**Task 1: Podcast transcript**
Dr Rupy: Robert, fantastic to have you here. We're going to get right into this. What are some of the signs, if people are listening or watching this now, that people can be aware of that can signal that they're eating too much sugar?
Dr Robert Lustig: Oh my gosh. Well, first of all, that's everyone. In fact, we're supposed to consume six to nine teaspoons of added sugar maximum. Obviously, lower is better. Our current median consumption is actually seventeen and a half in the United States. It's about fifteen here in the UK. So, pretty much everybody is consuming too much sugar. And it's not because they're spooning one lump or two into their coffee or tea, it's because of the consumption of ultra-processed foods. Now, what are the symptoms is what you're asking. Well, first of all, craving. Anybody who says, oh, I have a horrible sweet tooth, that's sugar addiction until proven otherwise. And people don't understand that. People think, well, sugar's just empty calories. No, in fact, sugar activates the reward centre of the brain, the nucleus accumbens, and everything that activates the reward centre in the extreme is addictive. So we have chemical addictions, cocaine, heroin, nicotine, alcohol, sugar. We have behavioural addictions, shopping, gambling, internet gaming, social media, pornography. There's an -aholic after every one of those. Chocoholic, shopaholic, sexaholic, alcoholic, etc. The fact of the matter is, sugar activates the nucleus accumbens, it activates dopamine. Therefore, in the extreme, it is addictive. Now, is it addictive in everyone? Is alcohol addictive in everyone? No. Forty percent of Americans are teetotallers, never touch the stuff. Forty percent are social drinkers, can pick it up, put it down, no problem. I'm in that group. Ten percent are binge drinkers and ten percent are chronic alcoholics. Now, how do you know which one you are? Well, about the same for how do you know whether you're a sugar addict or not. What I can say is that people who are sugar addicted tend to be irritable, tend to be fatigued, tend to be a little bit, shall we say, impulsive, a little bit angry, a little bit ADD if you will. And of course, the main way is they tend to be very tired. And they gain weight. And when they gain weight, they tend to gain weight in their liver and of course in their visceral fat. So their waist size will go up. So, those are the kind of symptomatology profile, if you will. In children, you know, we see irritability and difficulty concentrating. In middle schoolers, sugar consumption has been associated with violent behaviours in Boston middle schoolers. Uh, certainly it's been associated with, um, uh, you know, uh, uh, uh, depression and, uh, other, you know, psychiatric symptoms as well.
Dr Rupy: I want to talk about addiction in a bit more detail here because I'm of the opinion that you can be a -holic of all these different, um, uh, substances or behaviours. Uh, the traditional description of addiction is that you have withdrawal effects, we definitely see that with sugar. There are people on the other side that have a differing opinion that sugar is not addictive. What are those, those, um, uh, opinions and what are your rebuttals to some of those?
Dr Robert Lustig: So there is a group here in the UK and in Europe called NeuroFAST. And they believe that in fact, the problem is not food addiction, the problem is eating addiction. Well, if that's the case, then, you know, there's no specific food that is addictive. Well, what that does is that gives the industry carte blanche to basically put anything they want in. They give alcohol a pass, and then they give caffeine a pass. And, well, you know, alcohol, caffeine, I mean, like, sugar is not addictive, but alcohol and caffeine are, but you're giving them a pass. Like, how does that work? They also say sugar is energy and it's necessary for life. Garbage. Where does that come from? Now, it is true that glucose is energy. It is true that your liver can metabolise glucose for energy and so can your brain and so can every other organ in your body. That's true. But the question is, do your organs need glucose? And the answer is, they need it, but you don't have to consume it to get it. Because your body will make it. It will make it out of protein or fat. Process called gluconeogenesis. So, yes, you need glucose, but you don't need to eat glucose. Fructose, the sweet molecule in sugar, there is no biochemical reaction in the body that requires it. It is completely vestigial to all animal life on this planet. And it is a mitochondrial toxin. It inhibits three enzymes that are necessary for mitochondria to work properly. It inhibits AMP kinase, the fuel gauge on the liver cell. It inhibits ACADL, which is one of the enzymes that helps chop up the, uh, uh, uh, fatty acids into two carbon fragments so that they can be oxidised. And also, uh, the byproduct of fructose metabolism, uric acid, inhibits carnitine palmitoyl transferase one, which is necessary to regenerate carnitine, which is the shuttle mechanism to get the fatty acids into the mitochondria for oxidation in the first place. In other words, fructose is a chronic dose-dependent mitochondrial toxin. So, the fact that it has four calories per gram is kind of irrelevant. In the same way that alcohol has seven calories per gram and is kind of irrelevant. There is no dietician on the planet who would call alcohol food. Well, there should be no dietician on the planet that calls sugar food because it is not necessary. It is not a nutrient. Just because it's energy doesn't make it a nutrient. In fact, sugar is not food. The definition of food. What is the definition of food? Substrate that contributes to either growth or burning of an organism. Well, I've just shown you that sugar actually inhibits burning because it inhibits mitochondrial ATP generation. How about growth? My colleague, Dr. Efrat Monsenego-Ornan at Hebrew University Jerusalem, head of the Department of Nutrition, has shown that sugar actually impairs linear growth. It impairs cortical growth, it impairs trabecular growth. Right? It hijacks growth. It promotes cancer growth through fermentation, through the Warburg effect, but it in fact actually inhibits growth. So if a substrate actually inhibits burning and inhibits growth, is it a food? In fact, sugar is not a food. Sugar is a food additive. That's what sugar is. And we have plenty of data to support food additive addiction. So this is where the argument becomes actually not just semantic. Food versus eating addiction. Ultimately, what we're talking about is food additive addiction. And that's one of the things I'm trying to, you know, promote and get across to both the public and to NeuroFAST because, you know, they got to get with the freaking program.
Dr Rupy: And with the, uh, just on that, on that point around, uh, food addiction, I think it also comes down to how socially acceptable some of these items are. You know, if you take the, the glib example of smoking, it was very socially acceptable 60, 70 years ago and it took decades for it to become socially unacceptable. And I think we're still at the early stages when it comes to, to sugar as an additive.
Dr Robert Lustig: I couldn't agree with you more, Rupy. I mean, smoking went from fashion to filthy habit in 30 years. Okay? Now, how did that happen and why did it take 30 years? The answer is, we taught the children, the children grew up, and they voted. And the naysayers are all dead. Okay, this is a generational shift and unfortunately requires a generation to be able to see it. In the fact, we have had four, count them, four cultural tectonic shifts both in the US and UK over the last 30 years. And here they are. Number one, bicycle helmets and seatbelts. Number two, smoking in public places. Number three, drunk driving. Number four, condoms in bathrooms. Each of those was basically third rail of politics 30 years ago. If a legislator had stood up in a state house or Congress or Parliament or the Duma or anywhere else in the world and promoted any legislation about any one of those four things, they'd have gotten laughed right out of town. Nanny state, liberty interest, get out of my kitchen, get out of my bathroom, get out of my car. Today, they're all facts of life. No one's bellyaching about any of those. Oh, we're bellyaching about new stuff, like COVID vaccines. I mean, it's not like we'll ever solve this issue, but those four, you know, they're settled. There's no arguments about, you see anybody protesting seatbelts today? Lord Balfour in 1980 stood up in Parliament right across the street over here, okay, and basically told everybody that seatbelts were an affront against their personal liberty. I mean, let's get real here. All right? This takes a generational shift. And we've done it and we'll do it with sugar. We're about, I would say, 10 years into the 30-year cycle.
Dr Rupy: Yeah, yeah, yeah. I see. And it does feel like it's quite early in this, uh, in this journey of changing perceptions socially around sugar. And I guess, you know, one of the other things I think is quite important to distinguish is, uh, the different types of sugars that we have in our food supply. We mentioned ultra-processed foods, but maybe we could use the example of, uh, a whole food that contains natural sugars like fructose, um, an apple, let's say, uh, and a juice, which is somewhere along that processing, and then something where you have an apple-like substance added to something that's wrapped and you'll find in a, in a candy bar or whatever. And walk us through sort of what the, the body receives in those three silly examples.
Dr Robert Lustig: So, you know, people always say to me, you know, Dr. Lustig, you are so full of crap. Okay, because what you're basically telling us is don't eat fruit. I never said that. In fact, eat all the fruit you want, as long as it's fruit. Okay, so what's the difference between fruit and fruit juice? Okay, big difference. And the answer is the fibre. Now, people think fibre is what you throw in the garbage after you've juiced the fruit. In fact, the fibre is the reason to consume the fruit in the first place. The juice is nature's way of getting you to eat your fibre. So, like, why is fibre important? So, fibre is important for six different reasons. The first is it gives you a feeling of fullness. So it tells your brain you've eaten something, which is necessary to help start the mechanisms of satiety. It doesn't induce satiety, but it helps, you know, sort of mitigate, modulate the amount you eat. The second thing it does, the soluble and insoluble fibre within the fruit, and you need both, soluble fibre is like pectins or inulin, like what holds jelly together. Insoluble fibre is cellulose, like the stringy stuff in celery or cardboard for that matter. Okay? When you consume the whole fruit, you're getting both. And what happens is that the insoluble fibre sets up a lattice work, a fishnet, if you will, on the inside of your intestine. And the soluble fibre are globular, they plug the holes in the fishnet, like kelp would. And together, they form an impenetrable secondary barrier that prevents absorption of glucose, fructose, sucrose, simple starches from getting from the intestinal lumen into the bloodstream. So, you are delaying the absorption, you are delaying the glycemic response, therefore you are delaying the insulinemic response and you're attenuating it. And it's all about keeping that insulin down. Because insulin's the bad guy in this story. It's the thing that both drives weight gain and chronic metabolic disease. Anything you can do to keep your insulin down is good. And fibre is the best way to keep your insulin down. So when you're consuming the fruit, you're getting that second effect of the soluble and insoluble fibre mitigating the glucose and insulin rise. Well, if you're not absorbing it early, it goes further down the intestine where the microbiome will chew it up for its purposes. So you are feeding the gut. And it turns out that that gut will take that that fibre and will turn it into short-chain fatty acids which are shown to be anti-inflammatory, anti-Alzheimer's. And lastly, the fibre will act like little scrubbies on the inside of your colon preventing colon cancer. So six benefits to consuming the fruit as a whole fruit, but not because of the glucose, not because of the fructose, but rather because of the fibre. So, eat the fruit, don't drink the juice. Now, then we get to soda, or, you know, or worse. And now then you've got a whole another, you know, uh, uh, you know, level of toxicity.
Dr Rupy: Yeah, yeah, because with the juice, you're getting some, let's say, uh, polyphenols that you have in apple with the fibre mitigated. So you can make an argument that there is some benefit, although it still will spike your blood sugar.
Dr Robert Lustig: So, if you juice a fruit, you will still have soluble fibre. The soluble fibre, the globular soluble fibre will still be there. And that does have some metabolic benefit. It will still generate short-chain fatty acids. Okay? It still has a benefit. But of the six benefits that I just described, you will only get two of them. So you're short-changing yourself when you do that. So I am not for juicing. I know that the rest of the world thinks, you know, magic bullets are magic. I don't think so.
Dr Rupy: And does that go hand-in-hand with smoothies or is that further up the same thing?
Dr Robert Lustig: Same thing. Yeah. Yeah. Okay. Let's move on to sugar-sweetened beverages or sodas, uh, because this is a main line to the liver, I guess.
Dr Rupy: Indeed. Yeah. Uh, so talk us through what happens when you have a, uh, a high fructose, uh, corn syrup sweetened sugar beverage or...
Dr Robert Lustig: Well, first of all, uh, sucrose, table sugar, cane sugar, beet sugar, the stuff you put in your coffee, is what you have in your UK Coca-Cola. High fructose corn syrup is what we have in our US Coca-Cola. Does it matter? Not a bit. They are exactly the same. Now, I mean, technically they're not the same. Um, uh, sucrose is one glucose, one fructose with an O-glycosidic linkage linking the two. So it's a disaccharide. High fructose corn syrup is one glucose, one fructose, not bound together with that O-glycosidic linkage. So they are free. So they are monosaccharides. So people seem to think that that means something. No, it doesn't. It means nothing because the enzyme sucrase in your intestine will cleave that O-glycosidic linkage bond in about a nanosecond. You absorb the two molecules separately and they both go to the liver and do what we talked about. Basically, if you overwhelm your liver's capacity to metabolise fructose, the mitochondria who are being inhibited, right, as we just discussed, have no choice but to take the excess and turn it into liver fat. This is a process called de novo lipogenesis, new fat making. And fructose drives that de novo lipogenesis. And then that fat is sitting in the liver and has one of two fates. It can either be exported out as a VLDL, very low density lipoprotein, which you measure in your serum triglyceride and can serve as a substrate either for obesity or for cardiovascular disease, or that fat molecule, that fat, uh, molecule won't make it out at all and will precipitate in the liver as liver triacylglycerol, as a lipid droplet. And now you have non-alcoholic fatty liver disease, which predisposes you to diabetes and every other chronic metabolic disease. So, either way, it's a problem. If you overwhelm your mitochondria, you will make liver fat. And there are four things that overwhelm mitochondria. Fructose, alcohol, trans fats, and branched-chain amino acids. Leucine, isoleucine, valine. They are metabolised the same way. And because of that, when they are deaminated, they become branched-chain organic acids, they overwhelm the mitochondria, and the mitochondria has no choice but to turn those into fat as well. This is the work of Christopher Newgard at Duke. So, it's not that I'm fructose-centric, it's that I'm hepato-centric. The liver's where the action is. And anything that overloads your liver mitochondria becomes a toxin. Even things that we call food.
Dr Rupy: Let's give listeners and viewers some insight into why the liver is, uh, one of your focal points because I don't think many people grasp just how prominent and prevalent NAFLD is in the States and also burgeoning in the UK, particularly in a younger cohort.
Dr Robert Lustig: Yes. Uh, I mean, this is a disease that was never diagnosed before 1980. So, prior to 1980, if you saw fat in the liver on either an ultrasound or electron microscopy of the, you know, of a liver biopsy, okay, that was an alcoholic. The only place you saw fatty liver was an alcoholic. Okay? Well, today, okay, 20% of five-year-olds have fatty liver. 20% of five-year-olds. Not obese five-year-olds, five-year-olds. All right? 45% of the adult American population has fatty liver disease. This is a disease that had never existed before 1980 and now 45% of America has it. You want to talk about pandemics? This is the freaking pandemic and no one is talking about it. Now, why does it matter? The answer is because that fat is making the liver not do its job. That fat is generating a phenomenon called insulin resistance. It is preventing the ability of the liver to respond to the insulin signal. Now, the pancreas releases insulin in response to the glucose level. The insulin drains from the pancreas. Now, normally when a gland releases a hormone, it goes into the systemic circulation. And the volume of distribution of the systemic circulation is six litres. So, a little insulin will get diluted throughout the body if it went into the systemic circulation, but it doesn't. It goes straight to the liver through the portal vein. And the volume of distribution of the portal vein is about 250 millilitres, not six litres. So, a little insulin drives a very high insulin concentration in that portal vein. So when your liver's not working right, your pancreas has to make more insulin to make the liver do its job. Well, that's going to raise insulin levels at the level of the liver in order to get that liver to do its job. And that's going to end up raising insulin levels throughout the body. This generates hyperinsulinemia, this generates fat deposition, this generates chronic metabolic disease at the level of the coronary arteries, in terms of coronary vascular smooth muscle proliferation. It's going to generate insulin resistance at the level of the brain, starting the process of Alzheimer's, etc, etc, etc. So, the liver is the nidus for chronic metabolic disease. When the liver gets sick, all of the organs downstream of the liver get sick as well. So the liver is a primary target both for the disease process and also for therapeutics.
Dr Rupy: Yeah, yeah. And in terms of biomarkers for, uh, insulin resistance, uh, obviously type two diabetes, we use things like HbA1c. These are things that are quite further along and downstream in terms of when we see the red flags.
Dr Robert Lustig: Yeah, yeah. I mean, every one of the things you just mentioned, Rupy, the horse is already out of the barn. Those are late, late markers. So the question is, well, what are the early markers? I mean, how can you, you know, catch this, nip it in the bud? And the answer is the best test is a fasting insulin level. And I am here in the UK in part to get the NHS to get their freaking act together and start drawing fasting insulins. Now, this is not a slam dunk. And the reason it's not a slam dunk is because the American Diabetes Association and also Diabetes UK, I should add, do not believe in this. Okay, so why is it that the ADA says one thing and I say the exact opposite? Because I'm right and they're wrong. That's why. Now let me explain why that's true. The ADA says don't draw fasting insulin for two reasons, and both of them are specious. Both of them are incorrect. The first, they say fasting insulin levels are not, the assay is not standardised across platforms. That is true. I don't argue that. That is absolutely true. Radioimmunoassay, ELISA, you know, uh, um, uh, MRS, you know, different ways to measure insulin, not standardised. I agree with that. It turns out there is another species that is picked up in the insulin assay. It's called proinsulin. So, you're from your medical schooling, you know that your pancreas makes a peptide called proinsulin, and then an enzyme called prohormone convertase one cleaves a piece of peptide out of that proinsulin called C-peptide, and then you make the mature insulin molecule, and then the mature insulin molecule gets secreted in a vesicle from the pancreas. Proinsulin only has 5% of the activity of the mature insulin molecule. It's a prohormone, it's not really an active hormone. Well, when your pancreas is under duress, when you have a high glucose level and you got to get it down and you're significantly insulin resistant, your pancreas can't wait. Okay? And so it's not going to wait for that PC1 to cleave out that C-peptide. It's going to release the whole freaking molecule. And so you will end up with hyperproinsulinemia. This was actually work by Dr. John S. Yudkin, not John Yudkin, the famous British nutritionist, physiologist of the 1970s, the one who argued with Ancel Keys. This is his cousin, John S. Yudkin.
Dr Rupy: Oh, is that his cousin? Oh, right. Okay.
Dr Robert Lustig: Yeah, a cousin. A wonderful guy. I've met him several times. He is, he's a, he's a, uh, he's a major force in the field. And, uh, uh, my, I tip my hat to him. Okay, but hyperproinsulinemia. Well, it turns out the insulin assay will often pick up both. So the American Diabetes Association says, well, don't draw it. I mean, you're basically measuring two species at once. That's true. Who cares? It's high. That's what matters. And if it, and if you got treatment, it would go down and you could monitor that. So, I think that's a specious argument. I just think the ADA is just off base. Second reason they say, don't draw it. They say fasting insulin levels do not correlate with obesity. That is also true. It correlates with metabolic health.
Dr Rupy: Okay.
Dr Robert Lustig: And there are plenty of obese people who are metabolically healthy, and there are plenty of thin people who are metabolically ill. That's right. It doesn't correlate with obesity. It correlates with metabolic health. That's exactly the reason to draw it. So the reason they say not to draw it is actually the reason to draw it. So the ADA, you know, you got your head up your know-you-know-where, and I'm, I'll debate you any moment you would like, okay, in any forum you choose, and I'm going to win.
Dr Rupy: Is there a cost consideration with fasting insulin at all, or is there, is that a moot point?
Dr Robert Lustig: $14.50 in America.
Dr Rupy: Wow. Okay. And if it's that in America, it's probably going to be cheaper over here.
Dr Robert Lustig: Probably.
Dr Rupy: Yeah. Wow. Okay. Are there other markers that we can be looking at in the interim whilst we don't have fasting insulin as the standard across the NHS?
Dr Robert Lustig: Right. So, there are some other, um, uh, uh, metabolites that, uh, and intermediaries that are valuable. Uric acid is very valuable. Now, the problem with uric acid is the normal range. So uric acid, as you, as I said, is a byproduct of fructose metabolism. You know, so it goes from fructose-1-phosphate, okay, you know, when the, when the fructose gets phosphorylated to fructose-1-phosphate, ATP goes to ADP, then ADP goes to AMP, which goes to IMP, finally to uric acid. So uric acid will go up. Now, normally we think of uric acid as being associated with purines, with meat. It's also associated with sugar, both. All right? So it's a proxy for sugar consumption. And uric acid levels should be less than 5.5. But if you look at the lab slip, it'll tell you that the upper limit of normal is seven. Now, why is that? Why is 5.5 the my upper limit and the lab slip's upper limit is seven? The answer is because the entire curve has shifted to the right over the last 40 years because everyone has metabolic syndrome. Because 93% of Americans are metabolically unfit. That's why. All right? And so, basically, you know, how do you determine a normal range? You take 10,000 specimens from people who say they're healthy, you know, you figure out the mean and two standard deviations and you draw the line. All right? Well, if everyone's sick, you know, the whole curve has shifted to the right. So 5.5 is actually the upper limit of normal for uric acid. And that's a relatively earlier marker. The second one is ALT, alanine aminotransferase. So this is a marker for liver fat. Again, same issue. What's the normal range? The normal range is up to 25. Now, on the lab slip, the normal range is up to 40. Same issue. Over the last 40 years, it has moved from 25 to 40. When I started medical school in 1976, the upper limit was 25. It's now 40 because everyone's got fatty liver. So, these are two markers that are valuable and cheap and in a standard chem panel that you can use, but you have to be able to interpret them properly. And the first thing you have to do is get rid of the highs and the lows. I don't know about here with the NHS, but in America, that high-low, you know, the H and the L, you know, in that column, that's worth 10 bucks. That's an interpretation.
Dr Rupy: Oh, really?
Dr Robert Lustig: Oh, really.
Dr Rupy: Oh, wow. I didn't know that.
Dr Robert Lustig: Yeah, tell me about it. Blows my brains out. But this is the way it is.
Dr Rupy: Wow. Wow.
Dr Robert Lustig: So, um, those are, uh, valuable. Another thing that's valuable is the triglyceride to HDL ratio. That's a marker for insulin resistance. All right? And, you know, by the time you're waiting for fasting glucose or haemoglobin A1c, the horse is out of the barn.
Dr Rupy: Yeah, yeah. And in terms of, um, HbA1c, that's specifically looking at glycated haemoglobin with glucose.
Dr Robert Lustig: That is particularly looking at glycated haemoglobin at position one with glucose. Now, not the whole haemoglobin molecule, just position one, the lysine at position one. If you want to do a glycohaemoglobin, then you're getting the whole thing, but virtually everyone does A1c now. The point is that fructose also fructates haemoglobin, but it doesn't do it at position one, it does it at position 66 and 110, and we don't have a setup for measuring that properly. That's a research tool.
Dr Rupy: Ah, gotcha. And so, do you think there's ever a point in the future where we could get some sight over that? And would that be useful, particularly as fructose is in our food supply?
Dr Robert Lustig: That's a really good question, and I can't answer that. Um, the Japanese have done that in a research setting and shown that it occurs. Whether or not it will end up having clinical relevance and help us in any meaningful fashion, I would have to see data. And we're still waiting for that.
Dr Rupy: Give us an insight into some of the, uh, foods that might have hidden sources of sugar in, because I'm always asked about, okay, which foods should I avoid? And there's the obvious ones, but there's perhaps some less obvious choices that people aren't as aware of when it comes to sugar.
Dr Robert Lustig: It's everywhere. I mean, it's just everywhere. Um, you know, there's the obvious, the, you know, the sugar-sweetened beverages, that's 37%. There's the candy, cakes, ice cream, that's 16%. That leaves 49% of your, uh, sugar, uh, uh, uh, consumption in things you didn't know had it. Yoghurt, um, breakfast cereal is a huge one. Um, you know, um, salty snacks, uh, peanuts, uh, you know, barbecue potato chips, uh, you know, and the list goes on and on and on. I mean, Chinese chicken salad is dessert. Yeah. Okay? All right? That's the way you have to think about it. If a sugar is one of the first three ingredients, that is dessert.
Dr Rupy: Yeah.
Dr Robert Lustig: And that's how you have to think of it.
Dr Rupy: In your clinical experience, um, I remember hearing you talk about how you show parents to how you practically remove sugar from their diets, but also their kids' diets as well. I wonder if you could perhaps give us some anecdotes of what those children and adults would experience when they removed sugar after, let's say, 30 days.
Dr Robert Lustig: Right. So, in, in 2010 to 2014, we performed a study that we've now published five papers on, uh, where we took obese kids with metabolic syndrome from our own clinic at UCSF. So, Latino and African-American, all high sugar consumers, all with metabolic syndrome, you know, obesity plus at least one comorbidity. We figured out what they were eating at home on their home diet. We studied them on their home diet. And then for the next nine days, we catered their meals. No added sugar. We took the percent calories of added sugar from 28% down to 10%. We gave them fruit. That was their only source of sucrose, was fruit. Everything else, we wiped out the added sugar in the food. Now, if you do that, if you go from 28 to 10%, you're removing 350 to 400 calories a day out of the kid's diet. And if you do that for 10 days, the kid might lose weight. We didn't want them to lose weight. We actually, we wanted them to stay the same weight or even gain weight. Because we knew the critics would say, well, of course the kid got better, the kid lost weight. You know, so what? We didn't want them to lose weight. We needed them to stay the same or gain. So we had to replace the 350 to 400 calories a day of sugar that we had taken out with something that was equicaloric. We gave them extra starch. So, in the vernacular, we took the pastries out, we put the bagels in. We took the sweetened yoghurt out, we put the baked potato chips in. We took the chicken teriyaki out, we put the turkey hot dogs in. So we didn't give them good food, we gave them crappy food. We gave them processed food. We gave them food from local supermarkets, Safeway. Okay? Food you can buy, but, you know, not necessarily the food the kid would normally choose directly, but the parents were okay with it because it was, you know, Safeway food, they could get it themselves if they needed to. But we supplied it. And we gave them a scale. And every day we'd call them up, what'd you weigh? And if they were losing weight, eat more, you know, in order to maintain their weight stability over the course of the 10 days. And then we studied them again 10 days later in their fructose-restricted state. Every aspect of their metabolic health improved with no change in calories and no change in weight. 22% reduction in liver fat, 46% reduction in the conversion of sugar to fat in the liver, 49% reduction in triglyceride levels, 7% reduction in visceral fat, and most importantly, their pancreas started working right. Their pancreatic secretion and their insulin sensitivity all improved. In other words, we reversed their metabolic syndrome with no change in calories, no change in weight, showing this was not about the quantity of the food, it was about the quality of the food. And that sugar was indeed a direct, chronic, dose-dependent mitochondrial toxin.
Dr Rupy: And that should have been, perhaps not the nail in the coffin for the calories in, calories out argument, but certainly, you know, enough evidence for us to change our thinking at an industry level around calories in, calories out.
Dr Robert Lustig: Well, the food industry does not want to change. The food industry, you know, the energy balance model, the calories in, calories out model, that's how they got here. That's their gravy train. Because they say, well, you know, you get to choose what calories you want, and everyone has discretionary calories, and if you want to spend them on sugar, you know, you should be allowed to. So, they subscribe to the energy balance model because it's good for them. Now, it just so happens there are several other models. One is called the carbohydrate-insulin model, that it's the refined carbohydrate and sugar because of the insulin rise. And I thus far have subscribed to that. This, of course, has been also been promulgated by my colleague at Boston Children's, Dr. David Ludwig. I'm Lustig, he's Ludwig. Someday we're going to open a law firm. It turns out there's a third model called the redox model, which has to do with oxidation-reduction abnormalities and reactive oxygen species that ultimately cause, uh, leads to false metabolic signalling within cells and leads to proton leak, which leads to mitochondrial dysfunction, which is related to the two models but different. And then finally, most recently, we've developed the obesogen model, specific chemicals in the environment like bisphenol A and phthalates and, you know, uh, PFAS, you know, uh, polyfluorinated substances like Teflon, um, that also, you know, generate obesity as well. And it turns out what they all have in common, all the models, all four models, is reactive oxygen species. Oxidative stress. Oxidative stress by sending false signals to cells, tell the cells to basically metabolise differently because the cell thinks there's a proton leak. And so it thinks it needs to shut down its mitochondria. And so, we're trying to unify the various hypotheses and try to get rid of the calorie. The calorie needs to die. My job is to kill the calorie because the calorie is what the food industry hides behind.
Dr Rupy: Yeah, yeah, yeah. And I, I guess, uh, in addition to that, and I've, I know you've touched on this in the past, it's, um, what about stress? Stress and, and sugar.
Dr Robert Lustig: What about stress? Yeah, yeah. So, stress does several things. Number one, it causes insulin resistance on its own. Cortisol is a primary driver of insulin resistance. Cortisol is also a primary driver of amygdala activity. And one of the ways to try to mitigate increased amygdala activity is with food, but higher density food. So it increases appetite. All right? And so, um, stress basically makes everything worse. In addition, stress puts your prefrontal cortex to sleep. Puts it into suspended animation. So, any cognitive control that you might have had over your diet goes out the window as soon as you are chronically stressed. And so your amygdala just goes hog wild and, you know, says, feed me in order to feel good so that you can get a reward, uh, you know, system generation at the level of the nucleus accumbens. So my colleague in, uh, Paris and I, his name is Dr. Philippe Goscier, he's a robotics professor and a neuroscientist of interesting portfolio. Um, he and I have been working for the past three years on a computational model of the limbic system. And basically it all comes down to the amygdala, the fear centre. And there are a lot of things that alter that amygdala. And cortisol, obviously, you know, that's ground zero for what's going on. And so when your amygdala is under attack, okay, all hell breaks loose. And basically that's what's happened to our society in the last 50 years.
Dr Rupy: Yeah. I mean, as a general practitioner and even someone working in A&E, it's definitely something that I specifically ask and look for, uh, whenever somebody is complaining of a weight-related issue or a metabolically, uh, metabolical, um, issue. I think that's, uh, an important consideration.
Dr Robert Lustig: Absolutely. If you're stressed, you can't fix it.
Dr Rupy: Yeah, yeah.
Dr Robert Lustig: You got to, you got to unstress. Now, the question of course is, how do you do that?
Dr Rupy: Yeah, and there's the problem, hey.
Dr Robert Lustig: And that, and that is where individual, you know, personalised medicine really comes in. It is because everyone's got a different reason for their stress.
Dr Rupy: Yeah.
Dr Robert Lustig: And there's no, there's no one size fits all for that.
Dr Rupy: Yeah, yeah. Talking of collaborators, um, you've, you've collaborated with a colleague of mine, Rachel Gow, on, uh, ultra-processed food, the, the metabolic matrix. I wonder if you can talk to us a little bit more about, uh, ultra-processed foods and the impact on metabolic health.
Dr Robert Lustig: So, as I said, ultra-processed food is not food for the reasons that we've just discussed. Um, there is a company in the Middle East, the Nestlé of the Middle East, if you will. Uh, it's called KDD, Kuwaiti Danish Dairy Company. Um, and they make all sorts of crap. They make flavoured yoghurts, they make, uh, frozen, you know, ice cream, they make, uh, flavoured milks, they make confectionery, biscuits, tomato sauce. Okay. The CEO and founder of KDD is a Kuwaiti national born in the UK who fed Kuwait through the first Gulf War. And Queen Elizabeth knighted him. So he is Sir Mohammed. So how many Sir Mohammeds you know?
Dr Rupy: Not many.
Dr Robert Lustig: He is a wonderful guy.
Dr Rupy: Okay.
Dr Robert Lustig: Okay, and absolutely, he is a prince. The guy is an absolute, you know, um, stand-up guy. I love him. Okay? But Sir Mohammed, eating his own food, weighed 350 pounds and had type two diabetes and back pain at age 48. And so he went to his UK doctors and his UK doctors gave him insulin and oral hypoglycemics and he got worse. And he felt awful. And so he said, I got to figure out what to do. So he started going on the internet and doing his own, you know, research. And he found Jason Fung and me. Jason is an adult nephrologist in Toronto who has seen enough diabetic nephropathy in his day and has, you know, glommed on to intermittent fasting as a primary, you know, therapeutic tool. Fair enough. And found me. Anyway, he started doing what we said and he lost 100 pounds, his type two diabetes went away, his back pain resolved, and he thinks we hung the moon. Okay. That's all good. And then he has his aha moment, his moment of epiphany. Wait a second, if I did this to myself eating my own crap, what am I doing to the rest of the Middle East? And so he talked with his sister who's the chief financial officer and they agreed, you know, since they're privately held, they don't have Wall Street quarterly reports, they don't have shareholders to placate, that they would take the long view and they wanted to turn their company around and make it metabolically healthy. Now, how do you do that? So they called me. And they said, we would like to engage you in a long-term project to help us develop the method for being able to make processed food healthy. Now, initially when I heard that, I thought to myself, that's a fool's errand. But, you know, the more I thought about it, I said, you know, there are certain principles that we could certainly make things better. And so I convened a scientific advisory team, Dr. Gow, our fatty acid expert, uh, Dr. Tim Harlan, uh, who's head of culinary medicine at George Washington University.
Dr Rupy: Yeah, I know him well. Yeah.
Dr Robert Lustig: Wonderful guy. I love him. Okay? Best dressed doctor in America.
Dr Rupy: Yeah, he is. Yeah.
Dr Robert Lustig: I love him. I love Tim. He's like my bro. Um, Will from Alderson, my, uh, social media director and has been in the food business for a long time. And Andreas Kornstädt, uh, from Hamburg, who is a, uh, computer data scientist, Stanford trained. And we, uh, convened the five of us and we developed a protocol, a set of tiers criteria. Uh, uh, KDD, uh, uh, you know, submitted all of their various ingredients for, uh, chemical analysis by the company Eurofins. And basically what we did was over the course of, uh, the three years of the, uh, uh, of the project, we developed the roadmap for being able to take a company and take the item, you know, the 180 items, the 180 SKUs in this company and turn them around to be metabolically healthy. And to KDD's credit, 10% of their portfolio has turned around.
Dr Rupy: That's incredible. Yeah. That's absolutely incredible.
Dr Robert Lustig: Yeah.
Dr Rupy: That's like the, in my mind, that's almost like the pinnacle of your career. Everything that you've been doing and working up to this point is changing the giants that produce what is it, 80, 90% of our foods.
Dr Robert Lustig: Indeed. And the point is that, obviously, if KDD alone does it, it, you know, goes nowhere, but, you know, that's why we told KDD at the beginning of the project that our goal was to publish this. This had to reach, you know, the general public. And so that it could be used as a template for other companies to be able to do the same thing. And that was, you know, inherent in our, uh, in our initial agreement. And so we published this in Frontiers in Nutrition back on March 30th. It's called the Metabolic Matrix, re-engineering ultra-processed food to protect the liver, feed the gut, and support the brain.
Dr Rupy: This is wonderful. I'm getting sort of like goosebumps because if you're creating the playbook for a company the size, perhaps it's not as big as Nestlé or, you know,
Dr Robert Lustig: Well, it's not as big as Nestlé, but it's big enough.
Dr Rupy: It's big enough to demonstrate to the bigger players that this is possible and this is the direction of travel.
Dr Robert Lustig: Feasible, scalable, and profitable.
Dr Rupy: Absolutely. Yeah. Yeah. Because I, I always think, you know, these large companies, uh, get a bad rap for good reason, but they were tasked with creating portable, long shelf life, palatable foods and distributing them at a global scale. And they've done that fantastically at the expense of metabolic health.
Dr Robert Lustig: That's right. Metabolic health was the, um, you know, the, the sacrificial lamb.
Dr Rupy: Yeah, yeah, yeah, exactly. And so if you're demonstrating that you can do all those things plus metabolic health, that's phenomenal. That's really going to have a massive, uh, impact on, on health across, across the world.
Dr Robert Lustig: And that's the goal.
Dr Rupy: Brilliant. And how, I mean, it's probably going to be very involved, but how did you manage to get 10% of their entire SKU to be metabolically healthy? Was it the addition of things like functional fibres to the original products or is it a real sort of rewriting the recipe from scratch?
Dr Robert Lustig: We're adding fibres to things that normally didn't have fibre. We're adding, um, uh, uh, fatty acids, you know, omega-3s to things that didn't have omega-3s. So there's a lot of additions. There's a few subtractions. We're getting rid of the emulsifiers. We're getting rid of a lot of the artificial colours because they generate reactive oxygen species.
Dr Rupy: Interesting. And price?
Dr Robert Lustig: It's a little bit more expensive. What we learned was you can't get rid of all the sugar. If you go straight to non-caloric sweeteners, it doesn't taste very good.
Dr Rupy: Rupy, have you ever tasted a no-sugar chocolate bar?
Dr Rupy: Uh, I don't believe I have, although I may have tried, oh no, I did. I've tried a diabetic bar before. It wasn't very nice.
Dr Robert Lustig: Yeah, right. It wasn't very nice. Exactly right. It wasn't very nice. You would never go back for a second one if you had a choice, would you?
Dr Rupy: No, no.
Dr Robert Lustig: That's right. The fact of the matter is, you need a little sugar to activate that nucleus accumbens, to make it rewarding. The question is how much? So we had to walk the fine line between activation of the nucleus accumbens and not overloading the liver. One teaspoon per serving. One teaspoon. One teaspoon will get you the nucleus accumbens effect without the liver effect. Okay. One teaspoon per serving. That's not enough for an ice cream. That's not enough for a flavoured milk. What we learned was we could use a sugar extender beyond that, one that has metabolic benefits of its own. The one that we have chosen, the one we think is going to be the winner in this non-nutritive sweetener, uh, you know, battle, okay, is allulose.
Dr Rupy: Allulose, okay.
Dr Robert Lustig: Allulose. And allulose has some very promising metabolic, uh, health benefits, including lowering of LDL, raising of HDL, looks good. Uh, don't see any, you know, toxicities at the moment. It's an epimer of fructose. Uh, it's metabolised appropriately as opposed to generating, you know, byproducts like aspartame and stuff like that, not good. Um, problem right now is that allulose, number one, is 12 times as expensive as sugar. But it's coming down because demand is going up and there are new methods for production that will reduce, uh, cost. And also, currently the EFSA has said allulose is okay, but the Gulf Cooperation Council has not yet.
Dr Rupy: Okay.
Dr Robert Lustig: So we're actually waiting to institute those.
Dr Rupy: So, lots of work yet to do.
Dr Rupy: Yeah, yeah. And is allulose excreted by the liver or kidney?
Dr Robert Lustig: Kidney, sorry.
Dr Rupy: Kidney, sorry. Okay. Yeah, yeah. And there aren't any local effects that we know of allulose?
Dr Robert Lustig: Not that we know of.
Dr Rupy: Ah, interesting. Um, bringing this full circle, I guess, to the, uh, non-nutritive, um, the non-nutritive, um, uh, assets of, of sugar, have you come to the conclusion that it's not sugar per se, but the excess of sugar that is causing the issue?
Dr Robert Lustig: Yeah, I mean, basically, we have a limited capacity to metabolise anything. Paracelsus, 1537, you know, nothing is without poison. You know, the dose determines the poison. Indeed, that is correct. I mean, you know, in excess, water is toxic. In excess, oxygen is toxic. All right? But there's no abuse potential. With sugar, yeah, there is. Yeah. Yeah. With alcohol, there is. So when you're both toxic and addictive, you got a problem. So, we need to recognise that fact. Any substance that is both toxic and addictive and ubiquitous and has negative impact on society, we regulate. Tobacco, alcohol, opioids, etc. Okay? For sugar, we have nothing. And, you know, public health officials and politicians need to recognise this inconvenient truth in order to be able to make headway. We have 1500 years of alcohol control policy. Every country in the world has an alcohol control policy. We need sugar control policies.
Dr Rupy: Yeah. I agree. Um, look, we haven't scratched the surface when it comes to the genetic predispositions of laying down visceral fat across different backgrounds. Uh, there's a whole bunch of stuff I could ask you about the industry. We'll have to do this again at some point.
Dr Robert Lustig: I suppose so.
Dr Rupy: But this has been a pleasure. I appreciate your work. I appreciate your, uh, your, the vigour by which you're, you're, you're bringing this.
Dr Robert Lustig: Well, that's very kind of you. I don't know any other way to be.
Dr Rupy: I love it. That's great. Thank you very much. I appreciate your time.
Dr Robert Lustig: Thank you.
Dr Rupy: Thank you, man.
