166: Why Your Body Fights to Regain Lost Weight

6 years after The Biggest Loser, researchers found something remarkable. The contestants they studied were burning about 500 fewer calories a day at rest than their body composition predicted, even after regaining much of the weight. This is called metabolic adaptation. When you lose weight, a smaller body naturally needs less energy. But sometimes your metabolism slows beyond what that smaller size explains. One important signal is leptin, a hormone Leptin is a hormone made by your fat cells. As fat stores shrink, leptin falls. Your brain responds by increasing hunger and conserving energy. So maintaining weight loss can become harder from both directions. You want to eat more while your body burns less. Now, The Biggest Loser was an extreme example. This doesn't mean everyone who loses weight will experience that same slowdown. But it does raise an important question: how do you lose fat while protecting your muscle and support your metabolism afterward? This is lecture 166 of The Metabolic Classroom. Welcome back to The Metabolic Classroom. I'm Ben Bikman, metabolic scientist and professor of cell biology. Metabolic rate is one of the most misunderstood ideas in health. Much of the confusion comes from treating it as a personal trait, as if some people were born with a fast metabolism and others with a slow one. In reality, the biggest single determinant of how many calories a person burns is quite simply the size of their body. So more body means a higher metabolic rate and less body means a lower one. A larger person has more tissue to maintain, including muscle, organs, and even fat, which does have a metabolic demand all on its own. And all of these tissues cost energy in order to keep them alive. That relationship explains most of what happens to metabolic rate when someone loses weight, since a smaller body burns less fuel. After a large weight loss, though, many people find that their metabolic rate has fallen further than their smaller body would explain. And the contestants of a very pop— or at least a once popular TV show competition, The Biggest Loser— actually gives us the best documented example of this. Now, knowing why that extra drop happens, how to lose fat with less of that big drop, and what can be done once it's occurred matters for anyone who has lost a lot of weight And is now working to keep it off. All right, so let's discuss what the Biggest Loser effect means. Within that overall relationship, the type of fat tissue or type of total tissue matters. Fat-free mass, which includes muscle and organs, is the strongest predict— predictor of resting metabolic rate. So when some of the weight lost comes from fat-free mass, the predicted resting metabolic rate, that burn rate, will fall accordingly. Metabolic adaptation, sometimes called adaptive thermogenesis, is the additional drop beyond that prediction. Researchers measure resting metabolic rate and then compare it with what would be expected for a person of the same fat-free mass, fat mass, age, and sex, and the shortfall that remains is that adaptation. So in practical terms, after substantial fat loss, the calorie budget needed to hold the new weight can be lower than body composition equations would suggest. The Biggest Loser became the teaching case for this because the losses were so extreme, and also at the same time, the measurements they were taking were very thorough and they followed up. For years, contestants combined severe calorie restriction with hours of daily exercise, and they did lose enormous amounts of weight in just about 30 weeks. Researchers measured body composition through dual x-ray, dual energy x-ray absorptiometry. That's just DEXA, D-E-X-A. And also they measured resting metabolic rate by indirect calorimetry. This was during the competition, and they followed up 6 years later. During the competition, 16 contestants— not a big group, but they had severe obesity— they lost about 40% of their starting body weight. Most of it was fat, with only about 1/6 of that weight coming from fat-free mass. That is better preservation of fat-free mass than many diet-only programs achieve. Nevertheless, resting metabolic rate still fell far more than the change in body composition predicted. Resting metabolic rate at week 30 was about 660 calories per day below baseline, and metabolic adaptation was about 370 calories per day. In other words, more than half of that drop in metabolic rate could not be explained by the contestants' smaller bodies. Which means that to hold their new weight, they would have needed to eat about 370 fewer calories each day than a person of the same size and body composition who had never had to lose that weight in the first place. Exercise among the group raised activity energy expenditure during the show while they were actively exercising so aggressively, but it did not prevent that disproportionate slowing of resting metabolism. 6 years later, 14 of the original 16 contestants returned for testing. They had lost an average of about 58 kilograms during the competition. And by 6 years in, this, at that follow-up time, they had regained about 41 kilograms of it. Although the regain varied widely person to person. Resting metabolic rate was about 700 calories per day below the original baseline. Metabolic adaptation in this group had grown from roughly 275 calories per day at the end of the competition to roughly 500 calories per day at 6 years, even though body weight had partly rebounded. So 6 years after the show, with most of the lost weight back on and now a larger body that should have raised their metabolic rate, these former contestants were burning about 500 fewer calories each day than a person of the same size and body composition who had never lost that weight. And the gap was wider than it had been when they finished the competition. Now, of course, you know me well enough to know that I always like to look at hormones. There was something interesting here. Hormones moved with the changes in fat mass and energy status in this group. Fasting leptin fell from a very high baseline value to very low levels by the end of the competition. Then they rose again with the partial regain, but it still was below the baseline. It was— it never got as back up as high as where it started. Triiodothyronine, T3, the active form of thyroid hormone, also fell during the competition, and it later went back up a bit. And fasting insulin fell sharply with weight loss, and it rose again with weight regain. Studies that have been conducted outside of these studying these contestants also suggest the same. People who maintain a reduced body weight continue to expend less energy than predicted, and this adaptation can last for as long as reduced weight is held. That work describes the weight-reduced state as a coordinated physiological condition that the body actively maintains. The simplest part of the explanation is tissue loss. Since losing metabolically active tissue lowers metabolic demand, the biggest loser data matter because a large shortfall remained even after the fat-free mass had been measured and entered into the prediction, the equation. So muscle loss can worsen the problem, especially without resistance training or enough protein, but it cannot account for all of it. Leptin accounts for some part of this. Fat tissue secretes leptin. Roughly in proportion to fat mass. So when fat mass falls quickly and substantially, leptin falls quickly and substantially, and the brain will detect a lower leptin signal as a sign of depleted energy stores. Uh, I hope that makes sense. So if the— as leptin's coming down, that's the brain's conclusion that there's insufficient energy in the body. The response then is going to induce more hunger and a coordinated reduction in energy expenditure. In a particular inpatient study that where people had lost weight up to about 10%, restoring leptin to pre-weight loss levels returned energy expenditure to the pre-weight loss level. Also, the skeletal muscles were working efficiently as as efficiently as they were before, and sympathetic nervous system tone. So how much adrenaline is there, as well as circulating thyroid hormone levels returned to the pre-loss values. Leptin injections have no practical role as a consumer treatment, although this work does show that relative leptin insufficiently links fat loss to both a lower metabolic rate and a stronger drive to eat. Appetite follows a similar course. After substantial weight loss on a very low-energy diet, hunger stayed elevated for a year. And several appetite-regulating hormones, including leptin, remained altered compared with baseline. Hunger and metabolic slowing tend to travel together after large losses because both are part of the body's defense of its prior fat mass. It's as if the body has adapted to the fat mass that it has, and it wants to get back to it. Thyroid hormone does shift during weight— this form of weight loss. In a randomized trial, that produced similar fat loss through either calorie restriction or exercise. Calorie restriction lowered plasma thyroid T3 levels, while exercise-induced weight loss did not. The Biggest Loser contestants showed the same fall during the course of the competition. This pattern is, I think, fair to say, an adaptive energy-saving response, and it differs from primary hypothyroidism. in which the pattern of the thyroid stimulating hormone and the thyroid hormone don't look at all like what we see here. And of course, true, true hypothyroidism does need medical care, but the low normal thyroid hormone levels after aggressive weight loss indicates that the body has just moved into, if you will, a state of energy conservation. Now insulin is part of the response as well. Insulin falls when carbohydrate and total energy intake fall. And when fat loss improves insulin sensitivity and lower insulin does favor the release of stored fat. Research on adaptive thermogenesis describes an early phase of energy sparing during restriction that accompanies the fall in insulin as carbohydrate stores are depleted, followed by the later phase tied to low leptin as the body moves toward defending the long-term fat stores. There's something else here called just spontaneous movement. Spontaneous movement also often declines with weight loss. That this is a, what we could call a non-exercise activity thermogenesis, NEAT. It's the energy that someone spends just, they're standing, they're walking, they're fidgeting. This is outside normal exercise, normal formal physical activity. In 140 premenopausal women who lost weight on a very low-calorie diet, those who did no exercise training saw total energy expenditure, resting energy expenditure, and the non-exercise activity all fall. The women who did aerobic or resistance training preserved their total and their non-exercise expenditure. Now, The Biggest Loser contestants were very active during the show and still showed large resting adaptation, and at 6 years, their physical activity remained above baseline. So resting adaptation and activity are related, but they're separate parts of the total energy expenditure. The Biggest Loser contestants were compared with people who lost similar amounts of weight after gastric bypass surgery. In both groups, metabolic adaptation tracked the degree of energy imbalance and the fall in circulating leptin. So the faster and The deeper the deficit and the larger the decline in fat mass, the larger the fall in leptin and the stronger the conservation response tends to be. Extreme restriction also makes it easier to lose muscle along with fat, especially when protein is low and there's no resistance training. And then losing that muscle lowers metabolic rate on its own before any adaptation is added on top. The Biggest Loser contestants did a good job of protecting their muscles, since only about 1 pound in every 6 they lost came from muscle and other lean tissue, compared with nearly 1 pound in 3 for people who had gastric bypass surgery. Even still, their metabolic rates fell far more than their new size, their new body size, would explain, which tells us that keeping muscle matters but cannot by itself prevent the slowdown when the calorie deficit And the weight loss is as extreme as it was on the show. A slower approach that emphasizes protein and includes resistance training and controlling carbs usually is going to mean a smaller energy gap, a slower weight loss, but also better retention of muscle and a more modest fall in leptin. With that same kind of fat goal in mind, some adaptation will still occur since it's a normal part of energy regulation in animals. The smaller the body, the lower the cost. But the size and the cost to fat-free mass are usually a little more manageable with that form, with a slower form of weight loss. Now, no protocol guarantees zero metabolic adaptation, but several strategies reduce the odds of a severe version of it, like what we see with The Biggest Loser contestants. The first is to definitely preserve muscle very deliberately. Resistance training helps retain fat-free during a deficit. In a multi— in a meta-analysis of randomized trials, higher protein energy-restricted diets better preserved fat-free mass and limited the fall in resting energy expenditure compared with the standard, um, lower protein version. For most adults that are in a caloric deficit, that means you need to make protein, and I would say the fats that come with it, a clear priority at every meal. The second feature here is to train and keep moving throughout the rest of the day. Exercise during weight loss helps prevent the fall in the free living energy expenditure, just the cost of getting through your day. And that usually drops when it's just diet alone. And an hour in the gym is not going to offset an otherwise very sedentary life. So this is the idea of exercise snacks, just doing a bunch of small little things throughout the day. The third point here concerns what you eat once you reach that weight that you want to maintain, and it helps to begin with which fuel the body burns. Indirect calorimetry is a test that you can use not only to measure metabolic rate, but also something called the respiratory exchange ratio, the ratio of carbon dioxide produced to oxygen that is consumed. A higher value of that RER means the body is burning relatively more glucose and not very much fat. So the body's more in sugar burning mode, and that's the pattern that you would expect when insulin is elevated. Indeed, that's exactly what insulin does. If insulin's up, it tells the body to be in sugar burning mode. So that would be manifest as a high RER. And again, in contrast, if the body is burning more fat, then the RER value will be lower. I take time to explain this because I want to share— I want to bring in findings of a study called the Baltimore Longitudinal Study. It followed about 800 study subjects for about 10 years, and they wanted to understand what predicted weight gain. They found that a higher fasting respiratory exchange ratio, a higher RER value, predicted weight gain even after accounting for things like age and body size and fat-free mass. Interestingly, resting metabolic rate did not predict it, and neither did how far a man's metabolic rate, or the study subject's metabolic rate, sat above or below what they expected it to be. So let me just say that again. They looked at the metabolic rate and found that someone's starting metabolic rate over this 10-year period did not predict who would gain more or less weight. So among the group of the study subjects that started out where they weren't obese, those that were burning more glucose or sugar burning at rest had nearly 2.5 times the risk of gaining 5 kilograms or more than the group with the lower RER, the group that were more fat burning. Now, the association was a little modest, and this is an observational study. But even so, it suggests that the fuel the body burns during maintenance may matter more than the metabolic rate itself. And controlled feeding trials have tested what happens to energy expenditure when the diet shifts the fuel that is used, and then when it shifts deliberately to burn more fat. The first study that comes to mind was a crossover trial in which 21 young adults who had lost 10 to 15% of their body weight ate 3 diets for 4 weeks, each at the same calorie level: a low-fat diet, a low glycemic index diet, and a very low-carb diet. Total energy expenditure was about 300 calories per day higher on the low— on the very low-carb diet than on the low-fat diet. So the people that were eating a diet that kept their insulin low were just burning 300 more calories a day by just Living. No, no deliberate effort to increase exercise or anything similar. A larger trial actually followed up and had about 160 adults who had lost about 12% of their body weight, and they were on a high or moderate or low-carb diet for 20 weeks with protein constant across them. Total energy expenditure was about 200 to 280 calories per day higher on the low-carb diet. Before the weight loss began, the researchers measured how much insulin each participant released 30 minutes after drinking a standard dose of glucose, and they divided the participants into thirds based on that response. They planned this analysis in advance to test the specific prediction of the insulin model of obesity. In other words, the degree to which insulin predicts and causes obesity. What they found was fascinating. Among the people in the highest third of insulin secretion, So the people who secreted the most insulin in response to that glucose load, total energy expenditure on the low-carb diet was about 300 calories per day higher than on the high-carb diet, and about 480 calories per day higher among those who followed their assigned diet most closely. So the people who were the most strict to keep their weight stable, these high secretors on the low-carb diet also had to be fed more than their counterparts on the high-carb diet. So they got to eat several hundred calories more just to keep their body weight under control. And ghrelin, which is a hunger— a hormone that stimulates hunger, was lower on the low-carb diet, and leptin was lower as well, which the authors interpreted as a possible improvement in leptin sensitivity. The effect in the highest insulin secretors is on the same scale as the adaptation measured in The Biggest Loser contestants 6 years after the show. Although the 2 studies involve, of course, very different people at very different amounts of weight loss. So the comparison is more a matter of speaking to a trend than anything else. But these results fit the view that lowering insulin demand eases the energetic cost of the weight-reduced state. They are not— it's not universally accepted, these views, but I hope I've articulated them in a way to help you understand at least my view. So for an insulin-resistant person, a diet lower in refined carbs and higher in protein and natural fats will support fat use as the primary fuel with less of a constant insulin elevation, and it can help possibly preserve energy expenditure during this weight loss phase. Again, if you're keeping insulin low, metabolic rate is going to be higher, and that is what appeared to be part of what went wrong with those Biggest Loser contestants. Now, the last part of this is to, um, plan for maintenance before the weight loss ends. So after a large loss, maintenance calories are lower than before, and they may be lower than a standard calculator would suggest in light of this adaptive response. So building habits that work at that new calorie balance would matter, I think, more than how quickly you do lose that weight. Full reversal of metabolic adaptation, so trying to bring back up that gap of, of a lower calorie than you'd expect, is, is not— there's no established clinical outcome here or, or clinical intervention to help with that. But several steps can improve the situation. The most reliable is really maintaining or even building fat-free mass. If an earlier weight loss included substantial muscle loss, just aggressive, progressive resistance training and adequate protein and fat increase that metabolically active tissue, that, that muscle that raises the predicted portion of the resting metabolic rate, even if some of the adaptation still is there. Training also protects the free living energy expenditure after weight loss. So resistance training and daily movement deserve a pretty permanent place in any routine here. Anyone with symptoms that would suggest a thyroid problem should, of course, have it evaluated because adaptive changes in T3, the active thyroid hormone, do differ from actual true hypothyroidism. But thyroid hormone levels do change and they do come down. Also, food quality matters at this stage as well. Appetite signals can remain altered for well over a year after weight loss. If you got a lot of hunger and you have a lower caloric demand, that's a pretty terrible combination, especially in light of our modern easy access to refined insulin-spiking foods. That's going to be a pretty difficult combination to get over. Again, the higher hunger and the lower metabolic demand. Improving the consumption of protein, making sure it's very nutrient-dense sources coming from low glycemic load foods. All of this is going to help maintain an optimal metabolic milieu where your insulin is lower, metabolic rate is higher, muscle mass and other lean mass tissues will also be higher. The 6-year data in The Biggest Loser contestants also provides some realistic expectations. Adaptation can persist for years in people who keep their weight below its former peak, and those who maintain more Loss can show more ongoing slowing. That is kind of discouraging for anyone expecting a quick reset. That just does not happen. But it does make clear that long-term maintenance requires attention that goes well beyond the end of the active weight loss. And I think knowing that— well, knowledge, knowing is half the battle. People who know that can plan for it. So the extra fall in metabolic rate after large weight loss reflects low leptin, Low thyroid hormone, reduced sympathetic drive. So, you know, an, an altered response to epinephrine or adrenaline. You have muscle that doesn't quite work the same way as it did before. You're also going to be a little less spontaneous in your movement. You're going to be more sedentary without really being able to identify it. But all of this is going to work to try to defend the fat mass that your body adapted to. It kind of wants to get you back, but As the contestants showed, even when you do get back to your former weight, if you do, your metabolic rate doesn't come back. So the potential for you gaining back more than you lost, of course, goes up. Ample protein, resistance training, daily movement, a diet that helps keep your insulin low, but while providing adequate calories to keep your muscle and other lean mass fueled— that is the key. Those remain the most useful tools. Um, in the midst of the weight loss, and I would say even after some aggressive weight loss has already happened. That's it. Class dismissed. Until next time, more knowledge, better health.