Dr. David Ludwig - 'The Carbohydrate Insulin Model of Obesity'

well it's speaking of being woke it's early in the morning so I'm not sure I'm gonna be able to match Sara's level of enthusiasm but I'm gonna do my best and thanks true rod and Jeff for this invitation to attend this really impressive conference full audience here are my disclosures so the first law of thermodynamics says that energy can't be created or destroyed so applied to living systems gives us the familiar equation calorie intake - expenditure equals calories stored and since humans store most excess calories as fat we can change the right side of that equation to change in adiposity according to the conventional interpretation of this physical principle obesity represents the personal failure to control energy balance you heard this discussed yesterday in several talks including by Gary Talib's so according to this way of thinking about obesity this conventional interpretation we live in this modern environment with ubiquitous tasty foods certainly over the last half century and these tasty foods cause us to passively over consume but we don't have enough opportunity to burn off those extra calories because our jobs are mostly sedentary we don't exercise enough and so those calories build up in the bloodstream as glucose lipids other fuels and they get forced into fat cells making them anabolic or making them grow so the simple solution is eat less and move more of course we've heard that a thousand times this conventional view places responsibility specifically on you the individual to control your energy balance this is from my plate the USDA reaching a healthy weight is a balancing act the secret is learning how to balance your energy in and energy out now if you like the energy balanced approach to weight control you've got to love the first food guide pyramid because fat has more than twice the calories per gram or per byte of carbohydrate so the thinking was that all fats would be unhealthy both for the body weight and as will be discussed in other talks for cardiovascular disease risk factors whereas carbohydrates were all inherently good now it's really astounding to think that just 20 years ago statements like these came from leading nutrition experts society leadership the nutrition society leadership obesity society leadership for example one group said when people are allowed to eat from ranges of high fat or high sucrose sugar foods passive overconsumption only occurs with fat it follows that fat promotes over consumption while sugar probably prevents it and a second group said the evidence intriguingly suggests that it is specifically an increased intake of sugars rather than complex carbohydrates that dilutes fat energy so this is what this is saying is that these these opinions which were based on energy balance considerations alone this concept of physics that based on those considerations all carbohydrates are going to be good even sugar and all fats are going to be bad and that's exactly the advice the government gave to the food industry calling for thousands of new processed foods what fruits and vegetables processed foods that were reduced in fat and saturated fat and of course if you're cutting those down you've got to replace them with starch and sugar so the food aisles filled up with fat reduced foods such as these now it's become popular today to argue that these low fat junk foods were industry manipulation trying to make profits and public gullibility but that represents a bit of revisionist ik history in light of what we just saw the government and nutrition establishment the leadership specifically proposed changes in the food supply that would create these foods and as hoped the purse portion of calories increased from carbohydrate from fat decreased but of course the obesity epidemic emerged during this time period we know that very few people with conventional approaches to obesity can successfully keep weight off for the long term in this study which was a nationally representative survey one in six people could keep off just 10% of their excess weight 10% of their body weight for just one year so that's a dismal statistic so we have to ask why is this paradigm which sounds so simple just eat less move a little more you know just do it day after day and you'll ultimately achieve your goals why is this paradigm failed and practice well an obvious problem is it completely disregard disregards basically a century of research to argue that body weight is controlled by biology as much or more so than willpower with a complex interplay of hormones metabolic fuels and other signaling integrating multiple hormones multiple organ systems so we know that the law of physics that says that calorie intake expenditure and fat storage are linked that that's that can't be wrong that relationship is based on physics but perhaps our assumptions about causal direction are at issue so maybe the arrows don't move from left - right but they move from right to left now this in no way violates the law of thermodynamics either but it has a profoundly different implication to the cause and potential treatments of obesity so according to what could be termed the carbohydrate insulin model of obesity the problem begins at the right side of the of this figure something has triggered fat cells to take in and hold on to too many calories so there are too few calories in the bloodstream not too many as in the other model there are too few the brain perceives that as an energy crisis not enough calories to run metabolism to feed the brain to satisfy the needs of the other organs of the body and so that's why we become hungry and wind up overeating and the brain recognizing this potential metabolic problem also lowers energy expenditure by making us fatigued and less likely to move lowers resting energy expenditure changes muscular efficiency now if this model is true then the advice to just eat less and move more will be doomed to failure and actually might make the problem worse because it's further gonna restrict that already limited fuel supply circulating in the bloodstream so what could be triggering fat cells into this calorie storage overdrive this feeding frenzy well of course you've heard about insulin quite a bit in this conference so far insulin is the dominant anabolic hormone with regard to energy metabolism it regulates the availability of all of the metabolic fuels states of increased insulin action not insulin levels per se because we have to think of insulin resistance - but states of increased insulin action with more secretion or injection of insulin for somebody with type 2 diabetes or insulin promoting secreting tumors consistently leads to weight gain whereas states of decreased insulin action consistently are associated with weight loss such as under treatment of a child with type 1 diabetes who can't make enough insulin and without insulin treatment that child with type 1 diabetes can eat three five seven thousand calories a day but will continue to lose weight until getting back on to the right dose of insulin and what could be increasing insulin secretion will the type and amount of dietary carbohydrate this is just endocrinology 101 and the particular term of interest is glycemic load which integrates both both amount and type of carbohydrate and best predicts better than either of either type or amount by themselves better predicts how blood sugar and insulin will change after a meal or on a long term diet so let's take a look at some cute effects so in this study we gave children adolescents with obesity one of three bills on a crossover fashion so they got all three on different occasions basically a vegetable omelet with fruit for the low glycemic load meal the high glycemic load meal was instant oatmeal with a little milk and sugar this was a low fat high complex carbohydrate meal the instant oatmeal was had all of the fiber from the whole-grain it was just processed for instant cooking so it digests very quickly and then we also had a medium glycemic load meal of steel-cut oats very much the same foods as in the instant oatmeal breakfast but just processed differently so the glycemic impact will be lower and here's what we saw in terms of hormones looking the x-axis horizontal shows time from the meal for five hours so that's through the late postprandial state and as expected insulin rose more after the instant oatmeal in yellow compared to the steel-cut oats in red or pink and vegetable omelette in blue but another hormone which been mcpeck men's speaks eloquently about is oftentimes neglected which is glucagon will go dine is made from cells right next to insulin producing cells and it does the opposite of insulin insulin promotes storage whereas glucagon prepares the body to release calories from storage it pulls calories out of storage so glucagon was actually suppressed after the high glycemic load meal so that results in an extremely high ratio of insulin to glucagon that's going to be adult a metabolic double whammy that's going to tell it's going to direct the calories coming in from the meal into the liver into muscle into fat but a few hours later after those calories from the digestive tract have been absorbed and you need to access them from their store locations the persistent effects of these hormones are going to lock them down for a while it's going to prevent the liver from releasing glucose and it's going to prevent fat cells from releasing fatty acids and as a consequence we see this which is that glucose after that initial surge after the high glycemic index meal comes down into a relatively hypoglycemic range that was statistically significant difference and free fatty acids which are a key fuel in the late postprandial stage and in the fasting state were also suppressed more the body recognizes this as a metabolic crisis secreting epinephrine an emergency stress hormone in higher amounts after the high glycemic load meal rather than the medium or low and when we gave subjects free access to food they consumed hundreds of extra calories because again consistent with this notion that the brain is seeing a metabolic problem so same calories at at baseline and in the case of the two oatmeal's the same carbohydrate just different rates digestion but very different hormonal and hunger states a few hours later so what could be happening in the brain at this time a study that was conducted by Belinda Leonard's and you'll be getting the opportunity to hear from her tonight looked at twelve men who had high BMI in a double-blind fashion we gave them milkshakes that looked alike had similar sweetness in a randomized crossover fashion in fact the same macronutrient same protein fat and carbohydrate but in but one milkshake had corn syrup which is about as high glycemic impact as they as you can get the other had uncooked corn starch so it comes from the same plant still corn but because uncooked corn starch is a tough little molecule that doesn't digest quickly it has a much lower glycemic impact and we saw that when we followed blood sugar curves after the meal the high glycemic index milkshake led to a higher blood sugar response note though that at four hours after the meal on the right side despite the same calories the same carbohydrate people reported being significantly hungrier after the high glycemic index milkshake and at that time so the late postprandial period you know many people many studies are done just at one hour when blood sugar is surging okay you know if you eat a bagel and fat-free cream cheese and oranges for breakfast you might be feeling fine one hour later but that's not really the key issue the key question is how are you gonna be feeling 3 4 & 5 hours later when you may either have an extra snack an extra large snack or overeat at the next meal the late post prandial state is key and it's rarely examined we looked at it here this is brain activation by a form of functional magnetic resonance imaging at 4 hours and we found that one area consistently lit up more so after the high glycemic index milkshake than the low that area called the nucleus accumbens is considered the classic seat of the major addictions cocaine heroin alcoholism gambling raising a provocative possibility that these highly processed quick digesting carbohydrates hijack basic pleasure and reward systems in the body producing something that could legitimately be called food addiction all right all studies in humans are going to be inevitably confounded by one factor another which is a motivation to occasionally go to animal research to understand basic nutritional principles there's a I think there's too much animal research on diet because you know mice are not men but I think there are specific questions that can be productively addressed and we attempted to do so in this study which is that we took rats who were at risk for type 2 diabetes and gave them again identical diets same protein fat and carbohydrate but just varied the glycemic index from fast-digesting to slow digesting and we further maintained body weight the same between the two groups by pair feeding you know an argument could have been well maybe the fast digesting carbohydrate is tastier and so the rats just overrated so we wanted to factor that out and then we measured body composition at 18 weeks by radioactive hydrogen water and here's what we found so on the left you can see the curve of body weight between these two groups over 18 weeks and I think you'll agree that we kept weight basically the same between the two groups really no evidence of any difference in body weight but to do that we had to begin to restore calories in the high glycemic index group at around eight weeks what does that mean see these two groups started once the high glycemic group started gaining more weight on the same calories so what does that mean about its metabolism it was slowing down that animal was becoming more metabolically efficient slowing down its metabolism so we had to cut back its calories we had to put it on a diet same thing that is told to people who were gaining weight excessively so we gave it fewer calories to achieve the same body weight and we succeeded in doing that and despite that the high glycemic index animals still had much more body fat and since they had more body fat at the same weight they had less lead tissue muscle and organ mass now this is fortunately not after lunch this will be the only graphic slide I'll show you these two animals weighed the same the one on the left that ate the low glycemic index diet had very little visceral fat was metabolically healthy based on blood tests the one on the right was a metabolic mess with the highest risk fat this finding completely defies the calorie balance all calories are alike view of obesity management the animal on the right was gaining too much weight we put it on a diet we successfully prevented weight gain and it still was a major metabolic risk okay what about chronic effects in humans meta-analyses that consistently show low fat diets counter to hypothesis are inferior to all other higher fat diets now the differences here are not great there are a couple of kilos typically but these are mostly low intensity behavioral studies with poor compliance so it doesn't say what you could do if you got a intensive intervention such as the one Sarah described earlier so there are many specific predictions of the carbohydrate insulin model for which we have at least some evidence high fat versus lower fat diets produce more weight loss high glycemic load foods like sugary beverages refined grains and potatoes are associated with more weight gain than high fat foods such as olive oil nuts dark chocolate and then full fat dairy there's effect modification by something called insulin secretion we'll come back to that reduce metabolic fuel concentrations in the late post prandial phase after high glycemic load meals altered fuel partitioning and at least in animals increased body fat accumulation on energy controlled high glycemic index or load diets so one big area of controversy is whether there are calorie independent effects on energy expenditure this model predicts that at the same number of calories going in or better yet at the same body weight you're burning more your calorie burn will be greater on a low-carb diet that's a metabolic advantage now I think some popular low-carb diet books made excessive predictions about the six eight hundred calories you know if it were that big we would have seen it by now but if there are effects in the range of one to three hundred calories that would still be extremely important scientifically and very important clinically but harder to see in little trials yeah one of the chief critics of this model published a meta-analysis that looked at studies of low versus high carb diets on energy expenditure and said there is no difference and thus the carbohydrate insulin model is falsified but there's a big problem with this meta-analysis the median length duration of these studies is less than 6 days ok so why you know so people laughed about that so why so this group understands a basic principle that the physiological adaptations to a low carbohydrate I don't occur immediately how do we know that we'll just look at fasting that's one of the most potent stimuluses for ketogenesis beta-hydroxybutyrate takes three weeks or more to reach steady state look at you know six days see where six days would be you're barely half the way there and the same is true for low versus high carb diets these are this is a weight reducing low or high carb diet you know by one week you're barely half the way to steady-state ketones and so if you are habituated to a high carbohydrate diet and you suddenly go or put on a low carbohydrate diet you know your brain was reasonably happy within limits that we've discussed with the glucose that is provided on that high carbohydrate diet now you've just shut off the glucose supply we know that's not going to be a problem long-term because ketones rise and serve as an ultimate alternative fuel but what happens during those first few weeks when you've turned off the glucose but yet your ketones haven't reached steady state how do you feed the brain from your muscles so you've got a breakdown some protein for gluconeogenesis temporarily and we see that in this study nitrogen balance which is reflecting muscle amino acids is more negative this is not a big deal it means that when you start a low carb diet and this might be modifiable a little bit based on how much protein you consume but you can expect to learn lose about a pound of lean mass as you adapt that has no implications to long-term go said by one month we're back to balance but it means if you study people at three days six days nine days or 12 days they're going to look like a metabolic mess and of course you're not going to necessarily see optimal long term chronic effects extensive research documenting that this adaptation of process to a low-carb diet takes a while so we need the longer studies and that's in fact the purpose of this recently published research we did called FS to published in the BMJ in November and the aim was to evaluate the effects of three diets varying in carbohydrate to fat ratio on energy expenditure calorie burn over five months in a well powered study this was the design we had a run in phase and a test phase the run in phase was weight loss we brought people's weight down by about 10 percent at least 10 percent to put the body under some stress we know that with weight loss energy expenditure is going to drop people are going to be hungry the body is going to want to regain weight then we randomly randomly assign them to high moderate or low carbohydrate diets we collected data before weight loss right at the start of the trial before randomization at 10 weeks and at the end of the study 20 weeks we had 164 participants this contrast to the eight ten twelve participants in most feeding studies we had a hundred and sixty two of them were the intention-to-treat analysis and 120 were in the per protocol analysis those are the people whose weight during that weight maintenance phase remain stable and I should say during this weight maintenance phase we adjusted calorie intake to keep their weight the same so if somebody's metabolic rate went up and they started losing weight we would have given them more calories and the opposite would have occurred our aim was to keep everybody's weight within two kilograms and we were able to do that for the per protocol for most of the people just shows the participant characteristics mean age was about 38 they had a BMI on average of 30 to mostly women as is the case for usually the volunteers for nutrition studies are mostly women but we had pretty good ethnic variability these are the test diets high carbohydrate moderate and low 60/40 20% carb reciprocal relationship with fat 20 40 60 % protein was controlled at 20% on all diets the primary endpoint was total energy expenditure total calories burned by a technique called EE labeled water where you give these stable isotopes and you just follow the you get urine samples and then what do you do with those urine samples you put them in a fancy mass spec machine our collaborator in Texas bill Wong did this and you can see decay occurs of how deuterium or O 18 decay over time and the rates of those decay tell you based on the physics of this metabolic rate so this is I've been a skip over this this is the primary outcome you'll see the time 0 on the Left 10 weeks and 20 weeks the panel on the left was the full intention to treat the panel on the right were those who presumably had the best compliance their weight stayed stable and we found a highly statistically significant difference among diets that at the same body weight those on the low carb diet were burning about 200 to 280 calories a day more than those on the high carbohydrate type now if this is real this is this is important this is a provocative finding that the number the type of calories you consume affect the number of calories you burn implying that a focus on carbohydrate restriction could be more effective than a focus on calorie restriction and this is a little bit complicated my last data slide on this I'll just walk you through it briefly the carbohydrate insel model predicts that those who are high influence the crater's so for whatever genetic reasons or early life influences or sedentary behaviors for whatever reason some people secrete more insulin when they consume carbohydrate in this case an oral glucose tolerance test than other people so if you're a high insulin secretor you're going to be especially susceptible to the metabolic adverse effects of high carbohydrate diet and so we just divided people according to turtles groups of three that group of three on the right those are the ones with the highest influence secretion before they started the study middle group was medium and the group on the left have low insulin secretion so what this shows is that if you're a high insulin secretor you're is you are indeed especially sensitive with this 478 calorie difference between the low and high carbohydrate diet if you're in the middle group that difference is smaller and just borderline significant 248 calories if you're low insulin secretor there's very little difference not even statistically significant one size may not fit all you know when somebody says listen I cut out fat I ate a low fat vegan diet and I did great well you know that could be true but you know the people who cut back on fat during the 80s and 90s and gained massive amounts of weight and developed type 2 diabetes yeah I mean those are the ones that are showing up in your office and those are probably enriched in that right turtle so this is the study has a number of strengths listed here the main limitation is the possibility of non adherence and our sensitivity analysis because we fed people all of their meals but we didn't follow them 24 hours a day and it's possible that people on their own ate other things or didn't eat all of what we gave them so you know I guess you know you're doing potentially important work when your critics you know aim to aggressively attack your work and we've had these attacks one was our choice of baseline and so our chief credit so we used as the baseline the time right before an amazing for the comparison of the diet effects but our chief critic said we really should have used the pre weight-loss baseline and you know if when the analysis is done that way the effects are smaller but that's not really surprising people lose weight in different ways some people lose more fat some people lose more lean the further away you go from randomization the more noise there's gonna be so that's really not surprising virtually all dietary weight loss maintenance studies use the time point right before randomization such as in the diode Diogenes Diogenes study which is the largest diet study ever done to address this issue you can see that the baseline was after weight loss and just before they put on the diets and incidentally this shows a very consistent effect most weight gain Gate weight regain on the high glycemic load diet least on the low glycaemic for diet so many studies have been done using this pre randomization time point so I think we can cross out that concern another was randomization failure you know randomization supposed to take into account variability between people but you know you could have imbalances there's the complaint that weight and stability refeeding could confound the findings but there was really no difference between in weight between groups the overall weight change during baseline was very small 23 grams that easily fits within the definition of weight stability which is less than 250 grams a day so I think we can cross that one off validity is double labeled water has been challenged now this is a gold standard technique but some people have achieved critic has argued that de novo lipogenesis on a though on a high carb diet could confound EE labeled water so what is that well glucose comes down to a settle CoA and then can be built back up into triglycerides through de novo lipogenesis and that could trap two terraeum so the argument was that well maybe this could bias the study by thirty to sixty calories a day that's not the whole effect but you know that could be significant this concern comes from studies of pigs gaining a pound and a half a day during their most rapid growth rate among even among the pigs at weight stability there was no bias and our study was done at weight stability so The Critic have to postulate a huge amount of futile cycling going back around and around and around in order to come up with this estimate and we're short of time but I'll basically just say that there's no evidence for such high levels of de novo lipogenesis on weight stable diets that aren't loaded with sugar in fact uh you know the amount of de novo lipogenesis is in the range of about five grams a day or less and in fact there's concern that the other method the you know the method preferred by critics whole-room calorimetry is actually less accurate because it restrains physical activity level which is a mechanism through which diet can affect total energy expenditure if you're eating foods that help you feel better you're more likely to move and to be active and if you're constrained in a small chamber well that could miss the effect and the last thing I want to show you is address the criticism that the effect is mostly due to non adherence that people were just eating other foods and that's going to artificially inflate tea if the results of our study are real then the number of calories were giving people at weight stability should roughly equal the number of calories they're burning off at least as a group average so we presented preliminary data in our manuscript on this and the direction of effect was consistent but with this reviews were preliminary imprecise data and we didn't see statistical significance so we've been motivated to go back review all of the food production sheets determine calories consumed and then we should say calories provided on the test diets and then adjust for differences in fat mass and these are new data hot-off-the-press you're the first group seeing it so this is the on the Left the average number of calories the difference between the groups of calories provided on the three diets and on the right it's adjusted for changes in fat mass and you can see that there's the same relationship between high moderate and low as we saw for total energy expenditure these effects in other words we gave to maintain body weight we gave the low carbohydrate group about 300 350 calories more so that strongly suggests that our primary t total energy expenditure finding is not artefactual because there's such close consistency all right so I think we can argue now that there's at least some evidence for a calorie independent effect the carbohydrate insulin model I do want to point out is more than just a single hormone and a single nutrient many components of the diet affect fat storage either through insulin or independently as do sleep stress and physical activity so this becomes a an intellectual infrastructure for understanding how biology could influence fat storage beyond just the energy balance view which focuses on willpower okay I'm gonna skip over type 1 diabetes because I think we're out of time but fortunately Belinda Leonard's is going to be presenting this study tonight of glycemic of a low carb diet for people consuming type 1 diabetes and I would will conclude with this thought that the ideas implicit in the carbohydrate and insulin model may seem provocative at least compared to the conventional effective but they're not new a leading researcher wrote that the current energy theory of obesity which considers only an imbalance between intake and expenditure is unsatisfactory an increased appetite with the subsequent imbalance subsequent imbalance between intake and output of energy is the consequence of the abnormal on log that's a german term for amount of fat tissue it's a consequence rather than the cause of obesity and these this the statement was made by julius baer in 1941 thank you for your attention [Applause]

Channel: Low Carb Down Under

Views: 50,493

Rating: 4.8376513 out of 5

Keywords: Low Carb Down Under, LCDU, www.lowcarbdownunder.com.au, Low Carb Denver 2019, #LowCarbDenver, David Ludwig, Harvard Medical School, Pediatrics, Professor of Nutrition, CICO, Thermodynamics, Carbohydrate Insulin Model, Always Hungry?, Low Glycemic load diet, Obesity, weight loss

Id: OK1zePxBJu4

Length: 38min 38sec (2318 seconds)

Published: Tue Apr 23 2019

Reddit Comments

[u/NONcomD]

Dr. David Ludwig presents a very compelling case even to the sceptics. Very well articulated. Basically he tackles all the criticisms of carbohydrate-insulin obesity model and makes a strong counter argument. A great lecture.

[u/BobbleBobble]

This should almost be stickied, it's a great link and one that's much more likely to be compelling in debates thanks to his credentials (Harvard Med School, Boston Children's)

[u/GroupthinkRebellion]

About a decade ago, while listening to NPR, is when I first learned about ketogenics and how the whole nutrition and balanced diet stuff my generation learned in grade school was all just marketing for big business. I have learned many things since as well. I felt great watching this video as it affirmed everything i have learned on my personal journey since then. Thanks for posting.