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Speaker 1:
Welcome to the Dr. Gundry Podcast, the weekly podcast where Dr. G gives you the tools you need to boost your health and live your healthiest life.

Speaker 2:
Welcome to the Dr. Gundry Podcast. You know, it’s the unfortunate truth that a whopping 71% of Americans age 20 and over are overweight. And that statistic keeps climbing every year. But when it comes to why and how our bodies store fat, most people have more questions than they have answers. That’s why today I brought on a very special guest, who’s been on the cutting edge of research into the cause of obesity for more than a decade. He’s Dr. Richard Johnson, professor of medicine at the University of Colorado and chief of the division of renal medicine. He’s a physician, he’s a clinical scientist, and he’s the author of a new book, Nature Wants Us to Be Fat: The Surprising Science Behind Why We Gain Weight and ho- How We Can Prevent and Reverse It.
Nature wants us to be fat, did you hear that? So in just a minute, Dr. Johnson and I will explain why we believe the solution to obesity is as simple as flipping a switch. We’ll also break down exactly how and why certain foods trigger weight gain, and how you can turn your body into a fat-burning machine. So don’t go away. The research we’re about to share is not only fascinating, but has the potential to help you take control of your health and feel better than ever. We’ll be right back.
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All right, Dr. Johnson, it’s great to see you, welcome to the podcast and thanks so much for coming on. I’ve been really looking forward to this.

Speaker 3:
So have I. I’ve been following your work for, for a long time and, uh, it’s really been enjoyable to read what y- your, your insights, and, uh, now I have the opportunity to talk to you as well. So I’m, I’m very excited.

Speaker 2:
Well, you know, that title, uh, so if, I used to be fat, so I would’ve loved your book, because that p- title tells me nature wants me to be fat, so thank you f- so much for writing that book, ’cause now I can be fat.

Speaker 3:
(laughs)

Speaker 2:
That’s no- that’s not what you mean, right?

Speaker 3:
Well, I, it, that isn’t what I mean. I’m not saying it’s good to be fat. (laughs)

Speaker 2:
(laughs)

Speaker 3:
Bu- but it is true that there are many forces in nature, uh, almost like, uh, developed instincts that we have that drive us to try to eat foods that will make us, uh, gain weight. Uh, so there i- there’s no doubt that we have harnessed nature’s, um, you know, nature’s laws, uh, into helping us [inaudible 00:04:09] go the wrong direction. And it’s a pretty interesting story, so …

Speaker 2:
Yeah, why- w- elaborate on that. I actually, I wrote about that, uh … Let me, I’ll … In my first book, years ago, Dr. Gundry’s Diet Evolution, uh, I talked about how great apes, um, and you and I are great apes, uh-

Speaker 3:
(laughs)

Speaker 2:
… uh-

Speaker 3:
Sort of.

Speaker 2:
S- sort of.

Speaker 3:
(laughs)

Speaker 2:
Uh, great apes only gain weight, uh, during fruit season. And-

Speaker 3:
That’s right.

Speaker 2:
… uh, my editors, uh, at Random House at the time said, “That’s ridiculous. Uh, that’s ridiculous.” And this was in the early 2000s. And-

Speaker 3:
Yeah.

Speaker 2:
… there’s actually huge amount of literature published-

Speaker 3:
Oh, I, absolutely.

Speaker 2:
… s- s- so go into that, would you?

Speaker 3:
Well, I, I- yes. So just to answer your, you know, to, uh, confirm you on this, uh, orangutans, uh, will, are the ones that have been studied the most, and, um, they will, during the fruit season, they will gorge on fruit, they will gorge on fruit. They don’t eat one or two fruits like we do, which, and, and one or two fruits, uh, at a time is healthy, right? But when you eat large amounts of fruit, the fruit contains sugar, it’s sweet, and that sugar is fructose, which is also in table sugar. And that happens to be the primary nutrient that activates a process to try to, you know, shift the energy that we produce from active energy that we use to stored energy that is fat.
And so these orangutans will, uh, you know, there was an anthropologist, Cheryl Knott, who did these studies, and she would, you know, uh, watch the orangutans and (laughs) collect the urine off the trees, and, and she showed that, um, they actually, when they eat fruit, they basically go into a fat storage. They quit ma- making any ketones or anything like that, and they, they go into a fat storage, uh, setting. And then, um, they, they actually increase their fat storage maybe by 20%, uh, w- you know, they can get 15, 20% weight gain, and so they really become a little bit plump and (laughs) portly, you might say.
And then, during the, uh, rest of the season, the, where there’s, uh, where they’re having to eat, uh, uh, leaves and twigs and, uh, and f- very few fruits, they actually live off their fat during, during those, uh, e- uh, s- part of the, of the year. So, uh, and there are other, there are other primates that do it, too. There’s, uh, there’s, uh, a lemur, fat-tailed lemur, who, uh, (laughs) will eat a lotta fruit during the wet season, and then during the dry season they’ll, they’ll actually hibernate. I- i- you know, it’s not hibernation in the, in the summer, they call, it’s actually estivation, but for all purposes, they, it’s hibernation, they go into a hollow, a, a, you know, tree, and then they s- uh, basically drop their metabolism and live off their fat, and they use their fat not just for energy but also to make water, because during the dry season there’s not a lotta water.
And, and when you burn fat, you produce water. So burning fat not only produces energy but produces water, and some animals use fat as a way to give them water during times when there’s not. So yeah, there are these primates that, that eat a lotta fruit, and there’s a evolutionary story there. And, um, and, and the, the, the big part of our story was, uh, the discovery that animals want to, uh, you know, avoid starvation. (laughs) You know.

Speaker 2:
(laughs)

Speaker 3:
There- there’s, it, there’s nothing worse, the- there’s four great things that animals do not want at all costs. One is they don’t wanna starve, starvation’s bad. (laughs) It leads to death. Uh, dehydration’s another one, no animal likes to be really severely dehydrated. No animal wants to run out of oxygen if it’s like, uh, in a burrow and, and there’s not enough oxygen, th- no animal wants that. And no animal wants a predator. And so there’s this, uh, you know, so we’ve, we’ve learned that, you know, in biology, we’ve learned the responses that animals do to these, you know, these things.
But what, what we, you know, uh, obviously an animal would prefer to avoid it, you know, like the old, uh, g- ant and the grasshopper, it’d be nice to s- you know, prepare for, for a winter and to have that food stored away, uh, rather than be the grasshopper and suddenly it’s winter and (laughs) there’s no food and you’re gonna starve.
So what’s happened is that there is a absolutely incredible, uh, finding that, um, certain foods, when you eat them, actually, um, are preparing you for a period of time when there’s no food sh- w- no food around. And this is, uh, when animals eat these food, they activate an actual biologic switch that allows them to store fat. But it is- doesn’t just store fat. It, uh, it does a host of responses that are, are aimed at protecting it. And so we- we’ve actually developed tastes for these foods, in pr- uh, and so, so we have an instinctual desire to eat foods that can actually help store fat for us. So it’s all aimed as a survival mechanism way back when when food wasn’t always on the table, the grocery stores weren’t f- chock full of food and, and, um, and so, uh, it’s a biologic response. That’s why nature wants us to be fat, because there are these foods that actually trigger a biologic response to the store of fat.

Speaker 2:
Well, all right. Uh, you’ve whet my appetite, so to speak.

Speaker 3:
(laughs) Yeah. [inaudible 00:10:20]-

Speaker 2:
Wh- wha- what are those foods that, you know, are gonna activate this fat-storing switch?

Speaker 3:
So when we were, uh, looking at this, we realized that a lot of animals, uh, will, will eat fruit. And you just talk about this, not only the, uh, you know, orangutan, but things, uh, animals that hibernate, like bears, you know, in the fall, uh, the fruit starts to ripen, and the- that means it gets sweeter. And i- it’s almost like a link with nature, because the, when the fruits ripen, the seeds also mature, and so that, uh, when the fruit is eaten by the animal, the fruit actually, uh, the seeds can disperse, and then, uh, be used, you know, to plant and, I mean, to grow a new fruit tree. So, so fruit trees seem to know in nature that if they make the fruit ripe, that’s gonna increase the, its ability to survive, ’cause more f- animals will eat it and then disperse the, the, the seeds.
So the fruit, as the fruit ripens in the fall, the animals know, have learned that this actually helps them gain fat, and, uh, or, or whether or not they’ve learned it, they, it’s now part of the na-

Speaker 2:
It happens.

Speaker 3:
… nature’s response (laughs) it happens. So they start eating the fruit, and it’s been shown like for birds that are gonna migrate long distances, they have to store fat to travel the thousands of miles they go nonstop, and, and animals that nest. Uh, and there’s even fruit, uh, uh, fish that eat fruit and, um, and so it turns out that fruit seems to be used, um, when it’s eaten in excess to help animals gain weight.
So we were studying this and we realized that fruits, you know, are c- con- we consider them very healthy, but when you eat huge amounts, it seems to trigger a switch. And the main nutrient in fr- in fruit is a, is fructose, which is a, a sugar, which is also in table sugar (laughs) and high-fructose corn syrup. And it’s basically, uh, the main way we get fructose is from these added sugars, table sugar and high-fructose corn syrup, what makes up the vast majority of sugar people are eati- are fructose that people are eating.
And so what, what happened was we said, “Okay, let- we’re gonna give fructose to an animal,” and when we did it they, you know, normally animals will keep, regulate their weight really well. And, uh, i- th- you know, if they eat more one day, they eat less the next. If they exercise more one day, they exerci- you know, they, they rest the next day. You know, and, and animals, generally speaking, in, in the wild, try to maintain a regular weight, ’cause they don’t wanna get fat and get eaten by predators, and they don’t wanna … Y- you know, so they normally regulate their weight.
But if an animal, uh, is preparing for hibernation, they start eating this, a lotta fruit. Then suddenly what happens is it loses that ability to regulate its weight. I- they become hungry all the time, they become thirsty. They start foraging for food, this is all part of the biologic response. So they, they’re, they, they actually decrease their willpower, uh, because they, they have to have the strength to go into areas that, uh, they’d never been to, that are maybe dangerous. So they don’t wanna h- um, they, they, when they go in there, they have to look around rapidly. They can’t, um, deliberate, they can’t, you know, they, they basically, they have to reduce their recent memory a little bit, because, uh, they don’t wanna remember the predator that, that might be in that area too vividly. So they, they wanna kind of dampen the memory.
And so what they do is the- they actually reduce certain area of activity in the brain that allows them to forage, and they be- they actually become, uh, they, they actually start increasing their foraging behavior. And they, the- they, not only are they hungry, normally animals regulate their weight, as I mentioned. Uh, and in the first couple weeks where you’re eating a lotta fructose, if y- i- if you give it to animals, they do regulate their weight. So although they’ll, y- you can put fructose in the drinking water, they’ll eat, they’ll drink a lotta the water ’cause it tastes real good. But initially, they’ll reduce their chow intake so that they don’t gain weight.
But after about two weeks, two or three weeks, suddenly they lose that ability, uh, to, uh, control their appetite. And they keep eating, and they, they start eating more chow, even though they’re drinking all this fructose. So what happens is that their total f- energy intake goes up, and so they’re eating more and more calories, their food intake’s going up, and although they’re foraging, when they’re not foraging, they reduce their metabolism. So they become like couch potatoes. So their, their resting energy metabolism drops, but their, uh, but their m- their, their ability t- when they’re foraging is maintained. So it’s like this really cool system where they’re trying to conserve their energy, use it for when they need it. They use … You know. And, and so, and they become insulin-resistant. And insulin resistance helps reduce their energy metabolism, ’cause, you know, it reduces the glucose taken up in the muscles so there’s less energy, uh, being expent on the muscle, so that reduces the, the, the requirement, so that you can live off a lower level of energy.
So, uh, and then they, they do this phenomenal thing where they, uh, they work on those … in the [inaudible 00:15:56]. (laughs)

Speaker 2:
Yeah. (laughs) the [inaudible 00:15:58]-

Speaker 3:
They work on your [inaudible 00:16:00]. They go in there and they suppress activity. It’s just a general suppression of activity, and, and, and so what happens is they do it by inducing oxidative stress, not, not the, the, from the mitochondria, but they actually, uh, engage another enzyme called NADPH oxidase. Uh, no one wants to hear that, but anyway. They cause, uh, stress to the mitochondria, reduce the energy, the general amount of energy being produced, and they, and th- and what happens is the, uh, calories then get shunted over to fat, which is the stored energy. So instead of making ATP, the energy from, from food is, is shunted, uh, is transferred over to make fat. And so it’s this beautiful thing, uh, where they, uh, where it’s a great way to, to store fat.
So the animal, what’s incredible is the animal starts storing fat, even though they’re not, um, you know, they’re not in a starvation state. Th- they’re, they’re, they’re not starving, uh, but, but it’s preparing for starvation. So it’s helping you store fat so that when that event comes, you, you have the, enough fat to survive through that period. So it’s a, it’s an amazing, uh, set of responses, and we call it (laughs) the metabolic syndrome. We call it, “Hey, you know, this, this is abnormal, this is pathologic. We shouldn’t … You know, insulin resistance leads to diabetes and, and it also, like it raises blood pressure a little bit, and that can lead to hypertension.”
And so we thin of it as, um, as bad, and it is bad for us, because it, when you keep activating this switch, it does sh- shift from insulin resistance to diabetes, and it does move from, uh, elevated blood pressure to hypertension, and it does move from a temporary fat storage to help you during periods of (laughs) stress to, uh, to suddenly it, continuing, the fat continues to grow. And so the problem is this continued activation of the switch, um, and we’re doing it because we’re not just eating fruit, uh, a lot of fruit in the fall when, when the trees are r- you know, uh, when the fruit’s ripening. We can go to the store and we can eat sugar all year round. And, uh, and, you know, we’ve, we’ve developed a t- you know, we have a taste for sweet, and we have a taste for this. And so, uh, so we pick out these foods.
And, and, th- you know, that taste, uh, is actually, you know, was wh- what developed, we think, to, to, so that you could find these foods. And, uh, you know, in the days when things were, were, were tougher, you know, this was, uh, it was an advantage to be able to find those foods that are sweet, and, uh, that contained fructose.

Speaker 2:
So what, you mention that most animals, um, they’ll do fine for about two weeks, and then they suddenly shift over to this fat storage. What- what’s taking place, i- is it the insulin resistance that drives it, or, uh, what do your studies show?

Speaker 3:
Yeah, so, so it turns out that there’s, um, you know, as you know there’s this hormone leptin. And leptin is produced by the fat, and normally, uh, people, uh, whe- you know, leptin is the hormone that i- it’s linked with insulin, just as you say. But when you eat, leptin c- communicates to the brain when, when you’ve eaten enough. And so leptin is the hormone that tells you you’re full. But it’s been known for a long time that people who are overweight don’t, are resistant to leptin. The leptin levels go up, but they’ll still eat. You can enj- uh, if you have an animal that’s leptin-resistant, you can prove it, you know, by injecting leptin. So if you f- and then monitoring how much food they eat. So, you know, normally an animal that’s eating food, and if I inject it with leptin, it’s gonna reduce its food intake immediately, within 24 hours, the food intake is down. Uh, but if an animal has what we call leptin resistance, they’ll keep eating, and if I inject it with leptin (laughs) it still keeps eating. It doesn’t change.
And what we found was that, uh, fructose causes leptin resistance. But it takes several weeks. And, uh, we even did a s- we did a whole series of studies on this. Uh, you know, s- [inaudible 00:20:33] really interesting. So if you take an animal, and you, uh, give it fructose until it becomes leptin-resistant, you can take the sugar away, and it, a- and, uh, but it will continue to eat more calories than it wants for at least two to three weeks. So, uh, that leptin resistance will persist when you stop fructose.
And here’s a really interesting thing. Fructose itself, uh, you know, it does cause, you know, it will lead to weight gain just by itself. But it’s not, it’s not huge. What really causes the weight gain is the pre- eating a high-fat diet with fructose. So the fructose makes you leptin-resistant, but then the fat really accelerates the weight gain because it’s so energy dense.
So it turns out that weight gain, when we did studies, like we- we’ve done all these very careful studies, what drives weight gain is this combination of leptin resistance plus to many cal- you know, food. If you, if you make an animal leptin-resistant but you don’t give it extra food, uh, it, it will gain a tiny bit of weight from the drop in resting energy metabolism, but basically, uh, it will not gain much weight. And, but if you give, uh, and so if you do like isocaloric diets, like the, the sugar industry will do studies where they redu- they put everyone on the same number of calories, and then they say, “Well, sugar doesn’t cause weight gain.” And the answer is, “Yeah, sugar doesn’t cause weight gain when it’s isocaloric.” The way sugar causes weight gain is that the fructose makes you wanna eat more, and then when you eat more, that’s what causes the weight gain.
But what’s interesting, uh, Steve, is that if you give sugar and make it isocaloric, or even, uh, hypocaloric, where they’re on a diet. In other words, if you, if I put you on a caloric restriction but your diet is really high in sugar, you’re not gonna gain weight because you’re on a caloric restriction. Uh, but, you’re gonna- you could still get diabetes, and you s- could still get fatty liver, and you still could get, uh, hypertension. When we did it to animals we found that we could induce diabetes, high blood pressure, [inaudible 00:22:56] fatty liver. Even on a diet, where the animals are eating less than they normally eat, provided they’re eating a high-fructose diet.
So the fructose, um, is working two ways. It’s working through, you know, you know, th- through a, uh, a energy, classic energy balance story, where, uh, it’s f- making you eat more, and that’s driving weight gain. But this also has a direct metabolic effect that is independent of excess calories, and that’s what’s driving diabetes and all those things.
And, uh, so it’s sort of interesting that it unites the two major, two of the major theories out there, the energy balance people who say everything is just calories, um, and, and also the low carb people who point out how low carb diets are so much better, uh, in so many ways. And, um, and, and so it does kinda unite those.

Speaker 2:
Yeah, you know, there’s, uh, I guess there’s a fairly popular book, um, suggesting that diabetes can be cured by, by a fruit diet. Um, that you should just eat massive amounts of fruit and you’ll cure diabetes. And I’ve, I’ve, and these, this has not been written by physicians, by the way, uh, but by PhDs, and that’s okay. Uh, but I’ve had several of my diabetic patients read this book and try it, and what you observed is what I observed, is that this is one of the best ways to, uh, cause diabetes, worsen hemoglobin A1C, exactly because of the mechanisms you mentioned. Uh, any thoughts on that?

Speaker 3:
Yeah, no, I, I agree with you. So the fruit story’s, uh, an important story to understand, because, um, the, the nat- you know, as you know, as you’re like a world expert on, of, fruits contain a lot of polyphenols and, uh, really wonderful compounds that h- that block fructose. So natural fruits like, uh, can have vitamin C. I- uh, I’m actually a fan of vitamin C, we’ve done some work on it, we can show that it blocks fructose effects to some extent. Uh, you know, it contains epicatechin and quercetin and all these wonderful, uh, flavonols that, uh, can also block fructose effects, that, that has lots of fiber and it has potassium.
And so in general, uh, small amounts of fruit are great, because you get all these flavonols and vitamin C and fiber. And I’m a big fan of, of natural fruit in small amounts. And also, the f- wh- a natural fruit may have four or five grams of fructose, some of them, like an apple, may have a little bit more. Uh, you know, when you get up around f- (laughs) eight to 10 grams, I start getting a little nervous, but, but, you know, definitely are in that, uh, four, a lotta fruits are in the four, three to six gram range. And, and, and my friend Josh Rabinowitz, who’s a, a doctor at Princeton, has done this really wonderful work. And he’s shown that, uh, the, you know, the first three or four grams of fructose that you eat get inactivated in the intestine. And so, uh, it’s the fructose that gets to the liver that’s the problem.
And so, uh, when you just eat one or two fruit, a lotta that fructose, uh, is not, is being inactivated, you’re getting relatively little to the liver, and yet you’re gaining all these other good things. But if you, now if you take the fruit and you say, “Okay, I’m gonna make fruit j- I’m gonna make smoothies, and I’m gonna take 10 fruit, and I’m gonna drink this (laughs) juice in 30 seconds,” and now you’re getting this large amount of fructose, because you’re combining it with all the fruit, and you’re d- you’re drinking it really fast, so it’s gonna overwhelm the intestine, it’s gonna get to the liver. And now, and there’s no- you’ve taken out the pulp and the fiber and a lot of the good things, uh, and now you’re gonna get it.
You know, so I’ve had, just like you, I had patients come to see me where they were having trouble losing weight, and turns out they’re eating f- drinking fruit smoothies after every run, and all these things. And, and you can overdo the fruit.
Now, havi- having said that, you know, fruit smoothies are bad and fruit drinks are bad and, um, fruit juice you should be very careful with. You know, ha- having said all that, um, you know, we did do a study in which we, um, put, uh, overweight, uh, adults on a low-sugar diet, and one group also had to re- eliminate fruits, and the other group got to add back fruits t- so that they could eat a certain number of fruits. And it turned out that adding back fruits did not block the ability of the low-sugar diet to work. So they, we had a, we had success and los- in the patients losing weight, improving their metabolic syndrome. But the adding back s- of some fruits, you know.
So I think that one or two fruit, uh, with a meal is probably very good. Um, it has a lotta good things. But if you’re eating large amounts of fruit, if you’re eating that bowl of grapes at the (laughs) while you’re watching TV, or, or you’re, you’re, uh, you know, so, uh, so I agree with you 100%.

Speaker 2:
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Yeah, you know, I, I used to tell my patients, “Look, let’s go down to the San Diego zoo and look all i- look in all the cages. Nobody’s got a juicer, uh, in, i- in a-”

Speaker 3:
(laughs)

Speaker 2:
… “in a” … We’ve, we’ve just manipulated ways to, you know, mainline, uh, fructose. And-

Speaker 3:
(laughs) Exactly.

Speaker 2:
… and the other thing is, you know, we never had 747s bringing fruit from Chile and Argentina to Colorado in February. And-

Speaker 3:
Right.

Speaker 2:
… y- you know, I, I grew up in Nebraska, and I, there’s no fruit (laughs) in Nebraska in, in the winter. And we didn’t h- we did not have access to these things.

Speaker 3:
Yeah. So all this, all this is important. You know, we did, we also, um, another aspect of fruit juice, why I don’t like it, is we did a study with apple juice, and apple juice is about as sweet as soft drinks. So it has as much fructose as a soft drink. And we knew that the w- so the way the fructose works is it’s not working through its, uh, calories so much as it’s working by dropping the energy in the cells, right? M- mentioned it causes the [inaudible 00:36:05] (laughs) it reduces the energy produced in the [inaudible 00:36:09].

Speaker 2:
Yeah.

Speaker 3:
The amount of ATP coming out is reduced, and it, it shifts it to, uh, an archaic, ancient system called glycolysis, where, you know, that, that makes just small amounts of ATP. So ATP- P levels fall in the cell, with sh- when you, when you have fructose. So fructose can, uh, decrease the energy in the cell, and that is how the fructose activates this big switch. It’s not from the calories, it’s from this unique ability of it to reduce the energy in the cell.
Um, and so, uh, so that’s a very important point. So what we did is we realized that if we gave apple juice to, to people, that if we gave the apple juice in a large amount over a short period of time, that it would drop the energy in the cell very rapidly, because the concentration of fructose that hits the liver would be high, because it’s th- both the amount and the speed that makes up the concentration. Whereas if we gave the same amount of apple juice, but gave it over like an hour and a half, and delayed how long we gave it, that it would kinda trickle in and it wouldn’t have the same effect to activate the switch.
So in other words, the, how you, how you eat your food could make a difference. And what we found was it was exactly true. If you drank it, and you drank it fast, you could really activate this biologic switch to gain fat. Whereas if you could drag it out over a long period of time, it was like a calorie, it s- it lost its ability to activate the switch. And so, so i- it, it really relates to tha- the kid who (laughs) drinks that, guzzles down the soft drink when they’re thirsty out on the, you know, out in the heat, you know, uh, they’re activating the switch big-time that way, uh, and that’s why liquid sugars are so dangerous, because we tend to drink soft drinks and power drinks and energy drinks, we tend to drink them fast. And, and, you know, adding sugars to coffee and tea is not good when you add sugar to it.
I, I th- I went to this place in eastern Russia, uh, I mean, excuse me, far, uh, I’m sorry, western China, right on the edge. And it was this remote area where the, um, where the Chinese actually look like Russian people, it’s really interesting. They’re speaking Chinese, they’re part of China, but they’re actually not your typical Chinese. And these people would, would drink this tea, I s- Steve, I saw this guy come in, and he, he was very overweight. And he pulled out a little bag of sugar, and he put like three bags of sugar, little tiny bags, into one cup of tea. I mean, I shouldn’t have been staring, it was kinda rude of me, but, but I couldn’t bel- I (laughs) I couldn’t believe it. There was, like half of the tea was sugar. Half of the, you know. It was like this … How could you drink that?
And, uh, and, and the poor guy was very, very overweight. And, uh, but it turned out that that was the, uh, custom in that little town to, to have a lotta sugar in your tea. So, um, but anyway, so I’m sorry I digressed, but anyway. Uh, yes-

Speaker 2:
Well, tha- that’s like our custom of having a frappuccino, uh-

Speaker 3:
(laughs) Exactly.

Speaker 2:
… i- it’s (laughs) there’s-

Speaker 3:
Exactly.

Speaker 2:
Yeah, and, and-

Speaker 3:
So-

Speaker 2:
… we wonder why … Well, so you brought up an interesting point. Um, where’s y- where, what’s your take on a calorie is a calorie is a calorie, and it’s calories in and calories out? I, I know your take, but tell everybody else.

Speaker 3:
Yes, well, it isn’t that simple. I, I wish it were. Uh, when it comes to calorie- calories are what primarily drive weight gain. So it is true, calories are primarily what drive weight gain. But why you eat more calories is because you’ve, uh, you get leptin resistance. And, and that, you’re getting from sugar. We actually did studies, if you give fat to an animal, it will not develop leptin resistance. You give sugar to an animal, it will. And the, it’s the sugar that triggers, that really makes an animal want to eat more. Uh, so, uh, but, it, the, uh, the fructose in sugar is also, uh, what drives all the metabolic effects like prediabetes, like fatty liver, like elevated fats in your blood, like high blood pressure. And those are driven independently of excess calories, it can occur on low calorie- calories if you’re eating a lot of fructose.
And so, so they, it’s, it’s a little bit of both. But, um, in general, I, uh, I would say that it’s, it’s more important, food selection is more important, uh, in, in the trea- in treating and trying to, uh, g- get to weight loss. And I think your idea of, of, you know, developing healthy ketosis and, and, uh, mitochondrial uncoupling, and th- this is a wonderful way to lose weight, uh, and equally important probably is to avoid eating foods that make you wanna eat more calories. So, um, y- you, y- uncoupling is a great way to burn those calories you’re, you’re eating in excess, and really helping you lose weight. But, um, if we can also … And, and you’re, you, of course, recommend pretty much a lo- a lot of, along the same lines of what I, of what we discovered with our research. But, you know, f- uh, sugar and fructose are one of the key drivers that, um, that activate the switch to gain weight.
And, uh, and what really expanded our story, um, and we, we need to go there is this, the discovery that it isn’t just the fructose we eat that’s the problem. Uh, it’s the fructose that we can make. And our body c- can make fructose, and it does it only one way, and it does it from make- it makes it from glucose. And when, uh, when there’s too much glucose around, uh, the, you know, the body starts converting that to fructose. And this is the problem of, of high-carb diets that are just rich in, in starch, and, uh, these f- these foods like white (laughs) flour bread, or rice, uh, potatoes, uh, cereals tha- chips, potato chips. And, uh, these, these are starchy foods that release a lotta glucose. And so the body senses that extra glucose, and not only does it stimulate insulin to help move that glucose into the tissues, but what it’s doing is it starts to convert some of that glucose to fructose.
And when that happens, the fructose activates the switch. Makes you hungry, makes you wanna keep eating, makes you forage, makes you do a- all the things that regular fructose does f- from the diet, you can get it from when you make fructose. And we, we, uh, we had these animals that cannot metabolize fructose. They stayed skinny all their life, uh, they’re really an amazing a- animal, they don’t get fat, they don’t get hypertension, they’re s- protected from fatty liver. Um, you, you c- you know, it is possible to make them fat with butterfat, and we can talk about that. B- but it’s a very healthy fat, and this … Well, it’s not healthy fat, but they don’t have fatty liver and they don’t get diabetic and so forth.
But anyway, uh, with these animals, uh, we were able to show that, uh, if you feed glucose, you can also, um, block the, uh, you know, the glucose gets converted to fructose, and these animals are protected from obesity. But I can make animals get obesity and activate the switch just from things like bread, and rice, and, and glucose. So it turns out that there’s two, y- you know, it’s not just the fructose we eat, but, but certain carbs, not all carbs. There’s ver- a lotta great carbs, lotta great plant carbs, uh, you know, but there are a lotta carbs that are good, but the carbs that are really starchy, that increase the glucose levels in our blood, they get converted to fructose and they’re, they’re just as bad as sugar. So if you’re eating a lotta white bread, uh, (laughs) and rice and potatoes, you’re, you’re, you’re, you can get into trouble.
Um, and so that was the, uh, kind of a big discovery. And then we discovered that there were other foods that could activate the switch, too. I don’t know if you want me to go into all those, we, we could.

Speaker 2:
Yeah, let’s go into that, although I wanna stop you for a second, because you’re right, I have a number of people that, uh, swear, uh, that they do not eat any sugar. And yet, you know, they’re insulin resistance, they’re overweight, and then we start looking at their diet, and it’s a very high-starch diet. And sometimes they’re quote, you know, good starches, like sweet potatoes, or, um, and when we take those starches away from them, uh, that’s when things, you know, start turning around, for these i- individuals.
So, uh, th- your observation is great, that we, just by eating a lotta glucose, which is starch, um, you know, combined with (laughs) lots of glucoses, y- you can convert fructose and flip the switch. O- that’s a great observation.

Speaker 3:
Yes, i- it was, uh, it was really exciting, because, you know, originally I had thought it was just the fructose we eat, and I was on a, a podcast with Jimmy Low Carb Levita or whatever (laughs) you know, I think you know Jimmy more.

Speaker 2:
Yeah, Jimmy more.

Speaker 3:
Wonder- wonderful person. And, and I was talking about low-fructose diets, and he says, “Doc,” he says, “You know, I tried cutting out sugar,” and, and I had a lotta people who responded to my diet, you know. This was, uh, my first book way back when, 2008. And, uh, and he says, “You know, I’ve had a lot of people re- you know, I try to cut out sugar, doc, but, um, I found that I had to cut out all carbs to really, for it to really work.” And I, and now I know why, because, uh, th- i- it isn’t that you need to n- uh, reduce all carbs, it’s just you need to reduce the bad carbs, and these high glycemic carbs, which we call, you know, like starchy foods, they, they can activate the switch as well.
Now, we had another discovery. So once I knew that the body could make fructose, I started studying the, this, uh, you know, h- what regulates that? And it turns out that it’s turned on by low oxygen states, by low, uh, low blood flow. All, you know, all the things that those first four things I told you that animals try to avoid, like low oxygen, n- you know, n- nutrient load, like, ischemia. You can actually activate, whe- when you have a, if you have a heart attack, your heart will start making fructose. And there’s, you know, papers in Nature showing that when that happens, the fructose i- is meant to be a, to, to help, but what happens is it’s just, in, in humans, the reaction is just so over- o- too much, and, and it actually can cause cardiac disease. And, and in the kidney it can cause problems, and in the brain it can cause problems.
But, so it turns out that this fructose can be produced, uh, in the body, uh, whenever there’s stressful situations that kind of threaten it, m- make the organ feel threatened, then it starts to be produced. And if it’s produced too much, it’s a problem. So that was one thing. But the other thing was I was thinking about diet, and I realized that what really stimulates this r- a reaction to convert glucose to fructose is whe- is, uh, anything that raises the salt concentrations in the blood. Eh, what we call th- I mean, it’s, it’s basically, everybody has serum sodium that they get on their blood test. And we all ignore it, you know, unless it’s, uh, y- you know, we c- doctors, you, typically it’s normal, and, you know, you, you don’t normally get, people don’t normally c- call you and say, “Well, you know, your sodium is on the upper le- end of normal.”
But it turns out that, uh, the sodium concentration, uh, can control this reaction. And, and people who have a higher sodium concentration, ’cause they’re not drinking enough water so that the salt concentration’s higher in their blood. People who don’t drink a lotta water, uh, will have a higher serum sodium and they’ll have a higher risk for obesity. And if they have a lower serum sodium, even in the normal range, they’ll be more Likely to be skinny. And the- the- these data have now been published, we’ve actually looked at it as well, a- and i- you know, it’s phenomenal tha- that the sodium concentration, uh, which is governed a little bit by the, how much salt and water we’re, we’re having. So when I, uh, when I eat salt, if I eat salty food, the salt concentration goes up, and it helps convert the glucose in my body to fructose. And that’s why the french fry (laughs) is so bad, that’s why potato chips are so bad. Because the salt actually stimulates the, the conversion of the glucose to the fructose.

Speaker 2:
Oh man, so you mean I, I c- I can’t put, uh, some, uh, Himalayan salt on my raw pistachios anymore to make ’em really tasty?

Speaker 3:
I think you can’t, but there’s a trick. So let me tell you the trick. I, so I did this study. So I, uh, gave people salty soup. I, I did this, I, I mean, I say I, I’m a coauthor, but it was done in Turkey by my colleague Mehmet [inaudible 00:50:16]. So we wanted to see the power of salt. So what we did is we gave soup, and you can mask the amount of salt in soup. So, you know, we added this salt, and we, the soup was qu- quite salty, and one day, not super salty, but, you know, when the people drank the bowl of soup, the salt concentration, we could measure it in their blood, goes up within minutes, and it would just went u- it stayed in the normal range, you just went up like two points. So it went like from 138 to 140, you know?

Speaker 2:
Okay.

Speaker 3:
Still in the normal range, but it, when it did that, it activated the switch. We could show that with special blood tests, and also the blood pressure went up. So the salt was activating this switch, right? And, but then we gave one group, this was all done blinded, one group got water with it. And so they had to drink this water. And when they drank the water, even though they had the soup, now the prevented that salt concentration from going up, ’cause they neutralized it with the water. And the, and the switch wasn’t turned on. And so this tells me that the next time we go into a, a, a bar, not the [inaudible 00:51:23] bar, but a regular bar, if you wanna heat those pretzels, if you wanna eat those chips, it’s okay, but what you wanna do is drink water before to drop the serum sodiu- you don’t wanna get … As soon as you s- feel thirsty, you’ve activated the switch, basically.
So if you, uh, if you eat enough salt that you’re thirsty, you’ve, you’re activating the switch. So stay well-hydrated. So we, we even did a study with animals where we gave them sugar, and, uh, food. And believe it or not, when you give sugar, it also increases the salt concentration in the blood. It’s sort of interesting, it moves, moves the water into the cell and makes the water concentration, or the salt concentration in the blood go up. So even soft drinks, they’re, they’re dehydrating. And we all knew this. You know, everyone knows that if you drink a soft drink, it does not hydrate you well. In fact, your serum sodium-

Speaker 2:
It makes you thirsty.

Speaker 3:
Yeah! It makes you thirsty, your serum sodium goes up, that’s exactly right. And it activates that, it’s activating that process to make more fructose from the food you’re drinking, from the soft drink. So i- you know, um, so if you drink … W- we, we gave soft drinks to animals, uh, on regular diet, ch- just regular chow, or on western diet, and we could really, uh, increase their weight gain, uh, through this salt mechanism. Actually, i- we also just did studies where we increased salt, we gave animals just a high salt diet, and it takes a longer time than with sugar, takes like three to four months instead of three or four weeks. But y- suddenly the animals became hugely fat, and, uh, if we gave them water, we could suppress the development of obesity, we could give them extra water. And we did that by putting water in the f- in the chow, we injected water into the chow. And by doing that, uh, they ate the same amount of chow.
Uh, actually they started controlling their chow intake, so they’re eating less chow, because they, uh, they became more leptin-sensitive. But anyway, what happened is we could, we could treat obesity just by, uh, in- in- increasing water intake.

Speaker 2:
All right. Uh, since we’re talking about fructose, let’s talk about uric acid. Uh-

Speaker 3:
Oh, yes.

Speaker 2:
Ooh. So wha- so what’s the deal with uric acid? A lotta people think about uric acid, they heard about it with gout. Some people have heard about it with high blood pressure, kidney issues, one of your specialties. How, how is all this tied in?

Speaker 3:
Okay, so, so uric acid is a substance that’s, you know, got a lotta nitrogen, and it’s basically a breakdown product, it’s- that we have in our blood, and it’s, it’s broken down from the DNA, from the nuclear material in our, in the, in the food we eat. So when we’re eating protein and carbs and fat, we’re also eating, you know, the nuclei of the, of the plant or the n- you know, the, the thing that carries the DNA and RNA. And when those things get broken down in our body, they’re converted to uric acid. And so, um, uh, we a- all, all of us have uric acid in our blood, okay? And then we excrete it primarily through the intestines and the kidneys, and so normally we have a low, a relatively low level of uric acid. It’s actually higher than most other animals, but for us i- you know, it- and it doesn’t bother us.
So we have this substance in our blood, no one really cared about it, right, ’cause it’s not a problem unless i- the levels get high. But if we’re eating, uh, uh, foods that can produce uric acid, th- then the uric acid can go up in our blood. And one of the foods that does that is sugar. So fructose, when fructose, uh, is metabolized, um, there’s th- there- there’s basically, fructose is broken down to carbon dioxide and water. So fructose is like a sugar it’s broken down. But there’s this side reaction that occurs where fructose, uh, causes the ATP levels to fall, remember, the energy levels. And when that energy level falls, uric acid is generated, and the uric acid actually helps maintain the energy level at a low state, ’cause the uric acid actually is what is responsible for stunning the mitochondria, stunning the energy factories to keep the energy levels low.
And so the uric acid that’s produced actually has a biologic role inside the cell to kinda keep the energy level low. And that is a ch- associated with this activation of the switch. So, uh, we actually, to our s- surprise, many years ago, when we were studying fructose, we found that the uric acid in the fructose was what was responsible for driving the switch. And, um, and so, uh, th- it, and, and so that the switch is not driven by the calories of fructose, it’s driven by this side-chain reaction.
So, uh, what’s happened is we’ve discovered that foods that raise uric acid also can, can cause obesity. So right now, we have, think about it, we have five tastes. We have the sweet taste, which is h- there to help us find fructose. And we have the salt taste, that’s to help us find salty foods, which will help us make fructose. (laughs) Then we have bitter and sour, which are these tastes to help us avoid eating foods, ’cause they might contain toxins and so forth. And then there’s a fifth taste called, uh, the savory taste, or the umami taste. And this is the food taste that many of us love, it’s like the taste for Caesar salads and, uh, beer, for example, has, um, this, uh, savory flavor, uh, umami flavor from the yeast that’s in the, in the, uh, beer. And, uh, you know, there’s a lotta foods that we, we like, the rich, meaty extracts, you know, where you kinda simmer and you get that rich sauce.
Th- and, and it’s been shown that what umami is is it’s actually consists of two things. It consists of glutamate, uh, which is an amino acid, and it also consists of a, uh, breakdown product from, of these, uh, RNA an- and, uh, ATP is c- you know, the, the breakdown products, which are a part of this pathway f- that activate the switch. And what we’ve found (laughs) sadly was that these umami flavors actually, uh, also activate the switch. And, and they, even glutamate gets converted to uric acid, uh, partly of it, part of it is. And so what happens is they can activate the switch.
Now, the good news, Steve, is that by far, the biggest thing that’s driving the switch is sugar intake. It’s, we’re eating 75 grams of that a day, salt, we’re eating maybe seven grams of salt a day, eight grams, and that is obviously helping to drive the switch. And umami, we’re eating only like two to f- four grams of glutamate and, uh, a day, we’re not eating … So we’re eating much, much less. So it’s mu- much less important in that sense. But, um, umami becomes a problem.
And, and like certain rich f- meaty foods, pur- pure proteins, uh, espec- uh, you know, like organ meats, liver, uh, they- they’re very high in umami. So, um, uh, plant proteins have much less, uh, of the, of the umami than animal proteins, um, and so plant proteins are superior in some respects. Um, in the animal proteins, um, it also varies. So like processed red meats have a lot more umami than, uh, just regular red meat. And, um, um, but th- but y- it’s true, this, uh, puts a, a l- a slightly negative light on h- super high-protein diets. Because, uh, they’re- high-protein diets can contain a fair amount of umami. So, um, uh, and the umami can activate this switch.
Now, interestingly, the main way the switch is working is by the conversion of glucose to fructose. So if you’re on a low-carb diet, you’re not getting a lot of gl- glucose or fructose. And so even if you want to convert the glucose to fructose, if you’re on extreme low-carb diet, there’s not a lot of glucose around and there’s not a lot of fructose around. And so a low-carb diet, uh, will, is a very good diet in the sense that it helps p- to protect. And of course, you’ve brought up the benefits of ketosis as well, for energy burning, so …

Speaker 2:
So, uh, I’m gonna have to let you go and wrap up. What’d you learn after writing this book that you can share with our readers, anything, what happened?

Speaker 3:
Well, f- soft drinks, ar- a- any kind of liquid sugar is absolutely something to avoid. Um, s- you know, most of the time I would tell you that, you know, y- i- it’s not that you can’t eat, have cake on your birthday or things like that. But when it comes to soft drinks and liquid sugar, it’s really wise to try to avoid it, ’cause it is by far the easiest way to activate this switch, so th-
A second thing is the power of, of salt and water. We, you know, so many, uh, d- diets don’t talk about this enough. And what we’ve learned is that when you’re eating a lotta salt and i- and the, uh, and, and if you’re, you feel, get thirsty from it, that, you could be activating the switch. And so trying to cut back on salt, and drinking more water. And I, I recommend a glass of water with each meal, and a glass of water between meals. Um, don’t have to drink (laughs) gallons of water, I’m not telling you that. In fact, it’s dangerous to drink huge amounts of water. But a glass of water with each meal, glass of water between meals, glass of water at bedtime. Uh, th- you know, this will have a big impact, and a nice additional impact on your health in so many ways.
Uh, and then, you know, uh, you know, high glycemic carbs like bread, rice, potatoes, uh, really try to cut those back. Things like, uh, sweets and stuff, try to save them for special occasions. Uh, I love intermittent fasting, we didn’t talk about that, but time-restricted fasting, um, is a great move for all the benefits that you’ve written about. Um, and, um, and basically, uh, exercise. We haven’t talked about that, but, you know, it’s important to exercise. They’re good f- it’s good to help heal the mitochondria, uh, these energy factories, and over time these energy factories do get damaged. And so it’s really important to try to help, uh, help them recover with, with the techniques that you’ve proposed, uh, and exercise, and all these, all these things. So that’s my main message, Steve.

Speaker 4:
Hey, this is Dr. Drew, and I’d like to invite all of you to subscribe to the Dr. Drew Podcast. Uh, we are very proud of what we’re doing there at that podcast. I am interviewing some of the most interesting, well, people you could ever wanna talk to. Just whatever I find fascinating, whether there’s a smart person or an expert in a field that I’m interested in, or maybe I’m not even interested in, I’m only interested because I’ve heard them speak and become intrigued I think you’ll be intrigued as well. We get deep into topics that are quite important to the current age. Things like cognitive dissonance, cognitive distortions, how does our mind work? We, we talk about everything at the Dr. Drew Podcast that is of real relevance. We get all the way into deep physics and all sorts of stuff.
But trust me, it’s all very accessible, it’s very interesting. Headaches, if you’re even interested in learning about headaches, we get there. We go to the interesting topics of the day. Please join us at the Dr. Drew podcast.

Speaker 2:
Okay, it’s time for our review of the week. This comes from Kathy Taylor on YouTube. She says, “After your podcast on algae, i.e. spirulina and chlorella, I am using Bits, and so easy to take, and pure and clean. Thank you for that podcast. Great for travel and feeling great.” Well, thank you, Kathy. Um, that’s been a very popular podcast, and I’m glad to see that, uh, you’re finding some use, uh, for these. Just as a brief, uh, reminder, one of the things that’s attractive to me about chlorella, uh, is that chlorella is well-known for absorbing heavy metals. And you, uh, we are surrounded with heavy metals in our diet, in our water. And so just a simple thing of adding some chlorella into your diet, and it really doesn’t take much, may be one of the important things you can do.
By the way, if, those of you who’ve read the Longevity Paradox, may have noticed that I included a study about chlorella in terms of weight loss. And just adding chlorella to the diet of obese people actually helped with weight loss. So there’s a lotta things, as today’s program goes on with helping with weight loss, and certainly removing sugar. And remember, sugar is half-fructose. Sugar is sucrose, which is half glucose and half fructose. So just when you say, “Well, I don’t eat much fruit, so that’s not the problem,” any sugar is going to have lots of fructose, and that’s been our big problem, as Dr. Johnson pointed out.
All right, that’s it for today. Thanks for writing in, and who knows? Give us a comment wherever you get our podcast, and I might be reading your comment or question next week, because I’m Dr. Gundry, and I’m always looking out for you.
Thanks for joining me on this episode of the Dr. Gundry Podcast. Before you go, I just wanted to remind you that you can find the show on iTunes, Google Play, Stitcher, or wherever you get your podcasts. And if you wanna watch each episode of the Dr. Gundry Podcast, you could always find me on YouTube at youtube.com/drgundry. Because I’m Dr. Gundry, and I’m always looking out for you.