. Okay got it. And there's all sorts of different herbal teas. You can do what about mushrooms medicinal mushroom kind of teasing and people like I don't like chaga very much at all. But I've really gotten some benefits from lines managers had the lifecycle guys on about that and I just had Paul stamets on who's the famous mushroom guy. Is there a on love
Paul he's so cool. Is there anything that you've come across on using mushroom extracts not actually eating them is that be calories during
fast?
No studies. I am interested in mushrooms. I last few years. I started foraging I've got Paul's big
thick my silly running. I think I've got it right back there.
Yeah, and actually bought some some my what I get oyster and shiitake mycelium from his company in the spring and they're out in the wood chips right now.
Beautiful. Yeah. I'm I'm just
Commercially growing 1/4 steps on my farm here in BC, which is really nice.
Yeah and Paul Sal he's from your neck of the woods.
Yeah, he's one Island over he came out for the interview was fantastic. Sounds like you guys know each
other. I don't know him but you know and but fascinating chemicals and mushrooms lot more work needs to be done. There are there are some reasonable studies with things like turkey tail.
tea and some of the things Paul talked about but on the other hand, it's an area where there's
There's a big need for a lot of better science. Yeah, as you know, finally they're starting to do studies now with hallucinogenic mushrooms, one of the scientists that Hopkins and fact has shown in a couple published studies. Now that the psilocybin mushrooms are beneficial in people with depression and
You know and they're not addicted these yeah and contrast to the opioids. Right which is a huge problem these chemicals and mushrooms that seem to have some interesting effects on the nervous system.
Are not addictive, you know, which would seem to be a big Advantage.
It seems nonsensical that alcohol yeah katene and the opiates are legal and cause a lot of harm, but I don't know how anyone could be really addicted to the strong hallucinogens. There are people who'd associate associate because they're so traumatized but these are it's not an addiction. That's that's a just deep-seated trauma response, which is a different.
Always that's my wife says so and she's a karolinska train drug and alcohol addiction emergency doctor. So I'm going to I'm going to believe her there which is there people who abuse them but they're not addicted versus actual addiction. All right. I'm I'm really interested in compounds that I know that you're interested in a nerve growth factor in GF and bdnf brain-derived neurotrophic factor and I wrote about those in headstrong and I've used there's old.
Buddy's on mushrooms. There's a compound that he's one of my supplements from the fruit of coffee a polyphenol that raises b d and f coffee itself probably does According to some other research fasting. I believe raises bdnf. Can you walk through your perspective on increasing nerve growth factor and brain-derived neurotrophic Factor? What do you believe works? And how important is it for living a long time with a good
brain? Well, both bdnf.
Ngf are important for the development of the nervous system for the survival growth synapse formation. And then the fine-tuning of the structure of the brain during development If you eliminate the genes of either NG F or bdnf from mice, they died during development. So they're critical in the adult brain bdnf.
Is particularly important throughout the brain all over the brain in promoting the growth survival of neurons. It's critical for learning and memory.
and it's also we showed in my lab when I was back at the University of Kentucky in the
early 1990s that bdnf protects nerve cells against various types of stress oxidative stress metabolic stress something we call excitotoxin Express which is unconstrained neural network activity, like occurs dramatically and epilepsy, but we think to less dramatic extent in brain ageing and Alzheimer's disease, so
NG F on the other hand, there are only a small but important group of brain cells that are responsive the bdnf in the adult brain exercise is a potent stimulator of bdnf production in the brain.
Intermittent, fasting stimulates bdnf production and the combination of exercise and fasting get an additive effect in boosting bdnf and I had a graduate student Alexis Stranahan who showed that many years ago in studies where she combined running will exercise and Daily Time restricted feeding daily short fast and found she got a degree.
The fact increasing bdnf and then actually protecting synapses against diabetes, which is kind of another angle on this. It turns out that obesity and diabetes are not only bad for your heart. They're bad for your brain. Yeah, particularly as you get as you get older and we think that intermittent fasting well actually no it intermittent fasting and exercise can reverse
diabetes and obesity in humans. If a person can switch their eating pattern and get on an exercise program.
And and bdnf plays a role in that. So in individuals who are obese or and or diabetic bdnf levels are lower in their brains compared to normal weight metabolically healthy people
one of the things that that really changed my life when I weighed 300 pounds and I was having all kinds of cognitive dysfunction in my my 20s and early 30s. I started using a thing they called the Russians.
sleep machine through bro, electrical stimulation with alternating current between the years very different than the tdcs we use now and it turns out there are studies that show both tdcs and CES or alternating current raise bdnf very meaningfully and Center s I'd go to sleep with this thing and my I start my brain help to turn back on and now at 40 years of Zen the brain upgrade place that I started we use a clinical
Read Neuroscience level system that lets you have specific frequencies that are tunable and controllable by a computer and we do that to Prime the brain for for Better Learning of Altered States that you learn through neurofeedback. And you go all the way down to companies like Halo who's been on the show who makes you a tdcs headset when I do exercise I especially lately. I can't I can't keep up very well.
With my nine-year-old a ping-pong game ping-pong is a high reaction time thing. It keeps your brain. Young doctor Raymond told me to buy the ping pong table I did so I started saying all right, I need some more bdnf here. Like my son's kicking my butt. And we've got the pro-grade, you know, Carbon Fiber paddles and we're going at it like he's good either I'm bad, but I was not a understand a good competitor for him. So I started running the electrical current over my brain again using the Halo and all the sudden my learning
Up and at least 20 minutes after doing it. It's like the ball slows down and I can hit it. And so I believe that's a beating of sort of thing. But if you seen electrical stimulation magnets lights going to the bottom of swimming pools, I don't any other crazy Tech like that that's going to make our brains more
plastic that yeah, the answer is yes. And first I want to go back to when you were young and and obese.
Right and you did this alternating current stimulation of your brain. Did your did that reduce your appetite?
The reason I ask is it turns out that bdnf suppresses appetite interesting. This is I don't and think it
did. I'm just I'm going back to all the different times. I'd use it. I would often times use it when I was sleeping or like when I wanted to write even I was writing all my books there were times but I change the frequency on my device to go up into the gamma ranges,
but did it help you lose weight
it
Could have I feel like the thing that really helped me lose weight was getting rid of the inflammatory foods and things that were inhibiting mitochondrial function was the number one thing but it could have had an impact but for me it was well, I just wanted to ketosis and then I came out of ketosis and I went in and out and that got half my weight down and then the other half was oh hey guess what certain foods are going to make you inflamed no matter what so you got to change the type of fat that makes you it going because you gotta get rid of the nightshades if you're sensitive like I am and and that was the kind of the Genesis of the whole bulletproof diet.
Which was these Foods may or may not be good for you, but don't assume they're all good. Because if you're still fat after you try too hard, so for me, it was finding the guilty suspects.
So let's get back to stimulation and BDF bdnf was discovered in an animal model of epileptic seizures.
That was a lab in California. That was just kind of looking for genes that are responsive to epileptic seizures and b d and f is highly responsive. So as you know, one of the treatments for depression, which is still used in people who don't respond well to antidepressant drugs is electroconvulsive shock therapy, right and it's as highly
And it's highly potent in inducing bdnf expression. Wow. I didn't know that also, the the antidepressant drugs themselves the serotonin and norepinephrine reuptake Inhibitors Prozac Paxil Etc.
They increase bdnf levels in the brain and in animal studies, if you if you have web ways, we can genetically manipulate the my so that they can't respond to bdnf those mice do not show an antidepressant response to those drugs. So altogether the available evidence says bdnf is
Is an it's an antidepressant and dodging us antidepressant. I mentioned its potency up regulated by exercise exercises are really good antidepressant. And in fact, there may be people who exercise regularly and then have some injury and they stop exercising that can often precipitate a episode of depression.
Because you know they've been going along exercising and all of a sudden probably their bdnf levels are going down. So anyway, there is some evidence that even load direct current stimulation are transcranial magnetic stimulation can increase bdnf levels. Yeah caffeine.
Caffeine will increase bdnf levels. Okay. There you go.
I'm I'm intrigued about what you do to manage your bdnf levels and I just I want to for just warn everyone. Look you're an expert on Aging but you're also the age you are and you're a male and you have your genetic and lifestyle factors that we all have. So this isn't a do what you do, but I want to know what you do specifically for b d and f and in GF to keep yourself strong and
Things and then I don't know why you do it. So what's your personal practice for managing those given measure them?
Well, that's a problem because Wade I did we'd have to measure them in the brain or at least the three Brooke three-year-old spinal fluid. So it turns out that there is a B D and F and N JF in the blood but the levels of those trophic factors in the blood and animal studies are not well correlated with levels in the brain. It turns out that
nerve cells are not the only cells that produce bdnf.
Your hearts else interestingly produce bdnf and there's other cells. But anyway kind of the bottom line is unfortunately unlike ketones, which we can easily measure from a finger stick and blood we can't measure bdnf or ngf. There's no way non-invasively to do that. So I I'm just going by what the animal studies today sure. So again, my my normal routine is don't eat breakfast drink.
A lot of green tea in the morning don't drink green tea a couple hours before I exercise which I said around. Midday say one o'clock. Okay, because I found I can get some gastric reflux. Actually if I am interested I drink tea right before I exercise but then anyway, so then I exercise in the fasted State my diet during the six hour time window I eat is what most people would consider a variety of healthy.
Rhodes vegetables fruits a lot of nuts yogurt
if I ate meat its usually fish occasionally chicken, but not so much whole grain site. There's a lot of literature out there on whole grains one way in the other and you know, there's a there are people who are sensitive to gluten and so on but my take on the scientific literature is that whole grains are generally good for health. So you eat whole grains and whole grain societies to in
ketosis if you eat whole grains and fruit,
well I go up
I go into ketosis in the morning.
There you go. I was hoping you were going to say that yeah, we'll probably agree to disagree on whole grains for the average person. But some people tolerate him really well. Yeah, I know they completely shred other people over time. So those are in
the suspect David. Well, I don't know, you know, so refined grains are not good, but the whole grains have a lot of fiber which it was good for your gut microbiota and unquestionable and if you look at the actual scientific studies,
There's epidemiological evidence that whole grains are good. Even in the blue zones, which most of your listeners will be familiar with regions in the world where people on loot usually number a large number of people live to be a
hundred.
The ways to raise ketones externally there's MCT oils and if ones are different things there's Ketone salts and different ones do different things and dr. Vijay raise the bio identical issue there would I've actually had to keep some salt product ready to ship and I canceled it because like I'm not selling something that might feel good because harm later but you know, there are people who are Advocates of them, especially short-term use and things like that and then there's the Esters which dr. Beach and I talked about you talked about
Actually synthesize some six years ago, but there are 40,000 dollars a kilo. I couldn't commercialize them and they're still a hundred dollars for three doses kind of things wouldn't it for people to do it? Is there a risk that would put another way there is a risk with blood sugar if your blood sugar levels are high.
It doesn't mean that you have more energy and you've done a good thing. It means you're not metabolizing blood sugar. If your Ketone levels are exceptionally high. Is there any sort of a similar situation where hey there hi because you can't metabolize them, right you're going to drain them as fast as you can or should we not worry about you know, my my Ketone levels are higher than your Ketone
levels sort of things. Yeah. This is a good question. We know that with long-term fasts of weeks.
Or even months Arduino. Yep, we assume that it's important. It's important that the ketones behind because the cells are using the ketones. Yeah for energy, but as far as the exogenously elevating ketones with MCTS or Ketone Esther long-term chronically.
we don't know I my current thinking is intermittent elevations may be better than continuous and you know the cycling between activating mtor and inhibiting it up regulating a topology then going into a growth mode that switching back and forth is important and as much as the key tones play roles in that and in fact we showed
Ketones can stimulate bdnf production. Oh, wow, but but you know, however, this is very interesting. It turns out that bdnf is normally produced by neurons in an activity dependent manner that is its produced when the neuron is electrically active.
And so it's produced when and where it's needed.
And we found if we swamp neurons with bdnf continuously.
It's actually bad for them. Oh and interesting and we did this in a published study where we are looking at the autonomic nervous system. Remember I said that intermittent fasting increases parasympathetic activity and reduces heart rate. So and we had evidence there was a role for bdnf in that.
but
it gets a little complicated but the parasympathetic neurons that send their axons to the heart. The neurons themselves are located in the brainstem.
They use acetylcholine as a neurotransmitter and so bdnf track if we transparently apply bdnf to those neurons. They produce more acetylcholine heart rate goes down. However, if we continuously swamp
those neurons with b d and f then they deplete this little choline and the heart rate actually goes up. So my point is
your systems are very
intricate and are producing things where and when they're needed and it may not be good to continuously swamp the system. So we don't know for sure it with ketones, but my intuition says maybe it's not such a good idea to just have ketones up.
24/7 chronic
it I'd say the jury's out on it. I've I've gone from using brain octane just to my morning coffee to write I pretty much put on every meal, but my Ketone levels are generally not above .3 except in the morning. So I think they're higher than physiological but they're not high and what I feel like that does is that affects my ghrelin levels, so I'm just not hungry and so I can go
Long time without food my brain just feels effortless and we know that your neurons neurons will use ketones even the presence of glucose because of the studies you talked about earlier, but the glial cells, you know, the repair cells in the brain and I know I'm simplifying with glial cells do their but they they like glucose more than ketones, right? So it that's why I'm really concerned about the the keto bro diets out there, you know, if you eat another car begin your a bad human being
Being kind of thing cuz it feels like there's a role for
carbs. I think there is to Dave and
You know, there was a recently published study. It's suggestive paleo diets. Not good long-term. I don't think it's a good idea to just eat only fats and protein. In fact probably too much protein is definitely bad from the standpoint of Aging.
Oh, yeah, they pay their diet is there burned protein and be too much protein in fact my
My my new anti-aging book that's coming out soon. I read a lot about protein restriction. In fact, there's one day a week of protein fasting was part of the original bulletproof diet because it increases autopsy yet have less than 15 grams. But for you, what kind of protein is worse than
what kind of best well, you know, usually an animal Meats you've got a mixture of fats and protein and so the fish story is strong.
You know, you can't go wrong eating fish. Yeah, ideally some of the smaller fish with regards to the Mercury issue, but you know, red meat. Yeah, you don't need it at all you get plenty of protein.
No, everything's all goofed up. Wait parents told us you won't get any dessert which is sugar unless you finish your meal. Right? So eat all a lot overeat and then you can have your sugar and you know, read you got to eat your meat drink her milk to get protein. So kids are getting too much protein namtar pet mtor pathway is over activated their cells aren't removing the garbage.
And in fact the huge problem that's hard to tackle is how to change.
the family environment
Kids habits their eating habits, whether or not they exercise throughout their life for many people. It's determined by what their parents are doing in the animal studies.
That the biggest impact of the intermittent fasting is on average lifespan.
Hmm. But Not total
is not maximum. Although there's some effects. So then the other thing is healthspan. Yeah that that matters more. Yeah. I'm starting to I mentioned get some Orthopedic issues now, which is really my only health issues right now
people who are interested in your work probably easy way to find you is Googling Mark Matson.
And you're the first couple pages of results and your Ted Talk is totally worth watching and I'm just you know, thanks. Thanks for the Decades of work on anti-aging and fasting and neurology and I find it fascinating and you've done a good thing.
Well, thanks Dave. I've enjoyed a lot and you keep up the good work to it. As I said at the beginning of our conversation. There's a big need for translating this basic Research into practical things that people can apply to their own
lives.
Well, I will keep doing my best. I'll ask the hard questions and just to reiterate for people listening. I think we're both serious. If someone out there wants to do a PhD or some other kind of research project on antioxidants and intermittent fasting. It's a wide-open area that totally needs attention and I never thought about that until today so you stimulated a new idea. Thanks. Okay, Dave. All right, if you like today's episode, you know what to do head on out there and Skip breakfast. You'll like your life better.
Or if you do that most likely and if you hate your life and just get breakfast, you got to figure out all right, what's going on with my metabolism because I'm probably not as resilient as I'd like to be and then you can work on that. And if you want to know how to do that, there's a whole variety of episodes of bulletproof radio. We talked about a few of them today, which is this one again, get the show notes. You could read the bulletproof diet. You could read headstrong. I talk about intermittent fasting in both of those books and there's just so much knowledge available right now on the blog and
Two places and really if you don't know what else to do. Wake up. Skip breakfast don't put sugar in your coffee don't put artificial sweeteners in it and see what happens and you just might be okay.
bulletproof radio was created and is hosted by Dave asprey the executive producer Darcy Hines podcast assistant Bev hampson, his podcast is for information purposes only statements and Views expressed on this podcast or not medical advice this podcast including Dave asprey in the producers disclaim responsibility for any possible adverse effects from the use of information contained herein opinions of guests are their own in this podcast is not in daughter accept responsibility for statements made by guests because podcasters not make any representations or warranties about guess qualifications or credibility individuals on
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