How Food Choices Shape Memory, Cognition & Cravings | Dr. Scott Kanoski

1. 0:00 – 2:33

   Scott Kanoski

   1. SKDr. Scott Kanoski0:00

      When I started studying how diet impacts neurocognition and memory function, the first model we were studying was a high sugar model. The animals basically had ad libitum access to a sugar solution about the same percentage of calories as a soft drink that we consume, and otherwise they had healthy food and water. And with this model, the animals show hippocampal dependent memory deficits when they're older and these seem to persist later into life, even though they're not consuming the sugar anymore. There may be a role for the microbiome. There's some changes in the bacteria in the gut from the sugar model that, that may have a functional connection to the memory impairments. We've also looked at models where the animals are consuming like a total junk food diet, so we give them chocolate peanut butter cups, ruffled potato chips, rodent high fat, high sugar diet. They show these memory impairments that last even after you switch them to a healthy diet.

   2. AHAndrew Huberman0:56

      Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life. [music] I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Scott Kanoski. Dr. Scott Kanoski is a professor of Human and Evolutionary Biology and Neurobiology at the University of Southern California. His lab studies how hunger and memory interact and how the mind and body impact appetite, body weight regulation, food craving and choice. Dr. Kanoski's lab also studies how different types of nutrients impact brain development and brain function later in life. Today, we discuss many topics including GLP drugs, how they work, how they impact hunger, and how they impact things like longevity, cognition and drives in general. As you'll soon see, Dr. Scott Kanoski is an encyclopedia of useful information about how your brain and body control your relationship to food. And today he shares that knowledge with you in a clear, unbiased and in many cases, actionable way. It's a conversation about the interactions that occur between your brain and body involving hormones, neurotransmitters, your memory and your experiences that I'm confident will powerfully inform how you think about food, your food choices and nutrition in general. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my conversation with Dr. Scott

2. 2:33 – 7:06

   GLP-1, Natural GLP-1 Production; GLP-1 Drugs, Microdosing

   1. AHAndrew Huberman2:33

      Kanoski. Dr. Scott Kanoski, welcome.

   2. SKDr. Scott Kanoski2:36

      Thank you. Pleasure to be here. Thanks for the invitation.

   3. AHAndrew Huberman2:39

      You work on a topic that people experience every day, which is hunger, feeding and hopefully satiety. But we also have this obesity epidemic, which seems to be partially mitigated by the GLP drugs. But there's a lot to this whole thing that we call hunger and food and appetite and weight and all of that. And today you'll educate us about all of it. But to start things off, because it's on everybody's mind, what are the GLPs? What is this glucagon-like peptide one in its natural form in the body? And then perhaps we can talk about the drugs-

   4. SKDr. Scott Kanoski3:14

      Yeah

   5. AHAndrew Huberman3:14

      ... that increase their levels, because either everyone's taking one of these now, coming off of one of these now, thinking about taking one, hates the idea that anyone's taking them or is, has someone that they know is taking one. So GLPs are here.

   6. SKDr. Scott Kanoski3:32

      In its natural form, it's an incretin hormone, so it's secreted from the distal intestines around food ingestion. So there's a little bit of secretion before the, the meal actually starts. Then there's additional secretion during the meal and this gets into circulation. There's also a source of GLP-1 that's produced in the brain.

   7. AHAndrew Huberman3:52

      Hmm.

   8. SKDr. Scott Kanoski3:53

      In the brain stem, uh, nucleus tractus solitarius. There's a, a population of neurons that make GLP-1 and then extensively send GLP-1 message throughout the brain.

   9. AHAndrew Huberman4:03

      What do those do? Are they related to hunger as well?

   10. SKDr. Scott Kanoski4:05

       The peripheral GLP-1 and the central GLP-1 have very similar effects, so they, they're involved in hunger suppression, but they seem to be operating independently, so there doesn't seem to be a strong connection between the peripheral GLP-1 physiological system and, and the neurons that make GLP-1 in the brain. But they, they do both have appetite suppressing effects.

   11. AHAndrew Huberman4:25

       But presumably they're doing other things as well, right?

   12. SKDr. Scott Kanoski4:28

       Uh, yeah. They're, they're helping to regulate blood glucose levels to, to stimulate insulin secretion when, when there's high levels of glucose present in the blood. In fact, the first application of, of GLP-1 based drugs was for diabetes treatment, not for obesity. But because they also suppress appetite and food intake, which leads to body weight loss, um, now they're, they're probably more widely known for their, for their weight loss capacity in present day. But they started off as, as diabetes treatment.

   13. AHAndrew Huberman4:57

       My understanding is that the GLP-1 drugs, so Ozempic, Wegovy and on and on-

   14. SKDr. Scott Kanoski5:03

       Mm-hmm

   15. AHAndrew Huberman5:03

       ... that they increase levels of GLP-1 thousandfold more than we ever experience naturally.

   16. SKDr. Scott Kanoski5:10

       That's correct. Super physiological for sure.

   17. AHAndrew Huberman5:12

       Is there anything known about the potential downside to that, um, or upside?

   18. SKDr. Scott Kanoski5:18

       Well, I mean, most of what we know is, is an upside. I mean, the people have been taking GLP-1 based drugs for, for over a decade now and, and the clinical trials support the efficacy of these drugs. The, the-- there are side effects, nausea and, and emesis, emesis being vomiting, uh, the most common side effects and this can lead to discontinuation in a lot of people. They kind of tolerate it for a certain period of time and then at some point, uh, discontinue the treatment.

   19. AHAndrew Huberman5:45

       Hmm.

   20. SKDr. Scott Kanoski5:46

       Um, so if there's any primary limitation of these drugs, it's trying to, to mitigate those side effects and to, to have more long-term efficacy beyond the initial weight loss.

   21. AHAndrew Huberman5:57

       I hear that some people nowadays are taking far less than they are prescribed.

   22. SKDr. Scott Kanoski6:01

       Yeah.

   23. AHAndrew Huberman6:01

       So-called microdosing, a term borrowed obviously from the psychedelics community-

   24. SKDr. Scott Kanoski6:04

       Right

   25. AHAndrew Huberman6:05

       ... in order to offset some of the, um, side effects, still get some appetite suppression-

   26. SKDr. Scott Kanoski6:10

       Mm-hmm

   27. AHAndrew Huberman6:10

       ... and perhaps also reduce their cost 'cause some of these are quite expensive, although many are moving to generic forms. Are there any animal and/or human data that you're aware of on microdosing or is this just a natural experiment that people are doing?

   28. SKDr. Scott Kanoski6:23

       I'm not aware of any, any data on that. I, placebos are, are very effective, so there-

   29. AHAndrew Huberman6:30

       Mm-hmm

   30. SKDr. Scott Kanoski6:30

       ... could be some of that involved. I'm, I'm old-fashioned and I like to see the large clinical trials, uh, you know, randomized controlled clinical trials before I, I start to believe something's actually working.
3. 7:06 – 10:36

   GLP-1 Drugs & Benefits

   1. AHAndrew Huberman7:06

      I also hear about some non-weight loss related benefits of the GLPs. In fact, I know people who are of healthy body weight who are-

   2. SKDr. Scott Kanoski7:14

      Yeah

   3. AHAndrew Huberman7:14

      ... taking "microdoses" or even full doses in order to glean what they claim are some of the benefits on cognition, on energy. A friend who is diagnosed with chronic fatigue syndrome has been microdosing it, and she loves the effects. She's working with a physician, obviously.

   4. SKDr. Scott Kanoski7:33

      Mm-hmm.

   5. AHAndrew Huberman7:33

      She doesn't like the appetite suppression because she's already very lean and a little, not underweight, but close to it. So, but it speaks to the possibility that taking or elevating levels of GLP-1 could be beneficial for things unrelated to the weight loss.

   6. SKDr. Scott Kanoski7:47

      Absolutely. The, the receptor for GLP-1 is not exclusively expressed in regions of the brain that control appetite and food intake and, and glucose regulation. They're pretty densely expressed throughout the brain, and this is, uh, including regions that are in the, the reward circuitry in the brain, the mesostriatal pathway. Um, there's receptors in the midbrain VTA, the, the striatum, nucleus accumbens. One of my favorite brain regions is the hippocampus, which has a lot of GLP-1 receptors. So there's definitely possibility of, of applications for these drugs or, or different GLP-1 receptor agonists for substance abuse disorder and-

   7. AHAndrew Huberman8:26

      Mm-hmm

   8. SKDr. Scott Kanoski8:26

      ... and potentially even memory disorders and, and dementia.

   9. AHAndrew Huberman8:30

      Interesting.

   10. SKDr. Scott Kanoski8:30

       Um, and there's a lot of certainly preclinical data to support that.

   11. AHAndrew Huberman8:34

       Mm-hmm.

   12. SKDr. Scott Kanoski8:34

       Um, the, the clinical data are just ongoing and, and starting to come out now. And part of the idea with the applications of GLP-1 receptor agonists to things other than appetite suppression has to do with, uh, the i- the capacity of these drugs to get into the brain.

   13. AHAndrew Huberman8:51

       Mm-hmm.

   14. SKDr. Scott Kanoski8:51

       Um, this is somewhat of a controversial topic, uh, in our field of research. The first generation of GLP-1 drugs, so 2005 to 2012, we collected some preclinical evidence in rodents suggesting that, uh, a large part of the mechanism of action for food intake suppression was through brain action. So the drugs would get into the brain, activate receptors. Whether these newer generation GLP-1 drugs, like Ozempic, Wegovy, uh, are getting into the brain is less clear. Um-

   15. AHAndrew Huberman9:22

       Really?

   16. SKDr. Scott Kanoski9:22

       Again, controversial. So some, some studies will, mostly preclinical, exclusively preclinical, will tag the, the peptides with a fluorescent molecule and try to look at where it accumulates in the brain. And you see a lot of it clump into the, what's called the circumventricular organs, where there's no blood brain barrier, uh, protecting the brain from, from the circulation.

   17. AHAndrew Huberman9:44

       Hmm.

   18. SKDr. Scott Kanoski9:45

       Um, so there's a school of thought that these drugs are acting primarily in those circumventricular organs. But those studies are, are tricky because fluorescent molecules fade.

   19. AHAndrew Huberman9:55

       Mm-hmm.

   20. SKDr. Scott Kanoski9:55

       And the brain has autofluorescent signal.

   21. AHAndrew Huberman9:58

       Mm-hmm.

   22. SKDr. Scott Kanoski9:58

       So we, we could be missing something with those fluorescent studies. There's, um, better ways to do this, but it's expensive and complicated, where you radiolabel the peptides with, like, carbon-14 and you can actually determine if it's getting into the brain and where. Those studies, Elizabeth Rhea, Bill Banks, and colleagues at University of Washington are starting to do some of those. And it looks like some of the early generation of GLP-1 drugs readily get into the brain, and some of the newer ones, less clear. Maybe it, it takes a little bit longer. But the jury's still out.

   23. AHAndrew Huberman10:29

       Mm-hmm.

   24. SKDr. Scott Kanoski10:30

       Um, where, where they're getting into the brain is not something we have a clear understanding of at this point.

4. 10:36 – 13:24

   Sponsor: Our Place & Helix Sleep

   1. AHAndrew Huberman10:36

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5. 13:24 – 18:39

   GLP-1 & Hunger Suppression, Vagus Nerve; Food Noise

   1. AHAndrew Huberman13:24

      I'm sort of veering us toward reward and reinforcement-

   2. SKDr. Scott Kanoski13:27

      Mm-hmm

   3. AHAndrew Huberman13:28

      ... and memory, because even though those a- those are topics that come up in the context of drug seeking, of pleasure seeking, and on and on, in the context of food, you know, what we consider rewarding and what we crave are very closely related.

   4. SKDr. Scott Kanoski13:42

      Mm-hmm.

   5. AHAndrew Huberman13:42

      And memory for what we think is going to soothe us is also, um, or satisfy us at the level of food is also seems to be a strong component. I know you've worked in these areas, but as a way of, of getting directly there, I, I'm very curious how the GLPs are actually suppressing hunger. If... L- let's assume that it doesn't get into the brain, that these drugs aren't getting into the brain.

   6. SKDr. Scott Kanoski14:06

      Mm-hmm.

   7. AHAndrew Huberman14:07

      So if I take a full dose or a microdose of, of a GLP-1 drug, what is the sensation that people report? I've, I've never actually taken one, so I don't know.

   8. SKDr. Scott Kanoski14:16

      I have neither. [laughs]

   9. AHAndrew Huberman14:16

      Okay. So it... But I hear, like, presumably it's satiety. It... But does that mean fullness? Um, people will talk about reducing food noise in air quotes. What is this at the level of biology?

   10. SKDr. Scott Kanoski14:29

       So the GLP-1, normal physiological GLP-1 that, that we secrete in the body likely has a paracrine mechanism of action.

   11. AHAndrew Huberman14:38

       Could you describe paracrine really quick?

   12. SKDr. Scott Kanoski14:39

       Yeah. So the, the vagus nerve innervates our, our GI tract, and there's receptors for GLP-1 on the terminal. So right where the nerve is contacting the gastrointestinal tract, there's GLP-1 receptors. And this paracrine mechanism is where the GLP-1 is released from these L cells in the intestines and immediately act on nearby receptors that are expressed on, on the vagus nerve.

   13. AHAndrew Huberman15:02

       Mm-hmm.

   14. SKDr. Scott Kanoski15:02

       So that's one mechanism through which GLP-1, both the, the GLP-1 drugs as well as our physiological GLP-1 may be producing this, this feeling of satiation.

   15. AHAndrew Huberman15:12

       Mm-hmm.

   16. SKDr. Scott Kanoski15:13

       So the vagus nerve communicates a lot of within-meal signals that contribute to us stopping eating, right? At some point, we get full. This process is called satiation. GLP-1 is a big player in that, in that process.

   17. AHAndrew Huberman15:27

       Mm-hmm.

   18. SKDr. Scott Kanoski15:28

       Not exclusively through the vagus nerve, but, but probably largely through the vagus nerve, through this paracrine mode of action. So this sends a, a signal to the brainstem. That's the, the first site in the brain where the vagus nerve signals to, that the animal's had enough food at this point. The, the stomach's starting to expand. There's nutrients entering the intestines, and there's, uh, sort of a symphony of signals that, that some o- act through the vagus nerve, some don't, but eventually lead to this feeling of fullness and meal termination. And, and GLP-1 is one instrument in that symphony.

   19. AHAndrew Huberman16:03

       Does it turn off the desire for, for food as well? Like, people will talk about less food noise, and I know many people who are taking these drugs, some of whom are really bullish about also exercising, some who aren't.

   20. SKDr. Scott Kanoski16:15

       Yeah.

   21. AHAndrew Huberman16:15

       So we'll get to that a little later. But, um, they all talk about reduced food noise, which tells me that before there was noise, and I don't know because I haven't asked them whether they were aware of that noise.

   22. SKDr. Scott Kanoski16:28

       Right.

   23. AHAndrew Huberman16:28

       So I'm trying to imagine, having never taken one of these, what that noise is. I mean, when I see blueberries, I want to eat them.

   24. SKDr. Scott Kanoski16:34

       Mm-hmm.

   25. AHAndrew Huberman16:34

       But when I see bread or a steak or something, I may or may not want to eat them, depending on when I ate last, time of day, this kind of thing. So what is food noise?

   26. SKDr. Scott Kanoski16:47

       I am not someone who experiences food noise either, so it i- it's a bit of a, a strange idea to me.

   27. AHAndrew Huberman16:53

       Mm-hmm.

   28. SKDr. Scott Kanoski16:53

       Um, but I've certainly heard, same as you, anecdotal evidence of people who are taking GLP-1-based drugs and are saying that, "Wow, it really, really canceled the food noise." Whether that's based on receptor binding in the brain, in higher order brain regions that, that are involved in, in memory and cognition, hippocampus, prefrontal cortex, we don't know. Um, again, I think that's, that's one of the big gaps in this field is understanding where the drugs are acting.

   29. AHAndrew Huberman17:23

       Mm-hmm.

   30. SKDr. Scott Kanoski17:24

       Um, are they getting to these regions in the brain that, that are involved in higher order cognitive processes that may mediate the food noise?
6. 18:39 – 26:50

   Artificial Sweeteners & Appetite, Preclinical Studies

   1. AHAndrew Huberman18:39

      Gotcha. So that's all consistent that our body is telling our brain when we've had enough-

   2. SKDr. Scott Kanoski18:45

      Yeah

   3. AHAndrew Huberman18:45

      ... because of fullness of the gut and the presence of enough nutrients-

   4. SKDr. Scott Kanoski18:49

      Mm-hmm

   5. AHAndrew Huberman18:49

      ... have come in. I was gonna get to this later, but I think now's the appropriate time, given what you just said. Artificial sweeteners and low-calorie sweeteners are a really big topic online. There's some in my yerba-

   6. SKDr. Scott Kanoski19:04

      I believe I have some as well, yeah

   7. AHAndrew Huberman19:05

      ... Ste- stevia, right? So it'd be a low-calorie, quote-unquote, natural sweetener, although there's some manufacturing to take it from a plant to, like, a, a drink or a food. But, uh, different than, like, sucralose, et cetera-

   8. SKDr. Scott Kanoski19:17

      Yeah

   9. AHAndrew Huberman19:18

      ... um, of course. There seems to be three camps. One is the camp that believes that these things are terrible, that they alter blood glucose, they mess up the microbiome, and that they, um, maybe even cause brain cancer. I mean, that-

   10. SKDr. Scott Kanoski19:31

       [laughs]

   11. AHAndrew Huberman19:31

       ... people have made that argument about aspartame. Um, I'm not in that camp, but you, you will see people arguing this. The second group seems to be the ones that just say, "Look, this is not... It's a non-issue, that these are inert in reasonable quantities of consumption." And then there's the third group, which I think is, uh, quite a few people that kinda wonder, like, "Well, it's, quote-unquote, human-made," and like, "Maybe this stuff isn't good."

   12. SKDr. Scott Kanoski19:59

       Yeah.

   13. AHAndrew Huberman19:59

       W- what is the evidence, the, the research on consumption of, let's lump them for right now, low-calorie artificial sweeteners on development of appetite, development of the brain, development of the system that you work on, and what does it tell us?

   14. SKDr. Scott Kanoski20:17

       This is a very controversial topic.

   15. AHAndrew Huberman20:19

       Good.

   16. SKDr. Scott Kanoski20:20

       And I don't think we have definitive answers in any of, to support any of those three camps. So when we consume sweet taste, we have what's called a... There's a cephalic phase response, where we're releasing insulin before the nutrients actually get through the GI tract, just from the, the simple taste of sugar in the mouth. Uh, so this is part of our metabolism, right? If you, if this was a sugary drink, uh, you take a sip, you would have some insulin being released to kind of prepare the body, prepare the physiology for that perturbation in blood glucose levels.

   17. AHAndrew Huberman20:53

       Mm-hmm.

   18. SKDr. Scott Kanoski20:53

       And there is some evidence in preclinical animal models that if you disrupt the relationship between sweet taste in the mouth and the caloric consequences of consuming something, that you can have perturbations in, in appetite, uh, in, in glucose regulation. Um, kind of like you're tricking the wisdom of the body, right?

   19. AHAndrew Huberman21:15

       Mm-hmm.

   20. SKDr. Scott Kanoski21:15

       So sweet taste means calories are coming away, but now it, now it doesn't, and there's not a lot of definitive evidence i- in humans. There's been randomized clinical trials. Generally, uh, I won't, I won't get into all that, but there's no definitive evidence from the clinical trials in humans that it's good for or, or bad for weight loss.

   21. AHAndrew Huberman21:37

       Mm-hmm.

   22. SKDr. Scott Kanoski21:37

       There's some evidence in either direction. Um, in the preclinical animal model world, there's some evidence that if you give animals habitual exposure to artificial sweeteners, that this will, will disrupt their capacity to metabolize sweet taste later on, and can potentially lead to increased appetite and, and weight gain.

   23. AHAndrew Huberman21:57

       Interesting. So this is early life daily exposure to artificial sweeteners.

   24. SKDr. Scott Kanoski22:02

       Yeah. So we, we've done one study in my lab, and I can speak more confidently about that. Um-

   25. AHAndrew Huberman22:07

       Please.

   26. SKDr. Scott Kanoski22:08

       We had animals who were in the juvenile/adolescent stage of development. This is, um, the period of life in which we- we've studied a lot in, in my laboratory in terms of dietary factors on adult cognitive processes. And we gave the animals a little bit of artif- artificial sweeteners to consume each day, and we kept it within the FDA's acceptable daily intake levels. So this wasn't necessarily a sledgehammer. It might be something equivalent of six of these a day, something like that. And they consumed it voluntarily. We didn't put it in the drinking water. This was something they liked. They would just get their daily dose and, and carry on. And when the animals were adults, we then tested neurocognitive and metabolic effects of having that exposure during development. So at this point, they're no longer getting the, the sweeteners. They're just consuming healthy, uh, rodent chow and water. And in this case, we, we found that the animals had some memory impairments, which was an unexpected finding. We don't really know the mechanism for that. Um, but they also had some glucose regulatory, um, changes as well. So if you infuse glucose and, and bypass the mouth, there's a insulin spike, and the animals that had this exposure showed a larger insulin spike. They also showed changes in the sweet taste receptor expression on the tongue.

   27. AHAndrew Huberman23:26

       Yeah.

   28. SKDr. Scott Kanoski23:27

       Um, so we, we found some changes. Uh, this is not, not, like, whopping sledgehammer effects, but a- at least in that model with, with rodents consuming artificial sweeteners daily during that developmental stage, there is potentially some impact on, on neurocognitive and meta- co- metabolic processes when they're adults.

   29. AHAndrew Huberman23:47

       Mm-hmm. Interesting.

   30. SKDr. Scott Kanoski23:48

       But the caveat is this is a rodent model.
7. 26:50 – 33:42

   Memory & Meals; Stress; Eating & Individualization, Fasting

   1. AHAndrew Huberman26:50

      You know, if, if there's some association early in life or later in life and the food provides something beyond just comfort. What is the evidence that our memory of a food experience can play an important role in how we frame that food in our behavior?

   2. SKDr. Scott Kanoski27:06

      Our memory of eating occasions can have a powerful effect on how much we eat subsequently. Um, let me just give you a, a couple examples. So in one study from, uh, Suzanne Higgs and colleagues, they would have people consume a pizza lunch, and then they would have them come in a few hours later, and then they would prime them to really think about the memory of that pizza lunch in one group. Uh, another group was primed to think about something else. I don't remember exactly what the other experimental condition was, but not that lunch. And there might have been a third control group that w- had no priming, and they were given... They call them, uh, biscuits in the UK, but we, we call them cookies. They were given a, a biscuit/cookie taste test, and they would look at whether that memory priming had an effect on how much they ate at the, at the cookie taste test. And if they were primed to remember the lunch they had just consumed, they consumed fewer of these biscuits or cookies. So in, in general, the, the memory of recent eating will contribute to eating less at the subsequent eating o- occasion. There's another interesting study by Geoff Brunstrom and colleagues where they had, um, I think it was tomato soup. So it was a bowl that had a peristaltic pump that was either putting more soup into the bowl or pulling it out.

   3. AHAndrew Huberman28:25

      Mm-hmm.

   4. SKDr. Scott Kanoski28:26

      But the, uh, the participants were not aware that that was happening, so they saw a certain volume of, of soup, and they consumed the whole bowl, but that could have been a mismatch. It could be that they're seeing 300 and they're consuming 500 mLs.

   5. AHAndrew Huberman28:40

      [laughs]

   6. SKDr. Scott Kanoski28:40

      Or they're seeing 500, but they're actually pulling the soup out, so they're consuming 300.

   7. AHAndrew Huberman28:45

      Yeah.

   8. SKDr. Scott Kanoski28:45

      So this is a way to manipulate the memory of the meal. How much did you think that you, you consumed?

   9. AHAndrew Huberman28:50

      So it's sort of a magic bowl of soup where-

   10. SKDr. Scott Kanoski28:52

       Exactly, right

   11. AHAndrew Huberman28:52

       ... I'm continuing to, to eat soup, but the levels are not going down.

   12. SKDr. Scott Kanoski28:55

       They're... Yeah. The, the, or that or-

   13. AHAndrew Huberman28:57

       Or, or they're-

   14. SKDr. Scott Kanoski28:57

       Or they're going down-

   15. AHAndrew Huberman28:58

       ... going down faster

   16. SKDr. Scott Kanoski28:58

       ... more than they would-

   17. AHAndrew Huberman28:58

       Got it

   18. SKDr. Scott Kanoski28:59

       ... just by consuming it. And if you ask them to rate their hunger right after consuming the soup, it didn't matter what they saw. It was based on how much they actually consumed, right? So that, that's sort of-

   19. AHAndrew Huberman29:09

       That's good

   20. SKDr. Scott Kanoski29:09

       ... the, the wisdom of the body. Uh, but then a couple hours later, that, that flipped, and their hunger ratings are more driven by what they saw, what they think they consumed versus what they actually consumed.

   21. AHAndrew Huberman29:20

       Interesting.

   22. SKDr. Scott Kanoski29:21

       Yeah.

   23. AHAndrew Huberman29:22

       R- in fact, re- to me, really interesting because you said, like, the wisdom of the body piece is great. Like, you eat until you're full, until you're satiated. But then you said the memory of how much one thought they consumed impacts what you eat at your next meal.

   24. SKDr. Scott Kanoski29:38

       Uh, I don't think the study actually had them eating after that. This was a self-reported hunger rating.

   25. AHAndrew Huberman29:43

       Got it.

   26. SKDr. Scott Kanoski29:43

       But, you know, presumably it could extend to how much you would eat at a subsequent meal.

   27. AHAndrew Huberman29:48

       So, so much of it seems psychological.

   28. SKDr. Scott Kanoski29:50

       Yeah.

   29. AHAndrew Huberman29:51

       The, you know, ev- I think we've all experienced, like, when we're really, really busy, I know there are some people who just seem to eat a lot more during stress, and some people, like, their appetite just shuts off.

   30. SKDr. Scott Kanoski29:59

       Yeah.
8. 33:42 – 42:33

   Memory Impairments, Western Diet, High Sugar, Processed Food

   1. SKDr. Scott Kanoski33:42

      people.

   2. AHAndrew Huberman33:42

      Let's talk more about the memory system 'cause I'm, I'm intrigued by this. So you study not how memory impacts food intake, but how food intake impacts memory.

   3. SKDr. Scott Kanoski33:51

      I would say we're on both sides of that.

   4. AHAndrew Huberman33:53

      Okay. So let's talk about-

   5. SKDr. Scott Kanoski33:54

      Um

   6. AHAndrew Huberman33:54

      ... how food impacts memory. If I want my memory system to be as robust as possible, what should I avoid?

   7. SKDr. Scott Kanoski34:01

      [laughs]

   8. AHAndrew Huberman34:02

      Right? We can talk about what to do, but-

   9. SKDr. Scott Kanoski34:04

      Yeah

   10. AHAndrew Huberman34:04

       ... what, what, what clearly should one avoid besides alcohol, head injuries, uh, you know, uh, opiates, and methamphetamine? I think we all agree on that those are bad for memory.

   11. SKDr. Scott Kanoski34:14

       When I started studying how diet impacts neurocognition and memory function, we were working with adult animals, and we were using what we refer to as a Western diet. So this is a diet that maybe 35% of calories from fat, uh, 15% coming from sugar and, and a lot of that's simple sugar, so you know, simple sugar carbohydrates, not, not complex starch carbohydrates. And that in animal models can lead to hippocampal-dependent memory impairments. If the animals are on this diet for even, even, like, a week, but generally these studies take a f- a few months, and the hippocampal-dependent memory processes seem to be more susceptible to the negative impacts of this diet than other kinds of memories that don't rely on the hippocampus. So the hippocampus is somewhat of a canary in the coal mine. And when I started my lab at here in Los Angeles, um, we were looking at, um, development. So shifting away from adult models and looking at if you give animals individual components of a diet during the juvenile/adolescent phase of development, is there a, a longer term impact on their memory systems? And the first model we were studying was a high sugar model. Um, so the animals basically had ad libitum access to a sugar solution about the same percentage of calories as a, as a soft drink that we consume, and otherwise they had healthy food and water. And with this model, the animals show hippocampal-dependent memory deficits when they're older, and these seem to persist later into life even though they're not consuming the sugar anymore. So we, we had a few studies with that model. Um, there may be a role for the microbiome. There's some changes in, in the bacteria in the gut from the sugar model that, that may have a functional connection to the memory impairments. We've also looked at models where the animals are consuming Like a total junk food diet to try to look at, at mechanisms, um, but again, it's the same kind of thing. So if the animals consume a junk food diet, so we give them chocolate peanut butter cups, uh, ruffled potato chips, a rodent high fat, high sugar diet, they show these memory im- impairments that last even after you switch them to a healthy diet.

   12. AHAndrew Huberman36:35

       Yeah.

   13. SKDr. Scott Kanoski36:35

       Um, that's not to say that we couldn't reverse these memory impairments with some kind of other intervention other than just putting them back on a healthy diet, um, but at least in rodents and during this developmental window, these kinds of foods have a long-term impact on neurocognition. We have a pre-print, it's, which is, um, not a peer review publication yet. It's sort of in, in the process of becoming that, hopefully someday, where we were trying to look at food processing from a mechanistic individual variable perspective. So in... Food processing's a term we all hear, ultra-processed foods. The way this is studied in humans is there's this NOVA classification system where you have four different categories of food processing, where the ultra-processed food is basically just, you know, shitty food, and then, uh, the, the other end of the extreme is, you know, perfect raw vegetables and completely unprocessed food. And that's not really mechanistic in terms of what types of processing matter, 'cause foo- food processing, there's a lot of processes that happen to, to food in modernized food industry. So we wanted to try to take it one variable at a time, and we ended up heat treating the food. So this is an otherwise healthy food, and we baked it for an hour at, at a high degree, high temperature. And the idea behind this is that it induces something called the Maillard reaction. The Maillard is used in cooking because it enhances the flavor of food, so this is something that we do for a reason. Um, this is a chemical reaction that happens depending upon the, the nutrient composition, the pH, a lot of factors. But when you heat treat food, you can get this, this Maillard reaction and-

   14. AHAndrew Huberman38:16

       Do you wanna just describe the, the subjective experience of it? Like if I took a carrot-

   15. SKDr. Scott Kanoski38:22

       Yeah

   16. AHAndrew Huberman38:22

       ... and I just ate it, most people know what that tastes like. But my... If I took that carrot and I, um, sliced it and basted it with some, uh, butter, maybe a little bit of olive oil, some salt, and I stuck it in the oven and, um, cooked it until it was soft, it come out, it has almost like a meat-like quality to it, taste, um, that, um, it's a little tangy but savory. Um, is that, that's what you're referring to, right?

   17. SKDr. Scott Kanoski38:47

       Yeah. Yeah, I mean, the, the actual flavor components that are a result of the Maillard reaction are not, not well understood, so we-

   18. AHAndrew Huberman38:54

       Mm-hmm

   19. SKDr. Scott Kanoski38:54

       ... we can't point to certain flavonoids and say that, "Oh, this is, it's making it taste like this." But in general, you know, if you, if you bake a casserole, it's gonna taste better than before you baked it, right?

   20. AHAndrew Huberman39:06

       Yeah. Lord knows.

   21. SKDr. Scott Kanoski39:07

       Um-

   22. AHAndrew Huberman39:07

       Yeah

   23. SKDr. Scott Kanoski39:08

       ... so we were trying to, to create this chemical reaction in otherwise healthy food and what happens when you heat this food up is there's chemical byproducts of this process. They're called ad- advanced glycation end products.

   24. AHAndrew Huberman39:21

       Mm-hmm.

   25. SKDr. Scott Kanoski39:22

       The acronym is A-G-E, AGEs, and these chemicals are actually in our normal physiology. So we have AGEs circulating. We have receptors for AGEs. It's the RAGE receptor, which is pretty cool name for a receptor. And this system is n- it's generally associated with diabetes and aging and things that we don't think are, uh, great, great things. And when you heat food, depending upon the chemical composition of the food, the temperature, et cetera, you get these AGEs that are introduced into the food itself. So we're basically looking at if animals consume this AGE-enriched diet, is what we were calling it, during development, is there an impact on, on cognitive processes when they're adults? And it, it turns out, again, just the caveat is this is unpublished work, but a preprint, is that we, we see memory impairments with this AGE-enriched diet.

   26. AHAndrew Huberman40:15

       Okay.

   27. SKDr. Scott Kanoski40:15

       Uh, we think that there may be a role for the microbiome. There was a population of bacteria that was eliminated through the heat treatment process, and when we reintroduced it to the animals, uh, we were able to reverse these memory impairments.

   28. AHAndrew Huberman40:31

       When you say memory impairments, could you describe the type of a, of memory impairment?

   29. SKDr. Scott Kanoski40:36

       Yeah.

   30. AHAndrew Huberman40:36

       And, and, um, I'm not trying to review your paper, but the... are these big effects? I mean, they're obviously statistically significant or you wouldn't be describing them the way you are. But just to frame in our minds, uh, are, I mean, are these animals, can they remember where something was placed and come back to it later? Uh, or is it sort of like getting into challenges with higher order memory?
9. 42:33 – 43:46

   Sponsor: AG1

   1. AHAndrew Huberman42:33

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10. 43:46 – 49:40

    Dementia, Alzheimer’s Disease & Western Diet; Exercise

    1. AHAndrew Huberman43:47

       I don't want to, um, make too much of the findings, nor do I want to place you in the position of feeling like you have to, but I'm, I'm intrigued by this result because for the last five years or so there's been this unofficial naming of Alzheimer's-like dementias, um, type three diabetes, which I know drives certain physicians and neurologists absolutely bonkers because that's not an official diagnosis term. But I think we do, on the other hand, now well appreciate that diet impacts the brain and that really disrupted metabolic function, like chronically elevated insulin due to elevated blood glucose from either food intake or otherwise, is problematic for the brain. And as a consequence, a lot of people in the spheres that I find myself in these days are trying to offset their potential memory loss in the future or even treat the memory loss of their parents or spouse by saying, "Hey, look, at a minimum, we can control food intake." Might not be a cure, but you know, some are trying ketogenic diets-

    2. SKDr. Scott Kanoski44:55

       Mm-hmm

    3. AHAndrew Huberman44:55

       ... for instance. Some are trying to manage blood glucose using metformin or berberine, neither of which I do, I should be clear. Um, uh, some are taking even more aggressive measures. And now there's this, the discussion about the GLPs as like maybe these will improve longevity of brain function or improve-

    4. SKDr. Scott Kanoski45:12

       Yeah

    5. AHAndrew Huberman45:12

       ... memory. So I don't think it's too much of a leap to just chop it up around this topic. Uh, and just with the caveat that you're not talking about specific data, what are your thoughts on this, this notion that maybe some major component of age-related dementia, maybe even Alzheimer's, is earlier in life or current food intake related?

    6. SKDr. Scott Kanoski45:34

       Yeah, I, uh, there's pretty strong evidence from perspective studies. I mean, they're correlations, but from perspective studies showing that midlife dietary patterns and meta- metabolic status can be associated with an increased risk of dementia-

    7. AHAndrew Huberman45:48

       Mm

    8. SKDr. Scott Kanoski45:48

       ... uh, later in life, including visceral adiposity.

    9. AHAndrew Huberman45:51

       Mm-hmm.

    10. SKDr. Scott Kanoski45:51

        So the, the connections a- appear to be there. Um, in animal models we have transgenic models of, of Alzheimer's-

    11. AHAndrew Huberman46:00

        Mm-hmm

    12. SKDr. Scott Kanoski46:00

        ... where animals have gene mutations that lead them to, at a later point in their life, develop symptoms that are analogous to, to human Alzheimer's. And in the preclinical world, there's evidence that consuming a Western diet... So again, a high percentage of calories from fat and simple sugars can exacerbate that pathology-

    13. AHAndrew Huberman46:22

        Mm-hmm

    14. SKDr. Scott Kanoski46:22

        ... can essentially lead the animals to develop the, the symptoms of that Alzheimer's in this transgenic model earlier than they would if they were consuming a healthy diet. So the, the connections are, are there. I think it's more prospective than something you can deal with once symptoms arise. I d- I don't think that... I think it's, it's more important to have a healthy dietary pattern throughout life-

    15. AHAndrew Huberman46:47

        Mm-hmm

    16. SKDr. Scott Kanoski46:48

        ... as opposed to once there's a problem, you know, switching, switching at that point.

    17. AHAndrew Huberman46:52

        Yeah. So it's sort of the, and here I am heavily, uh, joking/stereotyping, sort of like were you raised in West Los Angeles, where everyone's talking about eating healthy all the time? [laughs] It's like a major topic of focus. Are you from an area, like, um, pr- an area of the country where nutrition isn't prioritized, or are you sort of like most people where grew up eating some healthy foods with a mix of some ice cream and pizza and-

    18. SKDr. Scott Kanoski47:24

        Yeah

    19. AHAndrew Huberman47:24

        ... and, uh, a little bit of alcohol for most? You know, like, it... I mean, most people are in this kind of mishmash, and yet we see people with Alzheimer's who are dealing with metabolic dysfunction, and we see people who get Alzheimer's who otherwise look-

    20. SKDr. Scott Kanoski47:39

        Yeah

    21. AHAndrew Huberman47:39

        ... healthy. And I, I don't see how we can draw a one-to-one correlation between-

    22. SKDr. Scott Kanoski47:43

        No, we definitely can't

    23. AHAndrew Huberman47:44

        ... food.

    24. SKDr. Scott Kanoski47:44

        Yeah.

    25. AHAndrew Huberman47:44

        Yeah. Yeah.

    26. SKDr. Scott Kanoski47:45

        Yeah. There, there's correlations-

    27. AHAndrew Huberman47:47

        Mm-hmm

    28. SKDr. Scott Kanoski47:47

        ... but it's, it's not a direct line.

    29. AHAndrew Huberman47:49

        Mm-hmm. It seems these days that people just feel really good talking about the fact that exercise is one of the few things we can do to maintain or improve brain function.

    30. SKDr. Scott Kanoski48:01

        Mm-hmm.
11. 49:40 – 57:10

    Vagus Nerve, Hippocampus & Memory, Hormones

    1. AHAndrew Huberman49:40

       What we're talking about here sits right at the edge of, like, where modern brain health and longevity care is at.

    2. SKDr. Scott Kanoski49:48

       Mm-hmm.

    3. AHAndrew Huberman49:49

       It's like i- uh, on the one hand we're talking about, like, what one eats, whether one exercises, and brain function. But to my knowledge, there's nothing else known about Alzheimer's that tells us to do something specific, besides also try and be a lifelong learner and social connection.

    4. SKDr. Scott Kanoski50:07

       Right. Right.

    5. AHAndrew Huberman50:07

       Okay, those are critical too, obviously. But there's tons of stuff it seems that can impair the system.

    6. SKDr. Scott Kanoski50:12

       Mm-hmm.

    7. AHAndrew Huberman50:12

       But we actually have in hand very few things besides exercise, quality nutrition, social connection, and a ongoing curiosity to try and maintain brain function. I realize this isn't your specific area of focus-

    8. SKDr. Scott Kanoski50:24

       Yeah

    9. AHAndrew Huberman50:24

       ... but when you look out on the landscape of dementia and Alzheimer's research, preclinical or in humans, what, like you've spent some time in the hippocampus as a researcher.

    10. SKDr. Scott Kanoski50:35

        Mm-hmm.

    11. AHAndrew Huberman50:35

        What, like do you think we're going to get to the place where what we call Alzheimer's is, is a reflection of a bunch of bad choices plus some genetic preloading of the system, um, some susceptibility that might be heightened in some people? Or do you think there's really a, a disease that s- that is independent of all that?

    12. SKDr. Scott Kanoski50:54

        We haven't come very far in terms of finding effective treatments for Alzheimer's, a- as I'm sure you know, and one thing that, that we've been doing in my lab is to try to think outside of the box-

    13. AHAndrew Huberman51:06

        Mm

    14. SKDr. Scott Kanoski51:06

        ... and try to think about how the gut might be connect- connecting to this pathology-

    15. AHAndrew Huberman51:11

        Mm

    16. SKDr. Scott Kanoski51:11

        ... as opposed to just looking at what chemical processes are, are changing in the brain.

    17. AHAndrew Huberman51:15

        Mm.

    18. SKDr. Scott Kanoski51:16

        One example of that is we've done some work with, with the vagus nerve-

    19. AHAndrew Huberman51:20

        Mm

    20. SKDr. Scott Kanoski51:21

        ... I think I, I mentioned earlier, and if you lesion the vagus nerve the, as it's coming out of the gut, the gastrointestinal innervating components of the nerve, animals show hippocampal dependent, uh, memory impairments. So there's a connection between the, the vagus nerve and the hippocampus and we're interested in trying to understand is that connection relevant to Alzheimer's and dementia pathology.

    21. AHAndrew Huberman51:47

        Hmm.

    22. SKDr. Scott Kanoski51:47

        We don't know yet. There was one study in a, a population in Taiwan that in the 1980s, maybe a little bit into '90s, people would get vagotomies, so they would get a truncal vagus nerve lesion for stomach ulcers. That was a, a somewhat common treatment at the time.

    23. AHAndrew Huberman52:07

        Medicine loves to start with a sledgehammer.

    24. SKDr. Scott Kanoski52:09

        Start with a sledgehammer.

    25. AHAndrew Huberman52:10

        You got ulcers, let's give you a vagotomy.

    26. SKDr. Scott Kanoski52:11

        Right. Let's cut off the nerve.

    27. AHAndrew Huberman52:12

        Let's cut your, let's cut, let's cut the major connection between the brain and body.

    28. SKDr. Scott Kanoski52:15

        Right.

    29. AHAndrew Huberman52:15

        Oh, goodness.

    30. SKDr. Scott Kanoski52:15

        And it was effective for that.
12. 57:10 – 1:04:32

    Sugar & Fat Consumption, Memory; Engineering Food for Quality

    1. AHAndrew Huberman57:10

       So here's the model I'm sort of-- simplistic model I'm coming up with in my head, that the, the hypothalamus has these switches. Find food, eat-

    2. SKDr. Scott Kanoski57:19

       Yeah

    3. AHAndrew Huberman57:19

       ... stop eating, et cetera. And we pretty much know what those switches are, the location of the neurons and so on because of the-

    4. SKDr. Scott Kanoski57:27

       Yeah

    5. AHAndrew Huberman57:27

       ... work of you and, uh, excellent colleagues in the field. And then there's this other system that we've been talking about that's a major topic of focus, this body to brain, vagus to hippocampus kind of, uh, memory system. And it's so interesting that, you know, when an animal or a human doesn't eat well, meaning enough macronutrients, sure, most people are getting enough macronutrients, at least in this country. I realize there are exceptions.

    6. SKDr. Scott Kanoski57:54

       Yeah.

    7. AHAndrew Huberman57:54

       But, but not enough micronutrients, not enough of the essential fatty acids, the vitamins and minerals, the protein relative to the calories they're taking in. When that ratio is skewed in the wrong direction, then the memory system suffers. And so if we adhere to the adage, use it or lose it, right? I, I kind of am getting this picture after all these years in neuroscience that, like, our brain develops and our parents and we do as well as we can. We don't control everything [chuckles] at, at the beginning, and then we do the, as well as we can, then we sort of land in this early stage of adulthood of like twen- mid-twenties, thirties. And then our goal is to hold on to what we have and improve on it if we can, right?

    8. SKDr. Scott Kanoski58:32

       Mm-hmm.

    9. AHAndrew Huberman58:33

       I mean, that, there's nothing, you know, new about the statement I just made, but that the gut is constantly updating, like, the body is getting what it needs. Therefore, if you're a neuron in the hippocampus, you can basically s- stay functional and alive. Otherwise, it sounds like neurons start cashing out. They might not die entirely, but I mean, this, it's a different picture of nutrition that I think is so important, and I think it fits well with what we're learning about dementia and Alzheimer's, that there is this blood sugar, but also nutrient-related aspect to it. So if this system from the body to the brain is, is really a core feature of keeping memory online [chuckles] and maybe even making it better, without feeling the need to make specific recommendations, how do you personally think about this in the context of your own food intake? Is it like, okay, eat well, but not too much. We know that. But what, what do you think about doing that could keep the system robust? Because presumably you want to do that. I realize, and I want to be very clear, I'm not asking you to make recommendations.

    10. SKDr. Scott Kanoski59:38

        Yeah, yeah.

    11. AHAndrew Huberman59:38

        But you're, you're more versed in this perhaps than anyone I've ever spoken to-

    12. SKDr. Scott Kanoski59:41

        Yeah

    13. AHAndrew Huberman59:41

        ... about this body-brain connection as it relates to memory and food intake. So I'm just curious where your mind is at. And bracket it as many times, as many caveats as you need to feel comfortable, but I'm curious w- and I'm certain many other people are curious.

    14. SKDr. Scott Kanoski59:56

        I don't make specific recommendations about what people should or shouldn't eat, but I do share our results with, with people who have kids who may be thinking about, you know, what, what do I feed my kid? And I always make the very important caveat that we're, we're studying rodents we think are a good model for, for memory systems, for, for energy metabolism. They are a good model for humans, but it's a very important caveat. That said, there is evidence in humans that support some of what we are doing in rodents. So, for example, um, Dick Stevenson and colleagues did some studies in healthy adults So this is undergrad students age approximate, and looked at their habitual dietary patterns and then how well they did on hippocampal-dependent memory tasks. So these otherwise healthy adults, they're not diabetic, really just normal healthy young adults, there was connections between habitual sugar consumption and saturated fatty acid consumption and how well they did on these memory tests. That's not to say that these can't easily be reversed by consuming-

    15. AHAndrew Huberman1:01:00

        Mm-hmm

    16. SKDr. Scott Kanoski1:01:00

        ... a healthier diet, but I do think it, it's worth looking into what we know in humans, which is very little because humans, um, unfortunately aren't that good at reporting what they actually eat.

    17. AHAndrew Huberman1:01:10

        Hmm.

    18. SKDr. Scott Kanoski1:01:11

        This is a major limitation in doing these kinds of studies. With rodents, we control at, what they eat, we measure it, we have 100% ac- near 100% accuracy of-

    19. AHAndrew Huberman1:01:20

        Mm-hmm

    20. SKDr. Scott Kanoski1:01:20

        ... of what they're eating and how much.

    21. AHAndrew Huberman1:01:21

        Even with phones nowadays where all they have to do is take a picture?

    22. SKDr. Scott Kanoski1:01:24

        It's, it's improved it, yeah.

    23. AHAndrew Huberman1:01:25

        Is it that they lie, or are they just too lazy, or are they-

    24. SKDr. Scott Kanoski1:01:28

        I, I don't, I don't want to say it's that, but I, it, the, it's just not an accurate process to date. I, I think having the, the apps involved are going to make it a little bit better.

    25. AHAndrew Huberman1:01:38

        Mm-hmm.

    26. SKDr. Scott Kanoski1:01:39

        There's caveats with both the animal model research because the rats and, and the human research because we don't have a lot of control about what they're eating and how accurate their reporting is. But that said, there, there does seem to be, um, evidence in humans to support what we're doing in, in rats.

    27. AHAndrew Huberman1:01:56

        Got it.

    28. SKDr. Scott Kanoski1:01:57

        So I, I guess that not making precise dietary recommendations, but excess sugar, not good.

    29. AHAndrew Huberman1:02:05

        Mm-hmm.

    30. SKDr. Scott Kanoski1:02:05

        Um, excess saturated fatty acids, not good.
13. 1:04:32 – 1:11:33

    GLP-1s, Nutrient Deficiency, Weight Loss & Other Effects

    1. AHAndrew Huberman1:04:32

       now. There's also an issue, uh, and I'd love your thoughts on this, in the, in the science field itself. I mean, years ago I used to occasionally come across an article in a journal Neuroscience, which, you know, back then, I think still now, is a respectable journal.

    2. SKDr. Scott Kanoski1:04:44

       Mm-hmm.

    3. AHAndrew Huberman1:04:45

       Um, it would be like blueberry intake correlated with improved cognition-

    4. SKDr. Scott Kanoski1:04:48

       Yeah

    5. AHAndrew Huberman1:04:48

       ... in rats. You'd occasionally see that, but I noticed that that kind of work got pushed aside, and there seems to be more of an emphasis on finding relationships between the bad stuff and deficits, and I, which I think is essential, but I, I feel like it's-

    6. SKDr. Scott Kanoski1:05:02

       And I'm guilt- I'm very, very much guilty of that, too. [laughs]

    7. AHAndrew Huberman1:05:04

       Well, and, and, uh, no, I think it's important work, but I feel like loss of function and sort of... well, gain of function-

    8. SKDr. Scott Kanoski1:05:10

       Yeah

    9. AHAndrew Huberman1:05:10

       ... is kind of a loaded term now, but it just means, like, things that push things in the, it potentially in the other direction.

    10. SKDr. Scott Kanoski1:05:15

        I think part, part of the problem with what you're getting at in the preclinical world is a standard rodent diet is very healthy, right? This is like 10 to 15% of calories from fat. The, the carbohydrate source is complex carbohydrates. So we're, we're kind of starting with a, a incredibly healthy baseline. That's not to say there's not more room for looking at certain extracts, supplementation, and whether they can have beneficial effects. But with the standard rodent diet, the animals are-

    11. AHAndrew Huberman1:05:45

        Hmm

    12. SKDr. Scott Kanoski1:05:45

        ... they're not showing memory impairments on that. Y- does that make sense?

    13. AHAndrew Huberman1:05:48

        Mm-hmm. Yep.

    14. SKDr. Scott Kanoski1:05:48

        It's sort of easier-

    15. AHAndrew Huberman1:05:49

        Yep

    16. SKDr. Scott Kanoski1:05:49

        ... to make something go wrong-

    17. AHAndrew Huberman1:05:51

        Yeah

    18. SKDr. Scott Kanoski1:05:51

        ... than to take an already healthy baseline and, and improve upon it.

    19. AHAndrew Huberman1:05:55

        Yeah. I mean, I think it's... I'm not going to blame science for this, but I feel like in some ways that's what led to this proliferation of, like, diet books and this is the way to m- you know-

    20. SKDr. Scott Kanoski1:06:04

        Yeah

    21. AHAndrew Huberman1:06:04

        ... make your brain healthy. This is the way... Because there was just, there was a lot of empty space for people to step in, and there didn't need to be any kind of formal structure that they had to obey.

    22. SKDr. Scott Kanoski1:06:15

        Yeah.

    23. AHAndrew Huberman1:06:15

        So in some sense it's like the landscape was perfect for that.

    24. SKDr. Scott Kanoski1:06:18

        Yeah, absolutely. L-

    25. AHAndrew Huberman1:06:19

        Yeah

    26. SKDr. Scott Kanoski1:06:19

        ... lacking a strong scientific lit- literature in this area, anything goes, right? It's-

    27. AHAndrew Huberman1:06:23

        Right. Right. 'Cause I think by now we all know what we shouldn't do.

    28. SKDr. Scott Kanoski1:06:27

        Yeah.

    29. AHAndrew Huberman1:06:27

        And we tr- and most Many people try not to. I, there's also, I've been reading about this, that with the, the advent of the GLPs, we're, we are entering perhaps the first time in nearly 75 years where we might start to see thiamine deficiencies and nutri- micronutrient deficiencies in a, like, fully modernized culture.

    30. SKDr. Scott Kanoski1:06:48

        Hm.
14. 1:11:33 – 1:12:54

    Sponsor: LMNT

    1. AHAndrew Huberman1:11:33

       I'd like to take a quick break and acknowledge one of our sponsors, LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means the electrolytes, sodium, magnesium, and potassium, all in the correct ratios, but no sugar. Proper hydration is critical for brain and body function. Even a slight degree of dehydration can diminish your cognitive and physical performance. It's also important that you get adequate electrolytes. The electrolytes, sodium, magnesium, and potassium, are vital for the functioning of all cells in your body, especially your neurons or your nerve cells. Drinking LMNT makes it very easy to ensure that you're getting adequate hydration and adequate electrolytes. My days tend to start really fast, meaning I have to jump right into work or right into exercise. So to make sure that I'm hydrated and I have sufficient electrolytes, when I first wake up in the morning, I drink 16 to 32 ounces of water with an LMNT packet dissolved in it. I also drink LMNT dissolved in water during any kind of physical exercise that I'm doing, especially on hot days when I'm sweating a lot and losing water and electrolytes. LMNT has a bunch of great-tasting flavors. In fact, I love them all. I love the watermelon, the raspberry, the citrus, and I really love the lemonade flavor. So if you'd like to try LMNT, you can go to drinklmnt.com/huberman to claim a free LMNT sample pack with any purchase. Again, that's drinklmnt.com/huberman to claim a free sample pack.

15. 1:12:54 – 1:21:05

    Vagus Nerve & Hippocampus, Eating & Acetylcholine

    1. AHAndrew Huberman1:12:54

       Let's say that, uh, you had a enormous vault of funds to do research on anything in this system, or any other system for that matter. Have you ever played that experiment, or it's just too painful to think about given today?

    2. SKDr. Scott Kanoski1:13:07

       It's, it's a little painful to think about.

    3. AHAndrew Huberman1:13:08

       All right. Well, well, if, if, um-

    4. SKDr. Scott Kanoski1:13:09

       Unless you're, unless you're offering the vault.

    5. AHAndrew Huberman1:13:11

       No, but if, if you could do any experiment here, like didn't have to write a grant to do it, and you felt like, what would that experiment be? Like, what, what do you think is really needed in this field to start to really connect the dots or that, or just that you think would be a fun, entertaining experiment? 'Cause let's face it, scientists like to do experiments also for fun.

    6. SKDr. Scott Kanoski1:13:32

       In many ways I'm lucky that we are doing some of those experiments now. Like the example I gave earlier with the, the vagus nerve stimulation device and this transgenic Alzheimer's model, it, that's what I want to be doing.

    7. AHAndrew Huberman1:13:43

       Mm-hmm.

    8. SKDr. Scott Kanoski1:13:43

       Is try to think about how, how the gut might be not just connected to the pathology, but potentially understanding that connection can lead to novel treatments that haven't really been considered or, or applied before. We are working on what I would like to be working on-

    9. AHAndrew Huberman1:13:59

       Mm-hmm

    10. SKDr. Scott Kanoski1:14:00

        ... which is in some ways it's a, a benefit of the, the NIH funding model, that you have flexibility in what you study. Of course, you, you put a proposal in and it's reviewed, and if you're lucky enough to get the funding, you're, you're doing a lot of what you intended to do. But you're, you're able to have a little bit of flexibility and, oh, we found this unexpected, uh, result, so we're going to go with this, this direction with it. Um, so yeah, I'm very fortunate to be doing what I want to be doing in, in the lab these days.

    11. AHAndrew Huberman1:14:29

        I'd like to know more about the nature of the signal from the vagus to the hippocampus.

    12. SKDr. Scott Kanoski1:14:34

        Mm-hmm.

    13. AHAndrew Huberman1:14:34

        I mean, these days most people who've heard of vagus think about it as a calming pathway. They've heard about humming or long exhale breathing, which is a different branch of the vagus.

    14. SKDr. Scott Kanoski1:14:41

        Yeah.

    15. AHAndrew Huberman1:14:42

        That's, that's all still true about calming the body, but my understanding is that the ascending, the from the body up to brain vagal connections are mostly, um, excitatory. They are mostly about creating more arousal in the brain, not more calm. And I think that confuses a lot of people, but my friends who do neurosurgery tell me that if a patient is, you know, maybe drifting under a bit, you can do vagal stimulation to make them more alert again. So clearly there, there's something there. So I'm curious what the nature of the signal from the gut to the brain is. Is it like we have food, we have nutrients, and that's sort of a bunch of gates. Like if you have enough fatty acids, enough protein, enough, um, glucose, then three gates have to be open, and then boom, there's a signal. 'Cause the, the gut-

    16. SKDr. Scott Kanoski1:15:30

        Yeah

    17. AHAndrew Huberman1:15:30

        ... the thing, even for neuroscientists, we tend to forget that the gut doesn't go, "Hey, we just ate this amazing lentil soup." It's just the lentil soup has an effect, and then electrical currents get sent up, and the signals in my mind are kind of crude. And so is it that then a bunch of excitation is released in the hippocampus, and now you can keep the neurons alive 'cause excitation is good for neurons?

    18. SKDr. Scott Kanoski1:15:52

        So the excitation-

    19. AHAndrew Huberman1:15:53

        Is that, like, kind of the picture?

    20. SKDr. Scott Kanoski1:15:54

        It's not one common signal, right? So there's, there's mechanoreceptors in the stomach-

    21. AHAndrew Huberman1:15:59

        Mm-hmm

    22. SKDr. Scott Kanoski1:15:59

        ... and they're picking up on distension of the stomach when, when food is in the stomach, and that, that's a vagal signal, but that's distinct from chemoreceptors in, in the intestines.

    23. AHAndrew Huberman1:16:09

        Mm-hmm.

    24. SKDr. Scott Kanoski1:16:09

        So you get this, um, sort of different timing of different signals as the meal is being... It's not as if there's just this unified electrical signal that's coming to the brain and, and these, um, the neurons of the vagus nerve and the nodose ganglia, they express different receptors.

    25. AHAndrew Huberman1:16:26

        Mm-hmm.

    26. SKDr. Scott Kanoski1:16:26

        They're very heterogeneous. It's, they're not all the same kind of neuron responding to the same thing.

    27. AHAndrew Huberman1:16:30

        Mm-hmm.

    28. SKDr. Scott Kanoski1:16:30

        We don't know a lot about, you know, what the signal is when it gets to the brain-

    29. AHAndrew Huberman1:16:34

        Mm-hmm

    30. SKDr. Scott Kanoski1:16:34

        ... stem, but we do know that there's, there's many different things that are contributing to that, that signaling pathway.
16. 1:21:05 – 1:27:21

    Hippocampus, Memory & Food; Interoceptive Awareness & Western Diet

    1. AHAndrew Huberman1:21:05

       How much is being done to really parse the, the character of the signal from the body to the brain? You know, the body-brain connection some years ago was considered really hippy-dippy.

    2. SKDr. Scott Kanoski1:21:16

       Yeah.

    3. AHAndrew Huberman1:21:16

       And now everyone talks about it, and the vagus is the superhighway champion of this body-brain thing. We talk about it in the context of breathing, meditation, trauma therapy, psychedelic therapies, learning-

    4. SKDr. Scott Kanoski1:21:30

       Mm-hmm

    5. AHAndrew Huberman1:21:30

       ... food, now food intake. And I get really excited when there's a repeating theme coming through on this podcast when I sit down with experts like yourself. And I, I'm wondering, especially as a person coming from the visual system, where we can describe, like, okay, when a human sees a bar of light at this orientation, of this intensity, we can trace the whole cascade now. That's a sensory system. This is a sensory system. Do we know what the nature of the signals are?

    6. SKDr. Scott Kanoski1:21:57

       But unlike the visual system, the interoceptive awareness is a very messy process. You know? It's, w- it's not a precise process. We, we can discriminate between I'm extremely hungry or I'm extremely full.

    7. AHAndrew Huberman1:22:11

       Mm-hmm. Um-

    8. SKDr. Scott Kanoski1:22:11

       But in between that, this is very much unlike the visual system. The, these sensory inputs coming in are... There's some neural, there's some endocrine. It's like a, a s- a symphony of chaos in some ways. I don't think we're ever gonna get to the precise level of, at least, maybe I shouldn't say ever, but in the near future, of really understanding the nature of that signal-

    9. AHAndrew Huberman1:22:33

       Mm-hmm

    10. SKDr. Scott Kanoski1:22:33

        ... um, the gestalt of that signal.

    11. AHAndrew Huberman1:22:35

        Mm-hmm.

    12. SKDr. Scott Kanoski1:22:36

        One thing I, I... Since I've been talking about the hippocampus a lot, it seems to be where this interoceptive awareness is being processed in the brain.

    13. AHAndrew Huberman1:22:44

        Hmm.

    14. SKDr. Scott Kanoski1:22:45

        So give you an e- example, if you take a, a human who's densely amnesic, who has damage to, uh, bilateral damage to the medial temporal lobe in- including the hippocampus, and these individuals have episodic memory impairments, so their, their memory span is, you know, b- between 10, 30, 40 seconds, depending upon the individual, and you have them eating food. They'll consume a meal. Uh, experimenter goes away, comes back with another meal. They'll eat the next meal. And this will happen even a third time. They don't remember eating the meal. But what's always fascinated me about this s- study and studies like this, uh, I think Paul Rozin did the first one, is that if you ask them to rate their hunger and satiety level, like, on a scale of zero to 10, they will be a seven out of 10 after eating three meals in a row. So of course they're getting this gut feedback to the brain. They're probably even feeling full, but they don't know how to interpret that signal. The hippocampus is needed to understand what that, that signal means. And there's analogous studies in rodents. Like, if you do a lesion to the hippocampus, a normal animal can learn that a high level of energy restriction is different from not being food restricted. Like, they can use that as a cue to predict something's about to happen, like a foot shock or a f- food pellet's coming. If you lesion the hippocampus, they, they can't do that. So it's, um, interoceptive agnosia. They seem to be unaware of what this interoceptive signaling means. Even if they're detecting it at the sensory level, it doesn't, doesn't mean what it's supposed to mean. Doesn't allow them to appropriately guide their behavior based on that, that signal or symphony of signals to do the appropriate action.

    15. AHAndrew Huberman1:24:32

        It seems that some people have so much interoceptive awareness, and other people do not.

    16. SKDr. Scott Kanoski1:24:39

        Yeah.

    17. AHAndrew Huberman1:24:39

        And I, I wonder how that relates to, uh, food intake. You know, we've hosted world-class choreographers on here and athletes-

    18. SKDr. Scott Kanoski1:24:47

        Yeah

    19. AHAndrew Huberman1:24:47

        ... and w- I always think of the people who move for a living as being really in tune with their body-

    20. SKDr. Scott Kanoski1:24:52

        Right

    21. AHAndrew Huberman1:24:52

        ... and obviously they are, but then there's the rest of the population where we're not really trained to think about-

    22. SKDr. Scott Kanoski1:24:59

        Mm-hmm

    23. AHAndrew Huberman1:24:59

        ... how our body feels in the context of daily living. We just kinda, like, live.

    24. SKDr. Scott Kanoski1:25:04

        When it comes to Interoceptive awareness of hunger versus fullness-

    25. AHAndrew Huberman1:25:09

        Mm-hmm

    26. SKDr. Scott Kanoski1:25:09

        ... that can be impaired with, with a high fat, high sugar diet as well. So that's, that's a, a process that is plastic and susceptible to what we eat.

    27. AHAndrew Huberman1:25:18

        I'm editorializing here again, but I feel like so much of the challenge in being a, or the task rather, of, um, being healthy, um, these days, especially in the United States, is trying to figure out, like, what the fundamental healthy baseline was or is, and trying to get to that. Because clearly processed foods, but also just the nature of life, like you even said earlier, like three meals a day for you, some people it's one meal a day. Like, th- they all can work, and that's great. That's also part of the challenge is people figuring out what works for them.

    28. SKDr. Scott Kanoski1:25:56

        Yeah.

    29. AHAndrew Huberman1:25:56

        And we don't really have, like, one system that our, our brain-body connection is optimized for or built for, and I'm guessing that's because we went through periods of feast and famine w- as we evolved. We need the system to be dynamic.

    30. SKDr. Scott Kanoski1:26:12

        Yeah, feast and famine, and also physical activity as it relates to our, our daily lives. So you and I are physically active, but here we are sitting down.
17. 1:27:21 – 1:34:00

    Omega-3s; Microbiome & Processed Foods

    1. AHAndrew Huberman1:27:21

       these are the issues that people really wonder about. Like, what should I eat to keep my memory? I guess the question what shouldn't I eat, what shouldn't I do is far easier to answer. But the omega-3 fatty acids seem to have a pretty decent literature.

    2. SKDr. Scott Kanoski1:27:36

       Yeah.

    3. AHAndrew Huberman1:27:36

       Uh, there's a woman, forgive me, I'm forgetting the name, uh, we'll put it in the show note caption, uh, who has a laboratory up at UC Santa Barbara who's looked at, um, supplementation with omega-3s during pregnancy and brain size and function-

    4. SKDr. Scott Kanoski1:27:48

       Mm-hmm

    5. AHAndrew Huberman1:27:48

       ... in, uh, human offspring. Um, it seems like the omega-3s, the polyphenols, enough protein, it seems like those are critical.

    6. SKDr. Scott Kanoski1:27:57

       Yeah, there's a few players that are established. You've, you've, you've hit on, on the main ones. Yeah.

    7. AHAndrew Huberman1:28:01

       What is your read of the omega-3 literature in terms of, uh, like if you g- have you done experiments where you give a- animals enhanced levels of omega-3?

    8. SKDr. Scott Kanoski1:28:09

       We have not done that.

    9. AHAndrew Huberman1:28:10

       Hmm.

    10. SKDr. Scott Kanoski1:28:10

        No. The, in my lab, w- we're focused more on what's, what's bad, you know, what, what's not-

    11. AHAndrew Huberman1:28:15

        Mm-hmm

    12. SKDr. Scott Kanoski1:28:15

        ... optimal for brain development, and the only interventions that we've done is either replace a bacterial population in the gut-

    13. AHAndrew Huberman1:28:24

        Mm-hmm

    14. SKDr. Scott Kanoski1:28:24

        ... or to just simply switch to a healthy diet.

    15. AHAndrew Huberman1:28:28

        Okay.

    16. SKDr. Scott Kanoski1:28:28

        So we, we... I'm aware of, of those studies, but we haven't-

    17. AHAndrew Huberman1:28:32

        Okay

    18. SKDr. Scott Kanoski1:28:32

        ... modeled that in, in our lab.

    19. AHAndrew Huberman1:28:34

        Tell me about the microbiome studies.

    20. SKDr. Scott Kanoski1:28:36

        Sure. Um, so we, we basically had... I'm not a microbiologist, so I just wanna lead with that. I'm a, my background is psychology, so I got into the microbiome, um, largely by accident and, and curiosity about 10 years ago. And we found that in this early life excessive sugar model that we were using in rats years ago, the microbiome was completely different. So if you do like a principal coordinate analysis and you kind of see the, the overall pattern of the bacterial population, the animals getting the sugar were just extremely different, and that could be for a lot of things. It could be from the sugar or it could be th- these animals are consuming a lot of their calories from the sugar, so they're getting less fiber and-

    21. AHAndrew Huberman1:29:19

        Mm-hmm

    22. SKDr. Scott Kanoski1:29:20

        ... and, and less, um, nutrients that are in the chow. That aside, there's definitely a, a change that's happening. And we looked at individual populations, can we correlate the abundance of this population with the animal's memory performance in one of these memory tests that I described earlier? And in one case, we had a population parabacteroides that was elevated in the sugar group, I think maybe twofold, enough that it was significant and noticeable, and it was negatively correlated with, uh, memory performance. So then we, in a separate study, we did an an- antibiotic treatment to kind of wipe out the bacterial population a little bit, not completely eliminate, and then in that state, we enriched this population into the gut, and the animals showed memory impairments even though they had never consumed sugar. So we were able to kind of replicate and, and in many cases, the memory impairments were more severe when we enriched this population.

    23. AHAndrew Huberman1:30:18

        Mm-hmm.

    24. SKDr. Scott Kanoski1:30:18

        But it was enriched maybe eightfold and-

    25. AHAndrew Huberman1:30:20

        Mm-hmm

    26. SKDr. Scott Kanoski1:30:21

        ... more than what you were getting from the sugar. So that's an example where we found a, a population that seemed to be, uh, negatively impacting the performance.

    27. AHAndrew Huberman1:30:30

        Mm-hmm.

    28. SKDr. Scott Kanoski1:30:31

        In the preprint paper that I mentioned earlier, where we have this heat-treated age-enriched diet model, we found another population. This one's lactococcus. It's a lactic acid-producing bacteria that was completely eliminated when we heat-treated the diet, and in this case, its performance was positively correlated with memory performance, and we were able to rescue the memory impairments by enriching that population.

    29. AHAndrew Huberman1:30:55

        Mm-hmm.

    30. SKDr. Scott Kanoski1:30:55

        So these are the kinds of things that we can do with, with microbiome studies. There's, of course, uh, fecal transplant. Um, we haven't done much of this, but a lot of people have in the field, where you, you just transplant the fecal and cecal content from one group of animals to another. And in that case, you can kind of replicate, um, some of the behaviors sim- simply by doing that. But in that case, you're changing everything. It's not just a, a single bacterial-
18. 1:34:00 – 1:37:23

    Microbiome, Antibiotics, C. diff Infection

    1. SKDr. Scott Kanoski1:34:00

       I think.

    2. AHAndrew Huberman1:34:00

       Yeah, the throwaway answer right now is diversity.

    3. SKDr. Scott Kanoski1:34:03

       Yeah.

    4. AHAndrew Huberman1:34:03

       It reminds me of, uh, the '90s. Uh, I'm old enough to remember. It was like exercise, and it was like, well, what kind of exercise? And people said, "Well, weight training isn't good because muscles will turn to fat after you stop. So you cardiovascular exercise." You say, what form? And now it's very nuanced. It's like some combination of high-intensity interval training, longer, slower training, resistor. Like, now we have answers because-

    5. SKDr. Scott Kanoski1:34:25

       Yeah

    6. AHAndrew Huberman1:34:25

       ... there's been 20-plus years or 30-plus years of really good studies and people attacking it seriously. I, I've got a family member who right now is taking a very high-dose, um, spectrum of antibiotics because they unfortunately had a, uh, a sepsis-type situation.

    7. SKDr. Scott Kanoski1:34:42

       Mm-hmm.

    8. AHAndrew Huberman1:34:42

       And they, they're very sharp in the mind ordinarily and they were saying, um, they're really struggling to think, like really struggling to think.

    9. SKDr. Scott Kanoski1:34:50

       Yeah.

    10. AHAndrew Huberman1:34:50

        And so they're trying to repopulate their gut bacteria with, uh, you know, the... I'm a big proponent based on Sonnenburg's work of low-sugar fermented food, so sauerkraut, kimchi-

    11. SKDr. Scott Kanoski1:34:59

        Mm-hmm

    12. AHAndrew Huberman1:34:59

        ... kefir, you know, all these incredible foods that we know really support the gut microbiome. And so they're doing that and feeling better but of course they're destroying their gut microbiome intentionally every day at the same time. And I said, "If you can just get through this period-

    13. SKDr. Scott Kanoski1:35:13

        Yeah

    14. AHAndrew Huberman1:35:13

        ... defeat the infection, you're gonna experience such a robust return, but it's a slow system." Like this isn't the kind of thing where you take a pill and you feel better. The, the gut microbacteria take, as my understanding is it can take weeks or months to really build up a, quote-unquote, "healthy gut microbiome." It's not something you just do overnight or with one meal.

    15. SKDr. Scott Kanoski1:35:30

        No, it's not, and it's very plastic, dynamic system. Like it... Wi- with some exceptions there's, um, have you heard of C- C. diff?

    16. AHAndrew Huberman1:35:38

        No.

    17. SKDr. Scott Kanoski1:35:38

        So this is a, a, like a intestinal issue where generally from people in a hospital who are taking antibiotics. Antibiotics deplete bacteria, and they'll deplete good and ba- bad bacteria. And with C. diff, there's bacteria that normally keep this C. diff in check, and with C. diff there's, um, a lot of this bacteria which leads to, um, sort of violent GI distress and can even lead to death. And there's an FDA-approved fecal transplant procedure for this specific syndrome. So, um, and it... I believe it's, it's typically with a single transplant-

    18. AHAndrew Huberman1:36:16

        Amazing

    19. SKDr. Scott Kanoski1:36:17

        ... is enough to c- correct this in, in a high percentage of individuals. Um-

    20. AHAndrew Huberman1:36:21

        Amazing

    21. SKDr. Scott Kanoski1:36:21

        ... so there, there, you know, there's a bright future for this.

    22. AHAndrew Huberman1:36:23

        Mm-hmm.

    23. SKDr. Scott Kanoski1:36:24

        I don't think we're there yet. I mean, to my knowledge that's the only FDA-approved.

    24. AHAndrew Huberman1:36:27

        Mm-hmm.

    25. SKDr. Scott Kanoski1:36:28

        There could be others, but that's the only one I'm aware of, fecal transplant or targeted bacterial treatment. Um, but I think it's just such a new field of research. We're, we're definitely in the baby stages of understanding this complex relationship.

    26. AHAndrew Huberman1:36:42

        Mm-hmm. I was a little bit dismayed when I heard early on that your ideal gut microbiome is really esta- the upper threshold of that is established in the first three years of life and I thought-

    27. SKDr. Scott Kanoski1:36:52

        Yeah

    28. AHAndrew Huberman1:36:52

        ... there's no way my parents got this exactly right.

    29. SKDr. Scott Kanoski1:36:54

        [laughs]

    30. AHAndrew Huberman1:36:55

        But then we learned that it's a little bit like the way learning and neuroplasticity was discussed. It used to be considered that, okay, up until your teens, early 20s, that was the opportunity for wiring the brain a particular way and then it's locked in, and we know that that's not True at all
19. 1:37:23 – 1:39:01

    Sponsor: Function

    1. AHAndrew Huberman1:37:23

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20. 1:39:01 – 1:43:39

    Foods to Enhance Microbiome; Rising Obesity & Highly Processed Food

    1. AHAndrew Huberman1:39:01

       Yeah, I, I now think about the gut so differently than I did even a couple of years ago based on conversations like this. Like, there's the vagal pathways, which we don't know the time scales they work on, but they can be relatively fast, and then there's the gut microbiome. I, I think about the gut, like, gut health as, and its relationship to general health, including brain health, as I need to give my gut mi- microbacteria the things they need so that they can create the things that my brain and body need. So it's just like raw materials.

    2. SKDr. Scott Kanoski1:39:32

       Mm-hmm.

    3. AHAndrew Huberman1:39:33

       Short-chain fatty acids-

    4. SKDr. Scott Kanoski1:39:34

       Yeah

    5. AHAndrew Huberman1:39:34

       ... leading to neurotransmitter-

    6. SKDr. Scott Kanoski1:39:35

       Butyrate

    7. AHAndrew Huberman1:39:35

       ... neuro- neuromodulator production like serotonin. I just need to give them what they need. And no, this isn't a, a, a, you know, a product endorsement because my observation is that it comes mainly from these low-sugar fermented foods, getting enough fiber, um, and not s- stressing too much, 'cause stress can also impair the gut microbiome [chuckles] and then getting enough sleep. And so maybe at the end of the day, it really is all about supporting the gut microbiome. Guessing there are other things, too. It seems that important. And I think I'm w- it's only really sinking in for me just how important it is. And as a child of the, born in '75, like, the '90s were just terrible for this. It was, like, low fat. I guess there was some emphasis on fiber.

    8. SKDr. Scott Kanoski1:40:15

       I lived through that period as well, yeah.

    9. AHAndrew Huberman1:40:17

       Yeah. It was, uh, it was the advent of margarines and the-

    10. SKDr. Scott Kanoski1:40:19

        Yeah

    11. AHAndrew Huberman1:40:19

        ... processed foods really came in.

    12. SKDr. Scott Kanoski1:40:21

        Olestra, the, the fat substitute.

    13. AHAndrew Huberman1:40:22

        Oh, yeah. Fortunately, I never, never had an Olestra chip.

    14. SKDr. Scott Kanoski1:40:25

        Yeah.

    15. AHAndrew Huberman1:40:25

        I wasn't interested in the, the, uh, the leakage.

    16. SKDr. Scott Kanoski1:40:29

        [laughs]

    17. AHAndrew Huberman1:40:29

        Yeah. That's it. That was enough of a barrier. Um, we'll move to reinforcement in a moment, but you reminded me of the '90s when the, the fen-phen, uh, drugs were released, uh, fenfluramine. These were supposed to be blockbuster drugs, kind of like the GLPs, but they were basically stimulants, right?

    18. SKDr. Scott Kanoski1:40:48

        Yeah.

    19. AHAndrew Huberman1:40:48

        And then people started having heart attacks. Is that what, is that what happened?

    20. SKDr. Scott Kanoski1:40:50

        Sympathomimetics. Yeah, there were some cardiovascular outcomes that, uh, were unwanted and-

    21. AHAndrew Huberman1:40:55

        Mm-hmm

    22. SKDr. Scott Kanoski1:40:55

        ... d- led to the discontinuation of that. And then the, uh, the obesity drug market was dormant for many, many years-

    23. AHAndrew Huberman1:41:01

        Okay

    24. SKDr. Scott Kanoski1:41:01

        ... until around 2010 and beyond when we, um, it wasn't just GLP-1 drugs. There was a few other ones that have kinda fallen out of favor because the GLP-1 drugs are the most effective. But yeah, there was a, a period of time and probably largely due to the fen-phen-

    25. AHAndrew Huberman1:41:17

        Mm-hmm

    26. SKDr. Scott Kanoski1:41:17

        ... issue where pharmaceutical companies were not interested in developing obesity drugs.

    27. AHAndrew Huberman1:41:23

        Mm-hmm.

    28. SKDr. Scott Kanoski1:41:23

        But at this point, 40, over 40% of US adults are obese. It's hard to-

    29. AHAndrew Huberman1:41:29

        Over 40%?

    30. SKDr. Scott Kanoski1:41:29

        Over 40%.
21. 1:43:39 – 1:49:50

    Dopamine & Food Choice, Change Food Cravings

    1. AHAndrew Huberman1:43:39

       all right. Re-in- I've alluded to it so many times now, it almost seems like a, like I'm teasing, but here we are, reward reinforcement, uh, enticement. Most people are familiar with the word dopamine. They think of it as pleasure. Most people, thanks to Anna Lembke's book, Dopamine Nation, now, and the book The Molecule of More, uh, which is also excellent, I, um, in my opinion, that dopamine is about craving, wanting, motivation-

    2. SKDr. Scott Kanoski1:44:02

       Mm-hmm

    3. AHAndrew Huberman1:44:03

       ... um, at least as much and probably more than it is about pleasure.

    4. SKDr. Scott Kanoski1:44:08

       That's true. Yeah.

    5. AHAndrew Huberman1:44:09

       So in the context of food and food intake and nutrient intake and memory, uh, what is the role of the reinforcement pathway, um, what you and I call the mesolimbic reward pathway?

    6. SKDr. Scott Kanoski1:44:22

       This system, which it, it, the most basic description of it would be a, a mid, mid-brain ventral tegmental area-

    7. AHAndrew Huberman1:44:29

       Okay

    8. SKDr. Scott Kanoski1:44:29

       ... to the nucleus accumbens. That's kind of the, the classic mesostriatal dopamine projection.

    9. AHAndrew Huberman1:44:35

       Okay.

    10. SKDr. Scott Kanoski1:44:35

        And this system is engaged by palatable foods, so like liquid sucrose, um, a high-fat sucrose combination. But there's a little bit more to it than that. So you can get the system engaged by a bland-tasting healthy food when an animal is food restricted, or you can get the, the system engaged by, by water when an animal is water restricted, or, um, even a sodium-deplete animal will show a, a dopamine release in this pathway to, to sodium consumption. So it's, it's n- it's very much dependent upon the, the animal's state.

    11. AHAndrew Huberman1:45:15

        Mm-hmm.

    12. SKDr. Scott Kanoski1:45:15

        That said, palatable foods tend to tickle that pathway more so than what we consider to be more healthy and, and bland foods.

    13. AHAndrew Huberman1:45:24

        Okay.

    14. SKDr. Scott Kanoski1:45:25

        And then of course, um, substances of abuse tap into the same system, um, albeit to a different degree, but it, it's definitely a common brain currency for, for things that we enjoy.

    15. AHAndrew Huberman1:45:38

        So when I hear you say that if we are food restricted or we just haven't... we're very hungry, doesn't have to be s- fasting, that, um, bland foods can activate the dopamine reward pathway.

    16. SKDr. Scott Kanoski1:45:50

        Yeah.

    17. AHAndrew Huberman1:45:50

        A reinforcement pathway. Excuse me. I'm trying to be more careful with my language.

    18. SKDr. Scott Kanoski1:45:54

        [laughs]

    19. AHAndrew Huberman1:45:54

        I wonder whether eating highly palatable foods or, or even just sweet foods changes our threshold for what we consider reinforcing and, and, and rewarding. I try to eat healthy, and I notice that I really love and crave blueberries and-

    20. SKDr. Scott Kanoski1:46:12

        Mm-hmm

    21. AHAndrew Huberman1:46:13

        ... uh, I keep mentioning them, but the, and other foods, but if I eat healthy foods and I like the way they taste, I find that I crave those foods. And I don't-

    22. SKDr. Scott Kanoski1:46:21

        Yeah

    23. AHAndrew Huberman1:46:21

        ... tend to crave other f- foods, presumably because I'm sated. I'm not, I'm not excessively hungry. But is there a way that we can recalibrate the system? It seems there is. You know?

    24. SKDr. Scott Kanoski1:46:31

        I think so. I mean, the examples you're saying make, make a lot of sense in, in individuals who consume a lot of sugar, who stop consuming it or, or consume much less, they, they change their preference. You know, something that they normally would have enjoyed is now too sweet.

    25. AHAndrew Huberman1:46:45

        Mm-hmm.

    26. SKDr. Scott Kanoski1:46:45

        So there's a lot of plasticity in terms of what we want to eat.

    27. AHAndrew Huberman1:46:50

        Mm-hmm.

    28. SKDr. Scott Kanoski1:46:51

        And that's based largely on what, what we choose to eat. We can, we can, we can change that, as you've described. Like you probably weren't craving blueberries when you were 12, maybe.

    29. AHAndrew Huberman1:47:02

        I mean, I've always liked fruit, but I liked other stuff too, and I... it's not like I actively avoid ice creams and things like that. But I, but I feel like it's different with food than it is with other reinforcing substances, because if somebody who really craves alcohol, who really craves stimulants, is deprived of those and then gets a small amount of it, I don't know that they say, "Oh, that just... I didn't like that experience." Usually it's like they really like that experience.

    30. SKDr. Scott Kanoski1:47:29

        Yeah.
22. 1:49:50 – 1:56:43

    Food Addiction, Highly Processed Foods; Political Lobbying

    1. AHAndrew Huberman1:49:50

       Humans have tried to use the aversion approach to learning, basically giving people things that make them feel sick or electrically shocking them to try and rewire-

    2. SKDr. Scott Kanoski1:49:59

       Yeah

    3. AHAndrew Huberman1:50:00

       ... everything from, uh, and these are n- not ethical studies, but people in the, in the old days, in like the '60s and '70s, they tried to use this to, like conversion therapy.

    4. SKDr. Scott Kanoski1:50:09

       Yeah. Right.

    5. AHAndrew Huberman1:50:10

       Like for s- for, uh, sexual orientation. Obviously terrible. Um, and fortunately, that's illegal, uh, now. But the, but I'm not aware of any like really good studies showing that people will quit smoking if they're like electrically shocked when they pick up a cigarette. My, my understanding of these studies, maybe this is [laughs] not true, but I, I was told by somebody who worked in this general area that people, uh, basically just figure out how to endure the shock. Like, that's how rewarding-

    6. SKDr. Scott Kanoski1:50:37

       Yeah. [laughs]

    7. AHAndrew Huberman1:50:37

       ... nicotine is. And it... I, I wonder if there's something going on with the processed food, um, aspect too because I don't know that people really enjoy those foods. I feel like there is... When we hear that they're addictive, I don't know that that's the proper word, but they are impairing people's health. But there seems to be this thing where people get into this kind of like, it's not pleasure, it's not anhedonia, but it's this kind of like min- I, I don't want to say mindless, but there's, there's some no man's land of eating and consuming, not getting the thing they're looking for. That looks a lot like addiction.

    8. SKDr. Scott Kanoski1:51:16

       Yeah.

    9. AHAndrew Huberman1:51:16

       That looks like chronic drug use. But it's not like they're getting high off the food.

    10. SKDr. Scott Kanoski1:51:21

        Yeah. I mean, it's, it's tricky making the, the comparisons because, yeah, there's a common currency in the brain for substance abuse and, and palatable foods, but you have to eat every day, you know?

    11. AHAndrew Huberman1:51:33

        Mm-hmm.

    12. SKDr. Scott Kanoski1:51:33

        Like, this isn't, it's not a, a choice. Like you-

    13. AHAndrew Huberman1:51:35

        Mm-hmm

    14. SKDr. Scott Kanoski1:51:36

        And there's a lot of controversy in, in whether there can be an addiction to food, and I'm not really going to take a side on either, uh, either side of that one. But if you look at the, the DSM criteria-

    15. AHAndrew Huberman1:51:49

        Mm-hmm

    16. SKDr. Scott Kanoski1:51:49

        ... for substance abuse or addiction, you can make an argument that there is food addiction based on those criterion.

    17. AHAndrew Huberman1:51:56

        Mm-hmm.

    18. SKDr. Scott Kanoski1:51:56

        But that doesn't mean that the, it's the same thing.

    19. AHAndrew Huberman1:51:58

        Yeah, continued use-

    20. SKDr. Scott Kanoski1:51:59

        Right. Exactly

    21. AHAndrew Huberman1:51:59

        ... uh, continued harm to self or others.

    22. SKDr. Scott Kanoski1:52:01

        Yeah. Yeah.

    23. AHAndrew Huberman1:52:01

        Um, yeah. Inability to stop despite, despite desire to s- these kinds of things. Late last year, there was a really interesting set of videos that were authenticated. The discussion was should, um, food stamps be u- uh, allowed to be used to, uh, purchase soda. And someone from the, um, American Heart Association was asked on this panel, "What do you think? Do you think soda is healthy?" And they, and they did this incredible but really dismaying, in my, in my opinion, tap dance around, "Well, you know, in the context of this and then this."

    24. SKDr. Scott Kanoski1:52:36

        Yeah.

    25. AHAndrew Huberman1:52:36

        And they, I mean, they, they did everything they could to avoid answering the question, basically.

    26. SKDr. Scott Kanoski1:52:40

        The sugar lobby's very powerful.

    27. AHAndrew Huberman1:52:41

        Yeah. So-

    28. SKDr. Scott Kanoski1:52:42

        Or has been historically

    29. AHAndrew Huberman1:52:43

        ... are these health associations, like the American Heart Association, are they really like in bed with the sugar lobby? To me, that seems a little bit like a-

    30. SKDr. Scott Kanoski1:52:50

        Mm-hmm
23. 1:56:43 – 2:00:11

    Oxytocin, Reduced Food Consumption, Social Eating

    1. AHAndrew Huberman1:56:43

       Uh, before we wrap, I do have a, a question about oxytocin.

    2. SKDr. Scott Kanoski1:56:48

       Yeah.

    3. AHAndrew Huberman1:56:48

       Most of us think of oxytocin as the love-

    4. SKDr. Scott Kanoski1:56:52

       Lovey-dovey

    5. AHAndrew Huberman1:56:52

       ... lovey-dovey, um, hormone neuromodulator. Educate us on the role of oxytocin in the context of food intake and nutrition.

    6. SKDr. Scott Kanoski1:57:02

       It's been known for quite some time that, that oxytocin can reduce appetite and food intake. And through careful studies from, uh, Harvey Grill and others, we have identified the brainstem as being the, the most robust target of oxytocin signaling to reduce food intake.

    7. AHAndrew Huberman1:57:21

       Mm-hmm.

    8. SKDr. Scott Kanoski1:57:21

       Um, so oxytocin is, uh, released or created in the PVH, in the hypothalamus, released into the circulation, but also there's projections from oxytocin producing neurons throughout the brain, and some of those neurons project to, directly to the brainstem.

    9. AHAndrew Huberman1:57:36

       Mm-hmm.

    10. SKDr. Scott Kanoski1:57:36

        And that system seems to be an important system for reducing food intake-

    11. AHAndrew Huberman1:57:41

        Mm-hmm

    12. SKDr. Scott Kanoski1:57:41

        ... mainly through the level of meal size-

    13. AHAndrew Huberman1:57:44

        Mm-hmm

    14. SKDr. Scott Kanoski1:57:44

        ... making meal s- size smaller.

    15. AHAndrew Huberman1:57:45

        Mm-hmm.

    16. SKDr. Scott Kanoski1:57:46

        Increasing satiation. We had a, a study recently where we were looking at its role in the hippocampus. And in this case we found some results that were a little bit surprising, I should say. Um, there's a phenomenon in, in hu- humans that rodents also show. It's called the social facilitation of eating. So if you and I are-- if you're eating alone, you might eat less than if you're eating with a group of people. And if those people are familiar to you, you're going to eat more than if they were unfamiliar. So that's kind of the, the, um, the gist of the phenomenon. And we can model this in rodents, and we found that that phenomenon requires oxytocin signaling in the hippocampus. So if you genetically turn down the signal, um, the animals don't show that effect.

    17. AHAndrew Huberman1:58:34

        Hmm.

    18. SKDr. Scott Kanoski1:58:34

        So this is kind of a different role for oxytocin because under these conditions in this brain region, it's actually promoting intake-

    19. AHAndrew Huberman1:58:41

        Mm-hmm

    20. SKDr. Scott Kanoski1:58:41

        ... in a social context.

    21. AHAndrew Huberman1:58:42

        Mm-hmm.

    22. SKDr. Scott Kanoski1:58:43

        So I think it's, it's really complicated like most things in the brain are. Um, but historically the, it's been a uni- unidirectional, uh, that oxytocin in the brain reduces food intake. Um, but some of recent findings from our lab and others are saying, "Well, maybe, yeah, but it might depend on the, the social context, for example, and where the signal's getting to."

    23. AHAndrew Huberman1:59:05

        Well, Scott, thank you so much for coming and sharing your mechanistic data. I l- love that you're highly mechanistic. Offline I want to know the, the literal organization of these, uh, cholinergic afferents to the hippocampus 'cause I think that's more of a aficionado question. But it's clear that you're studying a really, really important system, uh, for the health of all humans, and especially right now with the highly processed food thing, but also the GLPs and also the, this explosion of discoveries on the microbiome and the positive explosion of people that are interested in doing what they can for their brain and bodily health. You're, you're clear- clearly in the right area, evidenced by the fact that I said if you had a vault what, uh, of money, what would you study? And you're like, "What I'm doing right now."

    24. SKDr. Scott Kanoski1:59:49

        Yeah. [laughs]

    25. AHAndrew Huberman1:59:49

        So you're clearly in, uh, in the right, um, laboratory, which you run.

    26. SKDr. Scott Kanoski1:59:54

        Yeah.

    27. AHAndrew Huberman1:59:54

        So thank you. Thank you for doing the work that you do, and it's not lost on me, and it shouldn't be lost on the audience that you do that work with taxpayer dollars, so you're working on our behalf for our health. So, and you're very busy. So thanks for coming here today. Appreciate you.

    28. SKDr. Scott Kanoski2:00:06

        Thank you very much. Appreciate it. It's been fun.

    29. AHAndrew Huberman2:00:08

        Great. Next time bring your dog.

    30. SKDr. Scott Kanoski2:00:09

        I will.
24. 2:00:11 – 2:02:06

    Zero-Cost Support, YouTube, Spotify & Apple Follow, Reviews & Feedback, Sponsors, Social Media, Neural Network Newsletter

    1. AHAndrew Huberman2:00:11

       Thank you for joining me for today's discussion with Dr. Scott Kanoski. To learn more about his work, please see the links in the show note caption. If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review, and you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. And if you're not already following me on social media, I am hubermanlab on all social media platforms. So that's Instagram, X, Threads, Facebook, and LinkedIn. And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the information on the Huberman Lab podcast. Again, it's hubermanlab on all social media platforms. And if you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a zero-cost monthly newsletter that includes podcast summaries as well as what we call protocols in the form of one to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You simply go to hubermanlab.com, go to the Menu tab in the top right corner, scroll down to Newsletter, and enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Scott Kanoski. And last but certainly not least, thank you for your interest in science. [outro music]

Episode duration: 2:02:06