Obesogens, Oxidative Stress, Dietary Sugars & Fats, Statins, Diabetes & the True Causes of Metabolic Dysfunction & Chronic Disease | Robert Lustig

About the Guest: Robert Lustig, MD is a physician-researcher and expert of metabolic health. He is Professor emeritus of Pediatrics, Division of Endocrinology at the University of California, San Francisco (UCSF), specializing in neuroendocrinology with an emphasis on the regulation of energy balance by the central nervous system. His research and clinical practice has focused on childhood obesity and diabetes.

Episode Summary: Nick and Dr. Lustig discuss the true causes of obesity and metabolic discussion; how the in utero environment during pregnancy leads to multigenerational effects on health; different forms of sugar like fructose vs. glucose; different dietary fats like omega-6 and omega-3 PUFAs, and saturated fat; oxidative stress & mitochondria biology; how temperature, altitude & oxygen affect obesity; processed foods and how industry influences public perception; body positivity & public education; insulin, diabetes & fatty liver disease; statins & cardiovascular health; and more.

*My content is never meant to serve as medical advice.

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* Episode transcript below.

Full AI-generated transcript below. Beware of typos & mistranslations!

Robert Lustig 5:20

loaded question, Nick, to say the least, we've learned in the last 30 years about a new aspect of medicine. And it's called the developmental origins of health and disease or DOHaD. The first person to notice this was a epidemiologist working in Southampton, England, by the name of David Barker. And he was basically going through records of people who were born during the war during World War Two. And notice that these people were dying early. And he didn't know why. And, you know, it was years later that he noticed this. And he did an enormous amount of exculpatory work that to this day is, you know, kind of classic epidemiology. And he came to the realization that something was going on in utero, that was actually changing these fetuses physiology, that was ultimately leading to the ultimate development of chronic disease, cardiovascular disease, type two diabetes, etc. And he presented that and people started, you know, looking at this question, and they found, you know, similar stories elsewhere, and they started doing animal experiments. And sure enough, it looked like, what the mother was exposed to, ultimately is visited upon the baby, later on. Now, we had always thought that the placenta was this great barrier that kept the mother from the baby. And we had lots of reasons to think that because after all, you know, mom's immune system does not become the baby's immune system. And, you know, we thought that these various transporters that live in the placenta help, you know, determine, you know, the stuff that needs to get in and keep the stuff out that doesn't need to get in. And there are enzymes in the placenta, that keep, for instance, cortisol from getting to the baby. You know, unless, of course, the mother takes something that the enzyme can't work on, like, for instance, dexamethasone, and then it does go to the baby. So we had this notion that the placenta was all seeing and all knowing, and the ultimate, you know, suit of armor for for the baby. And that mother's diet didn't matter, and that mother's medicines didn't matter. And ultimately, when we learned about microbiome, that mother's microbiome didn't matter. That turns out all of that is hogwash. The placenta is not that great. It's, it'll let a lot of stuff across, and it doesn't do what we think it does. And so in fact, the fetus ends up swimming in the same cesspool of contaminants and environmental exposures that the rest of us do. And so it shouldn't be too surprising that those contaminants when they have effects on us, that they would also have effects on the fetus. Now, one of those that I happen to be particularly interested in so I've done a lot of work on obesity, are these chemicals which we now term obesogens. That is, they are chemicals that drive adiposity drive, weight gain, drive chronic disease in humans, both, you know, adults, and as it turns out, also fetuses having nothing to do with their potential inherent calories. So there are a lot of substances that have calories, but generate more adiposity than their calories like my favorite fructose. And there are plenty of chemicals that generate adiposity having nothing to do with calories, like for instance, polyflor alkylated substances pee fast like Teflon, okay, or BPA, Bisphenol A, which turns out to be an estrogen. And, you know, there's a whole host of compounds satellites plasticizers PBDE, is flame retardants. Parabens are things that are in cosmetics, things that are in vinyl flooring things that are in. Oh, and by the way, air pollution to boot. All right. And so you'd think the placenta would be a great way to keep the fetus away from all of these things. Because after all, fetuses don't use cosmetics. And fetuses don't breathe our air. But you know, what? They're still getting damaged. And that's what we've learned. And the obesogens hypothesis brings this question of what's really at the, at the notice of this obesity pandemic, that is really only about 50 years old, you know, before, you know, 1970, only 5% of the population was above the 95th percentile for body mass index. You know, this has all occurred in the last 50 years. And something has to explain it. And you know, our DNA hasn't changed. But our environment Sure has. And, you know, people want to say, Well, it's because of the food, you know, because people are gluttons and slots. No, it turns out that there are chemicals driving this. And that's, you know, part of, you know, what my research has been about for the last 25 years.

Nick Jikomes 11:18

So there are both food and non food obesogens substances that we're exposed to that promote obesity, and and promote metabolic dysfunction probably in other ways. Starting with some of the food obesogens you mentioned fructose. Yeah, that's the big one. How now how is it no BS a general how is it punching above its weight compared to say glucose or some other comparable food?

Robert Lustig 11:41

Right? Absolutely. This this is what I've spent my entire, you know, obesity career. I have two careers. One was working on why boys are boys and girls with girls from the neck up. That was what I did for the first 20 years of my career and then for the second 20 Zhan obesity. But why is fructose a an obese surgeon unrelated to its calories, because glucose has calories, and glucose stimulates insulin and insulin drives weight gain. So glucose should be just as big a problem for obesity as fructose. It turns out that the reason is because of the way it is metabolized, and also what it does to the brain. So there are three reasons that fructose is worse than glucose in terms of obesity, and also metabolic disease like diabetes. And those three things are number one. Fructose is not metabolized in all the organs in the body like glucose is fructose is metabolized in the liver. So an entire fructose bolus, like a 20 ounce coke. You drink it, that fructose all goes to the liver, the glucose will go anywhere, but the fructose all goes to the left. So

Nick Jikomes 13:02

pound for pound, you're putting more stress basically on the liver on that one organ, gram

Robert Lustig 13:07

for gram right gram for gram. You're putting more stress on the liver, because it's all going to deliver because only the liver has the glute five transporter for fructose. So what does the liver do with the fructose once it's in there? Well, for glucose, what it does is it tries to turn it into glycogen, which is a storage form of glucose, which is non toxic and which basically, every liver has some and you know, marathon runners have more because they're running marathons. So they load up with pasta, very specifically to drive their liver glycogen stores. And that's where you want to put extra energy because glycogen is for lack of a better word non toxic, but fructose does not go to glycogen. Okay, there is no direct pathway from fructose to glycogen. It goes instead down to the mitochondria through the Indian Meyerhof or glycolytic pathway, which takes you from fructose to ask to Koay and then as to co a then enters the mitochondria and the mitochondria would then burn the gas to co a through the Krebs cycle to generate carbon dioxide and water and ATP. And the whole goal of this is ATP. So fructose overwhelms the mitochondria because the mitochondria are fixed, they have V max, maximum velocity, they can only they cycle can only turn so fast. The only way to make the cycle turn faster is to have more mitochondria. By the way, that's why exercise is good. You make more mitochondria. Yeah, that's a good thing. I'm not saying exercise is bad. But you know ultimately mitochondria and is a mitochondria and then you know, it's not like You can, you know, sort of pressure test the mitochondria. And if you overwhelm a mitochondrion, okay, it's not going to work better or faster. And so what happens is you overwhelm it, it can't deal with the load, it ends up sending out a compound called citrate. And the citrate leaves the mitochondria and through a process called the citrate shuttle. And then now that citrate is in the cytosol of the cell, and now the cell has to do something with that citrate, and what it does is it takes the citrate down to sto Co A the sto Co A gets bound to another sto Co A to make millennial Co A, and then the cell starts adding to carbon fragments on to that millennial Co A, and so builds from a two carbon string to a 16 carbons string, which we call Paul metate. And the liver only makes Paul metate and this process is known as de novo lipogenesis new fat making, this is how your liver turns sugar, fructose, in particular, into fat, Paul metate fructose deposited through this de novo lipogenesis. Now, once the palmitate is made, the goal is to package it in a form that can be exported out of the liver. And so it gets added to a glycerol molecule to make a triacylglycerol or serum triglyceride. And then that triglyceride gets packaged with a bo B 100 lipo protein, and now you've got this little molecule, which we call VLDL. Very low density lipoprotein. That's, and that's a bad one. And then that gets exported out of the liver. And now that your serum triglycerides have risen, because you have consumed to sugar to an excess amount of sugar, and then that VLDL can either be a substrate for adiposity because insulin will work on that VLDL to deposit in your peripheral subcutaneous tissue and now that grows or it can be potentially a driver of cardiovascular disease if it unloads in the arterial wall, okay, but but some of the triglyceride will be manufactured and we'll never make it out. It won't be packaged, in which case now you have a lipid droplet. Now you have fatty liver disease. When you have fatty liver disease, now your insulin signaling in your liver cell doesn't work anymore. Now you have liver insulin resistance, and that makes the pancreas have to make more insulin to make the liver do its job. And that has its own negative side effects. Because insulin is a mitogenic factor. It is a growth factor. It causes vascular smooth muscle growth, it causes glandular growth, therefore leading to cancer. So it actually increases cardiovascular disease, and it increases cancer risk. And it basically is the library driver of chronic metabolic disease Plus, you're putting so much extra stress on the pancreatic beta cell to make that insulin that you will ultimately burn out now you have type two diabetes. But there's only one problem. There are three okay, we have no we have now described one. Now let's describe problem number two. Right? You like barbecue? Oh, yeah. Yeah, me too. Yeah, why do we paint our ribs with barbecue sauce to get that nice caramel color and the caramel flavoring right that you know. So good right. White of bananas Brown. point is this is a reaction which is known as the my yard or the browning reaction. The browning reaction is the caramelization reaction. This is why if you take sweetened condensed milk and you put it in a pressure cooker, you will get putting that that's a way to make a very cheap dessert. But it turns white substance into a brown substance. Well, we are all Browning all the time as we speak. Okay, if I went in, if I was a cardiovascular surgeon and I opened up your sternum kick your, the cartilage ends of your sternum would be brown today. Okay, you're a young guy. Okay. Mine are even browner. Okay, they started out white. Now they're brown. And the reason is because of this mired reaction. It's occurring all over your body. It's a current one all of the time. It is a, you know, byproduct of life. There is no life without the mired reaction. But the goal is to make that mired reaction run as slow as possible. And the reason is because every time that mired reaction occurs, you are taking that protein and you're making it less flexible, you're making it less functional. Because there are these glucose or fructose molecules hanging off of it, which change its conformation. And every time that reaction occurs, you are releasing a reactive oxygen species.

Nick Jikomes 20:35

So this is all like an oxygen dependent thing. Absolutely. Completely oxygen.

Robert Lustig 20:39

Okay. So bottom line is, you don't want that mired reaction to occur fast. You can't stop it, but you want it to occur as slow as possible. Well, turns out because of the nature of the stereochemistry of the fructose molecule, fructose engages in that mired reaction seven times faster than glucose. And it generates 100 times the number of reactive oxygen species. So that is the aging reaction. That is the reaction that causes wrinkles. That is the reaction that closes cataracts. That is actually the reaction that causes cardiovascular disease. So more fructose, more sugar, more cardiovascular disease, having nothing to do with insulin, and having nothing to do with energy, just because of the stereochemistry of this molecule. So unrelated to calories. And finally, number three, remember I said there were three fructose stimulates the reward center in the brain. So there's an area of the brain called the nucleus accumbens is the reward center. It's where cocaine, heroin, nicotine, alcohol, shopping, gambling, social media, internet, gaming, pornography all work. Okay, they all generated dopamine signal. So the question is fructose does that does glucose? And the answer is glucose does not do that. Glucose activates other places in the brain, mostly the basal ganglia and the cortex. But it actually does not stimulate the reward center, only fructose stimulates the reward center. So a little sugar means you're going to have a lot more sugar because of that reward.

Nick Jikomes 22:26

So this is what's fructose specifically, that is the sort of addictive sugar among the sugars. Exactly.

Robert Lustig 22:32

Fructose is addictive. And in fact, on February 15, so just three days from today, Dr. Nicola Vina, who is a neuroscientist at Mount Sinai, and who actually discovered sugar addiction. I mean, she's the one who basically put it on the map and I are going to be at the Commonwealth Club in San Francisco, discussing sugar addiction, both from a biochemical and from a public health standpoint. And

Nick Jikomes 22:59

when when you say fructose is addictive, it's it's not a metaphor, it's literally tapping into the same mechanisms that a drug of abuse would tap into. Exactly

Robert Lustig 23:06

right. So people who say, Oh, I have a horrible sweet tooth. That's sugar addiction till proven otherwise. It's not euphemistic that is hardcore biochemical. So

Nick Jikomes 23:19

fructose, so So tell me if this is a fair summary of what you've told us. So far, fructose is more obesogenic than glucose because the body metabolizes it differently. Right. And among other things, that tells us the body doesn't treat a calorie from over here the same way it does a calorie over there. I see that. That's why it's a problem to think about the whole weight loss thing as simply calories in calories out. Exactly. Right.

Robert Lustig 23:44

So everyone thinks it's about calories. Now, why do we think it's about calories? Because 100 years ago, this guy named Wilbur Atwater took a bomb calorimeter and threw some fat in it and exploded it and threw some protein in and exploded it and threw some carbohydrate in and exploded it. And he came to the calculation, that fat burn that nine calories per gram, and protein, burn that four calories per gram, and carbohydrate burned at four calories per gram also. And so he said, Well, fat, obviously, is more energy dense, which is true, but that is absolutely true. That is more energy dense. That's why there is fat because it's an easier way to put more calories in storage. And take up less room. Yeah, that's a good thing, I guess. Right. But from the standpoint of utilization that has nothing to do with anything All right. And it turns out that, that fat, just because it's nine calories per gram doesn't mean it doesn't have value or that it has, you know, too much value for it. And it's the target for trying to fix obesity, because you need certain fats, and you don't need other fats. And when you basically go fat free, which we all did for 50 years, okay, we actually got sicker, because we actually needed the fats. And what we did was we loaded up on the carbohydrate. Remember all the pasta bars from the 1980s, you know, as everybody tried to go fat free. That was the worst thing that we could have ever done. Because all we did was we took something that was actually good for us in our diet, and substitute something that was bad for us in our diet. Another example, which I love is, you know, as a pediatrician, chocolate milk, you know, they took the fat out of the milk. And then the kids wouldn't drink it because it tasted like dishwater. And what they do, they added the chocolate, right? They took the fat out, which was good. And they put in instead the sugar, which was bad. Because this has nothing to do with calories. And so I that is my mantra, kill the calorie, you know, hashtag kill the calorie. And we have shown 50 ways from Sunday, why obesity is not about calories.

Nick Jikomes 26:28

So you've told us about a carbohydrate. obesogen? That was the whole fructose discussion, we talked about how fructose affects the body differently than glucose. And because it's processed differently, and it's because of the way it's processed. It's more obesogenic Are there any obesogenic fats and what I'm thinking of here, based on what you just said, and some other things that that I've discussed on the podcast recently, there's two types of fats I would like to get your take on. So one are the basically the seed oils, the Omega six polyunsaturated fatty acids, and the extent to which there will be some genic. Then maybe after that, I want to ask you about you know, you were just talking about milk and other things. Saturated fat, because we've I've been told my whole life that saturated fat is, is the really problematic one that will drive cardiovascular disease and, and other bad things. Right.

Robert Lustig 27:18

So let's start with the Omega sixes. Okay. And I do believe you had Chris cannot be on your show. Ready? Yes. You know, major proponent of getting rid of omega sixes, and I love Chris, you know, great guy. I'm not sure that omega sixes are obesogenic. Specifically. However, they are pro-inflammatory. And when you are pro-inflammatory, you generate insulin resistance. And if you generate insulin resistance, then that is obesogenic. So, in that respect, they may be obesogenic indirectly as opposed to directly because they are pro-inflammatory. Now, omega sixes you need them. It's not like you can do without them. If you didn't have any Omega sixes, you would be eaten by the maggots. Right. They are part of your defense system against foreign invaders. And the reason is because omega six fatty acids which are in seed oils in canola oil, soybean oil is famous for it. So they are the precursors to arachidonic acid. arachidonic acid is the precursor to virtually all of the pro-inflammatory cytokines: thromboxanes, eicosanoids. missing one production of prostaglandins, the gland is prostaglandins, right? Sorry. So you need them. But you don't need too many of them. And it is estimated that what we need is an Omega six to Omega three, which is anti inflammatory Omega six Omega three ratio of about one to one would be optimal. But you can only really achieve that if you live on a coast. And worth, you know, three to one, four to one maybe tops. Our current Omega six Omega three ratio is 20 to 25. To one based on how many processed foods you eat.

Nick Jikomes 29:25

And when that little that little comment you made about living near the coast was that alluding to seafood?

Robert Lustig 29:31

Yeah, basically, seafood has omega threes and the reason is not because the seafood makes omega threes. The seafood eats the Omega threes. The Omega threes are made by algae. Algae make omega threes. The fish eat the algae, we eat the fish. So we get our omega threes thirdhand and they are anti inflammatory. We're talking about three omega threes. Ala alpha linoleic NIC acid ALA and that you can find in vegetables. But alpha linolenic acid ALA is been shown to have cardiovascular protection but not neural protection doesn't get to the brain. The next one is EPA I cosa Penta II Noack acid that gets to the brain. And that improves neural transmission, and is absolutely essential for brain health. The problem is that EPA is the one that smells fishy. So not a lot of processed foods. And they're so

Nick Jikomes 30:38

fresh EPA smells fishy. It's not just oxidized up. Well,

Robert Lustig 30:42

more oxidized EPA will smell fishy or got it without question. I mean, there's a little bit of a smell but not not nearly as much. And then finally, the last one is DHA, docosahexaenoic acid. The DHA is necessary for neuronal structure. Now, the problem is that ala does not really get converted to EPA or DHA, the percent conversion of that in the body is extremely low, like less than 1%.

Nick Jikomes 31:16

So if you tried to get all of your omega threes through a purely plant based diet, would that be problematic for that reason?

Robert Lustig 31:23

Yes, yes. And so people who are on plant based diets really do need to take some form of Omega three supplementation, because ala alone is not enough. So they can take fish oil, but then they're not vegan anymore. Because it came from fish, they can take algal oil and stay vegan, and that's okay. But algal oil is primarily DHA, not EPA. So it still becomes a little bit of a problem. So personally, I think the right, the best diet, if someone asked me what the best diet was, I would say pescatarian. Because you can basically have the best of both worlds in terms of what's your you're eating and effects on the on the environment. That would be my my personal choice. But you know, it is what it is I still like barbecue. So anyway, Omega sixes are highly inflammatory, because they are the precursors to these inflammatory cytokines. We need to get those down. And Chris Kenobi has basically argued, I think, effectively that those Omega sixes are driving multiple different diseases as well, including, in his case, acute macular degeneration are in and you know, for good reason. So, omega sixes are an issue. And

Nick Jikomes 32:54

probably if we just had to put put it in one sentence, the best way to reduce Omega six intake is probably just to reduce processed foods generally.

Robert Lustig 33:02

In general. Yes, absolutely. Because that's where they're headed. And then finally, you asked about saturated fat. Yep. Now, we have been told, for time immemorial, that saturated fat is the bad guy. I am here to say that saturated fat is not the bad guy. Saturated fat is cardiovascularly. Neutral. It's neither good nor bad, but it is necessary. You need saturated fat in order to be able to make a decent membrane, decent cell membrane.

Nick Jikomes 33:38

So there's actually an analogy here, maybe with the Omega sixes, which is you don't want too many Omega sixes. But they are essential. Can we think a similar way with the saturated fats?

Robert Lustig 33:48

Yeah, pretty much. You know, saturated fat has certain advantages. Number one, because it's saturated. You can heat it to any level you want. Right, and it won't cause the isomerization at the double bond to turn sis fatty acids into trans fatty acids. And trans fats are the devil incarnate. Trans fats are the single most poisonous thing you can put in your body that we call food. I see.

Nick Jikomes 34:20

So trans fats are very, very bad. And is telling me if this is a fair statement. Anytime you heat an unsaturated fat to high enough temperature, you're running the risk of creating some transfer, correct?

Robert Lustig 34:33

That's exactly right. So we want unsaturated fats we have demonstrated the benefit and value of unsaturated fats like for instance, olive oil, olive oils, oleic acid. oleic acid is the endogenous ligand of a transcription factor in the liver called PPA our alpha bruxism proliferation activated receptor Alpha. It's one of the things that runs the liver. It's fuel gauge on the liver cell. It's a good thing. And you know, I'm for olive oil, and I got a lot of it upstairs. But But olive oil has a relatively low smoking point of 310 degrees Fahrenheit. So cooking with it could be a problem. So depending on how you cook, cooking with olive oil, especially if you put it in a frying pan and you heat it something up, you know to fry something in olive oil could potentially be a problem because you could be making trans fats at home. And the more double bonds that any given fat has, the more risk you run of creating trans fats at home. So

Nick Jikomes 35:43

this is why this is like deep frying and Omega six polyunsaturated fats is so problematic. Exactly,

Robert Lustig 35:51

exactly. But of course, that's what every State Fair has. So what what are you going to do? So so saturated fat gets away from that saturated fat will not I summarize, because there's nothing to summarize. And the smoking point of saturated fat is much higher, so you will not get into any trouble. Now saturated fat got a bad rap. Because of all of this very bad epidemiology that was done back in the 1950s and 1960s. Right. Like guy named Ancel Keys, who was sort of famous in the literature. He was a hero even appeared on the cover of Time Magazine. Okay, and now he is a villain, and has been appropriately vilified. He was the one who basically correlated saturated fat consumption with mortality due to cardiovascular disease back in the 1950s. However, when you look at the data to cherry pick that he cherry picked it. Okay, he published a volume of a very long volume that an 800 Page volume called The Seven Countries Study.

Nick Jikomes 37:13

Geez, I don't know is that big? Yeah, it's pretty big. And

Robert Lustig 37:17

onto page 262 of that volume. And I know because I took it out. And I made, you know, like a slide of it. He basically said that the reason that sucrose sugar consumption was associated with cardiovascular disease, was because of the Association of sucrose with saturated fat. In other words, doughnuts. And all the countries that he picked in his seven countries, even though they're 22, he picked the seven that made his case, the seven that showed the highest incidence of mortality from cardiovascular disease world donut eaters. And the countries that we're not, we're not donut eaters.

Nick Jikomes 38:03

So it was obscuring the story. You told us earlier about milk dose?

Robert Lustig 38:07

Exactly. Exactly. Those people were not just eating high saturated fat, they were also eating high sugar. And what he did was he basically dropped it out.

Nick Jikomes 38:17

Is it made it? I don't, I don't want to spend too much more time on Ancel Keys because everyone's to death about him. Is it established fairly well, that he intentionally cherry pick this data?

Robert Lustig 38:30

Well, intent is complicated, as we have learned in the last two years. I'm not sure I never asked him. I don't know that anyone ever asked him if he intended. But there were 22 countries. And when he published it, there were only seven. We have the data on the other 15 and they don't fit. So I don't know. You tell me. Did he or didn't he?

Nick Jikomes 39:00

Got it? Okay, one more question about saturated fat, I think is important. Can we were talking about saturated fat. But are there multiple types of saturated fat that we should be distinguishing and thinking about analogous to the way that we talked about Omega sixes versus omega threes?

Robert Lustig 39:18

Well, in fact, that's right. So you know, we've learned the calories not a calorie and by the way, a an amino acids not an amino acid. And we've learned to carbohydrates, not a carbohydrate. We've even learned a fiber is not a fiber. And of course, a fat is not a fat. So there are two types of saturated fats. Not one, two, there's red meat saturated fats. And then there's dairy saturated fats, and they are not the same either. Even though dairy comes from a animal that also provides red meat So like, why is that, but it's true. So it turns out red meat is filled with even chain, saturated fatty acids, C 16, and C 18 palmitate. And stearic. And those, as I've said, are cardiovascularly, neutral.

Nick Jikomes 40:17

Got it? Red meat, saturated fats, even chained, those are cardiovascularly, neutral,

Robert Lustig 40:22

neutral, neutral, not not good or bad. Not good or bad. Neither good nor bad. Dairy saturated fat, so like in milk turns out to be odd chain, saturated fatty acids, C 15, and C 17. And those are chain saturated fatty acids have a specific phospholipid signature on their tail end, which is why they stay in solution. Because after all, that, you know, is in milk, right? I mean, yes, the cream rises to the top of distal fat and milk, even after the cream rises to the top that the phospholipid you know, allows both the you know, the oil and the water if you will to mix. And so they turn out to actually be protective against cardiovascular disease

Nick Jikomes 41:14

protective,

Robert Lustig 41:15

protective, dairy saturated fat is protective. So cardiovascular disease.

Nick Jikomes 41:21

So are you telling us that there's no saturated fats that are clearly negative across?

Robert Lustig 41:27

All right? That's right. There are no saturated fats that are clearly negative.

Nick Jikomes 41:32

They're neutral if they're even changed, like red meat. And they're actually protective if they're are chained, like from dairy.

Robert Lustig 41:38

Exactly right. So you also have to know that, you know, the reason everybody made a brouhaha over saturated fats was this molecule that came out of your liver called LDL. Now we've already talked about VLDL. Well, LDL and VLDL are not the same either. Okay, what makes VLDL sugar? What makes LDL, dietary fat? Dietary saturated fat? Okay, so there's no question that dietary saturated fat increases your LDL. And there's also no question that in large population studies, LDL levels correlate with cardiovascular disease. That is also true. Okay, the hazard risk ratio for high LDL, and coronary heart disease is 1.3. So if you have a high LDL, high LDL, you're a 30% more likely to die of a heart attack than if you don't have a high LDL. Okay, that's real. And I'm not even saying it's not I totally subscribe to that 1.3. Turns out the public health community has identified 1.3 as sort of what's necessary for a public health effort. So if it was 1.29, we wouldn't even be having this discussion. Because it'd be we'd be below the threshold. But we're at 1.3. That VLDL that I told you about before, the hazard risk ratio for high triglyceride and coronary heart disease is 1.8. So if you have a high triglyceride, you're 80% more likely to have a heart die of a heart attack than if you have a low triglyceride. So which one is worse? The LDL or the triglyceride? will clearly the triglyceride. So why are we spending all this time worried about the LDL when we're not even focused on the triglyceride? And the answer is because we had a medicine for it.

Nick Jikomes 43:46

So that's why that's why when my mother, my late middle aged mother recently went to the doctor, and her LDL was high, but her triglycerides, let's find the doctor was immediately like you should be on a statin.

Robert Lustig 43:59

Well, that's what the guidelines say. And the guidelines suck. Because they're not taking into account this whole issue. In addition, there's not one LDL,

Nick Jikomes 44:16

there's two, and we don't normally measure the VLDLs. When you go to the doctor, is that accurate? Number

Robert Lustig 44:22

one, you don't well, you measure serum triglyceride when you go to the duct, but there are two LDLs. So the LDL is its own thing, that there are two LDLs. There's one called large buoyant or type A and there's another one called small, denser type B. And it's been shown that the large buoyant is the one that dietary fat raises, but the large buoyant and that by the alleged board is 80% of your LDL concentration in your blood. But turns out the large points are cardiovascularly neutral. That's why I said you know, for the most part that cardiovascular neutral, because the large buoyant LDL do not contribute to Number one, they're large. They're so large, they don't fit under the surface of the endothelial cell to start the foam cell formation process to actually drive the plaque. And they're buoyant, they float. So they take, they go through laminar flow in your arteries and arterioles. And they basically don't set up a chance for those particles to be able to actually get into the end of psyllium to cause problems. So large buoyant, are cardiovascularly neutral, because they're not contributing to the pathogenetic process of heart disease. Conversely, small dents, they're small. Okay, they're, you know, I mean, from an angstrom standpoint, they're about 10 angstroms, smaller than the large Boyens. You know, 273 versus 283 microns or so, or angstroms, or entrance, they are small enough to get under the surface of the endothelial cell. And they're dense, they don't flood. So they fall out of laminar flow, so that they can approach the endothelial cell surface, so they can get underneath, and then they oxidize, and now you've got oxidized, small, dense LDL, and now you've got a pathogenetic substrate for heart disease, no ifs, ands, or buts. So the bottom line is a facet of fat. And LDL is not an LDL. Okay, and, you know, this whole concept that we should go fat free to solve the problem, actually only created two more, it created both obesity and type two diabetes,

Nick Jikomes 46:52

yeah, created those problems, and it did not solve the one that we thought it would. Right. So,

Robert Lustig 46:57

you know, we need to rethink how we did this and where we came from. And basically, you know, when you when you make a mistake, you admit the mistake and you're right, the ship, you know, we have not admitted the mistake, and we have not righted the ship. And so that's what I spend all of my time, basically trying to, you know, get the medical community to, you know, you know, sort of get get with the Get with the program.

Nick Jikomes 47:25

So, given what you told us about statins and LDL and all that, in your opinion, what are the what, What characteristics does someone have that justify a statin prescription?

Robert Lustig 47:38

So, statins stop you from making your own LDL. Okay, that that is true. And by the way, full disclosure, I have been on a statin for 33 years. Okay, I went on my Sasha takeback, sir. 31 years, 31 years. I've been on a statin since 1993. And the reason is because every one of my family has heart disease. My grandfather died at age 44 have a heart attack. My father had his first heart attack at age 61. Okay, everyone in my family has rampid heart disease. My sister when the 40 years ago, when I worked at Rockefeller, she was a research subject in Jim Breslow, his lab, and my colleague, and good friend Elliot Britton did heparin test on her to demonstrate that she had familial hypercholesterolemia. So I am a heterozygote. Oh,

Nick Jikomes 48:34

really? Yeah. So, I already know you have a specific genetic reason for this. I have

Robert Lustig 48:39

a specific genetic reason. So I have been on a statin for 31 years. And I've also tried myself off the statin more recently, and my LDL popped up from 70 to 300. Again,

Nick Jikomes 48:53

and how common is this condition? How common are one of like, you got one and

Robert Lustig 48:57

500 500? Okay. Okay. So I'm not against that. And they probably, you know, the reason I'm still sitting here talking to, okay, for the right patient. And if you have familial hypercholesterolemia, either homozygous or heterozygous, you need them. Okay, so I'm glad they're here. I'm not anti statin. I want to make that very clear. However, having said that, okay. of the people who are on statins today, which is a whole lot of people turns out, probably four out of every four out of five people who are on him don't need him. They were put on him for what we call primary prevention. That is, they went to the doctor, they got their labs drawn, doctor said, Oh, your LDL is a little high. Let's put you on a statin. And the reason is because the guidelines say so. So if you don't put somebody on a stand, you're not following the guidelines. And the guidelines are based on this hazard risk ratio. 1.3 So the question is for primary prevention, do statins work? We've been using statins for over 40 years. for primary prevention, do statins work? The answer is many meta analyses have been done. And they all show up for primary prevention that is not having had a heart attack yet, just having a high LDL, no event. The mean increase in lifespan for being on a statin is four days. Four days. Now, when you think about the fact that 20% of people who go on statins, end up with some level of rhabdomyolysis, you know, that muscle breaks down, they end up with severe inflammation, and 20% have high blood glucose, they have hyperglycemia. Because statins interfere with mitochondrial function, that's why they work to get your cholesterol done. Okay. You know, that's not a good thing. So you're putting people at risk for four days of increased longevity? And, you know, incurring this huge side effect profile.

Nick Jikomes 51:27

So let's just restate this explicitly, as you when you say you're putting people at risk with a step at risk for what's the

Robert Lustig 51:34

the rhabdomyolysis and hyperglycemia

Nick Jikomes 51:37

hyperglycemia. And muscle loss Basically, yes.

Robert Lustig 51:41

So, you know, bottom line, if you have said, if you've already had a heart attack, if you've already declared yourself, okay? Or if you have familial hypercholesterolemia, like I do, then you absolutely need a statin. And then the data on statin use and longevity is very, very strong and very robust. So for secondary prevention, totally, absolutely. Sign up. You need it. And if you're, if it's primary prevention, and you don't have FH, I think this is, you know, real travesty.

Nick Jikomes 52:19

If you have type, let's say you have type two diabetes, no personal history of heart attacks, and you know, no family history that's abnormal. Its average family history with respect to cardiovascular disease. What would what would your general position be if statins are a good idea for a diabetic? No.

Robert Lustig 52:37

So if you have type two diabetes, the first thing to do is get rid of the type two diabetes. Everyone assumes that type two diabetes is this chronic, unrelenting, progressive, destructive degenerative process that will never get better. And you know, you're going to be on medicine, whether it's insulin or oral hypoglycemics for the rest of your life. That's the general Gestalt amongst the cognoscenti in, in medicine, garbage. absolutely not true. absolutely not true. Numerous studies now show that a ketogenic diet can actually reverse type two diabetes verta Health 77% of people who go on a ketogenic diet, reverse not ameliorate reverse their type two diabetes, just by getting rid of the offending agent and what is the offending agent? Well, what is type two diabetes, it is extreme carbohydrate intolerance. So if you're intolerant to something, what's the best way to deal with it? Get it out of your diet. That's how you deal with an intolerance. If you are lactose intolerant, get the lactose out of your diet, okay, if you have you know, if you have peanut allergy, get the peanuts diet, whatever it is that you have an intolerance to, you know, get it out of your diet. So, but yeah, so carbohydrate out of your diet, you are on a ketogenic diet. And it turns out a ketogenic diet will reverse reverse type two diabetes now, there are other ways to do it, too. It's not like you have to be on a ketogenic diet, but that is one way and what it does is it is the you know, the the the test case, it is the, it is the you know, theory of the of the argument, okay? That if you fix the diet, you can fix your type two diabetes

Nick Jikomes 54:48

so, you know, I have family members who are type two diabetic, they're on statins. They're not, they're not given clear dietary guidelines by their physician except to cut out basically junk food which Which by that they mean like candy and things like that, but they're told for example, eat as much fruit as you want. Does that make sense to you?

Robert Lustig 55:11

It's complicated but let me let me try to explain fruit. Okay, so yes get rid of candy but there's a whole bunch of other things you have to get rid of too in order to you know make that right. I guess the you know, the question is okay, get rid of candy shirt shirt. Is Cheetos food is Cheetos food yes or no? Oh, not calories calories is Cheetos food. So what is the definition of food? That's, that's what we need to know. So, go to the dictionary, man got one up here if you want, I'll read it to you. Okay, I've learned I've memorized the definition of food is a substrate that contributes to either the growth or burning of an organism that is food growth or burned. So, the question is, does Ultra processed food contribute to growth? My colleague Dr. Front months and ego or non at Hebrew University, Jerusalem, has now looked at this and has shown actually that ultra processed food inhibits growth. It inhibits skeletal bone growth inhibits trabecular bone growth inhibits long bone growth, it actually reduces calcium in cortical bone, okay. It changes it difficile function. Okay, so it is inhibiting growth. And we also know it hijacks growth for cancer. You know, because it basically fructose in particular does not need to be burned in the mitochondria. Right? So it

Nick Jikomes 56:55

sounds like you're saying there's an inhibition of natural or good growth. And there's actually it's actually stimulating pathological forms of growth, correct.

Robert Lustig 57:05

About burning. So mitochondria burn, right. Fructose, which is in virtually all Ultra processed foods, I mean, it's been added to 73% of the items in the American grocery store, on purpose. Any of its three separate enzymes necessary for mitochondria to do their job. It inhibits MP kinase, which is the enzyme that drives mitochondrial biogenesis. So you get make more mitochondria and fresher mitochondria. It inhibits a CAD L, A soakaway dehydrogenase long chain which is necessary to cleave the two carbon fragments to engage in beta oxidation in the mitochondria so that you can burn in the first place. And finally inhibit CPT one a carnitine palmitoyltransferase. One A, which is the enzyme which regenerates carnitine carnitine is the shuttle mechanism by which the fatty acids get from outside the mitochondria to inside the mitochondria. So basically, you can't even import the fatty acids to burn. So Ultra processed food does not contribute to growth and does not contribute to burning. So is ultra processed food. Food is Cheetos food. What do you think what I was asking when I asked him? Yeah, bottom line is we think it's food because it has calories. Can you name something else that has calories? That's not food? alcohol, alcohol. Alcohol is not food. There's no dietician on the planet who will say that alcohol is food. But alcohol is calories. It's got seven calories per gram about trans fats. Trans fats are nine calories per gram, or trans fats, food, trans fats, it used to be food. And in 2013, the FDA said no, actually, they're poison. So just because something has calories doesn't make it food. And that's the key. That's, that's what we have to impress upon the population. And that's a different message than they have been getting for the last 50 years.

Nick Jikomes 59:21

So, you know, I originally wanted to ask you about obesogens and in my mind, I had food and non food obesogens. But it sounds like the way you would frame it is actually none of them are foods really, we there's just some that we normally think of as foods, and then the ones that we already don't think of as foods. That's right. Because these are all you would just call all of these obesogens or contaminants or even poisons.

Robert Lustig 59:44

Absolutely. They happen to be in our food but that doesn't make them fruit. That's exactly right. So so then that let's go back to the question you asked me at the beginning that started this diatribe fruit What about fruit, because fruit has fruit sugar fruit has fructose. So is it not food? The answer is, fruit is okay. And the reason it's okay, is because not only does it have the poison, but it also has the antidote, which is a fiber antidote is the fiber. No,

Nick Jikomes 1:00:22

I fully recognize this. And and I accept the argument here. I think it makes sense for a healthy person. But let's say you've you've you're talking about someone with type two diabetes whose goal should be to reverse that. My inclination would be to say, Well, why don't you just cut out all of the fructose? So yes, the fiber will prevent you from absorbing it as quickly. But wouldn't a better strategy would be to just cut it out completely until you reverse the diabetes?

Robert Lustig 1:00:47

I agree with that. If you have diabetes, if you have type two diabetes, almost assuredly, you also have fatty liver disease. Okay, the correlation between fatty liver disease and type two diabetes is extremely tight. Okay, it's almost for sure that the reason for your diabetes is because your livers not working right. And because your livers not working right, your pancreas had to make extra insulin to make your liver work, right. And now your pancreas is burned out. And so you got to give your pancreas a chance to regenerate. And you know, and work properly, the only way to do that is to make your liver work properly. So you got to burn off that liver fat, you got to get rid of that liver fat in order to fix the problem. And ketogenic diet, we'll do that. And the reason is because the LDLs that the liver makes out of your dietary fat don't get clogged, only the VLDL that comes from sugar gets clogged, the LDL is get exported right out the VLDLs sometimes don't. So if you're clearing LDL, and you're not making VLDL, your liver has a chance to be able to heal itself. And so that, to me, is where it starts. So if you have type two diabetes, and you have fatty liver disease, which if you don't know it, I'm telling you, odds are you do best thing to do is give your liver arrest. And the best way to give your liver arrest is don't challenge it. And fructose is a primary challenge. And so if you're asking me if you have type two diabetes alre