Diet-Induced Metabolic Changes: Strategies to Improve Long-term Weight Loss

Author: Colorado State University

- So, I'm gonna be talking today about issues related to body weight regulation and weight regain. I think one of the best ways to regulate our body weight around a healthy weight is for you to substitute public speaking for eating a lot. (laughter) I don't get to eat while you do. So, how did I get interested in this? I think, let me start by saying something that probably nobody in this room knows. When I graduated from high school... I've been involved in sports, all sports. Never worried about my weight at all. And I decided I would just take the summer off.

I had a job that required lots of hours. And I didn't exercise for almost three months. And then, when I went to college, I was on the gymnastics team and I had to lose a lot of weight. I had gained a lot of weight over the summer. So, my first year of college, actually within the first three months, I lost 25 pounds.

I never thought that I would ever have a weight issue because I just didn't have to worry about what I ate. But that summer told me that I really did. But I knew nothing about how to lose weight. So, I was trying to lose weight and I looked into the grapefruit diet. I actually ordered a little pamphlet from the newspaper about the grapefruit diet.

And I had really no idea. But I became fascinated with this idea that body weight is a phenomenon that is influenced by so many different factors. Both internal and external. And I've been privileged to be involved in a number of weight loss studies over the years. And, oftentimes, when I see some of the studies that have been here at CSU and I see individuals who have been in our studies and they've gained the weight back.

Diet-Induced Metabolic Changes: Strategies to Improve Long-term Weight Loss

We didn't do enough for them. And so, I've been very interested in issues not so much in weight loss. But, more recently, in how we can maximize the chances of long term success. Which I think is the goal. So, with that, we start with objectives.

I'm not going to read through all these. You can see these. But, basically, I'm going to go through some of the metabolic and biologic processes that influence our body weight. Some of the complexities of energy balance. Very little about factors of regulated food intake. We just don't have time. I underlined briefly because this is an incredibly large topic.

Only a short period of time. We only have three hours today. (laughter) We'll look at energy expenditure, weight loss induced changes, and appetite and energy expenditure. And I want to introduce to you an oddity in all this already. I feel like I'm talking to, preaching to the choir here.

Because I've had so many of you in class. We'll talk about the energy gap. And then finish with some possible lifestyle approaches that I think could narrow the gap and enhance long term weight loss. Now, my voice may be breaking up a little bit.

It's not because I'm going through puberty again. But I've talked two and a half hours already this morning. And so, I'll be a little bit hoarse.

So, let's take a true-false quiz real quick. I don't wanna spend more than a minute or so on this. The rapid increase in the prevalence of obesity indicates that, for most humans, body weight is not biologically or genetically regulated. In your mind, answer that true or false. Using the energy balance equation properly can allow us to accurately predict weight loss via the power of reduction or increased physical activity. The major determinant of basal or resting metabolic rates is the amount of a person's (coughing) muscle mass.

Or more than 90% of people who lose significant amounts of weight by dieting regain the lost weight in a year. Five, inability to successfully maintain lost weight is more behavioral than a metabolic issue. The loss of body fat after dieting usually results in decreased metabolic rate that's greater than predicted based on the loss of body mass. And then regular physical activity stimulates appetite and increased energy intake. Now, if you were to take this quiz and you get them all right, then you can take over. These are questions that might appear to have easy true-false responses. But, in fact, a lot of these, I think, we'd have to answer with it depends.

'Cause there's so much complexity to this that it's not gonna be answered with just a black and white true-false. And I put this quiz here because I want you thinking about these thoughts as we go through this. Now, a lot of this issue of weight regain has surfaced because of this study. And I think that Amanda also mentioned this. Biggest Losers. And, when we look at this, this is a fascinating study.

There are 14 individuals that were studied. They lost weight for 30 weeks. And you all probably have at least seen some trailers or maybe even some episodes of Biggest Loser. Diet and exercise. Massive amounts of weight loss. The average weight loss was 58 kilos. And then, over a six year period of time, the average weight regain was 41 kilos.

Pretty substantial amount of weight regain. Now, what is really disturbing about this is that, when we look at the RMR changes, we expect resting metabolic rate to drop because of loss of respiring mass. When it lose that much cellularity, then we expect metabolic rate's gonna drop. But then they gained back 41 kilos out of the 58.

And, when we see this, but their metabolic rates, after that six year period, is actually a little bit lower. Not significantly different than when they've lost all the weight. It was down, as we can see here, 610 calories the RMR decreased after the six years. And they gained so much of the weight back, as we can see here. Their metabolic rate's still down 704 calories from original. And this received a lot of publicity. And a lot of it very negative. Like there's nothing we can do about this.

We are metabolically destined, when we lose weight, to gain it back. Because of our metabolic changes. And I would circulate the fact that a lot of metabolic changes are gonna be very difficult.

But I think there's some things we can do that we'll be talking about. Alright, so, energy balance. Simple concept, but it's got a lot of complexity. I don't know if you have seen some of the writings from Gary Taubes. But I find these fascinating. He actually has a degree in physics, as I understand it.

But he's a science writer. And he says, "The assumption is that obesity is fundamentally caused merely by consuming more calories than our bodies choose to expend. But what if this assumption is wrong? What if the laws of physics have nothing to do with it?" And there's sort of... A lot of the popular press's idea that calories really don't matter. The energy balance equation, it's not balanced. And Taubes will talk about hormonal aspects of obesity. Wait a minute.

The laws of thermodynamics still have to hold truth. Otherwise, why even study this? Then everything is up for grabs. It's arbitrary. But, the fact is, our laws of thermodynamics clearly do hold true. But it's the fact that this energy balance is so complex. There's so many layers of complexity that it makes it very difficult sometimes when we encounter individuals that seem to defy the laws of thermodynamics.

They can't lose weight as readily as we would expect them to based on their diet or based on their exercise patterns. I think one of the reasons that we have issues with this or that there's a rock that's underneath the surface in the minds of many individuals who are practitioners in trying to help people lose weight is that our energy balance equation really is very dynamic. And what we mean here is, when we change our energy intake, inevitably, we're gonna change our energy expenditure. And our energy expenditure, when it changes, it influenced our energy intake. And the problem is we don't know how much of these changes are going to occur within an individual. What I'll show you..

I'll show you some data that suggests that here's the average response in regard to this given perturbation. And we think, "Well, average, that's what we're used to seeing as scientists." But the variability in response is incredible. And, in my mind, this is one of the areas of research you've got to push forward in trying to understand and not just look at... Here's the aggregate data that shows well, on average, this is what happens. Because there are so many people that are not average and respond very differently to a given metabolic perturbation. Alright, so, when we look at the biological contrl of appetite. I put up this slide simply because I wanted to recognize that, even though we have a lot of environmental factors that influence what we eat and how much we eat, we still also have internal factors that influence this. So, when we look at our GI tract, we've got episodic appetite signals that emanate from the GI tract that are gonna influence various neurons in the brain and influence, then, the expression of various neuropeptides that will influence our sense of hunger or sense of satiety.

And we got those that will dampen food intake. Appetite inhibiting. And these are cholecystokinen and PYY, GLP-1. And there are others, as well.

Then, we've got ghrelin, which is orexigenic, that tends to go up prior to eating when we've been fasting for a while. And it tends to increase our food intake. And this has been studied a lot in animals. Less in humans. But still we recognize that these are important factors. But one of the things that we wanna note over here, there's now a lot of interest in this idea that fat-free mass and resting metabolic rate may be signaling to our brain, as well. And there's a group in Britain and several groups in the United States that are looking at this issue.

And a lot of the focus has been on sort of the cross talk between organs. What the skeletal muscle communicate with our brain based on the fact that our skeleton muscle contributes significantly to the resting metabolic rate. And I would suggest that that's a possibility. Because we do know that there are mikines that are released. These molecules that could influence the activity of other cells and other tissues and organs. But I would suggest that our fat-free mass is far more than just our skeletal muscle. I think there's more likely that we have the liver and other organs that are contributing or sending signals to the brain. And that this fat-free mass that's contributing to influencing our energy intake is not just skeletal muscle.

But this is sort of a new area that is being focused on. Because there's a fairly strong correlation between our drive to eat and our fat-free mass. So, when we look at our current environment, we have, as you all know, an obesogenic environment.

And this is actually a hamburger that you can purchase in Pennsylvania. There's six pounds of ground beef to start with. Now, no single person's going to eat this whole thing. But the fact is we've got large serving sizes, as you well know. And it's widespread. Our food is relatively inexpensive.

It's highly palatable. Much of it is high energy density. And, again, this contributes to the obesogenic environment that we have.

And then, of course, we have foods that we can purchase commercially here in Colorado. These are all foods that we can purchase here in northern Colorado. Some in Centerra. Some here in Fort Collins.

And you can see these are single servings. So we can easily get close to 2,000 calories in a single meal. That doesn't mean that everybody is gonna eat that many calories in a single meal when they go out. Some are gonna take it home in a box.

A portion of it. And eat it later. But, nevertheless, this is gonna make it a little difficult, from an environmental standpoint, when we're talking about trying to counter some of the metabolic factors that would drive us toward weight regain. So, when we look at the energy expenditure side... You've all seen this before. Based on metabolic rate recognized... I view this as fairly synonymous with resting based on some research we did many years ago when we had people sleep here in the Gifford Building in our lab and we measured metabolic rate right when they woke up.

Everything was well controlled. Or we had them sleep at home and then we brought them here. And metabolic rates were no different. Whether we did inpatient or outpatient. And so, at least in our hands, the resting metabolic rate and basal is pretty similar. One of the ideas behind this is that it's our fat-free mass that contributes mostly to our resting metabolic rate. And we've got the thermic effect of food.

We've got non-exercise activity. Exercise. And this makes up our total daily energy expenditure.

The reason I put this slide in here is I want to recognize one thing about resting metabolic rate, which I alluded to already. And that's that even the muscle mass certainly is a predictor for fat-free mass. It's more than just skeletal muscle. And that's shown here on this.

So, when we look at the actual contribution of these various tissues and organs to the resting metabolic rate or basal metabolic rate, we could say that muscle contributes significantly. But it's very large in mass percentage of our total body weight. But then we don't get the liver.

You know, almost the same amount as skeletal muscle, but, yet, the liver is very small in size relative to muscle. The liver is a very active organ. And I'm sure that, in the very first talk that was given in this series by Mike Heigensully, he made sure that you knew the liver was the center of all good things. (laughter) I had to eat liver when I was a child once a week and it was the center of all bad things. (laughter) Of course, the brain, the heart, the kidneys.

These are all our internal organs that are gonna contribute significantly. So, if we look at our internal organs, relative to skeletal muscle, it makes up a far greater component of our resting energy expenditure than does muscle. But, still, you'll see individuals... "What if I started lifting weights?" You'll read these lay periodicals that will suggest that, if we begin a resistance exercise training program, we're gonna be able to increase our basal metabolic rate dramatically. Most people increase their lean mass maybe by a kilo or two as a result of resistance exercise several times a week. That's not gonna have much impact at all.

And many people will not have that much of an increase in their muscle mass, 'cause they spend more time talking in the gym than they do actually exercising. Alright, so our current environment also looks like this. So, anybody recognize this? Anybody from Illinois? - [Student] Marshall Fields. - This is the water tower place where Marshall Fields is located. Off Michigan Avenue. I took this picture years ago. I sat at the bottom of the entry to the mall.

It's got six or seven stores. And I just watched. So, they had stairs over here and they've got stairs on this side. And they've got escalators. And nobody takes the stairs. The hour or so that I sat and just watched at the bottom I can count the number of people that actually took the stairs on a single hand. It was just hardly anybody. And then, on the escalator, they don't really use it as an escalator to increase their speed 'cause they don't walk.

They use it like a conveyor. It's really an elevator. They just stand. And so, we have reduced requirement to engage in physical activity. And, of course, this contributes. And that's not good for any of you. Alright, so, let's begin a look at, then... 'Cause I don't wanna focus on what's causing obesity.

I want to look at some of the changes that occur with weight loss. So, when we look at the impact of weight loss on hunger and satiety and energy intake, I initially had a whole host of slides that we were gonna look at. Well, here's NPY and here's agouti-related protein. And we're gonna get into some of the neural physiology. I go, well, this is probably not the best thing to do. Cliff is here. Where's Cliff? And Cliff's last class in neurophysiology was probably 10 years ago. So, I thought, I better not do that.

(laughter) So, I've taken out a lot of slides. What I wanna focus on is sort of just recapping what I would have said on those slides. So, we look at weight loss effects on adiposity-related signals and gut signals that are interpreted by our brain. So, our adipose signals are insulin and leptin. Well, you all know that insulin is not secreted by our adipose cells, our fat cells.

But it's still considered an adiposity-related signal because it's secreted in proportion to the amount of body fat that we have. And it's not an incredibly tight relationship. Because there can be decompensation that occurs, for example with type II diabetes. But, nevertheless, insulin tends to go up in circulation as we become fatter. So, it is related to body fatness. Course, leptin is related. And insulin and leptin are considered to be, as their action on the brain, anorexogenic.

That is, they are gonna decrease appetite. And, also, they're gonna increase energy expenditure. Some are just mediated by increases in sympathetic nervous system activity. So, when we look at the impact of weight loss, insulin goes down and leptin goes down. And there's a scientist at the University of Colorado, Paul MacLean. He's spoken in our department before at the Smith Conference.

And he has used an animal model mostly. But he's written a review paper. Some of you have read the paper.

And it's really fascinating, because he demonstrates all the benefits that occur with weight loss. And also how some of these very beneficial changes sabotage the ability to maintain weight loss. And some of it is changes in leptin and changes in insulin that occur. So, insulin and leptin are gonna go down. Insulin goes down in the post-prandial state, as well. The hunger signals. So, I would have shown you a slide that took individuals who were obese and then showed their ghrelin concentrations over a 24 hour period. And then after they lost weight.

Ghrelin, remember, is a gut peptide. It circulates to the brain. And then stimulates food intake. So, it's not anorexogenic. It's orexogenic. And ghrelin goes up.

It's been well documented that this goes up with weight loss. And this could readily contribute to an increase in hunger that is characteristic of weight loss. And then, PYY and cholecystokinin, these are anorexogenic. And they go down with premeal or fasting.

And they also don't respond as well in the post-prandial state. And so, again, there tends to be less satiety that accompanies ingestion of food in response to weight loss. At least based on these signals. And I would have shown you, also, not only the changes in these gut peptides. But also the changes that occur in individuals in terms of their subjective ratings of hunger and fullness and these kinds of variables.

So, weight loss also can produce changes in our energy expenditure. So, we've got individuals who... There's their components of their energy expenditure. This is a total energy expenditure.

We've got RMR, thermic effect of food, exercise, non-exercise. And then they lose weight. And then they lose weight. The resting metabolic rate falls. And that's inevitable. I showed you that in a previous slide with the Biggest Losers. And it's interesting because, when an individual goes on a diet and they're in an energy deficit immediately, but they still haven't lost much weight, they can still see a decrease in their resting energy expenditure.

And some of that appears to be mediated rapidly by changes in circulating thyroid hormones, triiodothyronine, t-3. Also, potentially, a rapid decrease in insulin. And that's without much change in body weight. And then, of course, we expect that, because they have less cellular mass now, that their metabolic rate should be lower. But, in fact, in most people, their metabolic rate will fall further than we would predict based on their loss of respiring mass. So, that's an indication of greater energetic deficiency. The thermic effect of feeding, that's naturally going to go down. Because they're consuming fewer calories in order to lose weight.

I think all of you, or many of you, recognize there are differences in the thermic response to different macronutrients. So, protein has the highest thermic effect. So, our metabolic rates will go up higher with a higher protein intake, calorie for calorie, compared to the fats and carbohydrates.

But the thermic effect of feeding, that's the calories that we need in order to process the nutrients that we've ingested. And then, exercise thermogenesis. That can be variable.

Some individuals could actually increase their exercise in response to a weight loss diet. Non-exercise thermogenesis also can be quite variable. I indicated that these decrease, because, oftentimes, they do in individuals who have lost weight. An individual is exercising and now they weigh less. Then, the amount of calories that they're expending to move their mass is going to be less. And so, this can result in a decrease in exercise thermogenesis. And then, there's a group in New York that have been looking at energetic efficiency during sub-maximal low intensity exercise.

And what they suggest is that, when an individual's engaging in exercise in the order of about 25 watts, which is very low intensity, that they're actually more efficient following weight loss. That, in fact, they're expending fewer calories to accomplish that low amount of work. And that this contributes, then..

This increase in energetic efficiency contributes to a decrease in their total daily energy expenditure. And they would suggest that, for many individuals, the decrease in their total daily energy expenditure is more a function of the increase in energetic efficiency with very low intensity movement compared to the change in resting metabolic rate. So, it's quite interesting work.

This group has been doing work on this for the last 25 years or so. Really excellent work. So, when we look at the corrective or the adaptive responses to weight loss following the weight stabilization... And most of the studies that are really well done will do that.

They'll have individuals lose weight and then, rather than measuring a bunch of variables before and then right after they've lost weight, they want to stabilize them for a period of time at their new weight. That's not always easy to do. But it's really important.

Because there's a dynamic phase to weight loss. It's different than the static phase of weight loss. Where they've had that weight maintained for a period of, sometimes it's a matter of three weeks or sometimes it's several months. So, I think it's best to take a look at these dependent variables after weight stabilization. Even then, we see a decrease in RMR.

And much of that is because of the loss of body mass. But some of it, also, is because of an increase in energetic efficiency. There's a decrease in the thermic effect of feeding. Less food. Decrease in the energy cost of movement Again, because of increases in energetic efficiency and also the fact that they weigh less. Greater hunger, less satiety, greater energy efficiency, which I've been getting at here.

There's less energy required for a unit of respiring mass. And this, then, leads us to the concept of the energy gap. And this is a fascinating concept here. Best explained, I think, by this paper by Paul down in Denver. It's the biological pressure to regain weight as a consequence of the increase in appetite and suppressed energy expenditure that accompanies weight loss. So, the difference between appetite and expenditure requirements has been termed the energy gap. So, it looks like this. We want to diagram.

So, we got an individual here who has reached a fairly steady state in regard to intake and expenditure. But it's at the cost of obesity. But their hunger and their energy expenditure are fairly well matched.

So, they're regulating at this higher body weight. This is before weight loss. Then they lose weight. Hunger goes up. Energy expenditure goes down. And now they've got the gap that exists here.

And, in many ways, it's very unfortunate that this would occur. Because of this disconnect between these two sides where it's almost unfair. Here, my energy requirements go down, but I want more. And it makes it very difficult, then, for many individuals.

And Paul would suggest and others would suggest that much of the difficulty that individuals have is not because they can't maintain this new dietary pattern because they lack adequate willpower or they can't change their habits adequately. But, rather, because there's a metabolic drive to regain the weight based on the increases in hunger. Much of which can be explained by changes in gut peptides, adiposity-related signals, neuropeptides in the brain. And that our energy expenditure goes down.

Because of changes that occur in energetic efficiency and loss of body mass. So, it's potentially a very difficult situation. And many scientists would suggest that the very dismal rates of long term success for weight loss can be explained largely by these metabolic changes.

Well, you put the metabolic changes in the context of the environment in which we live and it's almost like there's a double whammy. I mean, how can we expect people to be very successful. If these metabolic changes are occurring at the same time that we live in the environment that we have. So, I would suggest that maintaining weight loss... We need to focus on minimizing the energy gap. And we have to ask ourselves is that even possible? I mean, the Biggest Losers somehow do not seem to be able to do that in spite of all the exercise they were engaging in when they were losing weight. So, it's a question that I don't have all the answers for. And I think there's probably a lot of brainstorming that needs to go on.

And I'm gonna again suggest that not everybody's gonna respond in the same way. And we've got to start looking at things on an individual basis and we'll need that. So, if we're going to take an individual who, on a previous slide, has lost lost weight.

And maybe they're still overweight, but they're experiencing the energy gap. Their hunger's gone up. Energy expenditure's gone down. What we wanna try and do then is to help them maintain this body mass by somehow attenuating the increase in hunger and also attenuating the decrease in energy expenditure. So that we can make it a little more feasible for these individuals to maintain long term weight loss. Again, I think it can be a tall order for many individuals. I didn't realize it would be a tall order, because, when I lost weight when I was in college, I had no trouble keeping it off. And I thought back on that time.

Why didn't I have trouble when so many other people... I think much of it related to exercise. Here, I'm gonna talk about exercise in a department that focuses on nutrition. And various here. And I appreciate your attendance here. People sometimes ask me, "Which do you think is more important, diet or exercise?" And I'm not gonna answer that question given the audience that we have here. I will have to say... Let me just mention one thing.

There are some prominent scientists that have been recorded in review papers or even in lectures that have suggested, based on their comments, that exercise is really unimportant when it comes to weight loss. And I think there's a little bit of truth to this given the fact that it takes a lot of exercise to create the same degree of calorie deficit that we can create by dieting. And it's not a fair comparison at all.

And we gotta look at what's occurring over the long term and not just over the short term. But almost all its head to head comparisons where they're not matching calories. But they're simply putting people in an exercise program versus diet. Diet does better.

That doesn't mean that exercise is unimportant. I'm gonna suggest that it's critically important. Okay, so let's look at some possible ways that we could attenuate this energy gap. We don't have any clear cut dietary recommendations for weight loss means. We don't even have any good dietary recommendations for weight loss. We got all kinds of diets.

And we have all kinds of diets in some ways because none of them are more effective than others. I think, if we had a diet that was really effective, the others would fall by the wayside. But there's lots of ways to lose weight. The National Weight Loss Control Registry... And I just put the names of the two individuals, Rita Wing and Jim Hill. The main investigators behind this. Who established this weight loss registry.

And it indicates all the publications, and there's a lot of them, that focused on this weight loss registry. To be in the registry, the individuals have to have successfully lost 30 pounds for a minimum of a year. The average is actually 33 kilograms of loss that's been maintained for five years. A very significant amount. Now, what this would suggest, right off the bat, is that it's possible to lose weight and maintain weight loss.

Now, I would also suggest that these individuals that are able to maintain the weight loss may be very different than individuals who are not in terms of metabolic factors, genetic factors, epigenetic factors that have contributed to their body weight or their ability to maintain weight loss. They can be very different. And this hasn't been studied much. Rather, what's been studied is their behaviors, primarily. But weight regain..

And I've just took a look at a lot of the studies and sort of compiled some bulleted points that distinguish weight regain with the ability to maintain weight loss. So, regain is associated with higher levels of depression. And, again, even though people have entered the National Weight Loss Registry, there are some that have gained the weight back, but they're still gonna study. So, higher levels of depression.

Binge eating is more common. Low levels of dietary restraint. Higher energy density eating habit and low levels of physical activity. Characteristic of these individuals who have gained weight back. And then, the opposite, the successful weight loss maintenance. Frequent weight monitoring.

In fact, oftentimes, weighing themselves every day. Sometimes I wonder is that a good thing? That the focus is so much on monitoring weight and being very vigilant about that. But, nevertheless, this is one of the factors that is associated with the weight loss maintenance. Very high levels of physical activity. Reduced sedentary activity. So, less TV, less screentime. Lower energy density diet.

So, there's a variety of these. And, actually, the lower carb diets are now starting to be looked at in these individuals. They were not involved when the weight loss registry was initiated. High levels of dietary restraint such that they have a regular vigilance on weekends and holidays. Knowing that these are periods of time where a lot of individuals are prone to overconsume calories.

So, I think there's things we can learn from this. But, again, this is observational. This is not experimental. But it's useful to recognize that some individuals are able to maintain some success with long term weight loss.

There's another registry which is in Greece. And this is a registry of both maintainers and regainers, is what they've been called in the literature, in this registry. The weight loss maintainers versus gainers have greater physical activity. So, we're gonna see some common themes here. A dietary pattern emphasizing home cooked meals. Stop eating out all the time. Fruits, vegetables, unprocessed grains, nuts, meat, proteins, low fat dairy.

Well, this is sort of like the Mediterranean diet, which we might expect in Greece. But lower intakes of salty snacks, sugary beverages, and alcohol. Eating more slowly. This showed up especially in women. And then greater protein intakes relative to body mass. So, this is, again, based on four different studies that I looked at focusing..

And this is the lead investigator in Greece. And a number of different complications. Again, some information that's useful. And, by the way, if you have questions, please ask us. Fire away.

Alright, how about dietary composition? Could that play a role? Well, it's interesting to see and fun to have been in this career to span the time frame when Atkins first came out with his diet back in 1973. And then, later, he came out with a second edition. And Atkins, of course, was vilified. How could anybody suggest that reducing carbohydrates and increasing fat would have any benefit that would produce weight loss? And, yet, he had years of anecdotal information from his own clinic that suggested people did lose weight on that diet. And, of course, he wrote about it.

Dean Ornish would have the totally opposite approach. And they didn't particularly like each other publicly when they debated. But it's fascinating where totally opposing views on what's the best way to regulate not just body weight, but also health. And Ornish as focused less on body weight and more on risk factors for cardiovascular disease. But the Ornish diet... He actually spoke at Fort Collins a number of years ago at the Lincoln Center.

And he emphasizes a very low fat approach. Primarily a vegetarian diet. And we would want to ask ourselves is one of these any better than the other in terms of attenuating the gap? So, let's look at that. So, nurses study that was done. And I wanna see if you can see something on here that probably isn't very real worldish. But, in this particular study by Rachel Maddenham, what she did is she had individuals, same individuals, both normal weight and obese individuals, eat meals that differed in their macronutrient composition significantly.

So, high protein, high carbohydrate, and high fat meals. So, here they are fasting and they eat the meal 30 minutes after. Then they rate their perceptions of hunger. And you can see, with the higher protein in the red, that they were well satiated. And so, their hunger was not as great for the next three hours. Relative to the blue. And that blue is reflected by a high fat approach.

And here, in black, we have the high carbohydrate approach. The high carbohydrate approach is, again, a significant amount of carbohydrates. So, this is pretty similar, also. And it will be suggesting that hunger is not gonna be as great in response to a meal that's high in protein. But I want us to notice something here. High protein's 65% of the calories counted as protein. That's incredibly high.

People don't eat that much protein typically. They could on an Atkins diet in a meal. But, even then, they're getting a fair amount of fat in an Atkins type diet. And fat is more energy dense than the protein is. So, on an Atkins diet, typically, more of their calories are coming from fat than protein. Even though they're eating a fair amount of meat. But, nevertheless, there's potential for protein to be more satisfying. So, then they looked at PYY.

Remember, this is the anorexogenic gut peptide. And they looked at the total, both in the normal and the obese, and then also the most active form. And what they saw sort of mirrored what they were looking at previously with their subjective ratings. That, in fact, PYY was elevated to a greater extent in that post-prandial period that was associated, then, with greater satiation during that period of time. So, a physiological and metabolic explanation for the subjective ratings in these individuals.

So, a study that was done more than 10 years ago now in Europe took individuals who were overweight and obese and they put them on a four week low energy diet. It was a pretty severely restricted diet. They lost between five and 10 percent of their body weight within just four weeks. So, they slimmed down. And then they randomized them into receiving weight maintenance counseling. And then half of them were randomized to this group, weight maintenance counseling.

They met the same number of times with a counselor, dietician, to help them maintain that weight loss. But this group got an additional 48 grams of dietary protein a day. So, they're not manipulating their diet.

Between the two groups, their usual diet. They're giving them counsel about what they should be eating and what they should be doing in trying to maintain. But this group is getting an additional 48 grams of dietary protein. And what happened? The additional protein group, during the three months of post-weight loss when they were attempting to maintain, there was a 50% lower body weight regain. And that consisted only of a regain of fat-free mass. Also, there was increase in dieting. Decreased energy efficiency. As measured in this study.

The actual protein intake as a percentage of calories, even though it increased by 48 grams, they calculated the percentage went from 15% protein in this group. Only 18% of total calories in this group. I haven't gone back and verified their calculations, but this is what they're reporting. And 18% is a reasonable amount of protein. Institute of Medicine says we can have anywhere between 10 and 35%. 35% is pretty high. But, nevertheless, 18%, that's more reasonable.

And so, there's the potential, then, for higher protein intake to have an impact on one aspect of this energy gap. And that's the increase in hunger. And I can remember being in graduate school years ago and the idea of an increase in protein intake was this is potentially detrimental. Because we're gonna leech some of the minerals from our bodies. We're gonna see potential stress on the liver and on the kidneys.

We have to dispose of the excess nitrogen then. But much of this... And I'm not a dietician.

So, if somebody wants to take exception to the things that I said, that's fine. But my understanding is that the Institute of Medicine is not gonna suggest that we can have a fairly high amount of protein if, in fact, there is gonna be damage occurring to a healthy individual. Still, I think 35% is unreasonable to maintain. But, I think, for an individual who has normal healthy liver and kidneys, 20% is very common. Especially among American men. We were doing a study a number of years ago.

And some of the study took place down in Denver, so we met with a research dietician down there. And we wanted the individuals to be on 15% of their calories from protein. And the research dietician down there said, "Well, we'll have to reduce their protein intake." Because the average male's getting more like 20% of their calories from protein here in the US. I edited a review paper by Heather Leidy. She suggests this.

Higher protein diets... They contained 1.2 to 1.6 grams of protein per kilogram per day. That's higher than the RDA. Can potentially include meal-specific protein quantities of at least 25 to 30 grams of protein per meal. Provided improvements in appetite, body weight management, and/or cardiometabolic risk factors compared to lower protein diets. And then she goes on to say that although greater satiety, weight loss, fat mass loss, and the preservation of lean masses are observed, the lack of dietary compliance can be an issue. Because a higher protein diet isn't necessarily very palatable. Although, I think this is where we need to marry the industry of food preparation with nutrition.

We try to do that in the department here. Where palatable foods also can be nutritious foods. So, on the same thing of macronutrient composition. So, I also think that Amanda mentioned this study. And this was a study that was done by David Ludwig and his colleagues at Harvard.

And they had individuals lose weight. So, they had a regular diet and they lost weight with a mixed diet. It wasn't any extreme diet. But a mixed diet. Reduced calorie. And then they randomly allocated them by order into test dietary periods for four weeks each.

So, they had test diet A, test diet B, test diet C. But one of the test diets was very low carbohydrates. One of the test diets was low glycemic index. And one of their test diet periods was low dietary fat.

And the composition, you can see here, carbohydrate relative to fat relative to protein. So, very large differences. And the unique aspect of this is they're really focused on weight maintenance.

The weight maintenance is only a short time. But they wanted to look at some of the issues related to the energy expenditure side of this energy gap that is created by weight loss. So, this is what they found, then. So, here's their baseline RMR values expressed in absolute terms, calories per day.

Here's their baseline prior to weight loss. RMR values expressed in calories per kilograms fat-free mass per day. So, it's standardized. And you can see that their metabolic rate fell when they went on their diet. But here's the low fat diet during that four week period of weight maintenance. Their metabolic rates fell on all of these.

They were lower during that compared to baseline. When they looked at it relative to fat-free mass, what they found was that, on the low fat diet, weight maintenance diet, their RMR was lowest compared to the low glycemic index diet and the very low carbohydrate diet. So, what happened with what we would predict was their metabolic rate fell to a greater extent than could be attributed to the loss of fat-free mass alone. So, they became more energetically efficient. But that change in energy efficiency was attenuated most by the very low carbohydrate approach.

And, remember, the low carbohydrate approach, only 10% of their calories coming from carbohydrates. So, this is very much like an Atkins diet. And, again, I'm not advocating this. I'm just showing some of the data that suggests this possibility that some of the change in resting energy expenditure, which makes up a significant portion of our 24 hour energy expenditure... Some of that could be modified by dietary composition during that period of weight maintenance. Here's the decrease in total daily energy expenditure.

Again, the very low carbohydrate diet came out the best relative to the low glycemic index diet and the low fat diet. Now, Doctor Ludwig has made a substantial amount of research with the glycemic index and glycemic load. If you read the paper, you'll find out that he still advocates this, the low glycemic index diet, because it was associated with a healthy increase in cortisol levels that accompanied the very low carbohydrate diet.

And also the C-reactive protein concentrations were lower. He would suggest that putting all that information together that the low glycemic index diet actually was better. That's up to the reader to judge. Again, this is an extreme diet.

And this was manipulated for four weeks experimentally. That's very different than what people are going to be doing in a real world situation where they're in control of what they're eating. And so, we have to take that into consideration. I just want to take a look at the diet. Now, there's a caveat. And the caveat is related to something I mentioned already. That's the variability of response. If you can see what's in blue, what you see in blue, that's the summary box.

You see that the responses are all over the map. And so, even though we look at the aggregate data in blue... So, here's our total energy expenditure. And it's highest with the very low carbohydrate. Here's the resting energy expenditure.

Highest with the very low carbohydrate. Look at the variability that's occurring here. Now, this adds another layer of complexity. Because how do we know how an individual is gonna respond? So, one of the true-false questions I asked is can we use appropriately the energy balance equation to accurately predict what the outcome is? In life contexts, we have a hard time doing that. Because we really don't know how people are gonna respond. And I'll show you some initial data for that. Dietary fiber. I'll move through this a little more quickly.

So, there's the potential for dietary fiber to attenuate some of the hunger that accompanies the energy gap from weight loss. Some of that could be potentially related to CCK and PYY changes. And reductions in ghrelin. This whole area of microbio is fascinating. I'll not talk about that today, because we have a lot more people in the department that know far more about it than I do. Some people suggest that fiber is important because of this time energy displacement.

That we have increased time to chew fiber and we're not getting the catalyzable carbohydrate from it. And that may be important, as well. Now, how about exercise? Let me talk a little bit about this. So, let's look at this exercise. We have an individual who's sedentary. And they want to lose weight. They've been told they need to start exercising. And their basal metabolic rate's 1.2 calories a minute.

That corresponds to 1728 calories per day from their basal metabolic rate. Their standing metabolic rate is gonna be a little bit higher, because, as they stand... And I'm probably burning a few more calories than some of you, 'cause I'm standing. I'm balancing. I gotta contract muscles in order to not fall over.

So, metabolic rate's gonna be a little bit higher. So, they started an exercise. They listened to some of the recommendations they hear.

I should be exercising 30 minutes a day, five days a week at least. So, they initiate a program. 30 minutes per session. Frequency five times. 150 minutes of exercise.

And their intensity for the exercise, because they're sedentary, can't be terribly high. So, at six METs. So, the metabolic rate has increased sixfold. For those of you that are not familiar with METs.

It's not a baseball team. (laughter) 7.2 calories is six times higher than their basal metabolic rate. So, the gross daily energy cost of the exercise. 30 minutes times 7.2, if my calculations are correct. 216 calories a day in exercise. But, remember, they would have expended some calories anyway. Even if they hadn't exercised during that 30 minute period.

So, I suggested, well let's multiply 30 times 1.4. That's their standing metabolic rate. Maybe they would have sat some of the 30 minutes. And they stood some of it.

Maybe they walked a little bit. Let's give them a value of 1.4. So, we multiply that times 30 to determine what they would have expended anyway had they not exercised. We subtract that from our 216. 174 calories times five days a week. That's 870 calories a week.

That pales in comparison to this dessert. (laughter) Which they can consume in 10 minutes. And so, we have to be appreciative of the reality of what exercise can do in terms of energy expenditure. Now, if you are a long distance runner, like Doctor Braun, you expend far more calories than 216 as the gross cost of the exercise value. Then, obviously, it contributes significantly.

But, for many individuals who are just beginning to exercise, they're unable to exercise at a duration and intensity that is going to contribute a substantial amount of calories or calorie expenditure relative to what we get from our food. So, what are the effects of acute and chronic... Well, I don't have time to get into all of that. But let's look at a study. Overweight obese individuals underwent prescribed, supervised exercise.

500 calories a day, five days a week, 12 weeks. We would predict, based on a static energy balance equation that they might lose about 3.7 kilo. Look at the variability of response. Here's an individual right here that gained fat. Here are four individuals that gained body weight. Here's the individual that lost 30 plus pounds.

Now, they had the same exercise intervention. It was monitored. It was supervised.

The variability of response is incredible. The investigators divided them up into compensators and non-compensators. Compensators, that is, somehow, they didn't lose as much weight as was predicted. And these lost at least as much as what's predicted. But most of them lost more. And what was the difference? The compensators had an increase of almost 250 calories in their dietary intake. This is based on self reports.

Which we know is known for inaccuracy. The non-compensators that lost more weight than predicted actually had a decrease in their response to the exercise. And these were randomly allocated. These were individuals motivated to lose weight by exercise. And the variability of response is huge. So, again, exercise has a place.

But we'd like to be able to understand what is it about exercise that could influence this compensation that's occurring? The same scientists have suggested this. Effective regular exercise on appetite regulation involves at least two processes. An increase in the overall drive to eating with a concomitant increase in the satiating efficiency of a fixed meal. So that, during that post-prandial period, there's less desire to end that by finding food. By eating another meal. And these processes do not operate with the same strength in all individuals. Again, complexity due to individual variation.

I want to finish off talking about this concept of energy flux as it relates to attenuating the energy gap. So, energy flux is a term that we use to describe a total throughput of energy in the body as a function of energy expenditure coupled to energy intake. While they're in energy balance. So, it refers to the absolute level of energy intake and expenditure under conditions of energy tolerance.

Well, this is an adaptation from a study that was done years ago in Asia looking at physical activity and calorie intake. And what was found in this particular study is that calorie intakes were lowest in those individuals who were moderately active. This was primarily occupational activity. Those individuals who had high levels of occupational physical activity, manual laborers mostly... These individuals had high energy intake. Look here, though, on the non-regulated zone, as it's been termed.

Individuals who were sedentary, sedentary occupations, had an energy intake that was much higher than these individuals who are moderately active. They did not regulate intake to match expenditure very well as sedentary individuals with sedentary occupations. Suggesting the possibility that we regulate our energy intake to match our expenditure best when we're active. These individuals also weigh more.

As we predict. So, here's the concept of low energy flux. Low energy expenditure, low energy intake. Here's high flux. Energy expenditure goes up. We need to match it with an increase in energy intake. Could physical activity, then, change this? Yeah, for certain, because of the higher energy expenditure that accompanies physical activity, resulting in the opportunity to balance our calories with greater energy intake.

But there's another way we can do this, as well. Suppose we have two adults, A and B. They lose significant weight. Both achieve weight stability over time. A does this by exercise. B's sedentary. So his energy intake over time is greater than his energy expenditure.

He gains weight. Over time, energy intake and expenditure is the same in this individual. And they eventually the same in person B. How did person B increase energy expenditure? By becoming obese.

So, we have two ways, then, to reach the state of energy flux. High energy expenditure with physical activity or we can change our body size. When we change our body size, our RMR goes up, energy cost of movement goes up, thermic effect of food goes up, and, eventually, we achieve energy balance. But it's at a cost of being obese. So, high flux, two different ways. Which one are we gonna choose? Well, that led us to this study. And I'll finish with this. So, again, the idea that, once people lose weight, we would like to be able to see an increased energy expenditure.

So, just focus on what's up here. Not what's down here. I'm not gonna present any of the data. But we had individuals that underwent some baseline testing and we put them on a hypocaloric diet. So, with Melissa's help and with the Ken O'Regan Center, we had graduate students that helped individuals lose weight.

And they lost about eight kilos, which was the equivalent to 7% of their body weight, over a period of time. We stabilize them for three weeks. And then we randomized them into low flux and high flux conditions with a washout in between. Now, five days is not very long. But we wanted to see if there are any differences in their metabolic characteristics in these two flux states over this five day period. And here's what we found. Energy intake, low flux, about 4400 calories.

High flux, about 3200 calories. 'Cause we were having them exercise. And we had them exercise a fair amount. But they were able to do it. Even though they were not used to it.

We then... And here's our macronutrient intake. So, we wanted to match macronutrient intake despite differences in calories. Here's their body weights over the five days. They stayed the same. So, we think they're in approximate energy balance.

Difficult to measure over a short period of time. Here's their metabolic rates. The resting metabolic rate was, on the average, 80 calories a day higher in the high flux state. Averaged over each of the mornings that we measured it on the high flux days compared to the low flux. They went up in every person except one. Here's then their fat oxidation was higher in all people except for one while they were having their resting metabolic rate measured. Remember, one aspect of the energy gap is increases in hunger. So, even though they're in energy balance, look at the differences in hunger on low flux versus high flux.

Low flux, a lot less hunger. Every single individual. In fact, we had individuals, almost all them said, "We can't eat all the calories you're giving us." We said, "You need to. Otherwise, you're gonna be losing weight." And so, they did not experience the same degree of hunger. Here's on average how full did you feel.

They're eating quite a bit during these days. Again, every single person on the high flux state had a greater sense of fullness. So, when we look at this, I would suggest that exercise may be an excellent substitute for, in this case, snacking. We didn't talk about that. But it may narrow the energy gap by increasing energy expenditure. Not just during the exercise time, but also the throughput of calories during the resting metabolic rate time. And what tipped us off to this originally... We found the same thing in athletes on several different studies.

And one or two done with Chris Bell over in health and exercise science when he was in Boulder. So, this can allow the consumption of more food and experience less severe hunger. And, again, regular exercise is considered to be the best predictor of long term weight loss maintenance. So, I'll close with a quote here by JP Flan. Regular, chronic exercise allows fat oxidation. And I would say energy expenditure, as well. To become commensurate with fat intake at a lower body fat content. So, exercise appears to be a substitute for expansion of the adipose tissue mass.

But one could easily conclude that expansion of the adipose tissue mass is the substitute for physical activity in bringing about weight maintenance. It's at the cost of being obese. So, true-false quiz again. I'm not going to go through that. But, again, I want us to sort of consider, based on what I've said, what our responses would be. So, I'm out of time. But I'll take a couple of questions. (applause) - [John] So, why did not basal metabolic rate go up in that group of the Biggest Losers? If they've gone up when you lose, and you start re-eating, it goes up.

- I don't understand, because it doesn't fit some of the prior research that's been done by Rudy Libel and their group. 'Cause they had individuals gain weight, as well. And their metabolic rates do go up. Overfeeding studies with Bob Buchard with James Levine have also shown increases in metabolic rate. In these studies, they didn't have them lose substantial weight and then see the weight regain. But I have no answer to that, John. It doesn't make any sense.

- [Woman] Do you think it might be the timing of the weight loss? I mean, losing a pound a day over... - I've heard other scientists address this issue. Eric Braverson, who's a very accomplished scientist, has suggested that maybe one reason for this is the fact that the weight was lost so rapidly. And, if the weight hadn't been lost as rapidly, maybe there would have been less of this metabolic change that occurred that seemed to have some permanency to it.

But I don't know if we have an answer to that till that's addressed experimentally. Other questions? Thank you. (applause).

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