Robert Lustig - Frontiers of Science

thank you so much weighing for that very very kind introduction and you are right my daughter does have me wrapped around her little finger there's no question about that but it's really an honor and a privilege and a pleasure to come back to Salt Lake City I've been here once or twice in the past I have friends here some of whom are on the University of Utah faculty whom I met with today so you know it's it's not a hard slog for me and you know it's only one timezone so you know there's a definite advantage anyway I very much appreciate all of you being here tonight I want to try to explain to you what has happened these last 40 years something has gone very wrong and the question is what people say you know the food's there yeah was there before we didn't have this problem people say the TV's there the video games are there the you know iPads are there they were there before but the fact is we have a crisis that is not explained by our diet and our exercise something else is going on and I'm going to try to explain to you how this has occurred what the biochemistry is in palatable doses so that it's you know doesn't overwhelm you and try to string it together in a way that will make evolutionary sense and then explain how our biochemistry has been hijacked for personal profit and that's where we're going that's my charge and hopefully by the end of tonight you'll see why so first of all I have no disclosures no food industry concern is putting me up to this I promise you so here's the past just 13 years ago six million kids are seriously overweight well with all of the media attention with all of the clinical programs that are available with all of the health clubs with all of the bottled water and with Michelle Obama's vegetable gardens we are now up to 20 million here's the present currently there are 30 percent more obese people walking the planet than there are undernourished people now 20 years ago this was exactly opposite and these over nursed people are living in the same homes and in the same villages as the undernourished people this does not look like a behavior this looks like an exposure this is what cholera looks like this is what influenza looks like this is what tuberculosis looks like well this isn't an infectious disease how do you explain this concept of exposure 371 million diabetics that's 6% of the world's population and they are chewing through all the healthcare resources there's nothing left for anyone else and this is a true not just here but in the developing world also so much so that ban ki-moon US Secretary General three years ago declared that non communicable disease was now a bigger problem for the developing world not just the developed world than was acute infectious disease including HIV that's a big statement with major ramifications and changes in allocation of resources by the way those resources are now going to Ebola okay but nonetheless at some point we're going to have to deal with this problem now if you look and I know it's hard to read you don't have to read it but this is from the New England Journal looking at the change in u.s. deaths from heart disease smoking down systolic blood pressure down total cholesterol down physical activity up these should all be things that help and improve things yet our mean life spans going down not up there's actually been a downtick in mean life expectancy in the United States over the last two years the reason is because BMI is going up diabetes is going up to offset the problem and worse yet they're getting sicker sooner and they're not dying anybody read the Atlantic article by Zeke Emanuel why I want to die at 75 anybody see that would you think of that you thought that was okay really I have bridge to sell you this is a disaster he basically he he makes a good point he says we haven't increased the time of living we have increased the time of dying indeed that is correct and more money goes into dying than into living and that's what's breaking the medical bank that is all true the question is does it have to be this way is there something we could do about it how about this so everybody loved Dilbert health problems and absenteeism are huge costs to this business so so give me a raise or I'll eat unhealthy food and avoid all forms of exercise you already do these things how could you possibly know that so this is what we call presenteeism everybody knows what absenteeism this is presenteeism presenteeism is a real disaster because people are occupying bodies and slots at companies not doing their job productivity is going down and companies are losing now on the positive side of the ledger not just the negative side of the ledger they've been worried about health care costs for now for many years but now they're actually having decreases in productivity so business is getting on board in fact insurance costs each and every one of your employers two thousand seven hundred and fifty one dollars extra per employee for obesity related disease whether the employee is obese or not and this is affecting productivity this means you can't hire as many people this is affecting unemployment this is affecting everybody not just the obese and not just the diabetic and here's what the future will look like if we do nothing experts predict 165 million Americans will be obese by the year 2030 100 million Americans will have diabetes by 25 but it really won't matter because Medicare will be broke by the year 2026 so basically like the Soup Nazi said no healthcare for you well to be honest with you I'm going to be 69 in the year 2026 and I want my friggin Medicare and I worked hard enough for it and you worked hard enough for it and it won't be there if we do nothing we got 13 years to turn this around and it ain't turning around and the final stake in the heart obamacare now I don't know if you like Obamacare or don't like Obamacare I don't even care the question is how are we going to pay for this putting 32 million sick people on to the rolls how are we going to do that the president says we're going to pay for this by providing preventative services so instead of going to the emergency room you go to the doctor and that will cost a whole lot less keep people out of the emergency room sounds great except for one little problem there is no medicalised prevention for any of these chronic metabolic diseases you're going to get it anyway there's just long-term treatment and Big Pharma loves it they love it so much they have actually diverted all of their resources away from acute infectious diseases like Ebola and instead have focused all of their efforts on chronic diseases like diabetes because you're going to have that for 20 or 30 or 40 years and all that time being less or non-productive this is a disaster this is a sinkhole and we can't climb out of it or can we in the meantime deaths from diabetes complications have declined but diabetes rates have gone up in all age groups to make up for it the costs keep going up diabetes cost the u.s. 245 billion dollars alone never mind all the other chronic metabolic diseases which account for 75% of the 2.7 trillion our healthcare budget type 2 diabetes as children's gone up 30% in the last five years and again one third of all Americans will have diabetes by the year 2050 that's where we're going the question is why is this happening and why is this not just happening in America why is this happening all over the world so let's talk evolution this is a statute and it is 22,000 years old it was unearthed in Vienna in 1908 sits in a museum of natural history there and it's called the Venus von villain Dorf and what it shows us is that the ancients knew about obesity before they knew about McDonald's okay obesity is part of the human condition obesity actually is in some ways adaptive but something went wrong how the world gets so obese and so fast in this short period of time so that brings us to this guy here Darwin okay what did what would he say about this so yes obesity continues to worsen prevalence Avera T increasing in all developed and developing countries increasing in all age groups and especially in children and recidivism is high virtually nobody can lose weight and keep it off we all know that the question is what's the explanation so the obvious explanation is well we're all just a bunch of gluttons and sloths right you eat too much you exercise too little just go to your doctor he'll tell you what would Darwin say about this he would say that we've got a mismatch between our biochemistry or our genetic and our environment he would say that somehow our environment has changed in such a way as to foment this current epidemic and the question is what about the environment did it so that we can fix it and turn it back so first you have to know like why is there obesity in the first place well obvious it's the rainy-day issue okay energy storage for a rainy day we had millions of years of famine we had all those years of foraging now we don't forage right except in our you know freezers you know but the point is we actually want to store energy it's part of our biological makeup so how is this selective advantage achieved well it's achieved through two phenomena that we have to describe two biochemical phenomena and this is where the science comes in something called leptin resistance and something called insulin resistance and I'm going to describe both of them to you so this is a complicated slide but it basically shows how the negative feedback pathway of energy balance works so let me try to describe it to you over here in blue we have four hormones okay we're not going to talk about two of them I'm just going to mention them in passing over here this one called ghrelin ghrelin comes from the stomach ghrelin is your hunger hormone when your stomach is empty ghrelin is up goes up tells your brain i'm hungry feed me you put food in the stomach ghrelin goes down so this is an elementary meal to meal hormone that regulates hunger or not then there's this other hormone over here called peptide YY which comes from the end of the small intestine and this is the satiety hormone this see this is the hormone that says I've had enough I don't need to eat another bite I am satiated this is the satiety hormone ghrelin in the stomach peptide YY in the end of the small intestine there's 22 feet of intestine between the two signals takes time so you eat the plate of food you're still hungry reason the ghrelin went down but you didn't get the satiety signal yet you're supposed to wait 20 minutes but of course kids say I'm still hungry parents give them a whole nother plate of food and therefore you've gained the extra calories extra weight so let your kid leave the table let them go do their homework let them go outside if they come 20 minutes later then they can have a second portion and not before this is one of the things we teach in our clinic and it's because of these two hormones that's all I'm going to mention about these two then there are these other two hormones over here leptin and insulin and that's where the action is now notice let leptin comes from your fat cell and goes to your brain here your hypothalamus this is ground zero for energy balance regulation and what it tells your brain is I've got enough energy on board my fat cells are big enough so that I can engage in expensive metabolic processes such as puberty and pregnancy I can burn energy at a normal rate and feel good about it because I'm not in deficit okay so leptin is a hormone that tells your brain your adiposity status and when your leptin is low your brain senses that as starvation everybody with me so far then you've got this other hormone over here called insulin now insulin is really interesting wearing spend a lot of time talking about insulin notice insulin goes to waves it goes to the fat cell and tells the fat self whatever you're not burning put it in your fat cell for storage it is the energy storage hormone it makes fat but it also goes to the brain same place as all the other hormones and what it tells the brain there is hey I'm in the middle of metabolizing a meal let me deal with what I've got now and so it's also part of the satiety signal so it does two jobs at once and notice that those two jobs are in opposite directions so it's telling the fat cell store and it's telling the brain stop and it is this dichotomy that will get us into trouble and you will see why so to explain how the system works I want to offer you a paradox okay here's the paradox what happens when you give a five-year-old kid come on some of you have children bounces off walls okay known as the sugar high and every parent knows it and every kindergarten teacher knows it that's why the cupcakes come out at the end of the day instead of in the middle because once the cupcakes come out that's it lessons over every every teacher noses why is this happening so you eat the cookie the insulin deposits the energy in the fat cell the fat cell makes leptin the leptin goes to the hypothalamus this area that controls energy balance and what it does is it tells a part of your nervous system called the sympathetic nervous system which is the fight-or-flight part of your nervous system that there's energy onboard there's extra go ahead and burn it off and so it activates the sympathetic nervous system tells your fat self give up some energy so that you can stay in negative yin yang energy balance so what you have here is a nice negative feedback pathway between the fat cell of the brain and your sympathetic nervous system to keep you in energy balance this is when everything's working right but here's the paradox what happens if you give an obese five-year-old kid a cookie they're in the pantry looking for more cookies anybody ever see a sugar high in an obese kid doesn't exist doesn't exist and the reason is because they can't see their leptin because if they could see their leptin they'd have a sugar high and that's exactly why they're obese is because they can't see their leptin because obesity is leptin resistance there's something blocking the leptin signal so let's talk about that so here are two patients of mine HIPAA tells me I can't tell you their names but this will guy over here okay that's an OB OB mouse okay this animal is deficient in the hormone leptin it has a mutation in the leptin gene so this animal's leptin level is zero so this animals brain is constantly seeing starvation no matter how much weight this animal gains this animals brain can't tell everybody got the picture not only does this animal eat everything in sight but this animal is the world's greatest couch potato okay and uh rats or mice make nests in the cage anybody who ever worked in labs they they make little nests in the side of the cage and build up the sawdust and everything these animals are such couch potatoes that if you plop them in the cage they stay where you put them they never move okay they're like tribbles they just like that okay the only reason this animal ever gets off is heinie is if you put the food on the other side of the cage and they waddle over there eat all the food and then stay there instead okay everybody got it terrible okay that's his litter mate over there so here's how leptin works so here's your hypothalamus again that's ground zero and leptin is telling your hypothalamus that you've got energy onboard when you can see it and so if your brain can see it then you're over in this Dimond over here called anorexia Genesis I'm not hungry because I don't need to be and I can burn energy at a normal rate and feel good about it because I have enough excess that I'm not worried that I'm going to get into trouble everybody got that okay and so it activates the sympathetic nervous system to go ahead to the fat cell and burn off some and it also tells the vagus nerve which is your energy intake nerve your energy storage nerve your appetite nerve hey calm down wait till later I don't need to eat right now so you have an activation of your sympathetic nervous system to burn it and you have an inactivation of your vagus nerve to stop if you're in this diamond over here but what if you can't see your leptin what if your leptin is low like this animal this left in the vision mouse that you're over here in this diamond instead our Rexha Genesis hey I'm hungry I need to eat and I need to eat now and worse yet because my brain is starving I'm gonna shut down my energy expenditure I'm going to stop exercising I am going to sit on the couch and play a video game is what I'm going to do and so your sympathetic nervous system goes down in order to conserve and your vagal tone goes up in order to number one get hungry increase appetite and number two a branch of the vagus nerve goes to the pancreas and tells the pancreas to release extra insulin remember which is your energy storage hormone so your vagus nerve and your pancreas are linked together in order to get you to store more energy in your fat cell and then your leptin would go up and then you're back into negative energy and negative feedback energy balance again everybody got that so far so good okay and we have leptin deficient people 14 of them 14 leptin deficient children now here's an example of one normal weight at birth and by 6 months of age patients already obese already overeating because this kid can't see his leptin because it ain't there leptin deficiency and the kid keeps gaining weight gaining weight gaining weight until he is 10 years old and weighs 220 pounds and then this kid starts getting daily injections of leptin recombinant leptin made in a bottle you know made in a laboratory and look what happens kid loses weight on a dime because you have replaced the hormone that is missing this is what I do as an endocrinologist hormone replacement therapy is my job whatever's missing you give it back so we're giving it back and look what happens the kid loses weight and it's all fat mass it's not even lean mass we have reversed the metabolic dysfunction because we have given the hormone that's thing everybody got it really cool for 14 people okay and they're all of Pakistani or Turkish extraction and they live in London or Istanbul great for them what about the rest of us rest of us unfortunately are not leptin deficient or we have a drug that worked we are instead leptin resistant we have boatloads of leptin we make leptin to beat the band and however much fat you have that's how much leptin you have but it ain't working because if it work and you wouldn't be obese something is blocking that leptin from working this X right here this question mark that's the Holy Grail something is blocking the leptin from reaching the hypothalamus and telling the hypothalamus what's going on that leptin block leptin resistance because if we could solve that if we knew what that was we can fix obesity it's that simple just find the block it's been harder than you think to find okay and a lot of drug companies have been spending a lot of money and they found it yet okay that's leptin now remember insulin insulin is cool right because it does two things at once it tells the fat cells store and it tells the brain stop remember two different directions so let's talk about insulin this is the patient that got me started in obesity research now 19 years ago this is a 15 year old boy in this picture and he weighs 364 pounds at age 7 this kid was perfectly normal weight for height perfectly normal kid and then he developed this brain tumor okay sitting in the middle of his energy balance pathway knocking out his hypothalamus this is a hypothermic kaya's Matic astrocytoma and it is a Goomba sitting in the middle of his energy balance pathway and he required surgery and we required radiation and he lost all his pituitary hormones which we replaced and he started gaining weight at the rate of 30 pounds per year non-stop ad nauseam ad infinitum to his current weight of 364 pounds so this form of intractable obesity due to brain damage which this kit has if we call hypothalamic obesity and this is how I got started in obesity research when I was at st. Jude Children's Research Hospital and I see one of my colleagues who I worked with many years ago from st. Jude's sitting in the second row okay so why does this happen two different hypotheses the first one you damage the hypothalamus you damage a satiety Center so you basically overeat because you're always insatiable you eat too much and therefore you become obese and if you become obese then your body has to make extra insulin in order to tend all of that fat in which case the insulin is due to the obesity everybody got that the problem is when you actually analyze these kids they're not eating more they're actually eating reasonable amounts for their size they're not eating more but boy oh boy are they exercising less they do not move these kids lose interest in everything and the parents would come to me when I was at st. Jude and they would say this is double jeopardy this is unfair my child almost died of this brain tumor we saved his life and now he's going to die of a complication of the therapy this is unfair there was something about it I said okay okay so we've researched the literature about what might be happening and it turned out that there's this other hypothesis that might be going on instead that damage to the hypothalamus drives this vagus nerve to tell the pancreas to release extra insulin and that extra insulin is what's driving the energy into fat instead now if this is the case the obesity causes the insulin nothing I can do about that because I can't fix a brain but if this were the case where the insulin causes the obesity I have a wait maybe a fixing them because there's a drug I can use to try to block insulin release from the pancreas this is a drug as an endocrinologist I know how to use called octreotide and as other uses as well but I used it to reduce this patients insulin everybody with me so the question is would this drug turn this problem around okay so here's patient number one first patient treated was a pilot trial initially and here she is pineal tumor 220 pounds and here she is one year later on the drug at a hundred and seventy two pounds having lost 48 pounds and there's an apocryphal story that goes with this patient because the patient was in patient number one she was on the drug at low dose for a week one week hadn't lost any weight yet and the mother called me up frantic I said dr. Lustig something's going on here I went oh my god we've got an adverse event and I have to stop the study you know I know my god no what happened to the patient what happened she's well normally we would go to Taco Bell and she would eat five tacos and an insurer Ito and she'd still be hungry well we just went to Taco Bell and she ate two tacos and she was full and she just vacuumed the house I go really what does she charge just well the fact the matter is this happened to many patients one patient started competitive swimming two patients started lifting weights at home one kid became the manager of his high school basketball team running around collecting all the basketballs these were kids who sat on the couch ate Doritos and slept and all of a sudden now they're active here's the competitive swimmer right here so here she is for BMI points later six months later having lost quite a bit of weight and she started competitive swimming but the study was over the drug is expensive no one was paying for it insurance company wouldn't cover it and here she is two and a quarter years later desperately trying to do something about her weight and her BMI has gone up 11 points we finally pervaded prevailed upon the insurance company they finally gave her the drug back and her BMI went back down to 27 everybody got it and here's the probe and patient I showed you at the beginning 364 pounds here he is at 326 first time he put took a picture with his shirt off and here is the ps/2 resistance this is the unbelievable you can't touch this so this is a beautiful young lady from Hawaii she's not even my patient Lily in the hair age 13 here one month after this picture was taken she was in a terrible car accident on h1 in Honolulu and she was in the Kaiser intensive care unit for a month comatose and she woke up and she started gaining weight at the rate of 30 pounds per year as well and here she is two and a half years later so I was giving Grand Rounds at Kaiser Honolulu and they invited the patient and her mother to come to the talk because they were thinking about putting her on octreotide and there we are together at the time and they went ahead and did it and here she is a year and a half later at her high school graduation now who here wants to tell me that this is gluttony and sloth who here wants to tell me this is this kids fault this is biochemistry the biochemistry drove the behavior the insulin drove the behavior the insulin made her eat too much and exercise too little and when we got the insulin down exactly the opposite we fixed her hormones hormone replacement therapy and she's better everybody got it cool so here's how you think about it and actually you should think about this for all patients each of us is really two compartments there's you your heart your liver your kidneys your lungs your muscles your lean body mass which burns energy and then there's your fat which stores it now the substrate for both compartments is glucose but glucose is never at substrate saturation for both compartments at the same time nobody can eat that much which means that there's a competition going on between the two compartments which compartment gets the glucose what determines that well your insulin does because when your insulin is up it goes to your fat because that's insulins job is to steal it away and put it in fat for storage everybody got it now normally your fat would make leptin and your leptin would tell your brain hey I don't need to eat so much I can calm down and burn it off and so your food would go down your glucose would go down so your insulin would go down and so more would go to you and so you'd stay in that nice negative yin-yang energy balance that I showed you before everybody with me so far but these kids they got a brain tumor they got a CNS insult okay so their vagus nerve is in overdrive because they can't see their leptin and their vagus nerve is telling their pancreas release all this insulin in order to make more fat to make more leptin which you they'll never see and they can't get better unless we get the insulin down if we get the insulin down then less glucose goes to their fat more goes to them they feel better they don't need to eat so much and they lose weight and they turn the process around so you'd say well that's a really cool parlor trick but what the hell does this have to do with garden-variety obesity that's out there on the street they don't have brain tumors well we did this to a bunch of obese adults without brain tumors and this is an example of a patient Christmas 1998 holding up some food and here she is 35 pounds later in her jogging talks because she showed me she wanted to exercise because she felt better and whenever we drop people's insulin they feel better they get more energy expenditure and how much energy you burn and how good you feel are synonymous energy expenditure equals quality of life things that make your energy expenditure go up make you feel good like ephedrine off the market caffeine for two hours like me exercise things that make your energy expenditure go down and make you feel lousy like hypothyroidism starvation so how much energy you burn has everything to do with how good you feel and if you're stealing energy away from your body and putting it in your fat you're going to gain weight you're going to be hungry and you're going to feel lousy and the insulin did it the biochemistry drove the behavior so the cause of leptin resistance is insulin insulin blocks leptin signaling insulin is the problem insulin is an endogenous that is you make it yourself leptin and tagging estate blog slept and signaling now why what what Darwin's say what would he say about this would he say that this made any sense at all actually it makes perfect sense and the reason is because there are two times in your life you actually have to gain the weight and that's puberty in pregnancy you don't gain weight during puberty know reproductive competency you don't gain weight during pregnancy baby is aborted survival of the species if your left and worked right all the time you could never gain the weight you'd be the 97 pound weakling on the beach trying to bulk up and never could there are two times in your life you actually have to gain the weight and they're both insulin resistant states because you have to raise your insulin in order to drive the energy into fat cells to be able to keep the process going makes sense and it doesn't it make sense that the same hormone that causes the energy storage in the periphery is the same hormone that blocks the leptin signaling to allow you to gain the weight in the first place in the brain they're yoked together so insulin block slept and insulin is an endogenous leptin antagonist this is very important to understand it's about the insulin okay so what's happened to our insulin so here our glucose tolerance tests amassed from 1970 to 2014 notice not much difference in terms of the glucose but look at the insulin ix 1970 1986 1999 2014 look at that insulin three to four times higher for the same glucose control we're all hyperinsulinemic now what changed and if your glucose intolerant that's even worse we're putting out insulin to beat the band in fact we're putting out so much insulin that we are out and we've gotten so fat that we've actually outgrown our insulin supply and when that happens you can't shunt sugar to fat anymore and now you've got type 2 diabetes that's what's happened our insulin is now three to four times higher and the question is why in 40 to 50 years our need for insulin has increased two to fourfold how did we come to - fourfold more insulin resistant in such a short period of time and that brings us to the question of diet so I'm not going to tell you why this has happened I'm gonna let Will Smith tell you why this has happened well I guess I'll use some answers Hoss what you feeling chatty all of a sudden sorry I can't talk right now I got some secret cases of my own I'm working on I hate to tell you away from your video game alright I'm hanging up the most destructive force in the universe sugar yeah if Hollywood knows this why don't you alright what I'm going to be describing to you is in these two publications therefore the lay public to some extent first one from the New York Times Magazine called is sugar toxic about our work at UCSF our research and this was a comment nature comment that we wrote about two years ago called the toxic truth about sugar that I wrote with my colleagues Laura Schmidt and Claire Brandis from the Institute for Health Policy Studies at UCSF so what are we talking about we're talking about the sweet stuff okay in America it's this stuff up here it's called high fructose corn syrup you've heard of it most demonized additive known to man everybody's talking about it so much so they actually had to make commercials supporting it right everybody remember those okay what is it one glucose one fructose six membered ring five-member ring they are not the same they are not the same now the rest of the world doesn't have high fructose corn syrup they have this stuff over here called sucrose table sugar cane sugar beet sugar the stuff you put in coffee the white stuff the crystals okay one glucose one fructose Oh like acidic linkage linking the two together the enzyme in your intestine sucrase cleaves this in about a nanosecond you absorb the two molecules basically same thing same thing everybody blames high fructose corn syrup for this problem because high fructose corn syrup started at the same time as the obesity epidemic started in the 1970s but it's high fructose corn syrup is no different high-fructose corn syrup is not worse than the sugar high fructose corn syrup is cheaper than sugar and because it's cheaper it found its way into everything and because we went low-fat this was the substitute that's what changed so it's about the money now here's what's happened to our fructose consumption our ancestors getting fruits and vegetables out of the ground 100 years ago consumed about 15 grams of sugar a day and that's including honey now prior to World War two we got to about 20 grams per day 1977 with just before 5:00 work toast corn syrup hit our shores we were up to about 37 grams a day that was about 8% of our total caloric intake now double that for sugar remember because it's doubled because glucose and fructose weigh the same okay 1994 55 grams of sugar a day fructose a day that's 10% of our total caloric intake and adolescents currently consume 75 grams of fructose per day that's 12% of total caloric intake and 25% consumed more than a hundred grams and actually there was an abstract that the obesity Society just two days ago where they said that all of these numbers are wrong they're actually 60% higher now that's one abstract don't know but big press release about it and it's in everything because of the 600,000 items in the American grocery store 80 percent now have added sugar in some fashion because the food industry knows when they add it you buy more it's the hook you'll see why here's what's going on worldwide so the American Heart Association says we're supposed to consume 150 to 200 calories in added sugar per day maximum that you can do less but that's the maximum so that's this color blue here you can see how many countries around the world are over that okay pretty much everybody and that's why we have an every country problem here's world sugar consumption tripling over the past 50 years here's per-capita consumption over here notice Brazil Brazil used to be so poor they were so poor they were always a sugar exporter because the Amazon but they couldn't even afford their own sugar now they're a brick country right they got Embraer jets and biodiesel and World Cups and Olympics now they can and now they have the highest rate of increase of type 2 diabetes in the world now not the highest prevalence but the highest rate of increase in prevalence who has the highest prevalence Saudi Arabia Kuwait UAE Qatar and Malaysia why then no alcohol I'm in Salt Lake City what am I saying no alcohol but they got soft drinks like they're going out of style because it's hot and the water supplies a question mark and no alcohol this is their reward and they reward themselves several times a day but barring the fact that I'm in Salt Lake City I would rather have alcohol because you can only drink yourself under the table once a day the point is that fructose is not glucose okay glucose is a six membered ring fructose is a five membered ring they are not the same in fact fructose is seven times more likely to bind to proteins and cause protein and lipid damage because of it called the mired reaction called advanced glycation end-products anybody here with diabetes anybody only couple what is the dr. measure measure something called the hemoglobin a1c you've heard of that that's glucose binding to proteins well fructose binds to proteins seven times faster okay fructose does not suppress that hunger hormone ghrelin so if you pretreat a kid with a can of soda and then let them loose at the fast-food restaurant do they eat less or do they eat more they eat more they just took on 150 calories in a can of soda but they eat more because they didn't get the hunger suppression signal of ghrelin okay fructose does not stimulate insulin remember insulins part of the satiety signals when your brain can see it remember okay and it doesn't stimulate leptin either so your brain doesn't know you ate and finally liver fructose metabolism is completely different from that of glucose and that matters because what happens in the liver has everything to do with whether you get sick or not it's about the liver and here's why so here's a liver cell right here and we're going to consume here 120 calories and glucose half a cup of rice as an example turns out 80 percent of that 120 will go to all the organs in the body because every organ in the body can metabolize glucose glucose is the energy of life every cell on the planet can metabolize glucose glucose is so important that if you don't consume it your body will make it your liver will make it it's called gluconeogenesis right so your body never runs out of glucose but only 20% enters the liver on any given meal everybody with me so your livers not getting overwhelmed so what happens to that glucose well most of it goes up right here to glycogen called liver starch and liver starch for lack of a better word is good liver starch is what your body wants to do with excess energy this is why marathoners carb load pasta load before a marathon races to build up the glycogen to give them some extra added stored energy and no amount of glycogen can hurt the liver we have kids with disorders of glycogen storage their livers are down to their knees their blood sugar is down to you know 10 they're in terrible shape but they do not get liver failure because glycogen doesn't harm the liver glycogen for lack of a better word is good let's talk about another carbohydrate alcohol it's not really a carbohydrate was close enough okay here's its formula but ethanol as you know is not just a carbohydrate it's a toxin and it's a toxin unrelated to its calories alcohols not dangerous because of its calories alcohol is dangerous because it's alcohol right car accidents acute toxicity and fry your liver chronic toxicity here are the acute effects everybody went to college right there they are okay well maybe not Salt Lake City but fructose does none of these things because the fructose is not metabolized in the brain now let's see what happens when you consume alcohol same number of calories of alcohol shot of maker's mark ok hundred twenty calories now twenty percent of them will actually be absorbed and metabolized in the gut before it ever gets to your liver eighty percent will hit your liver 96 calories and notice see glycogen anywhere no glycogen goes straight down here to the mitochondria the mitochondria have no choice but to take any excess from it's burning and turn it into liver fat this is liver fat right over here VLDL that's triglyceride triglyceride that's what you measure when you do a lipid profile and triglyceride for lack of a better word is bad because triglyceride can serve as a substrate for heart disease or obesity and if the triglyceride doesn't make it out of the liver now you have a lipid droplet now you have what's known as alcoholic fatty liver disease and that's what leads to cirrhosis so you can get you can have your choice of how you want to die heart disease obesity or cirrhosis toxin we all agree we regulate it now let's do fructose so when you consume sugar because you never consume fructose alone because fructose alone in nature doesn't exist you're always consuming sugar or high fructose corn syrup you're getting the whole fructose load because only the liver can metabolize it plus you're getting the 20% of the glucose so you're getting a whole bunch compared to say glucose where was only 24 calories now you get in 72 she get in three times the substrate that you have to deal with and what happens to it see glycogen anywhere no glycogen not it doesn't exist but you see a whole lot of arrows okay and their point they get a whole lot of bad stuff okay like lipid problems insulin resistance high blood pressure okay all this stuff and of course the lipid droplet because you make liver fat out of that excess fructose - fructose drives liver fat accumulation that's what we've learned over the last ten years so what's the difference between these two items can a coke can of beer 150 calories both okay clearly different makeups right goes you got 75 glucose 75 fructose here and you got 90 alcohol 60 mol toast that's glucose there alright first pass effect takes 10 percent off the top for alcohol so the number of calories hitting the liver is pretty much exactly the same so in America we have this thing called beer belly well we also have this thing called soda belly and that's what I have to deal with okay so the adult endocrinologist deal with the beer belly I have to deal with the soda belly but they're basically the same and they cause the same diseases the same fatty liver disease the same type 2 diabetes so fructose induces this insulin resistance this phenomenon which ultimately induces leptin resistance when your insulin goes high your brain can't see the leptin and the reason is because your liver got shot and you can choose whether you want it to be from a soft drink or whether you want it to be from a shot of alcohol why what's in it why does this make Darwinian sense well think about it this way the standard place you get fructose from is fruit but our ancestors only were exposed to fruit about one month a year it's called harvest time and what came after harvest time winter no food so wouldn't it make sense to bulk up and put some extra fat on your in your fat cells getting ready for this cycle of no food until spring came around called seasonal insulin resistance now if leptin worked all the time you couldn't store that energy you wouldn't be interested in trying to over consume so there's a selective advantage by inducing the seasonal insulin resistance by gorging on fruit when it's available while it was available because it ain't going to be available for very long everybody got it but now it's available 24/7 365 and in unlimited amounts and unopposed by fiber which can slow the absorption which can help your liver so that's what orange juice is so the question is how do I know this is true well here's why because orangutangs do this so this is the mass ting fruit orgy of Papua New Guinea where the orangutangs basically it's like girls gone wild okay they eat every piece of fruit in sight okay so here's the availability comes around January okay and while it's going on it's all fruit all the time there's nothing else that they're going to eat and during that period of time their calories are way up because they're going to be storing this stuff and these are ketones in the urine now how you collect orangutan urine is beyond me but they do I swear I do not understand this but here's the period of the masking fruit orgy there are no ketones because insulin blocks ketone formation because in some pushes on the fat cell so that's telling you their insulin levels are high when the fruit is available so they are hyperinsulinemic and they are storing more energy and they are eating all the fructose they can because when it's over it's bad okay so this is their way of cycling their weight and their energy storage to deal with their environment now the next question why do we love it so much so the question has come up is sugar addictive you know it's just the other white powder you know the lay public seems to know this you know here all these books you know that have been written about this issue so the question is is it real so we have five tastes on our tongue everybody knows the five case there's sweet of course there's salty sour umami and bitter right sugar covers up the other four so it covers up salty like Tex mix or honey roasted peanuts it covers up sour like German wines you know they've got a lot citric acid they're almost vinegar but you throw some of this reserve it's cold and so it's not so bad or lemonade right you put the sugar in you can't even tell umami like sweet and sour pork at the Chinese restaurant that's half soy sauce you would never eat that but you know you put some sugar and he came and tell and it covers up bitter like milk chocolate okay so does this make Darwinian sense the answers yeah this makes Darwinian sense too why because there are no foodstuffs in nature that are both sweet and acutely poisonous sweet was the signal to our ancestors that any given foodstuff was safe to eat this was the signal that let them know so liking sweet is ingrained in toward the NA we love it example who has children somebody has told Rijn salt lake city how many times do you have to give an infant a savory food before they will accept it there are scientific studies what's the medium 13 13 times to give an infant a savory food how many times do you have to give an infant a sweet food before they will accept it just once just once okay and they know it once they've had it they don't want anything else okay true okay another example Jamaican Aki fruit anybody ever been to Jamaica nobody okay so this is a fruit it's the national dish Aki foot they even put it in tins and send that around the world when it's immature when it's still on the tree it has a compound in it called hypoglycemia as your blood sugar and it causes something called Jamaican vomiting sickness and you can die from this and of course the Jamaicans know this but if you wait for the flower to bloom or you wait for it to fall on the ground the hypoglycemic tab alized and is now safe to eat and the Jamaican national dish so sweet means safe acutely not probably and our sugar craving is also Darwinian so anybody know what this stuff is I need neonatologist in the room this is called sweeties sweeties it is a super concentrated sucrose solution that you dip the pacifier in and put it in the newborn boy's mouth before you do the circumcision we Jews use wine much better okay but this releases opioids within the reward center and acts as an endogenous narcotic so we know this this isn't like you know rocket science okay so this brings us to okay what's all this sugar doing to us disease so here are the ten most obese states in the nation anybody from any of them I just live in Memphis Tennessee it's pretty bad right June yep you're the ten laziest states in the nation what's going on over there in Nevada right next door guys I guess you can only burn so much energy going like this right now it's like this okay here are the ten most unhappy states in the nation here's the adult diabetes rate here's the adult heart disease rate and here is soda per capita consumption what do you see you see correlation you see correlation now correlation is not causation so this is a snapshot in time is it that soda causes obesity laziness unhappiness diabetes and heart disease or is it that obese lazy unhappy diabetics with heart disease drown their sorrows in a can of soda you don't know you can't tell no directionality correlation so the question is do we have causation we asked the question last year what about the world's food supply predicts diabetes prevalence over the decade country by country so this is a study that we did published last year in plus one where we took the Food and Agriculture Organization statistics database called FAO stat and it listed line item country by country for every year 2000 to 2010 total calories fruits excluding wine fiber containing foods meat cereals oils and sugar sugar crops and sweeteners as line items everybody got it we then took that database and regressed it against the International Diabetes Federation database for diabetes prevalence country by country over the decade and then we took that and we corrected it and adjusted using the World Bank gross national income database to control for urbanisation poverty aging physical activity and obesity the confounders and we asked the question which of these things predicted diabetes not obesity diabetes everybody got it we had data on 204 countries but complete data 450 for the 50 we left out we're not different with a fancy test and here's the data monitoring quality and I'm not going to bore you with it this is for scientists you don't need to worry about it unless you want to you can tell me later and here are the things we controlled for okay GDP obesity urbanization aging and physical activity got it here's what we found during that decade diabetes prevalence rose five point five to seven percent that's a lot and we knew that right here's the effects model for sugar if it crosses zero it means it's not significant as you can see highly significant and here's the adjusted Association of sugar with diabetes prevalence so here's what you need to know only changes in sugar availability predicted changes in diabetes prevalence nothing else only sugar not total calories for every extra hundred fifty calories any country ate per day diabetes prevalence went up a total of 0.1% nothing but if those 150 calories happen to be a can of soda instead diabetes prevalence went up 11 fold 11 fold by 1.1 percent and we're not consuming one can of sodas worth of sugar per day we're consuming two and a half and if that abstract that the obesity society's correct correct three and a half so take that number of one point one percent and make it four point five percent okay so those countries where sugar consumption declined actually showed decreased die ladies prevalence and we anticipate that about 25% of the world's diabetes is predicted by sugar consumption sugar alone having nothing to do with calories irrespective of calories unrelated to calories just like alcohol is toxic because it's alcohol not because its calories sugar is toxic because it's sugar not because it's calories if it were calories then every calorie would be a problem but where those calories come from determines where they go it's called nutritional biochemistry the funny part is I learned this in 1975 and college and then I went to medical school and they beat it out of me and for 35 years okay I have selective amnesia and had totally forgotten about this and then the data started rolling in I started doing my own data and went oh my god and now then I remembered oh my god I knew this I knew this then so here's the way we see it this is sort of the hypothesis we proffered as to why this all happens so here's the fructose coming into the liver and here's that browning reaction that I told you about the hemoglobin a1c and that causes these little hydrogen peroxides to build up called reactive oxygen species over here called oxidative stress in addition the mitochondria the energy burning factors in your cells will also make those ro SS as they're burning the energy that's normal that's standard aging and finally in the periphery you're going to lay down some extra fat visceral fat and that's going to create inflammatory cytokines which then go to the liver and cause more reactive oxygen species so you have this reactive oxygen species pool sitting in the liver that has to be detoxified has to be quenched and the thing that does that are the antioxidants in the case of liver it's usually glutathione or vitamin E and those are in the peroxisome that's where these ro SS go to die and that's a good thing and that's why certain diabetes drugs are helped with some of the complications because they're upping the peroxisomes but if you don't have enough of these then the ro SS go here to a part of the cell called the endoplasmic reticulum which is where proteins get folded including the insulin molecule and if you don't fold the insulin molecule right what happens your insulin deficient and if you don't fold the insulin receptor right your insulin resistant and if your insulin efficient than your insulin resistant you're a type 2 diabetic plus you get the lipid droplet you make the insulin receptor even more problematic there you go metabolic syndrome and worse yet there is no drug target for this so when you overload your mitochondria as I just did on that slide it causes all of these problems it caused the cell dysfunction causes cell aging and causes cell death and it causes all this liver fat to accumulate which causes liver insulin resistance which drives the hyperinsulinemia the leptin resistance the continued eating the sloth and all the symptoms that we see the only options are get the substrate down reduce the fructose consumption that's called diet now not eat less eat less sugar reduce the flux to the liver reduce how fast it gets there that's cold fiber because fiber forms a gel on the inside of the intestine that acts as a secondary barrier and prevents it from getting there so fast giving your liver a chance to catch up and finally increase clearance and that's called exercise dye and exercise but not eat less exercise more eat less what yeah and finally to finish it up dollars so here's what's happened to your diet why you've been sitting at home you know chowing down on those M&Ms here's what's happened 1982 to 2012 meat down 10% because we're all told to go low-fat fruits and vegetables exactly the same no change we're all told we don't eat enough fruits and vegetables well maybe that's true but we're eating just as much as we always did and we didn't have this problem before but we got it now grains and baked goods thirteen to fourteen percent up of percent that's important because that's glucose and that's insulin and that's weight gain and that contributes as well I'm not saying it doesn't refined carbohydrate is a problem dairy products thirteen point two thousand ten point six percent because now we're all lactose intolerant and finally processed foods and sweets eleven point six to twenty two point nine percent this is what has changed because processed food is the problem because processed food is high sugar low fiber real food is low sugar high fiber and every diet that works and you can pick it low carb Atkins zone sugar Busters paleo vegan Mediterranean traditional Japanese down the line every one of those diets have two things in common low sugar high fiber and you know what a low sugar high fiber diet is called it's called real food food that came out of the ground or animals that ate food that came out of the ground that's what real food is not food that comes in a package or a wrapper or a can or you know a bottle or a jar that's processed food so who's winning this war it's a war it's your wallet against your health and it's the food industry against your health so who's winning this war well here is the sp500 over the past several years and here is the stock price for McDonald's Coke and Pepsi and you know here's the economic downturn of 2008 right over here and you can see they're doing very well thank you and here's Hormel Archer Daniels Midland General Mills ConAgra Proctor and Greenville and Kraft all against the SP want to make money invest in a food company because they have a winning formula because they know how to get you to buy more now societal intervention that's the question how are we going to fix this now normally we like markets to fix problems we like the market to do its magic but you know what the market has never been able to fix any substance of abuse it wasn't able to fix tobacco it wasn't able to fix alcohol and that's why we have elected officials is to work when the markets don't and the markets have failed miserably and this is why okay so the question is what are we going to do so you know that first if you smoke or drink or take drugs it's bad for me it's not just bad for you it's bad for me right secondhand smoke car accidents declining housing prices because you turned your house into a crack den you know altered work productivity and absenteeism right which talked about presenteeism so the question is how does your obesity affect me two hundred seventy four million dollars extra for jet fuel yeah discomfort on the subway sinking of boats due to the weight two thousand three Lake George in New York a ferry coded for fourteen hundred and sixty pound people had 25 200-pound people capsized that ain't going to do it either here's why 65 billion reduction in work productivity 50% increase in absenteeism fifty five fifty percent increase in health insurance premiums as we talked about even more than that wasted in health care resources so here's the problem ready the food industry grosses one trillion dollars a year grosses we spend 2.7 trillion dollars a year on health care of which 75% are chronic metabolic diseases due to this of which 75% of them would be preventable and recoupable if we would do something that means that we are spending 1.4 trillion dollars a year going down a rat hole that is completely unworkable that we cannot possibly get back every single year one point four trillion what do you think we could do with 1.4 trillion dollars I think we could balance the healthcare budget you think we could balance the budget if we solve this problem we are losing more money than the food industry is making that makes this unsustainable we are losing more money than they are making and obesity is the threat to national security and ultimately the government pays twice they pay for the corn subsidy which by the way is a tax on you because you have to pay extra for other foods that they're not subsidizing and then they pay for the ER visits and they can't afford it and neither can we so last slide summary obesity means leptin resistance or brain starvation the starvation response is what causes the recidivism not being weak-willed energy expenditure and quality of life are the same thing so how fast you burn energy determines how good you feel and when your insulin is high you're stealing it from your cells and putting it in your fat to feel bad defects in insulin signaling promote leptin resistance insulins and endogenous leptin antagonists fructose in particular because of this liver fat production in the in the liver induces the liver insulin resistance that we saw which drives this metabolic syndrome and wastes our health care dollars fructose is also addictive and drives excess food consumption our food environment has been fructose off' eyed by the food industry specifically because they make more money we have to get the insulin down and the food industry has absolutely no impetus to change its practices so it's up to our elected officials except they don't want to touch this so up to us guess what Berkeley pestis Oh detects how about that now I'm not for taxation per se I am for reduction in consumption any way we can get there but taxation is the low-hanging fruit it's the easy thing because the markets already been distorted who cares if we distort it a little more ultimately we have to solve this problem it's a step in the right direction it's a baby step but it's a step so for further reading lots and lots of academic articles here and more academic articles and more academic articles I'll you know this will be online and you can see it and some non academic stuff is the book that I wrote last year called fat chance which has all of the science I just explained to you plus some sugar has 56 names a Shoppers guide is an e-book that you can take to the store and actually figure out what's on the food label so you can buy the right thing instead of the long thing and finally the fat chance cookbook which I wrote with my colleague and friend and chef Cindy Gershon every recipe in this book vetted by a Mount Diablo high school student to be prepare a bowl and consumable and delicious in 30 minutes all real food because if you don't know how to cook your hostage to the food industry for the rest of your life it's that simple and now one-third of America does not know how to cook we have to get back to it time to bring back home ech and for boys too okay but don't call it home ech call it adult survival skills a SS now they'll take it there's a movie called fed up for those of you who know about it is going to be playing here in next Saturday evening everybody saw the trailer at the beginning there's going to be a PBS special hopefully your PBS station here in Salt Lake City will pick it up during the Thanksgiving to Christmas pledge break called sweet revenge turning the table on processed food where all of this information will be available in a whole lot shorter fashion and we have started a non-profit very specifically to change the conversation to change it away from personal responsibility which it's not to change it away from calories which it's not to change it away from obesity which it's not and to change it to the things that actually matter our health so called the Institute for Responsible nutrition there's our website responsible Foods org I hope you'll all sign up log on and let us tell you what we're doing and we're doing a lot and there's good stuff coming and I will tell you that on Monday watch for a big announcement from UCSF and it will be all over the Internet log on to that too I can't tell you what it is it's embargoed till then just know Monday okay with that I want to thank all of you for your attention I want to thank Wayne Potts and James ruff for inviting me today I want to thank the University of Utah for sponsoring this wonderful series and I'm here to answer your questions thank you you

Channel: University of Utah College of Science

Views: 84,626

Rating: 4.8712196 out of 5

Keywords: Science, College of Science, Utah, Utes, STEM, Mathematics, Physics, Astronomy, Biology, Chemistry, Research, Education, College, University, sugar, leptin, insulin, diabetes, ucsf, lustig, robert lustig, fructose, sucrose, events, health, frontiers of science, diet, nutrition

Id: uIIXUZwpB-U

Length: 75min 0sec (4500 seconds)

Published: Fri Nov 14 2014