A Root Cause Stopping You From Losing Body Fat (Not Carbs Or Sugar) | Dr. Robert Lustig

Dr. Rangan Chatterjee 0:00 I wanted to start off with something that you wrote in your latest book, Metabolical. Data shows that it is your liver and visceral fat that determine your health, not your weight or total body fat.

Dr. Robert Lustig 0:17 Stand by that. That's exactly right. It's not the fat you can see that counts, it's the fat you cannot see. And the reason is because those fat depots have different causes, different effects, and ultimately different drainage. The drainage is actually the important thing. So let's go through those three fat depots that you just mentioned and what causes them and what consequences there are for them. So the first fat depot is the one that's obvious, the one you can see, subcutaneous fat, big butt fat. Subcutaneous fat is where your body wants to store fat, and there's a lot of it, all right? And it has big vacuoles. In other words, wh- the place where the fat actually gets stored inside each of the adipose tissue cells. Now, it is possible to overstuff each of those vacuoles, and when you overstuff each of those vacuoles and you put m- down more and more subcutaneous fat, there is the possibility that that fat vacuole will expand and expand and expand, and the perilipin border that surrounds that fat vacuole will be stretched and stretched and stretched so severely because that, that fat vacuole has just gotten so big, you know, like a, like a balloon that's about to burst. And what happens is that when that happens, the perilipin border can't hold it anymore, and the fat starts to leak out into the adipose tissue cell, choking it off and killing it. And so now you have a dead adipose tissue cell with a whole lot of grease that has to be cleaned up. That sends out messages to the macrophages, the cleanup crew, which comes and then populates that fat and starts actually cleaning up the grease. And then that sends out inflammatory cytokines, and that is what starts the inflammatory response. Now, when that happens, the drainage of that adipose tissue, that subcutaneous adipose tissue, goes where? It goes into the entire systemic circulation. It goes into the inferior vena cava and therefore circulates throughout the entire body. So the volume of distribution is the volume of distribution of your blood supply, which is six liters. In other words, you have to, uh, cause a lot of inflammation in a lot of adipose tissue to be able to generate a concentration of cytokines that's enough to actually do damage to the rest of the body. How much? Maybe ten kilos, twenty-two pounds on average. Maybe a little more for certain races, maybe a little less for others. Okay. So is subcutaneous fat bad? And the answer is, when it gets super big, sure, but in general, no. In fact, that's the safe place to put the fat.

Dr. Rangan Chatterjee 3:37 Mm.

Dr. Robert Lustig 3:38 Now let's take fat depot number two, um, visceral fat, belly fat. Now, what causes belly fat? Stress. Stress causes belly fat. Food? Does food cause belly fat? Turns out, no, food does not cause belly fat. Stress causes belly fat. And the reason we know this is because you can take patients who are suicidal with major depressive disorder that have to be admitted to the hospital to keep them from killing themselves, stick them in an MRI scanner, and you can see that the subcutaneous fat's going down because these are pa- people who are anhedonic. They are not eating. They are losing weight. Losing weight is one of the cardinal features of major depressive disorder because you don't wanna eat because you wanna die. But visceral fat is going up. You are reapportioning the subcutaneous fat to the visceral fat despite the fact that you're not eating and you're losing weight. So that visceral fat is driven by cortisol. It is driven by stress. It is not driven by food. And, and when that fat gets too big, it starts releasing fatty acids and cytokines, and then that goes straight to the liver because the drainage for the visceral fat is the portal vein, and it goes straight to the liver. And so what's the volume of distribution then? Not six liters, more like two hundred and fifty cc's. And so a little visceral fat will increase the concentration reaching the liver by a lot. Okay? And how much visceral fat can you gain before you start getting sick? About five pounds. So about twenty-two pounds for subcutaneous fat, about five pounds for visceral fat. And then finally, fat depot number three, liver fat. And that liver fat is the worst because it's actually the fat right at the center, at the nidus of where the problem is. Because when your liver is sick, all hell breaks loose because that's the thing that drives the hyperinsulinemia the most, 'cause the pancreas has to basically tell the liver to do its job. And so the le- insulin levels go straight up based on the fat in the liver And how many kilos or how many pounds of fat can your liver hold before it gets sick? About a half a pound. So 22 pounds of subcutaneous fat versus five pounds of visceral fat versus half a pound of liver fat. And where'd that liver fat come from? Alcohol and sugar. So different fat depots, different risks, different drainages, different consequences.

Dr. Rangan Chatterjee 6:37 Mm-hmm. I mean, it's fascinating. Thank you for going through those three different fat depots. I really enjoyed reading that section in the book actually, and it was, it was so striking when you pointed out, as you just have now, that, yeah, the subcutaneous fat is where we, you know, we are designed to put excess energy that we take in. You know, in the olden days-

Dr. Robert Lustig 7:00 Yeah

Dr. Rangan Chatterjee 7:00 ... in the summer, we'd store the fat, and it would get us through the winter, right?

Dr. Robert Lustig 7:04 Exactly.

Dr. Rangan Chatterjee 7:05 That's not a problem for our health unless it goes beyond that sort of natural capacity, then it starts to become problematic.

Dr. Robert Lustig 7:15 Yeah, yeah.

Dr. Rangan Chatterjee 7:15 Then you mentioned the visceral fat. Now, hopefully listeners of my podcast have heard that term several times before, and we did touch on it in our first conversation together.

Dr. Robert Lustig 7:26 Mm-hmm.

Dr. Rangan Chatterjee 7:26 But that idea that visceral fat is driven by stress-

Dr. Robert Lustig 7:30 Yeah

Dr. Rangan Chatterjee 7:30 ... and not by food, that's quite interesting because, you know, let's say someone had no stress at all in their life. I don't know anyone [laughs] living in, uh-

Dr. Robert Lustig 7:41 I was gonna say, I, I was gonna say, uh, I'd like to meet them.

Dr. Rangan Chatterjee 7:43 [laughs] But let's just, uh, you know, uh, hypothetically speaking, someone has, you know, minimal stress in their life, but they are consuming energy in the form of food to excess.

Dr. Robert Lustig 7:56 Mm-hmm.

Dr. Rangan Chatterjee 7:56 Are you saying that in your view, unless there's also some kind of chronic stress on boards, then that food, that excess energy will be stored as subcutaneous fat or potentially liver fat, but it won't be stored as visceral fat without the stress?

Dr. Robert Lustig 8:16 Exactly. That's exactly what I'm saying. And the reason is because in order for that visceral fat to accumulate the fat, there has to be something wrong with the sympathetic nervous system. So that sympathetic nervous system is what's driving that adipose tissue fat depot. Now think about this. This is actually very important. The visceral adipose tissue has the beta-3 adrenergic receptor. Every single cell has the beta-3 adrenergic receptor, so it is taking information from the sympathetic nervous system, okay? And every cell has an adrenergic innervation. So when you are acutely stressed, acutely, message goes from the locus coeruleus in the brain via the intermediolateral cell column of the spinal cord out to, you know, the various peripheral nerves like the celiac nerve and the superior mesenteric nerve to the visceral fat, and sends a norepinephrine signal. And that norepinephrine signal says to that fat cell, "Give up your fat because we are in a stressful situation and we need energy. And so stop accumulating fat energy and start releasing it." And so you hit the pause button on lipoprotein lipase, which is making the fat, and you hit the go button on the hormone-sensitive lipase, which allows for the extrusion of free fatty acids, non-esterified fatty acids from that visceral fat, which then goes into the circulation, goes to the liver, and can either be manufactured into glucose or ketones for energy for the rest of the body, okay? That's the acute stress response. So the acute stress response, by stimulating norepinephrine, causes the visceral fat to give up fat. It is lipolytic. It is, you know, w- uh, fat losing in the, uh, visceral compartment. But chronic stress does the opposite. Now, how does chronic stress do the opposite? Why does chronic stress do the opposite? Chronic stress causes that visceral fat to accumulate instead. So number one, chronic stress has cortisol. Acute stress, you haven't gotten a cortisol bump. You know, it takes 10 minutes to generate a cortisol bump-

Dr. Rangan Chatterjee 11:07 Mm

Dr. Robert Lustig 11:07 ... in response to an acute stressor, okay? It's a norepinephrine response, and your adrenal gland doesn't have any cortisol stored. It has to make cortisol de novo from scratch, from cholesterol, 'cause there's no storage place for cortisol. So cortisol's always a delayed response. It comes in around 10 minutes. So for those first 10 minutes of, um, of an acute stress, you know, the lion chasing, you know, the, the pygmy on the savanna, okay, that's all norepinephrine.

Dr. Rangan Chatterjee 11:41 Mm.

Dr. Robert Lustig 11:41 And so you're gonna get all hormone-sensitive lipase activation. You're gonna get all that fat rushing out of the visceral adipose in order to generate the energy that the body needs to run away from the lion, all right? But then cortisol kicks in, and cortisol does something very different. Cortisol alters mitochondrial function. Cortisol also increases the enzymes that then lay down fat. And then something Even more remarkable happens. You're-- I'm sure you're aware, Rangan, that every adrenergic neuron in the body, whether it's in the brain or in the periphery, releases norepinephrine-

Dr. Rangan Chatterjee 12:25 Mm-hmm

Dr. Robert Lustig 12:25 ... and it also releases a second neuromodulator, a neuropeptide, and that neuropeptide's called neuropeptide Y.

Dr. Rangan Chatterjee 12:33 Yeah.

Dr. Robert Lustig 12:34 NPY. Okay? And they always are co-localized, and they always are co- uh, uh, secreted. It turns out NPY is the brake on the adrenergic nervous system. So the adrenergic nervous system is telling that fat cell, "Release, release, release, release," and then NPY is co-released, and it basically tells that fat cell and every other, uh, organ in the body, "Calm down. I'm the brake. You know, uh, if you keep doing this, we're gonna get into trouble." And so NPY binds to the Y2 receptor on that, uh, visceral fat cell and actually stops the process and actually starts promoting lipogenesis again. So in the face of chronic stress, you've got cortisol, and you've got NPY antagonizing that lipolysis, and it actually converts it to lipogenesis, and that's why acute stress and chronic stress are virtual opposites.

Dr. Rangan Chatterjee 13:44 Yeah, it's absolutely fascinating. And there, there's a wider point for me. In the modern world today in twenty twenty-four, there are so many different factors that are working against us when it comes to health.

Dr. Robert Lustig 14:00 Mm-hmm. You bet.

Dr. Rangan Chatterjee 14:01 It's easy to put it all in one area and, for example, say, "It's the food." Now, I don't deny that the food is a huge problem.

Dr. Robert Lustig 14:09 Mm-hmm.

Dr. Rangan Chatterjee 14:10 But as well as a lot of us having access to energy-dense, very tasty, nutrient-poor foods-

Dr. Robert Lustig 14:17 Right

Dr. Rangan Chatterjee 14:17 ... which we know and we'll definitely be covering in this conversation again, we're also not moving much at all because of our jobs and the way we travel and move around. We're sleep-deprived, which we know in and of itself can cause insulin resistance. Sleep deprivation is a stressor.

Dr. Robert Lustig 14:35 Well, cortisol rise.

Dr. Rangan Chatterjee 14:36 Exactly. It's a stressor in and of itself, and so if you-- if that's-

Dr. Robert Lustig 14:39 Yeah

Dr. Rangan Chatterjee 14:39 ... chronic sleep deprivation, that is a chronic stressor on the body.

Dr. Robert Lustig 14:44 Absolutely.

Dr. Rangan Chatterjee 14:44 But, but then you also have just looking around, people feel rushed. They feel busy. They don't feel they, they have time. You know, six, seven years ago, the World Health Organization put on their website that stress is the health epidemic of the twenty-first century. It's no wonder that people are struggling. It's no wonder that people are sick, because it seems as though for many of us, every single input coming into our bodies from our environment is not exactly helping us, is it? It's actually getting in the way of our overall health. But I guess fundamental to what you're writing about in your book, it's getting in the way of metabolic health, which really is health.

Dr. Robert Lustig 15:29 I hate to tell you, but it's not just getting in the way of metabolic health. It's getting in the way of mental health. It's getting in the way of global health. It's getting in the way of planetary health. It's getting in the way of everything. So I'm glad you brought this up because I wanted to talk about this with you, so [laughs] this is reciprocal. So this is good. Um, uh, four years ago, just before COVID hit, I won a Fulbright to study in Paris, and I had two jobs. One, unfortunately, when COVID did hit, I had to leave and, you know, go back to the US. But the second project has continued online, uh, two hours at a time, two days a week, for the last four years. So I have been working with a French colleague, and he is very interesting. His name is Professor Philippe Gaussier, and he is both a robotics professor and neuroscientist at, uh, the Université de Cergy-Pontoise, which is about seventeen miles northwest of Paris in a little town called Cergy. And he has a very unique skill set. Now, I mean robotics and neuroscience. And his job, his goal, is to make robots behave more like humans so that they would be more acceptable to humans. Now, in order for him to do that, he has to understand emotion. And so there are all of these, you know, neuroscientists out there studying the anterior fossa and, you know, neural networks and cognitive function and learning and, you know, machine learning and AI and what have you. And-- But almost nobody is studying the posterior fossa, the, the emotion part of the brain. And so we went out to build a computational model of the limbic system, and we have, and it's taken us four years, but it's pretty darn good, and it actually works. And it's pretty cool when you, when you actually look at it because what we've come to realize through the building of this model is that it's really about one area of the brain, the amygdala. Now, the amygdala, for your audience, is the fear center of the brain.

Dr. Rangan Chatterjee 17:58 Mm-hmm.

Dr. Robert Lustig 17:58 It is the stress center of the brain. And here we are talking about, you know, chronic stress. It is about amygdala dysfunction. And the point is, it's not the amygdala that is dysfunctional. The amygdala is actually doing its job. But what we've learned is that there are four brakes on the amygdala. And those brakes are not doing their job. They're what's dysfunctional.

Dr. Rangan Chatterjee 18:25 Mm-hmm.

Dr. Robert Lustig 18:26 So think of it this way. You have a car, okay? And the car has four wheels, and each wheel has a brake. So there are four brakes on the car. You step on the brake in the cabin, and all the wheels stop at the same time, and you stop, and then you go. All good. Now imagine one of those brakes fails. You hit the brake, what happens? Are you gonna stop? Yeah, you'll stop, but it's gonna be a pretty rough ride.

Dr. Rangan Chatterjee 18:56 Yeah.

Dr. Robert Lustig 18:57 Now imagine two brakes fail. You gonna stop? Yeah, you'll still stop. If the two brakes that fail are in the back, you'll glide to a stop. If the two brakes that fail are in the front, you're gonna lurch to a stop.

Dr. Rangan Chatterjee 19:14 Mm-hmm.

Dr. Robert Lustig 19:14 But what if the two brakes are on either side of the car? You're gonna do a 360, and possibly damage.

Dr. Rangan Chatterjee 19:20 Mm-hmm.

Dr. Robert Lustig 19:22 All right. Now what if three brakes fail? Are you gonna stop? You're gonna capsize, but you'll stop.

Dr. Rangan Chatterjee 19:30 Yeah.

Dr. Robert Lustig 19:32 And what if all four brakes fail at the same time? You are over the precipice and into the abyss, like the last scene of Thelma & Louise. [laughs] Well, that's what's happening to us because all four brakes on the amygdala are failing at the same time. So what are those four brakes, and why are they failing? So the first one is prefrontal cortex, reasoning. And the reason for the f- uh, failure, both cortisol and dopamine, okay? Which are both, you know, just gigantically elevated in our society. The second brake, the hippocampus, memory. And why is that failing? Also cortisol. Cortisol causes increased energy need and that it's not being supplied, and so you've got hippocampal atrophy. Third brake, the afferent vagus. The afferent vagus normally conducts neural impulses from the entire, uh, abdomen, you know, including the gut, all the way up to the nucleus tractus solitarius, and then a way station up to the amygdala. Well, what is that? That is where the serotonin goes from-

Dr. Rangan Chatterjee 20:53 Mm

Dr. Robert Lustig 20:53 ... the gut up to the brain, and so that is part of what we call interoception, your bodies being able to actually monitor itself.

Dr. Rangan Chatterjee 21:04 Mm-hmm.

Dr. Robert Lustig 21:04 Problem is, if you're eating ultra-processed food, those m- m- uh, microbes can't make serotonin right. And if you're eating ultra-processed food and you're insulin resistant, your liver's taking the tryptophan and turning it into kynurenine instead of serotonin, and you're not even getting levels up into the brain that you need. So basically, no tryptophan, no serotonin. No serotonin, no, um, brake. And then finally, number four, which is really exciting, oxytocin. So everybody thinks of oxytocin as the love hormone or the reproduction hormone or the milk ejection hormone. It's all of those things, but it's also the safety hormone. It's the thing that transduces the feeling of safety, and it's epigenetic b- because the oxytocin receptor is the most easily methylated protein in the brain. And all of these stresses like adverse childhood experiences and traumas and what have you, all end up methylating that oxytocin receptor so that you can't get the feeling of safety. You are under constant and chronic threat. And that is the fourth brake on the amygdala, and that's what everyone's complaining about, is that they don't feel safe.

Dr. Rangan Chatterjee 22:27 Yeah.

Dr. Robert Lustig 22:28 And so all four brakes are failing at the same time, and so the amygdala has run hog wild.

Dr. Rangan Chatterjee 22:36 Yeah.

Dr. Robert Lustig 22:36 And it is the driver of our systemic health crisis through all the processes we just discussed, the mental health crisis, the depression, the PTSD, the, uh, global health crisis in terms of, uh, social disparities and, uh, corporate determinants of health, and it is also the driver of the planetary health crisis in terms of, uh, inequality, uh, uh, war, uh, um, and climate change.

Dr. Rangan Chatterjee 23:10 I mean, thank you for sharing that. That's so, so interesting. As you were describing those four brakes that no longer work well at all for many of us, I was thinking about a thought experiment that I often do. I, a few years ago, set out this model of the four pillars of health, right? W- food, movement, sleep, and stress being the four areas that not only have the most impact on our short-term and long-term health, but also they're four areas that we have, you know, a fair degree of control over. Although that is arguable, depending on your life circumstance. And I often ask myself, which is the most important? And I know it's a bit of a ridiculous one 'cause they're all important, right? And it's gonna depend on the individual as to what's going on in their life, which is the pillar that they probably need to address the most. But often, I come to the conclusion that for many people, stroke most people, the stress pillar might be the most important one. And the way I sort of justify that is not only does chronic stress impact every single organ system in the body negatively, you know, we could spend half an hour just talking about what chronic stress does to the body-

Dr. Robert Lustig 24:28 Absolutely

Dr. Rangan Chatterjee 24:28 But also if we think about food, well, these days we're not always eating because of physical hunger, we're often eating because of emotional hunger. So chronic stress is driving us to comfort eat and eat more of these so-called unhealthy foods than if we weren't feeling so stressed. So-

Dr. Robert Lustig 24:49 Yeah

Dr. Rangan Chatterjee 24:50 ... what I'm trying to get to, Rob, is this idea that being under chronic stress drives so many problematic behaviors. You've spent a lot of your career raising awareness about the problems of too much sugar, the problems of highly processed foods.

Dr. Rangan Chatterjee 25:09 How do you think about food and stress in terms of their relative importance?

Dr. Robert Lustig 25:16 The fact of the matter is that virtually everyone, including myself, are stress eaters. Yeah, there are few people out there who are, you know, s- who stop eating because of stress, but most people are actually stress eaters. And there's a reason, is because there's a, there's a, a pathway of reward suppressing stress.

Dr. Rangan Chatterjee 25:38 Mm.

Dr. Robert Lustig 25:38 Okay? This is one of the pathways in the nucleus accumbens to calm it down. So dopamine, dopamine is an excitatory neurotransmitter, and it sends its, uh, pericar- uh, the pericarrier in the, uh, ventral tegmental area of the back of the brain, and it sends the processes to two places. Just two places. The first is the nucleus accumbens, the reward center, so you get a feeling of reward. And then the second is the prefrontal cortex. Okay? Now the prefrontal cortex is then supposed to send information back to the nucleus accumbens, basically calming it down. "Okay, yeah, I love this chocolate, but you know what? I don't need to eat any more of that." All right? That's, that's the reciprocal relationship that's supposed to occur between the reward system and the reasoning system. Well, that is broken. And what broke it? Cortisol.

Dr. Rangan Chatterjee 26:37 Mm.

Dr. Robert Lustig 26:38 'Cause cortisol causes the atrophy, the cell death and atrophy of those neurons in the prefrontal cortex. And you can actually see it on magnetic resonance imaging. You can actually see the reduction in volume, uh, in the face of chronic stress.

Dr. Rangan Chatterjee 26:58 Mm.

Dr. Robert Lustig 26:58 So, and, you know, in the face of obesity. So we know that this level of cognitive inhibition that normally controls that reward system has basically been, you know, um, taken, taken offline.

Dr. Rangan Chatterjee 27:15 Yeah.

Dr. Robert Lustig 27:16 And that's the whole point. That's one of the four breaks that you're describing. So this is not surprising or even remarkable for that matter. And this has actually been known for 40 years. This, this is work Robert Sapolsky did way back in the 1980s when he realized that the hippocampus was the most vulnerable, uh, um, uh, part of the brain, uh, to energy, uh, deprivation and, you know, that those neurons would die quickest. And the reason is because the mitochondria are being, uh, altered by cortisol so that they do not produce as much, uh, ATP, so they need more glucose in order to be able to survive. And so that's one of the reasons why you keep eating when you're stressed, is because you're basically trying to feed those hippocampi to keep them from dying.

Dr. Rangan Chatterjee 28:08 Yeah. You know, Rob, I think the first time I really became aware of this, and it's interesting hearing you talk about these three fat depots in the body, because I'm, I'm drawn to several previous patients, and they all had a particular pattern. And maybe this was about 10 years ago when I, I first started to, to see this and observe this and go, "Wow, stress is really playing a role here in terms of fat accumulation on the body." And it would typically be women, I would say in their mid to late 40s who I was seeing. Often they were mothers, and of course, yes, that is a time when they could be going through hormonal changes and, you know, perimenopausal and menopausal for sure. But what I would see with these particular patients is that they were eating pretty well, actually. They were trying their best to eat well, but they had a stressful life, a very busy life, and they were pushing themselves at the gym with lots of intense cardio. And I remember with one patient once thinking, "Okay, look, I, I... This just feels like there's too much of a stress load on your body." And I remember one patient in particular who I advised to stop doing intense cardio, and I said, "Honestly, I feel like you need something more relaxing for your movement, like yoga." And she was quite skeptical at first, but within weeks of stopping the intense cardio and doing, I think it was two yoga classes a week she would do after work on the way home, the weight around her belly started to come off, and I, I remember seeing that pattern, and I think that's very, very common. And I think, you know, in this era of health information overloads with people consuming, you know, all the time podcasts and YouTube videos and trying to learn, which I think is great on one level, I think one of the downsides sometimes is that people think they need to keep doing more and more. "Wow, I need to do that exercise, I need to add that in," to an already busy life. They're adding in more and more stress. So, you know, it kind of fits in with what you just described, right?

Dr. Robert Lustig 30:12 We didn't see it, we studied it. And [laughs] we had a whole study here at UCSF called the Shine Study where we did just that. We took post-men- pr- peri and post-menopausal women, okay, with metabolic syndrome And we divided them up into three groups. One, a standard exercise regimen. One, a mindfulness-based stress reduction regimen.

Dr. Rangan Chatterjee 30:40 Mm-hmm.

Dr. Robert Lustig 30:41 Okay? So basically meditation, okay? I.e., yoga. And number three, control. And asked the question, what happened? And it turned out that weight did not change. We were hoping weight would change. Weight did not change. But what did change was visceral fat, waist circumference, and insulin sensitivity. And we're well-- You know, we had papers in JAMA, you know. The bottom line is we know that stress is the bad guy. It's not the only bad guy.

Dr. Rangan Chatterjee 31:19 Mm.

Dr. Robert Lustig 31:20 Okay? There are other bad guys. I mean, bad food [laughs] is a bad guy, and stress basically makes you eat bad food, too, okay? But stress is a primary factor on its own, and the problem is that people don't know how to mitigate their stress.

Dr. Rangan Chatterjee 31:37 Yeah.

Dr. Robert Lustig 31:37 And they are actually prevented from mitigating their stress because our society doesn't allow them to do otherwise.

Dr. Rangan Chatterjee 31:46 In Metabolical, in the chapter where you write about the eight subcellular pathologies that underpin pretty much all of the chronic diseases that we have, you know, glycation, oxidative stress, mitochondrial dysfunction, insulin resistance, et cetera, et cetera. I underlined a section in the insulin resistance part which I think really relates to this part of our conversation. You wrote this, "Even those who are overweight and those who are under stress don't exhibit metabolic syndrome if their diet is unprocessed."

Dr. Robert Lustig 32:54 Yeah.

Dr. Rangan Chatterjee 32:55 That's really interesting because, look, as you say, you know, stress, too much stress for too long a period of time will drive us to eat poor quality food. At the same time, eating lots of poor quality food is a stressor on the body.

Dr. Robert Lustig 33:11 Exactly.

Dr. Rangan Chatterjee 33:11 So why is it, why is it that even if you're under chronic stress and you're overweight, why is it that people don't develop metabolic syndrome in the absence of these ultra-processed foods?

Dr. Robert Lustig 33:24 Um, I can sum it up in one word, reactive oxygen species. You have to be able to handle your reactive oxygen species. Every one of these things, including cortisol, generates reactive oxygen species. Mitochondria generate reactive oxygen species. The cytokines, you know, that are released from visceral fat bind to their receptors and activate NADPH oxidase to generate reactive oxygen species. Those reactive oxygen species do damage, the damage of metabolic syndrome, and it can be whether you're thin or whether you're fat. Now, you gotta get rid of the reactive oxygen species because they're the mover in terms of the damage, okay? And they are part of life. You can't get rid-- The only way to get rid of reactive oxygen species is to be dead [laughs] all right? They are going to be manufactured. You know, it is part of energy metabolism, it is part of protein metabolism, it is part of lipid metabolism to generate reactive oxygen species, all right? Little oxygen radicals, little hydrogen peroxides running around your cells, okay? Turns out those change energy metabolism. So you gotta clear the ROSs. Well, where do you clear the ROSs? A subcellular organ in the cell called the peroxisome. That's where the, that's where the antioxidants are. So the peroxisome is where ROSs go to die. That's where you quench-

Dr. Rangan Chatterjee 35:01 Mm

Dr. Robert Lustig 35:02 ... the effect of the reactive oxygen species. And it turns out that every mitochondrion is next to a peroxisome on purpose to be able to basically get rid of that ROS before it does damage, because that ROS will peroxidate a lipid or it'll denature a protein or whatever. It's gonna cause cellular dysfunction. Now, let's say you don't have enough antioxidants to cover your ROS burden, that your ROSs are greater than your antioxidant capacity. Now you can't clear them. So where do they go? They go to the endoplasmic reticulum, which is where proteins, as you know, get built. There's a little, you know, a little assembly line of adding amino acids. The transfer RNA is bringing the amino acids, you know-

Dr. Rangan Chatterjee 35:53 Mm-hmm

Dr. Robert Lustig 35:53 ... you're using the genetic code in order to build up, uh, proteins and then fold them. All right? Well, if you don't fold them right because of the ROSs, you have what we call ER stress, endoplasmic reticulum stress, also known as the unfolded protein response, also known as the pathogenesis of metabolic syndrome. Those three terms are synonymous. So if you can't fold your insulin molecule, you got type 2 diabetes. If you can't fold your insulin receptor molecule, you've got Metabolic syndrome, insulin resistance, and possibly Alzheimer's, and possibly, um, uh, cardiovascular disease, and possibly fatty liver disease, et cetera, et cetera. So getting rid of the ROSs is super important, and there's only one way to get rid of the ROSs, antioxidants, and there's only one way to get the antioxidants. You can't breathe them in. Ain't no antioxidants in your... in, in the air. You gotta get it in your food. So when you eat food, you can mitigate that metabolic syndrome pathology. But unfortunately, ultra-processed food only, because it's antioxidant poor, only contributes to an increase in reactive oxygen species. Because you're bringing on all of this carbohydrate, you're bringing on all of these trans fats, you're bringing on all of these things that generate ROSs without bringing on the antioxidants that can quench them.

Dr. Rangan Chatterjee 37:37 When you say antioxidants and you get these antioxidants from foods and from real foods-

Dr. Robert Lustig 37:44 Real food. And, and in partic- and in particular, fruits and vegetables. You know, I mean, that's one ... That's the primary, you know, uh, source of antioxidants. I mean, you know, I mean, you know, there, there are amino acids that are antioxidant, but y- what you really need are, you know, the, the, the biotin, the an- the cyanines, the, you know, flavonoids, the various other things that come from a, shall we say, a real food diet.

Dr. Rangan Chatterjee 38:13 A lot of the foods that contain those wonderful compounds, as you said, are fruits and vegetables, let's say.

Dr. Robert Lustig 38:19 Right.

Dr. Rangan Chatterjee 38:20 You know, blueberries, for example, would be ag- an example of a food that is rich in all the compounds you've just mentioned, which will help dampen down the ROS, the reactive oxygen species, right?

Dr. Robert Lustig 38:31 Yeah.

Dr. Rangan Chatterjee 38:31 How do you put that together with your take on fructose? So fructose is something you've spoken about on our first podcast together about the problems of excess fructose in our diet, and of course, fruit also contains fructose. So could you just help tease that apart for us? I don't ... I, I genuinely want this conversation to be helpful for people so they understand what's going on and they know what they can do. So I think that would be quite helpful, if you don't mind.

Dr. Robert Lustig 39:01 All right. It's very simple. Number one, berries, like blueberries, they don't have much fructose. I mean, they have a little, yeah, okay, yeah, they're, they're mildly sweet, but n- not, like, ridiculously so, number one. Number two, they got a lot of fiber, okay? And fiber turns out to be the antidote to sugar, and we'll show-- and I'll show you in a why in a minute. And number three, they have all these antioxidants. Right. Now, um, sugar is the bad guy, and the reason is 'cause fructose, this sweet molecule in sugar, is not glucose. Glucose is the energy of life. Every cell on the planet can, you know, u- uh, utilize glucose for energy. Glucose is so important that if you don't consume it, your body makes it. There, this, there's this process called gluconeogenesis where fat breakdown can generate glucose in the liver. Amino acid breakdown can generate glucose in the liver. So glucose is a- so essential, you don't have to consume it. That's how essential it is, okay? It is essential to have, it is not essential to consume. Now, fructose, on the other hand, is totally non-essential. There's no enzyme in the body that requires it. There is no, uh, benefit to it other than the fact that it incorporates energy ... You know, ha- has a certain amount of energy associated with it, okay? But it is completely vestigial to all animal life, all the way down to the amoeba, okay? I always used to say all vertebrate life, but in fact, all animal cell life. There is no reaction in any animal cell on the planet that requires fructose. Not necessary. Completely vestigial. It's a holdover from our plant ancestors, okay? Now, it does have energy. I'm not saying it doesn't. If you throw it into a bomb calorimeter, it'll burn at four calories per gram.

Dr. Rangan Chatterjee 41:03 Mm-hmm.

Dr. Robert Lustig 41:04 Yes, we can harness some of that energy, and, you know, that's of course ostensibly why it's in sports drinks. But the fact of the matter is, it is metabolized a completely different way from that of glucose. And instead of going to either ATP and carbon dioxide or to glycogen, which is a storage form of glucose, fructose goes straight to the mitochondria. If the mitochondria are overwhelmed and can't process all of it, then the mitochondria throw off the excess, and then the cell turns that into fat.

Dr. Rangan Chatterjee 41:40 Mm.

Dr. Robert Lustig 41:40 And we have just talked about liver fat being the worst of the bunch, and fructose is a primary dr- driver of liver fat accumulation, and therefore a primary driver of metabolic syndrome. Oh, and by the way, a primary driver of reactive oxygen species. Because of the stereochemistry of the fructose molecule, it engages in that reactive oxygen species generation seven times faster than glucose does. So it is a lipogenic substrate, and it is an oxidative stress all by itself. Now, but I said f- fruit is good, right? You ... I mean, you said fruit is good. It-- The reason the fruit is good is 'cause number one, it has the fiber, and number two, it has the antioxidants. It's not good because it has the fructose. The fructose is what makes you eat it, but it's not-- that's not why it's good. So how does the fiber act to mitigate the negative effects of fructose? There are two kinds of fiber, soluble and insoluble. You need both. So insoluble fiber is like, um, uh, cellulose, you know, like the stringy stuff in celery. Uh, soluble fiber is like pectins or inulin, like what holds jelly together, right?

Dr. Rangan Chatterjee 43:04 Mm.

Dr. Robert Lustig 43:04 You need both. Together, what happens is that the cellulose acts like a latticework, like a fish net on the inside of your intestine. The soluble fiber, the pectins and the inulin, they plug the holes in the fish net. And so together they form a secondary barrier.

Dr. Rangan Chatterjee 43:21 Mm-hmm.

Dr. Robert Lustig 43:21 And that prevents transport of glucose, fructose, sucrose, simple starches from the intestinal lumen into the, uh, portal circulation so that it never reaches-

Dr. Rangan Chatterjee 43:33 Yeah

Dr. Robert Lustig 43:33 ... the liver. And if it doesn't reach the liver, it goes further down the intestine and the bacteria chew it up for its own purposes. You have fed the microbiome. You have to feed your gut. Well, the fiber is the food for the gut. And so it takes the pressure off your liver, so fewer ROSs, and it feeds your gut so your microbiome can, number one, work for you, generate short-chain fatty acids, suppress inflammation, maintain the intestinal barrier integrity so that you don't get inflamed, so you don't get metabolic syndrome. So yes, even though the fructose is in the fruit, the antioxidants and the fiber-

Dr. Rangan Chatterjee 44:22 Mm

Dr. Robert Lustig 44:22 ... more than make up for it. But as soon as you squeeze it, now the fiber is gone.

Dr. Rangan Chatterjee 44:30 Yeah.

Dr. Robert Lustig 44:30 The antioxidants will still be there, that's true. But the fiber is gone, and so now you're gonna get this big fructose load hitting your liver.

Dr. Rangan Chatterjee 44:37 Yeah.

Dr. Robert Lustig 44:38 That's why I tell people, "Eat the fruit, don't drink the juice."

Dr. Rangan Chatterjee 44:41 There, there's a couple of things which have just come up for me as, as you were explaining that. First one, Rob, is to do with the fact that, that... It's to do with the fact that fruit does have fructose within it, just not that much, and your message, I think, is that it's the excess fructose that we're consuming that's causing problems. So-

Dr. Robert Lustig 45:05 Especially in the absence of the reactive oxygen species and fiber. Yeah.

Dr. Rangan Chatterjee 45:10 Yeah. So let's say someone is in perfect metabolic health, and we compare that to someone who has really poor metabolic health, like much of the US population, much of the UK population, and frankly much of the global population these days. Is the way they're going to... Let, let's take a high-sugar fruit like a mango for, for, for example.

Dr. Robert Lustig 45:37 Mm.

Dr. Rangan Chatterjee 45:38 If you're in perfect metabolic health, everything's working great, that mango is gonna have one effect on you, I'm guessing, compared to someone who has advanced metabolic syndrome and is very insulin resistant. I guess the point I'm trying to get to is too often I think we're trying to say, "This is good, this is bad. This food is good, this food is bad." Context matters massively. The state of your cellular health, the state of your mitochondrial health, the state of your insulin sensitivity, all that plays into whether that particular fruit is gonna be helpful. Because I think the truth is for some people who've got type 2 diabetes, actually having as much fruit as they want because it contains antioxidants, I personally haven't seen it to be the best idea. But then people will get very black and white. You're saying fruit is good or fruit is bad. It's like, well, no, hold on a minute. I'm saying for this individual patient who's very, very insulin resistant and is struggling, I'm not sure they need to be having lots of high-sugar fruits. How do you see it?

Dr. Robert Lustig 46:42 Uh, first of all, Rangan, I couldn't agree with you more, okay? You are 150% right, okay? The... You have said nothing I disagree with. In fact, I subscribe to it wholeheartedly, completely. People are black and white. People want rules. People want to be told, "This is good, this is bad. This is helpful, this is hurtful. This is good, this is evil." It's... And it's never that simple.

Dr. Rangan Chatterjee 47:15 Mm.

Dr. Robert Lustig 47:16 It's never that simple. What we have learned is that different foods affect different people different ways. That is what we have learnt. And there's absolutely no question that you take somebody who's in the prime of health, who is completely insulin sensitive, who's a marathon runner, and you give them a glass of orange juice, it's gonna have a different effect on them metabolically than if you take a, you know, 70-year-old sedentary type 2 diabetic who's got vascular, uh, uh, uh, problems and, you know, potentially kidney problems, and you give them a glass of... the same glass of orange juice. It's gonna have much worse effects. No argument. Completely. How do you know who you are? How do you know whether or not this food is okay for you and that food is not? We're still in the process of trying to figure all of that out. We have some tools. There are a few things that we can do now, right? Now, there are some general global things, you know, like for instance this thing called glycemic index, which I hate, okay? I think glycemic index needs to be blown up, but, you know, the dieticians still subscribe to it.

Dr. Rangan Chatterjee 48:38 Before you move on, Rob, could you explain why that is? 'Cause a lot of people will know that term and, and they, they'd be very interested to know why you're not a big fan of that term.

Dr. Robert Lustig 48:47 Not a big fan is being, is an understatement, okay?

Dr. Rangan Chatterjee 48:51 [laughs]

Dr. Robert Lustig 48:52 Kill the glycemic index now, all right? So let me explain for your audience what this is, okay? It is a tool that dieticians developed, um, that tells you how high does your plasma glucose rise after you eat 50 grams of carbohydrate in any given food. That's what glycemic index is, and it's all standardized against the rise that you would see with white bread. White bread would have a glycemic index of 100, okay? So it's straight glucose. There's nothing else in it. It's, it's polymerized carbohydrates, straight glucose. So if you eat a piece of white bread, you're gonna get a big glucose rise in your bloodstream, and everything else is compared against that. All right. The pro- s- that sounds good because when you generate a glucose response, you also generate an insulin response, and the glucose does one thing. It causes vascular endothelial, uh, cell dysfunction, and the insulin does another thing. It causes vascular smooth muscle proliferation and cell growth, okay? So they both have problems. The glucose has a problem, and the insulin that follows it has a problem. So obviously, the higher the glucose goes, the worse off you are metabolically. Now, that's true. That is true. I don't say that that's not true, but glycemic index is not the way to figure it out, and here's why. Two reasons. First, let's take carrots. Carrots are good. If you eat 50 grams of carbohydrate in carrots, your blood glucose is gonna go pretty high. So carrots have a high glycemic index. The question is, how many carrots do you have to eat to get 50 grams? You have to eat 700 grams of carrots to get 50 grams of carbohydrate. What's the rest? Fiber. So you are taking in 650 grams of fiber to get 50 grams of carbohydrate, okay? So it's not about glycemic index. It's about glycemic load.

Dr. Rangan Chatterjee 51:07 Mm-hmm.

Dr. Robert Lustig 51:08 Okay? You have to eat 1.4 pounds of carrots to get 50 grams of carbohydrate in carrots. Okay, you tell me, who does that other than Bugs Bunny?

Dr. Rangan Chatterjee 51:17 [laughs]

Dr. Robert Lustig 51:19 All right? So the concept of glycemic index is useless. G- glycemic load, that makes more sense because that takes into account the fiber issue. So that's the first reason. Second reason, fructose. So remember, glycemic index is how high does your blood glucose rise. Doesn't say anything about how high d- how high does your blood fructose rise 'cause you don't measure the blood fructose in the glucose level.

Dr. Rangan Chatterjee 51:48 Mm-hmm.

Dr. Robert Lustig 51:48 So when something is sugar, it's half glucose, half fructose, which means it w- the blood glucose will only rise half as high because the rest is fructose, and it's not captured in the measurement. Yet fructose is seven times worse in terms of re- generating reactive oxygen species and in terms of generating liver fat, both of which drive the phenomena of metabolic syndrome. That's not captured-

Dr. Rangan Chatterjee 52:15 Mm

Dr. Robert Lustig 52:15 ... in glycemic index 'cause it's only concerned about the glucose. It's not concerned about the fructose.

Dr. Rangan Chatterjee 52:21 Mm-hmm. I guess the other issue is we're all highly individual, aren't we? We're learning that more and more over the last, what, five, 10 years, that we all have different responses to the same food.

Dr. Robert Lustig 52:34 Exactly, and that's what Levels Health showed us by normal people wearing continuous glucose monitors. Now, the FDA says, "Don't do that," and the government says, "Don't do that," but the fact of the matter is we are learning a lot by having normal people wear continuous glucose monitors because we are seeing the variation that occurs across populations and what kinds of things actually influence the glucose excursions, which we know have information in them and we also know have pathology in them.

Dr. Rangan Chatterjee 53:11 Mm-hmm.

Dr. Robert Lustig 53:11 And the goal is to keep your glucose down, in part because keeping your glucose down means less endothelial cell dysfunction, and also, if you keep your glucose down, it means keeping your insulin down.

Dr. Rangan Chatterjee 53:25 Yeah.

Dr. Robert Lustig 53:25 And that means less cell growth, less chance for chronic metabolic disease also. So knowing how your body responds to a specific food turns out to actually be quite important.

Dr. Rangan Chatterjee 53:39 Yeah.

Dr. Robert Lustig 53:40 And there's no way to know that unless you're wearing a monitor.

Dr. Rangan Chatterjee 53:43 It's interesting that you said that you're looking at normal people wearing CGMs, wearing continuous glucose monitors, and seeing how they respond to certain foods.

Dr. Rangan Chatterjee 53:54 The word normal's quite interesting, isn't it? Because-

Dr. Robert Lustig 53:56 Yeah, 'cause no one's normal [laughs]

Dr. Rangan Chatterjee 53:58 ... you know, 88%, we, we, we hear of the US population have a degree of meta-

Dr. Robert Lustig 54:04 No, 93

Dr. Rangan Chatterjee 54:04 93%? It's gone up

Dr. Robert Lustig 54:05 93% are metabolically dysfunctional.

Dr. Rangan Chatterjee 54:07 So when you wrote Metabolical and the first time you came on my podcast, I think the figure was 88%. So already in the space of what, a year or two, that's gone up to 93%.

Dr. Robert Lustig 54:17 Right. There were two papers. The, the first paper was 2019, Arajo et al., and it was at 88%, and then the other pa- the next paper from, uh, Mozaffarian's group out of Tufts ca- uh, actually categorized it in 2021 at 93%. Maybe it was co- maybe it was COVID that did that, I don't know.

Dr. Rangan Chatterjee 54:35 Well, let's just pause on that for a minute because for anyone who's watching this or listening to this conversation and they haven't heard our first one, just explain what that means. 93% of the US population have a degree of metabolic dysfunction. Are you able to very succinctly summarize what is metabolic dysfunction, and why should people be worried about that statistic?

Dr. Robert Lustig 54:56 So metabolic dysfunction means mitochondrial dysfunction. That's what it means. So mitochondria are the little energy-burning factories inside each of your cells. Mitochondria are how you turn chemical compounds into energy to power cells. That's what mitochondria do. Mitochondria are refurbished bacteria, okay? They have their own DNA. They made an alliance with us back, you know, five billion years ago to basically be our powerhouse if we gave them, um, uh, safety and comfort [laughs] is basically the way it worked. It was a symbiotic relationship between the, the animals and the plants, because bacteria, you know, came from plants. So the prokaryote, the eukaryote. But they have their own DNA. They act on their own, and what we have to do is we have to be nice to our mitochondria, and that means not exposing them to toxins that can hurt them, and it means not exposing them to overwhelming nutrients that basically overwhelm them, okay? We have to be nice to our mitochondria. Our mitochondria have a set of, uh, proteins in order to maintain their, um, proton gradient to allow them to work.

Dr. Rangan Chatterjee 56:28 Mm-hmm.

Dr. Robert Lustig 56:28 And they're called complex one, complex two, complex three, complex four, complex five. And turns out there's this one at the end, which is sort of the molecular motor of the mitochondria, and it's called ATP synthase. And all of the food you eat, ultimately the electrons from that food end up going through the mitochondria and coming out as ATP through this ATP synthase. So when your mitochondria work, you can efficiently turn food into energy. But when your mitochondria are not working, and there are ways to knock your mitochondria off their game, stress, cortisol will do it. Um, uh, toxins in the environment will do it. Um, uh, the wrong fatty acids will do it, because the mitochondria are made of fatty acids. There are a whole bunch of things that can basically make your mitochondria not work right, and a lot of them are toxins in the environment, and unfortunately, stress is, is a big one-

Dr. Rangan Chatterjee 57:39 Mm

Dr. Robert Lustig 57:39 ... as we've talked about. So when your mitochondria are working subpar, you are not turning chemical, uh, uh, uh, energy into motor energy to power the cell properly.

Dr. Rangan Chatterjee 57:57 Mm-hmm.

Dr. Robert Lustig 57:57 That will generate the reactive oxygen species that will damage the cell. That will ultimately make you feel lousy and tired because you don't have the energy that you think you should have.

Dr. Rangan Chatterjee 58:08 Yeah.

Dr. Robert Lustig 58:09 And this is, of course, what happens in aging. This is what happens, uh, in stress. This is what happens in eating bad food.

Dr. Rangan Chatterjee 58:18 Yeah.

Dr. Robert Lustig 58:18 So, um, all of, all of these things are inexorably tied to how well your cells work and ultimately how well your mitochondria work. So maintaining mitochondrial integrity ha- has to be job one.

Dr. Rangan Chatterjee 58:36 Yeah. We'll be back to the conversation in just a moment. Now many of us struggle to find time to eat all of these incredible whole foods. That's why I'm a big fan of good quality whole food supplements like this one that's been in my own life for over three years now. It contains over 75 whole food source ingredients, vitamins, minerals, pre and probiotics, and can help us support our energy, focus, digestion, and our immune system. AG1 are giving my audience a fantastic offer, one-year supply of vitamin D and five free travel packs with your first order. You can see all details at drinkag1.com/livemore, or just click on the link below. And now back to the conversation. You know

Dr. Rangan Chatterjee 59:26 what I'd love to see? Uh, and I'm not, I'm not aware of any studies or research where they've done this. You, you might be, I hope you are. Um, but what I'd love to see is, you know, in some of the populations around the world where historically they would have 80% of their diet from carbohydrates, but whole food carbohydrates, let's say the Okinawans, maybe not the new generation, but the, the few decades ago, the generations who were eating whole foods and-

Dr. Robert Lustig 59:54 Right

Dr. Rangan Chatterjee 59:55 ... were having those purple sweet potatoes. I'd, I'd just love to know if they were wearing a CGM-

Dr. Robert Lustig 1:00:01 Mm-hmm

Dr. Rangan Chatterjee 1:00:01 ... what on earth was going on with their blood sugars? Because it, it would be quite interesting in that very low stress, um, environment where they're moving lots and they're getting good amounts of sleep and they've got strong community.

Dr. Robert Lustig 1:00:15 Yeah.

Dr. Rangan Chatterjee 1:00:15 When they're having these whole food sweet potatoes, you know, what is that doing? Is their sugar curve relatively flat? You know, I don't wear a, a CGM all the time. I probably wear one for two weeks, I would say every few months, right? So I, I don't personally wanna get overly reliant on it or too obsessed, but I use it maybe two or three times a year. I put it on for two weeks just to see where I'm at and give me an idea of the, the regular foods I'm consuming, what are they doing.

Dr. Robert Lustig 1:00:44 Right.

Dr. Rangan Chatterjee 1:00:44 And one of the things I discovered is that sweet potato wedges shoot my blood sugar up pretty high, you know?

Dr. Robert Lustig 1:00:54 So the, the thing we've learned, Rangan, and, and, you know, Levels Health is to be credited with this and, um, you know, I'm an a, you know, full, full disclosure, I'm an advisor to Levels. And one of the reasons is because I recognize that this is an important ... component of metabolic health-

Dr. Rangan Chatterjee 1:01:11 Mm-hmm

Dr. Robert Lustig 1:01:11 ... is maintaining, you know, your glucose homeostasis in a, in a good place because that basically translates into functioning mitochondria, and that's what I'm really espousing here. Um, but having said that, and, you know, n- not that it's an advertisement for Levels, but the bottom line is everybody has their, shall we say, bad food. [laughs] You know, their, their problem food. The food that they think is good for them, which turns out not to be so much. All right?

Dr. Rangan Chatterjee 1:01:46 Mm-hmm.

Dr. Robert Lustig 1:01:46 Everyone's got one. And, you know, everyone says oatmeal's good. Yeah, but for oatmeal, you know, s- th- th- oh, you know, like 25% of the population spikes like crazy, okay? Even though it's supposed to be something that's supposed to give you, you know, a consistent and, you know, w- w- non- non-spiky, uh, uh, glucose excursion. That does, turns out not to be true for a lot of people.

Dr. Rangan Chatterjee 1:02:12 Mm-hmm.

Dr. Robert Lustig 1:02:13 Um, different people, different problems. And so the only way to answer these questions is for you to do it yourself.

Dr. Rangan Chatterjee 1:02:22 Yeah. That's super interesting, Rob. Um, what do you say to opponents of continuous glucose monitors who say that looking at these blood sugar excursions... A- and again, for the, for, for, for someone who's never used one of these before, essentially you basically see in real time what your blood glucose is doing, and you can very quickly extrapolate, oh, when I eat this kind of food or this quantity of this type of food, this is what happens to my blood sugar. Now, it's not universally accepted that this is a good thing, right? Some opponents would say that-

Dr. Robert Lustig 1:03:02 Mm

Dr. Rangan Chatterjee 1:03:02 ... getting obsessed with these blood sugar ups and downs is pathologizing a normal physiological response. What do you say to that, Rob?

Dr. Robert Lustig 1:03:11 I'm ... [laughs] So there is no question that we have this thing out there now called orthorexia. So orthorexia is basically a pathological, uh, uh, hypervigilance about food, okay? And that anything can hurt you. And some people have actually, you know, accused me of contributing-

Dr. Rangan Chatterjee 1:03:38 Hmm

Dr. Robert Lustig 1:03:38 ... to this phenomenon and c- you know, concept of orthorexia. You know, look, there's always going to be the pendulum swinging one way and the other. When we didn't care about what our food did, look what happened. If you care too much about what your food does, you know, that's a problem, too. Somehow we have to find the place in the middle. And there are probably some people that should not wear CGMs because they can't manage the influx of data that comes in. But what we really need is the ability to acquire the information, the ability to integrate the information so that it means something. Because just because you gather data doesn't mean it actually is data you can use. You have to be able to integrate it, and then you have to be able to disseminate it to the patient-

Dr. Rangan Chatterjee 1:04:34 Hmm

Dr. Robert Lustig 1:04:34 ... in a meaningful way that they can understand. So three separate phenomena, acquisition, integration, dissemination. And you have to be able to do all three-

Dr. Rangan Chatterjee 1:04:46 Yeah

Dr. Robert Lustig 1:04:46 ... accurately and correctly, and for the right patient.

Dr. Rangan Chatterjee 1:04:50 Yeah.

Dr. Robert Lustig 1:04:50 You know? The fact is, we've had this problem throughout all of medicine. Ultimately, it i- is something you need to discuss with your doctor because your doctor knows you best. But the idea that you shouldn't use it because, yeah, some people might, uh, consider it a problem is, you know, that, that's, that's how you get into trouble, actually.

Dr. Rangan Chatterjee 1:05:13 Yeah.

Dr. Robert Lustig 1:05:13 So no, I'm not okay with that. Um, yes, I agree. Um, we need to, uh, take this down to the per-patient level.

Dr. Rangan Chatterjee 1:05:23 Yeah.

Dr. Robert Lustig 1:05:23 This shouldn't be a blanket, um, uh, recommendation across, uh-

Dr. Rangan Chatterjee 1:05:28 Yeah

Dr. Robert Lustig 1:05:28 ... all population.

Dr. Rangan Chatterjee 1:05:29 A- a- and I think sort of opponents to CGMs also, I think sometimes they make quite a black-and-white extreme argument, which is, yeah, if you eat just bacon three times a day, seven days a week, you'll have a completely perfect blood glucose stable response, right? But nobody's saying that only blood glucose matters.

Dr. Robert Lustig 1:05:52 No, no. And it ... That's correct. So first of all, there are a whole bunch of carnivores out there, okay? And, you know, carnivores will have the most stable of blood glucoses, and the reason is because they're not running on glucose, they're running on ketones 'cause they're carnivores. Right? The fact is that, um, the glucose excursion does matter, and the reduction in the glucose excursion can provide metabolic safety to some extent.

Dr. Rangan Chatterjee 1:06:19 Yeah.

Dr. Robert Lustig 1:06:20 Now, having said that, what if a patient with familial hypercholesterolemia decides to go carnivore? That's a really bad idea. [laughs] Okay? That's a really bad ... That's a great way to end up with cardiovascular disease really quick. Again, it's which patient are you and what's going on with you? And you have to do this individually.

Dr. Rangan Chatterjee 1:06:45 Yeah.

Dr. Robert Lustig 1:06:45 Now, one of the, uh, knocks against CGMs is, well, you don't have diabetes. Why do you need a CGM? It's actually because you don't have diabetes that you actually do need the CGM, all right? Because it will give you information to prevent diabetes-

Dr. Rangan Chatterjee 1:07:05 Yeah

Dr. Robert Lustig 1:07:05 ... not just treat it. And that's what we've learned is, you know, super important, especially when, you know, 45% of America is now pre-diabetic. Because they're insulin resistant. So how do you fix that? Well, glucose is one channel.

Dr. Rangan Chatterjee 1:07:24 It's one of them, yeah.

Dr. Robert Lustig 1:07:24 It's one way. It's only one. It's not all of them, okay?

Dr. Rangan Chatterjee 1:07:29 Yeah.

Dr. Robert Lustig 1:07:29 So ultimately, we're gonna need more channels, and I agree with that. We need ketones, we need lactate, and ultimately the one we need the most is insulin.

Dr. Rangan Chatterjee 1:07:38 Yeah.

Dr. Robert Lustig 1:07:38 We need an, a in real time insulin monitor to basically tell us how high does your insulin go when you eat certain foods? Now, the problem with insulin is because it's a peptide and because it's extremely low concentration, it's much harder to measure in real time. But people are working on that.

Dr. Rangan Chatterjee 1:07:58 Yeah.

Dr. Robert Lustig 1:07:58 And we'll probably have it in about four to five years. Does that mean we shouldn't be using glucose in the meantime? No. It just means that research will catch up to it-

Dr. Rangan Chatterjee 1:08:07 Yeah

Dr. Robert Lustig 1:08:07 ... and we'll have a better answer five years from now than we do today. But we still have an answer now.

Dr. Rangan Chatterjee 1:08:12 Yeah. I mean, anything generally speaking that you can do to educate yourself about your own individual responses, I think by and large for most people is a good thing, but it's a question of balance. I think our personality plays a role here as well. Some of us are more likely to become anxious and obsessed. Other people can look at the data, you know, in a much more distant way without it affecting every single food decision they make throughout the day. But, you know, one person's obsession is another person's care and attention, right?

Dr. Robert Lustig 1:08:46 Yeah.

Dr. Rangan Chatterjee 1:08:46 So it's, it's [laughs] very hard to say what is right for another person, I think.

Dr. Robert Lustig 1:08:51 Personal, having personal medical technology available to individual patients is, of course, going to have benefits and it's also gonna have drawbacks, okay? It's a tool.

Dr. Rangan Chatterjee 1:09:04 Mm.

Dr. Robert Lustig 1:09:04 Okay? Every tool has its good and bad side, okay?

Dr. Rangan Chatterjee 1:09:10 Mm.

Dr. Robert Lustig 1:09:10 Nuclear power can be a tool.

Dr. Rangan Chatterjee 1:09:13 Mm-hmm.

Dr. Robert Lustig 1:09:14 Right? In terms of generation of electricity or it can be a downside. It can be, you know, nuclear bomb. Okay, a hammer can hammer a nail, it can also hammer a skull. So just because something's a tool doesn't make it good or bad.

Dr. Rangan Chatterjee 1:09:28 Yeah, it's how you use it.

Dr. Robert Lustig 1:09:28 It depends on the user. It depends on the purpose.

Dr. Rangan Chatterjee 1:09:32 Yeah.

Dr. Robert Lustig 1:09:33 This is a tool, so for the right patient it can be a good tool. Now, there are a lot of doctors out there who don't know how to use it. They were never trained on it. They don't understand it. They never learned about this. And so they're gonna be faced with somebody walking into their office, you know, with all of this data saying, "Explain this to me," and they're not gonna be able to, and they're gonna be like, "Screw this," right? We already see this. You know, we have these people who are coming into cardiologist's office with Oura Rings, you know? "Oh my God, I threw a VPC. What am I gonna do now?" Turns out VPCs are normal.

Dr. Rangan Chatterjee 1:10:11 Can you just explain what a VPC is for the audience?

Dr. Robert Lustig 1:10:14 Ventricular premature contractions, where your heart goes ba-bum, you know, like that.

Dr. Rangan Chatterjee 1:10:18 Yeah.

Dr. Robert Lustig 1:10:19 Um, turns out w- you know, until we had Oura Rings, we didn't know how common they were, but they're common. So yes, this stuff happens, so we have to ultimately determine-

Dr. Rangan Chatterjee 1:10:30 Yeah

Dr. Robert Lustig 1:10:30 ... you know, like what's normal, what isn't, and you know, that expecting physicians to be able to, you know, uh, sit down with all of these data and be able to interpret this for any given patient might be asking too much of them.

Dr. Rangan Chatterjee 1:10:47 Yeah.

Dr. Robert Lustig 1:10:47 So the question is, how do you then, um, democratize this? How do you ultimately allow patients to be in possession of their own information so that they can utilize it properly? Well, that's the hard part. We ca- we can absolutely get people-

Dr. Rangan Chatterjee 1:11:06 Mm

Dr. Robert Lustig 1:11:06 ... to be in charge of their own information. The question is how do we know that-

Dr. Rangan Chatterjee 1:11:09 Yeah

Dr. Robert Lustig 1:11:09 ... they will utilize it properly? And that's where guardrails are needed.

Dr. Rangan Chatterjee 1:11:13 Yeah, for sure.

Dr. Robert Lustig 1:11:13 All right? Okay. The bo- bottom line is we have needed guardrails in our society for all sorts of things. Let me give you an example of what happens when guardrails work and when guardrails don't. Okay? In the last 75 years, there have been five major scientific breakthroughs that have changed the world. Five. Here they are. Nuclear weapons. As soon as they were used, everyone went straight to the table 'cause they saw the immense disaster that w- could, could be coming, and so they established guardrails, and those guardrails for the most part are still in place, aren't they? Number two, recombinant DNA back in the '70s, '80s. Okay? Everybody said, "Oh my God, you know, we're gonna unleash, you know, some virus [laughs] maybe." You know, maybe we've already seen it, I don't know. That, that's to be determined. Um, but the, what did they do? They established guardrails and now, you know, all this work is done in P4 facilities, you know, very specifically to keep it from getting out. Number three, CRISPR. Okay? CRISPR developed, you know, recently and that Chinese doctor made two designer babies, and everybody rushed to the table and established guardrails for how to be able to utilize this, you know, so that we don't actually, you know, re-engineer the human race. Number four, social media. How'd we do with that one? Not so hot. No guardrails, and look what happened. And now we got number five, AI. And I don't know what we're gonna do about that. Bottom line is every one of these has the potential for basically helping people-

Dr. Rangan Chatterjee 1:13:10 Mm

Dr. Robert Lustig 1:13:10 ... because they are tools, or hurting people if they are, you know, basically democratized into the wrong hands. We need guardrails for these things. Well, we need guardrails for CGMs too. We need guardrails for virtually everything we do in medicine. Okay? So I'm for patients owning their data. I am for patients understanding what's happening to them. I am for patients taking control of their own health within guidelines and within the guardrails that need to be set up for it. So that's how I feel.

Dr. Rangan Chatterjee 1:13:52 We started off this conversation, Rob, talking about the different fat depots, right? The three places where we can store fat, subcutaneous, visceral, and liver. And what was so interesting about that is that we can tolerate much more fat accumulation subcutaneously, you said 22 pounds on average, before it starts to cause a problem, whereas visceral fat we can only tolerate about five pounds or so before it starts causing, uh, real harm to us, whereas with the liver, it's only 0.3 pounds. Now, I ... Just to make sure everyone's following along with this, the subcutaneous fat we were saying was from, you know, consuming excess, and your body will store that excess in a relatively safe place unless it gets too much. You were saying stress is ultimately the key driver of visceral fat, which we know is really, really problematic. What is the key driver of liver fat? I think you mentioned it was sugar and alcohol, or I should say-

Dr. Robert Lustig 1:15:00 Sugar and alcohol

Dr. Rangan Chatterjee 1:15:01 ... fructose.

Dr. Robert Lustig 1:15:02 Sugar and alcohol.

Dr. Rangan Chatterjee 1:15:02 Well, is, is sugar as a term problematic? Because when we, when we use the term sugar, you know, we know that, you know, people will say, you know, sugar is essential for life, and they might be talking about glucose, or they might be saying blood sugar. And I sometimes say blood sugar when I mean blood glucose. Are we at a stage where we need to be a bit more precise? Because, you know, the term sugar can, can be so misleading, can't it?

Dr. Robert Lustig 1:15:28 Oh, I so agree. [laughs] This, this, uh, you, you have hit me right where I live. The fact is that, uh, there are corporate interests that ultimately misuse all sorts of verbiage-

Dr. Rangan Chatterjee 1:15:41 Mm-hmm

Dr. Robert Lustig 1:15:41 ... for their own purposes. Example, weight. Okay? What kind of weight are we talking about? You know, body weight, fat weight. Fat. Are we talking dietary fat? Are we talking, you know, liver fat? Are we talking visceral fat? Et cetera. Sugar. Right. Exactly. Are we talking dietary sugar? Are we talking blood sugar, which is really blood glucose? Okay. Ultimately, a sugar is not a sugar, a fat is not a fat.

Dr. Rangan Chatterjee 1:16:07 Mm-hmm.

Dr. Robert Lustig 1:16:07 A pound is not a pound, a calorie is not a calorie, a fiber is not a fiber, a protein is not a protein, an amino acid's not an amino acid. Okay? And down the line. Of course, we should be more exact, and I endeavor and strive to be more exact. Unfortunately, the population has not been educated into what these things are, so it tends to regress back to the mean. And so ... A- and of course, because corporations actually hide behind this, because they say, "Well, a sugar is a sugar, therefore I can put any amount of sugar I want in this thing," um, you know, it, it, it is a problem. So yes, educating the public has been a major, you know, uh, component of my, of my work.

Dr. Rangan Chatterjee 1:16:53 So, so wh- when we then are talking about what drives liver fat specifically, you're saying alcohol. And when you say sugar, do you essentially mean ex-

Dr. Robert Lustig 1:17:03 I mean fructose

Dr. Rangan Chatterjee 1:17:03 ... excess fructose?

Dr. Robert Lustig 1:17:05 I mean fructose. I don't mean glucose.

Dr. Rangan Chatterjee 1:17:07 Yeah.

Dr. Robert Lustig 1:17:07 I mean fructose. But because fructose is half of dietary sugar and there is no fructose alone in nature, it always comes with fiber.

Dr. Rangan Chatterjee 1:17:16 Yeah.

Dr. Robert Lustig 1:17:16 Except in honey, but, um, you know, how much honey are, are you eating? But pretty much everywhere else it comes with fiber.

Dr. Rangan Chatterjee 1:17:22 Let's just pause on honey for a minute, because many people will consume honey as a healthier option because it's-

Dr. Robert Lustig 1:17:30 Yeah

Dr. Rangan Chatterjee 1:17:30 ... natural compared to, let's say, table sugar or refined sugar.

Dr. Robert Lustig 1:17:34 Yeah.

Dr. Rangan Chatterjee 1:17:34 Now, I'm putting this out there just to get your view on this. The Hadza tribe in Tanzania, hunter-gatherer tribe that has been, you know, very, very well-studied by lots of different groups, are well known to gorge on honey when it is available. If they're on a hunt and they come across honey, from what I understand, they will often gorge on that honey. Now, I'm also aware that these guys have great gut microbiomes. They're very, very physically active. They do not touch ultra-processed food. It's all food from nature, et cetera, et cetera. So they're consuming potentially, on occasion, large volumes of honey. For the, the regular urban dweller who is listening to us chat now, um, should they learn anything from the Hadza about honey? Or for us, is it completely different?

Dr. Robert Lustig 1:18:33 Um, if you want to gorge on honey, have at it. All right? And the reason is because honey's so freaking expensive that if you gorge on it, [laughs] you're gonna be broke. [laughs] You're not gonna be able to afford it. Um, the big problem with honey is not honey. The big problem with honey is the fraud of honey, because almost all of the honey in the store is not honey. My colleague Mitchell Weinberg actually set up a, a, a check and balance system on honey to keep f- uh, honey fraud off the market. Almost all of the honey that you buy in commercial grocery stores, unless you buy them in very artisan shops, is actually a conglomeration of glucose syrup and, you know, fructose and, um, you know, some artificial, uh, uh, flavors. Honey fraud is the big- single biggest, uh, fraud item in food, uh, uh, worldwide.

Dr. Rangan Chatterjee 1:19:47 Wow!

Dr. Robert Lustig 1:19:47 There are other things too. There are wi- wine fraud, there's, um, uh, fish fraud, there's, uh, um, uh, scotch fraud. Uh, that's a big one. Uh, but honey is one of the biggest, and so they've actually developed a, uh, a method for determining whether or not, um, the honey you're eating is actually honey.

Dr. Rangan Chatterjee 1:20:08 First of all, I didn't know that. That's really, really interesting and slightly concerning. Um-

Dr. Robert Lustig 1:20:14 Yeah.

Dr. Rangan Chatterjee 1:20:14 In our first conversation, you explained that table sugar is sucrose, which is made up of glucose and fructose, okay?

Dr. Robert Lustig 1:20:23 Yep.

Dr. Rangan Chatterjee 1:20:24 What is natural, real honey? Like, what is that made of? I, I, assuming what we were buying, or let's say what the Hadza are gorging on in nature, right? What, what is that made up of?

Dr. Robert Lustig 1:20:36 It's made up of sucrose. It's made up of glucose and fructose, and it's got a couple of o- other bioactive compounds. Now, those bioactive compounds have never been shown to do anything. They may do something, but not usually in the g- uh, am- amounts and concentrations that people consume them in. There are a lot of people who say, "Well, honey is good for you." Show me. Show me the data that shows that honey is good for you. There are a lot of people who say it. I'm still waiting to see the data.

Dr. Rangan Chatterjee 1:21:10 Are, are you essentially saying that for someone who is probably not in the best metabolic health, which is most people, consuming honey from a metabolic health perspective is pretty much the same thing as consuming table sugar?

Dr. Robert Lustig 1:21:30 Yeah. The good thing about honey is because it's expensive and because it has its own unique flavor, people tend to use less of it. And anything that makes you use less of it, it, it-

Dr. Rangan Chatterjee 1:21:40 Yeah

Dr. Robert Lustig 1:21:40 ... as far as I'm concerned, is good. But from the standpoint of gram for gram, ounce for ounce, you know, um, calorie for calorie, it's basically no different from sucrose.

Dr. Rangan Chatterjee 1:21:51 Okay, so let's go back to liver fat for a minute then. So liver fat, it doesn't take much, uh, liver fat accumulation, 0.3 pounds as you mentioned, to start causing problems. Now, that doesn't sound like much at all, and you're saying that excess fructose and alcohol are the two main drivers of that.

Dr. Robert Lustig 1:22:10 One or the other-- There, there's a third dr- there are two other drivers of it as well. Trans fats did that like crazy.

Dr. Rangan Chatterjee 1:22:18 Yeah.

Dr. Robert Lustig 1:22:18 But as we, you know, we learned that, and in 2013, the FDA banned trans fats in foods. So that's good, except, by the way, there are still trans fats in foods. Uh, because of the FDA rules here in the United States that say if you are below 0.5 grams of trans fat, you can say zero.

Dr. Rangan Chatterjee 1:22:40 Mm.

Dr. Robert Lustig 1:22:41 You get to round down. So if you have 0.49, you get to say zero.

Dr. Rangan Chatterjee 1:22:48 Mm.

Dr. Robert Lustig 1:22:49 Now, we have learned that two grams of trans fats are cardiovascularly toxic. If you consume two grams of trans fats per day, you're gonna get heart disease. So if you consume four candy bars, let's say that they have no trans fats in them, there's a good chance that you will have gotten the equivalent of two grams. So just because it says none doesn't mean it's none. This is one of the other subterfuges of the food industry. So that's one thing, and then the fourth thing that causes this liver fat is branched-chain amino acids. So leucine, isoleucine, valine. Now, these three branched-chain amino acids are common. They are twenty percent of muscle. So if you-- If I took a muscle biopsy and I subjected it to, uh, uh, you know, a amino acid analysis, okay, twenty percent of the, uh, amino acids in muscle are branched-chain amino acids, and all three of those branched-chain amino acids are essential amino acids. You have to consume them. You can't make them. So leucine, isoleucine, valine, you have to consume them. It's not like you can make your, uh, diet branched-chain amino acid free. You need them.

Dr. Rangan Chatterjee 1:24:11 Mm.

Dr. Robert Lustig 1:24:12 But if you consume excess branched-chain amino acids and you're not laying down muscle, so you have no place to put the branched-chain amino acids into, and you consume excess, where does the excess go? So they go to the liver. The liver takes the amino group off. Now they're a branched-chain organic acid, and now they go into the Krebs cycle. They go into the tricarboxylic acid cycle in the mitochondria. You've now added extra substrate that the mitochondria can't process. It's-- overloads it. And so you're gonna throw off that citrate, and that citrate's gonna end up go-- undergoing de novo lipogenesis, and you're gonna make liver fat out of the amino acids because you didn't need them. So branched-chain amino acids, if you're a bodybuilder, are great, and so that's why bodybuilders-

Dr. Rangan Chatterjee 1:25:15 Yeah

Dr. Robert Lustig 1:25:15 ... you know, scoop protein powder, you know, when they make their smoothie shakes. And, uh, you know, if you're a bodybuilder, that's okay. But if you're not a bodybuilder and you're taking excess branched-chain amino acids, all you're doing is increasing your liver fat.

Dr. Rangan Chatterjee 1:25:29 Yeah.

Dr. Robert Lustig 1:25:30 And that's what we're seeing. And so the question is, all right, where is the, you know, Joe Schmo getting his branched-chain amino acids from? And the answer is corn. Corn-fed beef, chicken, and fish, which here in the United States is virtually all of our, um, uh-

Dr. Rangan Chatterjee 1:25:49 Wow

Dr. Robert Lustig 1:25:49 ... uh, protein supply.

Dr. Rangan Chatterjee 1:25:51 So that's different from grass-fed's.

Dr. Robert Lustig 1:25:54 Exactly. Grass-fed has less branched-chain amino acids.

Dr. Rangan Chatterjee 1:25:58 Hmm.

Dr. Rangan Chatterjee 1:26:00 It sounds, Rob, to me, i- if I sort of try and zoom out and take a big picture look at this, I feel like the liver needs some better PR, right?

Dr. Robert Lustig 1:26:13 Yeah.

Dr. Rangan Chatterjee 1:26:13 Because we, we-

Dr. Robert Lustig 1:26:14 It sure does

Dr. Rangan Chatterjee 1:26:14 ... we, we, you know, we, we are excited about brain health and heart health and muscle health. No one's getting excited about liver health, but [laughs] -

Dr. Robert Lustig 1:26:23 Yeah

Dr. Rangan Chatterjee 1:26:23 ... but, but-

Dr. Robert Lustig 1:26:24 Liver needs love

Dr. Rangan Chatterjee 1:26:25 ... liver needs love, right?

Dr. Robert Lustig 1:26:26 Liver needs love.

Dr. Rangan Chatterjee 1:26:26 The liver's the heart. The, it's arguably the most important organ when it comes to metabolic health. I don't know if you'd disagree with that.

Dr. Robert Lustig 1:26:34 Uh, when it comes to metabolic health, it is the organ of record, yes.

Dr. Rangan Chatterjee 1:26:39 Come on, pretend you're doing PR for, for the liver at the moment, Rob. You know, tell us why should we care about the liver?

Dr. Robert Lustig 1:26:45 'Cause when your liver works right, every other cell in your body works right. We've a- and we've actually looked at this. This is one of the reasons why in Metabolical, I, you know, espouse to protect the liver.

Dr. Rangan Chatterjee 1:27:01 Mm.

Dr. Robert Lustig 1:27:01 Okay? Promote metabolism, suppress inflammation. So prom- those are the two things that you have to do to be metabolically healthy. Promote metabolism, suppress inflammation. Promote metabolism where? Well, the liver, 'cause that's what does the metabolism. That's where virtually all the metabolism in your body gets done. It's where detoxification of poisons come, comes in. It's what ultimately sends out energy to the rest of the body, 'cause the liver is in charge of turning that energy into stuff that the rest of the body can use, whether it be ketones or glucose. Okay? It is the thing that ultimately impacts on your blood glucose control because it's where insulin works. Insulin works at the liver. That's why the pancreas is in series with the liver. That's why the pancreatic vein drains into the portal vein to go to the liver, not to the entire general circulation, because the liver is ground zero. Good liver, good body, and all the data shows that when you screw up the liver, everything upstream of the liver gets worse. That's what we've shown. So yes, you gotta protect your liver. And what do you have to protect it from? Well, you have to protect it from toxins. And what are those toxins? Well, the big one is fructose. Not the only one, but it's the big one, okay? Are there others? Sure. Cadmium, arsenic, you know, a lot of heavy metals are, you know, big ones there. And of course alcohol is the other, you know, huge one. And if your liver works right, you will be healthy.

Dr. Rangan Chatterjee 1:28:40 What is the best way for someone to assess the state of their liver?

Dr. Robert Lustig 1:28:46 Yeah. So that's a little bit harder, um, and it's a little more complicated. Uh, the easiest way, the cheapest way, the free way, if you will, but unfortunately th- not the specific way, is a waist circumference. So that anyone can do, but unfortunately it doesn't necessarily tell you everything you need to know, but it's a good start-

Dr. Rangan Chatterjee 1:29:11 Uh, and what-

Dr. Robert Lustig 1:29:11 ... and it's free

Dr. Rangan Chatterjee 1:29:11 ... and what do you look for?

Dr. Robert Lustig 1:29:13 Well, uh, if you're a male, uh, over 40 inches, if you're female over 35 means you probably have a liver problem.

Dr. Rangan Chatterjee 1:29:20 But that's... Can I just say on that, that's interesting, and you've also said that it's not perfect. To make sure you're taking action after watching this video, I've created a free guide to help you build healthy habits. We can all make short-term change, but can those changes become a fundamental part of our life? Often they don't, and that's why in this free guide, I share with you the six crucial steps you need to take. They're really, really effective. If you want to get hold of that free guide right now, all you have to do is click the link in the description box below. If I think about that through the lens of myself, I'm naturally slim. Now yes, I do look after myself and I pay close attention to the way I live my life, but I would say I'm naturally slim. If I got up to, I would say, a 37-inch waist, that would be huge for me, right? So the, the, so the reason I'm bringing that up is purely for the fact that 40 inches, it kind of depends on your starting point as well, 'cause I would even argue if I got to 36, 36.5, I would say for me, I'm carrying extra fat around my abdomen. So-

Dr. Robert Lustig 1:30:32 No question. Uh, no question this is racially determined as well. Um, you know, Asians, uh, will have liver fat at a much lower BMI.

Dr. Rangan Chatterjee 1:30:42 Yeah.

Dr. Robert Lustig 1:30:42 African Americans will have liver fat at a much higher BMI. So it's very, it's very individual and, and it- it's got race, uh, uh, dependency and sex dependency and age dependency.

Dr. Rangan Chatterjee 1:30:54 Okay.

Dr. Robert Lustig 1:30:55 Um, so it, that's one of the reasons why it's not that easy to use. Number two, lab tests. All right, what lab tests? Well, the easiest lab test, and the one that pretty much everyone gets once a year, is an ALT.

Dr. Rangan Chatterjee 1:31:12 Yeah.

Dr. Robert Lustig 1:31:13 Alanine aminotransferase. Now, the problem with alanine aminotransferase is it's sensitive but not specific. If your ALT is high, it usually means you have liver fat. Doesn't tell you why you have liver fat, but it usually means you have liver fat. But the question is, what's the cutoff? And this is where-

Dr. Rangan Chatterjee 1:31:36 Mm

Dr. Robert Lustig 1:31:36 ... things get a little dicey. Because the doctor will look at the lab slip and say, "Oh, your ALT is 30. You're fine." And the reason is because the upper limit of normal is 40 on the lab slip. Like hell it is. The upper limit of ALT should be 25. When I entered medical school in 1976, the upper limit for ALT was 25.

Dr. Rangan Chatterjee 1:32:04 Yeah.

Dr. Robert Lustig 1:32:05 And it should be 20 for African Americans. Okay? 25. But today it's 40. Did they change the assay? They changed the name, but they didn't change the assay. Are they changing what they're measuring? No, they're still measuring the same thing. So why is it that 50 years ago the upper limit for ALT was 25, and today the upper limit is 40? Very simple. 'Cause everyone has fatty liver now. 45% of the American population have fatty liver. So if you take 100,000 lab specimens from 100,000 people who say they're healthy-

Dr. Rangan Chatterjee 1:32:42 Yeah

Dr. Robert Lustig 1:32:42 ... and you run the ALT and you measure the mean, and then you measure two standard deviations from the mean, and that's where you draw the line for, you know, what's abnormal, the entire curve has shifted to the right, 'cause everyone's got fatty liver.

Dr. Rangan Chatterjee 1:32:57 Yeah.

Dr. Robert Lustig 1:32:57 And so two standard deviations from the mean is now 40. So that's what they put on the lab slip. So if your doctor's reading off the lab slip, "Oh, your ALT is 30, so you're fine," no, you're not fine. You're not fine at all. Okay? You're consistent with the general population.

Dr. Rangan Chatterjee 1:33:17 Mm.

Dr. Robert Lustig 1:33:18 But the general population is not fine either.

Dr. Rangan Chatterjee 1:33:21 Yeah.

Dr. Robert Lustig 1:33:23 So you have to be able to interpret the n- number properly. So that's the problem there. And then once you get past ALT, now we're getting into the rarefied air and the expensive stuff, and the imaging like ultrasound or the magnetic resonance spectroscopy or the pancr-

Dr. Rangan Chatterjee 1:33:43 Yeah

Dr. Robert Lustig 1:33:43 ... or, or the, uh, uh, uh, elastography. There's this thing, uh, you know, there's this, uh, calculation called FibroScan that will, you know, give you a little bit better answer. Um, but you know, now we're talking, you know, like real money.

Dr. Rangan Chatterjee 1:33:56 Yeah. I think the first two you mentioned there a, a- are so accessible [laughs] and cheap, right? Waist circumference, anyone can do that themselves at home just to get an idea. Even if they track that themselves, like over time, every six months, let's say you put it in your diary, you track it and you see which way it's going, that would be something really helpful to give you an indication of what might be going on inside, something that you can't see potentially. But also the ALT test, now I know people watch and listen to the show all over the world, but for anyone in the UK, that is available on the NHS. I mean, you can get that. Any adult can go in pretty much and get an ALT. It's a d- very, very cheap test. And you-

Dr. Robert Lustig 1:34:42 Standard test on a standard chem profile. The only thing to admonish your listeners, do not take normal-

Dr. Rangan Chatterjee 1:34:52 Yeah

Dr. Robert Lustig 1:34:52 ... for an answer.

Dr. Rangan Chatterjee 1:34:53 Yeah. Find out what it is.

Dr. Robert Lustig 1:34:54 Get the number.

Dr. Rangan Chatterjee 1:34:55 Get the number, and then maybe track it once a year and see which, which direction it's going in. And if you're concerned, discuss it with your doctor. I think that's really useful. I mean, that's how you can look for it in yourself, but it's a pretty reasonable assumption [laughs] that most of us, most of the population have got more liver fat than they would want. Is, is, is that a fair assumption?

Dr. Robert Lustig 1:35:20 That is a very fair assumption.

Dr. Rangan Chatterjee 1:35:22 Okay.

Dr. Robert Lustig 1:35:22 Much more common than anyone realized.

Dr. Rangan Chatterjee 1:35:25 Yeah, and because you can't see it.

Dr. Robert Lustig 1:35:27 And do you know what else is common? Nonalcoholic fatty pancreas disease.

Dr. Rangan Chatterjee 1:35:35 Wow.

Dr. Robert Lustig 1:35:35 Whoa. Not fatty liver, fatty pancreas disease. Okay? Now, how do you find that? Well, you have to set the MRI in a very special way to be able to actually see that, but we did that and we found nonalcoholic fatty pancreas disease, and it correlated with insulin release negatively.

Dr. Rangan Chatterjee 1:36:02 Mm.

Dr. Robert Lustig 1:36:02 So the more fat in the pancreas, the less insulin released. So it's very possible that the fat being laid down in the pancreas is actually one of the drivers of diabetes, which of course is responsive to sugar.

Dr. Rangan Chatterjee 1:36:14 I mean, if we had another hour, I'd, I'd love to go down that rabbit hole, but we'll save that for part three, Rob. [laughs]

Dr. Robert Lustig 1:36:20 [laughs]

Dr. Rangan Chatterjee 1:36:20 Um, that is really interesting. But there's a, there's a wider point there for me. I was thinking about this today. In our first conversation, we spoke at length about nonalcoholic fatty liver disease, okay?

Dr. Rangan Chatterjee 1:36:34 I thought the term's interesting. You know, it, it's ... We- we're kind of not really saying what it is. We're saying nonalcoholic, right? So we, we, we could say fructose-driven liver disease or sugar-driven liver disease, couldn't we? Or, you know, something else, but, but ... or, or ultra-processed food-driven liver disease, but we just say nonalcoholic. So it kind of doesn't quite land for us that what we're doing may be impacting our liver fats.

Dr. Robert Lustig 1:37:02 So the, the he- hepatologists here in the United States, in their infinite wisdom, have rebranded the disease. They've got a new name for it.

Dr. Rangan Chatterjee 1:37:11 Okay. [laughs]

Dr. Robert Lustig 1:37:13 [laughs] What is it? Okay. It is, ready? M-A-S-L-D, MASLD. [laughs] Instead of NAFLD, it's MASLD.

Dr. Rangan Chatterjee 1:37:23 Okay.

Dr. Robert Lustig 1:37:24 And what is MASLD? Metabolical associated steatotic liver disease. Now, which one of those two, NAFLD or MASLD-

Dr. Rangan Chatterjee 1:37:37 [laughs]

Dr. Robert Lustig 1:37:38 ... tells you what's going on? Neither. [laughs] Neither. I would like to call it processed food fatty liver disease. That's what I would call it.

Dr. Rangan Chatterjee 1:37:52 Yeah.

Dr. Robert Lustig 1:37:53 But that's not on the table, unfortunately. [laughs]

Dr. Rangan Chatterjee 1:37:59 How early does this liver fat start to accumulate? Are we seeing it in children now, for example?

Dr. Robert Lustig 1:38:06 Oh, yeah. No, we can see it in five-year-olds. I've seen it in three-year-olds.

Dr. Rangan Chatterjee 1:38:10 And, and hold on a minute. Let's just be really clear here. Uh, is it ... Should we be having zero liver fat? Is that what normal is?

Dr. Robert Lustig 1:38:18 Normal is zero.

Dr. Rangan Chatterjee 1:38:19 Right. Okay. So-

Dr. Robert Lustig 1:38:21 Up to, up to 5% usually means no damage.

Dr. Rangan Chatterjee 1:38:27 But, but really we should be aiming for zero ideally.

Dr. Robert Lustig 1:38:30 Should be aiming ... Should ... I- ideally zero to maybe .5%.

Dr. Rangan Chatterjee 1:38:34 So, so if, if we just go back to, again, the opening question, right, the three fat depots, which really appears to have been the theme of this entire conversation this time round, is it possible then if, if ... Theoretical question. If excess fructose and alcohol, and, yes, trans fats and, you know, excess branched-chain amino acids if you're not working out regularly, if those are-

Dr. Robert Lustig 1:39:04 Mm-hmm

Dr. Rangan Chatterjee 1:39:04 ... the key drivers of liver fat, right?

Dr. Robert Lustig 1:39:08 Mm.

Dr. Rangan Chatterjee 1:39:08 Is it in theory possible then if you are having a completely whole food diet, but you're probably eating s- a little bit too much of that whole food diet for your daily needs, and you have low to non-existing stress levels, so you're not driving visceral fat, and you're not having excess fructose, and you don't drink alcohol-

Dr. Robert Lustig 1:39:31 No

Dr. Rangan Chatterjee 1:39:31 ... is it in theory then possible that you will have subcutaneous fat but no visceral fat, no liver fat, and therefore be metabolically healthy?

Dr. Robert Lustig 1:39:45 20%. 20% of obese people are just that. They are metabolically healthy obese. We even have a name for them, MHO, metabolically healthy obese. They live a completely normal life, die at a completely normal age, not cost the taxpayer a dime. They just have increased subcutaneous fat tissue. So what?

Dr. Rangan Chatterjee 1:40:14 And if we were to look at their bloods, they probably have a normal-ish HbA1c, normal triglycerides, um, normal ALT that we just spoke about. So for all intents and purposes, it would just be a cosmetic, um, uh, I wouldn't even c- I don't even want to say, a issue. It's not an issue. It ... But it, the way-

Dr. Robert Lustig 1:40:34 It's not an issue

Dr. Rangan Chatterjee 1:40:35 ... the way society looks at it-

Dr. Robert Lustig 1:40:37 It's only an issue in your own head.

Dr. Rangan Chatterjee 1:40:39 Yeah.

Dr. Robert Lustig 1:40:40 If it's an issue, it's because you made it an issue, not because it is an issue. But yes, unfortunately, society is very cruel.

Dr. Rangan Chatterjee 1:40:49 Yeah.

Dr. Robert Lustig 1:40:49 And, you know, they, they will punish people for just about anything. Um-

Dr. Rangan Chatterjee 1:40:53 But that's interesting, isn't it? 20% are metabolically healthy.

Dr. Robert Lustig 1:40:58 Yeah.

Dr. Rangan Chatterjee 1:40:58 You know?

Dr. Robert Lustig 1:40:59 20% of the obese population's metabolically healthy. Conversely, 60% of the normal weight population is metabolically ill.

Dr. Rangan Chatterjee 1:41:10 Mm.

Dr. Robert Lustig 1:41:12 So just 'cause you're fat doesn't mean you're sick, and just because you're thin doesn't mean you're healthy. And this is why it's so important for people to know who they are and what they are and what caused them to be who or what they are, and that's one of the reasons for gathering these data-

Dr. Rangan Chatterjee 1:41:31 Mm

Dr. Robert Lustig 1:41:31 ... and figuring it out. And don't just let your doctor say, "Ah, your labs are normal. Go away."

Dr. Rangan Chatterjee 1:41:41 I've got two kids, Rob, 13 year old and an 11-year-old. Given everything you have researched throughout your career, given all the patients you've seen, if you were sitting in front of my children right now and you were gonna educate them on health and the importance of how they treat their bodies, what are the key things that you would say to them?

Dr. Robert Lustig 1:42:10 Eat real food.

Dr. Rangan Chatterjee 1:42:15 And if they say to you, "Dr. Lustig, what does that mean? What's real food?" What would you say?

Dr. Robert Lustig 1:42:20 [laughs] So real food is what came out of the ground or animals what, that ate what came out of the ground. [laughs] Real food does not have a label 'cause it doesn't need a label 'cause it's real. In fact, the only foods that have labels are foods that had had something done to it. So every label is a warning label. Does a radish have a label? Does a broccoli have a label? Does a steak have a label? None of them have labels because they're real food. Now, if something's been done to it, then there's a label. So the question is, okay, what is it that's been done to it? Maybe it, what was done to it was okay, like it got ... You know, it was milk that got irradiated f- you know, to e- up the vitamin D. Maybe that's a good thing. Um, maybe they added some, you know, um, uh, preservatives so that it ha- you know, stabilized the shelf life. Maybe that's a good thing, or maybe it's not a good thing 'cause we're now learning that certain preservatives are actually mitochondrial toxins. So it's not what's in the food, it's what's been done to the food that matters. All food is inherently good. It's what we do to the food that's not. And that's why I wrote this book, Metabolical, is to explain to people what's been done to their food that they don't know about, because the food industry doesn't want you to know about it, 'cause if you knew what they did to it, you wouldn't buy it.

Dr. Rangan Chatterjee 1:44:00 Yeah.

Dr. Robert Lustig 1:44:00 So eat real food, and the way you know you're eating real food is it doesn't have a label.

Dr. Rangan Chatterjee 1:44:11 That's good advice. I h- I hope, I very much hope, [laughs] I very much hope my children know that by now. [laughs]

Dr. Robert Lustig 1:44:18 [laughs]

Dr. Rangan Chatterjee 1:44:18 They certainly, I certainly think they do know that. Um-

Dr. Robert Lustig 1:44:23 Look, if you think Cheetos is food, you know, all, you know, it's, it's all over. That, you know, we have to undo this concept, you know, that people think that this is the case. So here's a question for you. Well, we, we can end on this. All right, uh, Rangan. Okay? In order to understand this, you have to actually know the definition of food. So what's the definition of food? Well, I'll tell you right now from the dictionary, okay? I memorized it. Substrate that contributes to either the growth or burning of an organism. That is the definition of food. Substrate that contributes to either growth or burning of an organism.

Dr. Rangan Chatterjee 1:45:11 What does that mean, burning of an organism?

Dr. Robert Lustig 1:45:14 In other words, used for energy utilization, burning. Okay? That's a perfectly fine definition. It is a 100% definition. Okay? I have zero problem with that definition. Okay. So let's go to burning first. Bottom line, fructose inhibits burning. Fructose has been added to 73% of the items in the American grocery store.

Dr. Rangan Chatterjee 1:45:42 Wow.

Dr. Robert Lustig 1:45:43 Okay? That's burning. Now let's take growth. My colleague, Dr. Efrat Monsonego-Ornan, who is the head of nutrition at Hebrew University Jerusalem, has actually studied this. It turns out that ultra-processed food inhibits growth. It inhibits skeletal growth, it inhibits trabecular bone, bone growth, it inhibits cancellous bone growth, it inhibits cortical bone growth. You can actually see it on electron microscopy. You can see the holes eaten out of the bone. You can see the problem with the epiphyses not m- you know, uh, uh, uh, gaining in, in, in length. Okay? You can measure the bone, you can measure the tensile strength of the bone. Basically, the bones break. One of the reasons for osteoporosis, one of the primary reasons for osteoporosis. So if a substrate does not contribute to growth and does not contribute to burning, is it a food?

Dr. Rangan Chatterjee 1:46:42 Yeah.

Dr. Robert Lustig 1:46:43 We have to teach that. We have to explain to people that ultra-processed food is not food. Just because the food industry called it that doesn't make it true.

Dr. Rangan Chatterjee 1:46:55 What, what if a child was to say to you, "Rob, okay, I, I get that, Dr. Lustig. This sounds really interesting. Um, but what happens if I want a bag of sweets once a week?" Right? "That's probably not food by your definition or by, or by the definition that you're, you're referring to. Is that okay?" And I think what I'm trying to get to is where is the balance point for people? Because very few people are going to eat exclusively just real foods, and so people wanna know, you know, well, how much? [laughs] You know, what, what can I get away with, as it were?

Dr. Robert Lustig 1:47:32 I totally understand. I, yeah, I, I get it. I get it. So I'm gonna give you two things. T- two, one is a tool and the other is a concept. Here's the concept. I, Robert Lustig, am for dessert. For dessert. I am not for dessert for breakfast, lunch, snacks, and dinner. So if you're gonna eat that bag of candy and that's dessert, hey, have at it. But that bag of candy has as much sugar as the Froot Loops you ate at breakfast and the Chinese chicken salad you ate at lunch and the chicken teriyaki you ate at dinner. So in fact, you ate four desserts today.

Dr. Rangan Chatterjee 1:48:23 Hmm.

Dr. Robert Lustig 1:48:25 So that's the problem. It's not the f- uh, uh, the, the sugar in the candy that's really the problem because you identified it as such. The problem is the sugar in everything else.

Dr. Rangan Chatterjee 1:48:38 Yeah.

Dr. Robert Lustig 1:48:39 The sugar in the 73% of the items [laughs] in the grocery store that you didn't know had it, like the tomato sauce and, you know, the, the, the, the bread and... So that's, that's, that's the concept. Now the tool. My colleagues and I have developed a tool to help people at the grocery store, and it is called PERFACT, P-E-R-F-A-C-T, and you can find it online at PERFACT, P-E-R-F-A-C-T.co, perfect.co. And what it is is it's a recommendation engine. Now, right now it's for the United States. We would like it to be for the UK, but it needs a branded foods database that lives online, and right now the only one that exists like that that we know of is Waitrose. So we need Tesco and we need, uh, Marks & Spencer, and we need, you know, all of your other stores to sort of ante up. So for Waitrose, we can do it. Um, but in the United States, we can basically tell you any given food at your grocery store, not only what's in it, but what's been done to it.

Dr. Rangan Chatterjee 1:49:53 Mm.

Dr. Robert Lustig 1:49:53 And so you can apply specific filters based on your metabolic status, whether it, you have metabolic syndrome, whether you're trying to avoid carbs, whether you're trying to avoid oxalate, whether you're trying to avoid peanuts, whether you're trying to avoid, um, uh, animal products 'cause you're vegan. Okay? And you can basically filter out everything in the store that is metabolically unhealthy for you.

Dr. Rangan Chatterjee 1:50:21 Yeah.

Dr. Robert Lustig 1:50:22 And it's free.

Dr. Rangan Chatterjee 1:50:23 Yeah. Brilliant. Well, we'll put that in the show notes for other people who wanna check that out.

Dr. Rangan Chatterjee 1:50:27 Robert, you're just doing such incredible work. You know, one of the, one of the most gratifying things about researching your work for these conversations is if you go and watch any of your YouTube videos, the amount of comments underneath from people who have literally said, "Dr. Lustig has changed my life. Dr. Lustig got me onto a low sugar, high fiber diet. Dr. Lustig really connects with me. For the first time, he told it straight up how it is, and that's what I needed to change my life," I know you get a lot of naysayers, particularly as you're growing and your, your message is growing, but that must be very gratifying to, to, to read and to, to hear from so many people what an impact you've had on them.

Dr. Robert Lustig 1:51:07 I, I, it is. It, it, I... There's no question. Uh, and I love to hear those stories because they give me purpose.

Dr. Rangan Chatterjee 1:51:16 Yeah.

Dr. Robert Lustig 1:51:16 They make me feel like I'm doing something valuable. What I don't like, and I truly don't like it, is when people, you know, it, when they think somehow I'm sort of like some rock star. You know? Like, no, no. It's the message, not the messenger. Okay? I would very much like to be anonymous. I would very much like to basically, you know, have this problem go away.

Dr. Rangan Chatterjee 1:51:41 Yeah.

Dr. Robert Lustig 1:51:42 You know? But it's not going away.

Dr. Rangan Chatterjee 1:51:44 Yeah.

Dr. Robert Lustig 1:51:44 And unfortunately, it's gonna need people like you and me to make it go away.

Dr. Rangan Chatterjee 1:51:49 Well, Robert, it's always a pleasure. You mentioned that eat real food is the key message you wanna give to children. I'm guessing that's the same message you wanna give to adults. Apart from that as a take home for people, is there any final bit of wisdom you wanna impart to people in terms of what they can do immediately to improve their health?

Dr. Robert Lustig 1:52:07 Um, you can't solve a problem unless you know what the problem is, and for the last 50 years, we've been told the wrong thing. So this is, what we have is we have a belief system. Okay? So here's a, here's a, here's a new construct for you, Rangan. Okay? Are you Hindu?

Dr. Rangan Chatterjee 1:52:31 Uh, yeah, my family are. I was certainly raised that way.

Dr. Robert Lustig 1:52:34 Oh, okay. You... Right. Do you ever think about being Jewish?

Dr. Rangan Chatterjee 1:52:39 Not really, no.

Dr. Robert Lustig 1:52:40 Oh, okay, 'cause Hindu worked for you, right?

Dr. Rangan Chatterjee 1:52:44 Okay.

Dr. Robert Lustig 1:52:45 In America, in America only, it, when I was a kid, you know, 1970 or so, only 2% of people changed religions. Today, it's 24%. Why is that? 'Cause whatever their religion is, it's not working for them. Okay? So they were taught a belief system, and they found that the belief system ultimately did not solve their issues or s- a- answer their questions, and so they are looking for something else. Well, we have had a belief system called calories for the past 50 years, and that's all it is, is a belief system. And believe it or not, it didn't work, and it hasn't worked, and the reason is 'cause it's not true. And so what I'm trying to do is I'm trying to reorient people so that they can actually understand what the truth, what the science says, and so that they can form their own narrative that will work for them. That's what I'm trying to do.

Dr. Rangan Chatterjee 1:53:54 Well, Robert, you're doing a great job. I think Metabolical is a fantastic book. Thank you for making time to come on the show again. I really appreciate it.

Dr. Robert Lustig 1:54:01 No, it's my pleasure, Rangan. Anytime.

Dr. Rangan Chatterjee 1:54:03 [upbeat music] If you enjoyed that conversation, I think you're really going to enjoy this one about the things that you can do right now to heal your body and prevent disease.

Host 1:54:13 How much vitamin D do you need to not get rickets? Probably 30 units. How much vitamin D do you need to optimize your immune system and prevent cancer and heart disease and all these other benefits? Probably 2,000 to 4,000