The Hidden Biological Switch That Can Be the Source of Weight & Fat Gain with Dr. Richard Johnson

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Hey, this is JJ Virgin. Welcome and thanks so much for joining me. This is Ask the Health Expert. Here I put the power of health and in your hands and give you access to the top people in health and wellness. In each episode I share safe ways to get healthy, lose weight, heal your gut, detox, and lots more. So if you want to get healthy and get off the dieting for life merry go round, I'll give you strategies that will help you look and feel better fast. So I went to a Bruno Mars concert. I think it was like maybe three or four years ago. And I remember in the middle that concert going, holy smokes, I've got to come back and see this guy as soon as possible. Now you're wondering what that has to do with anything. And here's what it has to do with. I was introd viewing Dr. Richard Johnson to the podcast a couple months ago and all I could think about as I was interviewing him as holy smokes, I have to get this guy back as soon as possible. So if you haven't listened to the other podcasts I did with him, you definitely want to listen to it and these two will complement each other. But literally as I was interviewing him, I'm like, I got to get him back now. Dr. Richard Johnson is honestly one of my heroes. When I was writing the Sugar Impact diet, his work on the sugar fix and was working free fructose and fructose metabolism was like my go to for the book. And so I think his team reached out because he wrote the book, Nature wants us to be Fat and was like, hey, I'd love to be on the podcast. And I'm like, oh my gosh, I cannot believe my heroes coming on the podcast. So we had him on, we got through a teensy bit of what we needed to talk about and he's back now and we are digging into so much stuff. We are digging into the biological switch that is how, how you gain weight, how you gain fat. So if you know how that's happening, you can know how to not have that happen, which we talk about in depth. We're going to talk about dehydration and how dehydration makes you store and hold on to body fat. Wild stuff there. The role of salt in that, how fructose can create gluten and peanut issues, allergies, like just so much stuff. So let me tell you a little bit about Dr. Richard Johnson before I bring him on. He's a practicing physician. He has been a medical scientist for over 25 years. And again, he's internationally recognized for his work in fructose. And oh my gosh, I'm just so excited about the information he's going to share here. He also has done a lot of work in uric acid as well and metabolic syndrome. He is a prolific scientist with research that's been funded by the NIH since the 1980s. He's published over 700 papers, lectured in over 45 countries. His work has been highly cited. And again, he wrote the Sugar Fix the Fat Switch and Nature Wants Us to Be Fat. And he now is in Denver at the University of Colorado. And again, we're going to be, we're going to be jumping around a bunch, but we're really focusing more on his Nature Wants Us to Be Fat book and this idea of this biological switch that could be leading to obesity and great stuff. So hang with me. I will be right back with Dr. Richard Johnson.

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Dr. Richard Johnson, I promise I will not fangirl all over you again. You probably just recovered from the last podcast interview where I did it. You are literally my hero. My hero.

Thank you.

So for those of you listening, I have another podcast with Richard that you are going to want to listen to where we talk a lot about fructose. His book the Sugar Fix, which is what I really use to go deep in Sugar Impact diet. And we are going to do a little overview, but we're going to go much more into nature wants us to be fat. This idea of this biological switch, dehydration, so many cool things to talk about. I'm super excited and you've got some new stuff to share with us, so I'm very, very excited about that. But before we go there, can you just give people just a brief overview of fructose and why it's so different than the other sugars and why it's problematic.

So almost all foods we eat are used to make energy, and when we eat the foods, we make energy. And the main energy we make is ATP, and that's the energy we use to do things. And if we make extra energy, it's stored as fat. So the all foods, when we eat them, we kind of top off our ATP levels to a certain level. A certain level we want to have high ATP and that gives us the energy to do what we want. Fructose is a nutrient that actually wants to help you store fat. So the way it works is it's really unique. It's the only nutrient that when you eat it, it actually makes energy, but the energy is stored preferentially as fat as opposed to ATP. The way it does that is a real cool trick. What it does is it lowers the ATP in the cell, it lowers your energy, which makes you hungry and makes you feel like you're at risk for starvation. But it does it purposely and then it blocks the ability of your fat to break down to replace the ATP. Now you're hungry and you're eating this food, which is energy, but it's being preferentially converted to F because there's a block in producing the ATP. So the energy shunted over to fat and you continue to be hungry until eventually the ATP levels slowly Come back up to normal. It's a trick. It's a trick to make you think that you don't have enough energy on board and that you need to eat more. In fact, you're true. Your ATP levels are tend to be low. That also can correlate with symptoms of low energy hunger, feeling a little bit tired. Things like that is what fructose purposely does. It was developed in nature as a biologic pathway to help animals to prepare for times when there was no food around. Hibernating animals like the bear, the way it beginning about eight weeks before it hibernates, it will start really gaining a lot of fat and it will get hungry and it will just can't control its appetite. This goes on for about eight weeks until it hibernates. Looks like what triggers that biologic switch in the bear is eating huge amounts of fruit now, not the kind of fruit we're eating where we're eating one or two fruits a day, maybe three fruits that have only four or five grams of fructose. The bear eats 10,000 grapes in a day. It eats a huge amount of fructose. And it really requires a fair amount of exposure to fructose to really activate this switch.

Well, what's a fair amount? Because I look at it and go, okay, well what about the apple juice? What about the agave syrup? What about the crystalline fructose they're using in sweeteners?

Yes, exactly. You're totally right. Those all can activate the switch. Soft drinks have so much fructose in them. Apple juice has. We've given apple juice to people and shown that you can activate the switch within minutes when you drink apple juice. And it relates a little bit too. It's sort of interesting. It's not just the amount of sugar, but the speed with which you ingest it. For example, we did a study. The reason is it's the way the switch is triggered. It's triggered by the concentration of fructose that the liver sees. You must remember that when we eat, our food goes into the stomach and then the intestine, then it's absorbed and it goes through the liver before it really hits the rest of the body. And the liver is the big processing place. It's the place where it processes a lot of these nutrients. So when you eat fructose, about the first 4 or 5 grams gets inactivated in the intestine. It's actually just degraded like a calorie. It's just a regular calorie. But the fructose that gets through the intestine gets to the liver and that's where the action occurs. And it's the concentration, that of fructose that the liver reacts to. If the concentration's very high, you'll get a big activation of the switch. If the concentration is low, you may get a very mild activation of the switch. In other words, the ATP levels will come down a small amount versus a large amount. The way this works then is it's not just the amount that you eat, but the speed with which you eat. If you drink a soft drink very fast, you're going to get a big slug of fructose all at once to the liver, especially if you do it on an empty stomach. But if you, you know, if you sipped the, the drink over four hours, there wouldn't be enough.

No one does.

Yeah, no one does. Yeah. It's like the big, it's the big lie. Drink this. Eat this piece of cake in two hours.

Okay.

Yeah, I'm going to take one little bite. Now what happens is everyone starts down the cake. Everyone guzzles the drinks, and this is the problem. So the trouble is, is that, you know, a lot of sweets, you know, they have a lot of sugar and sugar contains fructose and high fructose corn syrup contains fructose. Agave contains fructose. So the trouble is, if you get a large slug of it and you, or you, or you take it very rapidly, that's how you do it. And the big, big, big breakthrough in our work was when we discovered that, and it was already known in biology, but just no one really understood the importance of it, is that the body can make fruit.

I did not know this. Yes, I just saw this. I was stalking you again, okay? And then I saw that part and I'm like, holy smokes. So how does that happen?

Well, yeah, so this was a pretty cool discovery. So it was known for a long time that fructose was made in the body. And it was known that this occurs in diabetics. So you can take a diet. If you, if someone has poorly controlled diabetes and their blood sugars are high, the, the glucose, when it's high, some of it gets converted to fructose. And so there is this way, it's sort of interesting. The body can convert glucose to fructose, and the body can convert fructose to glucose. And it's very interesting. If you're starving and you eat sugar, I mean, if you're truly starving, the fructose will be converted to glucose as instant energy. Because remember, fructose is not really an instant energy. But normally when you're in a, in, in the regular setting, if you eat fructose, the fructose is going to stay as fructose, but in with glucose, it's a little bit different when you eat foods that have a high glucose content, like starch, starchy foods, breads, rice, potato, corn. Yes, exactly. So when you eat that, the glucose levels go up in your blood. So it sort of mimics what it is like in diabetes. And when the glucose levels go up, they get converted. And there's now studies in people showing that we make, you know, 5 to 10 grams of fructose a day, just regularly. And if you eat a high glycemic diet, you can make a lot of fructose. So.

So is your body doing that in order to then store it as fat or. Why wouldn't it just. I thought it just took the glucose, either put it, converted to glycogen, stored it in the muscles or the liver, or stored it as fat. Is that the step to store it as fat?

Yeah. So what? So glucose can be converted to fat, it can be converted to glycogen. So it's a fuel that, you know. So normally, if you eat huge amounts of food, if you eat what we call a hypercaloric diet. So if I put anybody on a large diet where they're eating a lot more calories than they need, they will change some of that into fat. Right. But what happens is, normally it's been shown that people tend to regulate their weight, especially when you're young. And it's really been shown in animals in the wild. So in animals in the wild, if you overfeed them for a week, they gain weight, but then if you stop overfeeding them, they'll go right back to the weight they should. In very young people, they can eat huge amounts of food. As you know, when you're 18, 20 years old, you can go out and eat everything you want and you won't gain weight because our weight regulates it. But what happens is, as we get older, we lose our ability to regulate our weight and we start gaining weight fairly easily. And what's been shown is that that is due to our body suddenly becoming resistant to a hormone called leptin. And leptin is the hormone that controls fullness, satiety. So when you eat normally, leptin says, hey, you've eaten enough. And if you eat too much because you just get excited, there's a correction the body corrects. But what happens is, as we get older, we start becoming resistant to leptin. The question is, what causes the leptin resistance? And that's what fructose does. We showed it years ago. A fat doesn't cause leptin resistance, fructose does. Fructose is what triggers the body to lose its control of appetite. When those bears suddenly, they'll eat twice what they normally eat. I mean, they'll gain eight to ten pounds a day. When they're in this, they call it hyperphagic phagic period. What it means is they just are eating a lot and they can't control their appetite. And that's what fructose does. When you give a large slug of fructose to an animal, they will lose their ability to control their appetite. Now it's really interesting. In animals there's an immediate issue where they'll eat more because the drop of the ATP makes them hung. But it takes about three, three or four weeks on a high fructose diet to make an animal leptin resistant. So if I want to make him leptin resistant, where he's going to eat so much or she's going to eat much more than she should, I have to feed them a high fructose diet for several weeks in the mouse. In people, what's happened is we're eating high fructose all the time. And so, but it can take years to really turn this system on big, big time. Some people can do it faster. So like if you're, if you wanted to do induced leptin resistance and you or me, if we were drinking soft drinks for breakfast, lunch and dinner, we're going to do it very quickly. You know, it's going to happen in weeks to months. We're going to suddenly lose our ability to control our weight. But if it's, you know, if it's just the high fructose corn syrup and the processed foods and things like this, it can take a while before this system really kicks in. And it also takes longer to induce if you're really like an athlete or if you're doing a lot of exercise. Because you know, if you're doing that, you can, you can last longer in the setting of a high sugar diet without actually getting into trouble. But over time this thing works. And the way it works is it erodes those mitochondria. The little things that make energy are ATP. And we have millions of these mitochondria, so it takes a while to suppress them enough, but that happens. And so if you're a super athlete, I Think you're a super athlete and your mitochondria is super strong and so you can weather it longer than others, but eventually it'll get everybody.

But that is not now a plug for you doing a lot of working out to go ahead and eat sugar. That was not what he said here.

Yeah, exactly right.

This leptin resistance, it's not like an on, off switch. You become more and more and more leptin resistant. It's not like the hibernating bear, while all of a sudden three weeks and he's really hungry. You probably become more hungry, more hungry, more hungry, more hungry. And you're just creating this really challenging situation to get out of because now you have to restore leptin sensitivity in order to be able to control your hunger. And I remember when they, the whole leptin thing first came out and they were injecting mice with leptin, thinking this was going to fix things.

Yeah, it doesn't. If you give leptin to an animal that's leptin resistant, that's how we actually prove that they're leptin resistant. We give them leptin and nothing happens. If you give leptin to a normal animal, they'll quit. They'll reduce their food intake. But here's what's really cool. If you can, like if you go on a low carb diet, you know, and so that you're, you're, now you're blocking the fructose you're eating because fructose is a carb. But also when you're on a low carb diet, you're on a low glucose diet. And so you're not making, you, not getting a lot of glucose. You can make glucose from protein and fat, but just, but it's, it's, it's harder and you don't make a lot. So most of the glucose we get is from our carbs. So if you go to a low carb diet, you're low on glucose and low on fructose, so you're not making much fructose either. And what happens is, as you probably know when you're on a low carb diet, after a few weeks, your, your hunger, you know, initially you're hungry for a while. I mean, but it takes about two weeks for the leptin resistance to start wearing down. And like in mice or rats, you know, after two or three weeks, they'll be left insensitive again. And so, yeah, at least in the, in the lab animal, you know, it hasn't really been Tested that well in people. But I do know that like people on low carb diets, they, they're craving for sugar and everything. Their, their hunger tends to go down after a couple weeks.

And plus you would have to look at like if you were looking at all of this, you know, and because I look at this go, all right, so how much fructose could someone really eat? Well, it depends on how much at one time and what, how much fiber is with it.

Right.

Obviously that's the difference with an apple or apple juice.

Yes.

And then it really depends on muscle mass as well. Like how insulin sensitive are they, how much muscle mass do they have? Right. You know, so yes, gives them a little leeway too. So just in repairing all of this and repairing leptin resistance, I would think that is part of it as well. Like what's going on with your overall, with your fitness level, your mitochondria, your cardio, your weight training. And it is why when you are helping someone, if you can add that stuff in, you just start to see the repair so much. Like if they're sleeping well, they've got their stress, know poor sleep now they're insulin resistant and you know, if you get them walking after a meal, heck, did you see that, that research just on the Soleus push ups?

No, I did not. Tell me what they found this, this.

Thing and I think what it really says is you standing desks. This guy out of the UK discovered that if he had people doing what he's calling a Soleus push up, basically when you're sitting at your desk, for people that are sedentary, that have to sit, can't do a standing desk or a treadmill desk or anything else, and are sitting most, if they just do helifts, that it has a dramatic impact on their blood sugar regulation.

There's this new data that's showing that the lean body mass, in other words how much muscle we have, can have a big impact on weight regulation. That if you can increase your lean body mass, actually you can. There's this problem that when you try to lose weight, you have to eat less to keep at that weight. This is like a trap. But when you're losing weight, you're losing lean body mass as well. Not just losing fat, but your muscle mass will come down a little bit and the food intake actually correlates the energy you need to stay in balance correlates with your muscle mass. So if you can maintain your muscle mass, then you can eat more relatively and stay in the same weight.

Okay, what you don't know is this is my next book. This is actually the whole premise of my next book is we've got to stop focusing on weight loss that we've got to start focusing first on. In fact, I'm working on the percentages so that you can figure out how much fat free mass, you know, And I'm using fat free mass interchangeably with lean body mass. I know they're a little bit different scales. Do fat free mass, how much? Because everyone's focused on their body fat. I'm like, no, no, no. We need to focus on your fat free mass and optimize that first. And you know, if you've got way too much mass, okay, you're going to lose all of it, but you want to preferentially lose a high percentage of body fat. But for most people that have 10, 20, 30 pounds to lose if they first focused on getting really active muscle tissue.

Yes.

Right.

Yeah.

100% anabolic resistance. And all of a sudden you've got this hungry muscle tissue that's gonna give you a little bit more of a margin for error. Like I recognized early on here I am a woman, I went, wow, if I really build up my upper body, I can eat more. Yes.

If I put on more muscle, I can eat more. More, yes. And it's good for you too, because the issue is, one of the problems is the reason the muscle mass gets less is insulin resistance actually blocks the ability for the muscle to get the nutrition it really wants. So if we can reverse the insulin resistance, that will help also with improving the muscle mass.

Yeah.

And it's a happen.

Do you lift weights?

I do, but I haven't in the last few months, so. You caught me.

Oh, boy.

I need to do it because. But I just been busy.

Oh, that is ridiculous. I can't believe you even.

Yeah, no, I'm going to. Next time you ask me, I'm going to be able to tell you yes.

Yeah. And I want to know what your fat free mass is. And then you're going to see. Look at this.

Yeah, that's okay. Yeah. I'm not even going to show my.

For those of you listening, I just showed my bicep to him. I'm muscle shaming you a bit.

Yes, you are. All right, but that's very interesting. I haven't published this yet, but I have a grant from the National Institute of Health because we can show that this biologic switch that I'm talking about drives sarcopenia. Oh, my goodness. And so when we can take animals in kidney failure, where the muscles are, they basically lose their muscle mass. They're quite weak. And when we block or knock out part of this pathway, we can make them muscular and healthy despite having kidney failure.

Wow.

So, yeah, it's pretty cool stuff. So this pathway that we're talking about, what it does is it wants. So think about it this way. If you want to survive a period where there's no food around you, what you want to do is you do want to have sufficient muscle mass to forage for food, but what you want to do is you want to preserve energy for the brain, and you want to preserve as much fat as you can so you can live as long as you can with no. When there's no food around. And so it drops your energy metabolism, it slows down your mitochondria, it reduces the amount of calories that the muscle uses and preserves it for the brain. But when you do this chronically, you end up being this. You losing your muscle mass, getting fat, developing high blood pressure, and all these terrible things. So what was meant to be a savior for you, and it probably would be in it if you were. If you're overweight, you're going to live longer when there's no food around than a person who's muscular but has no body fat.

But the chance there's no food around is pretty.

And instead, though, over time, you're going to get heart disease and you're going to get hypertension, diabetes. So it actually is not an advantage for us to activate the switch. And so what we want to do is try to figure out how to avoid that one area that you and I were talking about earlier, before we actually started the show here, was the importance of dehydration and hydration in the switch. And maybe this is a good time.

This is a great time. Well, before we do that, I'm just going to tease everybody. We got to take a short break. So we are going to talk about dehydration. We also have to talk about the gluten and peanut situation, the situation there. So we have many more things. So hang with me. We will be right back.

Some people think nature is like this, but actually it's like this. That's why Colombia engineers everything we make for anything nature can throw at you. Columbia engineered for whatever.

We're back. Let's talk dehydration, because you definitely have me intrigued with this one.

Yes. So, you know, normally, I mean, first off, if a person gets very dehydrated, they lose their, you know, they're Thirsty and often you lose your appetite. So if you're severely dehydrated, you know, it's not a good setting. And animals in the desert, if they get severely dehydrated, they have a lot of them have a secret weapon. And the secret weapon is that they will carry fat in some unusual location of their body. So in the desert you don't want to have it on your body because it will insulate you and overheat you. But like a lot of these desert animals will carry extra fat in their tail or they'll have a hump on their back or something where they'll store fat. And what's interesting is that fat can be a source of water. And when you break down fat, you actually produce water. It's one of the products when you burn fat, even though fat doesn't contain water, when you burn it, it makes water. So animals use it as a source of water in the desert. Marine mammals like the whale gets about a third of its water from, from the fat that it burns. And so, so it has fat all over its body because it does need the insulation in the cold ocean. But, but it will burn the fat as a source of water because it doesn't drink seawater. So, so anyway, so there's this really interesting thing that fat is actually a source not of just calories, but a source of water. What's interesting is that this has a biology. If you make an animal just mildly dehydrated, you can activate this switch and they will convert glucose to fructose in their body. The easiest way to make an animal mildly dehydrated is, is to eat salt. And when you eat salt, the salt concentration goes up in your blood and it makes you thirsty and it's basically creating mild dehydration. We were looking at this and we realized that salt actually can activate the switch because it's one of the ways the switch is activated is by high salt concentrations. We said, oh, maybe this is a mechanism where if you're mildly dehydrated, this switch gets turned on so that you can make fructose from carbs. So what we did is we gave salty foods to animals and we found that over time it took longer time than with sugar, but they became enormously fat and they got insulin resistant diabetic fatty liver, the whole nine yards. Then if we block this fructose pathway using genetic interrupted this gene and so forth, the mice could eat the salt and they didn't get fat. We knew that this was the mechanism. We started looking at people and others had too. And we found that there's all these studies that show that people who are overweight tend to be eating a lot of salt, not just sugar. And all this processed food has a lot of salt in it. And french fries. Why are french fries so bad? Because it's the starch and you got fat on it and then you've got salt. And the salt is helping convert that glucose to fructose in your body. So what we started to realize is that a lot of people are eating a lot of salt. And then we found it was in the literature. There's like 10, 20 studies that show that if you eat a high salt diet, then it predicts the development of obesity. And that people who are overweight are dehydrated like 3 to 12 times more than a lean person. And the serum sodium of very simple tests that you guys can go out and just when you get your blood work with your doc, just look at your serum sodium. Normal is 138 to 145. But if your sodium is on the upper end of normal, like 144, 140, 45, you are at risk of developing obesity and diabetes.

And so, so hold on a couple things like, because I assume we tightly control in our blood, so that's why it would still be in the normal range, but at the high end of the normal range, because your body is not going to let it get crazy high. If it does, then you're really in trouble.

Right.

So you're looking right at that.

You are 100. Right. And that's what happens. And so what happens is when the serum sodium goes up, if you're not drinking enough water, you stimulate a hormone from the brain called vasopressin. And this hormone gets secreted and it reduces the water loss through the kidney. So it makes the urine concentrated. So the urine becomes dark and yellow because it's all concentrated.

Say, do the pee test. Unless you're doing vitamins, the pee test.

Is a great way to. Yeah, if you pee and you would have dark yellow urine, very likely you're, you're dehydrated. It should. The color you want is not clear. It's like just the lightest yellow. That's.

So I have a question though, like, so in listening to all of this, the first thing you said is, you know, camels, lizards are out in the desert. They've got fat stores so that they can burn fat to rehydrate.

Correct?

Correct.

Well, then that makes you think, okay, well, if that's the case, if I'm dehydrated, wouldn't I then, wouldn't my body then burn fat to rehydrate me?

Yeah, I mean, if you're in serious life threatening dehydration, you're going to be burning fat. But you don't want to do that because that really is like, yes, starvation will let you lose weight too, but you don't want to be in a situation of starvation where everything is breaking down. So, you know, but, but what happens is if you, if it's kind of the reverse, if you're mildly dehydrated, you actually store fat. And if you're severely dehydrated, you'll burn.

Fat, which you're never going to get to severe, so you get to mild. And then the other question is, like with those tight controls in your blood, wouldn't that blood level of sodium vary? Like, you know, if you drank a bunch of water, you'd take it again and then it would be back into a lower range. Like, how quickly does that one, you know, like looking at fasting blood sugar and a hemoglobin A1C, you can see a hemoglobin A1C and see blood sugar over time. Or the snapshot of fasting blood sugar, is your sodium level the same that it's just a quick snapshot.

So here's the, here's the trick. The way that we correct the serum sodium is from this hormone vasopressin. So when we release vasopressin, it will help bring the serum sodium back down and help correct it. Because what we'll do is it, it actually decreases our body temperature slightly so that we lose less water through our skin and it decreases the loss of water vapor from the lung, it looks like, but its main action is to decrease the amount of water we excrete in our urine. But we realized that that hormone might actually have a role in driving fat because if it's trying to hold onto water, wouldn't stimulating fat be a good way to do that? Vasopressin is this hormone that everyone thought that its main action was on the kidney, but there were three receptors. Hormones act on receptors. And then the receptor is what drives things. You secrete thyroid hormone. It goes to the thyroid receptor and it does all the things that thyroid does. Vasopressin has three receptors, and one of them, no one knew what it really did. It was called the V1B receptor. What we did is when we studied it, we actually proved that vasopressin drives obesity and it actually stimulates all these things. That we talked about. The biologic switch is driven by vasopressin through the V1B receptor. There's an actual hormone that drives obesity. Just like leptin is the hormone that helps control your appetite. Vasopressin levels are high in people who are overweight, and they're high in people who are going to get overweight. It's actually very useful test. The blood test is called copeptin. It's not commercially available, really, but it should be at some point, because if you measure it, it will tell you what your risk is for developing obesity and diabetes.

And so if your vasopressin levels are high.

Yes.

Is the fix just to the switch is on?

Yeah.

You know, like.

Like.

Does this tell you to drink more water? It's that easy of a fix?

It's that easy a fix.

Holy smoke. You know what's funny? All these things that you hear about forever, right? You know, like, drink more water, they're actually. You come back to them later, and the science proves it out.

Yeah. You know, my specialty is I'm a kidney doctor. And it was the kidney doctors that would say, hey, listen, this is an old tale. It's not true that drinking water causes weight loss. That's just a story because the kidneys can hold on to water for you. And so I was taught that. But it turns out that we were wrong, that our specialty was wrong. And that vasopressin, when it goes up, yes, it goes up to help hold onto water, but at the expense that it also is driving fat as a waste to hold onto water. Wow.

That is.

Wow. And so what we did is we took animals and put them on a western diet. So they're eating high fat, high sugar. And these animals get fat very quickly because the sugar makes them leptin resistant. And then the fat is like the fuel. So the fat just drives the obesity because of this combination of fat and sugar. And when we started, then their vasopressin levels went up, and so the whole thing was turned on. So fructose also activates vasopressin directly. You don't have to eat salty food. If you eat fructose, vasopressin goes up, too. And so what we did is we put them on water. We just gave them extra water, and we actually put water in the. We injected water into the chow. We made these things called hydrogels. But basically, the chow had water in it. And they ate the chow just as they start off eating just as much of the chow as the regular animals. But over time, as they got this water, they became more leptin sensitive and they started eating less chow and their weight stabilized and actually tended to go down and their insulin resistance actually really plateaued and then started to improve. So it definitely helps. And it's like underrated. This is underrated. I mean, you know, if you go to a obesity or clinic, you know, they'll tell you all the things not to eat, but oftentimes, you know, they'll say, yeah, stay well hydrated. But it's, it should be.

Who knows what that means? What does that mean?

Yeah, yeah. So you really. So I, I will say that, you know, there are, there are diseases where you can hold onto water. So if you have heart failure and you drink a lot of water, you can dilute your serum sodium and get into trouble. And there's diseases where this, people can hold on to too much water. So you should talk to your doctor if you think you have some kind of illness that might affect your ability to hold to drink water policy.

Medical disclaimer, folks.

There it is right there.

Thank you.

Exactly. The other two groups where people have gotten into trouble is marathon runners. The teaching is to drink to thirst, because people can over drink water in marathons. Likewise, if you've had surgery, especially young women who have gynecologic surgery in the first two or three days, they hold onto water. But normally I would say you should drink at least eight glasses of water a day. The trick is to not make the urine look like water. You want the urine to have just the slightest yellow tinge, and that's the perfect place to be.

Okay, we're looking for perfect pea. This is another thing for everyone.

The perfect pea.

The perfect pea. I do want to get into that. The gluten peanut.

Yes.

Yes. You know, I have to know about this.

Yes. No, you do so, because, you know. So I went to a conference that was held by an allergist. And you know, I like to go and listen to research that's outside my area just because I get ideas. And it's really wonderful for me to get that exposure. Dr. Steve Dreskin was presenting his studies on what causes anaphylaxis or severe allergic reactions to food. As you probably know, in the last 30 years, there's been a huge increase in the number of food allergies. Gluten is a famous one that causes allergies. Peanuts is another famous one. Shrimp allergies. And then of course, there's allergies to dairy, although they're usually not an anaphylactic one. Anyway, but peanuts is probably one of the worst. He was studying peanut allergies in animals, and what they found was that you had to have an animal that was genetically predisposed to getting allergies. So they. Not all the animals would get allergies, but this particular strain could get allergies, really bad ones, to, like peanuts. So he was studying this one, but he found that in order for the animals to react to the peanuts, that they had to absorb the peanut proteins through the gut. And so normally the proteins are degraded in the gut, and so he had to create a leaky gut. And so a leaky gut is when you're eating food like gluten and things like that get across into the blood, and that's what triggers celiac disease, and that's what triggers allergies. So in order to have a food allergy, you have to have a leaky gut so that the proteins and so forth can get into the blood and trigger that allergic reaction. So if you could block a leaky gut, you could block food allergies. So the way he was doing this is he was giving these animals peanuts, and then he was giving them a toxin to make the leaky gut. He was actually giving cholera toxin. You know, cholera is this terrible disease that causes terrible diarrhea. Yeah, it's pretty, pretty, pretty severe. And I happen to know from studying fructose and from doing studies with fructose that I could create a leaky gut by just giving fructose because it actually causes a leaky gut. He got. And. And I always worried that children who are being given a lot of fruit juice by parents that don't know better, and so they give them, like, plum juice or apple juice or juices of pear juice. And. And these juices are high in fructose that they would cause a leaky gut. And I was surprised to see that, you know, that it was a leaky gut plus peanuts that made the allergy. So after his conference, I went up to him and I said, hey, let's collaborate and let's do the same experiment, but instead of giving cholera toxin, let's put them on soft drinks. And so what we basically did is we put the mice on soft drinks, and then when they got the peanuts, they anaphylaxed. We never published it, actually. I wish we had, but I would.

Love to refer to that in my next. I actually, in fact, last night I was doing a webinar, and I talked about, like, what's going to cause leaky gut? And I'm like, fructose and gluten, you know. Yeah, fructose and gluten. Fructose is. But the. The bigger. The thing now too is it's probably causing leaky brain too. You know, it's like. Which is just right.

So, yeah, there's actually, there is a real story between. Of fructose and dementia that I. This, you know, it's kind of scary. So the, the first thing is, you know, that, you know, the main cause of dementia right now is Alzheimer's disease. And, you know, this is a disease where people lose their memory first and. And then they. They slowly lose everything and, and they often are wandering around and there's this syndrome where they wander and it's a terrible disease. And basically the brain shrinks. And if you look in the brain, you see two characteristics. One thing called amyloid plaques and another thing called tau protein. And so when people found those two things, they said that's the cause of amyloid of Alzheimer's is these amyloid plaques. And so for the last 30 years, the pharma industry has been trying to find ways to block these amyloid plaques and tau proteins as ways to treat Alzheimer's. The trouble is that those therapies have generally failed. I mean, they fail. Like I saw something like there have been 15 different drugs tried for amyloid and they all failed. Or maybe one just showed tiny bit of benefit. And so this has made people think that there must be another underlying cause and something that occurs maybe earlier in the process. When people started studying this, they realized that there were three things going on in the brain. One was that the energy factories, those mitochondria, show up a signature of being damaged. Then the second thing is that there's a little bit of inflammation. And the third thing is that the brain develops insulin resistance. Although much of the brain doesn't use a lot of insulin, there are many areas in the brain that do use insulin and they become insulin resistant. So what's interesting is some of the risk factors for Alzheimer's turns out to be high sugar diets and high fructose corn syrup and. And high salty foods and high glycemic carbs and obesity and diabetes. And I think you can see that they're all linked with the switch. And if you give fructose to animals, guess what happens? They get those three changes in the brain. They get insulin resistance in the brain, they get the mitochondrial, same biosignature, and then they get the inflammation and they have trouble walking through mazes. And so that's pretty scary. And then so what's now been done is people have actually looked at early Alzheimer's disease and you have to look at it early before the brain is gone, basically, as the brain slowly, as you lose the neurons, you lose the evidence of what was going on there. But if you study it early, you find that people with Alzheimer's have high fructose levels in their brain, five to six times higher. So it was published in. There was an autopsy study where they looked at nine patients with Alzheimer's and nine people without, and they measured the fructose levels in the various parts of the brain. And the fructose levels were high, five to six fold higher correlating. And there was one control that had it. And then in retrospect, they realized that that person actually was having. Developing early Alzheimer's.

You know, the big, the challenge here is by the time someone starts to really be aware of it, and I think a lot of it too is they don't want to, you know, they ignore and avoid because it's so scary. And by the time it finally gets there, it's too late to do a lot of these things. So how do you catch it before it gets to that point? Like, you know, how do you know someone's insulin resistant in the brain? How would you know? Besides, like, doing an autopsy isn't going to.

There's a thing, there's a thing called a pet. There's a. Well, it's like a PET scan, like a spec.

Where you could see energy.

Yeah. Where you can, you can look at glucose uptake in the brain. So there are these scans, there's. People are measuring spinal fluid, but there's even some group that has looked for a peripheral marker, and they found a mitochondrial marker that is actually the hallmark of fructose metabolism. But they found it in Alzheimer's in peripheral white cells. So I think that there will be ways to do it. I think that the other thing that turns out is that it's not. So it's. You can get it from the sugar you eat, but it may be more linked with fructose being generated in the brain. It looks like it's more of a stimulation of fructose production in the brain, which happens with high glycemic carbs, salty foods. And so I think if we eat healthier, I mean, it's.

A lot of stuff gets fixed, you know.

Yes, a lot. A lot of stuff will get fixed. And you're exactly right. And it's not like we can't ever eat a potato or, you know, you can't ever have a cake on your kid's birthday. But what we really need to do is to just be aware that we're eating too much of these. These foods. And basically, I think that modest carb restriction, particularly with high glycemic carbs, like the Mediterranean diet, I have a diet that I think is just as good, maybe a little. You have a diet as well. And a lot of these, we all kind of convene on the same pathway. Eat more natural foods, eat healthier foods, try not to eat processed foods. There's a lot of.

Here's the thing, Richard, that I've been noticing, and especially it goes along with this idea that first of all, when people work out, a whole lot of things get fixed too.

Yes, right, absolutely.

It gives you the margin of error when you work out. So just working out, like you look at brain function, I mean, the best drug for brain function is exercise. Look what it does with bdnf. There's nothing comes close. I have a son with a severe traumatic brain injury, so. So I've been going through this process for 10 years. So, like anything brain related, I'm like, what do we need to do? And clearly exercise is hands down the winner. But, you know, if you look at all this and you go, all right, if we're focusing on not what you weigh, but what your weight's made up of, and looking at muscle mass is such a key determinant of, you know, healthy aging.

Yes, absolutely.

Because who wants to be old in a wheelchair? Well, then the next thing you have to do is why do we look at our diet and all we ever talk about are fat carbs? We never talk about protein. We underestimate how much protein people should eat. We villainize protein. When I'm pretty sure that wild salmon or grass fed beef you eat is not the thing that's giving you demand. I mean, it makes me crazy nuts. Because everyone gets afraid it's gonna hurt your kidneys. I'm like, not if you don't have kidney failure, you know?

Yeah, no thanks. Yeah, and I'm a kidney doc and I actually totally agree with you that people are not eating enough protein. There is especially protein leverage effect, these protein sparing effects. There are actually some very good data that having a higher protein intake is beneficial. You know, if you do have really bad kidney failure, you don't want to be eating red meat every night. That is for sure. But, you know, but. But in general, protein is really important and exercise is absolutely critical. So let me tell you what what we've learned about exercise from our work, and that is, and it's going to be completely consistent with what you're saying. What we've discovered is that this fructose pathway, when you, it causes damage to those mitochondria. And the mitochondria are what's critical for giving us the energy we need. Initially, it's a transient suppression of the mitochondria. So when you eat sugar, the mitochondrial function goes down and then it recovers. But if you keep doing it, it causes damage to the mitochondria over time and you can show that. And when the mitochondria get damaged now and they can't repair, you end up in a low energy state. And that's just bad for your muscle, it's bad for your brain, it's bad for everything. Exercise is a fantastic way to rejuvenate those mitochondria. It is by far the best way we have to stimulate the mitochondria to come back to be strong again. Exercise is great. And then also increasing your muscle mass will also help you so that you can eat the regular size meal you want to eat. So that combination of exercise to increase muscle mass, but also exercise to improve your mitochondria, it's not about burning calories, as I think everyone realizes, because you don't really burn that many calories relative to the work that you're doing. But it's making you healthier by improving your muscle mass and improving your.

So you'll be more insulin sensitive, you'll be able to burn fat when you're sitting on your butt, which is when you burn more fat, you'll be able to use more calories throughout the day. You know, early on I started my life as an exercise physiologist. And early on I, everything that we were doing at school was if you want to lose weight, you know, you know exactly what I'm going to say. You have to eat less, exercise more. You had to create a 50, 500 calorie deficit to lose a pound a week or a thousand to lose two. I mean, it was, it was, and I, and, and it wasn't working with my clients. Like, so I was paying my way through graduate and doctoral school and I'm doing this and I go, this is not working. And I thought, Richard, they were cheating. And then I discovered, oh, wait a minute, you know, your body's not a bank account. One of the first things that I started to shift, because everything back then was don't do any weight training till you've done lost the weight. And I kept. And I was at Gold's Gym in Venice, California, training people. I take them there on field trips, right? And what I saw is people that would rarely ever do cardio. They were doing all resistance training. They looked like. I remember one woman turned around and I figured she must have been about 20 and she was like 70 years old. I would have killed for her body. And I went, you know what? This is ridiculous. This is like changing the interest rate on your bank account. You can either go and spend all your money all the time, or you can just fix your interest rate and then you have money coming in. I'm going to teach them how to fix their interest rate by doing more resistance training. Focus there. First it all. You get more insulin sensitive, you're going to burn more calories. Everyone wants to have this great metabolism. I'm like, lift weights. So I love hearing this because it is literally what I started to look at 30 years ago. And I feel like I'm coming full circle now and, you know, with this. But it is. It's never been more important than now with the baby boomer aging and having the situation where you're going to have people who can't balance on one leg, can't get out of the chair.

Yeah, no, I lifted weights for probably 30 years.

Well, don't say in the past.

Yeah, I'm going to start tomorrow.

When are we starting? You can't stop this stuff. It's not like you can do it and you're done.

You're totally right. You're totally right.

I can't believe it. I'm totally busting you. Yeah.

No, you got me.

Okay, good. When are we starting this?

I will start. I will start tonight. I actually can do it. I can do it late afternoon.

That is fantastic.

Good.

I feel better now, too. I'll be able to sleep tonight. I gotta keep you around. This is selfish.

I'll send you a photo.

It's selfish behavior on my part because you're like my, you know, favorite researcher.

It's so important. It's. It is so important. I totally agree with you. All right.

This has been amazing. Thank you so, so, so much. We went all over the place on so many important things, but, boy, like, just listen to this. If you listen to this, listen to it like 10 times over and you'll go, okay, fructose. Like, we're going to just eat one to two, maybe three pieces of fruit. We got to start working out. Do not go salt and things like crazy and make sure you're drinking a lot of water and you've got the pretty what did we decide that pea was called? The perfect pea.

Yes.

Have the perfect pea.

As we say in nephrology, you're in good hands.

Ahaha. Thank you so much. For more info on this and other health topics I cover or to rate and review, find me on Instagram, Facebook and my website, jjvirgin.com and don't forget to subscribe to my show so you won't miss a single episode. Go to subscribetojay.com thanks again for being with me this week.

Foreign.

Hello listeners, this is Anne Bogle, author, blogger, and creator of the podcast what Should I Read next? Since 2016, I've been helping readers bring more joy and delight into their reading lives. Every week I check all things books and reading with a guest and guide them in discovering their next read. They share three books they love, one book they don't, and what they've been reading lately, and I recommend three titles they may enjoy reading next. Guests have said our conversations are like therapy, troubleshooting issues that have plagued their reading lives for years, and possibly the rest of their lives as well. And of course, recommending books that meet the moment. Whether they are looking for deep introspection to spur or encourage a life change or a frothy page turner to help them escape the stresses of work, school, everything, you'll learn something about yourself as a reader and you'll definitely walk away confident to choose your next read, with a whole list of new books and authors to try. So join us each Tuesday for what Should I Read Next? Subscribe now wherever you're listening to this podcast and Visit our website whatshould I read next podcast.com to find out more.