Plain English with Derek Thompson - A Grand, Unified Theory of Why Americans Are So Unhealthy

Episode Date: June 18, 2025

Americans are unusually overweight and chronically ill compared to similarly rich countries. This episode presents a grand, unified theory for why that's the case. Our food environment has become significantly more calorie-rich and industrialized in the past few decades, sending our obesity rates soaring, our visceral fat levels rising, and our chronic inflammation surging. The result is an astonishing rise in chronic illness in America. That's the bad news. The good news is that GLP-1 drugs, like Ozempic and Zepbound, seem to be astonishingly successful at reversing many of these trends. This episode blends two interviews with Dr. David Kessler and Dr. Eric Topol. Kessler was the commissioner of the Food and Drug Administration under the Bush and Clinton administrations, from 1990 to 1997. He helped lead Operation Warp Speed in its final months. He is the author of the book 'Diet, Drugs, and Dopamine.' Topol is a cardiologist and the founder and director of the Scripps Research Translational Institute. He is the author of the book 'Super Agers.' If you have questions, observations, or ideas for future episodes, email us at [e-mail]. Host: Derek Thompson Guests: Dr. David Kessler and Dr. Eric Topol Producer: Devon Baroldi Learn more about your ad choices. Visit podcastchoices.com/adchoices

Folks, it's Jay Kyle Mann from The Ringer, and as always, basketball is so freaking, freaking good. It's so good, in fact, that the Ringer's NBA draft show is finally back just in time for a ramp up to June. We've got you covered every week as we take an in-depth look at who's got next for the NBA's future. We'll talk to rising and falling stocks of the best and the brightest prospects in the 2025 NBA draft class. From Cooper Flag to Dylan Harper, the VJ Edgecom, and more. Tap in with me on the Ringer NBA Draft Show every Wednesday and make sure that you follow, subscribe, and hit us with those five-star ratings. Today, a grand theory of health and chronic disease in America. In the last few weeks, I've had two conversations with doctors that really struck me, one with David Kessler and another with Eric Topol.

And in this episode, I'm merging those two interviews into one show. Because the two doctors and I, we ended up talking about the same thing. diet, toxic fat, inflammation, chronic disease. And I came away from both conversations with this kind of grand hypothesis kicking around in my head, a way that Western diets lead to Americans being the sickest people in the Western world, in large part because of the way that what we eat turns into fat, which turns into inflammation, which leads to chronic disease. So what you're going to hear today is three people working together to build this grand theory up from the ground level.

But first, some facts. For many decades, the U.S. has had higher rates of obesity and chronic illness than similarly rich countries. It's not just the poor among us. Rich Americans die from heart disease more than similarly rich Europeans. In fact, every income group, every ethnic group and education group, that reaches the age of 50 here in America, arrives at that stage of their life more heavy, more unhealthy, and at higher risk for serious heart disease or metabolic diseases like diabetes.

In fact, according to the NIH, Americans who seem to have won the genetic and socioeconomic and behavioral lotteries, these are Americans who don't smoke, who are insured, college-educated, rich, are still in worse health than similar groups in comparison countries. Well, you might just say, let's just blame Americans. This is always an easy thing for pundits to do. Let's just judge people for eating like crap, for not walking enough, for not keeping up with their health insurance payments or their medicines, for not taking care of their bodies. It's very easy to judge, very satisfying for some.

But I'm not sure this blame game is very useful. While mysteries abound in health, the reason why Americans have such a high rate of obesity is, in fact, not a total mystery. Americans at every age and income simply eat more calories. I gained weight and lost it repeatedly over my lifetime. I mean, I have suits in every size, and I would gain the weight, and then eventually I would decide to lose it. I would lose it.

I thought I was done. I would go on with my life only to gain it back. That's Dr. David Kessler. He was the commissioner of the Food and Drug Administration under the Bush and Clinton administrations between 1990 and 1997. He helped to lead Operation Warp Speed in its final months. By all accounts, this is a man of very high conscientiousness,

ability, intelligence, responsibility. But for Kessler, questions of diet and weight and obesity hit very close to home. You know, why was I gaining it back? this mystery about weight, right, that has not been understood. And I think if you, I mean, why do we just keep on gaining it by? Why can't I control it? When he turns the spotlight inward, Kessler recalls that he used food to quash every emotion. I mean, certainly for me, I mean, if I observe how, when I ate, I mean, I ate to calm myself down. I ate to increase my focus.

I mean, I ate through the day. If I passed that refrigerator, I mean, just the refrigerator itself was a cue. I mean, I was grazing through the day. Now he spent years, decades really, thinking about the relationship between our bodies and our food environment. Why do Western countries, especially the United States, have so much obesity and obesity-related disease? For Kessler, the answer goes back a bit. way back a bit. Thousands of years ago, I mean, the food environment, you know, was characterized by scarcity.

I mean, in order to survive, our brains evolved to be able to focus our attention, to gate our attention on that energy-dense food. That's how we survive. I mean, if you were a bird and you were flying over and you needed to identify, sustenance and energy, your brains were wired. The brains were wired and this evolved through the species. The food environment of the 21st century is unusual. For one thing, calories are more available than ever. The USDA has a long-running data set on total calories produced by the U.S. food system, through production of foods in the U.S. like, say, Iowa corn, and the import of foods, like, say, French cheese.

This isn't a measure of food consumed, to be clear. I'm talking about a different measure, not of what we're eating, but of what producers are making available for us to eat, a measure of our environment. In 1900, calories available per person per day averaged around 3,300. In 1920, still 3,300. 1940, 1960, still around 3,300. Only starting in the 1970s does this flat line board a rocket ship. In the 21st century, today, caloric availability per person now consistently averages over 4,000.

Calorie-hungry brain, meat-calorie-rich environment. It's not that there's something wrong with our brains. if anything, our brains are working too well. Some scientists refer to this phenomenon as disevolution. We were evolved for one world. We live in another. Our biochemistry is outfitted for scarcity, and yet we're overrun with caloric abundance.

What we did was we took this energy-dense food, fat sugar and salt, you know, fat and sugar, fat and salt, this perfect trifecta that affects the brain's reward circuit. we put it on every corner. We made it available 24-7. We made it socially acceptable to eat any time. We're living in a food circus. I mean, what did we expect to happen?

I mean, we live in an environment of abundance. And so our brains are wired to, you know, find that energy-dense food. And, you know, we put all that energy-dense food and made it available and made it socially acceptable to eat any time. So we played right into those circuits. Kessler is most concerned about one category of our diet, ultra-processed food. As we explained in our previous episode in the series, the Nova Food Classification System has four categories.

Category one is minimally processed food, say raw broccoli. Nova 2 is food ingredients, butter, salt, sugar. Nova 3, or processed foods, is most of what you might cook at home, say, marinated chicken, or a homemade cookie. Nova 4 is ultra-processed food. This often includes industrial ingredients, artificial flavorings, food dyes, and other additives. This category is broad, containing everything from unsweetened almond milk to Twinkies. But Kessler is worried that most of the food, that's... most bad for us, mostly lives in this ultra-processed category. In fact, he says, a lot of this

category for stuff, it's barely even food. Food has a certain structure to it, has cellulose, it has fiber. Sure, I mean, it can have sweetness, it can have glucose, it can have fruitness. But if you look at the rate of absorption, right, the structure of food slows down. that absorption, I mean, of that glucose. So the rate of rise into the bloodstream is not constant spike after spike. And when we took these, call them ultra-processed or ultra-formulated foods, took out the structure. I mean, they go down in a wash, right? They are rapidly absorbed in the GI tract. They are, in essence, creating metabolic chaos. When somebody habitually eats more calories and they burn. Those extra calories

get stored as fat. Initially, most stored fat ends up under the skin. This is called subcutaneous fat. But as weight gain continues, more fat accumulates under and around internal organs in the stomach. This is what David Kessler calls

toxic fat. Toxic fat. It's the fat that is metabolically active. I'm not looking to give a clean bill of health to all other kinds of fat. But it's, they're There's certainly this fat in our abdomen that gets into our liver, into our pancreas, into layers of the heart that is, you know, that's causal in those chronic diseases. This visceral fat is not just a passive storage depot. It behaves differently than the fat right under your skin.

Visceral fat cells release a flood of acids into the veins that lead directly to our liver, where they wreck havoc on our metabolism. At the same time, scientists have found that visceral fat secretes different proteins that throw our immune system out of whack. This accumulation of fat in the liver and fat in these vital organs, it's been staring us in the face. I think increasingly cardiologists, nephrologists, neurologists, endocrinologists, some of the oncologists, possibly some of the neurodegenerologists, possibly some of the neurodegenergians, of diseases, but I think the medical community is beginning to wake up. Many ultra-processed foods have a quality that nutritionists sometimes call energy density. A full bite of broccoli has about three calories. That's category one. A full bite of marinated chicken breast might have 30, 35 calories. That's category three. A hostess Ho-ho? One bite,

130 calories. As food companies have gotten better, at packing sugary, fatty, salty, salty calories into single bites of food. Each chew now sends our insulin levels surging. Again, I'm going to use a scientific term here. There's been a doubling in hyperinsulinemia in this country. And that is a result, right, of, you know, these sweeteners coming in, being absorbed relatively rapidly.

scientists have not quite figured out. It happens very fast. You know, does the visceral fat cause the hyperinsulinia, this toxic fat, or does the hyperinsulenemia, you know, cause the visceral fat, which comes first, right? But if you look metabolically, right, you have these, we're hyperinsulinemic, and that is causing enormous amounts, I mean, of chronic disease. It's the environment where certain cancers get stimulated. I mean, it's pounding. the endothelial cells, I mean, of our arteries. In some, Western diets are filled with food that is packed with calories per bite, food that is so rich with sugars, salt, and fat, that we eat it in excess before our bodies can send us the signal that we're full.

Or the signal that we're full is, for some, overwhelmed by a compulsion to keep eating. All this eating and visceral fat is having a further effect on our bodies, inflammation. And this is really the whole ball of wax for why we have chronic disease through chronic inflammation that is unchecked. This is Eric Topal. He's a cardiologist and the founder and director of the Scripps Research Translational Institute. And if overeating and visceral fat are the first two steps in this grand theory, the third stage is inflammation. Well, I mean a way to consider it, you know, for a more familiar way, would be if you really banged up your knee and, I mean, pretty badly banged it up. And it now had fluid in it and it was hot because it's inflamed,

might even be red. Because basically what's happened is there's been a cellular response, driving inflammation, releasing these white cells of different types, are releasing all sorts of of proteins that get your body that knee joint and its surrounding tissue into a hot zone. I mean, if you measure temperature of the tissue, it gets hot. So that's inflammation in a joint, Topol says. It's the sort of inflammation that most people like you and me know and recognize. But now, picture something a little bit different. Picture inflammation happening in an artery.

Your artery didn't bang its knee on a chair. I don't even know what that would mean. But rather, it's reacting to a smaller set of smaller bangs, perturbations, brought on by our own behavior. This leads to chronic inflammation, the sort of inflammation that doesn't go away, like a swollen knee that heals. This is inflammation that lingers. So it's the same process as that kind of simplified knee model of trauma. But this is going on in tissue, whether it be the arteries, not just of the heart, but the arteries in the neck that go to the brain or the aorta or other arteries. That's atherosclerosis. Or it's in the brain. That is the same type of thing where you're having these cells releasing chemicals that are basically proteins that are basically they're trying to react. But in so doing, in their reaction, it's an untoward response because they're destroying, they're damaging tissue.

You don't really want to have your brain cell damaged or destroyed, right? So the inflammation isn't good. It's untoward or adverse. Our diet is full of these tiny little kneebangs, whether it's eating energy-dense food, not exercising, not getting enough sleep, or perhaps being exposed to toxic chemicals. Over time, these little perturbations add up, Topol says. They keep our arteries chronically inflamed. Our tissues chronically inflamed. Our brains chronically inflamed. The modern world hijacks our own immune system to attack our very bodies. You know, there's so many of these perturbations that are promoting inflammation at these different tissues that over time, as we age, you know, gets even more accentuated.

We're much more prone to this process. That's why it's called inflammation. You know, we do better when we're young, not to overdrive inflammation or keep our immune system at its highest level of protection. But as we get older, it's not as competent. It's just losing its kind of delicate, kind of Goldilocks balance

for too much, too little. And that's really what is the fine-tuning, the regulation, if you will, that changes as we get older. Today, inflammation plus aging. Inflamaging is one of the hotter fields in medicine. Researchers are testing whether anti-inflammatory medications, the sort we typically use to treat rheumatoid arthritis or allergies or eczema, can slow cancer and dementia in older patients by fighting what Topal calls untoward inflammation. For him, inflamaging is a major factor behind most age-related diseases. Okay, this is the

underpinning, the common thread to the big three age-related diseases, cancer, arthrosclerotic, cardiovascular heart disease, and neurodegenerative diseases. And basically, it's a the model that explains everything. That might sound a little oversimplified. But not much, Topol says. The more we learn, the more it seems that chronic inflammation in the body is a leading factor for cancer, heart disease, and Alzheimer's. So for cancer, it's critical that our immune system keeps up its guard, its integrity,

to guard against these alien cells that have these foreign proteins of cancer cells, and to react against that and squash it before it ever gets to grow. Now, with respect to the plaque of a cholesterol buildup in an artery wall, what you have there is basically an inflammation that's unhelpful. It's making that plaque grow more. It's making it susceptible to cracks that cause heart attacks and blood clots. So that's untoward inflammation. And then for Alzheimer's, you know, all of us, as we get older, will have some of this misfolded proteins in our brain like amyloid and cow.

But it's really the inflammation to these proteins that is what's causing the trouble where we have loss of our brain cells and loss of brain function, which leads to Alzheimer's and other neurodegenerative conditions. So all three of these, which by the way, Derek, it takes 20 years for these three conditions typically to take hold. So we have chronic inflammation over many years that are leading to gradual compromise of the tissue of the organs that are involved in these three processes. It's a compelling theory. You can see it almost like dominoes clicking into one another. From an environment that's super abundant in calories to a diet that's too rich. in calories, click. From eating too many calories to weight gain, click.

From weight gain to visceral fat, click. From visceral fat to metabolic disorder and inflammation, click. From inflammation to disease, final click. Now, this theory is not like gravity. This is not one plus one equals two. It's not proven beyond all doubt. You should think of it as a kind of grand hypothesis. But you have to admit, it's elegant as hell.

And if true, it's a frustrating reality for patients today. Because as Topol admits, Like I said, we don't have readily available inflammation markers. I wish we did. I hope we will soon. But we're still talking about at least a couple of years from now. In the meantime, there are things we can do right now to track proxies for our inflammation, like glucose.

You know, one way to get at this is a glucose sensor to see if you develop spikes, how big are the spikes? I mean, normally you'd like to see your glucose be steady, you know, 80, 90, less than 100 all the time. But if you have a spike to 250, after eating something, you say, huh, this is really giving me my pancreas a challenge here. Something is a little off track because you shouldn't, as a healthy person, have glucose spikes that are really high or really long,

like, you know, lasting an hour or hours, whatever. So that's one way to do it. And the theory that we're building up to in this episode, this relationship between caloric surplus, which leads to visceral fat, which leads to inflammation, it has to account for something else. The fact that different human bodies process food differently. You and I, Derek, we ate the exact same thing,

the same amount, the exact same time. We might have a very different response. So learning about our unique metabolic responses to what we eat, you know, when we eat, these are things, and even the sequence of what we eat, these are things that we're going to get more a handle on. But whether it will come out with specific individualized recommendations, it isn't clear. There's a big investment at an NIH program that's doing that right now in over 10,000 people. But, you know, we're years away from having an individualized diet recommendation. As I was listening to Topol, explain the

of inflammation, I thought about the times when I felt most swollen or blood hot. Yeah, that one time I ate too much steak. Or maybe when I go to the gym. And it made me think of something else. If exercise is inflammatory, why is it so good for us? When you exercise, it's like a test run to induce inflammation. And your body then gets groomed, if you will, trained to have your immune system and your inflammation response in the highest integrity. So when you don't exercise, you don't get the advantage of all this training. This kind of, this exercise can induce, you know, a low-level inflammation, but then ultimately, if you're doing this on a repetitive basis, it gets your immune system function and your inflammation into its highest functionality.

So it's really the exercise that does good rather than the sedentary that does bad. Exercise is critical. One scientist I spoke to last year called it the greatest medical intervention known to mankind. When it comes to weight and fat, exercise is particularly important. because energy balance is about calories in, calories out. And in rich countries, with our delirious food abundance, it's critical for people who can't control their calorie intake to increase their caloric burn rate,

to get into what Kessler calls an energy deficit state. The only way to be in an energy deficit state, you know, was this phrase, eat less, exercise more. But the problem was it failed for decades because no one could do it. but why could no one eat less and exercise more? Right? It was an absolute failure.

For decades, Kessler said, most people dealing with obesity and weight gain felt powerless to overcome their metabolism, their stomachs, their minds. They ate when they didn't want to. They gained weight that they wanted to lose. It would be nice, I think, in this part of the podcast, for me to just say,

everyone, just eat Mediterranean diets. Just eat more fish. Just eat more olive oil. Just eat less dessert. Oh, and by the way, just go to the gym, five days a week, 30 minutes, get some aerobic, get some weightlifting in. The obvious stuff here really is obvious to talk about. What's not obvious is how to actually incorporate it into modern lives. But now, a new tool has offered hope to millions of people called glugogogon-like peptide-1 receptor agonists. You probably know them. as GLP1 drugs, like OZempec, Wigovi, Zepbound, Mungara. They work primarily, they have multiple mechanisms, but primarily to something that's called delay gastric emptying. So food stays in your stomach longer. It just doesn't move through as much.

Think about normal times when our stomach sort of shuts down, when we're sick. You have the flu. right you you you you are ill you know your GI track stops you know working fully right food stays in your stomach what's the last thing you want to do put anything else in your GI track right food poisoning have you ever had food poisoning you eat something right and you remember years later i mean that memory still stays with you it's that serious but in food poisoning food just continues to accumulate your GI track shuts down the food

just piles into your stomach, it doesn't leave, you know, the pylaurus, it doesn't leave that sphincter into the rest of your intestines, and you feel like, you know, vomiting or throwing up, you just just have this sense of nausea. This is one of the findings in the early literature that I personally find most interesting. Being on GL-1s doesn't just get people to change how much they eat. They change what they eat. Ultra-processed food in declines. Fruit and vegetable consumption goes up. How the hell is a drug doing that? Kessler has his own theory. I mean, when I went on these GLP-1 drugs, I didn't want to put anything else in my stomach. I started eating smaller portions, and I didn't want, you know, fat and sugar in my stomach.

It was just going to sit there longer. So I started, you know, first of the time I started eating vegetables. I just didn't want to put more of this ultra-formulated foods in my stomach. GLP-1s haven't just been found to increase satiety. There are GLP-1 receptors in the brain as well. We know they get to the hindbrain, right? They get to the gut.

They'll have this delayed gastric temperature. They get to the hindbrain, they get to the area post-dreamer. They get to the NTS, the nucleus, solitarias. So, altogether, these drugs seem to slow gastric emptying, increased feelings of fullness, tweak our dopamine cycles, and dull our addictive circuits. Some studies have found that people on GLP-1 drugs curb other compulsions, like gambling

and smoking. What we have learned, and I would submit to you, Derek, that we're only at the beginning of the gut hormone story. We're talking about the gut hormones talking to the brain and to the immune system. Eric Topol is thrilled about the future of GLP-1s for their potential to reduce not only weight but also chronic inflammation. The drugs in the market have already shown their ability to be anti-inflammatory.

And what's to come might be even better. And we have two that are out there injectables. We're going to have pills. And they're terseparatide as a double receptor. Soon we're going to have a triple receptor. or zirotides, and then we're going to have all these other gut hormones, another 10 more of them. In combinations with the ones we have today or even more potent ones, some that get in the brain, much better directly. Don't rely on the gut-to-brain signals. So what I'm getting at here is

this has turned out to be one of the most extraordinary anti-inflammatory mediators that we have ever seen. They make statins look weak. Do you think there's a future in which a certain kind of GLP1 drug, maybe it's a double agonist, maybe it's a triple agonist, maybe it's some other approach will be generally recommended for far more people who don't have anything like type 2 diabetes or obesity? Because at some point, if I put together everything that you're saying in this episode, which is, number one, that inflammation is a major driver of the most common diseases that kill older Americans. And number two, that we sort of haphazardly accidentally, you know, looked at the GILMA monster's mouth, yada, yada, yada, have GLP1 drugs,

accidentally made this drug that is extraordinary at reducing the thing that's driving age-related diseases. Why wouldn't, at some point, the FDA or doctors, recommend, you know, that tens of millions more patients take, say, a diet Coke version of these drugs that don't have an enormous amount of weight loss potential. You know, if someone's already of normal weight, you don't want them losing another 20 pounds, but has some of this anti-inflammatory effect. Yeah, I think eventually we're going to get there that most people will be taking some type of gut hormone memetic, which is what these are, because the way to the body's inflammation and

immune system is so, as we've learned in recent years, is through the gut. I mean, no, we didn't think that. I never would have guessed it. We knew the gut microbiome was important. We just didn't know how important these gut hormones are. Now, one of the questions I have, though, Derek, is another alternative would be to manipulate the gut microbiome with pre-biose. and probiotics and probiotics. So whether we do it in the years ahead, I mean, talk about years ahead, through the bacteria in our gut lining, or it's their metabolites, or whether we do it with some variety of gut hormones that we are in the, I want to say we're early in the gut hormone era, right?

Whether it's one of the two, but this will become a standard part of medicine in the years ahead. This is why I'm so keen that we are having a newfound capability of preventing these big three diseases because we're seeing some things we had never envisioned. I mean, when I went to medical school, there was only one gut hormone we knew about. It's called insulin. Now we have 20, you know, and now we're seeing these kind of magical effects in the clinic and still many, many more of these to come in pill form, which will be much less expensive, easy to make. And then, of course, all sorts of permutations and combinations and doses. This is just early stuff that people don't realize how big this gut hormone and gut microbiome story is to unfold.

We started this miniseries with a simple question. Why are Americans so unhealthy? The unified theory presented here is simple. We live in an environment of extraordinary caloric abundance, including ultra-formulated foods, which overwhelm our natural hunt for calories and our feelings of fullness. This leaves most Americans in a state of constant caloric surplus. We consistently take in more calories than we're burning out,

and the basic physics of this imbalance predicts nothing short of inevitable weight gain. But we're not just gaining weight in our subcutaneous fat just under the skin. Deposites of visceral fat in our abdomen leak toxins, proteins that cause body-wide inflammation. And this chronic inflammation, this simmering fire inside our bodies,

is slowly wrecking havoc on our heart, our minds, ourselves. And unless we find some way to, on our own, reverse that cycle, one of the best tools that we have right now is this new category of GLP-1 drugs, which essentially work on two levels. First, they delay gastric emptying and make us feel full. And second, they seem to tweak

our dopamine reward systems in a way that gives people more control over their compulsive behavior. Because these changes are so dramatic, they can make people feel nauseous or just sick enough to avoid rich foods and graze on planar foods, which has the remarkable effect of shifting patients' entire diets toward healthier fare. I want to leave you with one final image. The human body is a car, finally tuned over thousands of years to have a million different parts. And two of those parts are a gas pedal and a brake. The modern food environment is a brick dropped on the gas pedal. Caloric availability makes it easy to overeat. Ultra-processed foods accelerate glucose absorption. The whole food environment in this metaphor is heavy pressure

on the accelerator. GLP-1's work because they slow everything down. They hit the brakes. Rather than accelerate glucose absorption, they slow gastric emptying. Rather than increase hunger, they increase feelings of fullness. Rather than flood us with food noise, that feeling at the back of your head that says, eat, eat, eat, they turn down the volume of the food noise and return us to our regularly scheduled thoughts. Perhaps that's why research shows that these drugs improve not only weight gain, but also health across a range of outcomes. They returned the car to its proper owner.

They remind the body that the brake pedal exists in the first place. Dr. Kessler, thank you very much. Thank you. Eric Topal. Thank you very much. Thank you, Derek. Enjoy it. And thank you all.