How To Build A Better BRAIN (+ Ketamine, Nicotine, Alcohol & More!) With Dr. Tommy Wood

How we use our brains is the primary determinant of how they function. You might think that we are at the same time overstimulated and then we're also understimulated from like a skill development. We can change our environment and as a result, we know we can change our brains. Whatever you want your brain to be good at is what you should be doing on a daily basis because that's what helps build and maintain function.

Tommy Wood, you're a neuroscientist who writes big books.

Yeah, I am now.

Well, I should say you're a big neuroscientist who writes big books. This is something that people might not realize. You're kind of like, at least in my mind, you're a little bit of a hybrid athlete.

I will say that I've gone back and forth. I've done a ton of the long-distance endurance stuff just like you have. I did off-road Ironmans, ultramarathons, all that kind of stuff. But nowadays I compete in strongman. I'm actually 3 days into a cut for a competition this weekend. So yeah, I try and do a bit. I try and, you know, work at multiple ends of that spectrum.

Yeah. What do you need to cut for strongman? Is it weight class based?

Yeah, so I compete in the Masters under 90 kilo category, so I have to get under 198, but I normally hang out at like sort of 215-ish. So I'll do a water cut to make, to make weight for the weekend.

So 3 days, what, what kind of activities you're going to be up to in 3 days? This like dragging a semi-truck with your teeth?

Or yeah, so, uh, events this time is going to be max weight 16-inch like wagon wheel deadlift. There's going to be a log, uh, a log for reps, sort of like a farmer's carry and max hold, um, thing. There's, uh, weight, uh, odd object over bars. There's gonna be like sandbags and, um, Atlas stones and kegs over, over a bar. And then there's gonna be a max bear hug carry with like a big beer keg. I think those are my 5 events this weekend.

Jeez, did you ever do a marathon or an Ironman?

Yes, uh, so I've done multiple marathons. I've done multiple marathons in multiple days. I did that a couple of times. And then I did the world's first fully off-road Ironman triathlon in 2012 out on the south coast of the UK.

Wait, the world's first fully— did you say fully off-road?

Fully off-road, yeah. So sea swim, mountain bike, and trail run, but Ironman distance.

Oh, wow. What's your marathon time? Your best marathon time?

My best was 3:27, I think. So I'm not super fast, but I can go for a reasonable amount of time.

Yeah, but you're big.

Yeah, I probably ran that at 210 pounds or something. Yeah.

So do you actually call yourself a hybrid athlete?

Yeah. Do you know what? Because I've never done both at the same time. I've either been doing strength sports or I've been doing endurance. So, yeah, I've never called myself a hybrid athlete, but I'd like to think that I have some capacity at both ends.

Yeah. I don't want to throw you a total curveball here, but I'm going to anyways. Have you ever thought about the kind of like the paradox of the AMPK and mTOR pathways kind of being simultaneously targeted with endurance, catabolism to a great extent, and anabolism?

[Speaker:BEN GREENFIELD] Yes. So, I think for— I've definitely looked like the concurrent training and whether those different stimuli interfere with one another. I've definitely thought about this a little bit. I think that if you want to be truly elite in one sport or the other, that's probably going to play a role, but I'm not truly elite. So I think they, to a certain extent, could help, could help one another. We know that strength training decreases injury risk in endurance athletes. We know that having some conditioning may make you better at, like, recovering and coming back between bouts for, like, even more intense work. I definitely find that in— when I compete in strongman, my absolute max strength isn't as good as some of the other guys, like the static strength, the deadlifts, the log presses, that kind of stuff. But then when it comes to a medley or a truck pull or something like that, I've got way more gas than the other guys, even if they're stronger than me. So I can use— those are the events that I usually do really well in. Yeah.

You ever fiddle around with obstacle course racing, like Spartan, Tough Mudder, anything like that?

I've done a couple. There was one that I did when I lived in Norway, and one part of it was we had to run up, um, like a, a ski jump. Slope, one of those. And then there was some monkey bars and rock carries and stuff like that. So, I get a little bit just to kind of try it out.

Yeah. That's what Spartan got into for a while was they built 80% of their damn races at ski resorts. So, you're basically running up and down these intensely steep pitches that people would normally take a chairlift up and ski down and you're hauling a sandbag up and sprinting down. So, this book, it is big. I read it cover to cover, half of it in my bathtub. That's where I do a lot of my reading. I have a hydrogen bathtub, so I'm motivated now to bathe. Why'd you call it The Stimulated Mind?

I will say it was my editor came up with the title, which is pretty common, but I quite like it because it's It's slightly thought-provoking, mainly because the core thesis of the book is that how we use our brains is the primary determinant of how they function. Very much like if you want to be bigger, stronger, fitter, your training is how you change physical function. And so how you use your brain is how you change brain function. It's the same. But nowadays you might think that we are at the same time overstimulated, multitasking, task switching, social media, technology, all that kind of stuff. And then we're also understimulated from a skill development, complex learning, focus, attention kind of stuff. So I like that it kind of will force people to think about that because there is a balance between this potential for overstimulus in the modern environment versus not getting enough of this kind of truly deep stimulus that our brains really need.

Yeah, I mean, it seems like one of the central thesis early on in the book is that the brain's kind of product of the environment. I think you mentioned that a couple of times. What do you mean when you say the brain's a product of the environment?

So what you see in all these different spheres that I work in, so I work in the developing brain, newborn babies with brain injury, I work in concussion and recovery, concussion recovery, I work with elite athletes, I work trying to figure out the confluence of factors that affect cognitive function across the lifespan and then risk of dementia later on. And what you see is that in each of those areas, the same core things are required for brain function and brain health. And one of those is that the environment that a brain is placed in essentially determines how it functions. So that's true in the developing brain. It's true when we're trying to recover from injury. It's true when we're thinking about the biggest risk factors for long-term cognitive decline and dementia. And so that's everything from nutrition, cognitive stimulus, social activity, all of these things that we have some control over. And the reason why I say the brain is product of the environment is because the human brain is more attuned to adapt to its environment than any other species' brain. It's kind of at birth, we're born with a brain that's Essentially, the most complex parts of the brain are completely undeveloped, and then they are shaped by the environment more than any other species. That's what's allowed us to thrive in so many different environments. But then how that relates to us is that we can change our environment, and as a result, we know we can change our brains.

What's an example of that? Like boots on the streets of, I don't know, like a career or a person you've worked with, or someone who had a brain that was operating in one way, changed the environment, and then witness some kind of, I don't know how you define it, anatomical, neurophysiological, or some other change in the way the brain worked?

I think that the most striking example that I have from my own research is actually in babies. And then there are several other studies that we could talk about in adults as well. But when I am doing work in the lab trying to develop therapies for babies with brain injury, we do a whole, a huge amount of stuff looking at like the drugs these babies get, the experience they get in hospital, right? They have some, something happens to them. They might have to spend several, several weeks in the intensive care unit. They get exposed to painful procedures. They get exposed to opioids and benzodiazepines that can negatively impact brain function. They have some kind of brain injury. Often they might bleed into their brain, a whole bunch of stuff going on. But then when we do these big studies looking at what determines or what predicts how well their brains function later on in childhood, the biggest predictor or the most important factor is the home environment. And there are different ways to measure this, but it's basically then related to socioeconomic status, reading, education, nutrition, all that kind of stuff that happens in home is more important than what happens in the hospital. So like even if you had an imperfect start to life, the environment you go back to is the most important thing.

Ben Greenfield: Fun thought experiment here, but if you did have a baby and you brought it from possibly a relatively disruptive hospital or clinical environment with the bright lights and the antibiotics, a lot of the other things you were talking about into the home and you could wave a magic wand and either eliminate some of the things that might be more harmful to a baby's brain or introduce the things that might be most beneficial from a brain health standpoint, what are some of the things that you would do?

The most important thing again is going to be giving that brain opportunities to learn because those stimuli are really what drive brain development. So, depending on the age, we're talking about reading to them and then learning to read. We're talking about playing sports. We're talking about in childhood something that we'd call risky play. So, that's types of play where there's maybe a small risk of injury, maybe there's a risk of getting lost, but it requires learning of complex motor skills, emotional regulation. So sports, languages, music, and then at the same time, you know, making sure they're getting a nutritious diet. So lots of B vitamins, omega-3s, you know, enough protein, iron, all these things that we know are critical for brain development. And then also late in life. And then a good social environment. So lots of other kids their own age and other people of a variety of ages, plus as much as you can, an environment that supports sleep. So bright light during the day, darkness at night, avoiding stimulants at night. Kids in particular are more susceptible to the effects of bright light at night on suppressing melatonin, even more so than adults are. So creating a sort of calm sort of dark environment, a calm environment that supports sleep. You tick those boxes, you've got your brain, and there's a lot of physical activity in there as well. I haven't mentioned that, but as a stimulus, but also for physical health, you've covered pretty much everything.

[Speaker:BEN GREENFIELD] Yeah, yeah. And I may have put the cart ahead of the horse there when I said healthy brain because I think you actually define that in the book, but how do you describe to people what a healthy brain would actually be.

My definition of a healthy brain is a brain that does what you want it to do when you want it to do it. And it's kind of, that's like slightly adapted from, there's like a WHO brain health definition or something. But I put it in, put it that way because each of us wants our brains to do different things, right? You want to be, you want to be good at different things than I want to be good at, or would expect to be good at different things than I'm good at. And you'll have different skills and different experiences. So It's all about just making sure that your brain has the capacity to do what you need it to do when you need it to do that. And that includes when things are optimal, right? We've slept well, we've exercised, we've eaten well, but it also includes being able to perform when we're sick or we're stressed or we're traveling. And it's having some kind of resilience in the system is going to be important too.

Okay, so resilience, induced by, in the case of a baby, risk, unpredictability, a somewhat natural environment like elimination of harsh lights, et cetera. That makes sense. But, you seem to be super interested in this idea of a reductionist approach to biology not really being a good way to approach the brain. And, you use the example of a broken radio in the book.

Yes. So this is one of my favorite, favorite sort of academic essays. It's called Can a Biologist Fix a Broken Radio by a guy called Yuri Lazebnik. What he describes is this idea of how we traditionally approach— I mean, he's talking about cancer biology, but it's the same when we're thinking about neuroscience, we're thinking about any of the sort of like the basic biomedical sciences. We tend to apply this reductionist approach, which says, if I can break this complex thing apart into all its different individual components, I will then be able to understand the whole. And in reality, we've dug deeper and deeper and deeper into the brain. We've gotten fancier and fancier techniques with microscopes and transcriptomics and metabolomics, and we can measure all the proteins and look at all the organelles. But we still don't understand fully how the brain works, right? So the brain has multiple different properties that seem where the, the whole is greater than the sum of its parts. And this is where reductionism kind of falls flat a little bit. So in this essay, he's talking about, you know, if you gave a biologist a radio, what they would do is they would, they would take it apart. They would look at all the individual components, they would count them. They would look at their colors, they would like change the color of the transistors to see if that affects their function and all this kind of stuff. But in reality, what they would have is just like a bunch of bits and they wouldn't necessarily know how they fit together. And especially because in biology it's not just like things are there, they're there or they're not, or they're off or they're on. Everything is kind of finely tuned and feeds back. And right, there's all these, you know, aspects of function that aren't fully described by structure. So the whole idea being that if you treat a brain the way you would treat a broken radio, you can't really understand it by just breaking it apart and looking at all the individual pieces. And so this is where we've gotten a little stuck in neuroscience is just assuming that if we can describe all the different parts of the brain and the different parts of all those cells, we'll figure out how our brain works. And in reality, we still haven't been able to do that. And it's unlikely that with that approach alone, we'll ever be able to do that.

Right. It's kind of like the anterior cingulate cortex does this and the hippocampus does this and the amygdala does this. And if we somehow decode each of those individual parameters, we can, with laser specificity, target certain areas of the brain. And you're saying it's not that simple.

No, no, exactly. One of the easiest ways to think about this is when we think about— so I talk a lot about pathology in the brain that accumulates with things like Alzheimer's disease. You heard about amyloid and tau and these proteins accumulate, and that's associated with cognitive decline and dementia. But just imagine at some point in the future you die and they look at your brain under a microscope and they can count the cells and they can count the amyloid and they can count the tau. But how much of what they're looking at under the microscope, how much does that tell you about who you were as a person, how your brain functioned, the skills you learned, right? The people you met with and interacted with and all these different things you did on a day-to-day basis. It actually tells you very, very little. And so the reductionist approach would say, I can look at this brain and I can count all these proteins, and that will tell me about how that brain functioned in real life. But we are so far from being able to do that because like Where does your personality sit in the brain? Where do your skills sit? They don't have that kind of like just sitting in one region and one function that you can count under a microscope. So, we need to have this bigger idea of what it means to have a functioning brain and then the inputs that go into that. Yeah.

And unless this podcast becomes just a doom scroll of shrugging and walking away and saying, "We don't know," you actually do have a lot of really good practical stuff in the book. Whenever I get an excuse to talk about penis on the podcast, I do just because it's such a fun word. So, you talk about pianists in the book and specifically related to training the functions that we want to keep. So, can you explain a little bit about the study on the, I'll just say it, piano players?

[Speaker:BEN GREENFIELD] Yes. So, this is kind of the whole point that gets into the middle part of the book, which is that even though I don't know, or we as a scientific community don't know exactly how all the different parts of the brain works and we can't isolate all its individual functions. If we step back, we do know a ton about how we can improve brain function, even if we don't know the exact mechanisms of what's going on. So if we can just sort of suspend our need to know exactly which neurotransmitter is doing what and which part of the brain, there's still a ton that we have control over that actually significantly impacts cognitive function. So this study, they took older and younger expert and amateur pianists. So you have 4 groups, right? Old and young, expert and amateur. And what they found was that when they were looking at complex skills related to piano playing, the older and younger— well, the experts outperformed the amateurs, as you might expect, but the older and younger experts, and so the younger experts were in their 20s and 30s, the older experts were in their 50s and 60s, they performed just as well as each other. And so that kind of goes against this idea that we have to or are destined to lose function as we get older. And the most important predictor of how well the older pianists performed on these on skills tests was how much they'd practiced. So, that essentially tells us that whatever we want our brain to be good at—

How much they'd practice the piano, not how much they'd practice the skill test. Yes.

Yeah, yeah. So, there's an important thing when we're testing brain function, which is that ideally we want the test to be different from the thing that we use to train it or otherwise, you're just training for the test. You know what I mean? But yeah, so you're absolutely right. So, it's how much they played the piano in the preceding 10 years was essentially the best the best predictor. So, whatever you want your brain to be good at is what you should be doing on a daily basis because that's what helps build and maintain function. [Speaker:BEN GREENFIELD] Okay.

Have you ever come across any evidence that there— this is kind of a nichey question, but that there are certain instruments that might lend themselves better to delaying brain aging or is it just kind of like anything that involves whatever? Hand-eye coordination, memory, recall, learning chords and scales, et cetera?

I haven't seen a comparison of different instruments, and I think that they would all have these sort of same core components because you can also see benefits just by teaching adults music theory, not even the instrument. You can see changes in brain structure and changes in executive function. So, I think there's some part of the process of, yes, the complex motor skills of playing an instrument, but then it's also just the structure and attention and focus to music and its structure has its own benefits.

Yeah. Would you, based on that, rank music pretty high in the kind of like the delaying brain aging strategy sector?

There are lots of studies that show that having a music-related hobby and maintaining that late into life is associated with a slower rate of cognitive decline and a lower risk of dementia. So yeah, that's Music is definitely very high on the list. Okay.

Assuming a heavy wagon wheel doesn't count as an instrument for you, do you mess around with music or instruments at all?

Not nearly as much as I did when I was a kid. My main instrument was my voice. I sang in a bunch of different bands and choirs. And then nowadays I've recently rekindled like electronic music stuff that I did as a kid. So like producing and like making drum and bass tracks. I do that for— I do that for fun.

Oh, is this like GarageBand type of stuff?

Yeah, exactly. And then you end up just recording little bits and loops and sort of fitting them together. That's my little foray into music.

Yeah. I recently did a podcast about magnesium L-threonate as something that seems to have some decent research behind it for assisting with formation of new synapses, particularly when someone was engaged in a learning activity. And they'd consumed, I think the guy interviewed was citing 140, 150 milligrams of magnesium L-threonate. And, it was really focused on this idea that the brain can change, in this case, when you combine a supplement with a complex learning task. But, in terms of the amount of change, I mean, you even say in the book that the brain can change itself What's that mean exactly when you say the brain can change?

There's a few different ways you can think about this. I generally think about it in terms of structure and function. So it's kind of like if we think about our muscles, structure is muscle mass and function is strength and power. And in general, they're related. A bigger muscle tends to be stronger, But equally, you can also sort of specialize them a little bit and you can get a better function for a given amount of structure. But in general, you're usually changing both to some degree. So when traditionally we thought about the adult brain, people often thought that it couldn't change or it didn't change except just to get worse over time. And I think one of the reasons for that is because we have conflated or confused neurogenesis versus neuroplasticity. So neurogenesis is the making of new neurons, and the adult brain doesn't really make new neurons except for in a couple of places, the dentate gyrus of the hippocampus and the olfactory bulbs, which is where we smell. Everything else, your number of neurons is relatively fixed.

From what age approximately?

Yeah. So the brain actually finishes growing sometime early in childhood, like 2 to 3 years old. After that, it's just refining connections, essentially. Even though we can't make new neurons in most parts of the brain, those neurons can continuously and do continuously make new connections, new synapses, and the strength of different synapses are changed, either increased, decreased, synapses are added and removed. This is the process of neuroplasticity, and that is what drives learning and skill development and function in adulthood. Plus alongside that, we also tend to ignore the fact that neurons only make up about half of the cells in the brain. There are a whole bunch of other cells related to myelin, related to fluid flow and function like astrocytes. Astrocytes also actually use electrical activity to communicate with neurons just like neurons do. And then microglia, which are the main immune cells of the brain. Plus all of those cells then contribute to the other structural components. All the cells are surrounded by proteins and all these different things, which can also change. So there's a whole number of things, even if we're not making new neurons, that contribute to changes in structure in the adult brain. So there are studies, like a classic study now more than 20 years old, they took adults, they taught them how to juggle and they saw structural changes on an MRI scan in the visual cortex of the brain. So like you're constantly trying to figure out where these balls are moving. That's a visual stimulus. And the structure of the brain changes as a result. But then we see this with resistance training, with aerobic exercise, with skill learning, like music, like languages, taxi drivers memorizing maps in London. That's another classic example of brain structure changing. As we stimulate the brain. So, you see that if you learn a new skill or you apply a new stimulus to the brain, the structure in the areas of the brain that are activated learning that skill physically changes. And with that comes improvements in function.

So, how much of the, I guess, the popular perception that you do get, for lack of a more scientific phrase, more dumb with age or less prone to be able to learn new things, or memory loss, et cetera, is something you'd attribute to the fact that we just stopped going to school and many people stop proactively learning and how much of it actually is like some kind of degradation? Because it sounds to me like what you're saying is as long as the stimuli continues, our brain synaptic, I guess, connectivity can continue into old age.

I will say that right now we can't completely prevent the aging process. We know that. We can definitely speed it up. So, part of all of this is not doing the things that speed up aging, which can be related to poor quality diet and no sleep and no physical activity and no cognitive stimulus and all that kind of stuff. But in general, and it's the same with physical function, the building and maintenance of function just depends on ongoing inputs. So, As we get older, in general, after we finish our period of education, which is when we build our initial capacity, if we go to work and we do the same thing every day and we stop learning new things and we stop engaging in new hobbies, our brain will adapt as a result. It will decrease function. Just like if we stop training, we tend to lose function. Some of it is just what happens in typical adult life. The other part is, what we expect. So if we expect to lose function as we get older, we stop doing the things that can help us build function, right? So, oh, I'm too old to learn that. I'm too old to lift that. I'm too old to do that, right? As a result, function starts to decline. The final part of that is that when we think about not being able to learn things as well as we could when we were kids, To an extent, that's right. So kids do tend to learn things a little bit more quickly, but that's a feature, not a bug, right? When you're an adult, your brain has already adapted to the environment that you've put it in, right? It's already tried to optimize its function based on its inputs. So you want it to be fixed to an extent. That doesn't mean it can't change. It means it just needs a good reason to change. So you need focused attention you need to show that it's important to actually drive this change.

And I think probably you could engage, you could have your cake and eat it too. You could engage in safe and comfortable activities during a workday that allow you to continue in the expert status that you've built through adult life and enhance income so you can fulfill Maslow's hierarchy. But then whatever, 5, 6, 7:00 PM, you can be doing crossword puzzles, learning guitar, learning piano, playing pickleball, juggling if that's your thing. And so, you can kind of alternate between low-level stimuli, safe environment that allows you to succeed and survive, and then unpredictable stimuli stacked at some point in the day.

The nature of your work is obviously an important stimulus you're going to get from day to day. For some people, if they have a very cognitively stimulating job. They spend a lot of time interacting with people, solving problems, learning new skills. We know that's associated with a slower risk of cognitive decline and a lower risk of dementia. But equally, not everybody's job is like that. And that's not a big deal because you can get those same benefits from other skills and hobbies that you do outside of work. The only thing to remember is that when you compare your adult self to your younger self, one of the main reasons why it feels like you don't learn as well is just because you're not investing the same kind of time and focus and attention to learning as you did when you were a kid. You're busy, you're stressed. So the brain still does adapt and learn. It's just that the environment of learning is sometimes a little bit trickier when we're adults. But if we're able to set aside time to do those things, like you mentioned, learn guitar, play pickleball, The brain can still change when we're older. It just comes down to investing the time to do that.

Yeah. You mentioned strength training and aerobics earlier as examples of something that might enhance plasticity, I think. Is there a type of exercise? A lot of the people who listen to my podcast, they love exercise, but is there a type that's best for the brain?

The answer is yes and no, depending on what you're looking at. So in general, the more movement, the better, and of any type. So there's basically this linear effect of total physical activity on cognitive function in healthy adults up to a point where if you're a very high-volume endurance athlete training 20, 30 hours a week, there are diminishing returns. Absolutely. But for most people, any kind of movement seems to be beneficial. When you then drill down into it, the spectrum of more aerobic or cardio-type exercises, like starting at sort of walking through to zone 2 work and then up to high-intensity interval training, that type of work seems to be particularly beneficial for the gray matter of the brain, the hippocampus, which is really important for memory, and then memory function. So you see that aerobic training or interval training seems to benefit the hippocampus and memory function. Resistance training seems to particularly benefit the white matter of the brain, which is kind of in the middle of the brain. That's where all the myelin is. That's responsible for fast connections and some of our more complex cognitive functions. Resistance training improves the structure and function of the white matter, and with that, improvements in things like executive function. And then, the final piece is sort of open skill coordinative exercise. So, you mentioned pickleball, tennis, ball sports, board sports, martial arts. Things where on top of the physical component, you have this complex motor skill aspect, that seems to have an even greater benefit for the brain and seems to benefit sort of like global cognition. So, multiple different cognitive functions because you're layering the physical challenge plus a cognitive stimulus.

[Speaker:BEN GREENFIELD] Yeah, unpredictability even and risk with stepping outside of the stale, safe gym environment. I think some of that can be replicated in the gym with whatever, Bosu balls, balance training devices, or say like with aerobics running outdoors on unpredictable undulating terrain versus a treadmill.

Obstacle course, they've tested obstacle courses versus track running. Yeah. So, something similar. Yeah.

Yeah. So, obviously, the unpredictability is important and that's something you could program in without necessarily having to step onto a field of sport. You don't have the time to do that, But dipping our toes in kind of the waters of physiology, a lot of people talk about glucose as a potential fuel for the brain or as a fuel for the brain, ketones as another. Lactate though isn't discussed as much. And, we know that lactic acid is produced through higher rep strength training and high-intensity interval training. How or have you come across, I guess, anything that shows that the higher levels of lactate that you're producing, the more benefits there might be to the brain to, I don't know, BDNF or vascular endothelial growth factor or something like that.

[Speaker:JAMES] I think most of this comes from the aerobic training, an interval training kind of world, but you see that acute sprint or interval training that acutely improves cognitive function. So, like a cognitive flexibility task, a Stroop test. And the degree of improvement seems to correlate with the amount of lactate production. That's up to a point because if you do truly exhaustive exercise, obviously cognitive function will decrease for a period of time. Anybody who's really crushed themselves doing intervals will know that their brain doesn't work as well afterwards. But while you're still just below that threshold, more lactate seems to be acutely associated with some improvements in cognitive function. But equally, when you look at the effect of intensity of aerobic or cardio-type training on cognitive function, there's absolutely an intensity-dependent effect with over long periods of time, high-intensity interval training, say, beating something like zone 2 training. And they've done that in studies. And I think the lactate is going to be this key regulator of that response. Because though we release lots of exokines, myokines during exercise, many of those don't actually get into the brain. So BDNF goes up during exercise, right? We can measure it in the blood, brain-derived neurotrophic factor, which supports the function of recently activated neurons and neuronal networks, supports the processes of neuroplasticity. But there's actually no transport mechanism for BDNF in the body to get into the brain. However, lactate gets straight into the brain through monocarboxylate transporters, the same transporters that take ketones into the brain, and switches on the production of BDNF. So lactate seems to be this key like messenger from like more intense exercise through to the production of stuff like BDNF in the brain.

[Speaker:BEN GREENFIELD] Yeah, it is interesting the mental fatigue that you talk about post whatever, like soul-crushing CrossFit WOD or something like that. I question how much of that is just like the central governor shutting down the body for survival as body temperature rises and fuel substrate like glycogen stores decrease versus an actual, a lower amount of brain stimulation. It seems to me like it's one of those things where kind of like you see a transient hyperglycemic occurrence in a sauna and yet long-term sauna use might actually help to stabilize blood glucose or improve insulin sensitivity, that is kind of like this really quick acute response from a very hard workout that makes you feel a little dumb right after, but the long-term payoff is potentially increased mental growth compared to an easy walk.

Yeah, 100%. It's just if we're thinking about acute versus long-term changes in brain function, a small amount of intense exercise acutely improves brain function. A lot may acutely decrease brain function, but yes, long-term you're still going to greater benefits just like any acute stressors. It's a pure hormetic effect, right? So, this is hormesis in action. So, yes, you're absolutely right.

Okay. So, completely subjective like n 1, but blood flow restriction training where you kind of occlude the extremities, they build up massive amounts of lactic acid, you remove them, that kind of floods back into the body. I feel as though I experience a significant increase in acuity, perception, verbal fluency, et cetera, after a workout like that. Am I just hallucinating or do you think that there might be something to that when it comes to blood flow restriction training?

Yeah. So, I think there's absolutely something to that. I think you're generating many similar responses as you would to an interval or sprint-type training, lactate being one of them, which like we said, As long as you're not reaching true exhaustion, which is hard with— it's hard to reach like central exhaustion with BFR training, then you're going to get this acute cognitive benefit afterwards. You're going to generate a lot of lactate. You can also generate, get a similar lactate response from like a heavy leg day. There was a study where in trained individuals, they're doing max reps on a leg press at like 60, 70, and 80% of their one rep max, you— they can get their lactate into like the low teens, which is very similar to interval training. So I, I think that you can get some of these same benefits from things like BFR from, uh, you know, a heavy like lower body or compound type movement. And, and I think lactate is going to be one of those key regulators.

Yeah, to contextualize that for those of you listening, high teens or even low teens is a lot of lactic acid. If you were to do a blood test during a graded exercise test, the point at which things really start to burn and you're beginning to accumulate lactic acid more quickly than it can be buffered is around 4. So, when we're talking about teens, that's a lot of lactic acid. It also makes me think about the emerging field of lactate sensors. I was actually speaking with a scientist the other day who's working on a wearable much like a CGM that will do continuous lactose or lactase or lactic acid lactate monitoring. And I would think that there might be kind of a new field of study emerging that might allow you to correlate that to, I don't know, your own internal testing of how you do on Brainscape or Lumosity at certain levels of blood lactate.

I've got a lot of questions about this recently, like how do we compare different types of exercise? How do we know we're getting enough lactate production to improve brain function? And right now, the answer is we don't know. So, The best study we have on this long-term is a study that did 6 months, 3 times a week of the Norwegian 4x4 protocol, right? So 4 minutes, 85 to 95% of maximum heart rate, 3-minute break, 4 times over, did that 3 times a week. Saw significant improvements in the structure and function of the hippocampus compared to control groups, and they were maintained for 5 years after training stopped. But that doesn't mean that you have to do the Norwegian 4x4. I think that you can make the argument that any type of training that that is similarly intense and produces a similar amount of lactate will probably have a similar benefit. But until we can do this kind of monitoring, right, continuous lactate monitoring, comparing lots of different exercise protocols, this kind of— we don't know what the perfect answer is. But I would argue that any type of exercise that gives a similar physiological response is probably going to improve brain function in a similar way, right?

Yeah, I think you can, you could make a case for approximation on a, on a weekly basis of some type of maximum sustainable pace, mildly anaerobic training with something close to a 1:1 work-to-rest ratio. For most people, that's like a 4 to 6 minute effort, 4 to 6 minute recovery that I guarantee you're going to develop a love-hate relationship with if you try. Yeah, big dividends. I mean, even just for VO2 max alone, I didn't know about the effects on the brain, but that's all the more motivation. A little bit of a shift here, This is obviously a huge area of concern for a lot of people, the emergence of AI, external brains, lowered need to memorize certain things or even write with complexity because of how much we can delegate and outsource now a lot of the heavy lifting. I don't know what you've come across, what you've studied, what your thoughts are on this, Are we shrinking our brains? Are we simply freeing up areas of the brain to focus on other creative tasks? What's your general theory or thought pattern around AI?

Yes. So I think that it's really going to depend on how we engage with it, and it could go in either direction. So the framework that I use for this, I've taken it from a friend of mine, Ken Ford, who's been working in the field of AI for 30s, 30s.

Yeah, he's down in Florida, right?

In Florida, IHMC, yeah. And so he talks about the idea of cognitive prosthetics versus cognitive orthotics. A prosthetic is something that you use if you are missing a function, right? So if you have a prosthetic leg because you're missing part or all of your leg, right?

Right.

An orthotic is something you use to boost your function. So if you have a structural issue or something with your foot, you can have an orthotic shoe that allows you to walk. But it's enhancing your capacity. And so we can use AI as orthotics, right? We can do the work ourselves and then say to whatever tool it is, you're like, what am I missing? What could I do better? What should I add? How can I improve this? Then it gives you feedback and you incorporate that feedback yourself. All of this requires you to be engaged in the work, to actually think yourself, and you're building your skills. So that's using it as an orthotic.

You've just described the exact opposite of how every high school student in America is using AI.

Exactly. But there is one study that, and I think everybody's heard of this study, the MIT essay study, social media exploded after it came out. But basically what they did is they took students writing essays and they had them in 3 groups. They had, you just had to write the essay using whatever you had in your brain, or then there was a group that could use a search engine, and then there was a group that could use a large language model to help them. As you go up those different levels of support, they saw decreased activity of the networks in the brain associated with doing the task. Then people remembered less of their work and they felt less ownership of their work, which makes sense because if you ask ChatGPT to write an essay for you, it's not your essay. So this kind of says that if you're just having this tool do the work for you, you are not going to develop that skill. And if you had that skill in the first place, you're probably going to lose that skill because you're no longer practicing it like we talked about earlier. But There was one subset of students who wrote the essay themselves first and then afterwards were allowed to use AI. And their final product was actually better because they did the work themselves and then they got feedback on it. And so it actually built their capacity.

They were interacting with the work.

Exactly.

I get that. I've attempted a few times to create almost like a podcast dossier file that allows me to research, generate intelligent questions, and refine the podcast interviewing process. I have used it 3 times in the past year, and those 3 podcasts were probably some of the worst podcasts I've ever recorded. I didn't know the guests, I didn't know the material, the questions weren't really questions I cared about as much as what the internet's cared about. And they were a train wreck. I'm sure I could have maybe studied the questions a little bit more and queried A&I and gone back and forth. But ultimately, that's a very simple example pertaining to my career and what I do. But I agree, grasp of the material seems to plummet.

Yeah. And I think that's what we expect, right? So if you're using it as an orthotic, you can augment your function, right? You're building on what you've already got. Or you can use it as a prosthetic instead of your brain, as if you didn't have one. And then your skills will atrophy because you're not actually engaging them. And if you're not practicing those things or you never learn them in the first place, then that's going to be associated with decreased function over time.

Yeah, I think the sweet spot is AI plus deep interaction with the output that the AI produces.

Exactly. Or ideally, you create some input, deep input first, then interact with the AI and that builds it from there. The one final part, which relates a little bit to your initial question, is that if we can have the AI do menial tasks that don't require a lot of skill on our part or aren't important skills that we want to maintain, and then that frees up time so we can go and learn to play the guitar or play pickleball or something, that's great too. So that could be a net benefit as well. So, there are a number of ways it could be beneficial, but it's really going to depend on how we interact with it.

[Speaker:BEN GREENFIELD] Yeah. I even find that when I'm helping people out with health or blood work questions, I can vastly accelerate my ability to be able to go in, compare, contrast, get really good contextualized data on, say, 14 lab reports that span genetics and stool and urine and blood. And upon studying those materials, that actually frees up time for me to take an even deeper dive with the client. Where if somebody's hiring me to work with them for an hour and I'm spending 40 minutes on just reviewing the labs and have 20 minutes left to talk with them, I think it's less beneficial for both of us.

[Speaker:BEN GREENFIELD] Yeah, exactly.

[Speaker:JASON] Speaking of blood and urine and stool, we haven't talked about food much. We briefly brought up ketones, but I'm just curious. I want to get personal actually. What do you eat? I know you're an odd duck because you're the hybrid athlete. You're doing power, you're doing endurance, but I'm just curious how you comprise your diet as a neuroscientist who's pretty aware of what the brain likes.

[Speaker:Ben Greenfield] 80, 90% of my diet is whole minimally processed nutrient-dense foods. So, I eat a lot of fruit and berries, meat, eggs, fish, vegetables. Depending on my training volume, I'll then add more or less carbs from a variety of sources. Could be rice, could be potatoes, could be pasta. And I sort of, that's where I, that's where I sort of like dial my, my total calorie intake. One final, you know, one thing that I do rely on relatively frequently is some kind of sort of processed protein type foods, be that bars or powders or something, just to make sure that I get, I get enough. So maybe I'll have something like that, you know, every day or two. Just sort of like fill in the gaps depending on what I've been eating. And then I'll take a few supplements, mainly again, just sort of like make sure I'm hitting targets on nutrients that I know are critical for the brain. So vitamin D in the winter, I'll often take a high-quality multivitamin, especially to get enough B vitamins we know are critical for brain function. And then I take, I take creatine, And recently started taking lithium orotate. There's some very interesting data out there on lithium on both mood and potentially on cognitive function and cognitive decline. But just kind of like making sure I'm hitting those nutrient base. Oh, and then if for whatever reason I'm not regularly eating seafood, I might take a high quality omega-3 supplement, although I usually eat seafood pretty regularly. So, so that's, I don't need that as much.

Yeah. Lithium is an interesting one. When I interviewed Dr. Sandra Kaufman, she made, a pretty decent case for 75 mg per day of lithium, which is much higher than a lot of standard OTC supplements have. Do you know if there's kind of like a dose-effect relationship or if what's generally in a lithium supplement reflects what has been demonstrated in clinical studies to have efficacy in humans?

When you look at the epidemiology of lithium in water and mental health outcomes, you're talking sort of 1 to 3 milligrams of lithium a day, which is pretty typical. So, an over-the-counter Lithium supplement might be 1 to 5 milligrams. So that's usually where I hang out. When you're talking about, say, bipolar disorder, it's several hundred milligrams. I don't know about good interventional data in humans in that sort of 75-milligram range. I know there are some clinical trials ongoing right now, but I'm not entirely sure what dose they're using. Some of the other stuff you have to kind of interpolate between animal studies and human studies. That can be sometimes difficult to translate across.

Yeah. After interviewing her, I got a source for 300-milligram tablets and used a pill splitter, cut them into 75-mg portions, used for a month. I didn't notice a thing, but maybe I need to, whatever, become bipolar and go back and repeat because a lot of the effects seem a little bit more clinically indicated.

There was a recent pilot study using lithium in mild cognitive impairment. So, that early sort of pre-Alzheimer's kind of state. It didn't see a significant benefit of lithium, but it was kind of like there was an— because the groups were quite small, but there was kind of this signal that maybe it was slowing decline compared to a control group. And I think they were using like 150 to 300 milligrams. So that was a big dose. So maybe that's going to be indicated in that more sort of clinical scenario. But yeah, I think for most people, if we're just thinking about some of the other evidence we have, then lower doses, maybe just like a milligram or two might be enough.

Yeah. Continuing the rapid fire, exogenous ketones, do you use them? Do you have a varietal in terms of a specific type?

So, do you know what? I don't routinely use them. I'm still waiting for a high-quality study in humans, which I think relates to me in terms of boosting cognitive function. I mean, there was one study that just came out published by a friend of mine, Andrew Koutnik. He's done several studies in this using the Vich monoester, either the one that like Delta-G does it, KetoneAid does it.

Yeah. And starting to— The 1,3-butanedial.

Yeah. Yeah. Cetoacetate monoester. Yeah.

Yeah.

And there's starting to be some evidence that in certain states, like chronic supplementation of ketones may improve certain aspects of cognitive function, maybe under like stressful conditions like hypoxia. Sometimes it seems to benefit people in, if they have like metabolic disease. But I, I haven't seen like a study that makes me think, oh yeah, this is really relevant to me. So in certain states, potentially I've tinkered with it, particularly when I've been like sleep deprived or stressed. Maybe I feel like subjectively I see some benefits in cognitive function, but right now I think the data is still super mixed and we don't know which supplement is best for which type of outcome. So, I've been really excited about exogenous ketones for cognition for a long time. We know there's some evidence in people who are already experiencing some decline that with MCT oil or something, you see some improvements in cognitive function. But I'm still kind of waiting to figure out exactly which type is going to be most beneficial in which setting.

Ben Greenfield: Yeah, going all the way back to like Mary Newport who's using coconut oil for her husband with dementia, all the way up to Chris Palmer championing metabolic stabilization as being something that's very good for the brain and even certain mental conditions. I think you could make a case that perhaps some of the efficacy of ketones for cognition or mental stability or what you might call a healthier brain is in people who struggle with glycemic variability, episodes of hypoglycemia, who are perhaps transitioning from a standard American diet into a healthier diet and yet still are pretty reliant on glucose as a substrate. Ketones in that scenario, I think, especially in people who are getting, let's say for example, brain fog from hypoglycemia and they need something else in the brain, but they're not yet producing significant ketones through burning fat. I think that's a population that at least subjectively for me, I've seen benefit quite a bit from something like drinking ketones.

Yeah. I mean, we know that metabolic disease, pre-diabetes, and type 2 diabetes are significant risk factors for cognitive decline and dementia. We know that if you have, you're somewhere on that stage of decline, you see decreased glucose uptake into the brain. I don't think, well, I think at least part of that is because those areas of the brain are less active, so they're asking for less glucose in the first place, right? This is why stimulus and how we use our brains is really important. But, you know, if you look at like Stephen Cunnane's work where they're giving MCT oil to individuals who are already experiencing some decline, you see increased uptake of ketones into the brain, right? They did in the C2 acetate PET scan. And with that you see improvements in cognitive function. So if, yes, if there's an energy access issue, which you might see in certain mental health conditions, you might see in certain like, you know, cognitively degraded states, then I do think ketones have a huge amount of promise. It's just which formulation, what dose. And I think that depending on the situation, a different ratio of acetoacetate, beta-hydroxybutyrate, is it the L-form, is it the D-form, is it an ester, All that kind of stuff. Luckily, we know lots of people who are doing that good work to sort of figure all that stuff out.

Yeah, yeah. I recently had Andrew on the podcast, so I'll link to that. By the way, the show notes are at BenGreenfieldLife.com/StimulatedMind. BenGreenfieldLife.com/StimulatedMind. Let's talk about some vices in the bit of time that we have left here. Turn this into a Drugs with Tommy episode. Alcohol, do you completely abstain? Do you think there's some benefit? You see some studies suggesting a possible beneficial effect of something like wine on Alzheimer's and dementia. Others suggest shrinking of gray matter. Where do you stand on alcohol?

Yeah. So, I don't completely abstain, but I also don't think there's any benefit, if that makes sense. But at the same time, at low levels of intake, I don't think there's a strong case for a negative effect. So when you look at most of the studies that relate alcohol intake to dementia risk, for example, you do these big meta-analyses. In reality, it seems that at lower levels of intake, there's no net effect, right? So a glass, like a glass of wine an evening on average. When you look at brain volumes, again, you see something similar. So lots of studies now done in the UK Biobank, where if you are averaging up to 1 UK unit of alcohol a day, which is 8 grams of ethanol, which is about half of a US standard drink, which is 14 grams of ethanol. If you're averaging that amount, no real effect on brain volume or dementia risk. If you're drinking more than that, brain volumes start to decrease and dementia risk starts to increase. There have been some recent studies that suggests that, like, and like, people will have seen this, any, any amount of alcohol is like bad for the brain, increases mortality risk, all that kind of stuff. But they use this really weird technique where they take people, they ask them how much they drink. Using that information, they develop a polygenic risk score for drinking. So like you use your, your genes to predict the amount that you might drink, and then they use that polygenic risk score to predict dementia risk. But you're already 2 steps away from the information that's important. And I don't think that that's a valid way to determine alcohol's effect on the brain. So I think that the best evidence we have is that small amounts occasionally, no net effect one way or the other. So that's essentially, you know, I go for date night with my wife once a week, have a cocktail, something like that, I think is fine. We do know it affects sleep quality. We do know at high doses can be neurotoxic as well as addictive. So, it's not good for you, but I think at sort of low levels of intake, probably no negative effect.

Ben Greenfield: Yeah. Even the sleep score studies, when I dig into those, most of them are within 2 hours of bedtime, in many cases 3+ servings. I don't think a glass of wine at 6:00 PM, bedtime at 10:00 PM is going to be that big of an issue from a sleep architecture standpoint for a lot of people. Okay. And then, a couple others. We're going to skip weed because I think it's pretty demonstrably proven that that one is bad news bears for the brain. What about, and I don't know if you have any opinion on this, if you don't, just feel free to tell me to quit bugging you about it. I was at a party last week in Austin, no surprises, and it seemed like ketamine trophies were going out like candy. Any thoughts on ketamine in the brain?

[Speaker:BEN GREENFIELD] This is interesting. So, in the setting where people are maybe using it from, from like a beneficial standpoint. I've never seen any kind of evidence for that. I certainly think that ketamine is interesting in the like mental health space, you know, ketamine-assisted therapy, that, that kind of stuff, as with, with, you know, many sort of psychedelic type therapies. But I've, I've never seen any good data on like ketamine being a good thing for the brain, sort of outside of that kind of very directed setting in, in, in the in the context of some kind of bigger psychiatric thing.

[Speaker:BEN GREENFIELD] Yeah, yeah. I would tend to agree. I think it's an NMDA antagonist, I believe. [FOREIGN LANGUAGE] There's some risk for glutamate excitotoxicity, et cetera. I think that if you have brain issues that are due to excess stress and anxiety because you haven't processed a past life event and need some kind of a treatment with a disinhibiting agent to allow you to process that, there are kind of more acute, more clinical use cases, but I don't hang around with a lot of people who do ketamine regularly who I think are brilliant, and I'll stop there.

And well, a big part of that context you give, right, the therapy is a really important part of that as well, right? It's not just taking the mind-altering substance.

Right, exactly. Therapy is not sniffing it at a music festival. Okay. Last one, because I know it's vasoconstrictive, nicotine. So some people get concerned about brain health, others swear by it as a focus-inducing agent. What are your thoughts on nicotine?

This is a really interesting one because the answer is slightly complicated. So if you give people an acute dose of nicotine, say in a gum or a patch, or a tablet, which they've done some studies, those who both historically take nicotine, right, they're smokers or something, or people who are nicotine naive, you do see some acute improvements in cognitive function. So focus and attention in particular, because acetylcholine is really important for that. So nicotine can acutely boost cognitive function. There are some studies that kind of suggest that chronic nicotine users have a lower risk of Parkinson's disease in particular, long term.

Yeah, yeah, I've seen that.

I don't think that's a reason to like take up vaping because I will say that we know nicotine is addictive. We know that it, it produces tolerance and withdrawal. So you need higher doses to have the same effect and then you get significant withdrawal if you stop taking it. So I'm— so like if people are using it intermittently because they find it helps, they find it helps them like focus when they really need to. I think that's okay. If you're relying on it every day, then I think it becomes problematic. I don't tend to use it. I don't tend to recommend it, but there are data out there that show that it can acutely improve some aspects of cognitive function. What I will say is that there are lots of studies that show that when we use stimulants to improve cognitive function, we think we're performing better, but often we're actually performing worse. So they've seen this with caffeine. They've seen this methylphenidate and many of the others are like amphetamine-type drugs that they use.

Yeah, I'm like, like subjective perceived brilliance.

Yeah. So like, yeah, it's the same with creativity and cannabis. Like, you think that your brain is working much better, but then if you like objectively score cognition, it's actually worse. So I think there's a little bit of this with nicotine as well. They're like, they're taking it like, this is a nootropic, I'm going to get a cognitive boost, I feel amazing. But actually, I'm not entirely sure that you're always going to be boosting cognitive function. Yeah.

And those of you who are calling me out because you may have seen me This is not nicotine, this is alpha-GPC, theanine, and paraxanthine, some can somebody gave me. It's called Ultra. So yeah, I'm kind of in a similar boat as you with nicotine. I use it occasionally, but yeah, especially because of the vasoconstrictive properties and even just the rise in resting heart rate alone, don't think it's the ideal staple. I know I just ruined a lot of people's day by saying that. Tommy, book's great, "Stimulated Mind: Future-Proof Your Brain from Dementia." Stay sharp at any age and look like Tommy Wood, hopefully, Dr. Tommy Wood. Thanks so much for doing this, man.

Thanks so much for having me. I'm super, super excited to be able to talk with you about it. Thank you so much for reading it. Often when you speak to somebody, they haven't actually read the book, so I appreciate you doing And see all the folded-over pages.

I read all the books. Again, excuse to take a long bath a few times a week. Alright, folks. Thanks for watching. Again, shownotes are at BenGreenfieldLife.com/StimulatedMind. Thanks, Tommy.

Thank you.

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