GLP-1 Drugs & Bariatric Surgery Explained by a Top Obesity Researcher | Dr. David Allison

24:47So you assign a whole school at once and you might have 10 schools, let's say. And it turns out that the statistics needed to analyze those are very different than the statistics needed to analyze when you individually randomize. And they, those cluster randomized trials, if analyzed correctly, have much lower statistical power than all other things being equal and individually randomized study. And so people, the investigators often don't like that because less statistical power means less chance of saying, eureka, I found something. And so often they analyze them without taking, without the correct analysis, without taking the clustering into account.

25:30We, my group and I tend to spot those often, but not always. And then we try to get them corrected if they need to be. And we've, as a result, we've had several papers corrected, several retracted, meaning the editors have said, this paper is not valid. We need to take it out. When you think about that and you look at the evidence, not for clinical treatment, but for community-based treatment, schools, communities, these kinds of things, for childhood obesity treatment or prevention with things like mild physical activity or nutrition education in schools, examples like that. Many of them that are purported to be successful, even when you look at evidence and somebody summarizes it, most of the time they come up when you summarize all the studies as essentially no effect.

26:23A few of the meta-analyses say small effect. Very small, but small. Now, what if I said, let's take those meta-analyses that combine many studies, say very small effect on average, and I said X percent of the studies in there are completely invalid. that purported to show an effect did it, remove those, or erase the data and write the correct data in, would even very small become zero. And so these are examples of where I think we've misled the public. We have and continue to misspend funds on methods that don't work, when we could be investing it either in research to find methods that do or in some methods we have that do.

27:11We mislead the public, and that's unfair, give false hope. We distract from doing things that might work. So I think these are pretty serious problems. I think they're pretty serious breaches in, at best, competence and, at worst, integrity among some researchers.

27:30Dr. Gabrielle Lyon:And I was looking at some data. The amount, so I did my fellowship at WashU and I finished that 2015. AI, I did it in Sam Klein's lab. Do you know Sam Klein? Of course. And I did a combination of geriatrics and nutritional sciences. We were not, AI wasn't there. I'd have to go to the library and, you know, maybe I was looking at PubMed. There was not the volume of information and papers that are coming out that are now being written by AI. And what do I mean by that? I was looking at the – so let's say there is a claim that's made, and maybe it's based on epidemiology. Those that eat red meat are more likely to have colon cancer or cancer or higher mortality.

28:20Dr. Gabrielle Lyon:and let's just say and then there are multiple studies epidemiology or however they make it that now uh curate this knowledge maybe it's from nhanes or some large data set and now instead of investigators writing and analyzing the data it's all done through ai and the amount and the volume of now low-quality studies seems to dilute good science, but also it's almost as if it's advertising. It's like scientific advertising. Yes. I've often felt that the field, many fields, but especially the field of nutrition epidemiology is often research, and I'm intentionally using the word research and not science, research as idea advertisement.

29:13And by that I mean the researcher has an idea. They think it's a good idea or an idea they want other people to believe or pay attention to. And a way of getting people to believe it or pay attention to it is to put some data out that seem to support it. And so a study is done not for the purpose of learning something, which might make it science, but it's done for the purpose of reinforcing beliefs. And so there might be some real research. They may have really collected data, but it's not data collected with the idea of advancing knowledge. It's just to reinforce an existing belief.

29:55Dr. Gabrielle Lyon:Are you seeing that? I was just trying to pull up the, again, I don't have my phone on me, But I was just looking at it was almost, I don't know, in this small timeframe, it was like 4 ,000 new studies coming out on this one topic, which again, it's not, are you seeing that people are using AI to put out junk research? And then if you wanted to create a narrative and you want to be really smart about creating a narrative, you can cherry pick any of these studies and say, oh, but but look, this is this proves that. And then it further dilutes the the scientific integrity. So something else really interesting.

30:35Dr. Gabrielle Lyon:Science versus trust. Do we need to trust? People will say, well, just trust the science. Do we need to trust the science? No, not because one shouldn't. Well, no, because science is fundamentally not about trust at a deep level. The very idea of science is that it gets its privileged role in talking about the state of the world by collecting data and the methods by which data are collected and the logic connecting those data and methods to conclusions. That's it. Science is the data, the methods used to collect the data, which give them their probative value, and the logic connecting the data and methods to conclusions.

31:24Anything else is not science. In order to be a meaningful assessment of science, one needs to look at the data and look at the methods and think about them and sometimes debate them and ask questions about them. And the same thing for the logic. And that's not trust. Right. So if you say to me, David, I just did this study and I found that eating this causes that. It's not that I don't like you or don't trust you or, you know, don't trust you as a person, but I'm going to ask some questions. What dose did you use? How did you administer it? How long did you study these people for? How did you measure the outcome?

32:00And you could be perfectly wonderful, smart person of great integrity. and I say, you know, the way you did that, Gabrielle, you destroyed the nutrient because you heated the thing and you didn't know that. And so I don't think your result is valid. That doesn't mean I'll trust you as a person, but I don't put my trust in the science. I put my trust in the methods. So we need to go through the methods. There's a narrative now at a more social level that we have an anti-science movement in this country, maybe the world, and that trust in science is way down. Neither of those things are true as far as I can tell.

32:43And my colleagues and I have written papers about this. Trust in science is down a little bit in this country, but not a lot. Trust in some things, Congress, the media, way, way down.

32:56Dr. Gabrielle Lyon:science relatively steady military relatively steady um nurses that's good people like nurses they trust nurses um what it seems to be is not a distrust in science or an anti-science movement pick your whoever you think gives the craziest information about health and so on and usually they talk about molecules and substances. They might even mention something about data and evidence. So it's not that they're not talking about science. They're not saying, demons told me this, and that's why I believe this. But you and I might look at it and say, but that's erroneous science or weak science or bad science or pseudoscience or something or non-science that you think is science.

33:47The trust issue is not trust in science as a process. The trust issue is trust in individual communicators of purported scientific information or trust in particular studies or facts. If you ask me, do I trust science as a process? Absolutely. I mean, that's totally who I am. I think that's the best and only really veridical way of obtaining knowledge about the objective world. But if you said to me, do you trust a lot of the science that comes out around dietary supplements? No. If you said to me, do you trust a lot of the science that comes out of academic researchers looking at intervention effects on obesity in children.

34:41No. I trust science, but I don't trust those studies because I don't think they're done very well. You said to me, do you trust the results on pharmaceuticals in the last 20 years, not going back more than 20, in the last 20 years that are registered, randomized controlled trials funded and conducted by pharmaceutical companies and submitted to the FDA. Yes. I think those are some of those rigorous studies in the world.

35:12Dr. Gabrielle Lyon:People have that wrong. There is this false perception. And one of the reasons I wanted to have you on was specifically to address this is that we are now in a new landscape.

35:25Dr. Gabrielle Lyon:As a career scientist, you've had to evolve to ask these questions. It's a new landscape with AI, social media, the velocity at which information spreads. I would say both good and bad, but it seems like it skews mostly overblown and large claims are made on low quality studies that then impact populations. Would you say that that's accurate? Yes, I would. Thank you to Timeline for sponsoring this episode. If you're a frequent listener to the show, you know I believe that muscle is the organ of longevity. It regulates metabolism, protects independence, and supports long-term health. But muscle health, surprisingly, isn't just about protein and resistance training.

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37:00Dr. Gabrielle Lyon:If muscle is the organ of longevity, supporting the engine inside that muscle matters. Go to timeline.com slash Dr. Lyon to get 35 % off a MitoPure subscription. And so you've really stepped in to say, okay, well, like for example, what's the evidence if we're told to drink eight glasses of water? Yet I've heard that, you've heard it, and we continue to repeat it. I tell my kids to do that. But there is, Is there evidence for that? There is not, to my knowledge, evidence for that particular one. I think what often happens, and again, sometimes it's very innocent, is there are layers, you might say, of digging as a scientist or as an individual who respects science, even if one is not in the moment a scientist.

37:54So I think any of us can be scientists at times and not be scientists at other times, regardless of whether you're employed as a scientist. I look at myself as an example. If you said to me, do you think that this particular medicine you take, David, is safe and effective? Well, let's just say effective.

38:13Dr. Gabrielle Lyon:We'll put safe aside for the moment. I would say, yes. So what's your basis for that? Is it scientific? I'd say, well, sort of. You know, if you said to me, have you actually pulled up all the raw data on that drug and examined it yourself? No. So why do you trust? Why do you think that that's important? Well, because the FDA said so. Well, so you mean you trust the FDA? Yes. Why do I trust the FDA and why do I not trust maybe somebody else? I trust the FDA because I know how they evaluate drugs. and they evaluate drugs in a very rigorous scientific way. Who knows what the future holds, but at least up until recently, I was like, I trust the FDA because I understand their processes.

39:06And so there is some trust that they execute their process as I believe they execute their process. But assuming that, then that's there. But another level is, have I looked at it myself? Yet one up from, I trust the uptakes, I know their processes. Well, I've heard this from lots of mainstream experts. For everyday life, that's probably a good signal. I said, do I really know it? No.

39:33Dr. Gabrielle Lyon:And is it? Because there's a lot of regurgitation of information that is not accurate. That's the grandfathering in. And that's where we have to go back and dig periodically. I caught myself in one of these very recently where, you know, listening to many podcasters who talk about growing muscle and reading some things, but reading at the mountaintops, though, is not going back to every original paper, but reading sort of summaries, listening to summaries. I would say things like, well, the most important thing is how much resistance training you do in the volume. and then the second, you know, might be how much calories and a third might be how much protein and then somewhere down below that is, you know, very important but probably a little more of sleep.

40:17And I stopped myself a few days ago and I said, what do you really know about sleep? How much sleep is needed? How big is the effect? So I do a little search. There's almost no randomized controlled trials randomly assigning people to different amounts or types of sleep while undergoing resistance training and looking at the causal effects on skeletal muscle strength, quality, or hypertrophy. That doesn't mean sleep's not important. It just means, oh, I guess I don't know.

41:01Dr. Gabrielle Lyon:And it's a really good point. Are there things, again, obviously you read all the time, and I would encourage everyone to sign up for Obesity and Energetics, which I've been getting for years. It's a newsletter. It's so well curated, really extraordinary. So we'll put a link to that and send that out. Completely free. Yes, it's amazing. You're good to go. It's amazing. Basically, it'll have headlines, null findings, scientific, you know, randomized control trials. It'll have all, it's just so well done. And, you know, as you think about the landscape, are there things where you have been pleasantly surprised?

41:36Dr. Gabrielle Lyon:So as we think about, like, say, obesity, where you hear this medication works and this is the outcome, are there trends or statements that you're like, OK, I think one, two and three are really, really good and they're on to something, where as opposed to drink more water, sleep more and I don't know, meditate in the sunlight, these are out. Yeah. The most obvious ones are the advances we've had in medical treatments in the last 20 years. And so it's the rise of bariatric surgery and the refinement of it and the recognition of its effects. I was not expecting that, the bariatric surgery, because now with the GLP ones.

42:17Well, and then subsequently, the strong pharmaceuticals, which I think many people, including me, feel will likely won't eliminate bariatric surgery, but will likely radically mitigate its use. Because what we've got is a treatment that's, or treatments that at least at present, even if they're not quite as powerful as bariatric surgery, they're getting close. and you can turn them off, right? You can't say tomorrow, you know, I don't, after all, I don't think I like this bariatric surgery so much. Switch it off. It doesn't work that way, right? But you could say, I don't like taking this drug.

43:00I'm going to stop tomorrow. So I think that we've got some tremendous growth there. I remember when leptin was first discovered, 1994, I think. and very shortly thereafter, one of the group, I think it was the Cambridge group, came out with a paper showing treatment of, I forget if it was just one member of the family or a subset of a family who had very, very rare homozygous inactivating mutations for leptin production. And they gave them exogenous leptin and great things happened clinically. And I was so envious of them, of the research group. Not because they got the paper in nature.

43:52Dr. Gabrielle Lyon:I mean, everyone wants their paper in nature. That was true. But because they were probably the first people in history to be able to honestly look a patient with obesity in the eye and say, I know why you're obese. And this was the leptin resistance hypothesis? This was the inability to make leptin. So leptin is a hormone produced from adipocytes that helps regulate hunger, right? Helps individuals stay lean, regulates long-term energy balance. Right. Exactly what it does sort of at, you might say, within the normal physiologic range among most of us who do make some leptin is, I think, still a little bit, you know, the jury's still out a little bit on that.

44:39Dr. Gabrielle Lyon:Totally agree with you. We used to, just a side note, early on in my practice, we used to measure leptin, adiponectin, and look at the ratios. And we're like, you know, after a period of time, what's the evidence of actually looking at this? And does this just relate to obesity? And what is the point? What is the information that we are now getting with this? And how are we furthering patients' health? And quite frankly, there isn't, unless there's some genetic mutation, I can't say that there's a reason to be doing that. Exactly. So there are many things that within the sort of, you might call the normal observed physiologic range, may not play such a big role or play the role we expect them to.

45:20But when you get them out of the physiologic range, then they can be huge. So GLP-1 is an example. Within the normal physiologic range of what we endogenously produce, I think there's debate about this, but the question is how important is that? How much difference does it make? But when you give a GLP-1 agonist that has a long half-life, now you're getting into super physiologic ranges. In the case of a leptin deficient human, you're getting into sub-physiologic, where you're having zero leptin, not low leptin. And when you get zero leptin, then big things happen. So zero leptin, you get hyperphagia, you get enormous hunger and excessive food intake and a very fatty body composition and other.

46:08Dr. Gabrielle Lyon:But super rare doesn't really happen. Probably a few dozen people on the planet. But anyway, some of those people were identified by the Cambridge group. And as I said, they were the first providers ever to be able to look a patient in the eye and say, I not only know why you have obesity, I know what to do about it. I know how to fix it. And say it honestly. Lots of people could say it. Lots of people still say it. They were the first people who would say it honestly. And that was tremendously, I was very envious of that ability. since then, until relatively recently, we haven't been able to make similar kinds of statements to many people.

46:57Now with the new anti-obesity drugs, I don't think we can necessarily say, now I know why you have obesity. That part I still think is a little bit unclear in many cases. But I think what we can say is, we do know how to help you.

47:14Dr. Gabrielle Lyon:So would you say comfortably that we now have a treatment, in essence, for the majority, 80 plus percent of obesity and also even type 2 diabetes? Certainly for obesity and type 2 diabetes, I'd say that's, you know, I'm not going to give an exact number, but that's in the spirit of things. That's in the realm of how I would answer. I think we always want more information. We will never have complete information. somewhere between where are we today and some hypothetical, perfect, complete information that we will never get to. We need a little more. We'll get a little more over time. But I think we're going to start to get to the time where we're going to flip the question, or at least we should flip the question around.

47:59And I realize what I'm about to say will be controversial, but I think it makes sense. There are many things for which we take for granted that just about everybody should do them, right? Even though these things are not exactly natural and we didn't always do them, but there comes a point where people say, yeah, yeah, of course, everybody should do that, unless there's some very rare exception. So should you wash your hands before you eat or after you use the restroom?

48:28Dr. Gabrielle Lyon:Yes. Should you use soap? But it's not natural and we didn't all evolve having bars of soap with us. That's okay. You should still wash your hands. And we think this is good for almost everybody. And you might say, but is there some rare individual has some skin disorder that maybe they shouldn't use? Maybe. But that's the exception. The rule is you wash your hands with soap. The rule is you should brush your teeth. And maybe there's some people who shouldn't brush their teeth. There's some strange gum disease. We won't get into vaccines because there's a lot of difference opinion on that. The point I was making is that you take some things like toothbrushing and hand washing and so on, and the norm is, of course, almost everybody should do that.

49:15And the real question is not who are the rare people who should, it's who are the rare people who maybe shouldn't. Great point. Okay. Now, let's take taking a statin, an SGLT2 inhibitor, a GLP-1 agonist, an antihypertensive drug that's known to be very mild and been studied for a very long time. And I think we are at the point where we should be starting to think about flipping the question from who should get it to who should it.

49:51Dr. Gabrielle Lyon:I don't think that's controversial at all. I think that's right on the money. And I think that, and I'm curious to your perspective, how that informs our dietary guidelines. Because we, you know, we talk about, say, for example, reducing saturated fat to 10 % or less of calories. Well, okay, so for some people, that might be really relevant, but it's not for who that's relevant. It's who that's not relevant for. And let me say this a different way. If 70, if, I don't know, 20 % of the population actually has a problem with LDL cholesterol that is impacted by saturated fat, then that means that 80 % of people might not necessarily have an issue with saturated fat.

50:39Dr. Gabrielle Lyon:And that could be one aspect or even triglycerides. what if you know i think it's roughly the number is low i'd have to look but 20 or less actually have elevated triglycerides that to me is a carbohydrate problem and then the next question would be well what percentage of people actually have to restrict carbohydrates versus those that don't but we make these recommendations for perhaps the few not the many right i'm curious to see your perspective. Hopefully that made some sense, some semblance of sense. I think there's multiple things embedded in what you're asking. I think one is, do we make recommendations for the few or the many?

51:21And the answer is sometimes we erroneously, I think, make them for the few rather than the many, and we should flip that. I think another thing is, what do we really know about these particular things you're talking about? Carbohydrate, saturated fats, and that's a whole different can of worms. And then I think there's this notion, this question of individual effects. And that is something my group and I are very interested in, we write a lot about. I think there's an implicit assumption that we're all very different. And, you know, the right diet for you is not the same as the right diet for me.

51:58And while I think that's intuitively a very appealing idea, and there's almost certainly some truth in it, it's based on a lot of assumption. So the idea that we all respond differently to things is usually not demonstrated. It's usually assumed. Even the well-meaning research-based clinician, scientist, who says, don't tell me this is not evidence-based. Look at my randomized controlled trial here. Look at the fact that some people had huge reductions in body weight on this drug and some small or none or gained weight. Look at the change in LDL cholesterol when I put people on this diet versus that diet.

52:44Look at how variable it was. And they say, you see great heterogeneity response. And I say, no, I don't see that. What I see is great heterogeneity of outcome. If outcome equal response, I wouldn't need control groups and studies. And so...

52:59Dr. Gabrielle Lyon:Outcomes. So let's pause there. That's really important. Can you say that again? And because it's a very important distinction. So let's say you and I both go on a weight loss drug. We're in a clinical trial. You lose 10 kilos. I lose zero kilos. The investigator comes along and says, good responder. Non-responder. I say, no. Good outcome? Not so good outcome. However, maybe what happened is the drug caused you to lose five kilos. You happened to also get the flu during that time and felt ill as heck, and that caused you to lose another five kilos. Your total weight loss was 10 kilos, but only 5 was due to the drug.

53:59I lost 0 kilos. It turns out, though, that right before I went on the study, I moved in next to a donut shop. Bad move, friend. Bad move. And I'm just loving it, and I'm eating donuts every day.

54:18Dr. Gabrielle Lyon:Long Island does, by the way, I would just say they've had some good food. There's some good donuts over there. And had I not been on the drug, I would have gained five kilos. So the donuts caused me to go up. I don't overcomplicate things. So basically, we can't, I mean, your point is well taken. Go ahead. I'll let you finish. But your point is well taken. Basically, there's so much that we don't. We know less than we know. Sure. The point is that the drug pulled me down five. The donuts pulled me up five. Yeah, you know, you integrated zero. But in fact, you and I had exactly the same response.

54:53The drug caused each of us to gain five less kilos or lose five more kilos than we otherwise would have done. But it's hidden behind other factors in our lives, the flu, the donuts. The standardized randomized control trial doesn't estimate that. It estimates the average effect. So it's not that it's wrong when I say across all people taking the drug, they lost five kilos more on average than people not taking the drug. The drug caused a five kilo weight loss on average. That's true. In that hypothetical I've given you, it caused exactly five kilo weight loss for both of us, but it's not obvious.

55:32And so that's something we need to keep in mind. Now, there will be other times when there are situations. Even if the drug causes exactly a 5 kilo weight loss, let us just suppose for the moment that you were exactly 5 kilos above the threshold for obesity. And I was not. I was 10 kilos above the threshold for obesity. Now we express the outcome as did it make you obese or not obese. It made you go from obese to not obese. It made me go from obese to still obese. Same weight loss, different outcome by measuring things differently. So now when you think of other thresholds, the threshold to have a heart attack, right?

56:21It could be that something lowers my LDL cholesterol exactly the same amount as it lowers your LDL cholesterol. But my LDL cholesterol had me up at the threshold of about to get a heart attack. Your LDL cholesterol, let's say, was not at that threshold. So it rescued me from the heart attack. It didn't rescue you.

56:43Dr. Gabrielle Lyon:So what, you know, is your, so you've mentioned your group a few times and your group is very well known for looking at evidence, statistical evidence. And I don't want to say policing, but saying, hey, does this really show what this says that it shows? And if it doesn't, you guys have to fix that. And you've been doing this, again, for many years, which, one, makes you popular in some groups and not so popular in other groups. you know, you've spent your entire career doing something that's a bit uncomfortable. I mean, unless that's always been comfortable. I mean, you know. It's still uncomfortable at times.

57:20Dr. Gabrielle Lyon:It makes you different because it's not that it's confrontational, but it's like, hey, it's accountability, which is something that we're lacking, I think, in the scientific space. So if someone is listening to this and their mind is blown, so they're scientists, they're doctors, They're going, oh, well, now I don't really know what I think I know. You probably have that group. And then you also have people listening going, well, darn it. I have no idea what to think and actually how to assess information because I don't have statistical rigor. I am dependent on outsourcing those types of things while also having to make very real decisions for my family.

58:07Dr. Gabrielle Lyon:What do people do? I think there's different levels of knowledge. And as I said, I used the example of myself. One of my heuristics, not my only one, but one of my heuristics is if the FDA has said this pharmaceutical for people like me is reasonably safe and it's effective, that's usually good enough for me to judge, to make the judgment that for someone like me, it's effective and reasonably safe. Safety is a social judgment. Effectiveness is not. Effectiveness is empirical judgment. That's an interesting statement. Safety is a social judgment. So when I got out of the car today and walked into your area here, there's some risk I could have been hit by a bus.

58:56Very low. Very low. And so I made the judgment that it's safe to get out of the car and walk across the street. But it wasn't zero. It was my social judgment that that risk was so low as to not it'd be worth thinking about. But somebody else might feel differently. That's a social judgment. Risk is a scientific concept. Risk is probability, long-range frequency. Safety is a social judgment. So. Interesting. I've never. Is it safe to go on a plane, to hang glide, to ride a bicycle, to ride a bicycle without a helmet, to get a vaccine? These are social judgments.

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1:01:51Dr. Gabrielle Lyon:Brad, who is on the internet saying that if you drink castor oil, you know, this has been shown to, I don't know, clear you immediately of worms or whatever it is. How, And all kidding aside, the decisions when you're younger seem less impactful, right? There's a lot of like my four-year-old, okay, eat the Twinkie off the floor or, you know, eat the carrot that's also been sitting in the yard for five days. There's like flexibility, right? They're doing immune system push-ups or whatever. But as you become more mature, so the postmenopausal woman who is confused about should she take calcium or not, should she make the decision to go on estrogen or not, these become real challenges.

1:02:36Dr. Gabrielle Lyon:And then the impact is much more meaningful. How do they begin to make decisions in a noisy landscape? I think the important thing, if one wants to be sort of rational and, well, the first question is, do you need to be rational and scientific about it? I would hate to argue with you. Can you imagine? RJ, one of the producers here. I mean, really, would you ever win? You would never win. You'd be like, oh, I never thought about that. I'm not going to be right about that. You know, the Nobel laureate who's now deceased, Danny Kahneman, talked about this in his book, Thinking Fast and Slow. and he said, you know, it talks about regret.

1:03:13And how do you avoid regret by, you know, making some decision and then later saying, why did I make that bad decision? And he said, here's two different ways you can approach it. And I kind of like these because I've had some regrets and in fact I have less regret now because I use this method. Really? Yeah. And so first is to make a decision. Say I'm going to go with this either one of two ways. I'm either going to say I'm willing to be wrong, and that's okay, and I'm going to randomly pick a path. And I'm not going to worry about it too much. And then if it turns out later that things go bad, I'm saying, it was random.

1:03:51You know, what the heck? Give me an example. Give me an example. I might say, look, I don't know if I should take this new job or that new job. How about flip a coin? I just can't decide. By the way, I do want to talk about your new job. Okay. We'll come back. And so then say, look, I didn't have a real good way of deciding, so I flipped a coin and it's not on me, it's a coin. The other way is to say - So it's removing responsibility, essentially. The other way is to say, I don't want to do it that way. This one's important to me to get right. I'm going to study the heck out of this thing. I'm going to turn over every stone to get every piece of critical information.

1:04:33I'm going to get experts to advise me. I'm going to carefully integrate this. I'm going to ask multiple experts. I'm going to think this through as carefully as I possibly can. I'm going to sleep on it. I'm not going to make a decision immediately. And then I'm going to make the best decision I could possibly make at that time. Now, it may turn out that a year later was a really bad decision. Not a bad decision, a decision that turned out to be really, to have a really bad consequence. And I'm going to say, I made the best decision anyone could reasonably make, knowing what I knew when I made it.

1:05:12Knowing what I know today, I would make a different decision. But at the time I made it, it was the best, most rational, intelligent decision that could be made. So it's not bad on me. So I still wish it hadn't happened in the bad thing, but I don't feel any guilt, any remorse, which is a lot of what we've read is about. So those are different ways of sort of making decision, you know, sort of saying, where do you want to go with this? And then I think, you know, more generally, if you say, look, I do care about this. I don't want it to be complete chance. Sometimes it might, you know, you might say, I don't know which tie to wear today and which would make me look, you know, more, more whatever I want to look in this setting.

1:05:52Clip a coin. Then you might say, well, here's an, I'm going to go get surgery or not for this thing. I think that one I want to think through a little bit. Should I get a hip replacement? Should I, whatever it is you want, you know, should I get plastic surgery for cosmetics? You know, think that through a little bit. And that's where I think, you know, we sort of want to work your way down to heuristics. And your mention about AI is one great example. I use AI a lot for myself, but I use it in a very particular way, which is I use it as an information gatherer and integrator, but I don't trust it completely.

1:06:30So I use it not in exactly the same way, but not unlike I would use conversations with anybody else I might have. If I talk to the Uber driver on the way over and I say, what do you think of the best barbecue restaurants in Houston? And he or she tells me the ones they think. I don't immediately think those are the best and those are the ones I will like the best. But I think it's a good lead, good lead. And then I might later say to you, if I'm looking for, hey, you've lived here, you're all longer, what do you think of the best barbecues? And if you say the same thing the Uber driver said, well, strengthen.

1:07:07If you say some different ones, okay, I've got some different ones. Then I might ask AI or Yelp or something. And so I think you start to integrate sources And then you'll say, how important is this? I'll say, what if I get it wrong and I don't pick the best?

1:07:22Dr. Gabrielle Lyon:So like, let's say you're choosing between vitamin D or amino acids and you go, okay, well, this isn't that big of a decision. So I don't care which vitamin D I choose. Then that takes very little effort, cognitive load, no big deal. What's the likely cost of being wrong? So the likely harm of taking a vitamin D supplement, as long as you don't go crazy with something like that, pretty low. um but over a lifetime so for example like the whole protein conversation i don't know i've been talking about protein for 20 years if you're in your 20s and you get it wrong and when i say get it wrong maybe you're eating closer to a minimum or you choose to eat some kind of way you know when i was in my 20s i was uh vegan and that's just an example that might the consequences for the first five years or even seven might seem small, not immediate, but let's say 30 years later.

1:08:29Dr. Gabrielle Lyon:Now, because I wasn't able to assess those outcomes, and you talk a lot about psychology, humans are, I don't know, they're creatures of habit. It's kind of like if you're wrong, you stay wrong over long periods of time. How, you know, with the landscape, if people might not even know how dangerous it is to be wrong. And so, you know, like, do you, obviously, you're in a whole different league. You have obesity energetics. You guys curate science. But even then, are there people that you go to that you trust that you would say, hey, for protein research, I look to Don Lehman. For high-intensity interval research, I look at Martin Gabala.

1:09:16Dr. Gabrielle Lyon:I trust. Do you know what I mean? Like there are ways in which you identify trust and that you could potentially help teach RJ, you know, one of the producers to think about how he can curate more trust for, let's say, even something simple like parenting. Absolutely. So there's no single source. I do go to a lot of podcasts. Yours, Huberman's, Peter Attia's, Lane Norton's. Lane's still waiting to be on anyway. Melissa Dobbins. And even though these names may sound lightweight or something, they're actually pretty good, I think. Barbell Medicine, Doxulift. So there are a number of ones I go to.

1:10:03But even them, I take with a grain of salt. Cigna Nutrition's another good one. The Proof with Simon Hill.

1:10:09Dr. Gabrielle Lyon:We're definitely editing that out. I don't agree with everything they say. I don't agree with everything you say. And I'm sure you don't agree with everything I say. That's okay. So I don't mind being wrong. I'm wrong all the time. I'm a mom, two kids. I'm wrong all the time. And it's okay. So, but anyway. So. As long as you have people that, you know, are smarter than you around you, that say, hey, man, guess what? Don's always like, no, Gabrielle, that's not right. You sound like an idiot. That's wrong. And then you go, okay, you know. I heard a funny statement somebody said recently. He said, if you're the smartest person in the room, you're in the wrong room.

1:10:48That's right.

1:10:50Dr. Gabrielle Lyon:But why podcasts? That's interesting. So you're a career scientist, and podcasts probably haven't been around for, I mean, again, the landscape for podcasts probably, I don't know. I mean, I suppose Joe Rogan's been the longest, but the scientific podcast, I mean, Andrew is a friend. And it's probably, I don't know, five, a little or five, maybe five to seven years. Not even that long. But for you, it's interesting that you would go to listen because you understand, have access to the data. What is it that you hope to get from hearing? So I like them because, you know, I can listen to them while I'm eating dinner.

1:11:31Or barbie jam, yes. I can listen to them while I'm out for a walk. So it's sad, it's entertaining. But also it's a way of my getting exposed to things I wouldn't know to ask about. So, you know, I can always go look up and say, oh, I'm wondering how much protein to eat. And then start to look up how much protein to eat. Or say, you know, oh, I'm wondering if, you know, this peptide is safe. Well, I don't even know the peptide existed. But now I listen to, oh, that's out there. Maybe I should look up whether that's safe. So it exposes me to things that I just didn't even know to ask about. They're entertaining.

1:12:13But again, they're my first draft. They're not my final decision. Unless, again, unless it's very light. If I hear you say, I like to make my ginger salad dressing this way, I might say, not a big risk. Maybe I'll try it. But if you said, this is my decision on surgery, and I'm going to advise someone on surgery or make a decision myself on surgery, no matter how much I respect and like you, I'm not stopping there. Now I'm going to say, let me check the references she cited, if she cited something. Let me go to another podcast. Let me go to AI. But when I do AI for this, again, first of all, I don't trust it.

1:12:53It's my first take. and I ask it very specific questions. I don't say, shall I eat my protein? What I say is, yes, Tom. relying only on randomized controlled trials in the English language scientific peer-reviewed literature. Summarize for me the results of efficacy of protein intake on these outcomes. Then summarize the results of safety information for protein intake on these outcomes or something like that. And then, even that's not my final take, then I may look up the papers that are cited to make sure they're real papers. They actually exist. Do they actually say what the AI says they say?

1:13:36Are there other papers it missed? Then I will go to, if it's about me, I may go to my personal physician and say this. Because as a scientist, I often have very deep knowledge on something, but I don't have the broad knowledge that a physician has. I'm not a physician. And I've had many occasions where I'm thinking deep thoughts about some health thing. And the physician who has, again, a much different training says, like, David, you're out there looking for zebras. Totally. It's a horse and it's right here in front of you. And I go, I didn't know that horse existed. Right? So I had one where at the end of the pandemic, as I think many of us were sort of emerging after the first year, I've been locked down the house for a year and weird things are happening and I had some tingling in my legs

1:14:28Dr. Gabrielle Lyon:and I'm thinking I feel like a diabetic myopathy and I'm checking my you know urinary glucose and no I don't have diabetes and you know I'm checking for Lyme disease no I don't have Lyme disease I go to the physician and I say you know I did this and I tell him that's my weight lifting I used to be able to do pull ups so you have a little neuropathy or something and I would have a weight belt and I could do pull ups with 90 pounds on a weight belt. And I only weigh like 125 pounds at the time. And he says, and I said, you know, when I stopped, it went away. And he said, yeah. He said, that's your lateral femoral nerve.

1:15:05He said, cops get that. The gun health is heavy or construction workers from the tool belt. He said, that's it. I'm like, yeah, never in my life would I have thought of that. So go to a general physician, talk to my friends who are physicians, read the literature, ask G8I to point me in the right direction, listen to a podcast. And again, if it's depending on how much I really feel like I must know this as opposed to operate on some heuristic trust, then maybe pull up every paper myself and read them myself. Now, that's as a scientist, right, as a general person who just wants to make intelligent decisions about their own life, you may not need to go to reading every paper and you may not have the ability to know what to ask more when reading every paper.

1:15:54But you can certainly go to your own physician. You can ask another physician. You can listen to a podcast. And if they start to converge, then you're good.

1:16:04Dr. Gabrielle Lyon:Yeah, it's the equivalent of looking at continuity of data over time. You know, when you see a scientific discovery and then it's in multiple different labs and here's the totality of evidence. I think that that makes a lot of sense. And you start to learn who you can trust. Yeah. So, you know, if I'm listening to Lane Norton and he's making some commentary on what studies show about a particular thing on protein intake, I know Lane well enough and I've listened to him long enough to know he's almost certainly, I won't say certainly. Don't you dare say he's right. Lane. I'm just kidding. Lane, you know, I trained with Lane.

1:16:42Dr. Gabrielle Lyon:She's a very dear friend. Well, more like a brother, but yes. He's almost certainly. Your mom are better looking. Got it right. Yes. Whereas if you were on some other topic, I might say, I'm not sure that's his strength. It's a really good perspective. Maybe not. Let me learn with somebody else. So I'll have people that I can trust to varying degrees. And even then, again, it's not absolute. It doesn't mean Lane's got everything right on protein. It doesn't mean that this person's got everything right on carbohydrate or whatever. So there's a couple very hot topics that seem to be trending right now.

1:17:19Dr. Gabrielle Lyon:seed oils, ultra-processed foods? Do you have opinions on either? Sure. Let's start with the ultra-processed foods. I think the value of the category and the meaningfulness of the category depends upon what one is doing with it. So if you are a scientist and you are studying social phenomena, and one of them is perceptions around ultra-processed food, fair game fine i don't have any concern criticism so if you are either a person recommending things to others for their health and diet or you're trying for yourself to choose things if you're looking for a general heuristic and by heuristic i mean a way of doing things that might have some benefit, but not a statement about the state of nature, about how things actually work.

1:18:20Dr. Gabrielle Lyon:Meaning, can you give me a more specific example? Sure. If I said to you, or I said to your kids, maybe it might be a third one. Good luck, yeah. They're very young. I didn't want them to go into that wooded area because there's a cliff and a stream and you can fall in and you can drown and there's wells and... It's a whole situation. Right on. Yeah. And I say, there's evil fairies that live in that forest. Don't go in there. Now, we can have an ethical conversation about... You might now have their attention. Should I be lying? But let's put that aside for the moment. You might say, that's a very effective way to get them not to go into that forest.

1:19:01And then say, well, if that's your goal and you don't have an ethical concern about lying, then you talk about fairies. Okay. Now if you said to me, no, no, no, I'm actually an epidemiologist and I'm trying to understand the degree of danger that comes from going into that forest or things like that. Um, and the causes and effects and what causes, you know, the bad outcomes. and so I'm a fairyologist I'd say no you're crazy you're not a fairyologist there's no fairies ology is the study of stuff you can't study stuff that doesn't exist and Richard Dawkins talks about that you know there's no fairyology so I think that's ultra processed foods if I wanted to say to you know I remember my dad who was a PhD in math education very very smart man but he always struggled with his weight.

1:20:03Dr. Gabrielle Lyon:Is that how, is that was one of the things that drove you? It got me interested. And he said, I remember him, he would say these things. He'd call me up and ask me how many calories is in this and that. And he'd say, look, I'm eating nuts. Isn't that great? You know, cause it's all natural. Isn't that healthy for my weight? Well, I'm having nuts and a martini. I'm like, well, well, the nuts are good food, but no, they're like calories. and the martini has some calories too. And that's not really all that helpful for you. But he can convince himself of any nonsense in nutrition if it let him have his martini and his nuts and a few other things.

1:20:40And I think, you know, we can look at these things as just ways of operating. And if it works for you, that's fine. So if I said to my dad, dad, here's the thing. You don't have to learn a lot of nutrition. You don't have to understand what protein is. You don't have to know what a carbohydrate is. All you got to do is this. Don't eat ultra processed foods. And I'll give you an easy way of identifying what an ultra processed food is. And let's suppose he could do that, which probably not. He probably wouldn't, but let's suppose he did. He probably would weigh less than otherwise. And if that's a good outcome, fine.

1:21:19And if you say, but aha, ultra processing. now, David, you've shown that ultra-processing, at least in your father, causes greater waking. No, I have shown no such thing. What I've shown is that telling my dad to not eat ultra-processing food led to this outcome. If I said to you, I want you to only eat foods that are in the peripheral aisles of the grocery store, not that you get in the central aisles of the grocery store, and it turned out that you wound up there by eating lots of fish and meat and eggs and et cetera, and not lots of cinnamon rolls, maybe you would weigh less. Okay. Does that mean if I move the cinnamon rolls to the periphery of the grocery store, they become better for you?

1:22:09Of course not. So just because telling you to eat a certain way leads to an outcome, and just because I can label things as being there, doesn't mean there's anything to do with the causal effect. So there's a man named Schwartz and he has a book called A Fly in the Ointment. It's a great funny book. And in it, he says, repeat after me, the effect of substances in the body depends on their molecular structure, not their ancestry. So if you tell me that this food that happens to be ultra-processed causes some different effect than that other food that happens not to be ultra-processed, I can accept that that could be true.

1:22:56If you tell me that it's because in that food that happens to be ultra-processed, this substance is in high levels, and that substances not in high levels in the non-ultra-processed food. I can accept that. It's about the substances. But if you tell me the substances are identical, got the same atoms in this food and in this food, these atoms were collected and packaged through something we call ultra-processing. These atoms were collected and packaged through something we don't call ultra-processing. But you are now going to make a claim that the effect is going to be different, I'd say, okay, now we're in fairyology land.

1:23:39Now you're in homeopathy. Yeah. You're thinking if you wrap the Bible three times on the tube containing the water, the water has a different effect. I don't think so.

1:23:53Dr. Gabrielle Lyon:Thanks to one of the sponsors of the show, Amp, because I can walk two doors down and get a great workout. And if you've ever walked into a workout and thought, am I lifting too heavy? Am I not lifting enough? Where is the weight? I can't find anything. And is this even working? You are not alone. Seriously, the uncertainty is one of the biggest reasons why people do not see results and they stop. Strength training is an essential daily routine. And AMP was founded to introduce it into everyone's life, home, and ambition. That's exactly why I've been using AMP. What makes it different is it removes the mental noise.

1:24:35Dr. Gabrielle Lyon:AMP AI uses your resistance to adjust sets and reps in real time so you are always training at the level that your body needs. No second guessing, no wasted time, and by the way, it has everything that you need. Your body responds to progressive stimulus and you need to do that correctly. You don't want just random workouts that you find out online or you find online. It mounts to your wall, takes up almost no space and gives me access to hundreds of movements from strength training to high intensity work. I am telling you, I love this technology. It is beautiful, it is on my wall and it is a system that meets me where I'm at, regardless of the day.

1:25:22Dr. Gabrielle Lyon:If I need some recovery, it's there. If your goal is to build muscle, get stronger, no more guesswork and be consistent, go to amp.ai. Check it out. That's amp.ai. Training should be effective and it doesn't have to be complicated. Tell me about your new position that you have just recently taken. So I'm very excited. I'm having a great time at this. I've done a few different things in my life. And there's, what do they say, eudaemonic pleasure and hedonical pleasure. The hedonic is what feels good right now. It's eating the chocolate cake. The eudaemonic, at least for me, is going to the gym.

1:26:07It feels great the moment I leave the gym and I'm so proud of how hard I worked and so on. While I was there, maybe not.

1:26:18My prior two jobs, one was at UAB, University of Alabama, being an NIH Nutrition and Obesity Research Center director. I loved it. I had a great time. After that, I went and I wanted to learn new things, and I went to what became a school of public health. It had just been transformed into a school of public health before I got there. My job was to sort of make it a reality, along with the colleagues of the School of Public Health. It was very science-based. And we did it. We transformed the school. It's hard work.

1:26:51Dr. Gabrielle Lyon:And this was, is this Indiana? Indiana. Indiana University, Bloomington. And I'm very proud of what the school and I accomplished. And then it was time to pass the baton. And that job was much more of a eudaimonic, pleasure job. I look back and say, I think that's what it's like to be a dean. You look back and say, did we do well? And thankfully I feel like the answer is yes. and something proud of what we accomplished. I'm glad I did it. I would do it again if circumstances came again. But if you said in any moment, you just randomly called me up and you said, you having fun today? No, today I'm dealing with a racism complaint or a sexism complaint or a plumbing problem or a budget problem or...

1:27:39Dr. Gabrielle Lyon:All the problems that exist. Whatever. Now, so I did that, I'm glad. and now I'm back to the science. But I'm back to the science in a way where I kind of have the best world of two worlds because I'm the director of a federal center and I have the budget and the building and the personnel of what's equivalent of a small school, so like the dean. So I have sort of the authority and resources of, not unlike a dean, but I'm all focused on research and helping people with research and research on not any topic, but on the topic of nutrition, obesity, exercise, particularly as regards to children, pregnant women, life course development.

1:28:28And so I'm having a great time. My colleagues, who I have the privilege of leading, are my intellectual peers. I'm interacting with people who are rock solid researchers, who are smart and energized and really committed to their science. We have good people at our center. And they know so much more than I know about their domain. I'm just thrilling. I'm having a great time.

1:28:58Dr. Gabrielle Lyon:And what are you guys working on? I know that you've got multiple projects. It's the USDA, I don't want to put your list. FDAARS Children's Nutrition Research Center at Baylor College of Medicine and Texas Children's Hospital. I mean, that was a lot of words. And you nailed that. What are the projects you're most excited? I know that you guys are working on a whole host of projects. But are there a handful that you're just like, wow, this is really transformative? Yeah, I think there are those that are my own research that I'm very involved in. And then there was that the center's involved in that, you know, as the leader, I try to support, but it's not my research.

1:29:42Some of the really exciting things with Dr. Marta Fioreto, she made a great presentation yesterday. and she was actually, she's looking in model organisms and she's studying whether exercise can mitigate the lifelong effects of in utero undernutrition on long-term obesity. So there are some effects in if, you know, an organism doesn't grow so well in utero that will lead it to be predisposed to obesity in later life? And does exercise mitigate that? So that's pretty exciting stuff. We've got others who have shown that certain factors may lead to longer or lesser lifespan, especially when given early, including, I'm probably going to pronounce it incorrectly, but urolithin.

1:30:50Dr. Gabrielle Lyon:Urolithin A. That may have effects that are opposite to what's sometimes reported under some circumstances. Dr. Yi Zhu, Z-H-U, is our expert on that. So cool. So we've got some interesting things going there. Then we've got some community-based things. Dr. Jaina Dave is working on the so-called food is medicine. And can she help people lead longer and healthier lives by adopting this perspective and adopting techniques? We have a wonderful setup with her and others. We have laboratories that nobody else has. We can bring in children and families to stay overnight in metabolic chambers. That's unbelievable.

1:31:43We have great body composition equipment. We have great staff who know how to help a young child experience calmness and security, even staying overnight in a facility like this because they're pros. So this is really nice. We're trying to upgrade our test kitchen and our feeding so we can actually do controlled feeding studies. so we don't just say, hey, why don't you eat this and let's see what happens? But we can say, come in, eat this in front of us. We'll feed you, and then we'll see what happens. So we know it's tight, and we're trying to raise some funds. So anybody out here who's got some funds is listening.

1:32:18We're trying to raise some funds to renovate those laboratories and have some of the most modernized, best test kitchens and feeding facilities for nutrition studies in children, pregnant women, and families.

1:32:30Dr. Gabrielle Lyon:It's really exciting. Um, it's a pretty extraordinary place that you're at. And, um, you guys are making a great team because the, the combination of scientific rigor with really intellectual integrity, scientific integrity is, is what I think is desperately needed. Um, I have one last question for you, Dr. David Allison. If you had a wish, you know, as we talk about these methods and these science and making good decisions, what would that be for people? I think it would be to take a step back from the specific and move to the general. In other words, take the priority off the question of, should I eat keto or low carb or get rid of food dyes or whatever and say, and you asked me this question earlier, how do I as an individual and how should we as a society make the best decisions in general?

1:33:37How do I evaluate things in general? And let's start by committing to that, committing to doing it rationally, intelligently, honestly, through science, and then say, what would it take to do that better? And let's explicitly not think about for the moment keto or carbs or fats or ultra-processed or protein. And let's think about X and Y. Because when we think about X and Y, we can leave our emotions at the door a little bit and come up with these generals and say, this is how I would think about it if it was X and Y. And then later when you say, now let's think about keto, and I get emotional and I say, blah, blah, blah, blah, or protein.

1:34:22And you can say, David, hold on. Remember six months ago, we went through this with X and Y and you said, this was a good way to make decisions. Let's apply that framework now. And I think if we can start committing to doing that as a society, as individuals, and I think we already have that commitment in principle in the scientific community, but in practice, we're not doing as well as we should. That's an important thing that Jay Bhattacharya, the current head of the NIH, is really pushing for. We need to do better in being open-minded, in evaluating evidence fairly, in not stretching and exaggerating, and in correcting mistakes when we find them.

1:35:05Dr. Gabrielle Lyon:Very well said. Thank you so much for sharing your time and expertise. Thank you. Thank you. It's been fun. Thank you.

1:35:16you