Ep. 286 The Impact of Fructose and Insulin on Brain Health

Your trusted source for nutrition, wellness, and mindset for thriving health.

I have the privilege of reconnecting with Dr. Rick Johnson today. Our paths first crossed in 2022 for an enlightening podcast episode, and I am thrilled to continue our journey! What truly sets him apart is his warm and humble nature which I had the honor of experiencing first-hand when we met at an event earlier this year.

Dr. Johnson is a beacon of knowledge in the fields of medicine, obesity, and diabetes. As a professor of medicine at the University of Colorado, his expertise extends far beyond the confines of academia. His groundbreaking research on sugar and fructose has unraveled the intricate web connecting these sweet substances to obesity, diabetes, and Alzheimer’s disease. 

Today, we delve deep into the latest research on the complex interrelationship between Alzheimer’s and fructose, exploring the role of inflammation, mitochondrial dysfunction, and insulin resistance. We untangle the mysteries surrounding Alzheimer’s, the sixth leading cause of death, and discover how the survival switch within our bodies can predispose us to insulin resistance, diabetes, and Alzheimer’s disease. Our conversation also explores the differences between high fructose corn syrup and naturally occurring fructose in sugar, the impact of processed salt versus more natural alternatives, the significance of hydration, and the profound effects of the standard American diet. We also examine the intriguing connection between alcohol, sugar, mood, and fructose-induced behaviors, shedding light on the role of uric acid and its contribution to impulsivity and non-alcoholic fatty liver disease. 

Join us for an enlightening discussion on multiple health issues as Dr. Rick Johnson imparts his knowledge and wisdom. Prepare to be enlightened and empowered as we embark on this transformative journey!

“We need to think more about how to keep the brain healthy, and eating healthy foods is probably the best thing you can do.”

– Dr. Rick Johnson


  • How fructose impacts brain health
  • How fructose may lead to the development of Alzheimer’s
  • The three characteristic stages of Alzheimer’s
  • Why Alzheimer’s is insulin resistance in the brain.
  • How dementia and obesity are both low-energy states caused by starvation of the brain
  • The link between sugar, salt, and Alzheimer’s
  • Why is sugar a toxin?
  • Should you be fearful of salt?
  • The importance of being metabolically healthy
  • The interrelationship between sugar and alcohol
  • How sugar impacts behavior.
  • The link between fructose and ADHD

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Dr. Johnson’s book, Nature Wants Us To Be Fat

Ep. 205 – Fructose – The Driver Behind Metabolic Disease with Dr. Rick Johnson


Cynthia Thurlow: Welcome to Everyday Wellness podcast. I’m your host, Nurse Practitioner, Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent, is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
Today, I had the honor of reconnecting with Dr. Rick Johnson. We connected in 2022 for podcast Episode 205. He is a professor of Medicine at the University of Colorado and is also a clinician and researcher. He’s an international expert on sugar and fructose, and has made many discoveries on how sugar and fructose play a role in obesity, diabetes, and Alzheimer’s disease. He is an absolutely delightful interview. He is so gracious and humble, and I had the honor of meeting him in real life at Low Carb Denver in February of 2023. Today, we dove deep into new research on the interrelationship between Alzheimer’s and fructose, the role of inflammation, mitochondrial dysfunction, and insulin resistance. How Alzheimer’s is the 6th leading cause of death and how the role of the survival switch can induce changes within the body that make it more likely for us to be prone to insulin resistance, diabetes, and Alzheimer’s disease.

We discuss the differences between high fructose corn syrup and fructose found in sugar, differences between processed salt and more natural forms of salt, the role of hydration, the impact of the standard American diet, the relationship between alcohol and sugar. As well as the role of mood and fructose and uric acid and that it induces foraging behaviors which increase impulsivity and also a propensity for nonalcoholic fatty liver disease as well as many other health issues. I know you will find this conversation as enlightening and helpful as I did.

Dr. Rick Johnson, it’s a pleasure to have you back on the podcast.

Dr. Rick Johnson: Wonderful to be back on your podcast, Cynthia.

Cynthia Thurlow: Yeah. And I’m so glad that you reached out because you were definitely one of the most downloaded podcasts in 2022. You make learning about fructose and the impact on our body fun and you make the information accessible and that is a gift. And so, I want to make sure we start the conversation just acknowledging that you have the ability-

Dr. Rick Johnson: Thank you. [laughter]

Cynthia Thurlow: -to translate complicated concepts into making them tangible for the general public.

Dr. Rick Johnson: That is just very nice to hear. Thank you so much. Appreciate it.

Cynthia Thurlow: You’re welcome. And your infectious enthusiasm, that’s one of the things that I was reflecting on. Dr. Johnson and I met in real life at Low Carb Denver this past February. And I remember talking to Ben Azadi and I said, “Rick is as nice in person as he is over Zoom links.” And I said, “It’s so nice when you recognize that there are so many clinicians and researchers doing really amazing work to help change lives and they’re as good at what they do as they are as a human being.” So, let’s start the conversation there just acknowledging that. But you mentioned when you reached out that there was some emerging research. And I know that you and Dr. Perlmutter and Dr. Bredesen had just published a research article talking about Alzheimer’s. And I think for most of the listeners, either they themselves, or loved ones, or family members are struggling with changes in cognition. So how does fructose impact brain health profoundly?

Dr. Rick Johnson: Well, it turns out that fructose probably has a really important role in Alzheimer’s disease. And we published a paper just a few months ago with, as you mentioned, David Perlmutter, who’s a famous neurologist and writer, and Dale Bredesen, who is a world expert on Alzheimer’s. And we had a whole group of scientists write this paper, and we made the case that the fructose story might be the best explanation for the development of Alzheimer’s. As far as I’m aware, there’s never really been a story that begins from the beginning to the end. There’re things that can explain this part of Alzheimer’s or this part, but nothing that really tells the whole story. And so, the power of this hypothesis and it’s a hypothesis, but it’s extraordinarily supported, really suggests that sugar, which contains fructose is at the heart of Alzheimer’s disease. And so, I don’t know if I can present the evidence or how you want me to do it, [laughs] but we can just begin with one thing and just kind of remind people that Alzheimer’s disease is extremely common disease.

It’s now the 6th most common cause of death. Just about everybody knows someone who has it or has had it. And it’s a terrible disease, it’s one that’s horrible to watch and horrible to have. It’s just sometimes slow and sometimes more rapid deterioration in your mental status. And it’s characterized by three findings. One, the brain shrinks terrible, and it will shrink and continue to shrink with a loss of the brain cells, the neurons and so that’s kind of the center problem. And it’s characterized by two additional things. One is there are these amyloid plaques which are kind of like these types of protein that kind of forms plaques in the brain outside the neurons. And then the neurons themselves will accumulate a protein called tau, and these tau aggregates and really screws up how the neurons think or work. And so, when this disease was first described in the early 20th century, it was thought to be pretty rare. And there were only like 30 cases reported for the first 50 years.

One of the problems is that they thought that if you got dementia when you’re like over 70 or over 75, that was, you know, a normal process to some extent that it was called senile dementia. And they started realizing that most of these cases were Alzheimer’s. So that there was kind of an under reporting of the number of cases. But there is clear evidence that Alzheimer’s has been increasing, even with taking that into consideration, that it’s been increasing significantly over the last number of decades and it’s probably continuing to increase. And it correlates with the intake of sugar and with obesity and diabetes. And obesity and diabetes are risk factors for Alzheimer’s. So originally scientists said, “Okay, this is a disease caused by the accumulation of amyloid of this tau protein.” So, there are literally a race to try to figure out how to block those amyloid plaques. And there were treatments that were aimed at inhibiting the production or degrading it. And over 20 different drugs went to market or went to test trials, I should say, and basically, they all failed.

There are a couple that have just a little bit of benefit and they’ve been approved, but we’re talking pretty marginal benefit and lots of side effects. And so, it’s been a disappointment. And people have started wondering, “Well, could the original hypothesis be wrong? Maybe it’s not an amyloid disorder, maybe it’s something else.” And so, they started looking at the earliest stages of Alzheimer’s and they found three characteristic findings that seem to occur even really before the amyloid plaques become prominent. And the first one is that there’s low-grade inflammation in the brain, low grade, very low grade that you can measure it. The second thing is that the energy factories that are in those neurons, they’re making energy, the brain consumes a lot of energy consumes like, it’s amazing how much energy the brain consumes compared to the rest of the body. It’s a high energy user. And that’s because those neurons need energy to really work at their max. And so, the energy is produced in the neurons through these things called mitochondria, which are these energy factories and they can generate large amounts of ATP, which is the fuel that the neurons use. And that fuel goes down in the very beginning, earliest level.

Studies showing very, very early on there’s like a 10% drop in the ATP levels and that’s pretty significant. And by the time dementia is really full blown, the amount of energy in the neurons is down 30-40%. I mean, it’s low. So, dementia is kind of a low energy state. And we see the same thing in obesity. Obesity is a low energy state. The ATP levels are low even though fat produces energy. So fat is like stored energy, but the active energy, the ATP tends to be low in people with obesity, with diabetes, with metabolic syndrome. And even as we age and actually, the whole issue of aging is associated with a fall in ATP. And we now know that’s because the mitochondria, these energy factories are getting sick. And so, there’s the energy factories get sick, there’s less ATP, and you kind of go into a low energy mode. So, you got inflammation, low ATP.

Then the third one is that the brain actually uses glucose as its main fuel. And glucose is in carbs obviously and we have a lot of glucose in our blood, and the brain is constantly taking it up. Now, many areas of the brain do not require insulin so there’s no need for insulin. The brain cells have figured out how to take up the glucose independently of insulin. But a certain part of the brain, particularly like the memory centers and the cortex, the main part [laughs] that does the thinking, a lot of those areas use insulin to take up glucose. And what happens is there’s a defect where the glucose is not being taken up very well and not being metabolized even when it gets in. So, the glucose and we call it insulin resistance, and it’s the same finding you see with diabetes and obesity, except it’s in the brain. It’s insulin resistance in the brain. And even if the glucose gets in, it’s also not being utilized well by those mitochondria. So, you have a problem with the fuel getting there and a problem with the energy being produced from the fuel. And you can imagine, if you’re not getting the energy in and you’re not getting that glucose, that those neurons are basically starving. So really, you can call it a starvation state. Alzheimer’s is a state where we’re starving our brains. Even when we have tons of food aboard, we’re eating, all this food we’re eating, but it’s not getting and being used by the organ that we want to protect the most. So, this is the problem.

Cynthia Thurlow: I think it’s really interesting, and you’re helping to paint this picture of what is going on physiologically in the brain as this kind of Alzheimer’s picture is evolving. And maybe we pivot just a second to talk about how our modern-day lifestyles, the foods we’re, like I say, choosing to consume. Last night, I was putting out on social media. It was a little snapshot of one of these paragraphs that I was reading, and it was talking about the 50% of the processed carbs from our standard American diet can generate enough fructose. So, again, different type of molecule to increase the risk for Alzheimer’s. So, understand this interrelationship between how we choose to eat and how that actually puts us at risk for developing neurocognitive issues.

Dr. Rick Johnson: I think you’re right on the money there. So, if we go right back to this one comment, we got three findings that precede amyloid, insulin resistance, inflammation, and mitochondrial dysfunction. So, your question is, “Okay, so we’re going back, but can we even go farther back? Can we go back to the very beginnings of what triggers, what is associated with Alzheimer’s?” And here’s what it is. First off, there are certain foods that have been reported to increase the risk for Alzheimer’s. One are processed foods, all those processed foods filled with sugar and salt that we thought of people love, the chips and stuff that you’re eating in the afternoon that have a little sugar in it, have a little salt. A lot of people know about this stuff. We know it’s bad but did you know that it increases your risk for Alzheimer’s? Papers show an epidemiological link.

Now, another one is sugar itself soft drinks. There’re even studies that show that the number of soft drinks you drink is associated in a mathematical way with an increased risk for Alzheimer’s. The more soft drinks you drink, the higher the risk you’re going to get it. And guess what? They did CT scans in one study, and they found that those people drinking, like, more than two soft drinks a week had an increased risk for a smaller brain, a shrinking brain. I mean, everyone brain size varies, but for shrinking brain, that’s not good. [laughs] Okay, soft drinks, sugar, salt. Salt been associated with increased risk. Salty foods and as you probably know from our last talk, we found that sugar is produced from salty foods and sugar meaning fructose. Just brief reminder to everyone that table sugar is sucrose, but it’s actually two sugars. It’s fructose and glucose bound together. And so, table sugar contains fructose and glucose, and fructose is what we think is the bad guy.

We think glucose isn’t great either, because when you eat a lot of glucose, first half, some of it gets converted to fructose. So, glucose is another source of fructose. I agree that chronically stimulating insulin with glucose probably isn’t good either. But it turns out that the fructose is probably more important in the brain health. So, the foods that are associated with obesity are the ones associated with Alzheimer’s and if you have obesity, you have an increased risk for Alzheimer’s. Interestingly, as a person develops Alzheimer’s, they often lose weight. It’s kind of a phenomenon that’s been observed in a lot of people with Alzheimer’s that in the months before, even before they’re diagnosed, they often start to lose weight. And it might relate to a variety of mechanisms. There’re different theories. I can go through them. But one possibility is that as you start developing dementia, you may actually reduce your food intake and start losing weight just because you’re not maintaining your nutrition.

Anyway, bottom line is diabetes. It’s a big risk factor. So, if you’ve got metabolic syndrome, you’ve got something chalked up against you, but it doesn’t mean you can’t turn it around. And your intermittent fasting protocols and low carb diets, these things are fantastic ways to help turn around this process. Okay, so anyway, so we’ve got these foods and conditions associated with the development of dementia also like trauma, like people who smack their head in football matches and things like this, you get a concussion from a car accident that can increase your risk. And so, it’s been kind of a mystery, how do all these things link together to cause Alzheimer’s? And so, the fructose theory came out of this. And basically, here’s how it goes. This is the fructose theory.

The first thing is that fructose causes insulin resistance. And it is so documented in systemically, like in the body. I’ve induced insulin resistance in people with sugar and in animals, and we know the mechanism and it induces low-grade inflammation, and it reduces ATP in cells. So that biosignature in the brain sounds like a fructose biosignature. The only question in the puzzle is that when you eat sugar, most of the fructose we get rid of in our intestine and our liver, and there is a little that spills over that gets to the brain, but it’s not a lot. And so, the question has been, “Why, if it’s fructose, does the fructose have to get to the brain, or is it kind of an effect from the body?” And what we’ve discovered is that our group as well as a couple of other groups, including a great group of scientists at Yale but what we found is that the brain can make fructose and the brain makes fructose when you eat carbs. And the brain makes fructose when you eat sugar. And the brain makes fructose when you eat salt. So, the exact foods that are associated with increased risk for Alzheimer’s also increase fructose in the brain. And the group at Yale actually did a study in people, and they found that if they infused glucose into the vein of a person, that after about 30 minutes, fructose levels start going up in the brain of humans.

Okay, so we now know that these foods that we’re eating can raise fructose levels in the brain. We also know that if we give sugar or fructose to a laboratory rat, that after about four weeks, actually, it’s even quicker, like three weeks, it will have trouble getting through a maze. So actually, all animals have trouble getting through a maze, but we can time it. So, you create this maze, and you can time how long it takes to get through the maze to the other side. And let’s say it takes 3 minutes and 30 seconds. But if you take that same animal and you try it the next day, it will slowly improve. And after a few weeks, it might get through in 2 minutes instead of 3.5 minutes. So, you can look at the improvement, but if you give it sugar, it doesn’t improve at all. [laughs] It will stay at 3. It’s like every time it goes in there, it’s new, [unintelligible [00:20:03] to go. And if you look in the brain, guess what you see in a sugar fed rat or a fructose fed rat. You see mitochondrial dysfunction. You see a fall in ATP. You see insulin resistance in the brain. You see inflammation in the brain. You see all the precursors. And a group in Egypt actually gave fructose for 18 weeks to a rat which is a long time, but not too long compared to its lifespan. And they found amyloid plaque and tau protein after 18 weeks. That’s scary, that’s the whole story.

Now, how about people? Well, if you look at their spinal, I mean, with autopsy studies– unfortunately, by the autopsy studies and, for example, they did one study where they looked at nine people who had Alzheimer’s versus nine age match control autopsies. And the people with Alzheimer’s had five-to-six-fold higher fructose levels in their brain. And also, when you make fructose, there are other things you look for. They found all those too. And then the enzymes involved in fructose metabolism, they found those elevated too. Everything was high. So now you’ve got the diet is associated. You can create it in the laboratory animal. The levels are high in the brain and so we got the whole story, but there’s a big kind of interesting catch, which I think is the most compelling evidence of

all and that is we have a mechanism for why this has happened. So why would sugar cause dementia? Why would we think that fructose might be a cause of dementia? Well, maybe it’s because fructose has a biologic action that normally is thought to be good, but if you keep hitting it, it can cause dementia.

So, it turns out that our studies found that fructose is involved in survival. Animals in the wild eat berries and tons of fructose so they can survive the winter. Getting a little bit of obesity actually provides them the energy they need because they can break the fat down when they’re hibernating, for example. And so being a little insulin resistant can be a good thing. It reduces the amount of energy used by the muscle and is a way of helping to reserve the energy for other parts of the system. It turns out that our work on fructose showed that it has another effect, which is to stimulate foraging. And foraging is a process that an animal uses to help it find food, and it’s actually a biologic response. If you want to forage effectively, you want to be a little hungry and you want to be thirsty, and you want to be hyperactive a little bit because you got to get out there and find things and get back. And you have to be impulsive because you have to be ready to go into areas that maybe not be that safe, have to be a little bit of a risk taker.

You can’t focus on anything too long because you got to be looking all the time where the food is. If you find it, you may want to binge eat it because you’ve got to eat and keep going before the predators come. And you have to be a little brave. You have to be maybe aggressive if you have to fight over the food, but basically you have to change your personality if you’re going to try to find food effectively. So, it turns out that foraging is controlled by certain regions of the brain. And so, the brain has areas that stimulate foraging, and they also have areas that kind of block things like control, self-control, that allow you to be more impulsive. For example, if you stimulate foraging in an animal, you know what happens? You try to stimulate one part of the brain called the anterior cingulate, and you try to inhibit another part of the brain called the posterior cingulate, and you try to inhibit the cortex of the brain so that you want to be thinking, but you don’t want to be thinking too much. You want to be able to say, “Okay, well, I’m willing to stick into that Lion’s den”.

There may be a lion there. [laughs] I want to steal that food behind them. So, you have to have that. So, you have to turn on some regions of the brain and turn off others. And when we give fructose to a human in that first 15 minutes, we can see all these kinds of effects. We can see a stimulation of the anterior cingulate, and we can see an inhibition of the posterior cingulate, and we can see an inhibition of the self-control areas, we can see inhibition of the areas involved in memory, and we can see stimulation of the visual cortex so that you can see the food. Well, it’s amazing. Fructose in humans really seems to show this and likewise, if you give glucose, you get the opposite effects. It’s kind of like satisfying. I got my fuel; I don’t need to forage. You got the fructose, though, it’s saying, “Hey, where’s the food?” And the reason is because fructose lowers the ATP in the cell and glucose doesn’t. So, it makes you feel like you’re starving, so it triggers this response. So, what’s fantastic is I was looking at this pattern and I recognized that that pattern is very similar to the pattern of what areas of the brain are typically involved in Alzheimer’s.

So, like the visual cortex is spared in Alzheimer’s, the anterior cingulate is spared in Alzheimer’s, and the areas that are involved in Alzheimer’s are the areas where fructose inhibits the blood flow, where it inhibits the metabolism. So, it seems like what happened is evolutionarily a long time ago, we developed this sensitivity of fructose to help us survive. And we used the fructose when we ate lots of it, like when the berries were present, we would eat this stuff and it would help us forage for food and help us. It would [00:26:41 unintelligible] [laughs] help us. But now, instead of eating small numbers of berries and this and that, and for short periods of time, we are slam dunk and we are eating so much sugar and salt and all these things that produce fructose in the brain that we go into a foraging, we’re binge eating, we’re foraging, we’re pulsive, we’re developing ADHD, we’re developing these behavioral disorders and we are starving the brains. And when we starve the brains chronically, guess what happens? You can get dementia. And so, whoever is listening to me, I don’t want you to say, “Oh my God, I’m never going to eat chocolate again.”

If you can get away without eating sugar, bless you, you probably will do better. Very small amounts of sugar are quite different than from, for example, a soft drink or a chocolate cake. But anyway, I’m not telling you never to eat sugar. I’m not telling you never to eat bread and all these things, in fact, unless you really want to be on a keto diet. And the keto diets can be great for a lot of people. But nevertheless, what I’m telling you is that the current diets that we’re eating is too much. There’s too much eat cards, the diet, going to the fast food, eating the processed food is not good. It is a toxin. Rob Lustig says, “Sugar is a toxin.” He’s got a very good point. Well, people on the normal Western diet are eating too much and it’s going to catch up with us.

Cynthia Thurlow: Absolutely. And I know one of the questions that listeners will be wondering is are we differentiating between fructose versus high fructose corn syrup? That was number one. And when we’re talking about salt, are we talking about iodized processed salt or are we also talking about natural forms of salt, like sea salt, Celtic Sea Salt? Because inevitably those are going to be the questions, I know I’m going to be asked. And since you’re the expert, help us understand. Are these similar? Are they dissimilar? Is high fructose corn syrup, I would imagine, is way worse than just plain fructose?

Dr. Rick Johnson: Oh, yeah. Absolutely. So, let’s go through that, so not all fructose is the same, not all salt is the same but in general, let’s just talk about it. So fructose, when it’s metabolized, drops the ATP level in the cell. So, fructose is fructose when it gets to wherever it goes. However, fructose in natural fruits is not really the same as fructose in a soft drink. The fructose is the same, but it’s the accompaniments. When you eat natural fruits, you’ve got fiber, vitamin C, and flavanols and all these things. We can actually show in animal studies that flavanols can block some of fructose effects, blocks the ATP depletion to some extent, especially like luteolin, [00:30:06 unintelligible] epicatechin in fruits can block some of it. We’ve actually done clinical studies. Potassium, if you raise potassium a little bit, that counters some of the effects of fructose, it’s amazing.

We did it in animal lowering uric acid or substances that lower uric acid can help to reduce the fructose effects. Vitamin C is really quite effective, but we don’t want to eat huge amounts of vitamin C because you get kidney stones. But still, vitamin C is an antagonist. It blocks some of the effects of fructose. So, if you’re eating a natural fruit, we’ve done studies. Natural fruits are safe. Okay? Natural fruits, if you just eat one fruit, for example, no problem. I don’t think you’re going to have any problem. Now, if you eat 10 fruits like an orangutan trying to gain weight for the dry season, they’ll eat like 100 fruits at one setting, you’re going to activate it. Okay? If you eat enough fructose, [laughs] it will overcome even the good stuff. Juice, I don’t like fruit juice because it’s concentrated. But if you eat fructose, for example, in the middle of a meal where you got all these other things like fibers and stuff that are slowing the absorption, it’s going to have a less effect than if you eat fructose as a snack when there’s no other food around. If you drink fructose and you load it up a huge amount in a short period of time, the concentration, it’s the concentration that’s the problem that will drop the ATP levels.

If you took a soft drink and you did a tiny sip every hour for 10 hours, it’s just going to be a calorie. You’re not going to get the amount of fructose at one time to actually lower the ATP significantly so, it’s all that. So, it’s more complicated. But what we do know is that if you eat a lot of foods and it really tastes sweet, you’re probably getting a bit of fructose there more than you want. And you probably want to try to avoid desserts, pastries, sugar, candies, all those things that’s going to add up. If you’re worried about the fructose in a carrot, don’t worry about it. The intestine actually removes about four or five grams. So, the problem with salt is when the salt concentration goes up in the blood, that triggers the fructose production, and it triggers it from carbs. So, if you’re on a low-carb diet and you’re eating salt, you don’t really have a lot of carbs to convert to fructose. So, salt in a low-carb diet has actually been thought to be helpful because people can often become a little salt depleted. But if you are eating carbs like French fries, [laughs] you’re in trouble because the salt is going to help convert the carbs to fructose. But can you block the salt effects? Yeah, you can. You can do it with water. So, if you drink enough water so that you don’t get thirsty, then you’re safe. And what about types of salt?

Well, I mean, there lot of people who used to get hypothyroid in the days when there wasn’t iodide available. So, I’m a believer in iodized salt. I love sea salt. It’s got a lot of other things in it, like magnesium and stuff that’s really healthy. I’m not anti-salt. I just am pro water. [laughs] So, what I mean is, if you’re going to eat salty food, drink a lot of water with it. As soon as you’re thirsty, you’re triggering the switch to convert the glucose to fructose. And then if you’re a marathon runner, you got to watch how much water you drink, because you can get water intoxicated. If you have heart disease or kidney disease, you should talk to your doctor before you drink tons of water. But pretty much everyone can drink about two to three liters of water a day, so that’s a good target. And if you’re exercising, you probably want to drink a little bit more, but don’t drink gallons and gallons of water without talking to your doctor.

Cynthia Thurlow: Yeah. It’s interesting. Back in my ER days, [Rick laughs] many years ago, we used to see people that were water intoxicated. And so, it’s like too much of any one thing is not beneficial. But I know I talk a lot about hydration and electrolytes being very important. And so, thank you for providing that distinction, because that was one of the questions that came in, should I be fearful of salt? And my message is generally, “No.” But if you’re eating less processed foods, whether you add a little bit of salt to your water or to your foods, as long as you’re staying hydrated, that’s really the key. That was the big takeaway for me from our last conversation. Don’t wait till you get dehydrated.

Dr. Rick Johnson: Yeah. The other thing is to realize that we get a lot of salt from processed food in popcorns and things like where people love the salt. And just be careful with processed food, be careful with popcorn. I don’t know if you ever done the experiment, but if you eat salted popcorn, your weight goes up, the next day. It’ll be like a kilogram [laughs] higher. You’ll gain, like, two or three pounds overnight. And a lot of that is water from the salt and water retention. But the salt is also stimulating glycogen and so you dramatically increase your glycogen. And when you increase your glycogen, you have to burn that before you burn fat. I’ve not seen studies, but I would predict that salted popcorn would predict obesity. [crosstalk] I think that it’s a risk factor.

Cynthia Thurlow: Well, and it’s interesting, because when you go to the movies, which I probably don’t do as much of now that my kids are teenagers and they don’t want to go to the movies with us, so if I’m just going with my husband, we always pass on the popcorn. And I remind my kids, I’m like, “That’s actually not butter that they’re putting on your popcorn that you’re consuming.” And since they’re teenagers and they’re very metabolically healthy if they eat that every once in a while. it’s my understanding that about 30 grams of carbohydrate is what our body can process in a meal if we’re metabolically healthy, and if you’re sitting down and eating a bucket of popcorn, how many grams of carbohydrate you’ve ingested, and then on top of that, how dehydrated you later become?

Dr. Rick Johnson: Oh, yeah, it’s really bad. But you bring up a really good point about young people being metabolically healthy. We’re born really with very good metabolic health, and average kid will have fairly good metabolic health, but you can poison it with sugar and salt. And so, we’re seeing childhood obesity. But it’s true. Like, if you have a 22-year-old who’s super athletic and doesn’t have an ounce of fat, you can give them sugar acutely, and you won’t see too much of a problem with their mitochondria because the mitochondria is super healthy. It’s like you can’t knock it down acutely with, like, one hit with a hammer. But if you keep hitting with a hammer, even the strongest nail will go into the hardest wood. And so, over time, you will see a problem but it’s true, the healthier you are. Like if you’re a Tour de France biker, you can drink soft drinks and it seems like it will have no effect on you. But probably it is a tiny bit.

Cynthia Thurlow: Yeah. It’s interesting.

Dr. Rick Johnson: You can’t detect it.

Cynthia Thurlow: Yeah. It’s interesting because I think there’s a lot of misinformation that kind of floats around. I think I said on Twitter recently that I do eat a little bit of fruit. Not a lot, but a little bit. And people were aghast. I thought you just ate meat. I thought you were low carb. And I said, “Well, I’m metabolically healthy, so if I want raspberries or blueberries or a just green banana, it’s not impacting my metabolic health.” Now, if I was 100 pounds overweight and was not metabolically healthy and I didn’t eat any vegetables and I just ate fruit, that might not be the best choice, but I think it’s helping people understand that if you are metabolically healthy, you probably have a little bit more wiggle room than someone who is not.

Dr. Rick Johnson: Right. I agree with you 100%.

Cynthia Thurlow: Exactly.

Dr. Rick Johnson: As usual, I pretty much agree with what you say.

Cynthia Thurlow: Oh, well, thank you. I know one of the things that we had discussed prior to the interview was talking about the role of sugar and alcohol. And I know that we’ve talked around this subject on the podcast with different guests for differing reasons, but you in particular had said that there’s a lot of emerging research about this interrelationship that I thought would be particularly relevant to listeners in terms of practical takeaways for them for their lifestyle.

Dr. Rick Johnson: Yeah. Well, the first thing is probably all I’ll remember the famous stuff that Rob Lustig would push forth and point out, “How sugar is alcohol without the buzz.” It’s his famous phrase. And he pointed out how sugar is a major cause of fatty liver and of metabolic problems. And alcohol also causes fatty liver and that fatty liver can progress to end-stage liver disease, and alcohol can cause end-stage liver disease, cirrhosis you know and so the two are in parallel. They go in parallel. And it’s also true for the liking of alcohol and the liking of sugar. So that it’s been known for a long time that if you like alcohol, you probably like sugar. And likewise, if you like sugar, you very much like alcohol. It’s not just the individual, it’s the family. So, if you have a father that likes alcohol, you probably like alcohol too, and you probably like sugar.

And there’s another well-known finding, which is that, like, if you are an alcoholic and you get admitted to the hospital and they take away your alcohol, you almost always will start drinking soft drinks even in the hospital. I pointed out when I go on rounds to my residency. I want you to just look at the side table and tell me what you see and 99% of the time they have soft drinks on the table. Now, this what I’m just telling you is not new. This has been known for a long long time. And of course, gosh, we know that combining alcohol and sugar is just one of the favorite things. The margaritas, the pina coladas, and people like sweet wines and port wines. So, it’s well known that a 7 and 7 gin or these various drinks often have sugar in them. Okay, so that part’s known. So, here’s what is really breaking science. And our group as well as another group did this work and also a group in China. So, there’s actually three groups that were involved in this. But what the finding was, was that when you drink alcohol, the alcohol stimulates that enzyme that makes fructose. And it works kind of like salt.

So, you know how when you drink alcohol, you’ll get thirsty? That thirst is similar to like, what if you eat salt? And if you eat salt, a lot of salt that activates an enzyme that converts glucose to fructose. So, it’s converting carbs. So, it’s not the alcohol that’s being turned into fructose. The alcohol is the catalyst. It’s the thing that stimulates the conversion of glucose to fructose. It’s like, for example, if you go into a bar and you start eating chips or pretzels or something with your beer, it’s not the alcohol and the beer that’s causing the conversion– It’s causing the conversion, but it’s the carbs that are being converted from the pretzel into fructose. Maybe I said that wrong. But anyway, the bottom line is when you drink alcohol, you generate fructose. And this group from, I believe they’re from Kentucky, published a really nice paper that included liver biopsy from people admitted with alcohol problems. And they showed that this enzyme that converts glucose to fructose was high in the liver, as were fructose levels.

Now, fructose in the liver is known to cause fatty liver and alcohol causes fatty liver. And like if you give alcohol plus sugar to an animal, it gets really bad fatty liver quickly. But now we have another possibility that the alcohol could stimulate the fructose, and that the fatty liver we see with alcohol may actually be due to the fructose. So, this is where we come in. So, what we did was we gave alcohol to animals that cannot metabolize fructose. So, they can make fructose, but they can’t turn it into fat. And so, when we gave the alcohol, the animals were protected from fatty liver. And so, we now know that the liver disease from alcohol is due to fructose. It isn’t like the two are the same. I mean, in terms of how they work. One actually dries fructose up and is causing fatty liver from making fructose, and then the fructose is metabolized. That means that fatty liver cirrhosis is a fructose disease, alcohol-induced liver disease is a fructose-dependent disease.

Now, admittedly, our paper on this is not published yet, but the data is very strong, and so I feel confident in the data. The other big surprise is that we found that when we blocked metabolism of fructose, animals reduce their liking of sugar. They still like sugar, but it blocks the addiction. And we found that the same was true for alcohol. So, if we block fructose metabolism, we can block alcohol in the animal, okay. And so, we have a grant from the National Institute of Health to try to make a drug to block fructose metabolism as a way to treat alcoholism. Because classic treatments for alcoholism is to block transmitters in the brain. And it’s dangerous when you do that because they’re transmitters up there, the neurotransmitters, they’re all doing things that are both good and bad. So, you don’t really want to block a lot of the neurotransmission and these different mediators completely.

You want to have them function. So, it’s better to go to the root of it. So, we can block fructose metabolism. Then we’re hoping that we’re going to actually come up with safer drugs, better drugs. So that’s what we’re trying to do. [chuckles] We still have a place to go. But if you’re a mouse, I can block alcoholism. [laughter] Haven’t gotten to the point where I can do it in a person yet, but I’m hopeful that this will be a new way to help treat alcoholism.

Cynthia Thurlow: Yeah. It’s interesting because as you were talking, that was my thought process is I’m sure that the pharmaceutical industry would love to be able to help formulate drugs that can treat this. Because as were talking about before we started recording, I think that especially in lieu of the past three years in particular, I think most people were probably drinking more alcohol [crosstalk] than they had been previously. And I would imagine that it has probably heightened individual’s awareness of how much they drink and whether or not they struggle with their relationship with alcohol.

Dr. Rick Johnson: Yeah. And what’s interesting is you can kind of dial it in so you can block the alcoholism fairly significantly, or like, partially at least, it looks like, you know, you can get a setting where the animals will still drink alcohol, but like 50% less. Yeah, anyway, so that also raises the possibility that this could be a mechanism to cause dementia, because we just talked about how fructose can cause dementia, and alcohol is also associated with loss of brain matter and increased risk for dementia. Everything’s metabolic.

Cynthia Thurlow: No, it is and it’s interesting. I have a family member that has a long-standing history of alcoholism and we have watched this family member’s cognitive status really decrease substantially, especially over the last several years, because in light of the pandemic not being able to get out and be around other people, just more drinking that further exacerbated this. And it makes a great deal of sense that if it’s fructose that’s driving a lot of these mechanistic principles, that it would impact their cognition quite substantially.

Dr. Rick Johnson: Right. Yeah, for a long time, there was an argument that one or two drinks a day were safe. But what’s happening is, as we get more information, it is a little bit concerning that there may be risks even with drinking two drinks a day, possibly even one drink a day. I drink occasionally and I like a glass of wine here and there, but I’m trying to drink a little bit less. The more [laughs] I study this I realize that maybe it’s not quite as safe as I thought. I always thought that one drink a day was fine, maybe two drinks a day, but I’m now down to the area of trying to limit to maybe one drink a day or not drink many days. Why do we need to drink?

Cynthia Thurlow: Right.

Dr. Rick Johnson: You don’t really need to drink, and if it’s not super healthy, maybe we should really try to cut it back. It’s Interesting.

Cynthia Thurlow: Right. Well, and I think in many ways, after interviewing so many experts, I think in particular alcoholism or people that have a propensity for drinking quite a bit of alcohol, it’s to work through uncomfortable feelings. And this is where I think there’s this complex interplay of behavioral science and the work that you’re doing and helping people understand the behaviors that they make. Now, one other thing I would love touch on before we close up our conversation today is to talk about the interrelationship between mood and fructose. And so, this is something I find really interesting as a parent of children who are now teenagers, the children that I saw that had the most impulsive behavior, the ones that were probably on medications for ADD, ADHD, what they were eating has a direct impact on behavior. And so, there’s a lot of evolving research in particular about ADHD and bipolar disorder being linked to sugar intake, fructose, and also metabolic disease.

Dr. Rick Johnson: Yeah. So, it’s absolutely true. Certain behavioral disorders are really linked with sugar intake and with fructose intake and with high uric acid. And uric acid is produced by fructose. And one is bipolar disease, “Oh boy, it’s really linked.” And same thing with ADHD. It’s very highly linked in this recent umbrella analysis that was published, I think it was in The Lancet, oh no, the BMJ rather, that found a link with ADHD again. And we’ve published on this linkage and it kind of makes sense. ADHD has a lot of kind of foraging-type behavior, impulsiveness, hyperactivity, inability to concentrate. And also, people with ADHD tend to have a higher uric acid. Interesting, the first effective treatments were done in people with bipolar disease who happen to have gout and high uric acid because there’s an association. And way back in the 1800s people started giving lithium because it can help lower uric acid levels. And then they saw that the lithium was helping the bipolar disease and they thought that the two were unrelated.

But we’re now going back to that relationship and realizing that there is a relationship between uric acid and bipolar disease. And there have been a number of randomized trials where the uric acid lowering drugs like allopurinol have been shown to improve bipolar disease and fructose levels are high in the brains of bipolar patients and been published. So, I think there probably really is a true risk factor association between sugar and ADHD and bipolar disease. You can induce behaviors in animals that are similar and there’s a mechanism when you drop– the quick rapid burning of ATP is associated with a hyperactive response. And then there’s kind of a crash when the ATP levels fall. And no one’s really done really good studies to link these biologic effects of fructose with ADHD where they can look at this. And I’ve written about this in my book, Nature Wants Us to Be Fat, and we’ve published on this as well. So, I think that it’s definitely a risk factor. Is it the only thing? Probably not.

There are probably other things driving it, but I think that it could explain it. One of the interesting findings is that there’s data that ADHD has been increasing with the obesity epidemic. And one of the aspects of that is that’s really linked with intake of sugars and high fructose corn syrup and juices in children. And so, what I recommend, if you’re a parent and you have kids that get hyperactive when they eat sugar, I would really recognize that sugar isn’t just causing like, hyperactivity during the time they’re eating sugar, but if you chronically are feeding them sugar and juices that it may lead to more chronic changes. They can suppress that mitochondrial energy production chronically and then they’re kind of, like, not going to do so well. They’re going to start developing more type ADHD symptoms that can become persistent. And so, omega-3 foods, walnuts, vitamin C. I recommend omega-3 foods. I recommend cutting back on high glycemic carbs, cut back on those French fries and the hamburger buns and try to cut back on sugar in every way you can, high fructose corn syrup.

If you have a kid who you’re worried about developing ADHD or bipolar disease and try to get that group probably needs the greatest attention because obesity is bad, but a lot of people who are obese still do pretty well in life. It doesn’t have to be an end all thing. But if you have really severe bipolar disease or ADHD, it’s really a handicap. It’s really a serious handicap and we need to be thinking of brain health. We need to do more thinking about how to keep the brain healthy. And eating healthy foods is probably the best thing you can do. Natural fruits, not fruit juice. Cut out the soft drinks. Just get rid of them and really cut back on processed foods, Kettle corn bad, okay. [laughter] because it’s got sugar and salt and carbs, yeah, caramel corn. You know I used to love caramel corn when I was a kid, but I would say with the salted peanuts in it, well, that’s probably not the best combination. [laughs]

Cynthia Thurlow: Well, it’s interesting, every time I walk through Chicago O’Hare Airport, they always have these big stores where they’re selling, like, huge bins of multi-flavored popcorn varieties.

Dr. Rick Johnson: Yeah.

Cynthia Thurlow: And I told my husband, because of course my teenagers were like, “Oh, buy us some popcorn, is what they said.” And I said, as soon as I read the ingredient list, I was like, “I can’t buy this. I don’t care how fun it is, we’ll make it at home.” But it was like seed oils on top of just a bunch of stuff you don’t want to be eating. Like make it at home. If you really are dying for some popcorn, make it at home. It’s a whole lot easier.

Dr. Rick Johnson: Yeah, they do. And also, like, cones, they have these little cones of nuts, which nuts are probably healthy, but then they coat them with cinnamon and sugar and salt, and they taste really good, [laughs] and you keep eating them, and they’re really bad for you. Yeah, now I know I’m a vulnerable person when it comes to those kinds of things because as a kid, it was something I always wanted. And what keeps me healthy is wisdom and being strong. But yeah, and it doesn’t hurt if you do the science and you see what it can do. It does kind of–[crosstalk]

Cynthia Thurlow: Good reinforcement.


Dr. Rick Johnson: You don’t want to be the lab rat.

Cynthia Thurlow: No, for sure not. I always enjoy these conversations. I know it’ll be invaluable for listeners. We’ll have to have you come back again and we can talk about the interrelationship of fructose and cancer risk. Please let my listeners know how to connect with you, how to purchase your books, how to support your research, etc.

Dr. Rick Johnson: Well, thank you very much. So, as you mentioned, I’m a researcher, I’m at the University of Colorado. I publish a lot. So, Richard J. Johnson, you can find me on published literature and reach me that way by email and so forth. But I have a book, Nature Wants Us to Be Fat. I have a website, drrichardjohnson.com. I have an Instagram, @drrichardjjohnson, and my book is available pretty much through all sources Amazon, Books A Million, Barnes & Noble. And I really appreciate the opportunity to talk to you, Cynthia. It’s always fantastic to work with you, to talk to you.

Cynthia Thurlow: Thank you. Likewise.

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