Dr. Robert Lustig: How Sugar & Processed Foods Impact Your Health

Andrew Huberman:
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Robert Lustig. Dr. Robert Lustig is an endocrinologist, that is, he's a specialist in the function of hormones in the body, and a professor of pediatric endocrinology at the University of California, San Francisco. He has authored more than 100 peer-reviewed studies exploring how different types of nutrients, that is, food, impact our cellular functioning, our organ functioning, and thereby our health. During today's discussion, we discuss the idea of whether or not a calorie is indeed a calorie, and whether or not our body weight and body composition only reflects the number of calories we eat versus the calories that we burn. We talk about how different food types, that is how the different macronutrients, protein, fat, and carbohydrates, are processed in the body, and the important role that fiber and the gut microbiome plays in that process. And we pay particular attention to the topic of how different types of sugars, and fructose in particular, can indeed be addictive to the brain and can modify the way that hormones in the body, in particular insulin, impact our liver health, kidney health, and indeed the health of all of our cells and organs. Indeed, Dr. Lustig is an expert in how sugar impacts the brain and body. We talk about how certain types of sugars can indeed be addictive in the same way that certain drugs of abuse and behaviors can become addictive. So, in other words, how sugar actually changes the way that the brain works. And we discuss how the food industry, that is, the commoditization and sale of particular types of food, has altered the way that we eat and indeed the foods that we crave. Today's discussion covers all of that, and by the end of today's discussion, you'll have a thorough understanding of how foods are processed when they enter your body and how those different food choices are impacting your immediate and long-term health. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. And now for my discussion with Dr. Robert Lustig. Dr. Robert Lustig, welcome.

Dr. Robert Lustig:
Pleasure. Truly, just being here, being invited, high honor, really appreciate it. And it's not doctor, it's just Rob.

Andrew Huberman:
Okay, Rob. I've been looking forward to this conversation for a long time. I've seen your now famous, can we also say infamous, but famous YouTube video about sugar. We'll put a link to it in the show note captions. It's been viewed many, many millions of times.

Dr. Robert Lustig:
Yeah, and I still can't figure out why that is.

Andrew Huberman:
Well, I can.

Dr. Robert Lustig:
I didn't think my mother would watch it, and she didn't, but 24 and a half million people did.

Andrew Huberman:
Well, I think people are very interested in what to eat, what not to eat, and we'll start off simply talking about what most everyone believes and understands, which is that a calorie is a form of heat energy that's given off during the processing of some food bit or something. If that's mysterious to people, just understand that a calorie is a unit of energy. And I was taught, and still many, many people worldwide believe that a calorie is a calorie, meaning if I consume more calories in whatever form than I metabolize by thinking, feeling, moving, exercising, et cetera, then I will gain weight. And if I consume fewer calories than I burn, I will lose weight. And we could talk a lot about where that weight loss comes from. Does it come from adipose, body fat stores, or from muscle, or from protein, or muscle, of course, is protein, et cetera. But let's start off with, is a calorie truly a calorie when it comes to the processing of different types of calories?

Dr. Robert Lustig:
Everyone thinks that obesity is about energy balance. That is calories in, calories out, therefore two behaviors, gluttony and sloth. Therefore, if you're fat, it's your fault. Therefore, diet and exercise. Therefore, any calorie can be part of a balanced diet. Therefore, don't pick on our calories, go pick on somebody else's calories. This is actually what the food industry uses to assuage their culpability for the change in the food supply and the rise in obesity and chronic disease, like diabetes. Now, it is true that a calorie is that unit of energy that raises one gram of water one degree centigrade. And so therefore, a calorie burned is a calorie burned. I don't argue that. That's true. That's the first law of thermodynamics. But that doesn't mean a calorie eaten is a calorie eaten. That's not the same, and that's where people get it wrong. So let me give you some examples of how that calorie eaten is not a calorie eaten. You like almonds?

Andrew Huberman:
I do.

Dr. Robert Lustig:
Me, too. Almonds are great. You eat 160 calories in almonds. How many of those do you absorb? 130. You eat 160, absorb 130. Where'd the other 30 go?

Andrew Huberman:
In the processing of that food energy?

Dr. Robert Lustig:
No. Turns out the fiber in those almonds, both soluble and insoluble fiber, and by the way, fiber's sort of the key to the kingdom in this story Forms a gel on the inside of your intestine. The insoluble fiber, the cellulose, forms a fishnet, if you will, a latticework on the inside of your duodenum. The soluble fiber, which are globular, plug the holes in that fishnet. Together, they form a secondary barrier. You can actually see it on electron microscopy, a whitish gel. And that prevents absorption of those 30 calories. So yes, 130 get absorbed, but many of them don't. They end up going further down the intestine to the next part, called the jejunum, and that's where the microbiome is. Now, everyone knows about the microbiome nowadays. It's all the bacteria. We always say when women are pregnant, "You're eating for two." Well, we're always eating for 100 trillion. Now, they have to eat. Well, what do they eat? They eat what you eat. The question is how much did you get versus how much did they get? Well, if you ate almonds, they're getting those 30 calories. So even though you count the calories at your lips, that doesn't matter. What really matters is counting the calories at your intestinal brush border, okay? And they're not the same. So, if you feed your gut, that's a good thing because then your gut will take those calories and turn it into things like short-chain fatty acids, which end up being protective against chronic metabolic disease. Acetate, propionate, butyrate, valerate, those are actually good. They're anti-inflammatory, anti-Alzheimer's, because you fed your microbiome. So, even though you ate 160, you absorbed 130. So a calorie eaten is not a calorie eaten, because if you ate it with fiber, it wasn't for you. It was for your bacteria. But that's not the way you count them up. So that's problem number one. Problem number two, amino acids. So, we all eat protein. Let's say you eat too much protein. You have the porterhouse steak. All right? Now, if you're a bodybuilder, those amino acids might go to muscle, and you might increase your muscle mass because you're a bodybuilder, because you're putting excess force on those muscles, and you're growing those muscles. Okay. But let's say you're not a bodybuilder. Let's say you're a mere mortal like me.

Andrew Huberman:
Or let's say you're a kid going through puberty who's synthesizing a lot of muscle-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... not because they're lifting weights, because they're in growth spurts.

Dr. Robert Lustig:
But because testosterone's making it happen.

Andrew Huberman:
Right.

Dr. Robert Lustig:
Yeah, absolutely. But let's say you're not. Let's say you're just schlumped off the street like Joe Schmo, okay? And you eat that porterhouse. You've taken on all these amino acids. There's no place to store it other than muscle, so your liver takes the excess and deamidates that amino acid, takes the amino group off to turn it from an amino acid into an organic acid, and then that organic acid can then enter the Krebs cycle, the tricarboxylic acid cycle, what goes on in the mitochondria in order to generate ATP, the chemical energy that your body needs in order to power itself. Okay. Now that's a good thing. It takes double the amount of energy to prepare that amino acid for burning as it does to prepare a carbohydrate for burning.

Andrew Huberman:
Or fat.

Dr. Robert Lustig:
Or fat.

Andrew Huberman:
Because when you asked about almonds, why the 160 versus 130, I thought it was the processing. It turned out it was fiber. You're saying for protein, let's make it realistic for a really nice big porterhouse steak, which I love, by the way.

Dr. Robert Lustig:
Yeah. Me too.

Andrew Huberman:
Let's say 800 calories.

Dr. Robert Lustig:
Yeah. Well, it turns out-

Andrew Huberman:
How much of that is... So that's what goes in your mouth.

Dr. Robert Lustig:
Right.

Andrew Huberman:
My mouth.

Dr. Robert Lustig:
Right.

Andrew Huberman:
How much of it is actually eaten in, to stay with your calorie eaten is not a calorie eaten, in the processing of that, what percentage actually goes into your total caloric intake?

Dr. Robert Lustig:
Right. So about 10% of everything you eat goes to just maintaining body temperature. It's called the thermic effect of food. But when you're eating protein, you actually generate more heat, and the reason is because it takes two ATP to phosphorylate that organic acid as opposed to one ATP to phosphorylate that carbohydrate for consumption. So you actually have a net loss of energy because it was an amino acid versus a monosaccharide, a sugar. Now, you brought up fat. Fat doesn't need to be phosphorylated, so it actually doesn't have any thermic effect of food at that point. So, depends on what it is as to whether or not you have loss.

Andrew Huberman:
Okay. Let's make it actually realistic. A 1,600-calorie-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... porterhouse with a nice slab of-

Dr. Robert Lustig:
Butter?

Andrew Huberman:
... of grass-fed butter on there.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
I do this every once in a while, not often, but-

Dr. Robert Lustig:
Yeah. With some creamed spinach and maybe some mushrooms along the side.

Andrew Huberman:
Honestly, when I'm eating a porterhouse, I don't want to adulterate the taste-

Dr. Robert Lustig:
Okay

Andrew Huberman:
... with anything else except maybe some butter, maybe a salad-

Dr. Robert Lustig:
Okay

Andrew Huberman:
... afterwards.

Dr. Robert Lustig:
All right.

Andrew Huberman:
But let's say 1,600 calories of... It's got some fat in there, for sure.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
Let's say 1,000 of those calories is protein.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
The other 600 are fat.

Dr. Robert Lustig:
Something like that.

Andrew Huberman:
Something like that, depending on how marbled it is.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
Okay, so based on what you just said about the thermic effect of food and protein in particular-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... of that 1,000 calories, how much actually can we count? I'm not a calorie counter, but does one include as calories truly ingested?

Dr. Robert Lustig:
Well, if you ingested 1,600-

Andrew Huberman:
Well, that's what went in the mouth, but-

Dr. Robert Lustig:
Right. But in terms-

Andrew Huberman:
... what is going to go against your burn deficit.

Dr. Robert Lustig:
Right. So I would have to actually do the math to figure that out, but yeah, as a guess-

Andrew Huberman:
Yeah, back of the envelope

Dr. Robert Lustig:
... back of the envelope calculation, you're going to lose about 25% of that.

Andrew Huberman:
Wow. So we're talking 750 calories.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
So, and to translate this a bit, so what we're saying here is if you're somebody who is trying to lose weight or maintain weight, or perhaps even gain weight, you eat a 1,600 calorie porterhouse with a slab of butter on it, 600 of those calories we're saying, and this is just, is fat, of the remaining 1,000 calories, that all went in your mouth. But-

Dr. Robert Lustig:
So you count it at your mouth.

Andrew Huberman:
Right. But then when you compare it against your energy burn for that day to maintain temperature, brain activity, physical activity, really it's only 750 calories.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
That's a huge difference.

Dr. Robert Lustig:
Exactly, and another reason why a calorie's not a calorie. Now let's take the third. Let's take fats. So here we have omega-3s, heart healthy, anti-inflammatory, anti-Alzheimer's, save your life. And over here we have trans fats, the devil incarnate. Consumable poison, because you can't break the trans double bond. You don't have the desaturase to break that trans double bond. So it basically accumulates, lines your arteries, lines your liver, causes chronic metabolic disease, causes insulin resistance. Omega-3s don't even get broken down for energy. Because they're so important, they stay intact because your brain needs them, your heart needs them. Whereas trans fats can't be broken down because of that trans double bond. One, save your life, other one, kill you. They're both nine calories per gram if you explode them in a bomb calorimeter, because a calorie burned is a calorie burned, but a calorie eaten is not a calorie eaten because one'll save your life, one'll kill you. And finally, the big kahuna, the one that blows everything else out of the water, fructose and glucose. All right, now glucose is the energy of life.

Andrew Huberman:
So here we're talking carbohydrates. I think most of our audience will be familiar with the so-called macronutrients. So we talked about fat, in this case almonds.

Dr. Robert Lustig:
Right.

Andrew Huberman:
There's some fiber in there, probably a little bit of carbohydrate.

Dr. Robert Lustig:
Little bit.

Andrew Huberman:
Little bit. Talked about the porterhouse with butter.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Making me hungry already. That's protein and fat.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
Very little, if any, carbohydrate.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Should be zero, essentially. Maybe one-

Dr. Robert Lustig:
Zero. Zero.

Andrew Huberman:
Yeah. And then now we're talking about carbohydrates, and we're going to subdivide that into glucose and fructose.

Dr. Robert Lustig:
Right. Galactose basically becomes glucose in the liver, so we can dispense with that, unless you have a disease called galactosemia, which is about one in 20,000, and it causes neonatal meningitis and it's a disease, as a pediatric endocrinologist, I would take care of. But we can dispense with that for the moment. All right, so glucose, fructose. Glucose is the energy of life. Every cell on the planet burns glucose for energy. Glucose is so damn important that if you don't consume it, your body makes it. So it will take an amino acid and turn it into glucose.

Andrew Huberman:
That's gluconeogenesis?

Dr. Robert Lustig:
Gluconeogenesis. That's right. It will take a fatty acid and turn it into glucose, and specifically the glycerol portion of the triglyceride will turn into glucose. So the Inuit, they didn't have any place to grow carbohydrate. They had ice, they had whale blubber. They still had a serum glucose level, and the reason is because you had to. You have to have a serum glucose level in order to power your brain, in order to power your heart. Yes, you can use ketones, of course you can, but only if you're in a ketogenic state will you use exclusively ketones. And you also need glucose for structural changes in specific proteins and particularly hormones. So glucose molecules will stud TSH, LH, FSH, different pituitary hormones, in order to increase their potency. It's one of the reasons why aging leads to defective hormonogenesis. For instance, hypogonadism, hypothyroidism is the loss of glycosylation on individual peptide hormones because of the inability to add glucose to those-

Andrew Huberman:
Because of insulin insensitivity

Dr. Robert Lustig:
No. It's an aging phenomenon.

Andrew Huberman:
Okay. We'll come back to this because I think it's really important.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
The idea that ingestion of carbohydrates and the, as you called it, the studding of carbohydrate molecules on hormones can augment the function of those hormones. And with aging, that's a less efficient process.

Dr. Robert Lustig:
It's a less efficient process, but it's not because of consumption. It's-

Andrew Huberman:
Right. I see the plenty of folks who are 65 and older eating plenty of carbohydrates.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
You're saying a lot of them have deficient thyroid-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... testosterone, estrogen-

Dr. Robert Lustig:
Right

Andrew Huberman:
... prolactin, et cetera, because of the way those carbohydrates are not studding the hormones.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
Interesting.

Dr. Robert Lustig:
So all of those are glycoprotein hormones.

Andrew Huberman:
Let's tee that up for later because I think that's an interesting-

Dr. Robert Lustig:
Yeah, it's a very important

Andrew Huberman:
... avenue to go down.

Dr. Robert Lustig:
Okay, and there's a disease in children, in babies called congenital disorders of glycosylation, where you can't put glucose molecules on specific proteins, and it causes severe mental retardation, all sorts of metabolic havoc, and a lot of those babies die for that matter. So that's an important thing. All right. But that's how important glucose is. Fructose, on the other hand, this sweet molecule, the molecule we seek, the reason why the food industry studs every food in the grocery store, 73% of all items in the American grocery store Have added sugar on purpose, for the food industry's purposes, not for yours, because fructose is addictive. Activates the nucleus accumbens, the reward center of the brain, in the same way that cocaine, heroin, nicotine, alcohol do, and drives dopamine receptors down, just like nicotine, alcohol, cocaine, heroin do. That molecule, fructose, is number one, completely vestigial to all vertebrate life. There is no biochemical reaction in any vertebrate that requires dietary fructose. That's number one. Number two-

Andrew Huberman:
Okay. Sorry, I'm going to just insert. So you're saying that even though we can process fructose-

Dr. Robert Lustig:
We have a limited capacity to process it in the same way we have a limited capacity to metabolize alcohol.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
Now, if you have one drink a day, you're okay. If you have two drinks a day, depends on how big you are. You and I can probably do two.

Andrew Huberman:
I would argue two drinks a week is the maximum, but let's not go there.

Dr. Robert Lustig:
Sure.

Andrew Huberman:
When you say processing of fructose is vestigial, what you're saying is that we don't need to do it.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
It's like the appendix. It's an organ for which it has no function.

Dr. Robert Lustig:
Exactly. And fructose has no function in the human body, period.

Andrew Huberman:
You don't need it.

Dr. Robert Lustig:
You don't need it.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Don't need it. But our diet is replete with it. In fact, our fructose consumption's gone up 25 fold since the beginning of the last century.

Andrew Huberman:
I have to ask this now. I love fruit.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
I eat berries galore.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Especially since the price of berries seems to have come down.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
It used to be that you only get them certain times a year.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
I'm what you call a drive-by blueberry eater.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
So I'll just walk past and just take a fistful. You can't put them in front of me without me eating them.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
This is even difficult for me when other people I don't know are eating them.

Dr. Robert Lustig:
Right.

Andrew Huberman:
So, I eat lots of blueberries-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... strawberries, blackberries if they're in season.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
I love them.

Dr. Robert Lustig:
No problem.

Andrew Huberman:
Loaded with fructose?

Dr. Robert Lustig:
No.

Andrew Huberman:
Plenty of fiber, low fructose?

Dr. Robert Lustig:
Low fructose.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
In berries, berries are the lowest fructose-

Andrew Huberman:
Thank goodness

Dr. Robert Lustig:
... of all the different fruits.

Andrew Huberman:
I was so worried about asking you this today.

Dr. Robert Lustig:
Not a bit.

Andrew Huberman:
Thank you. Okay.

Dr. Robert Lustig:
And fruit is okay because of the fiber. So the molecule, the fructose molecule's the same, whether it's in a berry or in a banana or for that matter, in a Coca-Cola. The fructose molecule is the same molecule. The difference is that in the berry, it comes with a whole lot of fiber. In the banana, it comes with a whole lot less fiber. And in the Coca-Cola, it doesn't come with any fiber. And the fiber is what mitigates the absorption. So when you consume the fructose with fiber, so your blueberries, you're feeding your microbiome. That fructose wasn't for you.

Andrew Huberman:
Got it. Such a relief, and I must say, recently I had a whole body MRI as a-

Dr. Robert Lustig:
Okay

Andrew Huberman:
... preemptive thing.

Dr. Robert Lustig:
How was that?

Andrew Huberman:
It was great. I got to watch Netflix in there.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
And I'd never had a whole body MRI. I learned a few things that were useful to me.

Dr. Robert Lustig:
Right.

Andrew Huberman:
I've got a clean bill of health, so that's great.

Dr. Robert Lustig:
All right. Well, that's good.

Andrew Huberman:
But one of the pieces of feedback I got is that my gut was filled with this very high contrast stuff.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And they asked, "Do you consume a lot of blueberries?" And I said, "Indeed I do. Why?" And they said, "Because that high contrast of it shows up white on the scan-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... is high concentrations of magnesium-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... that we see in people that ingest large amounts of blueberries, which is pretty rare.

Dr. Robert Lustig:
Hmm.

Andrew Huberman:
And yours are comparable to a bear in blueberry season."

Dr. Robert Lustig:
Wow.

Andrew Huberman:
And basically, my entire gut was filled with blueberries. I suppose I need to cut back a little bit. But now I know that fruit is okay, especially if the fruit has a lot of fiber.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
But fructose itself, especially if it's not partnered with fiber-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... is first of all, not required for survival at all-

Dr. Robert Lustig:
Right

Andrew Huberman:
... but you're telling me is problematic.

Dr. Robert Lustig:
Yeah. And let me tell you why it's problematic. We haven't gotten to that yet. We're just talking about whether it's vestigial versus needed. Now, let's talk about what fructose does. Turns out fructose inhibits three, count them, three separate enzymes necessary for normal mitochondrial function. Now, Eyal, your mitochondria make ATP. Your mitochondria have to work at peak efficiency. That's what metabolic health is, is mitochondria working at peak efficiency. Well, there are three enzymes that are inhibited by fructose. Number one, AMP kinase. All right? Now, AMP kinase is the fuel gauge on the liver cell. It's the thing that tells the liver to make more mitochondria, fresher mitochondria. Because if your AMP levels are high, that means you've dephosphorylated a bunch of ATPs and you have to regenerate them, so you need some more mitochondria. So it's a negative feedback pathway. Well, you need that AMP kinase to generate that mitochondrial biogenesis signal. Except that fructose, a metabolite of fructose called methylglyoxal, MGO, sits in the active site of the gamma subunit of that AMP kinase and actually binds to arginines in that active site, rendering that enzyme now dead. It's an irreversible inhibition because of the covalent bonding of that methylglyoxal, that aldehyde, to the arginine, and now that enzyme is dead.

Andrew Huberman:
Okay, so it basically acts like a key that doesn't turn the lock but prevents the key that you want in that lock-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... from entering the lock.

Dr. Robert Lustig:
Yeah. It's like gluing a lock shut. Yeah.

Andrew Huberman:
Got it.

Dr. Robert Lustig:
All right?

Andrew Huberman:
So that's one of the enzymes.

Dr. Robert Lustig:
That's one.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Second one, ACOD L, acyl-CoA dehydrogenase long chain So this is necessary to cleave two carbon fragments off fatty acids to prepare them for metabolism. So it inhibits that one. And then finally, it inhibits carnitine palmitoyltransferase 1, CPT1. Now, that's the enzyme that regenerates carnitine. Carnitine is the shuttle mechanism by which you get the fatty acids from the outer mitochondrial membrane through to the inner mitochondrial membrane so that they can be beta oxidized for energy. So if you don't have that CPT1, you're basically carnitine-less, and therefore, you can't generate beta oxidation.

Andrew Huberman:
You said fructose inhibits all three of these enzymatic pathways.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
As a biologist, I have to ask you, how potently does it inhibit them? I mean, because there are drugs that block receptors, and then there are drugs that block receptors with unbelievable affinity.

Dr. Robert Lustig:
Sure.

Andrew Huberman:
So, I mean, mechanistically in a dish, meaning in vitro, you can see all sorts of things. But how significant is this for obesity, for mitochondrial function in vivo in us?

Dr. Robert Lustig:
All right. So look, the dose determines the poison, right? Paracelsus, 1537. There are toxins that are parts per billion and will kill you, like sarin, ricin, cyanide. By the way, cyanide's a good analogy because it's working on mitochondria. It's basically causing mitochondria to be completely defective. All right? Then there are intermediate toxins like arsenic and carbon tetrachloride, parts per million, and they take a little longer to work. They're not going to kill you on the spot.

Andrew Huberman:
That's why I can eat an apple seed that has a little bit of arsenic in it, but I'm not going to die.

Dr. Robert Lustig:
Right. And by the way, tobacco smoke goes in there. And then finally, you have weak toxins, where it's not one exposure that will kill you, it's 10,000 exposures that'll kill you, like alcohol.

Andrew Huberman:
Or toxic people.

Dr. Robert Lustig:
Yeah. Or toxic-- Well

Andrew Huberman:
Sometimes it only takes one.

Dr. Robert Lustig:
Depends on how toxic.

Andrew Huberman:
I couldn't resist. Sorry. Sometimes it only-- Mildly toxic people.

Dr. Robert Lustig:
Anyway, the point is that fructose is in that last category.

Andrew Huberman:
Hmm.

Dr. Robert Lustig:
So it's not what you do one day that kills you. It's what you do every day that kills you. And if you basically eat ultra-processed food high in sugar for 10 years in a row, it's going to show up in terms of your comorbidities. And ultimately, yeah, it will kill you. And we have the data to show how many years you will lose. So right now in America, we pay an eight-year longevity tax. If you look at Japan, they have a mean age of death of 88. We have a mean age of 80. Okay? We're paying an eight-year longevity tax just by living here. And we're talking about the healthy people. Now, if you have obesity, it's a 15-year longevity tax, and if you have metabolic syndrome, it's a 20-year longevity tax. That is primarily, not completely, but primarily sugar. It's also omega-6s. It's also trans fats, left over because now they're gone, but people are still suffering the ravages of the trans fats from the previous generation.

Andrew Huberman:
Are they gone? I do remember as a kid when we had margarine in our refrigerator. This was actually a big debate in my home.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
One parent, I won't identify which- ... was pro margarine. The other was pro butter, anti margarine.

Dr. Robert Lustig:
Right.

Andrew Huberman:
The marriage didn't last, but there were other reasons.

Dr. Robert Lustig:
That's probably why.

Andrew Huberman:
Yeah. I went butter.

Dr. Robert Lustig:
Yeah. Butter is fine. In fact, Time declared, front cover, "Butter's back." Margarine was the bad guy, without question. And we know now, but back when we thought a calorie was a calorie, we thought, "Oh, margarine, it's the same nine calories per gram." And we said, "It lowers your triglycerides." Bad idea. It was. Because what it did was it lined your liver because you couldn't break that trans double bond. And so they're now gone from our food supply.

Andrew Huberman:
They're illegal.

Dr. Robert Lustig:
They're illegal. They're banned. But you can make trans fats in your own kitchen by taking olive oil and heating it to beyond the smoking point. So they're not completely gone. They're just gone from ultra-processed food. So now sugar's the big problem because of these three enzymes that you are inhibiting. The point is, we started this with a calorie's a calorie. Well, if you are inhibiting mitochondrial function, then a calorie is not a calorie, is it?

Andrew Huberman:
You're reducing the intensity of the furnace.

Dr. Robert Lustig:
Yeah, exactly. So this whole calorie's a calorie just makes no sense. And it hasn't worked at any level, and there is no study that actually shows that cutting calories makes a difference. And I can show you voluminous data that shows that virtually every weight loss study that led to caloric restriction basically didn't work, not for any length of time.

Andrew Huberman:
Just to round out our earlier discussion, because I find it fascinating, and I know other people will as well. You talked about that 160 calories, that's actually 130 at the business end of things-

Dr. Robert Lustig:
Yep

Andrew Huberman:
... of almonds. We talked about the porterhouse steak with butter and the 25% reduction in what's actually, quote unquote, "eaten." And I'll get back to this because this, quote unquote, "issue." I think the problem is there's a lack of useful language to dissociate this stuff.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Even just calling fat, fat, people think it means it's going to make you gain body fat.

Dr. Robert Lustig:
Totally.

Andrew Huberman:
If we called it adipose tissue and lipids, we would've avoided this confusion. So I don't want to get there just yet, but I want to make sure with-

Dr. Robert Lustig:
Well, the food industry does this on purpose.

Andrew Huberman:
Really?

Dr. Robert Lustig:
Oh, absolutely. So they tell you a sugar is a sugar, which is not true. They tell you a calorie is a calorie, which is not true, and they tell you a fat is a fat Which is not true. Okay? This is very specifically... So when you're talking about sugar, are you talking about dietary sugar, or are you talking about blood sugar? Because blood sugar is blood-

Andrew Huberman:
Right

Dr. Robert Lustig:
... glucose.

Andrew Huberman:
Right. Or cholesterol

Dr. Robert Lustig:
And I never use-

Andrew Huberman:
Dietary cholesterol or circulating cholesterol or you know.

Dr. Robert Lustig:
Absolutely.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
Okay. So we-

Andrew Huberman:
Yeah

Dr. Robert Lustig:
... we've done this to ourselves, but the food industry has really promulgated it because we farmed out nutrition policy and information to the food industry, so they actually use this for their purposes. It's one of the problems in this field.

Andrew Huberman:
For the third category of macronutrients, carbohydrates-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... you differentiated glucose and fructose.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
If I ingest, let's say, a half a bagel, since we were talking about New York- ... your city of origin. They have great bagels. On the West Coast, eh.

Dr. Robert Lustig:
Yeah, I know.

Andrew Huberman:
Yeah. It's not the same.

Dr. Robert Lustig:
It's pretty pitiful.

Andrew Huberman:
The same with the pizza dough. It's like they claim it's the water. Whatever it is, it's different back there, and it's better.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
Half a bagel, let's say 250 calories.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
Mostly carbohydrate.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
This is an unlined, no cream cheese, no schmear as they call it back there. No cream cheese, no butter, none of that thing. Just half a bagel.

Dr. Robert Lustig:
Just a half a bagel.

Andrew Huberman:
250 calories. So that's what I ate. You're saying that a calorie eaten is not a calorie eaten. How much of that carbohydrate, given that it's probably most-- Let's assume it's mostly glucose. Let's do it this way.

Dr. Robert Lustig:
Yeah. It's polymerized glucose.

Andrew Huberman:
Okay. Polymerized glucose.

Dr. Robert Lustig:
That's what it is.

Andrew Huberman:
How much of that is actually utilized or burned versus the original 250?

Dr. Robert Lustig:
So if you look at what happens to energy in the body, 65% of that which is ingested goes to resting energy expenditure, just to power the body. 10% goes to the thermic effect of food, and then 25% goes to activity. That's the breakdown of where the energy goes.

Andrew Huberman:
And that's calories from fat, protein, and carbohydrate.

Dr. Robert Lustig:
Yeah, from everything together.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
And glucose is a perfectly good example of how that works. The point is, though, that when you ingest glucose, you're getting a big glucose excursion in your bloodstream, so you're getting a big glucose spike, and that glucose spike has to come down. Well, what makes it come down? The hormone insulin. Insulin is the bad guy in this story. The higher your glucose goes, the more your pancreas will release insulin in order to bring that glucose down. Well, it turns out that glucose rise was not benign. That glucose rise led to endothelial dysfunction. Transient, but nonetheless endothelial dysfunction.

Andrew Huberman:
Could you just remind people what endothelial cells are?

Dr. Robert Lustig:
The inside of your arteries, okay? And it will change blood pressure. We've got plenty of data to demonstrate how it changes blood pressure, and over time, that will cause coronary artery disease, that will cause kidney disease, et cetera. But it's the insulin response that is really the bad guy. Now, people think insulin is good because it lowers blood glucose. After all, diabetics take insulin to lower their blood glucose. Okay. Let's take a diabetic, a patient with diabetes. Blood sugar is 300. That's bad. We give him a shot of insulin in the arm. Blood sugar goes down to 100. Blood sugar went from 300 to 100. Okay. Where did the 200 points of blood glucose go?

Andrew Huberman:
I'm assuming that the insulin sequestered it.

Dr. Robert Lustig:
To where?

Andrew Huberman:
I'm assuming to the liver.

Dr. Robert Lustig:
To the fat-

Andrew Huberman:
Interesting

Dr. Robert Lustig:
... for storage. That's insulin's job. Insulin takes whatever you're not burning and puts it into fat for storage. Insulin is not the diabetes hormone. Insulin is the energy storage hormone.

Andrew Huberman:
How quickly does it do that? Because-

Dr. Robert Lustig:
Pretty quick

Andrew Huberman:
... if I'm having a very busy day-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... or the diabetic person is having a very busy day, and they're moving around a lot-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... then you've got insulin-bound glucose in the bloodstream, for how long?

Dr. Robert Lustig:
No, no. Insulin doesn't bind glucose. Insulin binds to its receptor-

Andrew Huberman:
Sure. Sorry

Dr. Robert Lustig:
... and allows for glucose transporters to work.

Andrew Huberman:
So, but for some period of time while that person is active, there's an opportunity to utilize that glucose.

Dr. Robert Lustig:
Well, yeah.

Andrew Huberman:
Right.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
So how quickly is insulin managing that glucose? We know that the spike comes down quickly, but the glucose is not available for energy utilization after, what? It's sequestered to the adipose, to the fat tissue, within an hour? Is that about right?

Dr. Robert Lustig:
So about 90 minutes. Yeah.

Andrew Huberman:
Okay. So that's fast.

Dr. Robert Lustig:
If you're active, if you eat a muffin, and you're active, okay, your muscles are going to take up that glucose irrespective of insulin. In fact, muscles are insulin independent. They have glucose transporters, but they are insulin independent because if they weren't, then every patient in diabetic ketoacidosis would be paralyzed.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
Okay? So glucose will end up in muscles irrespective of energy status and insulin status.

Andrew Huberman:
And in muscles, it's used as immediate fuel and glycogen?

Dr. Robert Lustig:
Both.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Immediate fuel and glycogen storage-

Andrew Huberman:
Okay

Dr. Robert Lustig:
... in the muscle. Absolutely. All right? Now, if you're active, then you will clear glucose into muscle, therefore, your blood glucose won't rise as much because it went into muscle, and therefore, your pancreas will put out less insulin because it doesn't have to clear as much from the bloodstream. And that's okay. That's good. Right? But let's say you didn't exercise, so you've got a big glucose excursion, now you have a big insulin response, and that insulin is going to take the excess that's in your blood, it has to clear it, and it will go to fat for storage. That insulin rise turns out to be particularly egregious in terms of metabolic disease, and I can prove it There is a mouse, my favorite mouse. I love this mouse. This mouse turns medicine on its head and teaches every doctor why they have to go back to medical school and learn it right. This mouse is called the Podirko mouse, P-O-D-I-R-K-O.

Andrew Huberman:
Is it discovered by a Podirko?

Dr. Robert Lustig:
No. No. It was manufactured in Ron Kahn's lab. So this is a tissue-specific insulin receptor knockout mouse.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
I-R-K-O, insulin receptor-

Andrew Huberman:
So it lacks the insulin receptor in a specific-

Dr. Robert Lustig:
In the kidney

Andrew Huberman:
... in the kidney. Interesting.

Dr. Robert Lustig:
Podirko, glomerular podocyte insulin receptor knockout mouse.

Andrew Huberman:
Okay. We haven't talked too much about transgenic models and knock-ins and knockouts, so just in 10 seconds or less, basically, these are mice that are genetically engineered to lack the receptor for insulin, specifically in the kidney.

Dr. Robert Lustig:
Glomerular podocyte, the kidney.

Andrew Huberman:
In the kidney.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And everywhere else in this mouse-

Dr. Robert Lustig:
It's fine

Andrew Huberman:
... insulin does its thing normally.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
Okay, great.

Dr. Robert Lustig:
So these animals are euglycemic, normal blood glucose levels. These animals are normally glucose tolerant. So they go up, they go down just like every other mouse. These mice are not fat. These mice are not thin. These mice are mice, except they have the worst diabetic nephropathy on the planet.

Andrew Huberman:
So their kidney is degenerative.

Dr. Robert Lustig:
Their kidneys degenerate to nothing.

Andrew Huberman:
Yikes.

Dr. Robert Lustig:
Now, they have normal blood glucose levels. They have normal glucose tolerance. They have normal insulin tolerance, whole body. But their kidneys are dying. How come? Can't be the glucose. It's the insulin. Because insulin's the bad guy. Insulin's actually making the kidney disease. And so these animals that are insulin resistant, they have diabetic nephropathy without diabetes.

Andrew Huberman:
So the insulin is having a clearly negative effect on the kidneys without binding to the receptor.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
So circulating insulin can do stuff without binding to its receptor.

Dr. Robert Lustig:
Well, no, it binds to its receptor in different parts of the body.

Andrew Huberman:
Other parts of the body.

Dr. Robert Lustig:
Other parts of the body.

Andrew Huberman:
But in the kidney, it can't because it's a knockout.

Dr. Robert Lustig:
Because it's knockout, right. The point is, insulin does stuff by itself, and it turns out insulin drives growth. Now, every cell in your body wants to burn at one time in its life and wants to grow at another time in its life. Every cell has those two pathways, burning, growth, burning, growth. What determines whether a cell should be burning or whether a cell should be growing?

Andrew Huberman:
I don't know what makes it burning, but presumably it has something to do with mitochondria.

Dr. Robert Lustig:
It has everything to do with mitochondria. So every cell needs to burn and needs to grow at a different time in its life. Here's a way to think about it. We all start out as a zygote, a single cell. We end up an adult. Now, that single cell had to become two cells. Those two cells had to become four cells. Those four cells had to become eight cells, and on and on. So every cycle, there's a doubling. How many doublings to get from a zygote to an adult?

Andrew Huberman:
It's an exponential growth, so-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... I don't know it off the top of my head.

Dr. Robert Lustig:
Forty-one.

Andrew Huberman:
Forty-one?

Dr. Robert Lustig:
Forty-one. Two to the 41 doublings gets you to-

Andrew Huberman:
Gives you an organism?

Dr. Robert Lustig:
... 10 trillion cells.

Andrew Huberman:
We're 10 trillion cells?

Dr. Robert Lustig:
We're 10 trillion cells.

Andrew Huberman:
Do we know that?

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Two to the 41.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Okay, now, of those 41 doublings, some of them had to occur in utero, some of them had to occur postnatally. So I need two numbers that add up to 41. How many in utero, how many postnatally?

Andrew Huberman:
Well, you start off with a lot more than you end up with, but then you have cells that turn over throughout the lifespan, so this is a tough one.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
Because skin cells turn over.

Dr. Robert Lustig:
Sure.

Andrew Huberman:
With neurons, it's pretty straightforward because you're going to, at somewhere between three and ten-

Dr. Robert Lustig:
What you get is what you get.

Andrew Huberman:
Right. Well, and you're born with somewhere between three and 10 X of what you end up with, depending on the brain structure.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
But for whole body-wide, I don't know how you'd come up with that number.

Dr. Robert Lustig:
Thirty-six and five.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Thirty-six doublings prenatally, five doublings postnatally. And I can prove that to you, too. Typical baby weighs seven pounds. First doubling, 14 pounds, second doubling, 28 pounds, sixth doubling, 56 pounds, next doubling, 112 pounds, next doubling, 224 pounds. That's-

Andrew Huberman:
Hopefully it stops there

Dr. Robert Lustig:
... obese individual.

Andrew Huberman:
Hopefully it stops there.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
Not all people, 212 pounds are obese. But some people who are of certain heights or below are-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... 212 are obese.

Dr. Robert Lustig:
Okay. Point is, the cell has to know when to grow and when to burn. It turns out that the signal for that is oxygen, because oxygen's necessary for mitochondria to be able to burn. In the absence of oxygen, the cell only knows how to grow. And this is actually why Otto Warburg won the Nobel Prize in 1931 for the Warburg effect. He asked the question, how come cancer cells don't need oxygen to grow? And the answer is because no cell needs oxygen to grow. In fact, oxygen is the thing that prevents growth Famous article from the New England Journal of Medicine, 1951, "Mount Everest in Utero" because every fetus is oxygen deprived. So normal partial pressure of oxygen, 100 millimeters of mercury out here, right? If I checked your blood, it'd be about 100, right?

Andrew Huberman:
I hope so.

Dr. Robert Lustig:
How about a tumor cell?

Andrew Huberman:
I'm guessing tumor cell's probably... Is it double?

Dr. Robert Lustig:
About 44.

Andrew Huberman:
Wait, you just told me-

Dr. Robert Lustig:
Partial pressure of oxygen in a tumor cell is about 44.

Andrew Huberman:
But you just told me that, well, tumor cells, which grow like wild.

Dr. Robert Lustig:
Right. They grow like wild because they don't have oxygen.

Andrew Huberman:
So here's what's peculiar about it. Tumor cells are some of the most vascularized cells, or tumors are heavily vascularized.

Dr. Robert Lustig:
Well, they're trying to-

Andrew Huberman:
One way to try and kill one-

Dr. Robert Lustig:
To get nutrients

Andrew Huberman:
... is to devascularize the tumor cell.

Dr. Robert Lustig:
Right. Yes, and angiogenesis inhibition, et cetera, is a big deal. Judah Folkman and all that from Harvard.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
It's a big deal.

Andrew Huberman:
So the excess blood to a tumor is the attempt to bring in oxygen that it's not getting.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
As opposed to delivering lots of oxygen, and that's why it's growing.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
But a fetus, what's the partial pressure in the placenta?

Andrew Huberman:
I don't know.

Dr. Robert Lustig:
6 to 31. So it's actually like a mile above Mount Everest. That's how much oxygen the fetus gets. And it's for that reason that you've got 36 doublings. And then as soon as you're out, and you cut the cord and you start breathing and now your partial pressure's at 100, that's when growth slows down.

Andrew Huberman:
Has there been any effort to treat tumors by oxygenating tumors?

Dr. Robert Lustig:
Yes.

Andrew Huberman:
And what does that look like?

Dr. Robert Lustig:
It's hyperbaric oxygen therapy. It's a thing.

Andrew Huberman:
Oh, yeah.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Yeah. We will probably do an episode on hyperbaric chambers. The reason we haven't yet is it's pretty niche, but there are people who own these things, who sit in these things.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Okay, so we got here by way of the bagel.

Dr. Robert Lustig:
Right.

Andrew Huberman:
So I just want to orient us. You just had 250 calories of the bagel. We talked about glucose excursions.

Dr. Robert Lustig:
Right. But it's that insulin rise-

Andrew Huberman:
Right

Dr. Robert Lustig:
... that's driving the adiposity, and it's also driving the growth, okay? In the absence of oxygen, because if you have oxygen, then you don't need that much insulin.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Because you're going to burn instead of store.

Andrew Huberman:
Got it. In terms of the raw metabolism of carbohydrate, though, that glucose.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
If I eat 250 calories of glucose, how much of that did I, quote-unquote, "actually eat?" How much is used?

Dr. Robert Lustig:
How much is used?

Andrew Huberman:
Yeah. Let's assume that I'm at my desk working, or I'm walking around a little bit. I'm not exercising hard in the subsequent hour.

Dr. Robert Lustig:
So used for what, is the question. Used for-

Andrew Huberman:
I'm getting back to the calorie. Is a calorie a calorie? Clearly, the answer is no, based on the processing of different types of calories. We established it for fat, the almonds. We established it for protein.

Dr. Robert Lustig:
Right.

Andrew Huberman:
The porterhouse with butter. And now we're trying to establish that for the 250 calories of a bagel, which is glucose.

Dr. Robert Lustig:
Right. So the glucose has to be phosphorylated, so you're going to lose an ATP in the process. So ATP goes to ADP, and then that ADP will go to AMP, adenosine monophosphate, which will then go to IMP, inositol monophosphate, which will then go to uric acid.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
And that uric acid will be then released from the cell, circulate in the bloodstream, and hopefully go out in the kidney.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
In the process, that uric acid can inhibit mitochondrial function, and it can also inhibit endothelial nitric oxide synthase, which is the enzyme in your vasculature that is your endogenous blood pressure lowerer.

Andrew Huberman:
Right, by expanding blood vessels and capillaries.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
Right. This is the mechanistic foundation of the drugs that were originally used for improving prostate function, but are used to treat erectile dysfunction, which are the PDE-

Dr. Robert Lustig:
The PDE5 inhibitors

Andrew Huberman:
... inhibitors, which allow nitric oxide to be around longer and more of it, right?

Dr. Robert Lustig:
Right.

Andrew Huberman:
People use it for other purposes, too.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Now no one will forget if I cue it up with that example.

Dr. Robert Lustig:
Well, in the neonatal intensive care unit, it closes patent ductus arteriosus, which is a big deal in the neonatal world.

Andrew Huberman:
Well, okay. I want to ask you about that. So I heard two things. One is that glucose and the insulin that goes with it increases uric acid.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
Uric acid, while it has certain important functions in health, too much of it, you said, can inhibit nitric oxide.

Dr. Robert Lustig:
Yeah. Can inhibit nitric oxide.

Andrew Huberman:
So that means that the blood vessels and capillaries are going to stay more constricted-

Dr. Robert Lustig:
That's right

Andrew Huberman:
... so blood pressure is going to be higher than it would be normally.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
And then uric acid is also inhibiting mitochondrial function.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
Okay. But eating half a bagel isn't necessarily a terrible thing if it's within your caloric requirements.

Dr. Robert Lustig:
And it all depends on how much you clear and how high your insulin goes.

Andrew Huberman:
Now, let's compare that 250 calories of glucose to 250 calories of fructose.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Let's come up with a food example. 250 calories of fructose would be trivial to consume in the form of high fructose corn syrup, right?

Dr. Robert Lustig:
Well, so remember that high fructose corn syrup is half glucose, half fructose.

Andrew Huberman:
Oh, okay. So let's not use-

Dr. Robert Lustig:
So it'd be 125, 125.

Andrew Huberman:
So let's not use that. Well, so let's assume, so we can talk about a soda-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... to get that 250 calories easily.

Dr. Robert Lustig:
Right. Yep.

Andrew Huberman:
Especially if it's not a can or a European-sized bottle or can.

Dr. Robert Lustig:
Eight-ounce can of soda.

Andrew Huberman:
Okay. So eight-ounce can of soda And maybe let's include a food item. Let's talk like a store-bought packaged cookie.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
A couple of Oreos. Two Oreos.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
Probably get you to that 250 or maybe four Oreos.

Dr. Robert Lustig:
Maybe three Oreos, yeah.

Andrew Huberman:
Okay. Oreo lovers everywhere celebrating. Three, 250 calories of fructose. What's the effect on uric acid? What's the effect on caloric burn? What's the effect on anything for that matter that we should be aware of?

Dr. Robert Lustig:
All right, so first of all, the Oreo has plenty of fructose in it, so keep that in mind.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Let's say you consumed 250 calories in a bagel, because that's pretty much polymerized glucose, versus say the soda. So the bagel versus the soda, that's what you would ask.

Andrew Huberman:
Equivalent calories.

Dr. Robert Lustig:
Right. Equivalent calories.

Andrew Huberman:
Or the bagel versus, let's say, two Oreos and a little bit of... Yeah, two Oreos.

Dr. Robert Lustig:
Okay. So number one, there's only half the glucose in the soda because the other half is the fructose. So 125, 125. So your glucose rise won't be as high. Your glucose excursion will be lower. This is actually one of the reasons why there's this thing called glycemic index. And glycemic index is a canard. It's garbage. It is complete and utter BS.

Andrew Huberman:
The glycemic index?

Dr. Robert Lustig:
Absolute BS.

Andrew Huberman:
Okay. Oh.

Dr. Robert Lustig:
Nothing is more egregious in terms of argument than the glycemic index. And this is one of the things that dieticians promote and espouse, and one of the things that's got to go.

Andrew Huberman:
Okay, we'll-

Dr. Robert Lustig:
This is an idea that must die.

Andrew Huberman:
Okay, we'll get back to why the glycemic index has got to die. But so that 250 calories... And actually, can we make these equal, just for sake of simplicity? Can we say 250 calories of glucose from the bagel versus 250 calories of fructose? How do we get 250 calories of pure fructose?

Dr. Robert Lustig:
We don't.

Andrew Huberman:
You can't. Okay, you got to bring the glucose with.

Dr. Robert Lustig:
Lab fructose.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
You'd have to make it crystal fructose in a lab.

Andrew Huberman:
All right. Then let's stay with the Oreos, which is half glucose, half fructose.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
There is no fructose alone in nature.

Andrew Huberman:
Even crackers, some of the ones that are salty are also sweet. They have fructose in them.

Dr. Robert Lustig:
Yeah, absolutely.

Andrew Huberman:
High fructose corn syrup.

Dr. Robert Lustig:
On purpose.

Andrew Huberman:
Yeah. That's why it's impossible to eat just one.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
And so what's happening biochemically as a consequence of the fructose component specifically?

Dr. Robert Lustig:
So the fructose will, first of all, go into the intestine. The intestine will metabolize some of that fructose through what is known as intestinal de novo lipogenesis. About 10% of that fructose will be turned into fat right in the intestine.

Andrew Huberman:
And that's because fructose, it just wants to be fat?

Dr. Robert Lustig:
Yeah. Fructose wants to be fat. Fructose is the lipogenic substrate.

Andrew Huberman:
Here, we're not talking about body fat, we're talking about fat molecules that can potentially be used as energy.

Dr. Robert Lustig:
That's right. Triglyceride molecules.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Okay? So 10% of that fructose will be turned into triglyceride right in the intestine and be released into the bloodstream, and it is the reason for a postprandial triglyceride response.

Andrew Huberman:
Postprandial is, and I'm including myself in this group, is nerd speak for after eating lunch.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
Typically it's lunch.

Dr. Robert Lustig:
Indeed. So that's actually one of the drivers of cardiovascular pathology, that intestinal de novo lipogenesis, turning that fructose into triglyceride right in the intestine. Now, there's a limit to how fast and how much the intestine can do that. The rest of the fructose will be absorbed into the portal vein, but not before some of that fructose will make it further down and it will nitrate tight junction proteins. Now, let's talk about that.

Andrew Huberman:
Okay, portal vein of the kidney.

Dr. Robert Lustig:
Portal vein goes to the liver. Portal vein goes from the visceral, from the intestine, to the liver. That's the portal vein.

Andrew Huberman:
No kidney. It doesn't feed the kidney.

Dr. Robert Lustig:
No kidney.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
No kidney. Intestine to liver.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Okay? But fructose nitrates tight junction proteins. Now, let me explain that to your audience. Your intestine is a sewer. Definition of a sewer, a pipe with shit in it. Okay? That's a sewer. Our intestines are sewers. There's junk in the center, and the job of the intestine is to move the junk through to the anus, absorbing the good stuff while you can. The intestine is made up of cells, intestinal epithelial cells, that are bound together and they're bound with proteins that basically form a barrier. Those barriers are called tight junction proteins.

Andrew Huberman:
Things like claudins and things like that.

Dr. Robert Lustig:
Zonulin is the main one.

Andrew Huberman:
Zonulin.

Dr. Robert Lustig:
Okay, there are others, but zonulin is the one that is defective in celiac disease.

Andrew Huberman:
What defines a tight junction? Is it completely impermeable or semipermeable?

Dr. Robert Lustig:
Completely impermeable.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Unless its function is inhibited. Turns out, if you alter the phosphorylation status or the nitrate status of that tight junction, it will become transiently permeable.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
And so fructose nitrates tight junction proteins, causing them to be transiently permeable, allowing some of the junk in your intestine to get through into your bloodstream.

Andrew Huberman:
So this is leaky gut?

Dr. Robert Lustig:
This is leaky gut. This is what causes leaky gut. Fructose is a driver of leaky gut.

Andrew Huberman:
Got it.

Dr. Robert Lustig:
That causes inflammation at the level of the liver, which ultimately leads to systemic inflammation. One of the reasons why sensitivity CRP is high in patients who eat ultra-processed food.

Andrew Huberman:
CRP is C-reactive protein, which is a marker of essentially an inflammatory immune response.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
Yeah. You don't want it too high.

Dr. Robert Lustig:
And 93% of Americans today are inflamed.

Andrew Huberman:
Does that mean that 93% of Americans have leaky guts?

Dr. Robert Lustig:
Yeah. It does, because that's where it comes from.

Andrew Huberman:
So in addition to limiting fructose intake-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... what are things that support the tight junctions of the intestinal pathway?

Dr. Robert Lustig:
So there are three barriers in your intestine to keep the junk where it belongs, in the center, so that it can get pooped out your behind. All right? Three separate barriers. One is a physical barrier called the mucin layer. So it's a layer of mucus that actually sits on top of the intestinal epithelial cells. Now, that mucin is a polysaccharide, and the bacteria can use that mucin layer for its own purposes. It will eat your mucin layer if you don't feed your bacteria. You must feed your bacteria, or your bacteria will feed on you.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
Okay? So you are in concert with your microbiome. If you deprive your microbiome of the food that it needs, it will use you as its food, and that's one of the reasons why fiber is so important.

Andrew Huberman:
So fiber to build up this mucin layer is one way to reinforce the-

Dr. Robert Lustig:
Physical barrier

Andrew Huberman:
... the fence that is the tight junctions, et cetera-

Dr. Robert Lustig:
Exactly

Andrew Huberman:
... between your intestine and the bloodstream.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
This raises an interesting point about fasting. Many people, including myself, do a sort of pseudo intermittent fasting.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
I eat my first meal somewhere between 11:00 and noon. I'm not strict about this.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
The 11:00 versus noon thing, and probably eat my last bite of food somewhere around 8:00 PM, and occasionally it's outside that window. I've done this for a long time. It just feels best to me.

Dr. Robert Lustig:
Right.

Andrew Huberman:
But other people use a shorter eating window. One thing that I learned from a colleague at Yale-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... who studies the gut microbiome that was surprising to me is that when you eat in that way, there's a long stretch of time, sometimes longer for people that have a shorter eating window-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... longer fasting window, that is-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... where you're actually eating up your own intestinal lining. So this idea that fasting is so great for us, on the one hand might be true. On the other hand, you're actually consuming components of your... You're not feeding your gut microbiome, and you deplete it. But here's where I was positively surprised. When you do eat, provided that you eat enough fiber, and in particular, high quality fermented foods-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... low sugar fermented foods-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... it seems that the lining of the gut and the gut microbiome is replenished to a level that is greater than if you had eaten for longer periods of the 24-hour cycle.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Do I have that right?

Dr. Robert Lustig:
You do have it right, and I don't know why that is true, but it does seem to be the case. And fermented foods, in part because they've got already short-chain fatty acids in them-

Andrew Huberman:
Mm-hmm

Dr. Robert Lustig:
... seem to help.

Andrew Huberman:
Is that the preferred food of the microbiome?

Dr. Robert Lustig:
Well, it's what the microbiome actually turns fiber into. So it's probably helping your intestinal epithelial cells in the same way the microbiome turning fiber into short-chain fatty acids helps.

Andrew Huberman:
Got it.

Dr. Robert Lustig:
So it's what we call a postbiotic.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
So you have prebiotic, which is the food for the bacteria, you have the probiotic, which is the bacteria itself, and then you have the postbiotic, which is what the bacteria make in order to heal you.

Andrew Huberman:
Got it.

Dr. Robert Lustig:
Okay? And so short-chain fatty acids are postbiotics.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
And there are a lot of people selling short-chain fatty acids, drinks and supplements and what have you. Whether they work or not is another story.

Andrew Huberman:
If I consume fructose in the form of, let's say, a highly processed food, has minimal antioxidants, but it's got plenty of calories typically.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
And it's disrupting the tight junctions, making my gut leaky.

Dr. Robert Lustig:
Right.

Andrew Huberman:
But I'm also eating fiber.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
I'm having a meal that includes a salad. I'm having some probiotics.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And then I want a couple of Reese's Peanut Butter Cups, like the dark chocolate ones in particular. I don't do this anymore, but I used to eat like that more often. As time has gone on, I've become, I don't like to call it stricter, but I tend to like healthier foods over time.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
And I think you can get away with different things at different stages of life. Although you work with young people, very young people, so we'll get to this, but how much damage am I doing by ingesting any fructose in the form of a highly processed food?

Dr. Robert Lustig:
So I'll make it very simple, Andrew. I am for dessert. For dessert. I am not for dessert for breakfast, lunch, snacks, and dinner.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
Okay? So if you want to have a couple of Reese's Peanut Butter Cups as your dessert, in the same way as you might have a cognac for dessert, that's fine. I have no problem with that. The question is, are you going to eat Reese's Peanut Butter Cups for breakfast?

Andrew Huberman:
No, I don't eat breakfast.

Dr. Robert Lustig:
Well-

Andrew Huberman:
But no. I got it.

Dr. Robert Lustig:
The National-

Andrew Huberman:
But I see your point. Yeah

Dr. Robert Lustig:
... the National School Breakfast Program, which 29% of school children today consume, is a bowl of Froot Loops and a glass of orange juice.

Andrew Huberman:
Oh.

Dr. Robert Lustig:
That is 41 grams of sugar. American Heart Association says that the upper limit for children should be 12 grams of added sugar per day. That's 41 grams of added sugar, and it's just breakfast.

Andrew Huberman:
And that's fructose rich.

Dr. Robert Lustig:
Totally.

Andrew Huberman:
Right. Okay.

Dr. Robert Lustig:
Completely. So the question is, which dessert are we talking about?

Andrew Huberman:
Okay. Right, and can we adjust that morning meal to a different reality? Because I agree that there are plenty of kids eating that or a muffin that might be the equivalent.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
But what about the parent who says, "Okay, let's come up with a healthier option that the kid still likes," like a, I'm thinking back to my childhood, like a Honey Nut Cheerios or something. So not Froot Loops, which is kind of the extreme.

Dr. Robert Lustig:
Take a look at the side of the package.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
No difference.

Andrew Huberman:
And now let's say they go with some like ... waffles that are made. So with a pre-made mix, some milk, some butter, so mom or dad is making waffles. Great, it sounds healthier, but then if you do the breakdown and we're still ending up at very high, are we basically eating dessert for breakfast in that case too?

Dr. Robert Lustig:
Are we eating Eggo waffles or are we making waffles de novo from scratch in your own kitchen?

Andrew Huberman:
Let's say making-

Dr. Robert Lustig:
Big difference. Okay? Because the Eggo waffles, replete with sugar on purpose because the food industry knows when they add it, you buy more because it's addictive. Okay? And we actually have the demographic, the mechanistic, the imaging, and also the economic data to demonstrate that sugar's addictive and the food industry knows it. So have you ever heard of a phenomenon called price elasticity? Okay. Price elasticity is an economic term that is used to ask the question, if the price of a given good goes up by 1%, that should result in reduction in purchase or consumption, because price influences consumption. How much does it influence it? So if something's price elastic, when the price goes up, consumption goes down equivalently. A food that is price elastic, the most price elastic food is eggs. So when the price of eggs goes up 1%, consumption of eggs goes down 0.68%, meaning that eggs have a price elasticity of 0.32. Got it?

Andrew Huberman:
Got it.

Dr. Robert Lustig:
Now, what's the most price inelastic food? The top three most price inelastic foods are fast food-

Andrew Huberman:
Cereal?

Dr. Robert Lustig:
0.81.

Andrew Huberman:
Can I guess? I like a good quiz.

Dr. Robert Lustig:
Fast food 0.81, soft drinks at 0.79, and juice at 0.77.

Andrew Huberman:
Meaning people will pay not whatever, but they're willing to pay more, more readily willing to pay more.

Dr. Robert Lustig:
Because of the sugar. Because it's addictive. Because it's hedonic. So many years ago, Andrew, you probably remember something called Keynesian economics.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
And Keynesian economics was based on this concept of the rational actor. And the rational actor can determine value, which is utility over cost. And if you're a rational actor, you should be able to say, "Yeah, I'll buy that, but I won't buy that." Right? Okay. In 1979, Daniel Kahneman and Amos Tversky, Nobel Prize winner Daniel Kahneman, described the irrational actor. Now, the irrational actor cannot determine value, and the reason is because he is risk-averse, so the cost is always too great. So the utility may be the same, but the cost goes up because that's why they have aversive tendencies, the irrational actor. Jeffrey Sachs has described the hedonic actor, who also cannot determine value because it doesn't matter what it costs. They need their fix. And this is what's going on, and the food industry knows it. And that's why every food in the store has been spiked.

Andrew Huberman:
We talked about dessert for breakfast in the form of cereals.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
Some of which are disguised or couched as healthier. I think of like Honey Nut Cheerios. It seems healthier than Froot Loops.

Dr. Robert Lustig:
It's not.

Andrew Huberman:
It looks healthier just by way of color. It looks kind of weedy color. And in terms of lunch, one of the things that I love about Europe is that the breads are amazing.

Dr. Robert Lustig:
Yeah. The breads are terrific there.

Andrew Huberman:
And I like them because they're not as sweet.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
And so a sandwich from, not every deli, but from a typical sandwich shop or that one makes with store-bought bread, sliced bread in the US-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... has a lot of fructose.

Dr. Robert Lustig:
It does.

Andrew Huberman:
I looked this up prior to our-

Dr. Robert Lustig:
It does

Andrew Huberman:
... discussion today. So in some ways, dessert is being woven into foods that parents and/or kids, everyone, thinks are savory, we're actually eating sweets.

Dr. Robert Lustig:
Exactly right.

Andrew Huberman:
But we don't taste them as sweet at a conscious level necessarily, right?

Dr. Robert Lustig:
But our taste buds do.

Andrew Huberman:
Right.

Dr. Robert Lustig:
That's exactly right. So the question is, why do they do that? So question for your audience. You buy a loaf of bread at the local bakery. How soon before it stales?

Andrew Huberman:
Two days.

Dr. Robert Lustig:
Two days.

Andrew Huberman:
At best.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
If it's really great bread.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
The better the bread, the quicker it stales.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
You buy a loaf of bread at the neighborhood grocery store. How soon before it stales?

Andrew Huberman:
Oh, you've got probably a week, and then there's the moldy pieces at the end- ... that if you're in college and you were me, you're trying to scrape that off.

Dr. Robert Lustig:
Well, it can last up to three weeks, depending.

Andrew Huberman:
Right. You could throw it in the freezer.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
You probably do that with the bakery bread, but it's never the same.

Dr. Robert Lustig:
Never the same.

Andrew Huberman:
It's never the same.

Dr. Robert Lustig:
So the question is, why is that? And the answer is sugar. The answer is sugar. So the grocery store bread had sugar added to it on purpose because when you bake it, the sugar does not evaporate. It stays in the bread, and the sugar is hygroscopic, meaning it holds onto water. This is a phenomenon that the food industry uses called water activity. Okay? And so it will hold onto water, and so it will stay spongy, and it will not stale as quickly as the bakery store bread, which did not have that sugar added to it. So even something as benign as bread has been turned into something that ultimately leads to chronic metabolic disease.

Andrew Huberman:
We've pivoted somewhat from carbohydrate divided into glucose and fructose to a discussion of sugar. Could you tell us the link between sugar and fructose?

Dr. Robert Lustig:
Yeah

Andrew Huberman:
So table sugar, what percentage of table sugar is fructose? What percentage of brown sugar is fructose? What percentage of the sugar that's added to food is high-fructose corn syrup on average?

Dr. Robert Lustig:
Yeah

Andrew Huberman:
Just because here what we're talking about is what you're describing as an intentional lacing of food-

Dr. Robert Lustig:
Indeed

Andrew Huberman:
... with something that's addictive, but that's also processed very differently at the level of the kidney, at the level of the liver.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And it's bad. It's a bad situation.

Dr. Robert Lustig:
Absolutely.

Andrew Huberman:
So when we talk about sugar, I think we need to be as careful in describing what we really mean as when we talk about a calorie.

Dr. Robert Lustig:
I completely agree. So for your audience, let's be very clear on definitions.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Let's not use the word sugar because it has multiple definitions. Let's use sucrose. Sucrose is what you put in your coffee. It's the crystals. Alright. It's cane sugar, beet sugar, the stuff that you... Teaspoons of, right? This was all that was available for many years. That is one molecule of glucose, one molecule of fructose bound together, for the chemists out there, an O-glycosidic linkage. Okay? The enzyme in your intestine called sucrase cleaves this O-glycosidic linkage in about a nanosecond. You absorb the two molecules separately. The glucose goes to the entire body, generates an insulin response. The fructose goes straight to your liver, generates fat. That's sucrose. High-fructose corn syrup is essentially one molecule of glucose, one molecule of fructose, not bound together. No O-glycosidic linkage. So they're free. The enzyme sucrase doesn't care because the bond's already broken. Ultimately, they do the same thing, and that's why high-fructose corn syrup and sucrose are indistinguishable metabolically. What they are is they're very different economically, and the reason is because high-fructose corn syrup's half the price of sucrose. Because sucrose we get from importing, and high-fructose corn syrup we make at home. Sucrose is in bags. High-fructose corn syrup is in barrels. Sucrose you can sell at the store. High-fructose corn syrup you sell to the ultra-processed food manufacturer. You can't buy high-fructose corn syrup at the grocery store. So they're very different in terms of what they're used for. High-fructose corn syrup is particularly egregious because it's so miscible, because it's already a liquid. So you probably remember Chips Ahoy! cookies in the old days. Okay. Often it would seem like the sugar in the cookie had crystallized because the-

Andrew Huberman:
Mm

Dr. Robert Lustig:
... sugar content was so high.

Andrew Huberman:
It's been a while since I've had one. They weren't particularly good.

Dr. Robert Lustig:
Yeah. Well, now-

Andrew Huberman:
But you eat two of them, and then you think they're good, and then you want to eat four.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
That's what's so odd. The first bite is kind of like ugh.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
And then it's bombs away.

Dr. Robert Lustig:
There you go. Well, now it's chewy Chips Ahoy! cookies.

Andrew Huberman:
Oh, I remember-

Dr. Robert Lustig:
And the reason-

Andrew Huberman:
... the chewy Chips Ahoy! cookies

Dr. Robert Lustig:
... Remember chewy Chips Ahoy!

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
Well, that's high-fructose corn syrup. Because the two molecules are free, they don't crystallize, so you can actually up the dose.

Andrew Huberman:
Several times throughout today's discussion, you've been talking about the, quote-unquote, food industry.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
Okay, so I'm not a conspiracy theorist.

Dr. Robert Lustig:
I am.

Andrew Huberman:
But I-

Dr. Robert Lustig:
Now

Andrew Huberman:
But I understand that most businesses exist to make money.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Many businesses start off with good intentions and drift in order to stay competitive.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And many businesses, as we know, not all of which are entirely bad, such as the pharmaceutical industry, right? There are bad, there are instances of the opioid crisis, but then there are drugs from the pharmaceutical industry that help save lives. That's my stance. The food industry, I think there are good actors and there are bad actors, but we're talking about the food industry here. Okay. Well, we can talk about the exercise industry, or we can talk about the podcast industry. You got good actors and bad actors.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
But what you've alluded to several times here, and you're more informed than I am, is a concerted effort to lace food with a form of sugar that makes people crave more of that food and that is causing metabolic illness, disrupting mitochondria, and on and on.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
And you're the physician, not me. You've worked with patients who struggle with obesity and for various reasons. Not me. And so we could probably spend hours, if not days, talking about all the terrible things that the, quote-unquote, food industry has done. But what do you think is the pure motivation, right? I don't think that they want people to be sick, but they want to sell product, and this sells more product. So then it raises two questions. Why is it that more people don't know this information, although many more will know after today's conversation. But and certainly in government, it's a mix, regardless of what side of the aisle you're on or if you're right in between.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
There are clearly people that care about the health of themselves and others, so I can understand how things might have gotten to this point, but what do you think are the barriers to getting people to appreciate just what a problem this is, and getting people to change their choices in terms of what they're eating? Are they truly addicted to the point where they are sick, they can't make good decisions like a drug addict who's highly addicted to heroin is a sick person. They have an illness, and they need treatment. But until they get that treatment, they can't make good decisions.

Dr. Robert Lustig:
Let's take an analogy. Alcohol. 40% of Americans are teetotalers, never touch the stuff.

Andrew Huberman:
40% don't drink?

Dr. Robert Lustig:
40% don't drink.

Andrew Huberman:
Great. I'm not a big fan of alcohol. I've never seen it make anyone better at anything that really matters.

Dr. Robert Lustig:
No, because it's-

Andrew Huberman:
Except drinking

Dr. Robert Lustig:
... it's also-

Andrew Huberman:
And that doesn't really matter

Dr. Robert Lustig:
... completely vestigial. There's no biochemical reaction in the body that requires alcohol. Okay? For the same reason, by the way, fructose. Forty percent are social drinkers. You know, can pick up a beer, put it down. I'm in that category. 10% are binge drinkers and 10% are chronic alcoholics. Okay? Now, do you deprive the 40% of social drinkers because of the 20% of binge drinkers and chronic alcoholics?

Andrew Huberman:
No.

Dr. Robert Lustig:
No.

Andrew Huberman:
I believe people should be in choice, but I believe people should know what they are doing so that they can be in choice.

Dr. Robert Lustig:
Well..

Andrew Huberman:
Right? I always say, and I said this about the alcohol episode, which turned out to be one of our most prolific episodes, where I said that more than two drinks, zero is better than any and more than two drinks per week, you need to do other things to offset that, and it's problematic. Those are what the data say. But I would say do as you want, but know what you're doing.

Dr. Robert Lustig:
Well, so I would say that that's exactly what the food industry wants you to think. That is the food industry's mantra, is you have your own choice. Personal responsibility. So the question is, does personal responsibility work? And the answer is no, it doesn't. Every public health debacle in the history of mankind started out as a personal health issue before it became a public health crisis. And you can pick your personal responsibility issue, whether it be exposures, whether it be addictions, whether it be infections. Bottom line is, ultimately, it required a societal response. Okay? We can talk about syphilis, we can talk about tuberculosis, ultimately needed a public health response. We can talk about teen pregnancy, we can talk about-

Andrew Huberman:
Tobacco

Dr. Robert Lustig:
... tobacco. Ultimately needs a public health response because the sheer enormity of it and the egregiousness of it requires that public health response. Well, turns out this is no different. In order to exercise personal responsibility, four criteria have to be met. Those four criteria are the following. Number one, knowledge. You have to have the knowledge, because if you don't have the knowledge, then how can you exercise personal responsibility? Well, in fact, the public's being kept from the knowledge. We're doing this now in part to entrain that knowledge, to get people to understand what the problem is.

Andrew Huberman:
Yeah, I consider myself pretty informed about nutrition and health, but already today, I've learned two dozen facts about processing of fructose and calories generally that I had no knowledge of prior.

Dr. Robert Lustig:
Well, that's good. Okay? Because it's not about the math, it's about the science. Okay? They want it to be about calories. So we have this thing called food science, we have this thing called nutrition, and we have this thing called metabolic health. They are not the same.

Andrew Huberman:
Mm.

Dr. Robert Lustig:
Food science is what happens to food between the ground and the mouth. Nutrition is what happens to food between the mouth and the cell. Metabolic health is what happens to food inside the cell. But all of the chronic diseases that we are suffering from, type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, cancer, dementia, fatty liver disease, polycystic ovarian disease, those eight diseases, which make up 75% of healthcare expenditures in this country today, are all inside the cell because they are all mitochondrial dysfunction, and there is no medicine that gets to the mitochondria.

Andrew Huberman:
Although you and others at Stanford, Harvard, et cetera, are starting this, with metabolic psychiatry being one instance, right?

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
And UCSF as well. Forgive me-

Dr. Robert Lustig:
Absolutely. Yes

Andrew Huberman:
... I should mention UCSF upfront. Your home institution, a wonderful institution right up the road from Stanford. So, things are changing. People are starting to think about mitochondrial health.

Dr. Robert Lustig:
They are.

Andrew Huberman:
Okay, so you list off the first thing, and you said there are four things that stand as bare-

Dr. Robert Lustig:
Right

Andrew Huberman:
... the first one was knowledge.

Dr. Robert Lustig:
Knowledge.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Second, access. Because if you don't have access, then how can you exercise personal responsibility?

Andrew Huberman:
Access to healthier alternatives.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
Which means cost-effective. I love berries from the farmers market more than I love berries from the store. I love the farmers markets generally, but it takes time, energy to go there.

Dr. Robert Lustig:
It does.

Andrew Huberman:
And the cost is actually lower at the level of what you hand the vendor, typically.

Dr. Robert Lustig:
Right.

Andrew Huberman:
But volume is tough to achieve.

Dr. Robert Lustig:
Right.

Andrew Huberman:
They actually have me at a quota. I'm not allowed to buy as many berries as I want- ... because obviously there are other people who want berries.

Dr. Robert Lustig:
Okay. Yep.

Andrew Huberman:
So there's that, right? People have to feed their family.

Dr. Robert Lustig:
Well-

Andrew Huberman:
We're used to eating a lot of volume

Dr. Robert Lustig:
... but you're able to at least go there.

Andrew Huberman:
Sometimes.

Dr. Robert Lustig:
Okay?

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
We're talking about people who live in, quote, "food deserts." We're also talking about people who live in food swamps. Okay? And when we're talking about food swamps, we're not talking about a plethora of healthy foods. We're talking about all the junk. They live in the swamp of junk. So if you live in the swamp of junk, how are you supposed to exercise personal responsibility? Number three, affordability. So you have to be able to afford your choice, and society has to be able to afford your choice. And right now, we can't afford that choice because healthcare costs right now are at $4.1 trillion a year.

Andrew Huberman:
But like so many things in behavioral economics and health, it's so hard for people to see that the immediate choice is leading to a higher cost down the road. There are just too many nodes of separation for people to realize, hey, when I'm reaching for this cereal as opposed to making waffles for my kids from scratch, or they're thinking time efficiency, cost efficiency, volume, the kids not throwing tantrums because they're no longer getting the cereal, and it's very difficult to see this is the reason why healthcare costs are going up. There are just too many nodes of separation.

Dr. Robert Lustig:
Well, couldn't agree more. But ultimately, it's because the government separates and silos food industry profits from healthcare costs. If you actually combined those, because they ultimately are the same, you would see the problem. So globally, the food industry grosses $9 trillion a year. Healthcare costs globally cost $11 trillion a year, dietary-related healthcare costs. Environmental costs cost $7 trillion a year, and productivity costs cost $1 trillion a year. So when you do the math, nine minus 11 minus seven minus one means that there is a $10 trillion a year deficit because of us cleaning up the mess that the food industry makes.

Andrew Huberman:
And while numbers like that-

Dr. Robert Lustig:
That's not affordable.

Andrew Huberman:
Right. I agree, and while numbers like that land really hard, I find that for myself and for many people, statistics like that are hard to keep in mind in a way-- There's something about the human brain that hears that and goes, "Whoa." We're like, "That war cost that much, and this food issue costs that much."

Dr. Robert Lustig:
Yep.

Andrew Huberman:
And then we go to the store, and we're hungry.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And the kids are hungry.

Dr. Robert Lustig:
They're needy.

Andrew Huberman:
And so those nodes of separation, it's almost like a neural/memory/prefrontal cortex issue to me. And of course, I look at everything through the lens of neurobiology.

Dr. Robert Lustig:
Me too.

Andrew Huberman:
Not everything, but most everything. And so how could I not? How could we not? But then the issue is, well, there's still food on the shelves. What do we do to bring closer together these nodes?

Dr. Robert Lustig:
So the question is-

Andrew Huberman:
What would the government do?

Dr. Robert Lustig:
So the question is, is there food on the shelves? Let me finish the fourth one, and then I want to come back to that point. Let me just finish a concept.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
So affordability. And number four, externalities. Your choice can't hurt anybody else. But what if your choice does hurt somebody else? So like for tobacco, secondhand smoke.

Andrew Huberman:
Right.

Dr. Robert Lustig:
For alcohol, drunk driving.

Andrew Huberman:
What was the argument for teen pregnancy, that someone else was going to have to raise the kids?

Dr. Robert Lustig:
Exactly. All right. But what about for food? Okay. Well, how about the fact that your employer, Stanford University, has to pay $2,750 per year in obesity-related healthcare expenses that they have passed on to you, even though you're not obese? That is affecting you. So that guy's obesity right there, that is affecting you.

Andrew Huberman:
Ah. But there, nowadays, it's especially tricky even to have the conversation. I'm willing to have it now.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Which is that-

Dr. Robert Lustig:
Let's have it

Andrew Huberman:
... there's this whole concept of fat-shaming, right? So if somebody's obese, whose fault is it? And if we even talk about it, are we subject to attack, legitimate attack? So calling someone obese at a clinical level, you're an expert in endocrinology.

Dr. Robert Lustig:
Don't talk about obesity. Let's talk about diabetes.

Andrew Huberman:
Okay, so talk about-

Dr. Robert Lustig:
Different-

Andrew Huberman:
... the consequence of obesity.

Dr. Robert Lustig:
Yeah. Let's talk about the metabolic health issue itself. Okay? The fact is that diabetes is now 11.4% of America.

Andrew Huberman:
What was it 20 years ago?

Dr. Robert Lustig:
20 years ago, it was about 8%.

Andrew Huberman:
I was wondering this earlier. 20 years ago, there was a lot more margarine in refrigerators, but people were thinner, and there was less diabetes.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Everything you told us about margarine and trans fats is that it's bad. Now, butter is back, as "Time" Magazine and you said.

Dr. Robert Lustig:
Right.

Andrew Huberman:
So clearly can't be the transition away from trans fats that's increased obesity.

Dr. Robert Lustig:
Well, no.

Andrew Huberman:
So it's going to be the increase in sugar and-

Dr. Robert Lustig:
It's the increase in sugar

Andrew Huberman:
... and these hidden sugars in foods.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
All right. The key, though, is Pakistan and India and China. They are not fat, but they have 14% diabetes rates, and they're thin. And the reason is because of ultra-processed food.

Andrew Huberman:
Are there any countries in the world that don't allow high-fructose corn syrup, or at least not at the level that we do?

Dr. Robert Lustig:
Oh.

Andrew Huberman:
Their frequencies.

Dr. Robert Lustig:
Boatloads. Okay? There are boatloads of countries that don't import high-fructose corn syrup or don't make it.

Andrew Huberman:
So Scandinavian countries?

Dr. Robert Lustig:
Scandinavian countries, most of Europe. Other than the Asia-Pacific Rim, so Japan has it. In fact, it was invented in Japan, 1966, Saga Medical School, Takasaki et al. Korea has it, but Australia does not have it. Thailand does not have it, but they have just as much of an obesity and diabetes problem as we do because they have sucrose. Because high-fructose corn syrup and sucrose are no different metabolically. So it doesn't really matter.

Andrew Huberman:
It's that one-to-one ratio.

Dr. Robert Lustig:
It's the one-to-one thing. Exactly.

Andrew Huberman:
Of glucose and fructose.

Dr. Robert Lustig:
So here's the question, Andrew. Okay. So I want to go back to that. You said all this food is still on the shelves. Is it food? What is the definition of food?

Andrew Huberman:
Can I give the definition I think most people would give?

Dr. Robert Lustig:
Go ahead.

Andrew Huberman:
That's not necessarily the one I would give.

Dr. Robert Lustig:
Go ahead.

Andrew Huberman:
But something that contains caloric energy. I could eat this microphone, but it's not going to provide much useful energy.

Dr. Robert Lustig:
The definition of food, straight from the dictionary, and believe me, I looked it up and memorized it.

Andrew Huberman:
I believe you.

Dr. Robert Lustig:
Substrate that contributes to either growth or burning of an organism.

Andrew Huberman:
Interesting.

Dr. Robert Lustig:
That is the definition of food.

Andrew Huberman:
Sounds pretty scientific for-

Dr. Robert Lustig:
100% correct. Growth or burning. So any substrate that passes your lips that contributes to either growth or burning, that's food. Okay, let's do it. Let's do burning first. I just showed you that sugar, which is the marker of ultra-processed food, and 73% of the items in the grocery store are spiked with sugar, inhibits burning. It inhibits those three enzymes involved in mitochondrial function. Now let's do growth. My colleague, Dr. Efrat Monsonego Ornan, who is the chairman of nutrition at Hebrew University of Jerusalem, actually looked at this question and showed that ultra-processed food actually inhibits growth. It inhibits cortical bone growth. It inhibits trabecular bone growth. It inhibits cancellous bone growth. It inhibits linear bone growth. It hijacks growth for cancer because it inhibits mitochondria, and so you have to then grow instead of burn.

Andrew Huberman:
And this was work that was done in vivo or in vitro?

Dr. Robert Lustig:
In vivo.

Andrew Huberman:
In vivo. So these are people that are eating high amounts of highly processed foods.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
How did you find those in the Middle East?

Dr. Robert Lustig:
In Israel, they found them. So the bottom line is, if a substrate does not contribute to growth and does not contribute to burning, is it a food?

Andrew Huberman:
I see the answer is no.

Dr. Robert Lustig:
Well, that's 73% of what's in the grocery store. So I would argue, you said the food's there. No, it's not. That's not food. In fact, it's consumable poison.

Andrew Huberman:
So this leads to an important question of what's left? You remove all that, what's left?

Dr. Robert Lustig:
Okay.

Andrew Huberman:
Just anecdotally, and what I sometimes call anecdata. I've had several friends in their-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... 40s and early 50s say they want to lose weight and get in shape. And the-

Dr. Robert Lustig:
Right

Andrew Huberman:
... the thing that's worked every single time for them to lose significant amounts-

Dr. Robert Lustig:
Right

Andrew Huberman:
... of weight quickly and keep it off, and many of them were already exercising but then also increased their exercise-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... was I just, since I'm not a dietician, nutritionist, or anything, I just say, "Eat meat, fish, eggs, vegetables, fruits. You're not going to eat starches. You're not going to drink alcohol. You're not going to drink soda. You can still have coffee, tea. You can still have artificial sweeteners."

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
We'll get to artificial sweeteners in a little bit.

Dr. Robert Lustig:
Yeah. We have to go there.

Andrew Huberman:
And the reason I say no starches, even though I personally eat rice, oatmeal, pasta, things of that sort, some in moderation, depending on-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... what sort of exercise I'm doing and how much-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... is because of the fact that nowadays many of those things contain fructose.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
And inevitably, every one of those people is blown away by the fact that it, quote-unquote, "works," and assumes that it's all because of reduced calorie intake overall.

Dr. Robert Lustig:
Nope.

Andrew Huberman:
And they lose anywhere from 30 to 55 pounds-

Dr. Robert Lustig:
Exactly

Andrew Huberman:
... and keep it off and they're like, "Hey, this is great. I can actually still eat rib eye steaks and salads" but they're not eating croutons. And so in some sense, it looks extreme. It sounds ketogenic, but it's nothing like that.

Dr. Robert Lustig:
No.

Andrew Huberman:
You're just saying, basically, you're eliminating processed foods, you're eliminating liquid calories in general, and on and on. And so there's nothing sophisticated about it and my question to you is, how much of that weight loss effect do you think is a calories in versus calories out effect, because they're eating a lot of food in some cases, and how much of it do you think is the elimination or near elimination of this fructose or this glucose-fructose combination?

Dr. Robert Lustig:
It's nothing to do with the calories. It has everything to do with the insulin. If you get the insulin down, you're not shunting energy to fat. You can lose weight. Your fat will give up the triglycerides stored in it as soon as your insulin goes down. Insulin is pushing on your fat cell all the time, and as long as your insulin's up, your fat cell can't release it. The minute your insulin goes down, you can now engage in what we call lipolysis. Hormone-sensitive lipase is an enzyme in the fat cell that is inhibited by insulin. As soon as the insulin's gone, hormone-sensitive lipase can turn that stored triglyceride into free fatty acids and glycerol and release it, and you can lose weight. So get the insulin down and it all works. So the question is, what makes insulin go up? Well, two things. Refined carbohydrate and sugar. Those are the two things that make insulin go up. In addition, branched-chain amino acids make insulin go up as well. Leucine, isoleucine, valine, which is in corn-fed beef, chicken, and fish. Processed food. All right. Here's the deal in one concept. My colleague, Dr. Carlos Monteiro, who is a professor of public health at the University of São Paulo, has done the world a great service. He has developed a system for categorization of food processing. It is called the NOVA system. It just means new. But he has basically categorized every food anywhere in the world into one of four classes. The easiest way to explain this would be an example. Let's take an apple. NOVA Class one would be an apple picked off a tree. NOVA Class two would be apple slices, de-stemmed, de-seeded, de-skinned, maybe. NOVA Class three would be apple sauce, cooked, macerated, possibly a preservative added, maybe some extra sugar, maybe not. NOVA Class four would be a McDonald's apple pie. Now, does that McDonald's apple pie look anything like that apple?

Andrew Huberman:
No.

Dr. Robert Lustig:
Is there even any apple in it?

Andrew Huberman:
Maybe a tiny bit.

Dr. Robert Lustig:
Maybe not.

Andrew Huberman:
Maybe a tiny bit.

Dr. Robert Lustig:
It's all flavor-enhanced, et cetera. Okay. It turns out, and this is epidemiologic data, but nonetheless prospective epidemiologic data, so it's not useless. That NOVA Class four, that ultra-processed food category, which is 73% of the American grocery store, is the class that is associated with all of these chronic metabolic diseases. NOVA Class one through three, no problem.

Andrew Huberman:
Now, when you say associated, what percentage of one's daily total caloric intake needs to come from NOVA Class four before that statement you just made is true? Because I love the recommendation you made earlier or the, let's just say the contour of you don't have to avoid dessert, you can enjoy dessert.

Dr. Robert Lustig:
Right.

Andrew Huberman:
But don't eat dessert at other times of day.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And maybe you don't eat dessert every single night.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Is there a rule that people have to eat dessert every single night?

Dr. Robert Lustig:
So the answer is about 7 to 10%, would be the upper limit.

Andrew Huberman:
So you can get 7 to 10% of your caloric intake, daily caloric intake, from these NOVA Class four foods and still-

Dr. Robert Lustig:
And still be okay

Andrew Huberman:
... and still be okay.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
So this is-- I know-

Dr. Robert Lustig:
But that's not what's happening.

Andrew Huberman:
Right. I know some very healthy physicians who I used to observe how people ate and moved, because I would pay attention in our field, right? I was like, oh, people all around me at Stanford, UCSF, et cetera, were successful or else they wouldn't be there.

Dr. Robert Lustig:
Right.

Andrew Huberman:
I was like, who looks healthy? Who can make it up the stairs and doesn't have to take the elevator?

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
How much exercise are people doing at a given age?

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
Are they fanatic, like 4:00 in the morning runners? I'm not going to do that consistently-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... unless I have to. And I observed that many of the healthiest people I know, they move a lot during the day. They eat very well. Many of them skip breakfast or lunch. Not always. And then I also noticed that they would drink very little or no alcohol, but they would enjoy a... There's one physician at UCSF in particular I'm thinking of, who really enjoyed his dark chocolate Kit Kat after lunch. And he's sort of very ceremonial about the unraveling of the foil and the end of the day. And it was like, okay, so you're talking about that small percentage of calories.

Dr. Robert Lustig:
If that's all you do, hey, God bless you. But that's not what people are doing. That's the problem. Bottom line, that NOVA Class four is where all the action is in terms of chronic metabolic disease. So the question is, how can you avoid that? How do you know which is which? We have a solution. So my colleagues and I have developed a web-based tool that is available to the entire world right now, and you'll put it in your show notes.

Andrew Huberman:
Yeah, we'll put a link to this.

Dr. Robert Lustig:
Absolutely. It's called PERFACT. P-E-R F-A-C-T, and you can find it at perfect.co. And what it is, is it's a recommendation engine, not AI. And we're going to talk about AI in a minute. But it is a recommendation engine based on the science of human metabolism that categorizes foods based on not their nutrient content, but on their metabolic effect.

Andrew Huberman:
Interesting.

Dr. Robert Lustig:
And so there is a NOVA filter which will filter out all the NOVA Class four stuff, and it will go to your grocery store, and will tell you what you can buy that will be in NOVA Class one through three.

Andrew Huberman:
Ooh.

Dr. Robert Lustig:
Which turns out to only be 20% of the grocery store.

Andrew Huberman:
It means basically staying on the periphery of the grocery store, right?

Dr. Robert Lustig:
Well, that's-

Andrew Huberman:
In general

Dr. Robert Lustig:
... a lot of it. In general.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
Yes.

Andrew Huberman:
The produce, the meat, the dairy, the-

Dr. Robert Lustig:
Yeah. All the things you mentioned-

Andrew Huberman:
Yeah

Dr. Robert Lustig:
... in fact. So I'm not low carb, I'm low insulin. And there are a lot of ways to get to low insulin. Get rid of the refined carbohydrate, get rid of the sugar, increase the fiber, get rid of the branched-chain amino acids. Okay, so eating fish is a good place to be. Even eating a steak is okay if it's a pasture-fed steak. So let's talk about your steak. You mentioned-

Andrew Huberman:
Right, which is also better for the animals, right?

Dr. Robert Lustig:
It is, absolutely. So you mentioned marbling before. We love our marbling, right? We can cut our US grade A steaks with a butter knife because they're so tender, right? You ever been to Argentina?

Andrew Huberman:
Yeah, my father's Argentine.

Dr. Robert Lustig:
Oh, right. That's right, you're Argentinian.

Andrew Huberman:
Yeah. They only know-

Dr. Robert Lustig:
Of course

Andrew Huberman:
... grass-fed steak.

Dr. Robert Lustig:
Duh.

Andrew Huberman:
The idea that cows would eat anything but grass is sort of like the idea that-

Dr. Robert Lustig:
Mendoza Valley

Andrew Huberman:
... fish would fly.

Dr. Robert Lustig:
Absolutely. New Zealand, same thing.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
Okay? The meat is gorgeous. It's homogeneous, it's pink, it's delightful. I've been to Argentina. The meat is fantastic, but you have to use a steak knife. You can't use a butter knife.

Andrew Huberman:
And it takes more chewing.

Dr. Robert Lustig:
And it takes more chewing-

Andrew Huberman:
It does. It takes more chewing

Dr. Robert Lustig:
... because there's sinew. It's a different experience entirely.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
It's delicious, but it is kind of a little bit tougher.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
All right. Turns out that marbling is intramyocellular lipid That animal has metabolic syndrome.

Andrew Huberman:
The American corn-fed?

Dr. Robert Lustig:
The American corn-fed animal, because that corn is filled with branched-chain amino acids, leucine, isoleucine, valine. Branched-chain amino acids are what's in protein powder. That's what bodybuilders put in their smoothies to build muscle. And if you're building muscle, that's okay, because 20% of the amino acids in muscle are branched-chain. So, if you've got a place to put them, have at it.

Andrew Huberman:
Yeah, there's a need there.

Dr. Robert Lustig:
There's a need there.

Andrew Huberman:
Because they're breaking down muscle.

Dr. Robert Lustig:
Yeah, fine. But if you're not, if you're, again, a mere mortal like me, you consume those excess branched-chain amino acids, they're going to go to the liver, they're going to be deamidated, like we talked about earlier, and they're going to end up as branched-chain organic acids. They're going to flood the mitochondria, the mitochondria are not going to be able to deal with the volume, and so they're going to divert the excess and turn that into fat. And so now you've got hypertriglyceridemia and chance for fatty liver disease and insulin resistance. So what kind of meat you eat has a lot to do with your metabolic health.

Andrew Huberman:
What about the egg, the whole egg? Near perfect protein score in terms of its availability.

Dr. Robert Lustig:
Eggs are terrific.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
There's nothing wrong with eggs. Now, there are better eggs than others.

Andrew Huberman:
Mm-hmm. Pasture.

Dr. Robert Lustig:
Well, there's yellow yolk eggs and there are orange yolk eggs.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
What's the difference between a yellow yolk egg and an orange yolk egg?

Andrew Huberman:
I'm guessing it's something about the feed of the mother chicken, and I'm guessing it probably also has something to do with choline content.

Dr. Robert Lustig:
Omega-3s.

Andrew Huberman:
Ah, interesting.

Dr. Robert Lustig:
Okay. The orange yolk egg has a lot of Omega-3s in it.

Andrew Huberman:
What are other great sources of Omega-3s? I know some off the top of my head, but I'd like to hear it from you.

Dr. Robert Lustig:
Okay. So marine life is number one. Okay? Fish.

Andrew Huberman:
Provided you're not bringing heavy metals with it.

Dr. Robert Lustig:
Well, yes. So I mean, that's always the argument. The question is, is it the mercury or is it the Omega-3s? And ultimately, I think it's the Omega-3s that is more important. But yes, I do understand the mercury issue. Ultimately, there are three Omega-3s. There's ALA, alpha-linolenic acid, which you can get in vegetables. There is EPA, eicosapentaenoic acid, which you can only get in marine life.

Andrew Huberman:
Fish oil, cod liver oil.

Dr. Robert Lustig:
Right. And finally, DHA, docosahexaenoic acid, which you also get from marine life, but you can get from algae. So you can get algal oil, which the vegans will use.

Andrew Huberman:
Do you personally take anything to increase your Omega-3 intake?

Dr. Robert Lustig:
Yeah. I take fish oil.

Andrew Huberman:
I know there's even prescription Omega-3s.

Dr. Robert Lustig:
I take fish oil.

Andrew Huberman:
You take a fish oil?

Dr. Robert Lustig:
Yep.

Andrew Huberman:
Yeah. The thresholds-

Dr. Robert Lustig:
I only take three supplements

Andrew Huberman:
Okay, I'd like to know what those are. I will say that I always say behavior is first, right? Dos and don'ts.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
Behavior is nutrition, then only if needed and one can afford it, then supplementation and prescription drugs. And I'm a big consumer of supplements and always have been, frankly.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
So what are the three? So you take-

Dr. Robert Lustig:
Fish oil

Andrew Huberman:
... fish oil. And do you take to get above a certain threshold of EPA?

Dr. Robert Lustig:
Yeah, about 1,000 milligrams a day.

Andrew Huberman:
I'd say about a gram a day of EPA.

Dr. Robert Lustig:
Gram a day.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Vitamin C.

Andrew Huberman:
How much vitamin C do you take?

Dr. Robert Lustig:
1,000 milligrams a day.

Andrew Huberman:
You and Linus Pauling.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
Well, it's actually for my rosacea. I've got a skin issue that helps-

Andrew Huberman:
And vitamin C helps with-

Dr. Robert Lustig:
Helps with that.

Andrew Huberman:
Interesting

Dr. Robert Lustig:
And finally, vitamin D. Now, I will tell you, vitamin D is a complicated one. All right? And we can talk about vitamin D and how either important or non-important it is, because there's a quirk to vitamin D, and it's important for your audience to know about it because everybody and his brother's touting vitamin D-

Andrew Huberman:
Well, it's funny because-

Dr. Robert Lustig:
... as a cure for everything

Andrew Huberman:
... it's sort of funny because-

Dr. Robert Lustig:
And it's not true

Andrew Huberman:
... that you have your supplement lovers, haters, and agnostics, but vitamin D somehow made it through the shoot. Everyone's pro vitamin D. It's really interesting.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Somehow vitamin D, people are comfortable taking a vitamin D gel cap, but other supplements where you say, "Oh, maybe this might be good for Omega-3s and fish oil," then people are a little bit more standoffish. It's really interesting the kind of psychosocial stuff around this.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
How much vitamin D do you personally take?

Dr. Robert Lustig:
I take 5,000 units a day.

Andrew Huberman:
Okay. So do I.

Dr. Robert Lustig:
Vitamin D's complicated, though. Here's the problem. If you look at the literature, vitamin D deficiency is associated with all these chronic metabolic diseases. However, supplementation with vitamin D has not fixed any of those.

Andrew Huberman:
Hmm.

Dr. Robert Lustig:
So if you're vitamin D deficient, why wouldn't supplementation fix it? Couple of reasons. One, one of the reasons for vitamin D deficiency is because everyone's drinking soft drinks. That's one reason, but there's a more important reason.

Andrew Huberman:
Sugar and artificially sweetened soft drinks?

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Can deplete vitamin D utilization.

Dr. Robert Lustig:
Well, you're not consuming dairy because you're consuming soft drinks.

Andrew Huberman:
But I can't tolerate milk anymore.

Dr. Robert Lustig:
Well-

Andrew Huberman:
Yeah

Dr. Robert Lustig:
... then you take vitamin D. But here's the real nugget of truth, and this is a little complicated, but the endocrinologists in the audience will get it. Vitamin D is a pre-prohormone. It's not active at all. Vitamin D is converted in the liver, first step, to a compound called 25-hydroxyvitamin D. That is a prohormone. It also is inactive. It has no activity whatsoever. From there, 25-hydroxyvitamin D can be metabolized one of two ways. It can either be 1-alpha hydroxylated in the kidney to the active form, 1,25-dihydroxyvitamin D, which will then do all of the business of vitamin D.

Andrew Huberman:
Such as?

Dr. Robert Lustig:
Calcium absorption from the gut, suppression of the immune system at the toll-like receptor 4.

Andrew Huberman:
That sounds like a bad thing.

Dr. Robert Lustig:
No, that's a good thing.

Andrew Huberman:
I know, but I had to bring that up.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
Because when you say suppression of the immune system, people go, "I'm immunosuppressed." That sounds like AIDS.

Dr. Robert Lustig:
It suppresses inflammation.

Andrew Huberman:
Got it.

Dr. Robert Lustig:
It's a good thing. Okay? Suppression of inflammation. And that's actually the point that we're getting to. So, there are a lot of good things about 1,25-dihydroxyvitamin D. However, that 25-hydroxy D that came out of the liver can be metabolized a different way. It can be 24-hydroxylated in inflammatory tissue, like tuberculosis, sarcoid, gut inflammation. And so you will end up taking your 25-hydroxy D, which is a prohormone, and turning it into the inactive 24,25-dihydroxy D, which then just gets excreted out. So, in other words, you consumed all this vitamin D, and it didn't go where you needed it to go, and the reason was because you're inflamed. You have to fix the inflammation before the vitamin D can be effective, and 93% of Americans are inflamed. So, giving them vitamin D is not going to do a damn thing.

Andrew Huberman:
Got it. Is reducing fructose intake one of the primary ways to reduce systemic inflammation?

Dr. Robert Lustig:
Absolutely.

Andrew Huberman:
What are some others?

Dr. Robert Lustig:
Reducing oxidative stress in general, so heavy metals like cadmium. Cadmium's very high in chocolate, especially South American chocolate. Sorry.

Andrew Huberman:
No, I'm not a fan of chocolate. I occasionally like a little dark chocolate, but-

Dr. Robert Lustig:
Okay

Andrew Huberman:
... so if people are going to eat chocolate, they should be careful how much chocolate they eat-

Dr. Robert Lustig:
Well-

Andrew Huberman:
... in general

Dr. Robert Lustig:
... especially if it's South American chocolate and processed chocolate. I mean, the really good stuff.

Andrew Huberman:
We're going to be on the hit list of so many industries after-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... this episode comes out.

Dr. Robert Lustig:
Well, that's okay.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
All I can tell you is, I've been on the hit list for a decade, and I'm still here.

Andrew Huberman:
You're just one big target.

Dr. Robert Lustig:
Yeah, right.

Andrew Huberman:
Got it.

Dr. Robert Lustig:
It's on my back, it tagged me.

Andrew Huberman:
It's everywhere.

Dr. Robert Lustig:
I already got that. The main thing is to make that gut work right. So fiber, short-chain fatty acid production from fiber-

Andrew Huberman:
Mm-hmm

Dr. Robert Lustig:
... is a huge boon and benefit.

Andrew Huberman:
To reduce inflammation.

Dr. Robert Lustig:
To reduce inflammation.

Andrew Huberman:
How about improving sleep? Is there any evidence that chronic slight sleep deprivation can increase inflammation?

Dr. Robert Lustig:
Well, what it will do is it'll increase cortisol, and chronically increased cortisol will definitely lead to increased inflammation. Which is funny, because cortisol is usually considered the anti-inflammatory-

Andrew Huberman:
Right

Dr. Robert Lustig:
... but only acutely.

Andrew Huberman:
Right.

Dr. Robert Lustig:
Chronic cortisol elevation does the opposite.

Andrew Huberman:
Yeah. If we can contribute to-- I have this secret agenda, which is not a secret, which is that people think cortisol is bad, when in fact, acutely, cortisol does wonderful things, provided it's happening at the right time of day.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Late-shifted cortisol, bad.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Too much or too frequent cortisol, bad. But cortisol, you need it. It's so essential.

Dr. Robert Lustig:
Well-

Andrew Huberman:
And I think most people just hear cortisol, and it's been associated with all things bad, and maybe we can help shift that narrative a bit.

Dr. Robert Lustig:
Yeah, I'm very happy. I mean, as an endocrinologist, this is my wheelhouse.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
This is where I live. Cortisol is a good news/bad news deal, like so many things. Short-term gain for long-term pain. Okay? So when you are in what we call allostasis, that is perturbation of homeostasis, that is a stress, an acute stress, cortisol is one of the things that helps you manage that bodily and mental stress. So, an English test, a car accident, running away from the lion, the famous pygmy running away from the lion. All of those require cortisol in order to manage and mitigate that stress.

Andrew Huberman:
The upcoming 2024 election.

Dr. Robert Lustig:
That's chronic stress.

Andrew Huberman:
Sorry.

Dr. Robert Lustig:
That is not acute stress.

Andrew Huberman:
I didn't mean to laugh.

Dr. Robert Lustig:
That's the worst.

Andrew Huberman:
That'll be the only mention of politics on this podcast.

Dr. Robert Lustig:
And we don't have to go there. But we're all chronically stressed, and we can talk about why that is and what's going on, and I'm actually very interested in that. And a colleague of mine in Paris and I have built a computational model of the limbic system, which focuses on the stress center of the brain, the amygdala, to understand how chronic stress is different from acute stress, and how that chronic stress ultimately leads to metabolic and mental health disaster.

Andrew Huberman:
Very interested in learning more about that. Before we touch on that, you've worked a lot with kids.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
People age, as you put it, 0 to 19. I don't know about the exact numbers, but when I was growing up, there were some kids in school that were overweight, but it was the occasional kid.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Now it seems, depending on where one draws the threshold for overweight, it seems that there are a lot of kids that are overweight.

Dr. Robert Lustig:
How about 25% obese and 40% overweight?

Andrew Huberman:
Okay, so obviously a serious problem.

Dr. Robert Lustig:
Serious problem.

Andrew Huberman:
Now and going forward.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
What about adults in the US? I remember seeing, at a meeting, a map of obesity in the US over time, and it very quickly filled in from very few people were obese to very many. Colorado was this ... was this beacon of fit people, but now it's no longer-

Dr. Robert Lustig:
No, and that's bullshit too.

Andrew Huberman:
Oh, okay. Cool.

Dr. Robert Lustig:
I'll tell you why. There are four things that could increase mitochondrial biogenesis.

Andrew Huberman:
You can tell me altitude is one of them.

Dr. Robert Lustig:
Cold.

Andrew Huberman:
Yeah, cold.

Dr. Robert Lustig:
That's why Colorado's less obese. Altitude, that's why Colorado's less obese. And what were the other two? I forget. But those were the reasons. It had nothing to do with being more fit. It had to do with cold and altitude. Example, Switzerland compared to Germany. They got the same crappy food, but Switzerland has half the obesity that Germany does-

Andrew Huberman:
I love-

Dr. Robert Lustig:
... because Switzerland is higher.

Andrew Huberman:
Oh, I love the food. When I go to Munich, I love the schnitzels and the-

Dr. Robert Lustig:
Yeah, it's wonderful

Andrew Huberman:
... and the sauerkrauts and the-

Dr. Robert Lustig:
Yeah, they got that in Switzerland too.

Andrew Huberman:
Okay, so they have great food.

Dr. Robert Lustig:
But Switzerland's less obese.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
All right? Same way Colorado's less obese. It's because of the altitude.

Andrew Huberman:
You mentioned cold. Many listeners of this podcast are at least interested in some also practice deliberate cold exposure, cold showers, cold plunges.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Mainly for the, I think the best data are the increases in catecholamines, epinephrine, norepinephrine, dopamine that are long-lasting. People feel a big state shift. They feel better.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
But when one looks at the effects on metabolism-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... they're pretty slight.

Dr. Robert Lustig:
They are slight.

Andrew Huberman:
They're slight. However, studies like that, to me, always seem shortsighted in the sense that if there's a longer arc of effect on the mitochondria that's affecting other things in terms of how calories are processed or how calories are feeding into mitochondrial function or dysfunction, there I could see how it might shift the scale, so to speak. Cold is an amazingly powerful stimulus.

Dr. Robert Lustig:
It is. Absolutely.

Andrew Huberman:
And I think of light, cold, food, movement as kind of like the core four ways in which you can shift physiology easily.

Dr. Robert Lustig:
All of these things are imminently manipulable and for almost $0.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
Okay? But you have to know what you're doing.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
And right now, we've been actually kept from that knowledge and if you're addicted, it's really hard to un-addict yourself.

Andrew Huberman:
So that brings us back to this thing about food industry conspiracies, government conspiracies, and the rest. Boy, this is going to be an interesting-

Dr. Robert Lustig:
We can go there

Andrew Huberman:
... section. But what do we do? So if you and I go up to Capitol Hill-

Dr. Robert Lustig:
Which I've done.

Andrew Huberman:
Yeah, which you've done, and maybe I'll join you someday. And you're at UCSF, I'm down at Stanford. You're a clinician, I'm a scientist and a public health advocate, podcaster.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And we explain to people, "Hey, listen, the food is laced with a drug. It's not even really food."

Dr. Robert Lustig:
That's right. It's not food.

Andrew Huberman:
It's an aggregate of food and non-food parts that make you think it's food. It's sort of like telling people, "Hey, your kids are, they're swimming in a swimming pool. Looks like water, but it's actually part poison and it's harming them. It's giving them..." If you say those kinds of things, congressmen and women are reasonably smart people, right? Aren't they going to do something about it?

Dr. Robert Lustig:
No.

Andrew Huberman:
So where is the conflict? Is it that the food industry has the government by the short hairs?

Dr. Robert Lustig:
That's exactly right.

Andrew Huberman:
And they have them by the short hairs where? Are they lining their pockets? Where is the leverage actually exerted?

Dr. Robert Lustig:
Okay, so they are lining their pockets, that's number one. That is absolutely true, and we have the data to support that. Blanche Lincoln, who was a senator from Arkansas, who was the chairman of the Nutrition Committee, you had to see her campaign contributions every time she was up for re-election.

Andrew Huberman:
So it's all about getting re-elected or it's about them having a third home in the Hamptons?

Dr. Robert Lustig:
So I think it's the third home in the Hamptons-

Andrew Huberman:
Okay. Wow

Dr. Robert Lustig:
... more than anything.

Andrew Huberman:
Okay, so it's really as bad as-

Dr. Robert Lustig:
It is

Andrew Huberman:
... as some of the documentaries-

Dr. Robert Lustig:
Without question

Andrew Huberman:
... would make us believe. Okay.

Dr. Robert Lustig:
Without question.

Andrew Huberman:
Goodness. Okay.

Dr. Robert Lustig:
And we have the data. There is an organization that I absolutely want to call out because they are the most egregious political organization on the face of the Earth. They're called the American Legislative Exchange Council, ALEC, or ALEC. And they write bills. They are a bill mill, okay? And they are for whoever gives them money. And who gives them money? Big Pharma, big agro, big oil, and Big Food.

Andrew Huberman:
So you're including Big Pharma. You're a physician. You've written scripts before. You've written prescriptions for patients before.

Dr. Robert Lustig:
That's true.

Andrew Huberman:
Isn't that pharma that provides the drugs that allows your patients to feel better?

Dr. Robert Lustig:
Well, the question is do they? Do they feel better? This is a big question. You want to go there? We can go there.

Andrew Huberman:
But you're writing the script. I'm just trying to-

Dr. Robert Lustig:
I'm not

Andrew Huberman:
... I'm not trying to challenge you, but I see. There have to be instances where someone's thyroid deficient and you give them a drug.

Dr. Robert Lustig:
Absolutely.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
So if you've got a disease and a medicine will replace what's missing, sure. Okay? So for deficiency diseases, which as an endocrinologist, that's what I do, absolutely. And I did that with no compunction of impropriety whatsoever. But that's not what we're talking about here. Let's talk about what we're really talking about. Let's start with statins. Statins lower LDL. Okay. Do statins reduce heart disease? Yes or no?

Andrew Huberman:
I seem to be whiffing today on all the quizzes, and it's kind of becoming fun for me at this level. I'm going to go with no, but I will say my friend, and I think he's an expert physician as well, Peter Attia and others-

Dr. Robert Lustig:
I do

Andrew Huberman:
... has talked about some of the positive attributes of statins in certain cases for certain patients.

Dr. Robert Lustig:
In certain cases, that's exactly right, and I completely agree. And by the way, Peter's a friend, and someday we'll All, go out drinking together.

Andrew Huberman:
Yeah. Well, I won't drink but any-

Dr. Robert Lustig:
All right. Well-

Andrew Huberman:
How about we share a steak?

Dr. Robert Lustig:
Share a steak.

Andrew Huberman:
There we go.

Dr. Robert Lustig:
Absolutely.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
You got it.

Andrew Huberman:
You guys, I don't know if you drink.

Dr. Robert Lustig:
Peter-

Andrew Huberman:
He drinks a little bit

Dr. Robert Lustig:
... Peter, if you're listening, okay.

Andrew Huberman:
He drinks a little bit. I don't-

Dr. Robert Lustig:
Porterhouse on me

Andrew Huberman:
... yeah, I don't do the dessert or the-

Dr. Robert Lustig:
Okay

Andrew Huberman:
... or the alcohol anymore. But I'm-

Dr. Robert Lustig:
Okay

Andrew Huberman:
... and it's not so I can live to be 120. It's so I can wake up the next morning and keep up with you guys.

Dr. Robert Lustig:
It's fine. Yeah, I get it. So for primary prevention, that is, your LDL's high, you need a statin. That's primary prevention. You haven't declared yourself, you haven't had an event. For primary prevention, the mean increase in lifespan for being on a statin is four days.

Andrew Huberman:
Four days?

Dr. Robert Lustig:
Four days.

Andrew Huberman:
Four days.

Dr. Robert Lustig:
And then-

Andrew Huberman:
Sorry to chuckle. That's-

Dr. Robert Lustig:
And the risk for diabetes is 20% increase.

Andrew Huberman:
What about any improvement in quality of life?

Dr. Robert Lustig:
None, for primary prevention. Now, for secondary prevention, in other words, you've already declared yourself, you already have a problem. For secondary prevention, that's where statins shine. So there's a value to them. I'm not arguing that. And if you have familial hypercholesterolemia, which is one in 500, okay, not only do you need a statin, but you need a low-fat diet and a priest. Okay? So there is definitely a value to statins, but not for primary prevention. But that's what every doctor's doing. "Oh, your LDL, it's over 80. You need a statin." That's ridiculous. That is absolutely a joke, and the data show that. In fact, my colleague Aseem Malhotra in the UK participated in an analysis where they took the entire UK population and they took out everybody under age 65. So you're looking at people 65 to 90, and it turned out that the LDL level correlated with longevity. The higher the LDL, the longer they lived, when you took out all the people who had problems. So LDL is not really the problem, and the reason is because there are two LDLs. There's one called large buoyant, and there's one called small dense. Turns out dietary fat raises your large buoyant. Your large buoyant is irrelevant. It is cardiovascularly neutral. But that's the one that statins affects. The small dense, that's the atherogenic particle. When your small dense LDL is high, that means you are not clearing triglyceride peripherally, because that's what small dense show you. That's what happens to triglyceride, is they become small, dense.

Andrew Huberman:
Can I take a guess and say that the best way to reduce small dense is to reduce insulin?

Dr. Robert Lustig:
Yes, by reducing sugar. Because that triglyceride is made in the liver. It's all palmitate, and that's the only fat that the liver knows how to make. And so triglyceride is your liver output of carbohydrate. That's how you have to look at triglyceride. So triglyceride turns out to be much more important as a cardiovascular risk factor than LDL ever was.

Andrew Huberman:
So does big pharma and big food, do they know all of this?

Dr. Robert Lustig:
Yes.

Andrew Huberman:
I mean, have they-

Dr. Robert Lustig:
I know they know because they've told me so.

Andrew Huberman:
And-

Dr. Robert Lustig:
But they have statins to sell

Andrew Huberman:
... and foods in the Nova class four.

Dr. Robert Lustig:
Mm-hmm. They know this, too.

Andrew Huberman:
So, I'm an optimist. What's it going to take to really move the needle? You described the four barriers. We're trying to add to the knowledge component now. What's it going to take? Is it going to take having a president in office or congresspeople in office that really understand and care about this stuff?

Dr. Robert Lustig:
Yeah. It will.

Andrew Huberman:
I mean, to really revamp the whole system.

Dr. Robert Lustig:
Yeah. So right now, the system is completely and utterly broken. Completely and utterly broken. And there's a reason why it's completely and utterly broken, is because the food industry likes it that way.

Andrew Huberman:
Well, it's profitable for them, obviously.

Dr. Robert Lustig:
There are 51 different federal agencies that manage our food. 51, and none of them know what the other one's doing. And the food industry likes it that way.

Andrew Huberman:
So communication across these 51 organizations would help?

Dr. Robert Lustig:
Well, if we had a centralized food czar or if we split the food off the FDA, because it's not the FDA, it's the DA, or the FDA is not the Food and Drug Administration, it's the Federal Drug Administration. They spend a lot of time on drugs. They spend almost no time on food.

Andrew Huberman:
Well, let's think about where there's been success. So I can recall when people smoked on planes. I actually recall going to a gym in Europe and there was an ashtray molded into the squat rack.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
That was telling.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
I don't see people smoking cigarettes around Stanford Hospital anymore, but I remember when they initially said that people couldn't smoke anywhere except in this one little designated area.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And that's typically what you see nowadays. And my understanding of the anti-smoking campaign, at least for kids, for people 18 and younger, was that telling people it was bad for their health didn't work.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
Showing them lungs that were decrepit didn't work.

Dr. Robert Lustig:
Right. Did not work.

Andrew Huberman:
What worked was showing them commercials of cackling, hand-writhing, white guys who were talking about how much money they were making-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... off of these naive kids-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... who were buying cigarettes and other tobacco products.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
So it became the effective campaign to end smoking in young people was to hijack their inherent rebelliousness of youth.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
And then they were like No.

Dr. Robert Lustig:
Yeah. Stick it to the man

Andrew Huberman:
We're not going to smoke.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Stick it to them.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
As my friend calls it, the two-finger business card. Like, no. And so that worked.

Dr. Robert Lustig:
To some extent.

Andrew Huberman:
Vaping's making a comeback. Vaping's a separate episode.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
We won't get into that, because nicotine is still addictive.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
But you don't see a lot of people smoking cigarettes. So it worked. Something that you would never imagine could ever work, worked.

Dr. Robert Lustig:
Well, so yes, no. That's part of it. I'm not going to tell you that it's not. It is part of it. And we actually have an example of how that could be applied to another toxic substance, sugar. We had Berkeley versus big soda. That's how Berkeley ended up with its soda tax that dates back to 2015.

Andrew Huberman:
The City of Berkeley.

Dr. Robert Lustig:
City of Berkeley. We just celebrated the five-year anniversary of the Berkeley soda tax, and we've been able to actually look. Gestational diabetes, way down. Obesity, down slightly. Not a lot, but a little bit. Cardiovascular disease, down. Dean Schillinger and Chris Madsen at UCSF and UC Berkeley just presented at San Francisco General just three weeks ago.

Andrew Huberman:
So a soda tax like the cigarette tax.

Dr. Robert Lustig:
Like the-

Andrew Huberman:
Just make soda expensive.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
So you're telling me that a can of Coke that I buy on Shattuck Avenue in Berkeley costs more than a can of Coke that I buy on University Avenue in Palo Alto?

Dr. Robert Lustig:
It does.

Andrew Huberman:
Huh, okay.

Dr. Robert Lustig:
By a dime.

Andrew Huberman:
And that was sufficient enough to create this kind of change?

Dr. Robert Lustig:
Well, yes, it is.

Andrew Huberman:
Because money hurts.

Dr. Robert Lustig:
Because money hurts. Exactly. So, Andrew, there have been four, count them, four cultural tectonic shifts in America in the last 30 years, and they're all undeniable. Here they are. Number one, bicycle helmets and seat belts.

Andrew Huberman:
Oh yeah, everybody uses those.

Dr. Robert Lustig:
Two, smoking in public places.

Andrew Huberman:
Nobody does that.

Dr. Robert Lustig:
Three, drunk driving.

Andrew Huberman:
Hopefully fewer people are doing that.

Dr. Robert Lustig:
Four, condoms in bathrooms.

Andrew Huberman:
Condoms in bathrooms?

Dr. Robert Lustig:
In bathrooms. In public bathrooms.

Andrew Huberman:
Yeah, you see those more available.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
All right. 30 years ago, if a legislator stood up in a state house and proposed legislation for any one of those four, and I don't care if it's in a state house or in Congress or in Parliament or in the Duma or anywhere else in the world, they'd have gotten laughed right out of town. Nanny state, liberty interest, get out of my kitchen, get out of my bathroom, get out of my car. Today, they're all facts of life. Nobody's bellyaching about any of those. The point is, we were able to solve those four public health debacles. How did we do it? How did we solve those four? No one could imagine that we would ever solve smoking, right? But we did, sort of. We brought consumption down by half. That's pretty good when you think about it, for an addictive substance.

Andrew Huberman:
How many fewer people are dying of lung cancer nowadays in the US?

Dr. Robert Lustig:
It's like 80% lower.

Andrew Huberman:
Wow. Well, there's also been improvements in treatment, but-

Dr. Robert Lustig:
Yeah. But it's the incidence

Andrew Huberman:
... diagnosed with-

Dr. Robert Lustig:
It's incidence

Andrew Huberman:
... the incidence.

Dr. Robert Lustig:
Incidence has gone down.

Andrew Huberman:
Amazing.

Dr. Robert Lustig:
Because tobacco's gone down. So the question is, how did that happen? And the answer is very-- And why did it take 30 years to do it? We taught the children, the children grew up, and they voted, and the naysayers are dead. That's how you make a cultural tectonic shift. So we now have this real food movement. We have people who are arguing against ultra-processed food. We have kids who are demanding different in their schools. And by the way, what is the biggest fast food franchise in the United States?

Andrew Huberman:
I'm going to get this wrong.

Dr. Robert Lustig:
Try me again.

Andrew Huberman:
I don't know. I've never tried it, but I've heard of... Is it Chick-fil-A?

Dr. Robert Lustig:
Nope.

Andrew Huberman:
Is it McDonald's? I don't know.

Dr. Robert Lustig:
It is this nation's public schools.

Andrew Huberman:
Ah.

Dr. Robert Lustig:
You can add up McDonald's, Subway, Burger King, Chick-fil-A, and Wendy's, and every other fast food franchise, Jack in the Box, every fast food franchise in the entire country, and it would only be half our nation's public schools.

Andrew Huberman:
Wow. So could you imagine a world where there were no class three or class four NOVA foods allowed in public schools?

Dr. Robert Lustig:
And we're doing it. So I am the chief science officer of a nonprofit, and put this in the show notes, called Eat Real, eatreal.org. And we have a new business model for public schools. So in 1971, the Department of Education issued an administrative ordinance called Resolution 242, and they did this purely on monetary reasons. This was under Nixon. And what this Resolution 242 said was that all school cafeterias all throughout the country had to make book. They had to basically cover their costs. They couldn't be loss leaders for the school. They had to fend for themselves. Well, this sent every food service director in the country scurrying for, "How am I going to do this? Because I got all these lunch ladies, personnel, and food preparation equipment, and costs that are mounting. How am I going to Break even. And they couldn't do it. So in walks Aramark and Cisco and Guggenheim and McDonald's, and they say, "Hey, we'll do it for you. We'll provide every kid in America with a nutritious meal every single day."

Andrew Huberman:
Hot lunch.

Dr. Robert Lustig:
Well, they didn't say hot.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
They just said lunch.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Nutritious. They said nutritious.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
And I put that in air quotes too, because it wasn't nutritious. And here's the added benefit. You can take your food preparation facilities and your footprint in the school, and you can turn that into classrooms because you're going to need them. And that was the goal. Because as soon as you've moved the food preparation facilities out of the school, you are now hostage to the food industry for the rest of your life.

Andrew Huberman:
And I could also see how that allows room for them to use these commoditized foods, foods that have very long shelf life.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
Right? Because you want to make sure that if you only sold two-thirds of the lunches that were prepared, that on next Tuesday after the weekend, you could still give them food that isn't moldy.

Dr. Robert Lustig:
Exactly right. And I will tell you, so that's how it happened, and you can actually trace IQ scores and reading and math scores in this country down from 1971 to today.

Andrew Huberman:
When I went to school, I was allowed to get... I called it hot lunch because it was usually hot. I was allowed to get the school lunch one day a week.

Dr. Robert Lustig:
One day a week.

Andrew Huberman:
The other days, I had to bring my lunch.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
That one day was pretty special, like you felt like you were getting a treat.

Dr. Robert Lustig:
Right.

Andrew Huberman:
It was usually like a corn dog- ... or a hamburger. The hamburger was pretty paltry, but the-

Dr. Robert Lustig:
It's a commoditized hamburger.

Andrew Huberman:
Yeah, a commoditized hamburger.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
You had to go looking for the patty portion.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
And the bread was sweetened. And so it was different.

Dr. Robert Lustig:
Right.

Andrew Huberman:
But, I don't remember nearly as much obesity. I went to high school in the early '90s.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
So you're saying that now if I went to a high school, it would be a lot more sodas and donuts and-

Dr. Robert Lustig:
Totally. Pizza

Andrew Huberman:
... pizza and... Got it.

Dr. Robert Lustig:
Yeah. Pizza's a vegetable, didn't you know?

Andrew Huberman:
They claim it's a vegetable?

Dr. Robert Lustig:
Congress said pizza's a vegetable. Amy Klobuchar made pizza a vegetable.

Andrew Huberman:
Maybe they need their eyes checked.

Dr. Robert Lustig:
Because the biggest frozen pizza producer is in Minnesota.

Andrew Huberman:
I mean-

Dr. Robert Lustig:
Called Schwans

Andrew Huberman:
... the ketchup as a vegetable was a stretch, but at least it made sense on the NOVA system of going from tomato all the way to-

Dr. Robert Lustig:
To ketchup

Andrew Huberman:
... to ketchup.

Dr. Robert Lustig:
Since high fructose corn syrup is the primary ingredient in ketchup. Indeed. So the point is that our kids are suffering under the weight, the burden of this chronic disaster of ultra-processed food, which is not food. And no wonder they're all obese and sick and doing so poorly in school. And by the way, also depressed. Ultra-processed food has now been shown in three separate studies to correlate with depression in teenagers.

Andrew Huberman:
So what is the relationship between processed food, or maybe we call it NOVA system level three, four foods-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... and depression and other psychiatric challenges? And if you could, can you separate out metabolic syndrome from obesity in answering that? Is there something inherently depressing about carrying excess adipose tissue, setting aside any kind of aesthetic-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... stuff, how people want to look or are perceived. Just, is there anything bad about carrying a lot of body fat, independent of the metabolic syndrome for mood and overall sense of wellbeing?

Dr. Robert Lustig:
No, I'm really glad you asked that, Andrew. We should have actually covered this earlier. Everyone thinks fat is fat. As we've learned, fat is not fat.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
And a fat is not a fat, but body fat is not body fat. There are three fat depots, and they are metabolically different. The first is the, does this bathing suit make me look fat, fat? By the way, never answer that question. That's called subcutaneous fat or big butt fat, if you will. So here's a question. How many pounds or kilos of subcutaneous fat do you have to gain before you become metabolically ill?

Andrew Huberman:
I have no idea.

Dr. Robert Lustig:
About 10 kilos, about 22 pounds.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Why? The reason is because that subcutaneous fat drains into the systemic circulation. So you have to have a lot of cytokines coming from those subcutaneous adipocytes to raise the blood level of cytokines to the point where it starts doing damage at the level of the liver.

Andrew Huberman:
So fats are releasing cytokines, which are pro-inflammatory?

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
And they're doing that at rest. Any fat cell?

Dr. Robert Lustig:
Any fat cell.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Any fat cell. But if it's going to the systemic circulation, you have a volume of distribution of six liters. So you have to have a lot of cytokines to get the concentration up.

Andrew Huberman:
Now, just out of fairness to the fat, how many cytokines does a muscle cell release? Are we unfairly picking on adipose tissue? Because why would adipose tissue be pro-inflammatory? A single fat cell. Okay, I've got a fat cell sitting in my shoulder someplace, right? I'm not zero fat at my shoulder. Why would it be pro-inflammatory?

Dr. Robert Lustig:
So in fact, the fat cell itself is not. Here's what happens. The fat cell has a fat vacuole. It has a storage place for this lipid droplet You stuff it, you stuff it, you stuff it, the fat vacuole gets bigger, bigger, bigger. The perilipin border that encompasses that fat vacuole, that borders the space, ultimately can't get any bigger, and it starts breaking down. When that happens, it spills the grease into the fat cell. The fat cell dies, becomes necrotic. That calls macrophages in to clean up the grease, and it's the macrophages that release the cytokines. All right?

Andrew Huberman:
Okay.

Dr. Robert Lustig:
So in fact, the fat cell is not the problem. It's the breakdown of the grease that leads to the macrophage activation.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
That's the problem. But when you do it in subcutaneous fat, it's going into this six-liter tank, and so the concentration doesn't go up very much. So 10 kilos before you start seeing some effect. Fat depot number two, visceral or big belly fat. Now, how many pounds or kilos of big belly fat do you have to gain before you get metabolically ill?

Andrew Huberman:
I don't know, but I'm guessing it's less than 22 pounds.

Dr. Robert Lustig:
It's way less.

Andrew Huberman:
Oh, for once I got an answer right today.

Dr. Robert Lustig:
Yeah, that's right. About five. About five pounds. Now, the question is why? Number one, the visceral fat does not drain into the systemic circulation. It drains into the portal vein, which goes straight to the liver. So you're getting a bigger load going straight to the liver of cytokines.

Andrew Huberman:
Not to the kidney.

Dr. Robert Lustig:
Not to the kidneys.

Andrew Huberman:
The good thing about getting an answer wrong, folks-

Dr. Robert Lustig:
Not to the kidneys

Andrew Huberman:
... is that you never forget the correct answer. That's what I always tell my students, right? So I'll never forget that.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
Got it.

Dr. Robert Lustig:
And the question is, what made the visceral fat in the first place? Was it calories? No. It's cortisol. It's stress. It's the combination of the sympathetic nervous system and cortisol. And the reason we know this is because you can take patients with major depressive disorder, with endogenous depression, who are suicidal, who have to be admitted to the hospital to keep themselves from killing themselves, stick them in a scanner, and they are losing subcutaneous fat like crazy because they're not eating, but they're gaining visceral fat because of the high cortisol and the stress.

Andrew Huberman:
So there's something about the adrenocorticoid receptors in that area that just preferentially depot fat there when cortisol is high.

Dr. Robert Lustig:
Indeed. Because that's the metabolically active fat. Right? And five pounds will do it. And then finally, the third fat depot, the liver. Now, how many pounds of fat can the liver store before you become metabolically ill?

Andrew Huberman:
Oh, got to be even less because the liver's not nearly as large as the abdominal region.

Dr. Robert Lustig:
Half a pound. Quarter of a kilo.

Andrew Huberman:
How much does a healthy liver weigh?

Dr. Robert Lustig:
A healthy liver weighs 1,500 grams.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Okay? So it's not very-

Andrew Huberman:
I'm trying to translate quickly to pounds. So we're going as standard to metric.

Dr. Robert Lustig:
So 1,500 grams would be three pounds. So-

Andrew Huberman:
Okay

Dr. Robert Lustig:
... basically half a pound. Okay? So not very much. Because that's where the action is, and so when you have fat in your liver, it causes metabolic dysfunction right away. And the question is, where did that fat come from? That came from alcohol or sugar. So alcohol and sugar, most metabolically egregious because it affects the liver directly. Stress, second most because it affects the visceral fat. And subcutaneous fat, the least important in terms of metabolic derangement. So yes, it may not look good in a bathing suit, but from a metabolic standpoint, it is actually the least important. So the question then becomes, all right, what are you trying to fix? If you're trying to fix liver fat, it's really easy. Get rid of the alcohol and the sugar, except of course they're both addictive.

Andrew Huberman:
Will that also liberate any fat that's already in the liver?

Dr. Robert Lustig:
Absolutely, and that's one of the reasons why intermittent fasting works, is because it gives your liver a chance to basically offload what it's already stored. That's one of the things that intermittent fasting will buy you, is a little less liver fat. So that's a good thing. All right? Now, stress on the other hand, as you know and as we've talked about, and as you've had Dr. Lisle Apple on your podcast before. Stress is tough. Trying to mitigate stress, especially in today's environment, and I hope you'll invite me back sometime to talk about the role of stress on the amygdala.

Andrew Huberman:
Yeah, gladly.

Dr. Robert Lustig:
Okay. And then finally, the subcutaneous fat. So when people go on diet sweeteners, what are they doing? Are they really reducing the fat? And the answer is no.

Andrew Huberman:
When you're talking about artificial sweeteners?

Dr. Robert Lustig:
Artificial diet sweeteners of any sort. And you can pick your artificial sweetener, so aspartame or-

Andrew Huberman:
Sucralose

Dr. Robert Lustig:
... sucralose.

Andrew Huberman:
Stevia.

Dr. Robert Lustig:
Stevia, monk fruit, the new ones.

Andrew Huberman:
Yeah, the one that people are more excited about nowadays is allulose.

Dr. Robert Lustig:
Allulose, yeah.

Andrew Huberman:
It's expensive. It tends to have less of an artificial sweetener taste that people can detect.

Dr. Robert Lustig:
Right.

Andrew Huberman:
So you're saying that regardless of-- Oh, and we should-- I'm remembering from the comment section, I do read them Artificial sweeteners and non-caloric sweeteners.

Dr. Robert Lustig:
Yes.

Andrew Huberman:
Because the moment you say artificial, people say, "What about stevia? What about allulose?"

Dr. Robert Lustig:
Right.

Andrew Huberman:
So let's just say non-caloric sweeteners.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
Can wrap our arms around that entire category-

Dr. Robert Lustig:
Sure

Andrew Huberman:
... unless we need to distinguish among the different participants in that category. So you're saying that even though people can lower their total caloric intake pretty effectively, I've seen the studies that show if dieters who consume water only as their main liquid versus diet sodas-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... with aspartame typically, or stevia, the diet soda drinkers actually lose more weight. We know that, but you're saying there may be deposition of fat in the liver in those individuals, specifically because of the artificial sweetener.

Dr. Robert Lustig:
Because of the insulin. Turns out there's still an insulin response. So very famous-

Andrew Huberman:
Mm-hmm

Dr. Robert Lustig:
... study done in Copenhagen. 100 normal individuals, 25 in four different groups. One group, one liter of sugared soda per day for six months.

Andrew Huberman:
One liter, that's a lot of sugared soda.

Dr. Robert Lustig:
Yeah. One group, one liter of diet soda per day for six months.

Andrew Huberman:
I probably did that in graduate school.

Dr. Robert Lustig:
One group, one liter of milk per day for six months.

Andrew Huberman:
I probably did that when I was an infant.

Dr. Robert Lustig:
And finally, final group, one liter of water per day for six months.

Andrew Huberman:
I do that now. I do more than that, but yeah.

Dr. Robert Lustig:
The one liter of soda per day in six months gained 10 kilos.

Andrew Huberman:
The sugary soda?

Dr. Robert Lustig:
The sugary soda.

Andrew Huberman:
10 kilos. Okay.

Dr. Robert Lustig:
10 kilos. No surprise. The one liter of water per day lost two kilos. Also, no surprise. Those were the easy ones. Now let's do the ones in the middle. One liter of milk per day. No change.

Andrew Huberman:
Presumably, that was full-fat milk. We're talking about Europe.

Dr. Robert Lustig:
Full-fat milk.

Andrew Huberman:
Yeah, they like their full-fat milk.

Dr. Robert Lustig:
No change. Why is that? They're taking on an enormous increase in total caloric intake.

Andrew Huberman:
I'm guessing that there was a blunted insulin response due to the fat in the milk?

Dr. Robert Lustig:
And also because lactose is not a very big driver of insulin response, and because there's a satiety effect.

Andrew Huberman:
That's like food.

Dr. Robert Lustig:
They eat less.

Andrew Huberman:
Yeah. It's like food.

Dr. Robert Lustig:
Like food. And finally, the key, the kicker to the whole thing, diet soda. The one liter of diet soda. What would you predict their weight would do?

Andrew Huberman:
More weight loss than in the water group, based on my understanding of the literature.

Dr. Robert Lustig:
They gained two kilos.

Andrew Huberman:
Wild. Because they ate more.

Dr. Robert Lustig:
Well, you tell me. Why did they gain two kilos if they were consuming a liter of diet soda, which are zero calories? The answer is because they still generated an insulin response.

Andrew Huberman:
And that insulin response generated more hunger?

Dr. Robert Lustig:
More weight and more hunger. Exactly. And that's the key. So they didn't gain the 10 kilos, they gained two kilos. So it looks better compared to the sugared version, but it looks like a problem compared to the water version or even the milk version.

Andrew Huberman:
So unless you bootstrap calories and hold that constant, you're going to see a weight gain due to artificial sweetener intake.

Dr. Robert Lustig:
Exactly right. And that's been shown 50 ways from Sunday in a whole bunch of different studies. So compared to sugar, yeah, it's better. But compared to water, it's way worse. And the reason is the insulin response. You put something sweet on the tongue, message goes tongue to brain, sugar's coming. Message goes brain to pancreas through the vagus nerve. Sugar's coming, release the insulin. And so tongue doesn't know if it's sugar or not. The pancreas releases the insulin, which drives energy into fat, whether it was from the diet sweetener or not.

Andrew Huberman:
I saw some really interesting data from Dana Small's group at Yale-

Dr. Robert Lustig:
Mm-hmm. Yep

Andrew Huberman:
... showing that when people have a diet soda with food, so this is like the Diet Coke with the sandwich or with the burger, maybe even with the pasta, the insulin response from the food and the insulin response from the diet soda are compounded, but there's a classical conditioning effect, Pavlovian effect-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... such that then later, if they just drink the diet soda, they get an even bigger insulin response just to the diet soda than they would have originally if they'd only had the diet soda separate from food. So in other words, the food-induced insulin response is conditioning a greater insulin response from the diet soda.

Dr. Robert Lustig:
And we actually have another study that demonstrates the same thing out of Singapore, Teh et al. in the "American Journal of Clinical Nutrition" 2018, I believe, that looked at a similar paradigm. Here's what they did. They took a bunch of people, and they admitted them to their clinical research center four times a week apart, and they did them in random order. And each time, they started the morning, they're fasting, and they did either a sucrose tolerance test or an aspartame tolerance test or a sucralose tolerance test or a monk fruit tolerance test. So two hours ingesting one of the four and measuring glucose and insulin over the course of the next two hours.

Andrew Huberman:
Fasted.

Dr. Robert Lustig:
Fasted.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Okay. Then it was time for lunch, and they let them have whatever lunch they want. It was a metabolic buffet. They could eat whatever they wanted off the buffet, except that they were being clocked. And the same for dinner. They were being clocked, but they could eat whatever they want.

Andrew Huberman:
In a given period of time.

Dr. Robert Lustig:
In the 24 hours.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Or from 7:00 a.m. to 7:00 p.m., whenever they went home. Okay? Turned out The sucrose tolerance test generated an insulin response, as you'd expect. The monk fruit, the sucralose, and the aspartame did not. But then when they ate lunch, if they'd had one of the three diet sweeteners in the morning, they ate more at lunch and more at dinner and generated an increased insulin response both at lunch and dinner, so that the area under the curve for the whole day was exactly the same.

Andrew Huberman:
So they ate significantly more?

Dr. Robert Lustig:
Yeah. Because they had the diet soda in the morning.

Andrew Huberman:
Wild. Well, I drink drinks that contain stevia, and I don't worry about it too much. But what you're saying is even if I bootstrap my calories, there's a possibility that the insulin response could have direct effects on the liver.

Dr. Robert Lustig:
Exactly right.

Andrew Huberman:
And not for the better.

Dr. Robert Lustig:
And not for the better. Now, having said that, we have undertaken an interesting project, which I don't know if you know about. In 2020, during the pandemic, I was approached by a food company in the Middle East called Kuwaiti Danish Dairy Company, KDD. It's the Nestle of the Middle East. Now, they make all sorts of junk: frozen yogurt, flavored milks, ice cream, confectionery, biscuits, tomato sauce. Okay? Kuwait has an 18% diabetes rate and an 80% obesity rate.

Andrew Huberman:
Eight-zero?

Dr. Robert Lustig:
Eight-zero.

Andrew Huberman:
Wow.

Dr. Robert Lustig:
In the adults. All right? Now, the company recognized that they wanted to be a metabolically healthy company, and they knew they weren't. They contacted me and said, "Would you put together a scientific advisory team to advise us what we need to do to change the food in order to be a metabolically healthy company? And we want to lead." And I said, "I'd be happy to do that with one proviso. We get to publish what we did so that it can serve as a roadmap for the rest of the food industry." And they said, "Fine." And so I convened a scientific advisory team with my colleague Wolfram Alderson, who started the very first farmers market in Los Angeles and is now actually the Director of Sustainability and Nutrition for KDD. Tim Harlan, who is the head of Culinary Medicine at George Washington University, Rachel Gal, who is a fatty acid expert who ran the Omega-3 for ADD trial at the NIH, and Andreas Cornstadt, who's actually a computer scientist from Stanford. And we basically stripped down every single thing that KDD did in terms of procurement, in terms of ingredients, in terms of packaging. We submitted every single ingredient to biochemical analysis because you couldn't trust what the vendors were basically telling KDD was in the food. We had to actually know what was in the food, and that was a half a million dollars all by itself. This was not a cheap little sojourn into the woods. This was a big deal. We basically re-engineered their entire 180-item portfolio, and they have now turned over 10% of their products to be metabolically healthy. And the precepts that we set in this paper, which is in "Frontiers in Nutrition" in March of this year, 2023. Three things, three principles. If you adhere to these three principles, you can turn any food healthy, including ultra-processed food. Number one, protect the liver. Number two, feed the gut. Number three, support the brain. If you have a food that does all three of those, it is healthy. If you have a food that does none of those three, then it's poison because it's not food.

Andrew Huberman:
I was going to say, it doesn't sound like food-

Dr. Robert Lustig:
Not food

Andrew Huberman:
... is the right descriptor in that case.

Dr. Robert Lustig:
Exactly. And if it does one or two, but not all three, then it's going to be somewhere in between. So the goal was to take all of KDD's products and move them from the lowest tier up to the highest tier by adhering to these three principles. And we came up with some very simple things. Number one, got to get rid of the sugar. Number two, got to add fiber. Number three, got to add omega-3s. Number four, got to do something about the emulsifiers. Because the emulsifiers are causing the gut inflammation, because after all, emulsifiers are detergents. They hold fat and water together. They burn a hole in the mucin layer. So they're actually contributing to that gut inflammation, and emulsifiers are strewn throughout ultra-processed food dom.

Andrew Huberman:
We've heard about hidden sugars a lot during today's episode and elsewhere, but based on everything you told us about artificial, excuse me, low-calorie sweeteners-

Dr. Robert Lustig:
Yep

Andrew Huberman:
... it makes more sense to me now why foods that are not touted as diet foods would be laced with things like sucralose, because it should drive the craving for that food through increases in insulin and craving of other foods later that day and later that evening. Is that why non-caloric sweeteners are added to all sorts of foods now? Because typically, one thinks non-caloric sweeteners probably only added to, quote-unquote, "diet foods," low-calorie foods, but that's not their only use.

Dr. Robert Lustig:
You're right. That's not the case, and they are adding diet sweeteners to foods that you didn't know had diet sweeteners in them. That's right. There are two reasons that this happens. One is insulin, because insulin blocks leptin signaling at the level of the hypothalamus and the nucleus accumbens. So if it blocks leptin, leptin is the hormone that your fat cells make that tells your brain you've had enough. So if insulin blocks leptin, it makes you hungrier, and it also extinguishes-- it stops the extinguishing of reward by that food so that you want more of it. So it does both, because leptin normally suppresses food intake and reduces craving.

Andrew Huberman:
The analogy that comes to mind is a slot machine that encourages you to feed more money and hit go to pull the lever, but that also blinds you to the outcome, so even if you win, you don't even know that you have wins. It's also blinding you to your losses. You're effectively becoming an automaton-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... of just eating without any kind of conscious understanding of what you're bringing in or tasting the food any longer.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
Right? It's not this like-- And Anna Lembke, when she came on the podcast, author of "Dopamine Nation" and obviously head of our dual diagnosis addiction clinic at Stanford-

Dr. Robert Lustig:
I know Anna well

Andrew Huberman:
... talked about these consumptive behaviors where people are scrolling social media or consuming porn or consuming drugs or alcohol in a way that they're not in touch with the pleasure of the substance or behavior anymore.

Dr. Robert Lustig:
Right.

Andrew Huberman:
They become automatons. But if they don't do it, they feel lousy. So the pleasure is gone, the pain is definitely waiting.

Dr. Robert Lustig:
Tolerance and dependence. That's the definition of addiction. So dopamine is an excitatory neurotransmitter. It excites the next neuron always. There is no such thing as dopamine inhibiting a postsynaptic neuron. Dopamine stimulates the next neuron, and it doesn't matter which dopamine receptor it is, one through five. It's always excitatory. Now, neurons like to be excited. That's why they have receptors. But neurons like to be tickled, not bludgeoned. Chronic overstimulation of any neuron, and you know this, leads to neuronal cell death. And the reason is because the neuron needs energy. The neuron is the most energy-dependent tissue in the body. It needs those mitochondria to be pumping out ATP like crazy to engage in neurotransmission. Well, when you're firing non-stop, you risk cell death. So the excitatory neuron, the postsynaptic neuron, has a plan B. It down-regulates the receptor. It down-regulates the dopamine receptor. So there's less chance that any stray dopamine molecule will find a receptor to bind to. And this is its plan B in order to try to mitigate the risk of dying. Well, what does that mean in human terms? It means you get a hit, you get a rush, receptors go down. Next time you need a bigger hit to get the same rush, and receptors go down, and you need a bigger hit and a bigger hit and a bigger hit until finally you need a huge hit to get nothing. That's called tolerance. And then when the neurons do start to die, that's called addiction. That's what we've got, and that's what's happened in terms of food addiction. So the question is what's addictive? Is fat addictive? No, because if fat was addictive, then all the people on the Atkins diet or on the ketogenic diet would be gaining weight, not losing it.

Andrew Huberman:
And I'd be craving ribeyes all day. I like a ribeye pretty often, actually. But I know people say no. But hey, look, my lipids are in line and I don't eat many starches, and I certainly avoid sugar.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Although now I'm thinking I might want to really reduce my low-calorie sweetener intake. I don't see myself reducing my stevia intake to zero, because it's in some things I really like.

Dr. Robert Lustig:
Andrew, I am not the food police.

Andrew Huberman:
Oh, right.

Dr. Robert Lustig:
You know?

Andrew Huberman:
I always say that too. I'm not a cop. But data are data and health data are interesting.

Dr. Robert Lustig:
The data say that that's not helping you any. That's what the data say.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
Point is that the fat's not the problem. The salt's not the problem. The caffeine's a problem.

Andrew Huberman:
Really?

Dr. Robert Lustig:
Caffeine's a classic addictive substance-

Andrew Huberman:
Right

Dr. Robert Lustig:
... at every level.

Andrew Huberman:
Yeah, but in terms of-

Dr. Robert Lustig:
And sugar's a problem

Andrew Huberman:
But if one can cut out caffeine by the early afternoon or even sooner in the day, and it's not consumed to excess, and it's in the form or coffee, yerba mate, some other form that's healthy, is it really that much of a problem?

Dr. Robert Lustig:
Um.

Andrew Huberman:
I love coffee and yerba mate.

Dr. Robert Lustig:
Me too. That's my addiction.

Andrew Huberman:
Like with a capital L underlined boldface highlight. Yeah.

Dr. Robert Lustig:
I feel your pain. And the answer is, no one has shown that coffee is toxic. It is addictive, but it's not toxic. Now, if you mix the coffee with alcohol, now you got Four Loko, now it's toxic.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
But in and of itself, caffeine is not toxic, and that's why there's a Starbucks on every street corner.

Andrew Huberman:
But it is highly reinforcing. I did an episode on caffeine where it covered some data that was published in the journal "Science," one of the three apex journals. And if you put caffeine, unbeknownst to the consumer, into plain yogurt-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... people will crave plain yogurt-

Dr. Robert Lustig:
Indeed

Andrew Huberman:
... much more. People like the feeling of being caffeiny, as long as it's not creating anxiety levels-

Dr. Robert Lustig:
Right

Andrew Huberman:
... of energy.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
I'm going to stick with caffeine.

Dr. Robert Lustig:
That's fine. Yeah, and so will I.

Andrew Huberman:
We've been talking a little bit about the hypothalamus as well as some peripheral gut-based mechanisms for hunger and satiety.

Dr. Robert Lustig:
Right.

Andrew Huberman:
This is a great opportunity to talk about some of the GLP-1 agonists that are now widely used, so typically called Ozempic, but GLP-1, glucagon-like peptide 1.

Dr. Robert Lustig:
Right.

Andrew Huberman:
Originally discovered in the Gila monster-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... which eats very seldom, and some really smart biologist, I love biology like this, said, "How come they don't have to eat very much?" Well, their blood is loaded with GLP-1.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And so they only have to eat one whatever Gila monsters, um delight in per year or something outrageous like that. Humans make GLP-1 as well. My understanding is that GLP-1, not that's injected, but that one makes naturally, is acting on both the brain and the gut to increase satiety.

Dr. Robert Lustig:
So it is acting on the brain, no argument, but the primary action is on the gut. GLP-1 decreases the rate of gastric emptying. That is its primary driver. Yes, it does affect the brain. I'm not arguing that it does, but the primary effect is to reduce the rate of gastric emptying. So you stay fuller longer because the food doesn't move through the stomach and the intestine as fast.

Andrew Huberman:
Interesting. In South America, in Uruguay and Argentina, it was long thought that yerba mate consumption, which we know very modestly increases GLP-1, and by the way, a lot of other things do too.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
That people were taking it after meals for its laxative effect-

Dr. Robert Lustig:
Mm

Andrew Huberman:
... partially, but that's not pleasant for-

Dr. Robert Lustig:
But that's also at the colon.

Andrew Huberman:
That's at the level of the colon.

Dr. Robert Lustig:
Rather than the stomach.

Andrew Huberman:
But it is used fairly effectively for people to space their meals without snacking. And maybe it's the GLP-1, maybe it's something else.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
But people are injecting themselves with GLP-1 analogs now, agonism analogs.

Dr. Robert Lustig:
At $1,300 a month. Yep.

Andrew Huberman:
Is that what it costs?

Dr. Robert Lustig:
That's what it costs right now.

Andrew Huberman:
And it seems to be pretty effective at inducing weight loss, although a significant amount of that weight loss seems to be from skeletal muscle tissue.

Dr. Robert Lustig:
And we need to talk about that.

Andrew Huberman:
So what are your thoughts on Ozempic as a primary? Earlier you talked about primary and secondary control.

Dr. Robert Lustig:
Right.

Andrew Huberman:
You referred to it a little bit differently in the context of statins.

Dr. Robert Lustig:
Right.

Andrew Huberman:
So a kid comes in who's obese or slightly overweight.

Dr. Robert Lustig:
Right.

Andrew Huberman:
And it's like, "Mm, I don't know what to do. I'm trying to eat better, exercise." Or a person comes in and says, "Hey, I've had a really hard time getting that last 29 pounds off for so many years."

Dr. Robert Lustig:
Yep.

Andrew Huberman:
"Will you prescribe me Ozempic?"

Dr. Robert Lustig:
So the short answer is, number one, I'm retired, so I'm not prescribing anything. But let's go there. The data show that GLP-1 analogs, like semaglutide and now tirzepatide, which is Lilly's version, Mounjaro is the diabetes version, Zepbound is the obesity version.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
In the same way that Ozempic is the diabetes version for Novo Nordisk, and Wegovy is the obesity version.

Andrew Huberman:
But they're all GLP-1 inhibitors.

Dr. Robert Lustig:
They're all GLP-1 analogs.

Andrew Huberman:
They're synthesized in a lab. It looks like GLP-1, smells like GLP-1, acts like GLP-1 when injected.

Dr. Robert Lustig:
Tirzepatide, the Lilly one, actually has a dual function. It binds to the GIP receptor, so it might have double duty. And the data show that it's actually even slightly more effective at weight loss than the Novo Nordisk version. So we'll be seeing a shift in terms of consumer preference soon, no doubt. But here's the thing. You look at the data, one year of treatment, 16% weight loss. Now that sounds great, and I'm not saying it's bad. It's good.

Andrew Huberman:
And people are not craving food all the time. Is that because people are feeling full longer?

Dr. Robert Lustig:
Right.

Andrew Huberman:
So they're eating less.

Dr. Robert Lustig:
They're eating less. And so-

Andrew Huberman:
This is the calorie in, calorie out model.

Dr. Robert Lustig:
They're eating less.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
And so they are losing weight. I'm not arguing that.

Andrew Huberman:
And they might be craving alcohol less according to some recent reports.

Dr. Robert Lustig:
Yes. Well, we can go there for a minute, too, in a second. Here's the problem. When you look at that 16% weight loss, as you just said, when you put people in a DEXA scanner, they have lost equal amounts of fat and muscle. Now, is it good to lose muscle? No, it is not good. Ask any little old lady who breaks her hip if she wishes she had a little bit more muscle.

Andrew Huberman:
Or somebody who died had lost a lot of muscle because they weren't offsetting the weight loss with resistance training or some other form of exercise, and the amount of food that they can eat in order to maintain that weight, to put it in scientific terms, sucks.

Dr. Robert Lustig:
And we mentioned Peter Attia earlier, okay? In "Outlive," he's made it very clear that sarcopenia, lack of muscle mass, is one of the drivers of mortality. So losing muscle is not a good idea. But you lose equal amounts of fat and muscle. What else causes loss of equal amounts of fat and muscle? Starvation. In fact, the reason that all these GLP-1 analogs work is because you stop eating.

Andrew Huberman:
Like the Gila monster.

Dr. Robert Lustig:
It's starvation. Yeah, just like the Gila monster.

Andrew Huberman:
Although the Gila monsters look pretty chubby to me.

Dr. Robert Lustig:
Well, ask another Gila monster.

Andrew Huberman:
Yeah, I did, but unfortunately, whatever answer it provided was not interpretable.

Dr. Robert Lustig:
Indeed. The point is that starvation is not so good. And if you think about why it's working, it's reducing the rate of gastric emptying. Well, it turns out that that's the reason for its side effects, the reduction in gastric emptying. That's why you get nausea. That's why you get vomiting. That's why you get pancreatitis. And most importantly now, gastroparesis. Your stomach turns to stone, and you can't move any food through your intestine at all. And worse yet, when you stop the medicine, the gastroparesis doesn't get better. This is not a good idea.

Andrew Huberman:
This is like the opposite of the yerba mate-induced effect, which has a sort of prolaxive gastric emptying, maybe GLP-1 agonism. Gosh. Okay. So it's obvious why people who've struggled to lose weight like it.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
Especially if their struggle to lose weight was, at least in their mind, the consequence of being hungry all the time and needing to eat more.

Dr. Robert Lustig:
Or was it because of the reward and their dependence?

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
Because, in fact Yes. These GLP-1 analogues reduce reward, and that's one of the reasons why they've noticed that reduction in alcohol consumption as well. And that sounds like a good thing, except there are also numerous cases now of major depressive disorder in response to these drugs.

Andrew Huberman:
It's almost like naltrexone or something for the treatment of addiction-

Dr. Robert Lustig:
Well-

Andrew Huberman:
... which sometimes can be useful, but attempting to remove the amplitude of that reward signal, on paper it makes sense, but it doesn't always play out.

Dr. Robert Lustig:
And in practice, it doesn't play out. That's right. And so I'm going to refer you now to an old literature that was from 2006. There was a drug that was approved in Europe called Rimonabant, okay? A trade name Acomplia. And it was approved in Europe for weight loss, and it was pretty good at weight loss. It caused about 20% weight loss. It also caused severe depression and 21 suicides.

Andrew Huberman:
So it's no longer available.

Dr. Robert Lustig:
Yeah, it was pulled from the European market, never approved in the United States. And the reason this happened was because this was the anti-marijuana drug. This was the anti-munchies drug. This was an endocannabinoid antagonist. Well, when you reduce reward, you also reduce your desire to live, and that's why this concern about reduction in alcohol consumption, we've already seen major depressive disorder in patients receiving Ozempic. So are we going to see the same thing play out as we did for Rimonabant? I'm worried about it.

Andrew Huberman:
Or Fen-phen.

Dr. Robert Lustig:
Well, Fen-phen didn't have-

Andrew Huberman:
No, it was cardiac.

Dr. Robert Lustig:
It was cardiac, right.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
We had cardiac problems due to the fenfluramine, because of the serotonin 1B receptor agonism.

Andrew Huberman:
Right. I'm just referring to the fact that these, quote, unquote, "blockbuster drugs" for obesity, they tend to follow a contour of very promising, very exciting, a lot of people losing weight. Suicides are very promising, a lot of people losing weight. Cardiac issues, very promising, losing weight, and now you're saying the stomach turns to stone. It sounds so biblical.

Dr. Robert Lustig:
Well, indeed. So that's the question. And then finally, we can really talk biblical. If everyone in America who qualified for Ozempic got it, that would be 2.1 trillion to the healthcare system, which is currently at 4.1 trillion. So that would be a greater than 50% increase in healthcare costs, okay, at 1,300 a month. Conversely, if we just got sugar consumption down to USDA guidelines by basically putting some limits on how much added sugar the food industry can put into any given product, like Froot Loops, we could reduce weight by 29% and save $3.0 trillion. So we'd get better weight loss and we'd save $5.1 trillion, which makes more sense to the US government.

Andrew Huberman:
Well, earlier you were alluding to government, big food, big pharma relationships. There's a huge win here for whoever's manufacturing these GLP-1 analogues.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
But the question is, who's paying the tab?

Dr. Robert Lustig:
Well, we are. Now, the question is, why can't the government see that? And the answer is because the government's on the dole, too. Because the government, through tariffs on US-made foods, grosses $56 billion a year. So they're a player. They're not just a regulator, they're an actor.

Andrew Huberman:
To play devil's advocate a little bit, listen, I'm going to be the last person to step in and try and defend government as a unified body. I'm not qualified to do that. But you could see how if you looked at it like checkers instead of chess, you'd say, okay, here's a drug that's going to allow many millions of people to reduce their overall body weight. Overall body weight is a risk factor for a number of things, and there will be savings on the back end as a consequence of that weight loss. So that's the checkers version.

Dr. Robert Lustig:
Right.

Andrew Huberman:
The chess version is how you're describing it. And I think that clearly, people in government are, well, most, some perhaps are smart enough to play chess, not checkers, or to at least understand it, but there's very little incentive for the chess model. So what would, quote, unquote, "solve this problem" is the same thing that happened to Fen-phen or this Rimonabant?

Dr. Robert Lustig:
Rimonabant.

Andrew Huberman:
Which is if suddenly there's a major issue with the drug, then everyone stops taking it, and traditionally, that's how it's gone. It sounds like these GLP-1 analogues are going to make it through the chute, though.

Dr. Robert Lustig:
Yeah. There is a very clear downside to these medicines. On the other hand, there's an upside. And so I'm not sad that these medicines exist. I'm for them. I'm not against them. I'm for them for the right patient.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
And right now, it's not the right patient who's getting them.

Andrew Huberman:
Just like the statins. So what if somebody who's taking one of these analogues makes it a point to do resistance training? And here, you mentioned bodybuilders earlier. I'm not suggesting they become bodybuilders, but we now know, and I think Peter Attia and others would agree, that everybody should be doing some form of muscle loss offsetting resistance exercise.

Dr. Robert Lustig:
Agree.

Andrew Huberman:
At least past their reaching their adult height or something.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
I know there are those that say weight training doesn't blunt your height. But anyway, let's just say that from-

Dr. Robert Lustig:
Hit training

Andrew Huberman:
... early 20s onward, doing something.

Dr. Robert Lustig:
Especially if you're on these medicines.

Andrew Huberman:
Right.

Dr. Robert Lustig:
In order to maintain muscle mass.

Andrew Huberman:
Right. So that's a different picture, right? People are drinking less alcohol. Again, I'm playing devil's advocate here.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
So if we look at these compounds not in a vacuum, but okay, the person who's been carrying that extra 30 pounds is now only carrying a few extra pounds of adipose tissue. They've lost a lot of muscle, but now they feel well enough to exercise.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
The depression part worries me.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
But anyway, I'm just trying to round the contour of it.

Dr. Robert Lustig:
What we've seen in children, because that's who I took care of, was that often they needed a jump start, okay? And there were different ways to get them to jump start.

Andrew Huberman:
Stomach stapling.

Dr. Robert Lustig:
Well, that's not jump start. That's-

Andrew Huberman:
But that was what a lot-

Dr. Robert Lustig:
Way down the line

Andrew Huberman:
... of people did. I have a friend, he was, and sadly still is, really big.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
And he always talked about the stomach stapling like, "If I could just get-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... 50 pounds down quickly, then I could exercise, but exercise is painful," this kind of thing. And sadly, he's continued to maintain or creep up in a very excessive weight.

Dr. Robert Lustig:
And that's the point, is that this concept of jump start actually, if you're only doing it yourself, doesn't really work. And the question is, why is his weight creeping up if he's had the stomach stapling? And the answer is because he's a sugar addict.

Andrew Huberman:
Yeah. He's definitely addicted to the super big gulp soda and that, yeah.

Dr. Robert Lustig:
If you drink your calories, it doesn't really matter, does it?

Andrew Huberman:
No, and he's got such terrible psoriasis, and joint pain, and all this, that the prospect of exercising is like a-- You might as well tell him to flap his wings and go to Mars.

Dr. Robert Lustig:
Fructose is a driver of immune dysfunction. You can tell him, from me, if he got off the sugar, his psoriasis would get better, his weight would get better, his arthritis would get better, and he could have that jump start.

Andrew Huberman:
This is a perfect example to bridge to the brain component of all this, because I've long wondered, based on what I understand about neural circuitry and neuroplasticity, I know we share in this knowledge, that at some point, carrying a lot of adipose tissue means that the brain sort of represents the body differently. We know there are these somatotopic maps of self-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... but that the neural machinery in the hypothalamus, sure, which is responsible for motivated states-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... et cetera, but also just the entire mapping of the self-

Dr. Robert Lustig:
Yep

Andrew Huberman:
... changes. In other words, if one is fat long enough-

Dr. Robert Lustig:
Mm-hmm

Andrew Huberman:
... that it becomes increasingly hard to get to a healthy weight because of the way that the neural circuitry is impacted. It basically remaps to maintain that fat person, not necessarily even just at the level of appetite, but just in terms of what do big animals do? I had a bulldog that weighed 90 pounds, bulldog mastiff. He was very economical with his movement.

Dr. Robert Lustig:
Yes.

Andrew Huberman:
He was extremely powerful.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
He could run, at least when he was younger.

Dr. Robert Lustig:
Indeed.

Andrew Huberman:
But if he could be still, he was still. As opposed to-

Dr. Robert Lustig:
Yeah

Andrew Huberman:
... certain smaller animals that are peripatetic, right?

Dr. Robert Lustig:
Because he was leptin resistant.

Andrew Huberman:
Mm-hmm.

Dr. Robert Lustig:
So leptin, as we talked about briefly, is the hormone that tells your brain you've had enough. If you are leptin sensitive, you are happy to burn. If you are leptin resistant, your brain thinks you're starving. And if your brain thinks you're starving, it's going to affect your behavior in two ways. It's going to make you want to eat, and it's also going to make you want to conserve because the goal is to try to increase the leptin levels in order to overcome that resistance, which, of course, you can never do because all you're going to do is lay down more fat and make more leptin.

Andrew Huberman:
That makes so much sense because leptin comes from the adipose tissue.

Dr. Robert Lustig:
Exactly. So that leptin resistance is what you have to be able to break through. You have to fix the leptin sensitivity. Well, what's the driver of the leptin resistance? Insulin. Insulin inhibits leptin signaling, and it does it at three separate places in the POMC neuron, the pro-opiomelanocortin neuron in the hypothalamus. It does it at IRS-2, insulin receptor substrate 2, it does it at SOCS-3, suppressor of cytokine signaling 3, and it does it at PIP3, phosphatidylinositol triphosphate. Those three separate arms of the leptin receptor are all basically put to sleep by high insulin. Insulin blocks leptin signaling. So the higher the insulin goes, the more your brain thinks you're starving. And the more your brain thinks you're starving, the hungrier you get, and the less you want to move. So the gluttony and sloth that we've been talking about all in our podcast is really biochemical. It is secondary to this phenomenon of insulin blocking leptin signaling. You got to fix that first. Get the insulin down any way you can. And the best way, get rid of the refined carbohydrate and sugar. That's where you start.

Andrew Huberman:
It makes so much sense.

Dr. Robert Lustig:
It works, too. How about that?

Andrew Huberman:
That's always good.

Dr. Robert Lustig:
It is.

Andrew Huberman:
I once heard you say, I think it was in a conversation with Peter Attia on his podcast, and this really stuck in my mind, that when a person consumes glucose, that it activates a number of different brain sites.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
Neurons loving glucose.

Dr. Robert Lustig:
Mm-hmm.

Andrew Huberman:
But that when one ingests fructose, that it preferentially activates neurons in the reward pathway.

Dr. Robert Lustig:
That's right.

Andrew Huberman:
At maybe seven times the magnitude or something like that.

Dr. Robert Lustig:
Well, glucose activates the basal ganglia. This is work from Wolnerhausen in Switzerland, and also Eric Stice at Oregon Health Sciences.

Andrew Huberman:
It's the circuits for movement, and planning, and execution.

Dr. Robert Lustig:
Exactly.

Andrew Huberman:
Yeah.

Dr. Robert Lustig:
Okay? Fructose basically stimulates the nucleus accumbens, the reward center. It is just like heroin, just like cocaine, just like nicotine. It activates the reward center. It doesn't do anything for the basal ganglia. So it is addictive. Anything that stimulates the reward center in the extreme is addictive. So we have chemical addictions, heroin, cocaine, nicotine, alcohol, sugar. We have behavioral addictions, shopping, gambling, internet gaming, social media, pornography. Doesn't matter. They all stimulate dopamine in the reward center, and in the extreme, they are all addictive. So the question is, if you are addicted, is that personal responsibility?

Andrew Huberman:
Well, it's a question I think about a lot because I know a lot of people in the addiction recovery community, both from the treatment end and the addict end.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
And this always comes down to this question when somebody is suffering from an addiction of any kind, and they're resistant to getting treatment. If you look at them as being sick, at least in that moment, is a sick person in the best or worst or at least diminished position to guide their own treatment? So for instance, somebody with dementia, would you ask them, "Do you want to go see a neurologist?" You might ask them that, but are they the best person to make that decision?

Dr. Robert Lustig:
Well, this is the problem. So this is where personal responsibility falls down. So personal responsibility, as we talked about, four criteria have to be met. None of them are met. That's the first issue. Second one is a little bit, shall we say, cheekier. Who invented personal responsibility? Any idea?

Andrew Huberman:
I'm definitely going to get this one wrong.

Dr. Robert Lustig:
Yeah, you're going to get this one wrong.

Andrew Huberman:
Oh.

Dr. Robert Lustig:
Are you ready? Go ahead.

Andrew Huberman:
Yeah, I don't know.

Dr. Robert Lustig:
The tobacco industry.

Andrew Huberman:
The notion of personal responsibility?

Dr. Robert Lustig:
They invented it. There was no personal responsibility until tobacco in 1962, because they were getting killed on the science, and they needed to invent another reason for you to smoke. In fact, there's a paper that came out, Dorfman et al., that looked at The New York Times and The Washington Post, and they did an entire lit search of all the output of those two newspapers for decades to look for the term personal responsibility. And the very first time it was ever mentioned was 1962. And it didn't pick up in speed until 1986, which was the same year as Cipollone v. Liggett at the Supreme Court, which basically said that the cigarette industry was guilty of plying people with an addictive substance. So this is very specifically industry driven, and we have the data to prove it.

Andrew Huberman:
Amazing. Well, I wonder, along the lines of personal responsibility, given that many listeners to this conversation are going to be thinking about their own food intake and food choices, and that of their children and other relatives, that we could play a little, not a game, but a little rapid-ish fire Q&A. Never done this before on this podcast, but I think it's particularly appropriate for a discussion like this that wicks out into so many areas. And I absolutely will invite you back and perhaps along with-

Dr. Robert Lustig:
My pleasure

Andrew Huberman:
... Melissa Apple to talk about some of the exciting work you guys are doing because there's so much we could cover. But people are going to wonder, in a very practical sense, whether or not they should or should not be consuming certain things. And I know you're not the food police.

Dr. Robert Lustig:
I'm not the food police.

Andrew Huberman:
And I'm not a cop, and I do believe people should be in choice about these matters. But I also believe that because you're a guest on the podcast and you're highly informed and have done clinical work and research for so many years in this area, and you have such a clear stance on the role of big food. And we really, really appreciate your honesty and directness, but now you'd be willing to provide a comment about a couple of different terms that I'll throw out. And if you choose to say really nothing to say about that, fine. That would be a quick pass.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
So here we go. And we covered a little bit of this earlier, but fruit in whole form. So has fructose but has fiber, so thumbs up, thumbs sideways, or thumbs down for fruit consumption?

Dr. Robert Lustig:
Fruit is fine. Fruit juice is not.

Andrew Huberman:
Great. Thank you. White rice versus brown rice, and among the white rices, the sticky rice and the rices with added sugars, which you find in a lot of restaurants.

Dr. Robert Lustig:
Brown rice because of the fiber. White rice, polished, number one, all the vitamin B1 gone, and, of course, a much larger glucose excursion. That glycemic index thing, which of course I hate, it's glycemic load that matters. And that is a very high glycemic load. So brown rice.

Andrew Huberman:
So brown rice is better than white rice?

Dr. Robert Lustig:
Yes.

Andrew Huberman:
Okay. In a meaningful way?

Dr. Robert Lustig:
In a meaningful way.

Andrew Huberman:
Okay. Earlier you mentioned tomato sauce. I love tomato sauce that's made from just tomatoes. So are most tomato sauces filled with sugar?

Dr. Robert Lustig:
Perfect, our little recommendation engine, looked at this question, and it turns out that only 10% of the available tomato sauces out on the market don't have added sugar. So you have to know which ones, well, you can look yourself, or you can look up Perfect, and it will tell you which ones you can buy.

Andrew Huberman:
If people chose to consume bread, which many people do, is there a way to, just across the board without just baking your own or looking at the ingredients list to make a better choice? Is it like sourdoughs tend to have less sugar than blank?

Dr. Robert Lustig:
Well, sourdough has been fermented, so it will have actually consumed some of the sugar, so it would be a better choice. But really the best choice is the highest fiber breads. Now, if you look at a wheat berry, it is 25% fiber. The husk is 25% of the weight of that wheat berry. That means that the carbohydrate to fiber ratio of a wheat berry is three to one. So a good bread should have a carbohydrate to fiber ratio of somewhere between three to one to five to one, tops. Anything above that means that they've stripped the fiber away. So that's something you could do, but the easier way is to actually look it up on Perfect.

Andrew Huberman:
You mentioned meat and meat sourcing, egg and chicken sourcing earlier. May we just revisit that? Meat, fish and eggs, thumbs up, thumbs sideways, thumbs down, or it depends?

Dr. Robert Lustig:
It depends. It depends on where the meat came from. It depends on whether it was pasture-raised. Depends on whether it's organic or not. If the animal was injected with antibiotics, stay away from it because those antibiotics are in the meat. They're going to basically sterilize your gut, and then the bad bacteria are going to take over. We haven't really talked much about the microbiome today, but that's a whole podcast all by itself.

Andrew Huberman:
Well, we can touch on it a little bit more. For low sugar fermented foods, thumbs up, thumbs sideways, thumbs down?

Dr. Robert Lustig:
Fermented foods, short chain fatty acids, all good.

Andrew Huberman:
What are your favorite sources of fermented foods?

Dr. Robert Lustig:
I like kimchi.

Andrew Huberman:
Yeah. I like kimchi too. I like some of the live sauerkrauts.

Dr. Robert Lustig:
Yeah. That's also good, but with the right accoutrement. The one thing I would be careful about is yogurt. Okay? So there are yogurts with live cultures, and there are a whole lot of yogurts with dead cultures. And if it's a yogurt with dead cultures, it's kind of irrelevant, and the chances are they've actually covered up the sourness with sugar. So, large commercially available yogurt, be very careful. Okay? If it's a artisan yogurt made by people you know or trust, that's a very different story. Yogurts with live cultures.

Andrew Huberman:
Intermittent fasting, do you practice it and what do you think about it?

Dr. Robert Lustig:
I don't practice it, but I am for it for the right patient. Turns out who's the right patient? The patient with liver fat. Because the reason it works is because it gives the liver a chance to basically burn off the fat that it's stored.

Andrew Huberman:
Zero-calorie soda.

Dr. Robert Lustig:
Pff.

Andrew Huberman:
Got it. A definite no. And I don't even have to ask about sugary soda because that's-

Dr. Robert Lustig:
That's basically just poison in a can.

Andrew Huberman:
Food combinations. I have a feeling I know what your answer is, but the glycemic index, which we know your feelings on now, asserts that if you combine some fat with a sugary-- like eating ice cream, you have a more blunted insulin response than if you were to eat pure sugar of equivalent calories. But, what are your thoughts on food combinations as a way to blunt the insulin response?

Dr. Robert Lustig:
Food combinations are great if there's some fiber associated with it.

Andrew Huberman:
It comes back to fiber again.

Dr. Robert Lustig:
And by the way, full disclosure, I am the chief medical officer of a fiber company.

Andrew Huberman:
What is it?

Dr. Robert Lustig:
It is called Biolumen, and it is a proprietary fiber. It is a microcellulose sponge, seven microns in diameter, so the size of a red blood cell. You swallow it, it goes to your stomach, it expands 70 fold over its original size. And so it'll give you a feeling of fullness because it's taking up space in the stomach. But more importantly, when it expands, the nooks and the crannies in the sponge become available, and embedded in those nooks and crannies are a set of proprietary hydrogels, soluble fiber, which sequester glucose, fructose, sucrose, simple starches, and render them unavailable for early absorption in the duodenum, thus reducing the glucose response, reducing the insulin response, protecting the liver, and moving it through the intestine so that microbiome can chew it up for its own purposes, feeding the gut. We can reduce glucose absorption by 36%, fructose absorption by 38%, sucrose absorption by 40%, simple starch absorption by 9%, and increase short chain fatty acid production by 60% without an increase in gas.

Andrew Huberman:
When do people take this?

Dr. Robert Lustig:
With meals.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
So it comes as a sachet. One teaspoon, sprinkle it on your food or take it in a drink, just mix it in and slug it down, and then eat breakfast, lunch or dinner. And it will basically act like you ate real food. It will turn processed food into real food in the intestine. And we have clinical trial data that demonstrates that.

Andrew Huberman:
Is it available as a commercial product?

Dr. Robert Lustig:
It is available. It is called Munch Munch. Now, I hate that name.

Andrew Huberman:
I hate it too.

Dr. Robert Lustig:
I didn't make it up.

Andrew Huberman:
Well, you need to get your market-

Dr. Robert Lustig:
The marketers did that.

Andrew Huberman:
Your marketing team sucks, but the product sounds amazing.

Dr. Robert Lustig:
Yeah. So biolumen.tech.

Andrew Huberman:
Great. Thank you for that. Sorry Munch Munch marketing team, but you got to munch munch to a new product name. But it sounds like a very interesting product, and it actually answered my next question, which was about fiber supplements.

Dr. Robert Lustig:
Fiber is good, but there are two kinds of fiber. There's soluble and there's insoluble, and they are not the same. So soluble is what goes into Fiber One bars, that psyllium, inulin, uh Pectin, like what holds jelly together, that's good. I'm not saying it's bad, but you need the insoluble fiber, the cellulose, the stringy stuff in celery, the cardboard, if you will. Together, they form this gel that we talked about earlier. If you only consume the soluble fiber, which is what the food industry will add to food, because the insoluble fiber is not miscible. If you only add the soluble fiber back, you're not getting the benefits of the entire fiber complement.

Andrew Huberman:
Earlier when talking about the NOVA system and how most all of our foods are nine-- Let's say, I know it was 7% to 10%, let's say 95%. Let's err on the side of better. 95% of our food should come from NOVA system class one or class two foods.

Dr. Robert Lustig:
Or three.

Andrew Huberman:
Or three. Okay.

Dr. Robert Lustig:
Or three.

Andrew Huberman:
Staying away from those NOVA class four foods.

Dr. Robert Lustig:
Yep.

Andrew Huberman:
Could you give us some examples of NOVA class one and class two foods, just broadly speaking?

Dr. Robert Lustig:
Okay. NOVA class one is any food without a label. Period. If you see a label on a food, it's a warning label.

Andrew Huberman:
Well, ground beef has a label. Okay, so that's-

Dr. Robert Lustig:
Well, does it?

Andrew Huberman:
So you're talking about apple. Well, when I buy it, it has a label. I'm asking this because people are going to wonder, so-

Dr. Robert Lustig:
Well, it doesn't have a nutrition facts label. Is there a nutrition facts label on a thing of ground beef?

Andrew Huberman:
I buy that ground beef, or I consume venison, where if you flip it over, it says how many calories, how many protein. So there's a label.

Dr. Robert Lustig:
All right.

Andrew Huberman:
But it's just beef or venison.

Dr. Robert Lustig:
Okay.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Then that's class one.

Andrew Huberman:
Okay, egg?

Dr. Robert Lustig:
Egg is class one.

Andrew Huberman:
So, and then, of course, fruit, apples, orange. Okay, so it doesn't matter if it has a name tag, as long as it doesn't have a nutrition facts-

Dr. Robert Lustig:
A nutrition facts label

Andrew Huberman:
Got it.

Dr. Robert Lustig:
Real food does not need a label. It's only if they did something to it that it needs a label. So you have to look at every label as a warning label. Now, the problem with the label is it only tells you what's in the food. What you really need to know is what's been done to the food. Because it's the ultra-processed food that's the problem. They don't want to tell you that. That's secret. Okay? Secret from a proprietary standpoint, but also secret because if you knew what they did to it, you wouldn't eat it. You would never buy it. And they don't want you to know. So they only tell you what's in the food. That's not what's important. It's what's been done to the food that's important. And that's why this NOVA class four is so important, and that's why Perfect is so important, because it'll do the work for you.

Andrew Huberman:
Great. We'll definitely provide links to all of these. So if you could pick one thing to recommend to people that want to improve their health-

Dr. Robert Lustig:
Get rid of sugar.

Andrew Huberman:
Okay.

Dr. Robert Lustig:
Period.

Andrew Huberman:
Very clear.

Dr. Robert Lustig:
That's number one. Number two, go for a walk.

Andrew Huberman:
The exercise piece. Yeah.

Dr. Robert Lustig:
Go for a walk.

Andrew Huberman:
And if you could recommend one thing that the general public can do to try and assist in this advocacy for not redefining but actually clearly defining what is food and what isn't, and making people aware at the level of policy and change and school lunches. If there were one thing, what can we do? You've clearly activated my neurons surrounding the set of problems that exist and the paths to correct them, but should we be writing to our congresspeople? Should we be getting angry at hospitals because they've got all these fast food machines, and the cafeteria food is like-

Dr. Robert Lustig:
That would be good

Andrew Huberman:
... is illness promoting?

Dr. Robert Lustig:
At UCSF, we've gotten rid of all sugar beverages. We have the Healthy Beverage Initiative. So you can-

Andrew Huberman:
No Coke machines at UCSF?

Dr. Robert Lustig:
No Coke machines at UCSF.

Andrew Huberman:
Wow. Stanford, check that out, because people always send me pictures of the Coke machines in the School of Medicine. I'm like, "Listen, I didn't put them there," but I-

Dr. Robert Lustig:
We have to model for the public. Where was the first place that smoking was banned? Hospitals. Okay? Because we knew. So if you get rid of the sugared soda at the hospital, you're telling people something. So yeah, I think that every hospital and really every public venue in America needs to clear out the junk.

Andrew Huberman:
So post photos of junk that are supposed to be in health-promoting institutions, and I guess we're trying to cancel junk food.

Dr. Robert Lustig:
Shame.

Andrew Huberman:
We're trying to cancel junk food. I'm pretty opposed to cancel culture, but here we go. We're going to cancel. Marvelous. It's actionable, it's straightforward, it's low cost, low time investment. Zero cost, very low time investment. So thank you for that.

Dr. Robert Lustig:
And look up Eat Real, because we're doing it for your kids, so you need to help support it. Any school district in America can do it. So what do we do? We have a business model whereby the food services director either purchases or rents a dilapidated factory in the center of the district, repurposes it into a food preparation facility. They can make 27 to 30,000 meals a day with a skeleton crew. And you control what's in it, and because you're buying in volume, it actually reduces the cost, so it's cheaper than buying it from Sysco or Aramark or Sodexo or wherever. And then you farm it out via truck or bus to all the different schools, so every kid gets a hot meal made from scratch each day, and we can solve this problem.

Andrew Huberman:
Can't help but ask this one last question. For people that want to cut out sugar, which you clearly stated is the most important thing to do for one's health, how do we know how much sugar is in something? So should people be looking at labels and just looking for how much sugar, how much carbohydrate, or could we even go so far as to say if it says High fructose corn syrup, then it's on the no-fly list. Don't eat it.

Dr. Robert Lustig:
So the problem is that there are 262 names for sugar, and the food industry uses all of them. And the reason they use all of them is because they can include a different sugar as number five, number six, number seven, number eight, number nine on the list, and when you add it up, it becomes number one. They hide it in plain sight, and they do it on purpose. Now, do I expect everybody to memorize all 262 names? No, of course not. Can you figure it out yourself? Well, the answer is no, unless they have the line where it says added sugars. If it says added sugars, it is either sucrose or high fructose corn syrup. No one's adding lactose. Okay? That's not happening.

Andrew Huberman:
Or glucose.

Dr. Robert Lustig:
They're not even adding glucose, because glucose isn't that sweet. Glucose is not that interesting. You don't see people going around chugging Karo syrup, do you? Okay? That's glucose. Who cares? Yeah, it might be good in a molasses cookie, but that's it. All right? So it's fructose. So you need to know what's been added. So if it says added sugars, that's a good place to start. No greater than one teaspoon per serving. No greater than four grams per serving of added sugars. Anything greater than that, leave at the store.

Andrew Huberman:
And aim for those NOVA type one, type two.

Dr. Robert Lustig:
And aim for NOVA types one, two, and three. And if you don't know whether it's NOVA type one, two, or three, you can use Perfect. And if you don't look at that, then go look at the nutrition facts label, and anything that has more than four ingredients is NOVA class four.

Andrew Huberman:
Robert Lustig, thank you so much. You've provided such an incredible education in nutritional biochemistry, the processing of fat, protein, carbohydrate, sugar, fructose in particular, the clear detriments of consuming fructose on so many different organ systems. I love, love, love that you separated out food science, nutrition, and metabolic health.

Dr. Robert Lustig:
Yeah.

Andrew Huberman:
That's a gazillion dollar delineation for people to understand and to shape their understanding of all the information that's out there and bins into these different categories. You've given us so many actionable tools, new conceptual frameworks. You've given us a real tour de force today in-

Dr. Robert Lustig:
Thank you

Andrew Huberman:
... just oh-so-clear language. So I want to thank you.

Dr. Robert Lustig:
Oh, thank you.

Andrew Huberman:
I've learned a ton, and I know everyone else has as well. And if people have questions, they can of course put them in the comments section on YouTube. That's the best place. We'll provide links to all the companies and websites that you referenced and some of your other work. And listen, I'm so grateful that you exist and that you've done the work that you've done, and your passion and your advocacy for health is just oh-so-clear. So thank you so much for your time.

Dr. Robert Lustig:
So I want to thank you. And the reason I want to thank you is first of all, inviting me. That's nice. That's good. But the reason is because people need to understand science. I am completely in agreement with you. The public needs to understand science. They listen to you because you, number one, provide the science, and number two, you don't talk down to them. You treat them as equals. And that is truly remarkable, and so I want to thank you for your service.

Andrew Huberman:
Well, you're most welcome. It's a labor of love, and I think it was the great Max Delbrück that said, "When teaching, assume zero knowledge and infinite intelligence." And I do believe that humans are infinitely intelligent, although sometimes as a whole, we mask it. People deserve the knowledge, so thank you so much for sharing that knowledge today, and let's absolutely have you back.

Dr. Robert Lustig:
My pleasure. Thank you.

Andrew Huberman:
Thank you for joining me for today's discussion with Dr. Robert Lustig about nutrition and how sugar impacts the health of our brain and body. To learn more about Dr. Lustig's work and to find links to the many books that he's written on this and other topics, please see the show note captions. If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please subscribe to the podcast on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review. If you have questions for me or comments about the podcast or guests you'd like me to consider on the Huberman Lab Podcast, please put those in the comments section on YouTube. I do read all the comments. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. Not so much on today's episode, but on many previous episodes of the Huberman Lab Podcast, we discuss supplements. While supplements aren't necessary for everybody, many people derive tremendous benefit from them for things like improving sleep, for hormone support, and for improving focus. To learn more about the supplements discussed on the Huberman Lab Podcast, go to Live Momentous, spelled O-U-S, so livemomentous.com/huberman. If you're not already following me on social media, I am hubermanlab on Instagram, X, formerly called Twitter, LinkedIn, Facebook, and Threads. And at all of those places, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab Podcast, but much of which is distinct from the content covered on the Huberman Lab Podcast. So again, it's hubermanlab on all social media channels. If you haven't already subscribed to our Neural Network Newsletter, our Neural Network Newsletter is a zero-cost newsletter that comes out every month. It includes podcast summaries, as well as protocols in the form of short PDFs of maybe just one to three pages where I list out the specific protocols, for instance, for improving dopamine functioning, or for improving your sleep, or for deliberate cold exposure, deliberate heat exposure, or fitness protocols, and on and on, all of which are presented in brief fashion, very direct, just the protocols listed out. Again, completely zero cost. To sign up, you simply go to hubermanlab.com, go to the menu function, scroll down to Newsletter, and enter your email. And I should point out that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Robert Lustig. And last but certainly not least, thank you for your interest in science.