How Fructose Drives Obesity, Type 2 Diabetes, And Chronic Disease

Coming up on this episode of the Doctor's Pharmacy.

Uric acid elevation in metabolic syndrome is no longer an innocent bystander, but playing a central role. It doesn't just happen to be elevated, it is the cause. Hey everyone, it's Dr. Mark.

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You'Ll see the discount code in your cart. Hi, this is Lauren Fillion, one of the producers of the Doctor's Pharmacy Podcast. We live in a food environment that can make it hard to maintain a healthy metabolism and 88% of people are metabolically unhealthy. But reducing our sugar intake, especially fructose, is a huge step we can take towards metabolic health. The problem with fructose metabolism is that it generates uric acid in the body. which is a key contributor to metabolic syndrome. In today's episode, we feature three conversations from the doctor's pharmacy on how limiting our fructose intake and minimizing uric acid levels can prevent and reduce inflammation and chronic disease. Dr. Hyman speaks with Dr. David Perlmutter on how fructose and uric acid affect our physiology, with Dr. Casey Means on the importance of measuring uric acid, and.

With Dr. Richard Johnson on fructose's impact on our energy.

Let's jump in.

Fructose is a bad player, right? We see correlations between fructose consumption and the very things that we're talking about, but we've never really understood, well, how in the heck does that happen? What's the link? And what Dr. Johnson was doing 20 years ago is he was creating hypertension, elevated blood pressure in laboratory animals by feeding them fructose, they would develop high blood pressure. And he noted that as a matter of fact, that their uric, in doing a blood panel, looking at all kinds of things, that their uric acid levels would go up when he gave them fructose. Well, you would expect that because unlike glucose, fructose is metabolized directly into uric acid. That's where it comes from, from fructose. There are two other sources we'll talk about. so he noted that he said, well, isn't that interesting? Uric acid levels increased. Then he did something really fascinating. He gave them a lot of fructose, but he blocked the uric acid production by giving them a gout pill called allopurinol.

Yeah.

And lo and behold, here they're eating all this fructose and they're not getting high blood pressure because uric acid was not elevated.

Fascinating.

That is huge.

Fascinating.

And he determined then by repeating the study in men, the same thing happened. Give them a lot of fructose within a couple of weeks, blood pressure goes up, weight goes up, insulin resistance increases, blood sugar goes up. But if you give them allopurinol, and you know, where you and I are going with this today is not to say everyone should take this drug. We'll talk about what you can do. But lo and behold, the same thing happened in humans. So that was groundbreaking and At that point, you know, he began his research. But it's interesting to note that in 1894, Dr. Alexander Haig, a different Alexander Haig, wrote a book entitled Uric Acid, a Factor in the Causation of Disease, and looked at things like dementia and hypertension and depression and certainly rheumatism or joint problems, and really discussed it way back then, but it remained buried, you know, until just about 20 years ago. Now, researchers around the world are looking at this and describing what to do. So, yes, it's a marker. You were correct in saying you notice that it's elevated. But there was an interesting report that came out of Turkey and Japan in 2016 that looked at uric acid elevation in metabolic syndrome as no longer being in the title innocent bystander, but playing a central role that it's actually mechanistically involved in causing these problems. It doesn't just happen to be elevated because people have a crappy diet or they're not exercising or sleeping well. It is the cause, a cause, an important cause. Wow. So, so, David, people are listening probably.

Going, well, gee, does that mean I can't have an apple or is it just high fructose corn syrup that you get in soda and processed food?

Like what, what's the deal? It's a great question. I can't, I can tell you it's something I'm asked every day. And here's what the literature tells us. And it's really quite interesting. in that if you eat apple, if you eat five grams of fructose or two apples, 10, 15 grams of fructose, all well and good. An apple has quercetin, it has other bioflavonoids. It has fiber, fiber, which slows fructose absorption. It has vitamin C, which aids in uric acid excretion, as opposed to drinking a 12 ounce glass, 42 grams of fructose, you know, of orange juice or apple juice or certainly a soda. those are the potent sources of fructose that we need to stay away from immediately tells your body something very important. That fructose signals your body that winter's coming. It's telling your body that caloric scarcity is coming. You might starve. You better make fat. You better turn on your production of glucose to power your brain. You better elevate your blood pressure because you're not going to have water to drink. It's setting the stage for survival. And this is a fascinating story that dates back about 15 million years ago when the Earth cooled. And there was some very powerful selective pressure on our primate ancestors for survival during times of food scarcity. And it turns out that around that time there was a mutation, was actually a series of mutations in the genes that made an enzyme called uricase. Uricase breaks down uric acid and would lead to a lower uric acid level. But this mutation disrupted how uricase worked. So those who inherited this mutation had higher levels of uric acid. They made more fat, they survived. So we, as humans and other great apes, still have that mutation in uricase. So we have four to five times higher levels of uric acid than other non-primate mammals. These days, what we're experiencing is called an evolutionary environmental mismatch. So we're stuck with these outdated physiology that allowed our Paleolithic ancestors to survive, our hunter-gatherer forebears to survive when there wasn't any food. if they could stumble on some berries, a little bit of fructose, make a little bit more fat, didn't take a lot. Not that it made them fat, but just enough fat to hold them over till they could find food, you know, whether it was on the ground dead or they dug it up or whatever.

Well, David, I know you spent a lot of time on your boat up in Alaska, but, you know, the grizzly bears up there, they, they eat salmon in the early part of the summer, and they don't really gain much weight. Then they go up in the mountains and they eat all the berries and they gain like 500 pounds from eating berries. Right? and what you're saying is really important because we have a lot of mechanisms that are adapted to starvation. People don't realize this, that we have hundreds of genes and mechanisms in our body that are really good at dealing with scarcity, but almost none that are dealing with abundance. Because we've never had to deal with this before. We never lived in a food carnival before. We never lived in a food Lollapalooza, you know, where there's everything all the time in abundance and the worst possible crap you could imagine.

So our bodies don't know how to cope with it. And so this mechanism, which is actually designed to help us stay alive, is actually killing us now. that's right. And again, we call it an evolutionary environmental mismatch. I wrote my first article on this in the Miami Herald in 1971 when I was 16.

Oh, wow. You're ahead of the game, David.

I was, you know, it's crazy. I said, what about us, the people of today who are sort of saddled with this outdated machinery? That was how I ended the article. Because evolution isn't going to save us. We're not going to be able to evolve quickly enough the mechanisms to deal with exactly what Mark, you've been writing about for years, years. And this is this horrendous assault upon our physiology by the very foods that are now global. You know, we used to talk about the American diet, the standard American diet, the Western diet. It's global now. Face it. And, you know, we talked about in brainwash how that threatens connections in the brain that make us less empathetic. But, you know, that's for another conversation we've, you and I have already had with Austin. Well, that's a good podcast.

You should all listen to that podcast because just to summarize it quickly, if I get this wrong, tell me. but essentially our modern diet, which is super inflammatory, disconnects our frontal lobe, which is the adult in the room, from the limbic brain, which is the reptile, lizard, fight or flight, reproduction, feeding behavior, which is very triggerable. And so, all of a sudden, the grown up in the room is not managing the intense emotions of this limbic part of our brain. And so, we act in ways that are destructive or violent or aggressive. And we see that in our society now as being a massively divided society, whether it's your paleo or your vegan or Republican or Democrat or Jewish or Palestinian or Muslim or Christian. It just goes on and on. And your argument is that part of that divisiveness could be related to what we're eating.

That's right. And you know, what a match made in heaven that you and I are talking today because it's been your nothing for so long. And you know, for me it's more about, well, what are the implications of that as it relates to behavior and the brain? And now we know that this uric acid, because of its elevation, threatens some really important physiology. As an example, it compromises the action of a chemical called nitric oxide. We need nitric oxide to do two very important things. It allows our blood vessels to relax so we have good blood flow to our kidneys, our heart, and certainly to our brains. And in addition, nitric oxide and that effect of nitric oxide in blood vessels is what helps insulin do its job. Insulin requires nitric oxide to get out of the artery and also into the muscle cell to let it change glucose into glycogen to help keep our blood sugars under control. That is threatened by uric acid. And, you know, one other really interesting mechanism I think that you hinted about on when you were talking about the bears eating all the berries to get ready to hibernate. is that that's a uric acid mediated event in them. They shift over between two very important pathways of metabolism. One is called AMP kinase and the other is called AMP deaminase. When we are stimulating AMP deaminase, we are favoring fat production, we are favoring locking up our fat, we are favoring the metabolic issues that we want to avoid. AMP kinase, on the other hand, which is not something that uric acid favors, is when we burn our fat, it keeps our blood sugars in check, your insulin sensitivity goes up. And, you know, basically that's what we do. We want to stimulate AMP kinase, why we exercise. It's why diabetics take metformin is to stimulate this AMP kinase. That's exactly what's not happening. when bears are getting ready to hibernate, once they're hibernating and they're burning their fat, then AMP kinase is activated. And it looks like uric acid is involved in that switch one way or the other. Where does the AMP come from? Very interesting. The AMP comes from the metabolism of fructose. When fructose is metabolized, it's an energy consuming event, unlike glucose. is converted into AMP, then where does the AMP go? We just talked about that. So it's totally a different kettle of fish. You know how fructose is metabolized. Fructose is the sugar of energy storage and glucose is the currency of energy utilization. And as different as night and day, you know, the real concern is that the metabolism of fructose into uric acid feeds back to cause more metabolism of fructose. It's a feed forward cycle. So uric acid stimulates the production of an enzyme called fructokinase, which is the first enzyme to break down fructose. So it just, it's self-perpetuating and what does that fructose do? It inhibits leptin sensitivity, so we eat more.

It has a hunger, the hunger suppressing hormone.

Right.

And that's inhibited by our consumption of fructose. So we eat, and this was a great mechanism when to get ready for winter, you know, so we would eat more. That's why the Bears are doing what they're doing. They're preparing to hibernate.

And if any of you, we just.

Eat all winters, if any of your viewers are getting ready to hibernate, then have at it. You know this, then that's for you. Eat a lot of fructose. But I think it's, you know, to get back to your original question that you and I talked about or learned about uric acid in the context of gout. If you had high uric acid, you might get gout, you might get kidney stones. But now we have a term that's called, it's pathetic, it's called asymptomatic hyperuricemia, which means you have elevated uric acid, but hey, you don't have gout, therefore it's not important. And asymptomatic hyperuricemia, it's clearly associated with hypertension, with obesity, with chronic kidney disease, and non-alcoholic fatty liver disease. One interesting study out of Japan looked at individuals with so-called asymptomatic hyperuricemia and found that they had significant increased risk for becoming overweight, for developing problems with their lipids, and even hypertension. You know, important components of the metabolic syndrome. And, you know, you started off with our discussion saying that 88% of American adults have at least one component of the metabolic syndrome. It means only 12% of American adults are metabolically healthy. And these are the big issues of our day. You know, you can talk about viruses all you want. Sure, that's important, but that's not what's killing most people on our planet. What's killing most people right now are the chronic degenerative conditions. coronary artery disease, Alzheimer's, cancer, diabetes.

These are metabolic issues.

Almost 50 million deaths a year.

Yeah.

And, and related to this.

Million deaths a year. Mostly with an M. That's right. Yeah.

And David, I just want to sort of loop back a little bit because I want people to understand what this fructose thing is. So basically we're getting it from high fructose corn syrup, which you said is 55% fructose.

But it's actually, in some studies I've.

Seen up to 75% fructose. And also it's important for people to understand that in traditional sugar, Fructose and glucose are bound together with a chemical bond. So they take some metabolism and they don't, they're not as quickly absorbed. Fructose in high fructose corn syrup is free fructose. And the other thing that you didn't quite mention, I'd love to hear your opinion about this, is work from Bruce Ames where fructose requires energy to be absorbed as opposed to sugar, which has a transport channel that doesn't require the use of energy. And when you use that energy for fructose and you're having mostly fructose as your sugar, It's causing depletion of ATP in your gut, which then causes the tight junctions, which are the things that prevent you from having a leaky gut to keep your cells stuck together like Legos. It causes those to separate and then you get leaky gut, which then even exacerbates the problem of obesity and insulin resistance and diabetes through another mechanism, which is endotoxemia from the metabolic byproducts of bacteria and weird things in the gut. So it may be that fructose is causing problems with many, many reasons. partly obviously these metabolic effects, but also the gut effects which exacerbate the metabolic effects.

That's right. And again, this is all amplified by then the metabolism, which is an energy dependent event, ATP to AMP, then to uric acid. And that uric acid then enhances in the gut more pro-inflammatory bacteria, also dramatically increases the gut permeability, therefore increases inflammation. And how interesting it is that one disease that is associated with elevated uric acid, which is gout, has actually been demonstrated to be significantly improved in people undergoing what's called a fecal microbial transplant, where healthy fecal material is taken from an individual and then put into the colon of a person with gout, remarkable reduction in the number of gout attacks without any significant dietary change. That's amazing. True. So, you know, we're back to talking about the gut, you know, a place where you and I default to over the years, and rightfully so. But so uric acid itself is having such a dramatic effect on, on the gut.

Just on the microbiome itself, right? You bet.

Enhances inflammation. So if, if we recognize that inflammation is certainly a centerpiece of the damage done by uric acid, then all of the downstream issues related to inflammation might well be anticipated to be increased in people with high uric acid levels. And in fact, that's what we see in a 2018 study looking at 42,000, I think I mentioned earlier, 42,000 men and 49,000 women and followed these individuals over an eight-year period of time. What did they find? They found that all-cause mortality was dramatically increased in those individuals with high levels of uric acid. that those who had high uric acid had a significant increased risk of cardiovascular related mortality of close to 40% and about a 35% increased risk of stroke related mortality. This is a big study. I mean, we're talking about 100,000 people followed over eight years, having a 35 to 40% increased risk of death from either a heart attack or stroke. and here's something else that the study found I think was really interesting. That is for every point elevation of uric acid above seven, seven milligrams per deciliter, for every point there is an eight to 13% increased risk of all cause mortality. So this is mortality when we look at the cardiovascular, we look at the stroke, this is mortality related to issues that have inflammation as their cornerstone. So it's very important that we consider this, that we consider that uric acid is not just happens to be elevated, that it's playing a mechanistic causal role, and that we should do what we can to check our uric acid levels. You can use a home monitor. I'm going to send you one. Or, you know, people get their annual blood work. Uric acid is almost always on the annual blood work. What is it? and for your viewers, the place where it needs to be is at or below 5.5, the units are milligrams per deciliter here in America. Typically, the lab will call it out if it's at seven or higher because that's the level that it starts to become an issue as it relates to gout and kidney stones. But as it relates to the metabolic issues that we're talking about, the increased blood sugar, the hypertension, the risk for all the things that we're talking about, we want it at 5.5 or lower. and again, you can go online, go to Amazon, buy a uric acid monitor and check your level. I recently checked mine again, and it's 4.6, so I'm feeling good about that.

That's good. So basically, this uric acid phenomena is really not well understood by most physicians. It's really driven by diet, but normally our processed diet, high fructose corn syrup, and it drives all these secondary effects of cardiovascular disease, death, alzheimer's, cancer, diabetes, and it's something that you can actually easily measure. Your doctor can check it for you when you go to the office. It should be less than five and a half, as you said. What should we do in terms of our diet to reduce uric acid? And what are the worst things that cause uric acid and what actually helps reduce uric acid?

Sure. Let's talk about the causes or the sources of uric acid. Where is it coming from? Did we mention fructose?

Yes, you did.

Fructose is the gorilla in the room, right? So fructose, again, was our signal that scarcity was coming, that winter is coming, eat the berries. Fructose is telling your body, make fat, raise blood sugar, raise blood pressure because you might not have water to drink. So fructose is by and large the biggest player. Fruit juice, sodas, added the sauces. added to just about anything that's in a package these days.

Salad dressing.

You bet. And we love it because it's- Tomato sauce. And again, fruit is okay. An apple a day keeps the doctor away. Not apples and cherries and, you know, high fructose fruits all day long, but have some fruit by all means. The next thing to consider that's certainly less important are something called purines. Purines, all fruits, vegetables and meats, really anything we eat has in it some DNA and RNA. When our bodies break that down, then purines are formed and purines are directly metabolized into uric acid. And interestingly, uric acid favors that and enhances the production of purines in our bodies. Again, a feed forward cycle. It's trying to keep us alive during times of food scarcity. So again, we want to avoid those foods that are really rich in purines. I mentioned them already. The organ meats, the shellfish, the smaller fish that we were favoring over time, the anchovies and the sardines. Sure, you can have the anchovies in your, in your Caesar salad, but you don't want to make big meals having six ounces or more of, of any of those. Oh, I love anchovies. Yeah, me too. White anchovies, one of my favorites. And the last thing to consider, I think it's needs a little bit of we need to double click on this a bit, and that is alcohol, because alcohol shares the exact same metabolic pathway as fructose, as Robert Lustig has called it. Fructose is alcohol without the buzz. So it similarly consumes ATP down to AMP. But in this case, it really matters what kind of alcohol a person is drinking. Wine consumption in med men has about zero effect on uric acid. Wine consumption in women actually is associated with lower uric acid. Hard liquor will raise uric acid, but the worst offender is beer. Why? Because beer not only contains alcohol, but it contains purines that we just talked about from the yeast, the brewer's yeast that is used to make beer. So now we understand the biochemistry that underlies the beer belly. It's coming from this elevation of uric acid packing the fat away, getting ready for winter. So if you're gonna choose a beverage, coffee, a good choice actually associated with lower uric acid. So those are the big things that we should avoid. I will make one other comment as it relates to high-purine foods. Many people will pull up a list of high-purine foods and see many vegetables, things like broccoli, the cruciferous vegetables in general, like kale, Many vegetables have high levels of purines. Their consumption, though, is associated with lower uric acid. Why? Because again, fiber, bioflavonoids, vitamin C, which increases uric acid excretion. So eat all the vegetables like that that you want. You'll never hear, I don't never say never, but it's gonna be hard for me to imagine there'll be a time when I tell people not to eat broccoli or broccoli sprouts. Exactly. That's gonna be a tough one for me.

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Fructose alone will not spike blood sugar or insulin, but we know from the mechanisms of how insulin resistance develops that it directly contributes to insulin resistance through a really interesting pathway. Fructose is broken down into a byproduct called uric acid, which goes into the mitochondria, you know, the seed of our metabolism in the cell, and generates oxidative stress, you know, this damaging free radical activity that actually causes the mitochondria to become dysfunctional and process glucose less effectively and shunt glucose to fat storage. So then you start getting fatty liver disease because of fructose, and that fatty liver disease causes liver insulin resistance, which then makes you less able to stabilize and regulate your blood sugar. So fructose has this really interesting side pathway that ultimately leads to more instability in glucose but will not show up on a CGM if eaten in isolation. Now, of course, it's a really important thing.

I just want to stop there because you said something super important. If you're, for example, eat a sugary soda with high fructose corn syrup, you'll get a mixture of glucose and sucrose. But if you have pure fructose, which is like agave, for example, that, that's just pure fructose. And that actually turns out to be pretty bad for you. If you're eating fructose in the matrix of a fruit, it's probably not as bad.

Right.

It's actually can be okay to have it in a complex of a meal. We'll talk about food pairing in a minute. But the idea that, that you can be eating certain Foods, fructose, which, which a lot of, a lot of, like, for example, processed food is mostly fructose. Like they use high fructose corn syrup. But it could be 75 fructose. And that, that isn't going to spike your blood sugar, like you said, but it's going to create a cascade of events that actually makes you more likely to get diabetic by increasing the uric acid in the liver, the insulin resistance. And, the uric acid story is a very fascinating one. And, David Perlmutter just wrote a book about it called Drop Acid, which isn't what you think it's about. It's about the uric acid in the.

Blood that's causing some of these issues. And, fructose is a huge culprit. So, I just wanted to pause there. It's so important. So, So going off of like, what else should we be thinking about? I would love to see a uric acid continuous monitor because then all of a sudden, if we could measure both those things, then we start to see a more holistic view of how food is affecting us because ultimately our mission at Levels is to help people know how food affects their bodies so we can reverse the metabolic disease epidemic. But right now there's still some blind spots. So, like you mentioned, David Perlmutter is coming out with a book called Drop Acid about how fructose is affecting our health. We also in February are getting another book by Rick Johnson from University of Colorado that's called Nature Wants Us to Be Fat, which is also all about uric acid. And so I think we're going to be starting to talk a lot more about that come February, which is awesome because fructose is absolutely killing us. There's just absolutely, you know, really no two butts about that. And like you said, it's not the fructose that comes in fruit. which is in a complex of fiber in a whole food, slower to digest and smaller quantities. It's the refined liquid versions that go into our processed foods and that we find in juice that we should really avoid. Because what happens is we over, the liver knows how to process fructose and it knows how to just produce small amounts of uric acid that our body knows how to handle. It's when we overwhelm those pathways in a short period of time, that we get the uric acid skyrocketing and create that oxidative stress. So it's really a lot about pacing. And they've even done research showing that if you drink a Coca-Cola slower, like over the course of an hour or two hours versus in five minutes, it actually has less of a damaging effect on liver because you have to think we're just we're just made up of a ton of cells that are trying their hardest to process this stuff, right? And so if you can process and clear process and clear, It's better than if you just jam it down your throat and overwhelm the enzymatic, you know, all these enzymes in the body that are trying so hard to get through it. And then you end up creating an excess of these damaging byproducts that ultimately lead to organ dysfunction. So fructose is a big one. The second big one I would mention is the pro-oxidative stress-inducing foods that come from more like refined fat. So it's like the seed oils that we talked about. Again, the name of the game is in many ways oxidative stress, which is this process that damages our mitochondria. So you want to avoid those refined seed oils that are in everything that's packaged. And you really be vigilant about looking at labels and trying to opt for things that only have oils like avocado oil, olive oil, coconut oil, ghee, butter that are less prone to oxidation.

So are you saying this based on your data from levels around the refined seed oils or just in a general way?

Not saying that based on our data set. None of these actually, these ones for this question, not talking about our data set. The thing is about the data set is that what we're seeing is the real time response to different foods, but the next layer of this onion, when we have lots and lots of people using this type of technology over long periods of time is we think we'll start to see the longer term, the lagging effects of how these other products like fructose and refined seed oils and excess alcohol over the longer term lead to glucose instability. A lot of that we just don't have much knowledge about because we haven't been looking at pre-disease very much in our medical system. We don't really study healthy people and how they go from healthy to pre-disease to disease, because that's not the way that our healthcare system works. We wait until disease and symptoms emerges and then we react. And that's a problem. So I think we're going to see a shift here in starting to understand, but this is more based on what we just know from the mechanisms, the fructose and the seed oils.

Take us through how fructose actually causes a problem. You eat fructose, and how does it get all the way down? Take us on the scientific pathways that you're talking about.

So it turns out that, you know, almost all, basically anytime you eat calories, the calories are then go in and they're used to help produce energy. And you produce energy, energy is called ATP. And a lot of it is produced by these energy factories called mitochondria. So when you eat food, you're trying to make energy. and that energy is used to help us do whatever we want. There's really two, maybe three types of energy. Really, there's the immediate energy that we make, which is called ATP, and that's what we're using to, you know, and I'm using to talk to you is my brain is using ATP, et cetera. If there's excess energy, it can be stored as fat, and stored fat is a stored form of energy. and then, you know, the burning of it, the produced production of energy can also generate heat, and heat is kind of a wasted or dissipated energy. But anyway, basically, when you eat food, you're trying to make energy.

So.

So when we eat fructose, instead of making all the ATP we normally would make, we start, we actually dampen the production of ATP. and produce more stored fat. So there's the mitochondria, which are normally making the ATP, are suppressed. There's a suppression of the mitochondria. And so they make less ATP. And so more of the calories that we're eating go into fat. And this is associated with a fallen ATP in the cell. So I call it a fallen energy. it's true it's not a true fall in total energy because more stored energy is being formed, more fat is being made as there's less ATP being made. And so it's kind of shunting the calories to fat and reducing the amount of ATP. Now when that happens, you have a lower ATP in the cell and so your body reacts to that by saying, hey, I don't have enough energy. I'm gonna eat more. I'm thirsty. I'm gonna drink more. I'm gonna forage for food. You know, this is, it triggers these biologic responses that want, makes you end up eating more and so forth and.

Eventually exercising less, right?

And exercising less, yes.

And so the way that you're saying is if being overweight and storing the fat makes you eat more and exercise less.

Yes, I guess that's the opposite.

Or what? Exactly what David said.

Yeah. Yeah.

So anyway, so the way it works is that when fructose is metabolized, there is this production of uric acid.

Now we're getting into it. Yes.

And so uric acid is a breakdown product of energy. And what happens is, you know, we always use a little bit of energy to make energy. So, you know, you have to use some energy to absorb the food you eat. You have to use some energy to break down the food we eat. Fructose is like all foods this way, but the enzyme that breaks down fructose breaks it down so rapidly and it uses a little energy in the process that there's a drop in the ATP in the cell to about, you know, goes down 30%. and that's not true for other foods. So this is unique about fructose. Alcohol does it too, by the way, but fructose is really the only food that really does it. And when that happens and the energy drops, it triggers a reaction. And that reaction of all things tends to remove, you know, ATP gets converted to, you know, AMP and then AMP goes back to ATP. but there's a reaction that sweeps away the AMP and makes uric acid from it. And now you can't rejuvenate your ATP very well. It's hard to make it because you've removed, it broke down and then you can't repair it so well because you've removed it to make uric acid.

Okay, okay, hold on, hold on, that's a lot. I was wanting to pack there because people are listening and I'm trying to follow you and this is my thing. So just let me unpack it a little bit. Because basically saying is you absorb fructose, you eat fructose. By the way, when you eat fructose, it uses extra energy to be absorbed. So that causes an energy deficit. Then you store fat, which actually causes you to actually want to eat more but exercise less. But then when you deplete the energy in the cell, you create AMP, which is basically the byproduct of actually yeah.

Well, let me, let me take you through this again.

Okay.

So what happens is when you, when you eat fructose, you burn ATP faster than normal.

Yes.

And so that ATP level drops, and then there's a, the generation of uric acid from that. When the energy drops, that triggers a reaction to make uric acid.

Got it.

And then the uric acid. goes into where the energy factories are, what we call the mitochondria, and causes oxidative stress to those mitochondria. And that's the key. And that suppresses the mitochondria from making more ATP. So there's an initial consumption, and then there's decreased production.

So it's a double whammy.

It's a double whammy. So it lowers the ATP, but then doesn't let you bring it back up very quickly. and so everything's kind of suppressed. Now you have a low ATP, and when that oxidative stress occurs to the mitochondria, it blocks the mitochondria from working, but opens the pathways to make fat. And it also blocks the burning of fat. So there's this shunting of calories into fat, and now the fat can't get burned, so it starts to accumulate. but your energy is still low. So you've been eating all this food, but your energy is still low, so you keep eating. And you keep eating until it repairs. But what's happened is you've lost your control, your normal amount that you would eat. Now you're going to eat more and you're going to be accumulating fat. So it's this brilliant system by reducing the ATP, it reduces It keeps that ATP level low and no other nutrient does that. It's just fructose. It drops the energy level and it makes you feel hungry, makes you thirsty, make you want to eat more. But instead of the food making the ATP levels go back up, the energy is going into the fat. So the energy balance is maintained. Energy balance is maintained, but the energy is going into stored energy, which is fat, not, you know, it's, So the energy balance people, you know, the law of thermodynamics is true. And, and, and, but what's happening is your energy levels are low and you're still hungry. So you're gonna keep eating. And so this is the trick. But the key here is that, is.

It, you know, thermodynamics, who can argue with that? It's physics and I'm not about to overturn the laws of physics and the mind of God.

Okay.

But there, the, what people don't realize about the first law of thermodynamics, which is basically all energy is conserved, right? Right. It means all energy is conserved in a closed system. So in a vacuum, a thousand calories of broccoli, a thousand calories of soda are exactly the same. They basically release the same amount of energy, which a calorie is the amount of energy required to raise one liter of water, one degree Celsius. That's it. And so you literally would create the same rise in temperature of the water with a thousand calories of broccoli or soda. But when you eat them, there's all this other stuff's happening, like you're talking about leaky metabolic toxemia and how it affects your liver and how it affects fat storage and ATP. So it's not a closed system. So the energy balance doesn't quite work in a closed, in a, in a, in a, in a metabolic.

Yeah. So if you give a thousand calories of sugar and a thousand calories of broccoli and you clamp me so that I don't eat anymore, because that, if I eat the sugar, I'm going to stay hungry. Okay. I would eat more. but you clamp me so that I don't eat anymore. The fat, the calories from sugar are going to activate, cause oxidative stress to my mitochondria, and I'm going to start making fat from glucose and so forth that I have in my blood already. It's going to start working to make fat from what I have. So even though both groups got a thousand calories, I'm going to start getting fatty liver and I'm going to become insulin resistant and I'm going to get a leaky gut, all that from the sugar, even though they're the exact same number of calories. But if I measure my weight, it's going to reflect that fact that each group got a thousand calories. The only difference is that the sugar also drafts my energy metabolism, so it's going to make me gain a little bit more weight than the other one.

Because.

But is that true?

Is that true? Because, because, like, you know, that David Ludwig study where he took, he did this with rats, then you with humans, where they, they basically gave a, if it was a feeding study where they took insulin resistant patients and they, they kind of created a basic Cal, like equalization in the patients. And then they had basically had them do a crossover trial where they, where they ate a high fat, low carb diet or a high carb, low fat diet. And, and the ones when they were eating the high fat, low carb diet, they burned 400 more calories a day, even eating the same amount of calories. Like they're eating the same amount of calories. So the energy balance thing, I just wonder, how does that work? Yeah, yeah, yeah. Explain that. So I don't understand.

On the low carb diet, they're going to burn more calories, and on a high carb diet, they're going to burn less calories. so, so if you, even if they're getting the same number of calories, okay, so the, the energy balance equation says that my weight is going to reflect how much I eat and how much I burn. And if we have everyone eat the same amount, but one's a low carb, high fat, the low carb is going to cause more calories to be burned. So the burning it doesn't relate to how much comes in. It relates to what you're eating, right?

Yeah.

So when you have a high carb diet, you want to eat more and you want to burn less. And if you eat a low carb diet, you're going to want to eat less and burn more. A low carb diet is great. You and I both know this. And so a low carb diet is going to make, you know, is going to create more satiety. You're going to feel more full easily. But let's say, for argument's sake, let's.

Say, okay, I mean, obviously we should be eating high fructose corn syrup. We should be in junk food, processed food. And most people are aware of that. But let's talk about carbs kind of in the context of this fructose conversation because, you know, it wasn't that David was feeding these people a high fructose corn syrup diet. They were eating like a high starch diet. which was beans, grains, healthier starches. And yet, you know, when you look at, at the, you know, the data with vegans and meat eaters, it's super confusing. And I, you know, I think people are trying to sort through what makes sense and, and is a vegan diet a healthy diet or not? And how does this relate to this conversation about fructose and insulin resistance and.

And, well, there is a big story here which we haven't really talked about. and that is, you know, originally when I was studying this, I was focused on sugar and high fructose corn syrup because they contained fructose. But people pointed out to me that things like bread and starch can also cause obesity. And so how can I account for that if the story is about fructose? And if you look in the wild, there are a lot of animals that will get fat that are not eating fruit or fruit dose. You know, that, you know, how does the whale get?

Not just eating berries, right? The whales.

Yeah.

Yeah. They're not eating too many berries, I don't think.

So.

So the question was, you know, what is that? And we realized that the body can also make fruit dose. It isn't just about the fruit dose that you. eat, but it's also that the body has one way it can make fructose and it makes fructose from glucose. And so what we did is we did a study where we gave glucose in the drinking water to mice. And lo and behold, they became fat and insulin resistant and diabetic, all the, all these things. And they weren't eating fructose, they were eating starch or pure glucose. Pure glucose. and so we said, you know, how is, can this be? Is it, maybe it's the glucose insulin pathway. And so what we did is we, we looked in their bodies and we found that when they're eating a lot of glucose, that they were making fructose in their bodies. And so what we did is we gave the glucose to animals that could not break, metabolize fructose. so they're not getting, so these mice are eating glucose, they're making insulin, but they're not able to metabolize fructose. And they were, guess what? They still gained weight, but not as much. It was much less. And they still got a little bit of fat, but not as much as the control animals, even though the control animals were eating the same amount. And, but what that was striking was the fructose resistant or the animals that could not metabolize fructose, they were completely protected from insulin resistance. They were completely protected from really liver.

Even if they had a lot of glucose.

Yeah.

And they were not eating fructose. They were just, they were making fructose from the glucose. And so, so what we now know is that high glycemic carbs, cause obesity two ways. One way is because when the glucose goes up in the blood after you eat these things like bread, rice, potatoes, you know, makes your glucose go up in the blood. And that triggers the production of fructose as well as the secretion of insulin. And the insulin is driving a little bit of the obesity. This is what Dave Ludwig's work has shown. Yeah, but, but, but. A lot of the obesity is driven by the production of fructose. And fructose is actually what's responsible for activating the switch. So it's what makes the fatty liver and the insulin resistance and all this stuff. And then we said, oh my God, there's another way to get fat from fructose, and that's to make fructose.

Wow. So basically you're screwed, 'cause if you're eating bread, whatever, you think, oh it's got no fructose, but actually starch is basically a lot of glucose molecules stuck together. that in itself can generate through this pathway more fructose in the body, which then causes more fatty liver, more weight gain, and vicious cycle of pre-diabetes and diabetes.

So now the high fructose corn syrup and the table sugar is a double whammy because they contain fructose, but they also contain glucose. And as you mentioned earlier, if you eat fructose, it's a little hard to absorb it. But if you mix it with glucose, you can absorb the fructose really easily. And the fructose also increases the glucose absorption. So you're getting a double whammy. When you're drinking a soft drink, you're getting the fructose in the soft drink and then the glucose is coming in and it's stimulating insulin, which isn't so good, but it's also being converted to fructose. And then the fructose causes insulin resistance. and then that makes the insulin levels high all the time, and that helps block the fat from burning too. So now you've got this big story where, and then you realize why low-carb diets are so beneficial, why you can go on a low-carb, high-fat diet and not gain weight, because the low-carb is blocking both the starches and the fruit dose, which are really key for activating.

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