 Thank you for inviting me, it's a pleasure to be here. Caveat, this is a first time talk, so if it's lousy, I apologize. So, past year there have been a lot, one of the hardest things I have in this business is to seem to get across this idea of what we mean or I mean when I talk about, you know, not being about calories. And so I wanted to present that, sort of see if I could clarify that in the talk and at the end of the talk, half the talk, we'll be presenting some tests that could be done that would demonstrate whether or not it's calories or carbohydrates that are driving obesity. So the conventional wisdom, we know the fundamental cause of obesity is an energy imbalance between calories consumed and calories expended. There's virtually no way to get around this whenever I talk about it. You know, someone accuses me of being a quack if I argue otherwise. The first idea is obesity is an energy balance disorder. You see this line in a lot of the technical papers on the subject. It's just, you know, what we're worried about ultimately is that too much food, too little physical activity causes this thing called overeating, energy ingraded and energy out, and the result is obesity and the obesity epidemic. So the alternative hypothesis, the argument that I've been making in my books that comes originally from pre-World War II researchers in Europe is that obesity is a fat accumulation disorder. Okay, to me this seems like the simplest possible thing you could say about the subject, right? Having too much fat is a disorder of having too much fat. And what we want to know in that circumstance is what regulates fat accumulation. So in this hypothesis what we end up with is this idea that grains, starches, sugars, carb rich foods, disturb insulin signaling, and we end up with excess fat accumulation, obesity, and the obesity epidemic, so we have a different cause and the different, the same result just by changing how we think of the disorder. The challenge is how do we tell which is right and how do we tell them apart? Are we dealing with an energy balance disorder? Are we dealing with the fat accumulation disorder? Because if somebody's getting fatter, they're going to be taking in more calories than they expend. This is a given, this is what we know for sure. We have the energy balance equation, the first law of thermodynamics. It's always true. It's always true that it's a law of physics, that's why we call it a law. And it's basically changing energy stored in the system is equal to the energy in minus the energy out. Delta E store equals E in minus E out. And this is what we're going to start from in both these equations, both these hypotheses. And in the energy balance disorder version of this equation, E in minus E out are causal. So you change energy in and you change energy out or you change energy out and you end up with the change in energy storage. So if we increase E in or we decrease E out, we're going to increase the amount of energy stored in the fat tissue, you're going to get fatter. So this is what it looks like. Now if obesity is energy balance disorder and carbohydrates make us fat, which is something that I've been arguing, the reason they make us fat is because they just eat too much of them, right? We increase E in because of the carbohydrates and that increases the amount of Delta E stored. We also eat too much of everything because the calories are calorie, but carbohydrates are particularly easy to overeat. Now if obesity is energy balance and then carbohydrate disorder and then carbohydrate diets work possibly because they increase satiety and so we eat less. So you get rid of the carbs in the diet, you eat more protein and fat, these satiate you, they decrease E in, that's the cause, and the effect is they decrease the E stored. Now another way to look at this is maybe these things work because they provide a metabolic advantage. So we decrease the carbs in the diet, we eat more protein, which generates more dietary induced thermogenesis. Now the second law of thermodynamics gets involved and we expend more energy for calorie consumed, breaking down the protein and metabolizing it. So in this scenario we increase E out by eating more protein and decrease E storage as a result and we're still working in this energy balance disorder paradigm. Now the alternative, oh okay let me one more slide, if obesity and energy balance disorder, what you end up realizing is that it's the brain that regulates body fat mass. I read my book Why We Get Fat, I have a whole chapter where I go off on the idea that gluttony and sloth are involved and when you're talking about overeating and you're talking about sedentary behavior, you're talking about behaviors causing a physiological problem, too much fat and I don't think this is a behavioral defect. But you could see even when you get to sort of the kind of state of the art in the energy balance hypothesis, you have a lot of factors that determine their genetic developmental factors, inflammation, environmental factors and diet. They all determine ultimately in the red circle expenditure and intake and the central nervous system regulates body fat mass in this paradigm by coordinated adjustments of intake and expenditure. The actual fat mass itself isn't involved. It's just sort of passively embracing or sending signals back to the brain but the brain is determining whether we get fat by modulating expenditure intake. So what we worry about is full body energy balance. This is why it becomes a brain thing. We worry about how much energy we take in the whole body and how much energy we expend and it's what comes in here and what goes out here and the fat cells themselves, the fat masses are kind of passive players and all this and when I use this metaphor in the book it says though we want to know why this room is so crowded and what we're thinking about is well it's crowded because we took in more people than we expended and we let out and that's why it got crowded so there's positive people balance but it's even worse than that. It's as though we're saying more people came into Cambridge than left Cambridge and that's why the room is crowded and what we want to know is why did people actually walk through these doors and maybe they walked through the doors because there was a compelling speaker in here or there were free drinks in here or there was somebody who thought was going to be a compelling speaker who was less compelling. Maybe there's free food, maybe the fire extinguishing system broke out there so it's pouring outside so everybody ran into this room because that's the only way they'd get wet outside. Maybe we put huge people standing at the doors, bouncers, and every time somebody walked by they told them and threw them in and so the argument would be instead of caring about how many people came into Cambridge and left what we care about is what the factors inside this room, what are the variables that might have pulled people in or drawn them in here or not let them left or what are the factors outside that might have forced them to flee the outside to come in or even what are the factors at the room membrane, the bouncers who pulled people in or pushed people out and then we start to get a real explanation for why the room is so crowded. So we don't care about full energy balance. What we care about is fat cell energy balance. Here's where that hypothesis matters. Here's a fat cell, you've got the fat cell membrane and if more energy goes into the fat cell then leaves it, that fat cell is going to get fatter. And the fatty acids involved, there's permeability of the cell membrane involved, there's enzymes on the cell membrane that could pull fatty acids in, there's enzymes inside the fat cell that'll break down fat and allow it to exit. And so what we really want to know, what I think we want to know is not how much energy goes into or out of the body, into or out of Cambridge but what are the factors that regulate how much energy goes into or out of the fat cell, into or out of this room. So a brief argument favor this to me is just puberty. And when we think about any other hypothesis of obesity that involves energy balance in general, we know boys and girls start puberty with roughly the same amount of body fat and then they grow and they get bigger and boys lose fat and gain muscle and girls gain fat in specific places. So they're both taking in more energy than they expend because they're getting bigger, they're getting heavier. That's what that first law of thermodynamics tells us. But why does it turn into muscle in boys and why does it turn into fat in girls? Because by the time the girls get out of puberty, they have 50% more body fat than the boys. And why does the fat go to specific places? So if we just look at the girls now, and we think of this girl getting fatter and turning into a woman, she's developing breasts, her hips are filling out. Let's say she's getting fatter also, so she's getting a gut. But she's taking in more energy than they expend. How does the fuel know whether to go to the fat and the gut, which is the excess fat, whether to go to her hips or her breasts, which is becoming a woman, which is regulated by sex hormones, or just, you know, we're building muscle, she's getting bigger, we're building bone, we're building connective tissue, and we're somehow, ultimately, there has to be something determining the cells themselves are getting the excess energy. The cells have to be making the decision on some point in cohort with the hormones that are being secreted. We know that sex hormones are determining the fact that the boy is gaining muscle and the girl is gaining fat in specific places. So there has to be some interaction between the hormonal milieu and the cells themselves to make sure they get what they want, irrespective of the fact that there's just too much fuel around anyway because this person's getting bigger. So a good way to phrase it, this was actually, and I'm from an article written in Science Magazine, on cancer, and it struck me, actually the two, Lou Candley and Craig Thompson are both people who actually believe that sugar and carbohydrates could be causes of cancer, and in science, they said multi-cellular organisms, most cells are exposed to a constant supply of nutrients. Survival of the organism requires console systems that prevent the barren individual cell proliferation when nutrient availability exceeds the levels needed to support cell division. Uncontrolled proliferation is prevented because mammalian cells do not normally take up nutrients from their environment unless stimulated to do so by growth factors. There's always enough or an excessive amount of fuel available to the cells. If there wasn't, your cells would always be in danger of starvation. So why do some of them take up more energy? That is irrespective of what's happening on this full body level. And the answer in fat cells, as this is a 1990 paper put it, you know, in humans, adipose tissue is the main site of energy storage. So the balance between inflow and outflow of free fatty acids and adipocytes is finally regulated by a number of hormones and neurotransmitters which elicit the appropriate response to the metabolic state of the individual. That's how it's very well regulated. And among these extracellular signaling, insulin is thought to be the most powerful inhibitor of free fatty acid release. Many studies have documented this. So if we look at it, this is from a 2010 textbook by Keith Frane, sort of the leading expert in the world on fat metabolism. And I could demonstrate, you know, hormonal regulation of fat cells. We have fat storage. It's insulin, insulin, insulin, insulin, insulin. Other hormones play a role. We know sex hormones play a role. But in response to the nutrient content of the diet, pretty much we're talking about insulin. It's been known since early 1960s. Same with hormonal suppression of fat mobilization. It's insulin. Okay, release of fatty acids from fat cells. Okay, so here's the hormonal defect, the fat accumulation version of the energy balance equation. This guy, Delta E, lives in a hormonal enzymatic central nervous system soup of regulators. Okay? It is regulated very tightly. And anything that lowers the regulation to reduce Delta E is going to cause a change in E in and out E out. So cause and effect are reversed. Here what we're interested is this hormonal regulation of the fat storage. Okay, and in this world, if obesity is a hormonal enzymatic disorder, if it's a fat accumulation disorder, then you could argue that carbostricted diets work because they reduce insulin, which reduces fat storage. So the cause is a reduction in insulin. The effect is a reduction in fat storage. Another effect is intake gets lower or energy out gets smaller because we know if Delta E gets smaller, then this person has to be under-eating. He has to expend more energy than the end. So this is a cause. This is an effect lowering fat accumulation, lowering hunger, increasing expenditure. Okay, so the question, one question is, hasn't this issue been settled? You know, some carbs, calories thing. And we recently did a very comprehensive review of the literature going back to, I think the first study was in 1932. There have been 80-some years of studies, 80-plus in total. They include over 4,000 subjects, 1.2 million subjects days. And I can tell you beyond a shadow of it there are no definitive answers to this, okay? The primary problem with virtually all these studies, whenever we think about this, is that total calories include carbohydrate calories. Okay, carbohydrate calories represent about 50-55% typically of the amount of calories we eat. So if somebody does a study where they say, I'm going to restrict intake, E in, and I'm going to lower calories, they lower carbohydrates as well. And as a result, they change insulin signaling, even though they think of this diet as working. And under these circumstances, the two hypotheses, the two paradigms can look identical. Okay, so here's a good example. This is the Israeli Atkins Mediterranean Diet, low-fat diet trial, shy it out, came out in the New England Journal. And you could see that there was a, you know, here's the very low-carb diet, the Mediterranean diet. And at least in here, when people are complying with the diet, definitely you get a significant difference in weight. If you actually look at what these people were eating, what do you see on the low-fat diet? This is the low-fat diet. So they're eating after two years, 570 calories less than they were when they started. But of those 570 calories, 330 less are carbohydrates. So even in the low-fat arm of this study, the greatest reduction in calories is in carbohydrates. So now when you see an effect, and when you ever hear people say, look, some people do better on low-fat diets, some people do better on low-carb, the question you have to ask yourself is the difference could be that a low-carb diet restricts carbohydrates more than a low-fat diet. So some people get better on a moderate dose of the drug, carbohydrate restriction, and some people get better only on a, you know, serious dose of the drug. But the question is, how do you tell the difference? When we looked over these 80-some studies, there were a lot of recurring problems. You know, a lot of them are just free-living studies. So we give people an Atkins book, an Ornish book, American Heart Association recommendations. We counsel them, we send them off into the world, and we don't actually study the effect of changing the macronutrient composition. We study the effect of telling people to change the macronutrient composition. And those are two entirely different things, as we all know. A lot of them were small samples, like half a dozen patients, three patients. They lasted for a week or two, three weeks. Some of them calorie restrict both diets. A lot of them do this. A lot of these studies tell people to eat, say, 1,200 calories of the low-fat diet and 1,200 calories of the low-carb diet. But now, first of all, you've assumed that in order for them to lose weight, they have to eat less. So you've built into the study one of the hypotheses you want to test. And because, as we said, if you restrict calories, you're going to restrict carbs, so both diets are going to be carbohydrate restricted. And you might be studying a diet that's restricted by 600 calories to a diet that's restricted by, say, 8 or 900 calories. And now you have to have carbohydrate calories, and now you have to ask yourself, would I expect to see an effect? Instead of thinking this is a low-fat diet, this is a low-carb diet, you ask yourself, would I expect to see an effect if I restrict by 600 calories of carbs versus 900? And the answer is probably not. Often, they included low carbohydrate diets that are still relatively high in carbs. Often, they manipulated fat and protein, some of the latest overfeeding studies add protein or fat to the diet and then try to make some assumption they don't actually lower carbs, they don't lower insulin secretion. And sometimes they use naturally lean subjects to study fat accumulation, which boggles my mind. The most famous one of these studies is this 1992 study by Live One Hersh. Energy intake required to maintain body weight is not affected by wide variation in diet composition. Even with extreme change in the fat carb ratio, there was no detectable evidence of significant variation in energy need. But there was a caveat. They used lean people, minnowage lean people, who are arguably tolerant, have already proven if they're lean by their 40s and 50s that they can tolerate a high-carb diet, because that's what they're eating. So the caveats are similar results might not have been obtained in a group of obese individuals or lean individuals predisposed to obese today. Aren't those the people we want to study? The ones who actually get fat? It's like trying to study the effect of cigarettes on lung cancer and people who don't get lung cancer. Okay, so how do we test it? This was one test that came out a month ago. If you guys, I wrote about this, I did an op-ed on The New York Times, David Ludwig and his colleagues from Harvard Medical School. This was an interesting test. Many people can lose weight for a few months, but most have difficulty maintaining clinically significant weight loss. One explanation relates to behavior and that motivation to adhere to restrictive regimes, typically diminishes with time, which means they fall off the diet. An alternative explanation is that weight loss elicits biological adaptation, specifically a decline in energy expenditure in an increase in hunger that promote weight gain. Okay, this is a very well-accepted finding in the field. If you lose weight and you get smaller, you expend less energy, so you have to eat even less than you normally would to maintain your weight. There was a whole New York Times magazine article written about this last January. So this is what they do. They take 21 obese or overweight patients. They semi-starved them, so they lose 10 to 15% of their body weight. And then they put them on three different diets, what it's called a crossover design. So it's like a month on this diet, a month on that diet, a month on that one, or some order. Energy expenditure. So they know they use this technique, a doubly labeled water. They say these people are like, Joe here is expending 2,600 calories in his weight-reduced state. We're going to give him 2,600 calories a day. So our energy balance hypothesis says it's not going to gain weight, but we're going to do it in a low-fat diet with 60% fat. Whoa, that should be 60% carbs, 20% fat. This is what happens when you give a talk for the first time. 100% energy expenditure, a low GI diet. So that's 50% fat, 40% carbs with their low glycemic index. 100% energy expenditure in a ketogenic diet, although it probably wasn't ketogenic, actually we know it wasn't ketogenic, 60% fat, 30% protein. And they go through these, they cycle through these in random order. And so here's our intervention. You could think of it as our intervention lowers insulin in different levels. The glycemic index a little bit, low carb diet a little more. We fix energy in because we're going to feed them exactly what they were expending when the study started. And what we want to know is what is the effect on delta E stored and the effect on E out? Okay? So our predictions, our energy balance equations says all three groups maintain weight and energy expenditure remains constant because we're feeding them exactly as much as they're expending. We're making E in equal to E out. Our fat accumulation disorder says the greater the carb restriction, the greater the decrease in insulin, the greater the energy expenditure, and the greater the weight loss. Okay? And what you see, this is hard to make out, but here is total energy expenditure. So they measure their energy expenditure prior to the weight and prior to losing weight it's around 3200 calories on average. And the low fat diet, they expend around 2800 calories. And the low glycemic index, they expend around 2900 calories, 120-odd calories more. And on the very low carbohydrate diet they expend 300 calories more. Okay? What's fascinating, if you look at this chart, told us, oh, here's low fat, low glycemic index. So this is high carb, lower carb, lowest carb. And here's the energy at weight maintenance. Okay? You know, that they start at. And about half the subjects actually, excuse me, this is the energy they're expending before they lose the weight. So before their weight reduced and about half the subjects on the very low carbohydrate diet actually increase their expenditure above that which they were expending before they lost the weight to begin with. The funny thing is, they did the studies for 28 days. So e-out, they decrease insulin, e-out shoots up. The less carbs, the greater the increase in energy expenditure. We spoke to the researcher who did the study, David Ludwig, we had dinner with him last night. They saw a reduction in delta E. They had to if e-out went up. And this stayed the same. But it wasn't significant enough to report and what they want to do is do the study for instead of 28 days, do it for six months or nine months, and then you'll be able to see whether or not you get a change in what you have to do. So there are other tests as well. Okay? The Ludwig test started off just by weight reducing people. Okay, so you semi-starved people so they lose 10 to 15 percent and then you fix their energy expenditure and the assumption was which diet is better for weight maintenance. This is in part, I think, because the researchers didn't believe that you could lose weight on a diet without decreasing energy expenditure, so you can start with obese and overweight men, reduce their insulin, fix their calories at whatever they're eating when they're obese or overweight. So let's say I'm an obese guy and I eat 3,000 calories a day. I'm going to keep my diet at 3,000 calories but I'm going to change the macronutrient composition. So I'm in a lower insulin. Delta E should go down if we lower insulin. That's what our theory says. An e-out should go up independent because this isn't a caloric issue. So we should be able to take n obese or overweight men, let's say four dozen, and randomize them into two groups with a high calorie diet so we measure their energy expenditure and we give them a nice balanced diet 35 percent fat, 15 percent protein 35, well it should be 50 percent carbs lean meat, whole grains, fruits and vegetables exactly what we're told to eat but exactly the amount of energy they were expending or a high calorie ketogenic diet 100 percent energy expenditure less than 40 grams a day sort of Atkins induction. We've got to do it for longer than four weeks because over four weeks you're going to get a lot of water loss so ideally 2, 3, 4 months the longer the better and the reason we go for a ketogenic diet is because of this graph which I find could be the most important graph in this field and if you plot this came out of a study the Defranzo study in 1990 Defranzo was the inventor of the technique to measure insulin levels this insulin clamp and if you plot fatty acid mobilization by insulin levels you see as insulin comes down the amount of fatty acid turn over in oxidation you get is relatively stable and then you get below a certain number and it shoots up insulin regulation of plasma free fatty acid is maximally manifested low physiological research is a refer to and this is being like the fat tissue being extraordinarily sensitive to insulin you get below a certain level and suddenly boom it's dumping fatty acid the bloodstream and your lean tissue is oxidizing and if we go to a ketogenic diet if we lower insulin levels as low as we can get them we can be confident that we're beneath that level and that we're going to be able to see an effect okay so here are the predictions of this other experiment the energy balance disorder weight and energy expenditure remains constant remember measuring the people's energy expenditure and we're giving them an intake exactly equal to that so e n equals e out there's no change in weight the fat accumulation disorder the carbostricted groups lose weight and increase energy expenditure despite e n equaling e out because we're lowering insulin lowering fat storage increasing fatty acid mobilization they're going to lose weight and expend more energy it's an easy experiment to do the caveat is when you're done with it if you've shown that you can feed someone exactly what they're eating and get them to lose weight then you write up the paper and you send it to the reviewers and the reviewers say obviously they didn't eat what you gave them right because we know that the only way to lose weight is to eat less and you're saying they didn't eat less so you got to put them in a metabolic ward you got to isolate them and be able to prove that they ate everything you gave them and now the experiment gets difficult expensive you got to be rigorous you got to be meticulous it can be done and we're hoping to get people to do it but it'll take time here's another example remember calories actually this is what I mean by calories being irrelevant as long as we decrease insulin we should decrease delta e this fat stored in the fat tissue even if we increase intake so we could do an experiment where we give you more food let's say we measure your expenditure my expenditure I was eating 3,000 calories a day and I was weight stable now I'm going to give me 3,600 calories a day 120% of the energy I was expending okay but it's going to be a ketogenic diet so it's going to lower insulin now I actually I put 2 arrows here in a question mark because we don't actually know if I'll be able to eat that diet and that's a little technical to get into right now but I may be too satiated because I'm burning too many fatty acids but if I can eat it and it lowers insulin then we have to have e-out go up and it's got to go up more than e-in so for feeding you 120% of your expenditure of your expenditure and you start losing weight then you have to be expending more than 20% more than what you're expending to begin with a very large effect and it should be measurable so here's a study, an obese or overweight man you get a high calorie balanced diet 120% energy expenditure exactly what we're told to you but 20% more than you're eating today and you study it against a ketogenic diet again you have to monitor and isolate the study because if these people actually lose weight well then they need what you gave them predictions, the energy balance disorder people are going to say both groups are going to gain weight because we're feeding them more than they were expending e-in is bigger than e-out they get fatter this is what you want in an experiment you want an experiment that compares in which the two different hypotheses give you two different answers the fat accumulation disorder is going to say if you decrease insulin those people are going to lose weight and their energy expenditure will have to go up and we can measure that as well I actually presented this experiment at the Pennington Biomedical Research Center about three years ago trying to get them to do it because they have the facilities and the director of the center Claude Bouchard spent his whole life doing what are called overfeeding experiments and he said I've done overfeeding experiments my whole life he's French-Canadian and I predict both groups are going to gain weight because they always gain weight and Eric Raveson was a science director the institute was sitting in the audience and I asked him what he thought because I had asked him that morning and he had studied nutrition and metabolism very carefully and he had told me that morning that the ketogenic diet group would lose weight it doesn't matter if you overfeed them if you lower insulin and lower fat accumulation they're going to lose weight if you lower insulin they're going to lose fat and burn it but I had to ask him four times to say it loud enough so that people could see that he disagreed with the director of the institute okay there are other tests you could do and they're all based on questions we can ask okay so if a beneficial effect of calorie restriction intervention we semi-starve someone that's attributed in a paper either the calorie restriction or the weight loss often you see they'll semi-starve people they say look diabetes went away that means losing weight resolves diabetes but if the losing weight was caused by the restriction in carbohydrates when they restricted calories which is possible then it's possible that some or all of the effect that they saw was due to the restriction of carbohydrates not due to the restriction in calories or the weight loss here is the most extreme example of this I ever found this was a paper that came out about three years ago in science they wanted to see if calorie restriction makes primates live longer primates live a long time these monkeys live about 27 years on average so they started this study in the late 70's and they calorie restricted them here's a calorie restricted animal versus a normal animal at 27 years of age you can see how healthy this one looks here's the first occurrence of age related disease charts so here's the control diet here's the calorie restricted diet if you think it's 30% less calories and they wanted it this is great if you calorie restrict someone they live longer so here's what they were eating this is the primate diet 30% cornstarch almost 30% sugar 10% corn oil I said to the research who did this study Rick Weindrich, I said Rick what are the possibility the reason they live longer is because in the 30 calorie restricted they live by 30% and cornstarch for 30% and he said that's probably the reason I agree with you the problem is in order to get their study funded they had to propose to use this diet which is a diet recommended by this group the AIN for feeding primates in captivity and so you don't know you have no idea but I would argue that you restrict the sugar from a natural diet they might live who knows how long these monkeys will live here's another example reversal of non-alcoholic fatty liver disease hepatic insulin resistance so they semi-starved people with the 1200 calorie diet in conclusion these days to support the hypothesis that moderate weight loss normalizes fasting blood sugar in patients with poorly controlled type 2 diabetes and it gets rid of their hepatic their fatty liver disease but in restricting calories to 1200 calories which is what they fed them they've restricted carbohydrates in half also so maybe it's the carbs so how would you test it that's pretty simple you take your obese overweight diabetics so here's this diet they put them on which is 1200 calories about 600 from carbs so you do one arm with that diet and then you do one arm at 100% of energy expenditure so let's say they were expending 2500 calories originally or you let them eat as much as they want or you let them eat as much as they want but you match the carbohydrates so if these two studies get the same effect it suggests that the reduction in carbohydrates was the beneficial factor and then you could also do an ad libenum or a ketogenic diet where you drop the carbs all the way down and see if you get even a better result but you start doing multiple arms where you acknowledge that when you reduce calories you also restrict carbs so let's do an arm where we restrict carbs but not calories and see if the carbs are the problem the other question is if you see a study that shows a deleterious effect of calorie restriction so now we semi-starved people when something bad happens and then you do that in an obese subject so they attribute it to either calorie restriction or the attendant fat loss and you ask the question is it possible that the same thing would happen in a lean subject so you do these studies where they restrict obese subjects so you find out that they expend less energy and you would say well obviously there's something about the obese state that people want to stick to their set point is high but you can do the same thing in a lean subject and see if they also show the same results I know these actually in this case they do because those studies were done in 1917 in other words is the effect caused by an obese individual losing weight or is it caused by the semi-starvation that you use to make the subject lean what happens if the subjects lose weight without semi-starvation remember we don't have to starve them we just have to lower their insulin levels in this alternative universe so here's a classic example of this study this is Rudolibu where they semi-starved people and low and behold energy expenditure drops and this is why we think it's so hard to maintain weight loss but you could do the same study very similar to the other study you could do obese or overweight subjects and lean subjects so we could see if the effect we saw holds if we semi-starved lean people they too will have their energy expenditure dropped literally five or close to five and again we just we manipulate the carbohydrate content and the calorie content for the diet so when we actually get our results we could see what caused the effect was it the semi-starvation was it the fat loss in these cases this is how you would do it so you basically lower insulin you fix energy in it's effectively the same study that Ludwig did that I talked about earlier but you got to do it for longer than a month and then there are a whole host of these studies and I'm going to wrap up with this there are studies that show that if you semi-starve obese subjects and do MRIs of their brain to look at the neural activity their brain levels their brain activity changes when they look at good tasting food and people assume this is because they're obese and they're leptin resistant and we give them leptin and it fixes it but we could do the same thing with lean subjects who aren't obese and see if they have the same brain functions because if they do then we can argue that the reason these people are doing this is because they're semi-starved not because they've been lost weight at some level of semi-starvation to maintain the weight loss so this is how you do that study I'm going to wrap it up here you get the point there's specific experiments all this can be settled with good science the problem so far is the research community because they haven't believed they've believed that this energy balance idea was so firmly set like it was passed down from Mount I'm going to forget the name of the mountain this is what happens when you're lecturing on tablets and so they never thought to ask the question and if you don't think that a low-fat diet is also a low-carb diet you don't think to ask the question and our job in this business my job, one of the things I'm dedicating myself to is to get these people to understand that these questions have to be asked but it's not good enough to just say oh yeah that's possible that part of the job of science is to see if the possible is real or not and unfortunately we can't do these experiments journalists can't do them bloggers can't do them but the research community can and so we hope that in the next five years we'll get them to do it and then these issues will all be settled anyway thank you very much