How Your Biology Fights Weight Loss Maintenance with Paul MacLean

James Hill:
Welcome to Weight Loss And, where we delve into the world of weight loss. I'm Jim Hill.

Holly Wyatt:
And I'm Holly Wyatt. We're both dedicated to helping you lose weight, keep it off, and live your best life while you're doing it.

James Hill:
Indeed, we now realize successful weight loss combines the science and art of medicine, knowing what to do and why you will do it.

Holly Wyatt:
Yes, the “And” allows us to talk about all the other stuff that makes your journey so much bigger, better, and exciting.

James Hill:
Ready for the “And” factor?

Holly Wyatt:
Let's dive in.

James Hill:
Here we go.

Holly Wyatt:
Today, we're going to jump into something that I think a lot of people have felt, especially after losing weight. That moment when the scale starts to creep up, when you start feeling the hunger, it gets louder, when food feels more tempting than it did the month before. And when you're doing the same things you've been doing, but the body is responding completely differently. They're not working, maybe. And you start to think, why does it feel like my body wants the weight to come back. What's going on? And the truth is, it kind of does. I hate to say that, but I think it kind of does. And it's not emotional or moral. It's biological. After weight loss, there's a whole series of survival systems that kick in, a system built for a world that doesn't have grocery stores or Uber Eats. And these systems are powerful. They're real. And they explain why weight maintenance or not being able to continue to lose weight requires a different strategy than when you start out.

James Hill:
Today's episode, we really wanted to do a deep dive into what's happening in the body after weight loss. And to do that, we wanted to bring in a scientist, Holly, who's taught us a lot about this topic, our former colleague at the University of Colorado, Dr. Paul McLean. Paul's professor of medicine at the University of Colorado Anschutz Medical Campus. He is director of their Nutrition Obesity Research Center. We talk about NORCs all the time, so Paul is the NORC director in Colorado, and he's one of the world's leading experts on the biology of weight regain. His research has mapped out hormonal shifts, metabolic adaptations, energy expenditure changes, and brain-level responses that make weight regain not just common, but too often expected. He's helped move the conversation away from willpower and blame (we don't want that, Holly), and toward an understanding of how the body actually works after weight loss. Paul, welcome to the show.

Paul MacLean:
Jim and Holly, thanks for the invitation. It's great to be here. This is one of my favorite topics, so I'm excited to be with you today.

Holly Wyatt:
Ours too, so this is going to be good.

James Hill:
Yeah, Paul. So the big question here, and we'll hit lots of aspects of this. Why the heck is it hard to keep weight off? We talk to people and they say, I have lost weight 10 times and I gain it back. And people seem to be better at losing weight than keeping it off. What's the problem here?

Paul MacLean:
Yeah, I think the simple answer is that once we lose weight, there are very strong, persistent adaptations that occur in our body that are bringing that weight back on. They culminate in two very simple things, making you want to eat more and expend less.

James Hill:
Wow, that's pretty powerful.

Paul MacLean:
Exactly. Those two things come together. And those two biological pressures are persistent and make us want to bring that weight back on.

Holly Wyatt:
And what is it that causes that to happen? Is it the weight loss? Is it that you haven't been eating as much calories? Do we know what's the signal the body is looking at to then try to say, eat more and we're not going to burn as many calories?

Paul MacLean:
Yes, I think what's happening in the body is the body at the cellular level is sensing an energy deprivation. And this energy deprivation in your muscles, in your adipose tissue, in your liver, in all the peripheral cells, when you try to restrict energy, these cells sense that energy deprivation, and they send signals back to the brain. There are neuronal signals, there's hormonal signals, there's nutrient signals, and these signals go back to the brain and all culminate in the same message. We need more energy. And what happens with the brain, the brain has alterations that alter food-eating behaviors, food-seeking and food-eating behaviors. And at the same time, it sends signals out to the body to become more conservative, to reduce their energy, and to try to survive in an environment where nutrients are rare.

James Hill:
So, Paul, it seems like your body... It doesn't want you to lose weight. It wants to be at the weight you were before you lost weight. Why the heck would that be a reasonable thing for human biology?

Paul MacLean:
Well, this is just a normal system. In times of famine, it's protecting you from wasting away to nothing. It's putting the fire under you to go find energy, be conservative, and don't waste away to nothing. But there's also biological adaptations when we overeat that are protecting you from gaining too much weight. So this is a normal system in the body of sensing nutrients and sensing how much energy you have. I mean, all three of us are at different weights because our individual biology is kind of set up differently through our genetics and our environment and our behavior to kind of be at a different body weight. But that same system's in place for each one of us of defending too much weight loss or too much weight gain.

Holly Wyatt:
So is it body weight that it's defending or is it the amount of energy coming into the system? Is it based on I'm eating a low amount of calories and I've been eating less calories or been in a negative energy balance for a certain period of time that signals the body to make some of these adaptations? Or is it literally that there's less weight or fat on the body?

Paul MacLean:
Well, this is kind of a debatable issue about what is actually defended. However, for me, I'm in the camp that you're sensing a nutrient deprivation at the cellular level, and that translates to a nutrient deprivation at the organism, at the level of our whole bodies. And it's not necessarily that we're defending a particular body weight or fat mass, but I think that that's manifest in what's happening at the molecular, cellular, and at the whole body level.

James Hill:
Paul, if you look in the literature, there's so much research around weight loss and not nearly so much around weight loss maintenance. What drew you to that question? Why did you get so interested in keeping the weight off when everybody was looking at how do you produce weight loss?

Paul MacLean:
You know, for me, it came from personal. I have a personal vested interest in this. I come from a family where we are obesity prone. My brothers and sisters, my mom and my dad, we all have had issues controlling weight. And so I grew up watching my mother going on a diet, getting really cranky. She'd lose weight, but she'd get cranky, but then she would gain weight back. And so I saw her many times with many different diets, lose a lot of weight and go through this cycle, and have it come back on. And so when I joined you in Colorado 25, 30 years ago and had that opportunity to study weight loss and weight maintenance, it was really the phenomenon of weight regain that attracted my interest. We went after the mechanisms of why does that happen? It seems like everybody can lose weight many times. But it was the problem, this phenomenon of weight regain that really attracted my attention.

Holly Wyatt:
So you talked about the metabolic adaptations, and we talk about that a lot in the show, the idea that your metabolism adapts, and I think that's what you're talking about, especially on the energy expenditure side. Is that more than can be explained by the weight loss? We've talked in the show, when you lose weight, your energy expenditure goes down because you're smaller and your metabolic rate will be lower and you won't take as much energy to move like you would when you're at a larger size, but do you feel like that goes down more than you can explain by the change in your body size?

Paul MacLean:
So, Holly, this is a little bit of a controversial issue, and it really comes down to, in the literature, people adjusting their data and normalizing their data and trying to come up with an answer. For me, I do believe that your cells, your muscles, and at the tissue level, they do become more energetically efficient with weight loss and nutrient deprivation. It's controversial because of the mathematics behind how we normalize or try to normalize our data and compare our data. But in vitro studies, when you're studying just cells or animal models, where we can really focus in on biology, it's very easy to tell and to measure that this energetic efficiency actually happens. It's not as profound as what happens on the food eating behavior side, but it's there and it does contribute to that energy gap that drives weight regain.

James Hill:
So, Paul, the end of the day then, when you lose weight, your energy expenditure goes down, whether it's totally appropriate for weight loss or not. Bottom line is you need fewer calories to maintain your reduced weight. So what's the problem? Why can't we just eat less? What happens on the appetite side?

Paul MacLean:
Yeah, so on the appetite side, those signals, those hormonal signals that are coming from the periphery, the neural signals that are coming from the periphery, and circulating nutrients, which when they were plenty in circulation, they're very high. After weight loss, they all go down. All of these signals are going back to the brain in some very key neural nodes to adjust the neural signaling here to increase food seeking and food eating and altering food preference and adjusting the food reward systems, all pointing your brain and increasing that food noise to drive food consumption and bringing that weight back on.

Holly Wyatt:
I agree. I think it's both, but I do think the food noise and that constant pressure to think about food, to want food, to not be as satisfied with the food you're eating is what kind of starts to drive more than maybe even the energy expenditure side of things. But it's probably a combination. But I know the question I want to ask, and this is a very selfish question. I get this all the time. So if that happens, is there anything you can do to change it or will it get better over time? If you went back into energy balance, for instance, eating a few more calories, trying to be in balance, not gaining weight, would those signals change? Like, what do we do about that?

Paul MacLean:
Well, I might propose a bit of an analogy here that might help frame some of our discussion and some of our questions. If you can imagine me holding a rubber band between two of my fingers and imagine that that rubber band is my biology. When I try to lose weight, I want to take my other hand and pull that rubber band out. The further I get away, that's how much weight loss it is. But that biology becomes very stretched and tensile, and that's not going to change when you lose weight. We have found very little evidence that that pressure to snap back into place, that rubber band snapping back into place, it doesn't resolve over time. What may happen over time, at least in humans, is that we become more normalized to the behavioral changes that we try, and we can change our habits, and we can change our exercise strategies, and those become more normalized to us. But we found very little evidence that that rubber band resolved.

Holly Wyatt:
The tension. You can't lessen the tension on that band.

Paul MacLean:
Yes. And then that tension is persistent and it stays there. And sometimes we've seen even in our animal models, it even becomes stronger over time.

Holly Wyatt:
Oh, Paul, you're depressing me. Don't tell me this.

Paul MacLean:
I know. It's not a happy story there, but.

Holly Wyatt:
But it sounds like you're thinking about set point, though.

James Hill:
But no, no, but it's the reality, though, so that if you're going to maintain a weight, you have to fight against your biology. Your biology is going to do it. We've depressed people so far, but we're going to talk about it can be done. And Paul, in the National Weight Control Registry, these are people that have kept weight off long time. They say it doesn't necessarily get easier, but they get to the point where they know they're going to do it. They get in the rituals and routines. So they're still fighting the biology, but they create routines and rituals that allow them to do it and succeed long term.

Paul MacLean:
Absolutely. And when you can establish those habits, I would equate that in our analogy is changing the rubber band to be something less elastic so that it becomes easier over time to pull that back. Medications can do the same thing. Bariatric surgery does the same thing. In our analogy, it would be like changing the type of rubber band you have around your fingers trying to pull it back. It doesn't eliminate the entire system. It doesn't reset once the weight is lost, but it does. It can make things easier for people to adapt and sustain their behavior change over long term.

James Hill:
One of the things that I think people, even our colleagues, Paul, fail to understand is that losing weight is a very different process than keeping weight off. I mean, if you think about it, losing weight, you can do all kinds of things temporarily. You can avoid parties and buffets and everything. But for weight loss maintenance, you've got to live your life. And one of the things, for example, that Holly and I have seen over time is that when we try to do behavioral interventions, we try to do both weight loss and weight loss maintenance. The problem is people never get to the point of where they're happy with weight loss, so they never learn the skills of weight loss maintenance. I think the new GLP-1 medications may help us focus a little bit more on weight loss maintenance because now you have the meds doing the heavy lifting on weight loss. Let's teach people skills for weight loss maintenance that are different from weight loss skills. What do you think about that?

Paul MacLean:
I completely agree. I think these new medications give substantial weight loss and reinvigorate or motivate folks that, hey, this this can change and I can actually get rid of some of my comorbidities. And here's how I can live my life if I can maintain this weight loss. I think it's not uncommon for this to be a motivational tool for people to alter their diet, get rid of their food noise, and reestablish some better eating habits with portion control, with diet preference, and even in some cases to become more physically active.

James Hill:
In your model of losing weight decreases energy expenditure increases appetite, the meds are working on the appetite side, but they aren't working on the expenditure side. They're just sort of managing your intake so you can eat less to match your lower energy expenditure.

Paul MacLean:
Yeah, and getting rid of the food noise so you can pay attention to something else. I think if you've talked to anybody who's lost a significant amount of weight through dieting and caloric restriction, that food noise is loud. It's really persistent. It's all over the place. And it's really hard to reestablish new habits and pay attention to other things besides the food when you're in that state. The tension there is is great.

Holly Wyatt:
Yeah. So, you go on the medications and the medications while you're on them kind of maybe keep that the energy intake side from from showing up. It kind of blocks some of those hormones that normally would cause you to think about food and want to eat more food and kind of keeps it. But then you go off the medications. That comes back. So that rubber band is stretched again. What I'm really interested in is not only the routines and rituals that help you focus in a different way, but are there any ways you can eat or move with activity that do make that stretch a little bit less? That you can mimic the effect of the GLP-1s, but mimic it with maybe certain combinations of foods or certain timing of foods or certain types of food or physical activity to try to not take the stretch completely away, because I don't think that's going to happen, but just make it a little bit less? Or is there some way that maybe it becomes less over time as you maintain?

Paul MacLean:
It's a good question. And we do know that physical activity is one of those regular, the more vigorous, the better, but regular physical activity. There's evidence that it potentiates post, perennial, or after a meal, the GLP-1 response. In some of our animal model studies, we've actually shown that exercise counters those biological drivers, both on the food intake side, it not only adds to the energy expenditure side of the equation, but those metabolic adaptations that happen in muscle, in liver, in adipose tissue. Exercise counters the molecular adaptations in each one of those tissues and counters that biological drive to regain. So physical activity, we believe, is one of those things that essentially changes the type of rubber band that's snapping back in your biology.

James Hill:
Paul, I'm glad you brought that up because oftentimes people and these are pointing the finger maybe at some of our nutrition colleagues that say, “Oh, physical activity, you exercise more, you just eat more. It doesn't do anything. And maybe it burns a few more calories.” But what you're talking about is something Holly and I talk about all the time. It does more than burn calories. Maybe to oversimplify, what I think it does is to optimize your metabolism. It sort of brings your metabolism back to factory settings, if you will. The obesity and the sedentariness has basically messed up your metabolism, and exercise to some extent can repair that.

Paul MacLean:
Absolutely. In muscles, it enhances oxidative capacity and increases the capacity to take up and oxidize dietary fat. In adipose tissue, exercise counters that lipogenic response or the desire of adipose tissue to suck up nutrients and turn it into fat. And it does the same thing in the liver. So all of those adaptations change the body to become more efficient in taking up and storing nutrients. Exercise diminishes or attenuates them out in the periphery and reduces that nutrient deprivation signal that goes to the brain.

James Hill:
Holly, I love this. We hammer the importance of physical activity and exercise all the time. And it's more than just burning calories. It really is optimizing your metabolism.

Holly Wyatt:
Yeah, this is the good news, right? I was so depressed. And now I'm like, okay, wait a minute. I think we can do some things that not only are behaviors and habits that help, which is very important, but also with the physiology. Because so many people come to me and say, you know, my physiology is broken, it's sluggish. But I do think there's things you can do, even like you say, after you've lost weight and it's really primed, it's set up, It's that rubber band is stretched back, ready to go. I can still do something that makes my metabolism work like I think it was supposed to work. It's we're in an environment now where it's not working at its optimal level.

James Hill:
So, Holly, you brought up the environment. Paul, how does the interaction of the adaptations to weight loss and the current environment sort of create a difficult time for people to keep weight off?

Paul MacLean:
Oh, I think it's a critical component. Biology is just one set of pressures that are affecting how we settle in with our level of adiposity. The fact that we're surrounded by energy dense, highly processed foods readily available. I can go into my pantry right now and there's just so much there that's available to me all the time. And we're surrounded by environmental conditions that promote a sedentary lifestyle. So I think this is what we refer to as an obesogenic environment, is pervasive, it's strong, it's powerful, it counters a lot of what we try to do to change our behavior and our lifestyle to become more healthy. It's very powerful.

Holly Wyatt:
Yeah. So you think about food and Jim and I disagree on this. I think we've always had this food noise. Jim thinks maybe it's just it's new. I think it's always been there. But you have this food noise and now food is just a few feet away in your cupboard. Very energy dense. It's very quick to get versus years ago. It wasn't in there as easy to get or the energy density of it wasn't the same. So it just, you know, you eat more because of the environment, even though the signal may be the same.

James Hill:
So my point is, Paul, here is that I think we're struggling with factors that caused obesity. And the fact that generations of obesity have caused our metabolism to adjust. So I'm looking at, you know, what was different in 1940 than today? Some of the factors in the environment caused obesity, but I think being obese feeds back to your metabolism and even how your brain acts. So, I think obesity now is different than it was 40 years ago.

Paul MacLean:
I think that it's very possible, Jim. I think the ultimate outcome is probably the same in what biology looks like and how it responds to environmental change. But it's very clear that regardless of how we got there to the obese condition, you can change environmental conditions. And we see this more clearly in animal models. You can change environmental conditions and alter the obese state. And if we alter conditions like making animals work for food, making it harder, giving them different preferences where certain foods are harder to get to, or they have to be physically active, that changes their phenotype. And I think, you know, we were in a completely different environment 50 years ago of how we got our food, what food was available, how physically active we had to be on our jobs, at school, at play. I mean, I remember 30 years ago, Jim, you were showing me pictures of kids on the playground today versus kids back in the 50s. And it's a world of difference of how often kids were outside. Even when we were kids, we would go outside and go into the forest and my parents wouldn't see us for the entire day. That's a rarity these days, right?

Holly Wyatt:
It's hilarious. someone was saying, you know, there used to be a thing that would come on at 10 p.m. And it said, do you know where your kids are? It's time to call them in, you know.

James Hill:
The TV cut off at like 11 o'clock or something. But you know what, Paul, when we were kids, we only got three channels on TV and two of them didn't come in that good. And so going outside was an easy alternative. Now with hundreds of channels and video games, you understand why sedentary activities are so appealing.

Paul MacLean:
Absolutely. You know, back then I didn't even like what was on the three channels. Now you have choices of a hundred things that you do want to watch or you do want to play. It's crazy.

Holly Wyatt:
I want to switch a little bit because I know these are some questions I get a lot and I want to pick your brain about them. Does it matter the speed at which you lose the weight or how you choose to lose the weight? Does the speed or how you choose to lose it impact how hard it could be in weight loss maintenance. I like separating weight loss from weight loss maintenance. You're successful, but how you do the weight loss, does that impact these, the stretch of the rubber bands, let's say, in weight loss maintenance?

Paul MacLean:
It's a very good question. And I think that there is some evidence out there that you could use intermittent fasting or you could use this diet or that. And there's very nuanced adjustments to how the body adapts in those biological adaptations. But on the whole, not really. To me, my interpretation of the evidence out there, it's about the amount of weight loss. So the amount of weight loss is really saying how far are you pulling that rubber band back and how much does it want to snap back? You can do that in different ways and you might affect this hormone or that hormone, but it's really about the amount. The more weight you lose, the stronger those biological adaptations emerge and become a player in weight regain.

Holly Wyatt:
One more to that. What about cycles? What about how many times you've lost the weight? So how many times you pulled back the rubber band and then let it go? Does that matter?

Paul MacLean:
It's a very good question and it's a little bit controversial, but it was something I was very interested in because I saw this in my mother's struggles throughout her life. The way I see the literature is that those that are genetically, have a genetic predisposition for obesity, either for like an acquired obesity throughout their life or an inherited obesity, may be susceptible for some yo-yo dieting that expands fat mass, and over time, that nutrient deprivation signal from the peripheral tissues to the brain can become stronger. I don't think that it's a wholesale “yes, yo-yo dieting does this in everybody” but I do think that there are some of us who are susceptible, particularly to the expansion of our adipose tissue, that may be susceptible to that phenomenon with yo-yo dieting.

Holly Wyatt:
So when people gain it back, maybe certain individuals gain back more fat or more cells or something that then kind of sets up the next situation for making it a little more difficult.

Paul MacLean:
Yes.

Holly Wyatt:
But not everybody is what I'm hearing you say.

Paul MacLean:
I don't think that happens in everybody. I think there's an underlying genetic susceptibility to that. But we have found examples when we try to take our animal models and model the human condition, those that are genetically prone, we do see that fat expansion over time and that weight and adiposity drift up over time with weight cycling.

James Hill:
Paul, what about exercise? What's your advice on types of exercise, amount, intensity? What do we know about characteristics of exercise that might help people maintain weight?

Paul MacLean:
Well, exercise does a couple of things. When we look at exercise, not only does it increase cardiometabolic fitness and oxidative capacity, which helps our peripheral tissues regulate metabolism better, but it helps sustain lean body mass. And those two things are very key. So if you're thinking about that, the more exercise you do and the more vigorous you make it, the better for hitting those two points. To me, I think that there's a debate out there in the literature about, oh, you know, we should do strength training only or we should do high intensity intermittent training or this or that. I think it comes down to volume being the most thing, the biggest factor here. Doing more is better. And regardless of what type of exercise you do, it has the potential to counter those biological adaptations in the periphery and in the brain.

James Hill:
Okay. Holly, I think we need to do some rapid fire questions for Paul.

Holly Wyatt:
All right.

James Hill:
I'll do them this time.

Holly Wyatt:
Okay. All right.

James Hill:
So quick question and answer off the top of your head, Paul. The most surprising biological fact about weight regain.

Paul MacLean:
I think that happened for me about 25 to 30 years ago, Jim, when I just started. And it was so surprising to me how strong and persistent the biological drive to regain is. That was just surprising to me to see.

James Hill:
All right. The one behavior that makes the biggest difference.

Paul MacLean:
Yeah, we've talked about it. I think that behavioral intervention is exercise.

James Hill:
Yeah.

Paul MacLean:
The more, the better.

James Hill:
I love it. One myth that refuses to die.

Paul MacLean:
Oh, I think even to this day that people think that when they lose weight and they've lost a significant amount of weight that they're starting off with a clean slate. No, that rubber band is pulled back. And in the weight-reduced state, your body is a very different beast than it was before you even gained the weight.

James Hill:
All right, last one. One thing you wish every doctor understood.

Paul MacLean:
Given the complications that come with excess adiposity, that I think that they really should be pulling out all stops and not only using, you know, not only and considering all. Consider all the options. Bariatric surgery, these medications can be very beneficial in helping us in addition to the behavior changes that we're trying to get people to do. So don't be afraid to see this as a disease that needs to be treated with all of the options that we have on the table.

James Hill:
Okay, Holly, you want to do a couple of listener questions?

Holly Wyatt:
Yeah, a couple of them. I think we've hinted at some of them, but these are the things that our listeners really want to know about. So will I ever stop feeling so hungry after losing the weight? We've talked a little bit about this, but what would you tell someone who's out there? They've lost some weight. They're feeling hungry. Is it going to get better, Paul?

Paul MacLean:
Well, I might have a two-part answer there. Probably not. But I think the good news is that you might be able to establish a new normal for you about how you pay attention to that hunger, and use some behavioral strategies to pay attention to other things or replace what that hunger's doing or how you respond to that hunger signal.

Holly Wyatt:
Okay. This is a good one. We didn't touch on this as much. My sister, actually, they lost weight together. This is someone who lost weight with their sister. They lost about the same amount of weight. Her sister was able to maintain, and she was not able to maintain. What explains the difference?

Paul MacLean:
Well, I think we all need to understand that there is a lot of individual variability in how we have gained the weight, how we have lost the weight, and our strategies of how we try to maintain our weight loss. This variability comes not only in our biology, in our genetics, in our biology, but in the environmental pressures that we face, our behavioral strategies, and the psychosocial pressures that are going on in our brain. And so I would sit down her and her sister and say, what are you guys doing different?

Holly Wyatt:
Yeah.

Paul MacLean:
And it could be your biology. It could be your environment. And it could be what you're doing.

Holly Wyatt:
I think it just shows it's complex, right? Yes, there could be genes that are involved and the biology is different for you in weight loss maintenance. There could be environmental factors involved. There could be different behaviors. There could be different stressors. It's so many things that kind of come together. But I think a lot of times people think, oh, you know, she succeeded and I failed. And it's something like personal about me and my willpower. And I think the idea is there's so many things, even genetics, even between two sisters.

Paul MacLean:
Even between sisters.

Holly Wyatt:
Yeah. All right, Jim. I think it's time for the vulnerability questions.

James Hill:
Okay, Paul, you've done a lot of work. On the biology of weight management. And you've also told us that you come from a family that struggles with weight. How has your work influenced how you're working to manage your weight?

Paul MacLean:
Yeah, so just like my brothers and sisters, I struggled throughout my life. But when I was young, I played soccer and I played hockey and I was exceptionally physically active. And my motivation to be physically active was about playing something where I scored a goal. And when I became a dad, I coached soccer and I coached basketball and things like that. And so I stayed physically active. Now that my kids are up and gone, my body doesn't handle hockey very well anymore. And those goal scoring games, I don't play nearly as much. And so, I, like everyone else, have become more more sedentary and I gained gained weight. And so one of the things that has helped me out is being on one of the GLP-1 agonists over the past year. I've been able to lose 35 pounds.

Paul MacLean:
And over time, that has allowed me to be, I'm still not super regularly physically active, but I do, I am more physically active now that I've lost weight. And I try, me and my wife try different strategies to increase our physical activity. But one thing that it really has done for me, is getting rid of some of that food noise, it's allowed me to pay attention to portion control and how I eat food and recognize when I'm hungry, when I'm not, and pay attention to my food eating behaviors a lot more. So it's been a really good thing for me. And it's gotten rid of a couple of comorbidities that were hanging out with me with that excess weight.

Holly Wyatt:
So what you talked about, Paul, is it gave you a new awareness, a new awareness of the food noise that was in your head. Now that it's lessened or decreased or gone or whatever, now you kind of understand it in a different way.

Paul MacLean:
Very much so.

Holly Wyatt:
And I think it's that awareness that can be very powerful for people moving forward, whether they choose to stay on the drug or whether they choose to discontinue the drug.

Paul MacLean:
Exactly. I completely agree, Holly.

Holly Wyatt:
You don't know what you don't know until you don't have it sometimes, right?

Paul MacLean:
And removing that food noise really allows you to pay attention to a lot more.

Holly Wyatt:
Yeah. All right. I want to do one more vulnerability because that was really good. Your research really has a lot of what I call tough realities. Sometimes I didn't even like what we were hearing at the beginning, right? I was like, oh, wait a minute. This is not what I want, the message I want to get out there. Has there ever been a time where you learned something that surprised you or maybe you got something wrong at first and then later you're like, oh, wait a minute. I didn't look at that exactly right. You know, science has evolved. I'm shocked, but this is a little different than I thought it was.

Paul MacLean:
I think one of the biggest things that surprised me, I think I did mention earlier, was how strong and persistent things were. Jim and I, way back, we had this hypothesis that if we just weight reduced, maintain this weight reduction over a period of time, that there would be resolution to this biological drive. And we studied that and studied that and did some very complicated studies together. And it was just so depressing. The longer we went, the stronger they became and how powerful this biology was. And so I was equally surprised, having been depressed with that message and that data, that we could intervene with exercise and other things and we could cut off or diminish or attenuate some of those biological, those molecular adaptations with exercise. And obviously, the medications that have come out are very promising. And so those are probably the two biggest surprises for me throughout my career.

Holly Wyatt:
Wow. So it was like, yeah, it doesn't go away, but we can do something about it. And that's kind of how it's evolved. Love that.

James Hill:
All right. Well, Paul, this has been an amazing episode. Holly, I'm going to sum up here and you can correct me if I'm wrong. But what we learned in this episode is that weight regain is a biological response, not a personal failure. Hunger, hormones, metabolism, brain changes all shift with weight loss and make it easier to regain the weight. These adaptations are real, they're measurable, and they're expected. And that's important. If you're going to lose weight, these adaptations are going to occur. However, that's the depressing part. The optimist part was with the right strategies, you can maintain the weight despite the biology in some ways working against you. And we do see that. We see that in the National Weight Control Registry. We see it in other areas. The message that we want to get out is that long-term success is absolutely possible.

James Hill:
The GLP-1 meds are another new tool for doing it. We know so much about lifestyle issues to maintain weight, particularly exercise, smart eating, resilience, those kinds of things. So even though there's strong biology opposing weight loss, it is possible to succeed at losing weight and keeping it off. Paul, did I get that okay?

Paul MacLean:
That sounds like a great summary of our discussion.

James Hill:
Well, thank you so much. Boy, a lot of good stuff in this episode, Holly.

Holly Wyatt:
Yeah, I think that this was great. It really is helping people understand what's happening in their bodies after weight loss. And that's a good thing.

James Hill:
Yep.

Paul MacLean:
I appreciate the invitation and being here with you both today. It was a lot of fun.

James Hill:
Well, we'll be back soon with another episode with more science, stories, and strategies. See you next time on Weight Loss And.

Holly Wyatt:
Bye, everybody.

James Hill:
And that's a wrap for today's episode of Weight Loss And. We hope you enjoy diving into the world of weight loss with us.

Holly Wyatt:
If you want to stay connected and continue exploring the “Ands” of weight loss, be sure to follow our podcast on your favorite platform.

James Hill:
We'd also love to hear from you. Share your thoughts, questions, or topic suggestions by reaching out at weightlossand.com. Your feedback helps us tailor future episodes to your needs.

Holly Wyatt:
And remember, the journey doesn't end here. Keep applying the knowledge and strategies you've learned and embrace the power of the “And” in your own weight loss journey.