Fructose and its byproduct uric acid may play a role in the development of Alzheimer’s, thanks to an evolutionary adaptation hijacked by the modern diet. Fructose can be directly consumed, or the body can convert high-glycemic carbohydrates and other foods to fructose. Fructose suppresses some cognitive functions. Dr. Richard Johnson and Dr. Rob Lustig discuss a new study, of which Johnson was an author, on how fructose may be a potential driver in Alzheimer’s, and they hypothesize about fructose’s potential connection to the development of other conditions.
- Study: Could Alzheimer’s disease be a maladaptation of an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism? https://doi.org/10.1016/j.ajcnut.2023.01.002
- Dr. Richard Johnson, MD: https://drrichardjohnson.com
- Nature Wants Us To Be Fat by Richard Johnson, MD: https://drrichardjohnson.com/books/
- The Sugar Fix by Richard Johnson, MD: https://drrichardjohnson.com/books/
- The Fat Switch by Richard Johnson, MD: https://drrichardjohnson.com/books/
- Richard Johnson, MD, on Instagram: https://www.instagram.com/drrichardjjohnson/
- Robert Lustig, MD: https://robertlustig.com
- Robert Lustig, MD, on Instagram: https://www.instagram.com/robertlustigmd/
- Robert Lustig, MD, on Twitter: https://twitter.com/RobertLustigMD
- Metabolical by Robert Lustig, MD: https://robertlustig.com/metabolical/
9:50 — Fructose is the driver of some diseases that are on the rise in kids
Dr. Robert Lustig explains the reason children now get Type 2 diabetes and fatty liver disease, conditions they didn’t get about a half a century ago.
I opened up my Lehninger—my biochemistry text from 1974 from college‚ and I said, “Alright, these were the diseases of alcohol.” So I turned to the alcohol page, and then I turned the page and there was fructose. And I started looking at the pathways, and I went, “Wait a second, they’re exactly the same. There’s no difference. And then I said, “Well, yeah, of course that makes sense, because after all, where do you get alcohol from?” Fermentation of fructose. It’s called wine. So I went to this meeting at the NIH and I said, “I think fructose is the driver. I think that it is the environmental obesogen, which is now a real term, that is driving this obesity and metabolic syndrome epidemic, particularly in children.”
11:53 — Fructose is a driver of obesity and metabolic syndrome
Dr. Richard Johnson explains how fructose is a root cause of poor metabolic health.
Fructose gets metabolized like a calorie, but the uric acid is generated from fructose. It’s generated because the ATP levels fall in the cell, and the ATP turnover leads to the uric acid. So, just like you were thinking it was a toxin, I thought, “Oh my gosh. This suggests that fructose is causing metabolic syndrome through a pathway that does not involve calories.” It was true that these animals were eating more, and when we measured it, we found, just like you did, that leptin levels were high, but they weren’t responding to leptin. So if we injected leptin in the rats, they kept eating. Normally, if you inject leptin, animals will quit eating. And so we also realized that most people with obesity have leptin resistance as well. So we went on and tried and showed that the fructose actually induced the leptin resistance in the brain. But a high-fat diet alone did not; it was specific to fructose. And so that was kind of a big breakthrough where we go, “Oh my gosh, fructose makes animals eat more. And that is one of the reasons you gain weight.”
15:36 — Pharmaceutical treatments for Alzheimer’s disease aren’t as effective as researchers had hoped
When it comes to Alzheimer’s disease, pharmaceutical companies have focused on reversing amyloid plaque buildup, but treatments thus far don’t address the underlying cause.
First off, most people, when they think about Alzheimer’s disease, think about the fact that this is a terrible, terrible disease that leads to atrophy of the brain and the building up of amyloid plaques in the brain and also a thing called tau protein aggregation. For the last 50 years, Alzheimer’s disease has really been thought to be due to these amyloid plaques. And so there’s been this huge movement to try to find out what’s causing the amyloid plaques and how we can reverse it. And pharmaceutical companies have generated all these different ways to try to block the amyloid plaques. And as you know, it’s weak. The data shows maybe a little bit of improvement here and there, but it’s nothing like what we were hoping for.
17:32— The research focus of Alzheimer’s is slowly shifting to understanding insulin resistance in the brain
Dr. Johnson and Dr. Lustig discuss how amyloid plaque buildup in Alzheimer’s is likely the body’s defense of the underlying cause of the disease.
I think that the movement has been that the amyloid plaques can’t be the primary cause. There must be something underneath. And there’s been a lot of interest in the last 10 years on three key findings that people see early in Alzheimer’s. And the first finding is that there tends to be insulin resistance in the brain. And a lot of the brain doesn’t need insulin. It will take up glucose, independently of insulin in some areas of the brain, but there are certain regions that are insulin dependent. And you can show in animal models as well as in humans that there’s a degree of insulin resistance and there are even people giving intranasal insulin as a potential way to try to help treat that with some possible benefit. But it’d be much better to know the cods of the insulin resistance in the brain than just to give insulin… A second one is that the neurons seem to have some dysfunction of their mitochondria—the little energy factories that make ATP—and ATP levels fall early. There’s this mitochondrial dysfunction and there’s inflammation. So these three things: neuroinflammation, mitochondrial dysfunction, and insulin resistance.
20:41 — Is fructose a root cause of Alzheimer’s?
Dr. Johnson and Dr. Lustig discuss the polyol pathway, how glucose can be converted to fructose, which is potentially a driver of Alzheimer’s.
The body can make fructose and you don’t have to necessarily eat fructose. But when you eat sugar, the body makes fructose. So the body makes fructose in response to sugar, and the body makes fructose in response to high-glycemic carbs, like potatoes and rice. And it also makes it in response to salty foods. All three pathways are due to a particular enzymatic reaction that I call the polyol pathway. But what it is, is glucose can be converted to fructose. And so when you eat a lot of high-glycemic carbs, the glucose levels go up in the blood… So there are these foods that we eat that can generate fructose. And when it goes up, it goes up in the brain as well as in other tissues. So this led me to think, “Well, perhaps what’s going on is we’re eating foods that are raising fructose levels in the brain.” And then I started looking at it, and I realized that there are all these data that show that sugar intake is a risk factor for Alzheimer’s. It’s a risk factor for cerebral atrophy. High-glycemic carbs are a risk factor. Salty foods are a risk factor. All the things that generate fructose are risk factors for Alzheimer’s and obesity and diabetes, which are signatures for fructose production or intake.
26:26 — New research suggests fructose induces a foraging response
Fructose, whether consumed or produced in the body via the polyol pathway, encourages foraging, a survival instinct.
If you give fructose to a starving animal, it will be converted to glucose because it wants fuel, immediate fuel. But if you give fructose to a fed animal, it will lower the ATP and activate this process that leads to obesity and metabolic syndrome. And it’s really interesting that animals will eat fructose to prepare for times when there’s no food around. Like the bear will eat fructose in the fall—, it will eat thousands of berries. It doesn’t eat one natural fruit. It’ll eat thousands, and it will activate this switch, and it activates it by dropping the mitochondrial production of ATP. It induces insulin resistance and all these things as a mechanism to aid survival. Well, one of the really cool things that we have kind of discovered, or at least have really looked at carefully with others, is that fructose stimulates foraging. And so when fructose goes up in the brain, for example, or when you give sugar, you’ll stimulate a foraging response.
28:20 — Fructose inhibits areas of the brain to encourage successful foraging
For early humans, foraging, as a mode of survival, required quick assessment, impulsive action, and risk taking. Therefore, foraging was more successful when cognitive functions—like control and reasoning, attention to time, and recent memories—were suppressed. Fructose decreases energy to parts of the brain related to these cognitive functions.
It turns out that to do this foraging, you actually have to suppress certain areas of the brain, like the cortex, really involved in self-control. Especially the frontal cortex. And so when you give fructose, you inhibit the activity of that area so that you have less self-control, sort of like alcohol actually. Likewise, if you give fructose, you’ll inhibit the area for recent memory. Because the recent memory is—you don’t want to really have vivid memories of how dangerous it is where you’re going to go. It will also stimulate impulsivity and all these things.
46:48 — We need more research on fructose
Fructose and the polyol pathway may be implicated in other disease beyond Alzheimer’s.
It’s amazing how complicated fructose is—how it all, in excess, leads to morbidity. And as we get towards the end of the hour, it’s really fun talking to you about how we can learn more and more about what fructose does and how it probably has roles in not just obesity and metabolic syndrome, but also neurologic diseases and ADHD and bipolar and Alzheimer’s and seizures and and GI illnesses and anaphylaxis.
1:03:10 —Is fructose a factor in violence?
Dr. Johnson and Dr. Lustig discuss whether fructose’s impacts on the brain are linked to behavioral concerns.
There is no doubt that fructose decreases self-control. It increases impulsivity. And so if you happen to be a person who’s quite impulsive to begin with, and you’re eating a lot of sugar, it may make you more impulsive. It may make you have a little bit less self-control, kind of like a drink, you know? And then you do things that you may not normally do. But my belief is violence would decrease if we could reduce sugar intake. In my book, I talk about it a lot. I quote lots of papers that link sugar intake and high-fructose corn syrup and fructose intake with violent acts.
Richard Johnson (00:00:06):
When I was studying fructose in the animals, I was showing that they induce insulin resistance systemically and that they induce mitochondrial dysfunction, reduce the ATP levels and suppress the mitochondria, and they cause inflammation. I go, “Wait, this is the same bio-signature as what’s going on in the brain. Fructose could be doing this.” What’s very interesting is that if you eat fructose or sugar, most of it is removed in the liver and only a tiny begets to the brain. So it seemed like there was some paradox, there was some problem. Why is it that very little fructose gets to the brain if fructose is driving the disease in the brain?
Ben Grynol (00:00:52):
I’m Ben Grynol, part of the early startup team here at Levels. We’re building tech that helps people to understand their metabolic health. And along the way, we have conversations with thought leaders about research-backed information so you can take your health into your own hands. This is A Whole New Level.
Could Alzheimer’s disease be a mal adaptation or an evolutionary survival pathway mediated by intracerebral fructose and uric acid metabolism? Well, that’s the name of a new paper co-authored by Dr. Rick Johnson, friend of Levels, author of the most recent book Nature Wants Us to Be Fat. He sat down with Levels’ advisor, friend, author, many things, Dr. Rob Lustig, whom many of you are familiar with by now. The two of them, they discussed about this cross section of fructose, uric acid, insulin, and metabolic health.
There’s so many different implications for biomarkers in the body. They’re in constant fluctuation, and Dr. Johnson is one of the world’s leading experts when it comes to fructose. There’s more research that’s being done every day as it relates to things like kidney disease and metabolic function. What we know is, when things like glucose go up in the blood, fructose starts to be produced in the brain. Eventually, people can develop insulin resistance in the brain, and many people are referring to Alzheimer’s as a type 3 diabetes. It is very much insulin resistance in the brain. So Rob and Rick sat down and they discussed the paper and they discussed this cross section of uric acid, fructose, kidney disease, insulin resistance, all of these things as they relate to metabolic syndrome. Anyway, no need to wait, here is a very fruitful conversation, no pun intended, with Rob and Rick.
Robert Lustig (00:03:02):
I am delighted to be here. My name is Rob Lustig. I am a pediatric endocrinologist at the University of California San Francisco, and I have been waiting for this for months now. My colleague, Dr. Rick Johnson, is going to introduce himself, but he is the head of adult nephrology at the University of Colorado in Denver. Boulder, I should say.
Richard Johnson (00:03:25):
You are more than just a doctor. You are a leader in the field of fructose, and I’m so happy to be on the show with you. But anyway, I’m Rick Johnson. I’m a nephrologist here at the University of Colorado, as you said, and no longer the division chief, but I’m very active in research and doing all kinds of things.
Robert Lustig (00:03:46):
I would say all kinds of things. One of the things that I want to ask you, Rick, is you are a nephrologist, you are a kidney doctor, how did you get so far afield to basically study carbohydrates and specifically sugar? What captivated you about this topic?
Richard Johnson (00:04:10):
Well, I tend to go far afield in my work. I basically follow my nose and follow where my research takes me. So I was trying to understand the role of uric acid in hypertension. And it’s known that the kidney has a really important role in hypertension and in regulating salt excretion. So I was studying uric acid, and we had this kind of amazing surprise because uric acid is associated with hypertension, but no one really thought it might have a causal role in hypertension. But when we raised uric acid in rats, they became hypertensive. I go, “What? How can that be? How can just raising the uric acid in a rat?” Because high blood pressure can’t be. So we did like a hundred animals, and it was true. So that launched me in a new direction, which was a uric acid as a potential mediator of kidney and disease and high blood pressure.
And then as we started studying it more, we said, “Hey, why do so many people have a high uric acid in our population?” So one of the things that can do it is sugar, and particularly the fructose component. I know you yourself were studying this in parallel with me. So what we did then was we gave sugar and we also gave fructose to animals, and their uric acid went up and their blood pressure went up. It seemed like sugar might be a cause of high blood pressure. And then I go, “Wow.” But what was really surprising was that, maybe not so surprising, but the animals got fat and they got metabolic syndrome. They got fatty liver and they got all these different things. So we lowered the uric acid with a drug to see if we could have an effect on the blood pressure, and the blood pressure came down.
But Taca, the guy working with me, comes into my office and says, “Hey, Rick, not only did we block high blood pressure, but they’re less fat. They have less fat in their liver, they have less fat in their blood, they are less insulin resistant.” And then we go, “Oh, could uric acid be involved in much more than just blood pressure and kidney disease? Could it have a role in how sugar may cause metabolic syndrome?” Because it’s the fructose that raised the uric acid, suddenly I was studying fructose, so a kidney doctor transforms into studying metabolism. And that took me into the world of endocrinology and obesity and into discovering you, Robert.
Robert Lustig (00:07:02):
Yeah. We all come at this from completely different ways. My origin story in this is totally different. I was taking care of kids with brain tumors at St. Jude Children’s Research Hospital, and I had a stable, a cadre of about 40 kids who had survived their brain tumor to become massively obese. Now, this form of obesity was well known in the literature, but no one knew or caused it, called hypothalamic obesity due to hypothalamic damage because the hypothalamus is the, as you know, the hormonal regulatory center of pretty much the entire body and also of weight. And that hormone, that pesky hormone leptin had just been discovered in 1994. I moved to St. Jude in 1995 and I said, “Well, let’s measure their leptin levels.” Well, their leptin levels were sky-high because after all, they were obese. So obviously it wasn’t because they were leptin deficient, which of course is not surprising, but they were clearly leptin resistant. And the question is, why were they leptin resistant?
Well, I was aware from my neuroendocrine training that you could lesion the ventromedial hypothalamus in a rat with an electrode and they would become massively obese. And not only that, you could block that effect by cutting the vagus nerve. So the thought was, “Well, they can’t see their leptin because of the brain tumor. Their brain senses starvation because they can’t see their leptin. They’re sending a message to the pancreas to release insulin via the vagus nerve, and that insulin is driving the weight gain.” That was the first aha. I can’t cut a vagus nerve because I’m not a surgeon, but is there anything else I could do? Well, we had a drug available to us that could suppress insulin called octreotide. So we gave octreotide to these kids in a pilot trial, and low and behold, they started losing weight. But not only did they start losing weight, they started being more physically active.
This was really remarkable. This was an untoward effect that was very positive. And the parents would say, “I got my kid back.” And the kids would say, “This is the first time my head hasn’t been in the clouds since the tumor.” I mean, these were kids who sat on the couch, ate Doritos and slept, and now all of a sudden they’re running around with basketballs and trying to swim. This was really remarkable. So we did a double-blind placebo control trial and built a quality of life and activity questionnaire into that one. And sure enough, same thing happened. So this taught me that the behaviors that we associate with obesity, gluttony, and sloth are biochemically driven, and one of the major drivers of it is this hormone insulin. So that of course has nothing to do with fructose, but what it did say to me was, “All right, these kids are very rare, but we know what’s going on with them, what’s going on with everybody else? And why does everybody else have a high insulin when they don’t have a brain tumor?” And that’s where fructose came in.
So I was giving a talk at the National Institute of Environmental Health Sciences at their 100th anniversary. It was a two-day symposium, the first day was going to be on successes, so lead poisoning and pollution and asthma. And the second day was going to be on new challenges. So the morning was obesity and metabolic syndrome, and the afternoon was ADD and autism. So they asked me to come to this meeting at NIH and tell them what I thought was the biggest environmental factor involved in obesity and metabolic syndrome. And I figure they probably thought I was going to come talk about bisphenol A or PFAS or PBDE, a flame retardant, or phthalates, plasticizers, something in the environment we could remove easily. And I thought that just isn’t it, it just isn’t it.
I said, “All right, I’m a pediatrician. What are the two diseases that children get today that they never got before?” Because children are always the canaries in the coal mine for everything, including by the way Alzheimer’s, and we’ll get there in a minute. The two diseases were type 2 diabetes and fatty liver disease. When I started medical school, that was unheard of in children. It was even unheard of in adults unless you were an alcoholic. So then I said, “Well, all right, fatty liver disease and type 2 diabetes.” I opened up my Lehninger, my biochemistry text from 1974 from college, and I said, “All right, these were the diseases of alcohol.” So I turned to the alcohol page and then I turned the page and there was fructose, and I started looking at the pathways, and I looked at the pathways and I went, “Wait a second. They’re exactly the same. There’s no difference.” And then I said, “Well, yeah, of course that makes sense because after all, where do you get alcohol from? Fermentation of fructose. It’s called wine.”
So I went to this meeting at the NIH and I said, “I think fructose is the driver. I think that it is the environmental obesogen, which is now a real term that is driving this obesity metabolic syndrome epidemic, particularly in children. I gave my talk, and then as soon as my talk was over, it was the coffee break, bathroom break, and nobody came back into the room. I had to use the bathroom. So I went out to the bathroom and they tackled me. There’s a bunch of toxicologists tackled me in the frigging bathroom, screaming at me saying, “Oh my god, oh my god, he’s right. Fructose is a toxin. You have to tell the world about this.” I got to tell you, I have never been tackled by a bunch of toxicologists before.
Richard Johnson (00:13:45):
That’s a fantastic story. Yeah. So when we found that we could lower uric acid and prove this fructose, we realized that we were dealing with something that was working independently of calories because lowering uric acid isn’t part of the caloric pathway of fructose. It’s involved in this side chain reaction of fructose metabolism. So fructose gets metabolized like a calorie, but when the uric acid is generated from fructose, it’s generated because the ATP levels fall on the cell and the ATP turnover leads to the uric acid. So just like you were thinking it was a toxin, I thought, “Oh my gosh, this suggests that fructose is causing metabolic syndrome through a pathway that does not involve calories.” But it was true that these animals were eating more, and when we measured it, we found, just like you did, that leptin levels were high, but they weren’t responding to leptin. So if we injected leptin in the rats, they kept eating. Normally, if you inject leptin, animals will quit eating. So we also realized that most people with obesity have leptin resistance as well.
So we went on and showed that the fructose actually induced the leptin resistance in the brain, but high fat diet alone did not. It was specific to fructose. So that was kind of a big breakthrough where we go, “Oh my gosh, fructose makes animals eat more.” And that is one of the reasons you gain weight. If we pair fed them so that they couldn’t eat more, they still gained a little weight because of the black and resting energy metabolism. But nevertheless, they really didn’t gain much weight, but they still developed diabetes, they still developed fatty liver, they still developed visceral fat. So it was working, fructose is working independently of calories, but also is driving calorie intake. So you and I converged with the concept of the leptin resistance being involved and that insulin levels go up. So that’s very, very interesting. Yeah, we keep converging throughout.
Robert Lustig (00:16:13):
Well, I mean we’re both on the same track and have benefited from each other’s work. We’ve never published together, but I think we have to fix that, Rick. I really do.
Richard Johnson (00:16:23):
Yeah, let’s fix that. I would love to publish with you.
Robert Lustig (00:16:27):
Yeah. So the thing obviously that got Levels excited and the reason why we’re doing this podcast right now is because of the paper that you published with David Perlmutter and Dale Bredesen on fructose and Alzheimer’s. Now I got to tell you, this is something that has been stuck in my head. It’s been a bee in my bonnet for years. And when I say years, I mean years. I didn’t have a weigh in per se, but I actually have talked to several people about it, including Dale, and I’ve also talked to Stan Prusiner, the Nobel Prize winner who discovered prions about this. So I have my own pet theory about why this is and why sugar might be a root, not the only, but a root cause of Alzheimer’s disease. So since you are an author of the paper, in fact, first author of the paper, why don’t you give the audience sort of the, shall we say, too long, didn’t read version of why fructose might be a bad guy in your brain?
Richard Johnson (00:17:44):
Yes. Most people, when they think about Alzheimer’s disease, they think about the fact that this is a terrible, terrible disease that leads to atrophy of the brain and the building up of amyloid plaques in the brain, and also a thing called tau protein aggregation. So for the last 50 years, Alzheimer’s disease has really been thought to be due to these amyloid plaques. So there’s been this huge movement to try to find out what’s causing the amyloid plaques and how we can reverse it. And their pharmaceutical agency or companies have generated all these different ways to try to block the amyloid plaques. And as you know, it’s weak. The data shows maybe a little bit of improvement here and there, but it’s nothing like what we were hoping for.
Robert Lustig (00:18:40):
Yeah. But I’m now really concerned because of this whole scandal that science and nature have uncovered, that there’s actually been some doctoring of some photos back from the 2002 paper that originally identified amyloid as the problem. So maybe amyloid is not really the problem. I’ve also heard that amyloid might be the body’s defense against the problem as opposed to the problem itself. Just because amyloid shows up on the scene, doesn’t mean it’s the cause. Just because something’s there, doesn’t mean it’s the causation. It might be the innocent bystander.
Richard Johnson (00:19:23):
Right. But anyway, I think that the movement has been that the amyloid plaques can’t be the primary cause, there must be something underneath. So there’s been a lot of interest in the last 10 years on three key findings that people see early in Alzheimer’s. And the first finding is that there tends to be insulin resistance in the brain. A lot of the brain doesn’t need insulin. It will take up glucose, independently of insulin, some areas of the brain, but there are certain regions that are insulin dependent. You can show in animal models as well as in humans that there’s a degree of insulin resistance, and there are even people giving intranasal insulin as a potential way to try to help treat that with some possible benefit. But it’d be much better to know the cause of the insulin resistance in the brain than just to give insulin.
Robert Lustig (00:20:21):
We should mention that we now know that there are specific trophic factors in the brain. People often think of the brain as fixed, it grows, and then those synapses are fixed, and there’s no regeneration, there’s no remodeling. It’s a static structure. And I’ll tell you, my very first project in science back in 1984 showed that estrogen, a different trophic factor, remodeled synapses in the hypothalamus. This was unheard of, and I got a lot of flack for it at the time. And now it’s common knowledge. But the idea that the brain is plastic and that things can change what’s going on in the brain, and there are trophic factors, and the ones that are most relevant to this story are insulin and leptin and also brain-derived neurotrophic factor, BDNF. And they are altering synaptogenesis. And when they’re not working, synapsis can fall out. Well, guess what? That’s Alzheimer’s. So the fact that you are insulin resistant in your brain is clearly not a good thing, not just from a metabolic standpoint, but from a neural architecture standpoint.
Richard Johnson (00:21:48):
Yeah, exactly. And you’re exactly right about the BDNF and all these other different growth factors and the plasticity. But anyway, so insulin resistance is one of those factors that you can see early on in Alzheimer’s, and some people call it brain diabetes or whatever. A second one is that the neurons seem to have some dysfunction of their mitochondria, the little energy factories that make ATP, and ATP levels fall early. There’s this mitochondrial dysfunction and there’s inflammation. So these three things, neuroinflammation, mitochondrial dysfunction, and insulin resistance. And when I was studying fructose in the animals, I was showing that they induce insulin resistance systemically and that they induce mitochondrial dysfunction, reduce the ATP levels and suppress the mitochondria, and they cause inflammation. I go, “Wait, this is the same bio-signature as what’s going on in the brain. Fructose could be doing this.”
What’s very interesting is that if you eat fructose or sugar, most of it is removed in the liver and only a tiny begets to the brain. So it seemed like there was some paradox, there was some problem. Why is it that very little fructose gets to the brain if fructose is driving the disease in the brain like what I was thinking? And then we had these really cool, not so cool discoveries, Robert, that the body can make fructose and that you don’t have to necessarily eat fructose. But when you eat sugar, the body makes fructose. So the body makes fructose in response to sugar, and the body makes fructose in response to high glycemic carbs like potatoes and rice. And it also makes it in response to salty foods, and all three pathways is due to a particular enzymatic reaction that I call the polyol pathway. But what it is, is glucose can be converted to fructose.
So when you eat a lot of high glycemic carbs, the glucose levels go up in the blood. That’s why CGM is so helpful. That’s why levels is so important group because they provide these CGMs. But when the glucose goes up in the blood, fructose starts to be produced in the brain. And this has even been shown by a group at Yale in humans, that if you raise blood glucose, fructose levels go up in the brain in humans after about 40 minutes. And it’s very significant. And we found that high glycemic carbs and salty food, salt actually triggers that reaction of glucose to fructose. So there are these foods that we eat that can generate fructose, and when it goes up, it goes up in the brain as well as in other tissues.
So this led me to think, “Well, perhaps what’s going on is we’re eating foods that are raising fructose levels in the brain.” And then I started looking at it and I realized that there are all these data that show that sugar intake coral is a risk factor for Alzheimer’s. It’s a risk factor for cerebral atrophy. High glycemic carbs are a risk factor. Salty foods are a risk factor. All the things that generate fructose are risk factors for Alzheimer’s and obesity and diabetes, which are signatures for fructose production or intake. They also are risk factors. So then we had this connection between the risk factors for Alzheimer’s are the same risk factors for raising fructose in the brain.
Robert Lustig (00:25:40):
You know what another way to make fructose in the brain? Be pregnant.
Richard Johnson (00:25:45):
Yes, yes, absolutely. And also trauma. Trauma is a risk factor for the brain. When the brain gets a concussion, there’s a what we call a little bit of ischemia, and the ischemia generates fructose in the brain in response to a concussion.
Robert Lustig (00:26:02):
This is an important point for our audience who’s listening. Okay? Normally, the food industry tells you, “Oh, fructose is fine. It gets converted to glucose in the liver.” That can be true. That’s why they put the high fructose corn syrup in the Gatorade. It was because, in fact, the fructose can enter glycogen, can become glycogen through a backdoor pathway, through fructose 1,6-bisphosphatase and ultimately be diverted away from the mitochondria and toward glycogen. That is actually true if your glycogen depleted. Ostensibly, that’s the reason why fructose is in sports drinks.
However, and this is credit to you, glucose can also be converted to fructose, and it’s through this thing called the polyol pathway. And the polyol pathway is not known to everybody. And it’s worth a moment to sort of talk about why this happens. By the way, the polyol pathway is the reason for cataracts, because glucose gets converted to sorbitol, which is a sugar alcohol, and that’s an osmolite, which holds on to water, and that ultimately is the nidus for cataracts. So this occurs, it occurs in the eye, occurs in the brain, and then that sorbitol gets converted to fructose. So Rick, why do we do this? Why is this a pathway that matters? Why is it there? And why didn’t we develop a mutation to get rid of that instead of the uricase mutation that you’re famous for?
Richard Johnson (00:27:51):
Yes. So anyway, that’s a great question. So when we were looking at this, we were saying, “Why is it that fructose can do all these things?” And it’s true, if you give fructose to a starving animal, it will be converted to glucose because it wants fuel, immediate fuel. But if you give fructose to a fed animal, it will lower the ATP and activate this process that leads to obesity and metabolic syndrome. And it’s really interesting that animals will eat fructose to prepare for times when there’s no food around. Like the bear will eat fructose in the fall, in the berries, it’ll eat thousands of berries. It doesn’t eat one natural fruit. It’ll eat thousands, and it will activate this switch, and it activates it by dropping the ATP, reduces mitochondrial production of ATP. It induces insulin resistance and all these things as a mechanism to aid survival.
Well, one of the really cool things that we’ve discovered, or at least have really looked at carefully with others, is that fructose stimulates foraging. So when fructose goes up in the brain, for example, or when you give sugar, you’ll stimulate a foraging response. And that foraging response turns out to be very important in Alzheimer’s. Because the way that you stimulate foraging… To forage, you have to go into an area that you’ve not been. I mean, you’re looking for food, you have to be willing to go into areas where you’ve not been search for food, look around, you have to look quickly. You can’t spend a lot of time, you can’t deliberate, you can’t have a lot of self-control. You need to just be able to plunge in and do it, get the food, get out, got to go into that lion’s den, et cetera, et cetera.
Robert Lustig (00:29:44):
Sounds like every convenience store I’ve ever been to.
Richard Johnson (00:29:47):
Exactly. So go in there and forage around. Anyway. So it turns out that to do this foraging, you actually have to suppress certain areas of the brain. The cortex is really involved in self-control, especially the frontal cortex. So when you give fructose, you inhibit the activity of that area so that you have less self-control, sort of like alcohol actually. Likewise, if you give fructose, you’ll inhibit the area for recent memory because the recent memory is, you don’t want to really have vivid memories of how dangerous it is, where you’re going to go. And yeah, it will also stimulate impulsivity in all these things. And the way it does it, it works on certain regions of the brain. And guess what? Those are the insulin dependent regions of the brain. And certain areas of the brain, it stimulates, like the anterior cingulate, for example, is a part of the brain that’s important for foraging, and fructose stimulates that. But other areas, it inhibits.
And then when you look at that, you find this amazing thing. Alzheimer’s affects the areas of the brain that are inhibited by fructose. And the areas that are stimulated by fructose are preserved. So like the occipital cortex so that you can see the food, it’s not affected very much in Alzheimer’s. The interior cingulate, which dries the foraging, that’s not really affected in Alzheimer’s. But the cerebral cortex, the hippocampus, the entorhinal cortex, all these different areas that are inhibited by fructose are actually the signature of where it occurs. And it’s the same areas where insulin resistance occurs.
Robert Lustig (00:31:29):
So let’s talk about that for a minute because we had a hypothesis a long time ago, my colleague Dr. Alejandro Gugliucci at Touro University and I talked about why does fructose do this. It’s in my book Metabolical, I believe it’s even in your book Nature Wants Us to Be Fat. There’s this enzyme that is responsible for how cells and how neurons burn energy. And that enzyme is called AMP kinase. So AMP kinase is basically the signal to your cell that there’s not enough energy around. Now, why? Because the substrate that contains the energy is this molecule called ATP, adenosine triphosphate. And the energy is in the phosphate bonds, as you know, but the audience may not. So when you need energy, you cleave off a phosphate, and then the electrons from that then basically get diverted through the electron transport chain to generate true energy.
So, the ATP is the substrate for energy production, but when your cells run out of energy, they turn the ATP into ADP, adenosine diphosphate, two phosphates, and then finally AMP, adenosine monophosphate, only one phosphate. So every time a phosphate comes off, energy’s released, but it also leads to energy depletion, like I said, the fuel gauge on the cell. Well, that AMP kinase is the stimulator of new mitochondria. It is the thing that tells the cell, “Hey, there’s not enough energy around here. I need to make more mitochondria in order to be able to make more energy.” So it is the signal for mitochondrial biogenesis. Well, that AMP kinase is really unique. It has three components. It has three sub-units, alpha, beta, gamma, and in the gamma subunit is the active site for the AMP, for the adenosine monophosphate, in order for it to turn that enzyme on.
Well, there is a molecule, an intermediate metabolite of fructose called methylglyoxal. And methylglyoxal, MGO, and lots of people have worked on this, people in England and people here at the Buck Institute of Aging, that methylglyoxal has an aldehyde on it, and it fits just right into that active site in that gamma subunit. And when it does, that aldehyde binds to an arginine and basically kills the enzyme. It doesn’t just inhibit the enzyme, it kills it, irreversibly inhibits it, and so that enzyme is now dead. So basically what fructose is doing through this metabolite is depleting your ability to generate mitochondria. So your energy’s on its way down and your ability to create new energy is now basically knocked out. So this notion of Alzheimer’s might be due to a depletion in neuronal energetics.
Richard Johnson (00:35:05):
It’s exactly it. We have the same hypothesis, Robert, because when we give fructose to animals, we inhibit AMP kinase, but we do even more than that. So what we do is the fructose consumes ATP acutely, but then it generates this oxidative stress that suppresses the mitochondria from making ATP. So the ATTP levels can’t go up because the mitochondria is not making it. And then the rescue systems, the AMP kinase, but that’s inhibited as well. So what happens is, fructose lowers the ATP in the cell through all these pathways, the oxidative stress mitochondria, the inhibition of AMP kinase, just as you say. And we actually found that uric acid inhibits AMP kinase as well. So it drops the energy in the cell, and that is the signal to eat more, to forage. That is the foraging signal.
Robert Lustig (00:36:07):
And by the way, one of the earliest signs of Alzheimer’s is actually increased food intake and obesity.
Richard Johnson (00:36:14):
Yes, yes, actually. So anyway, to kind of wrap this, our hypothesis together, basically, if you give sugar to animals, which has fructose in it, after about eight weeks, they have trouble walking through a maze. Normally they can get through a maze, and as the more times they go through it, the faster they go. If you give them fructose, when they go through the maze, they don’t get faster. They continue to have trouble getting through the maze. Then, if you look in their brains, you find insulin resistance, you find mitochondrial dysfunction, you find a drop in BDNF, your nerve growth factor, you find a drop in ATP, mitochondrial dysfunction. It is exactly what we’re talking about. And then if you go out to 16 weeks, they actually start developing amyloid plaques and tau protein.
Robert Lustig (00:37:15):
So let me go there for a minute. This is what I talked to Stan Prusiner about many years ago, because I came to him and I said, “Could fructose be a driver of Alzheimer’s?” He said, “Well, maybe.” And he told me why he thought that might be true. He said, “So you have this thing called amyloid.” All right, it’s there. It’s not like you make the amyloid. It’s in a different form, okay? It is in IAPP before it becomes amyloid. It’s intercellular amyloid polypeptide before it becomes amyloid, which is this gunk that basically forms the plaque, but it’s a protein before that. Well, that IAPP, before it becomes gunk, it’s an alpha helix, just like DNA is an alpha helix. So it’s wound around, and it is soluble when it is an alpha helix. But in order to maintain that confirmation, in order to maintain that, alpha helical structure requires energy. That’s an energy dependent process. It’s one of the things the energy in the neuron is used for, is maintaining these proteins in their correct confirmation.
When the energy in the cell goes down because the mitochondrial dysfunctional, because of the AMP kinase and all the things we’ve just talked about, and the levels of energy in the cell are going down, those alpha helices in the IAPP can’t stay alpha helices anymore because that’s an energy dependent process. So what happens is, they go from an alpha helix to beta sheet. And beta sheeting basically is a collapsing of those coils onto themselves. And when that happens, it’s kind of like dominoes. They start basically, more proteins become part of the new problematic structure, which of course is exactly what happens with prions. This is why Stan Prusiner was so excited about this. So this is something that happens in neurons routinely when there’s an energy problem.
Richard Johnson (00:39:35):
It looks like you and I are getting to the same place, but we took separate roads. We both took roads less traveled by. You and I both got to the same place. A drop in ATP is probably the key issue driving Alzheimer’s. And there’s only one nutrient. There’s only one nutrient that lowers ATP in a cell, and that’s fructose. And fructose levels are high in patients with Alzheimer’s, five to sixfold higher than in normal age-matched controls. So I think your idea about inhibition of AMPK, these are fantastic. I wish that I’d written the paper with you, Rob. Would’ve been a stronger paper.
Robert Lustig (00:40:22):
It’s quite all right. We can still do it. It’s okay. But I do, I think that ATP is sort of the linchpin in this story to some extent. However, there’s even more. There’s even more. I mean, if it was just one thing, then we could get a drug that it ain’t going to happen. And here’s why I think it’s more than that. I don’t know how well you look at the GI literature, Rick, but you might have seen this paper that came out a couple of months ago now. The first author is Evanoff, and it came from Elinav’s Lab at the Weizmann in Rehovot, Israel. What they did was they said, “Everyone says a high fat diet causes metabolic syndrome, but it also causes Alzheimer’s. It causes all the chronic metabolic diseases, but a ketogenic diet, which is the highest fat diet, doesn’t.”
So the question is, what’s going on at the level of the gut? Because they study the gut. And what they found was that the gut has three, count them, three separate barriers in it. Because your gut’s a sewer, there’s a lot of you know what in there. Your gut’s not the cleanest place in the world. Okay?
Richard Johnson (00:41:48):
Robert Lustig (00:41:51):
You want all that stuff to stay in your gut and not end up in your bloodstream. Right? So there are three barriers in your intestine to keep the junk out. The first is the physical barrier, the mucin layer. The second is the biochemical barrier, the tight junctions, the proteins that bind the cells together, the most famous of which of course is zonulins, which is what goes wrong in celiac disease. But there’s a third barrier too, the immunologic barrier. And as you know, there’s more immune cells in the gut than anywhere else in the body. And the reason is to keep the junk out. One of the major cell types that does this is a cell called the Th17 cell, and it makes a protein called IL-17, interleukin 17, very specifically to maintain intestinal integrity.
Now, what they did, what Evanoff et al. did was they exposed animals to a regular diet, a high fat with sugar diet, and a ketogenic diet that is a high fat without sugar diet. And what they showed was that the th17 cells and the IL-17 in the intestine was perfectly fine with the regular diet, and it was perfectly fine with the ketogenic diet, but with the high fat diet with a little bit of sugar. In other words, our diet, the cafeteria diet, the standard American diet, the SAD diet, the sad diet, our diet, the th17 cells were completely depleted, the IL-17 was low, and the junk in the intestine made it across into the bloodstream.
Richard Johnson (00:43:53):
Yeah, exactly. The sugar, it’s the fructose that causes the leaky gut syndrome. A long time ago, we were giving fructose and we could show that we could disrupt the tight junctions by just giving fructose to a mouse and increasing the gut leak. And I’ll tell you a cool story. It’s the same sort of story that you just said, but we didn’t look at the th17 pathway, IL-17, and that’s really important and that’s a major paper. But anyway, but I will tell you kind of a fun story. So I was aware that sugar could cause leaky gut, and a leaky gut is really important for allergies, food allergies like peanut allergies and stuff like that. Little children are getting allergies more. They’re getting these anaphylactic reactions more. There was an immunologist who is Steve Dreskin, who was speaking at the university, and he had created a model of anaphylactic shock to peanuts in which he gave peanut antigens to animals, in which he disrupted the intestinal barrier by giving them toxins, not botulinum, cholera toxins, sorry.
So he would give cholera toxin to make the leaky gut and then the peanut antigens would trigger an anaphylactic episode. And I went up to him afterwards and said, “I think I can have you do this experiment without giving cholera toxin. Why don’t you just give fruit juice or fructose?” So we did some studies together and when he gave fructose, it caused the gut leak and then the animals anaphylaxis. We never actually published the paper because we needed to do more animals. But basically, I think that the reason food allergies are so prominent in the last few decades is because of this sad use of giving fruit juice to little toddlers and stuff. But it’s this leaky gut.
Robert Lustig (00:45:57):
And there’s actually data to support that. But it may be an effect on the intestinal cell itself, or it may be an effect on the specific microorganisms in the intestine. Example: group A strep, group A strep. Now, we know that the bacteria that causes tooth decay in your mouth is strep mutans, and it loves fructose, it loves fructose. It has very specific enzymes that make that fructose a preferential substrate just for it. So it’s what burns the hole in your tooth because it can metabolize the fructose and none of the other bacteria can. Well, turns out they’re a group A strep in your intestine that love fructose just as much, and they create toxins. And strep is famous for creating toxins. After all, what is rheumatic fever? What is pandas? This new progressive autoimmune neuropathic disease associated with strep. It was what Sydenham’s chorea was way back when. The point is, all of these end up having neurologic manifestations. Because of what went on in the gut, because we fed the wrong bacteria, the substrate they love.
Richard Johnson (00:47:42):
It’s amazing how complicated fructose is, but how in excess leads to morbidity. As we get towards the end of the hour, it’s really fun talking to you about how we can learn more and more about what fructose does and how it probably has roles in not just obesity, metabolic syndrome, but neurologic diseases and ADHD and bipolar disease and Alzheimer’s and seizures and GI illnesses and anaphylaxis. Really, it’s such a major driver.
Robert Lustig (00:48:29):
I’ll throw another log on the fire: response to COVID, response to COVID.
Richard Johnson (00:48:36):
Yeah, no, it’s the inflammatory response. One of my friends did some studies on COVID and found that the hallmark for long COVID syndrome is mitochondrial suppression, low ATP, and this bio-signature of increased glycolysis, decreased mitochondrial oxidative phosphorylation is what you see with cancers. But it’s also what you see with fructose and it’s also what you see with long-term COVID, and it’s a very interesting observation.
Robert Lustig (00:49:13):
Well, in addition, we know that you can get COVID, but that doesn’t mean you’re going to die of it. Who dies of it? The three demographic groups: BIPOC, people of color, obesity and preexisting conditions, all of which are metabolic syndrome. All right, what do those three demographic groups share? Processed food, high-sugar processed food. That’s what all three share. So the question is, we now know, we’ve known this actually since 2020 when COVID hit, it’s not the virus that kills you, it’s the immune response to the virus that kills you, the hyper response, the basically out-of-control immunologic response. Basically, the chain reaction basically gets out of control. There are breaks on the immune response. The immune response is one of the few things in the body that has a positive feedback cycle. Normally, everything in the body is homeostasis, a negative feedback cycle, where you get a stimulus and then that actually ratchets down our response to it.
But the immune response is one of the places where there’s a positive feedback cycle, where a little makes a lot. And the reason of course is you got to get rid of the infection. But ultimately, there has to be something to reign it in, otherwise it’s an atomic bomb that blows up and you’re dead. And that’s basically what the COVID immune response is, is the lack of the break on the immune response. Well, turns out if you take immune cells and you give them glucose, they do what immune cells do, which is not much. If you take immune cells like macrophages and you give them fructose because fructose inhibits an enzyme in the immune cell called glutamine synthase, this apparently is one of the things that generates that immune response. The TNF alpha levels go sky-high. The interleukin 6 levels go sky-high. Basically, fructose is an immune activator. Fructose releases the break.
Richard Johnson (00:51:39):
Yeah. And the high uric acid also contributes, I think, and may be involved in that process. We found, for example, when I was working on the wards, and the COVID patients came in, the young people who died tended to have metabolic syndrome and obesity. We found a relationship of serum uric acid with morbidity and poor outcomes. And uric acid is a reflection of the processed foods and the fructose and the metabolic syndrome. So I agree with you. Fructose is a big animal that does a lot of things to a lot of systems. I know you have this interest in fructose in cancer and fructose in alcoholism. And we’ve also linked fructose is driving the Warburg effect, for example, which is fructose is the perfect fuel for cancer cells. And fructose is involved in alcoholism too. So maybe, we need to have another session to dive in more because it’s sort of scary.
When I started seeing that fructose could be involved in so many processes, I looked in the mirror, I said, “Am I tricking myself?” It’s like, too many diseases that fructose is important. But then you do the studies and you block it or whatever, and it seems like we’ve discovered a really important pathway. And I think the reason is because fructose is the only nutrient that lowers the energy in a cell. Most foods, when you eat it, you increase the ATP and the excess can go into fat. In fructose, you drop the ATP, so the energy that comes in to maintain energy balance goes into the fat directly. So you maintain a low ATP but high fat program. And that’s what people with metabolic syndrome have. That’s what people with diabetes have. That’s what people with Alzheimer’s have. So we’re looking at a signature, and fructose is the artist that signs the letter.
Robert Lustig (00:53:56):
I couldn’t agree more. All of these diseases that are now prevalent in our world, and I like to name them, they’re eight in my view: type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, cancer, dementia, fatty liver disease, polycystic ovarian disease. All of those are the components of metabolic syndrome. All of them don’t have a drug treatment. All of them are going up in our society and really any society that adopted the western diet. And all of them are due to mitochondrial dysfunction. And the problem is there’s no drug that gets to the mitochondria.
Richard Johnson (00:54:50):
But there is a dietary approach that we can recommend. It’s not to never eat sugar, it’s just that we have to reduce it dramatically. I mean, it’s going to be impossible for a lot of people not to because it’s in so many foods. But very small amounts. Casey Means has talked about ways you can block the glycemic response. There’s a lot of things that we can do to make diet healthier, making healthier choices.
Robert Lustig (00:55:26):
I agree with that in principle, but the problem is the practice. There’s education and there’s implementation. The problem that dissociates those two is another phenomenon, which we did not get to, but maybe we should, it’s called addiction.
Richard Johnson (00:55:47):
I totally understand addiction. And actually, that is the great spoiler, isn’t it?
Robert Lustig (00:55:52):
It is. It’s the thing that makes this so problematic. And I do liken it to alcohol because fructose and alcohol have such similar signatures in the body and also in the brain. So 40% of Americans are teetotalers, don’t touch the stuff; 40% are social drinkers, can pick up a beer, put it down, I’m in there; 10% are binge drinkers; and 10% are chronic alcoholics. Now, what makes somebody a social drinker and somebody else a binge drinker or a chronic alcoholic, we still don’t know. To this day, we still don’t know what distinguishes those phenomena. But what we know is that you can consume a little alcohol and it’d be okay. But if you consume a lot of alcohol, it’s not. And if you are addicted, you can’t consume a little.
Richard Johnson (00:56:46):
Right, exactly. It will trigger you to eat. Yeah, it’s not enough. Yeah, you’re right. That’s a great analogy.
Robert Lustig (00:56:53):
So this is what I see with sugar. So the concept that we need to eat less. Yes, absolutely. I totally agree. And I dedicated my retirement to trying to fix that. But addiction is the obstacle. And I’ll be honest with you, it’s not just the obstacle for the individual or for the metabolic syndrome patient. It’s an obstacle for the politicians to be able to help us with this, in the same way it took so long to fix tobacco.
Richard Johnson (00:57:34):
I agree with you on that. I think that if you’re a sugarholic, and many of us are, you eat that one ice cream cone, and that alcohol drink suddenly triggers a binge. So yeah, I agree with you. It is something we have to work on. There’s this really interesting finding, which is that when we give alcohol to animals, the alcohol actually triggers the polyol pathway and generates fructose. And there’s now other groups too that has shown that alcohol can actually stimulate fructose production. What happened is, we’re making inhibitors for fructose. We’re still a long ways away, Robert. But when we do give these inhibitors, it reduces the craving for sugar. But interestingly, it also reduces the craving for alcohol. So the craving for alcohol is linked with the fructose. And we’re beginning to think that craving is due to ATP depletion in the brain, in the nucleus accumbens.
Robert Lustig (00:58:52):
Well, it actually may be ATP depletion in the tongue. So you might look at the work of Dr. Monica Dus, who’s a neuroscientist at U of Michigan, on this. This is her bailiwick, and she actually redid her lab to study this phenomenon, the sugar phenomenon because of my work, your work, et cetera. Yeah, D-U-S.
Richard Johnson (00:59:20):
That’s interesting. I know that if you block the taste, animals still get addicted to sugar. We did that. So we knocked out taste completely in the tongue. And animals will still be addicted to fructose. They won’t be this artificial sugars, but they will be the fructose. But they may still be getting ATP depletion in the tongue. That’s a really interesting question.
Robert Lustig (00:59:46):
Wow. Well, unfortunately, from a public health standpoint, we have a long way to go. But the good news, I’m wrapping up here, the good news is, we have the science. Now, turning the science into policy is always, that’s the alchemy of public health. But we have the science, and 20 years ago we didn’t have anything. We had calories and saturated fat. And today we have a very different paradigm
Richard Johnson (01:00:19):
Your book really lays out a lot of that science. My book also kind of details these fructose-based pathways based on the science from our group and others as well.
Robert Lustig (01:00:33):
Well, we should mention the name of your book, Nature Wants Us to Be Fat. Now I got to tell you, I don’t know why anybody would want to read that one.
Richard Johnson (01:00:45):
Exactly. Nature Wants Us to Be Fat. But it does provide solutions, Rob.
Robert Lustig (01:00:51):
Richard Johnson (01:00:52):
I admit that the title may make you think, “Well, I don’t really want to read that because I don’t want to know more about that.” But actually it tries to teach you what foods are good, what foods are bad, what foods drive this switch, what foods counter this switch. I mean, one of the great powers of the book is the evidence that hydration is a very powerful tool for blocking fructose effects. I mean, who would ever think that? But it turns out that water intake can be very beneficial, and that it suppresses some of the mechanism by which fructose causes obesity. And we also identified vasopressin. The hormone from the brain is activated by fructose. And when you block the vasopressin from the specific receptor called the V1b, you can block the effects of metabolic syndrome and so forth from fructose. So vasopressin, which is suppressed by water, has a role in metabolic syndrome. And that’s why people who are obese tend to have high vasopressin levels.
Robert Lustig (01:02:02):
Well, so let me throw a different line of thinking at you. Oxytocin is the safety neurotransmitter.
Richard Johnson (01:02:12):
Robert Lustig (01:02:14):
Vasopressin is the threat neurotransmitter. If we are turning our vasopressin in our brain on by sugar consumption, then we think we’re constantly under threat, which of course is what we see in society today. And of course it has many, many ramifications in terms of both behavior and also continued consumption because one of the ways to assuage that threat is more consumption. And this is sort of pie in the sky, do you think if we could get the sugar in our diet down, we could solve some of the violence we’re seeing in our society today?
Richard Johnson (01:03:07):
I do think it has a role. I always worry about blaming food. There’s the murders in San Francisco 20 years ago that were linked with Twinkies, the Twinkie defense. So I don’t really want to completely blame sugar for the mass shootings and so forth, but there is no doubt that fructose decreases self-control, it increases impulsivity. So if you happen to be a person who’s quite impulsive to begin with and you’re eating a lot of sugar, it may make you more impulsive. It may have a little bit less self-control, kind of like a drink, and then you do things that you may not normally do. But yeah, I think violence would decrease. My belief is violence would decrease if we could reduce sugar intake. In my book, I talk about it a lot. I quote lots of papers that link sugar intake and high fructose corn syrup and fructose intake with violent acts. I don’t want to go there, but I do think it’s a contributor. How about that?
Robert Lustig (01:04:21):
Maybe we can convict the food companies instead. After all, if you can convict a bartender for letting somebody out after too many drinks, maybe we could convict a soda company for supplying the substrate in the first place.
Richard Johnson (01:04:40):
I’m all for it if the argument can be made strong. It’s something I hadn’t thought of, but I do think it could be a contributor. So I’m going to not try to make a committed response to you on that one. But it’s a very, very good thinking.
Robert Lustig (01:04:56):
Well, we know that the more sugar, the less attention people can pay to podcasts. So we better wrap this up.
Richard Johnson (01:05:15):
Exactly. It’s just a delight talking to you. I have to tell you.
Robert Lustig (01:05:18):
Yeah, it is so my pleasure. We go back ways now and we’ve been riding this train in different cars, but going in the same place. It’s truly been a pleasure.
Richard Johnson (01:05:29):
Let’s make sure you and I write a paper together going forward.
Robert Lustig (01:05:32):
Yeah, let’s get this done. It’ll be more forceful coming from both of us.
Richard Johnson (01:05:36):