GLP-1s and the ‘Wild West’ of Wellness

and so much reason to hope all at the same time, let me say a hear you.

I'm Ezra Klein from New York Times opinion, host of the Ezra Klein Show.

“And for me, the best way to beat back that be willedered feeling is to talk it out with”

the people who have ideas and frameworks for making sense of it. Here's going to be plenty to talk about. You can find the Ezra Klein Show wherever you get your podcasts. [MUSIC PLAYING] Here's a number that actually shocked me when I learned it.

This from a new Kaiser family foundation poll. One out of eight Americans is no taking a GLP-1. One out of eight. Maybe I shouldn't have been so shocked because the number is higher in my social circles. I have tried these for reasons I'll explain.

But they're a strange medication, right? They don't make you lose weight, they make you not want to eat food. But then they do all these other things. They seem to protect people's heart health independent of losing weight. They're protective of kidneys, of livers.

There is ongoing research about dementia and Alzheimer's. They've all these strange effects on addiction and desire. But should everyone be on these?

“And like, what does it mean for society to have access to drugs that regulate desire in this way?”

What does it mean for the sick? What does it mean for the well? I want you to episode on this for a while, but I haven't known quite how to approach it. And then Julie Blues, who's a contributing writer at New York Times opinion, and co-authored the book Food Intelligence,

and also was a health and science reporter with me back at Box. She started doing a lot of reporting on GLP-1s, and she's written a lot of great pieces on them, including doing some really interesting survey work. One of the survey questions that really stuck with me was of people on them, more than 60% would continue with them,

even if they didn't help them lose weight. So why is that? Well, I want to ask Julie, she's someone who I really, really trust to look at the science of these questions in the most rigorous way possible, and also to look at the experiences patients are having on them

in the most compassionate and curious way possible.

As always, my email, as a client show at nytimes.com.

Julie Blues, welcome to the show. Thank you so much, it's a pleasure to be here. So I was shocked by this number. According to the Kaiser Family Foundation's poll, one in eight Americans are currently taking a GLP-1.

Why? Yes, it was surprising to me too. So one of the ways we can understand this is there's this very long history of people seeking out, basically the magical elixir for weight loss, right? So I think that's one piece of it, and now we finally have something

that rivals the only other effective medical intervention we've had to help people lose weight, which is bariatric surgery. On the other hand, there's a lot of people who are living with diabetes, and I think that's another reason that we see so many people who are on these drugs. In addition, I think these drugs have really met a particular moment,

which is this algorithmic social media age. They're everywhere in the U.S. We already had this relatively unrestricted approach to marketing pharmaceuticals. We see them advertised everywhere. We've seen this telemedicine industry flourish since COVID,

but also around these drugs.

“And I think that's why we're seeing these shocking numbers.”

So I want to start on the part of this that people actually don't talk about that much, which is diabetes, which is what these drugs are originally approved for. As you say, a huge number of Americans have diabetes and have terrible health consequences often from it, including limb amputation and blindness. What do these drugs do for diabetes?

Yes, so our bodies produce GLP1 naturally. So we have this hormone that's produced in our gut. It our brains into a lesser extent in the pancreas. Basically, though, this synthetic version of a hormone we produce naturally.

And the big breakthrough for diabetes was that they're stimulating the pancreas to release insulin,

only in the context of high blood sugar. So it's not like when you take insulin and you need to be careful about what you're eating and you're at risk of really low blood sugar levels and the dangers that come with that.

So as researchers who are working on this are trying higher and higher doses

to help people with diabetes get more and more benefit, they start to discover these weight loss results in the trial. So people start to spontaneously lose weight. Then later we're finding all these slew of other benefits. Did no one would have predicted, no pharma company would have been on this.

We're only at the beginning of what's been called this ozampic era.

“I think we're really just at the beginning of discovering the benefits and the harms of these drugs.”

Okay, so you have the recognition which is just something people begin observing that diabetics on these drugs begin to lose weight and they don't feel hungry. And as researchers begin testing the first generation of this ozampic, but we now in that context call the govi. How big is the effect size?

What do we actually know about what govi does for weight loss? There's another one which is slightly more advanced. It has more mechanisms of action to zepatide, which is also goes by zepound. How much weight do people lose on these? So it depends on the drug, but we're talking like 15 to 30%.

So it's the first time we have a drug that really rivals the more effective types of bariatric surgery.

Key point is that it's turning down appetite.

So it's not ramping up metabolism or energy burn. And the idea was that this is a gut hormone. That's the thing that a lot of people focused on. It's released after eating. And it helps people signal satiety.

It helps them feel full and know that they've eaten. And we're just giving a really souped up version of this gut hormone.

“And it turns out that actually you need to stimulate the brain glp1 system”

to get the weight loss effects. So you only interfere with appetite once you reach this brain glp1 system. And you've written a whole book about the metabolism. And one of the arguments of that book, one of the arguments of books in this space that I think people don't appreciate is that hunger is a function of the brain.

And it's a function of the brain's reaction and predictions about the world around it.

We always have this idea that people just feel hungry.

And then you know, you should use a brain to decide if you want to eat. But your brain is deciding if you're hungry and you're sort of fighting. It's an instinct. So I'd like to spend a minute on this idea that hunger is a function of the stomach versus hunger is a function of the brain and sort of how research is moved from one to the other.

Yeah, the way we describe it in the book, we use this analogy of breathing. So if I tell you, like, take control of your breath right now. Like breathe more slowly or breathe more quickly or hold your breath. You can take control for short periods of time. But eventually physiology takes over.

And the same thing is true of what we eat. So we have this illusion of control over individual meals and snacks. But there's this symphony of internal signals that's going on inside of us all the time. And the brain is sort of leading this symphony.

“And the decisions we make are much less a product of conscious control that I think many people appreciate.”

So when you're taking a GLP one, you're getting a much higher, longer lasting version of what your body produces. And it has to reach the brain through the gut brain barrier. So it has to reach through the gut brain barrier. And the theory is that it's reaching into the part of the brain that usually signals that there's a toxin in circulation. And so that shuts down your appetite and increases your nausea.

Like what you would get during food poisoning or something. Exactly or what you would have on the, the, these are the most common side effects of these drugs, right? So it reaches into that. So it reaches into that drug. We've invented it as we've made your brain slightly think it's being poisoned all the time. I think that's one way to put it up to really answer this.

Modernity, baby. No, and then the context of our completely toxic food environment, right? It's just turning down your appetite by reaching into this GLP one brain system. So it reaches through the gut brain barrier, but it acts as a neurotransmitter in the brain. And from there, it reaches other parts of the brain.

This is a very active area of research. But that's the sort of bottom line and this dialing down of appetite is the key feature of these drugs. One of the things that I find interesting about the GLP ones is we basically created this food environment that does not exist in nature of hyper sugary, hyper fatty, hyper salty, hyper calorie dense foods. Our brains are evolved over very, very long periods of time to treat those as getting three cherries on the salt machine and to really, really want them.

So we've put people into this hyper stimulating environment. But we didn't change everybody's brain to turn down the level of hunger when you come into something that is very calorie dense of very sugar dense.

where the Mars company is spending God knows how much an R&D to make my kids want M&M's.

And it doesn't work for people and then we blame them and tell them they're not done a good job exercising their willpower and self control. You also someone who struggled with weight. Yeah, I was very, very heavy until I was almost in it all, like I lost like 60ish pounds, 50ish pounds when I was 16. And then ever since like I fight my food desires, like if we had a bowl of Oreos on this table, 30, 50% of my mental energy the whole time we were talking but did not eat the Oreos. Yeah, absolutely, I remember we had lunch in Washington when I was doing lots of obesity reporting and you said why am I a person who if the chocolate cake is there like 50% of my brain is focus on the chocolate cake.

And I didn't have a good answer for you then.

Do you have one now?

“I do, yeah, I think it's said, you know, so when we think about something like common obesity, so there's many different types of obesity.”

But what most people have is called common obesity and it arises from these tiny like over a thousand genetic variants that all act almost all act in the brain. And so you have a neurobiology probably that's different from someone who doesn't have to fight the chocolate cake.

And I actually did genetic testing for the book and I'm also someone who struggles with my weight.

Turns out I have a higher genetic risk than like 90% of the population. But this risk in a particular environment won't be expressed. But as you said, when you put people like us in environments where there's lots of M&Ms and lots of chocolate cake, it becomes much harder.

“And I think most people don't have this privilege, let's say, of being able to finally curate their environment to control their weight and maybe the way we might have had.”

I have a family member who I'm not related to by blood and one thing that always amazes me is she will order dessert and she loves dessert and she loves chocolate cake and she like eat half the cake and then take the rest home. And I always look at that and I think whatever is happening in you is not happening or me or possibly vice versa, whatever is happening in me is not happening in you. And then I feel in other ways elsewhere in my life. I can have a cigarette or a puff on a vape. I've no interest in another. It does not excite any desire in me.

I can have a whiskey and leave half of it or glass of wine. I don't particularly want to keep going and I've had people in my life who struggle with alcoholism. And I don't have will power they don't. Something is happening in their bodies or in their minds that is not happening in mind. And I've always thought the way we blame people for this is so cruel. Because it is so often people who don't have the propulsive desire blaming people who do for not exercising will power, but those people aren't exercising will power. I'm not exercising will power to not have more cigarettes. I don't want them.

I know absolutely I have this conversation all the time with my husband. For some people the cards are just stacked against them. One person that really helped my thinking on this was Robert Sapolsky who you've probably talked about. He talks about how we have these potentials or vulnerabilities that are created by our genetics. And then in different environments they're either expressed or activated or not expressed right. Like it's extremely hard to do the right thing to buy the foods that you know you should be eating or taxisize every day when you're working the night shift and you're raising kids and you're the single mom or dad or whatever it is.

“Like how you're going to do all the things that you know you need to be doing to protect your health and to fight against this neurobiology that you might have.”

This is the interplay of biology neurobiologies you're saying it. This thing we call will power which is a very poorly specified concept and then environment. To me this question of environment is really important. I'll use myself as the example you know when I lost a lot of weight. I mean when I was younger a lot younger. I was a high school student with nothing to do and I was able to really really hold that when I was a young adult. And I have not been able to die successfully since I kids because I can't control the food environment.

I have money. I can you know go to the gym. I have a certain amount of autonomy over my schedule. So as you say when you add in things like the night shift. When you add in not having the money to get healthy foods or go to the gym. When you add in having more kids or less time. How it works very very differently when you're able to have the autonomy or the money to create a certain kind of environment around you that is conducive to living the certain way right you're a

Reserve discipline that gets depleted like if I don't sleep enough I eat more.

Right absolutely and you're designed to eat more when you don't sleep enough and you're absolutely right that this symphony of internal signals that I was referring to earlier it's interplaying with our environment. So one thing I really appreciated about your work on the GOP ones is a reporter and somebody who's very deep in the science is you've done a tremendous amount of interviewing people on them. And you've interviewed many of the kinds of people and again to me this has always been the cruelty of this conversation who were exercising a tremendous amount of constant will power going on and off like very restrictive diets you know losing 30 pounds gaining it back.

What is it like for them for the people for seeing huge amounts of of weight loss how do they describe the experience of being on a GOP one versus what it's like off of one.

“I think the big common thread for people in whom the drugs are effective for weight loss is this idea that suddenly this will power that they're always searching for that they feel they didn't have enough of suddenly they have it.”

Suddenly it's not that hard to say no to the extra piece of cake or the cake altogether they're eating smaller portions. They're cravings change like that there's a lot of discussion about food noise so that's this when the cake is there 30 to 50% of your brain is on the cake or you have cravings that distract you.

A lot of people say that this just disappears you set a second ago for whom the drugs are effective.

For whom are they effective and for whom aren't they effective and why. Well this is another area we don't fully understand but it seems like there are some people who are quite sensitive to the drugs and others who are sensitive to the drugs and there might be a genetic component to this too. That's sort of a frontier area of science and so I think the quest that a lot of the companies are on is to understand like how how do we differentiate the people who might need higher doses initially are much lower doses because they're having so much sensitivity to the drugs and side effects.

And what not they're having such a strong response are losing weight too fast so they're absolutely is this variation in how people are responding. Tell me about the side effects of these GLP one drugs in studies people often don't stay on the mat long people do cycle off of them sometimes for cost but sometimes for other reasons like what is unpleasant on them what can go wrong. So the most common that we know of right now are the gastrointestinal side effects so the nausea the vomiting the diarrhea those are the most common but it seems like there's other emerging potential problems so there are lawsuits around severe stomach problems damage to the ocular nerve.

So I damage and those that I don't think we have clear answers on how common that is but but the basis of those lawsuits is that people weren't properly warned that this could happen.

“One thing that a lot of people don't seem to be warned about is the fact that you have to stay on them to keep reaping the weight loss benefits.”

There's an idea that a lot of people have a lose the weight. I'll learn how to eat properly and then I'll go off the drugs. I'm always surprised that even people who got the drugs from their doctors don't seem to have. What happens when people go off the drugs? You tend to regain the weight. And it's still hungry again. I've heard this and it's definitely true in the data but I guess like people in my life have chronic conditions and the drugs are on like they just have to stay on them. You know you stop taking statins and the effect goes away.

I feel like that's like people who are used to drugs to treat acute conditions not being used to drugs to treat chronic conditions.

“But I think that this is the thing like that goes back to the beginning of the conversation that a lot of people still have this idea that they should just be able to”

weigh out of it, right? I think these drugs helped reveal how much we are products of our physiology and that with this you know you take this drug and suddenly again you have the will power you didn't have for your whole life. But there's still this expectation. It's like any other diet and that feels like a place where people haven't been warned. But as we've been saying there are now so many people on the drugs and I think these more rare side effects we're going to start to learn more about. I want to talk about a possible social side effect which is our culture's expectations for people's bodies should look like have been

Punishing for a long time, particularly punishing for women and girls. I think we've interestingly been entering an era where they're increasingly punishing on boys and men and there's this whole thing of like male looks Maxing and the guys in the Marvel movies are completely jack now and on all kinds of things you probably shouldn't be taking.

But I think a lot of the cultural effect of them has come from celebrities and influencers who all of a sudden show up in our much thinner at times skeletal now in ways that

When you have the body's natural hunger signals coming back at you is harder to do you know there was like this big body positivity movement and I was always going to be a very uphill climb in this country.

“But how do you think about GOP ones as possibly a pharmaceutical accelerator of you know fairly dangerous body expectations because now it's like well if you want to look thinner why not just go on a GOP one.”

That's absolutely a strand in this conversation and in this moment that we're living in the place that it freaks me help the most is I talked to pediatricians who are prescribing the drugs in children. There's no screening yet for these drugs and eating disorders and young people and they've they anecdotally have seen people use these as aids for essentially eating disorders and kind of exacerbating eating disorder behavior.

One of the underlying assumptions of the health that every size or far activism or body positivity movements was that you can control your body size therefore you must accept it.

We had surgery before it wasn't as accessible as scalable but now we do have this medication where people do have the option right. At least ones were sensitive to it and the ones who can afford it and access it and all of that. We've seen influential people in these the body positivity fat activism movement come forward and really grapple with starting on these drugs and losing weight on them and one thing that those movements did that was really important. It was highlight how much shame and stigma people who are living with obesity face every day especially women.

So like there was this great economist article a few years ago where they parse the data on the pay penalty and they did such a great job of highlighting the discrimination and stigma that people the obesity face.

“But I think there was really a dangerous glossing over of the health effects of carrying extra weight.”

That even if there is this variation and individuals at the population level it's very clear that the higher you go up to BMI later the more health risk you're carrying. I've spoken to people who are part of these movements they had issues with movement. They had problems with their blood sugar they were concerned about fertility and they were so grateful to be able to now have a medication that could help with those issues. They became very polarized it was either your fat accepting or fat phobic and I think we're kind of moving to something maybe in between.

But you but I take your point on that but put that side of the debate over here that was always a like an effort that was running up against the mainstream of American culture which believes very strongly in thinness as a synonym for virtue. And you know one thing that people I know were worried about and frankly that I'm worried about I mean I feel like I would not have had this concern for like young boys which is what I have a while ago and now I look at the rise of male looks maxors and it looks a lot like toxic diet culture that girls were exposed to before.

You know and obviously clavicular who is the avatar of that has talked a lot about being on you know glp ones for some form of these drugs. I wonder what it's going to do when it is just that much easier for people at the top of society to exert. Hair to for unknown levels of control over their bodies and when they're doing it with these like wild stacks of glp ones and peptides and you know a. You know you know you know you know you know you know you know you know you know you know you know a.

“I think it's something like one percent of children who are eligible are taking these drugs now.”

But I think that number is expected to rise stratosphereically pretty quickly especially with the expanded access and going to pill form.

So much there's a lot we don't know an adults there's so much we don't know about what it means to suppress appetite during these critical phases of growth and development.

At the same time diet cause diseases like obesity and diabetes they hit young people particularly hard.

So now we have this treatment or thing that can actually help young people in a way we couldn't accept with bariatric surgery before.

What is it going to mean for them when we're yes blunting appetite I'm not only with the pressures on body image at that age but also on yeah your muscles bones.

“Puberty all these things right we're about to put all these young people on these drugs right like I think about my kids and the pressures that they're going to face.”

I think about I don't know if you've done this thought experiment but imagine being like Chubby 16 year old Ezra now would you have gone on one of these drugs at 16 you know I also I think my way fluctuated a lot but I think around 17 or 18 I would have had obesity.

And what I have pushed like my parents to say you know I really wanted GLP one and where would I be now what I've had a happier childhood and like our teens and early 20s.

If I had one of these drugs what I have learned to eat in the way that I've learned to eat by changing my food environment. I don't know like I've but the pressures I think young people are going to face now growing up in the culture that we have it's scary it's punishing I'm terrified for my kids when I hope that there's some sort of correction but I don't know if the correction is coming or how you know.

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So the conversation we've been having here sort of tracks what I would call like the first cycle of ozempic coverage excitement.

And then a new thing begins happening and it's sort of when I began paying closer attention. There was a study that came out that particularly caught Maya as a former healthcare reporter which was that we were seeing huge drops in mortality from any form of cardiac event. But the drops didn't seem to be connected or didn't need to be connected to losing weight.

“So can you explain what we saw then and then how that begins to shift the story here?”

Yeah, so we have this drug that comes on the market for diabetes in the diabetes trials as we start ramping up the doses people start to lose weight. And then for any diabetes drug now that comes on to the market, there's a requirement that companies must look into what these drugs do to cardiovascular events to look for harms does this increase the risk of a cardiovascular event. And I know the past weight loss drugs like fenfen which were not diabetes drugs like did increase the risk of cardiovascular events right we've had wonder weight loss drugs before and they gave people heart issues.

Exactly, so they're looking for harms and instead they find this 20% risk reduction. And put that in context for me, how big is that? It's big. Stattens are drugs that are targeting these conditions and the risk reduction is something like 29%. What's really significant about it is it seems that more and more of the benefits the researchers are discovering from these drugs seem to be weight independent. In other words, whatever one expected is you make people lose weight inflammation in the body goes down your metabolism of fat and sugar and improve so maybe you see improvements in fatty liver disease or diabetes or whatever it is.

I think the kidney, there's a slew of benefits that seem to be weight independent.

Possible benefits on dementia. I mean, my understanding this is that observationally people on these seem to have much lower risk of dementia. They did a study seeing if it A randomized control trial seeing if it improves people who have Alzheimer's and it didn't, but we're not sure about whether or not it can prevent Alzheimer's and some people seem to believe Alzheimer's or dementia are metabolically activated. And so now there's this whole question of is it cognitively protective. So the Alzheimer's trials, so these were really much anticipated randomized control trials to see what would happen with these drugs and Alzheimer's and they had negative results.

And so it was a big disappointment to the community and to the companies.

But there is this question of in a different population or with the different dogs or a different drug will we see the benefits and that's an active question.

“Yeah, if you're intervening earlier, it's an active question and area of study. So I don't think that case is closed and sleep apnea is a big one sleep apnea is weight dependent. So you need to lose the weight to see the benefit.”

But that's another indication that these drugs are approved for now. So these weight independent results. They break our theory of the mechanism of health improvement here a little bit. So as doctors and scientists try to grapple with this, how does there sense of what the drug is doing and why it is helping the body change.

So there's a researcher in Toronto, Dan Drucker who helped discover this whole class of drugs and he described to me like let's let basically there's these three buckets.

So one is the weight loss bucket that's clear. It's going to help you lose weight and you'll get the benefits from the weight loss. The second bucket is reducing inflammation. So inflammation is when you're exposed to a pathogen and infection and injury. Your body mounts this immune response and it can signal healing. But when it goes into kind of overdrive at low levels, you have this chronic inflammation and that's a hallmark of many of these diseases we've been talking about obesity diabetes cardiovascular disease.

These drugs seem to lower work on inflammation. They seem to lower inflammation. And this to me is the most exciting area because we've had drugs in the past that kind of shut down inflammation like steroids. Let's say, but you put people at risk because you're essentially shutting down the immune system. You're putting people at higher risk for cancer or other infections. But the way this is described to me is that GLP1 seems to act as these fine tuners of inflammation. So they have this more subtle approach.

And it's not something we've really had in medicine before. So we're using these drugs. So GLP1 and there's other drugs that are coming on the market with like the dual and triple agonists that use more than GLP1.

“And the question is like, are we going to discover these other hormones that we can subtly manipulate the immune system and inflammation with?”

And so we might just be at the beginning of this. And I think the other exciting facet of it is we might really get amazing insights into the immune system through these drugs that we haven't had before because we haven't been able to do these more subtle manipulations. But the third way these drugs seem to help people is by directly targeting the organs that are involved in particular diseases. So sending signals to the liver to heal scarring involved in fatty liver disease or to clear the fat from the liver or whatever it is to promote healing in the liver or the kidneys. So that's a third way these drugs seem to be helping people.

Do any of that? Your guess is as good as there's models in mice of what's going on, but how this is working inside of us we don't know. My family has a lot of cardiovascular disease in it that has hit members of my family young. And as everybody sort of around me being being going on GOP once, I began reading these things about cardiac events. I was like, am I an idiot for not being on one? Are we all going to be on one of these in a few years? And so I've tried them. I want to talk about that experience in a minute, but I want to ask that underlying question of you. Given these three buckets you just described and how many things they seem to be helping to treat.

“Increasingly seem to me, like, shouldn't everybody be on low dose? Was that bigger to a appetite?”

If you're seeing reduction in possible reductions in dementia that we don't really know, but reductions in weight, reductions in cardiovascular events, reductions in liver and kidney disease. We're losing sleep after the improved blood sugar. We'll talk about the addiction and compulsivity findings later. But it began to seem like a thing we should be putting in the water.

We did this poll with the times for a piece on of GOP one users and ask them, like, what's your experience been like?

“And I went into that poll thinking we would get these kind of negative results. I had a feeling that a lot of the headlines in the media had been quite triumphalist about these wonder drugs.”

But we weren't reporting with the lived experiences of people on these drugs was really like with the side effects and cycling in and of insurance. And what we got back was people kind of generally feeling great. And having benefits that they didn't expect and that they wanted to stay on the drug for reasons other than which the drugs were prescribed.

This was amazing to me that 63% of people in your survey said, even if the drug didn't work for weight loss, I'd want to stay on it.

No, this was shocked me. I did not expect this. One of the most amazing stories to me is the woman who had post-concussion syndrome for almost a decade whose life was. Essentially, I don't want to say shut down, but it was she was suffering deeply with symptoms and she started to find mice and cell research suggesting these drugs could benefit post-concussion syndrome. So she talked to her doctor, she got the prescription and she tries it and within days she starts to experience benefit and now she's back to her normal life.

But the big key is we haven't done a randomized control trial on this. We don't have the high quality evidence to say, is this going to be everyone with post-concussion syndrome 80% of people are like 2%.

In addition, we don't understand how these drugs interact, for example, if you were on for a bit, but some other type of like a cancer therapy or something like this.

We don't know how does this fine tuning of the immune system I talked about work when you're taking an immunotherapy, for example, there are so many unknowns and researchers are always going to be cautious. But I ask almost all the researchers I talked to this question and they all say we're not at that stage where we should just all be honest. I understand why the researchers have to say, well, look, we don't know.

“But we don't know actually isn't an answer to that question. You have to make a decision, like as a person, with one life and a life where you have a chance of getting heart disease, a chance of developing dementia,”

a chance of developing kidney disease, a chance of developing all these different things. And you have to look at these studies or the coverage of these studies, more to the point and say, or say with your doctor, do I think I should be on this thing that seems to modulate inflammation, which appears to be a source cause of all kinds of major chronic and acute illnesses, people develop or not. And one reason I think you're seeing like really, really aggressive experimentation, particularly around this class of drugs, is because something that has all these effects for the well or for chronic conditions,

saying, well, I don't know in 12 years, maybe we'll know more, you actually kind of have to make a yes or no decision as a person, because if you miss out on protecting your body from the chronic effects of ongoing inflammation for five years, we'll miss out on five years of protection and you have accumulated five years of damage. But I know different doctors feel differently about this, and I feel like we're in this place, it's actually like really tender and tricky.

“Absolutely, but I think the question I was answering earlier was this, should it be in the drinking water?”

Sure, yeah, I didn't mean to make a manager. No, no, no, no, no, but yeah, no, but this question of, should you, as a individual with your particular family history and your underlying disease risk profile, or whatever you've struggled with, already, should you be on the drug? That's a conversation, people, and you should certainly have with your doctor and get the prescription and have someone monitor you. What scares me about this GLP1 areas, how many people are circumventing the medical system, they're getting these very low barrier prescriptions through telemedicine,

medicine, they're going to like illicit research chemicals through people like influencers on TikTok, there's so much enthusiasm and I've seen this happen with other drugs. It's like seems to do everything and then we dial it back, we're not quite there yet that we can just say put it in the drinking water. So, I went on the lowest dose of two zepatide, like two and a half milligrams, and I did not have the experience that people in your survey had. So, on the one hand, it's like the most interesting drug or one of them that I've ever tried, you know, legal or non legal, because I seem to be sensitive to it and all of a sudden I didn't want to eat, which is never an experience I've had before.

Like living in somebody else's brain, the way I've described it to people, I used to sign machine analogy earlier, it's like being a gambler who loves slots and going up to sign machine and pulling the thing and getting with three cherries and then nothing lights up.

And it would be good or it smelled something and I hadn't noticed that the thing would then trigger another feeling which was desire because like the feelings were so connected for me. But all of a sudden I would have that same experience and then the desire wouldn't trigger.

And I would walk by the candy bowl and not stop, or I would leave half the burrito on my plate. It was in a way, revelatory. The problem is it may be quite the pressed interesting.

And and he'd on it and whether that was because I was needing enough or what what was going on, but the thing where people report more energy and and more focus and feeling cheerier. For me, it really dold experience. I think it's a very, very, very handy to present experience.

“Well, and that's why I think it's interesting to bring in my own experience because there is this whole thing where it's working on some kind of reward mechanism too on a maybe dopamine.”

But people are reporting not just a desire to eat less, but desire to do all kinds of things less.

Drink alcohol, take drugs, online shop, and then this and he don't anything is also being reported by people. You've seen about the whole reward system dynamic of it. Yes, so this is your reporting. Yes, so this has been a very exciting area and one that we've paid a lot of attention to. I think in particular in the media because the anecdotes are so startling and I think they're real. I've talked to people who have reported like reversals of alcoholism, the desire to smoke sex addiction, like any kind of addictive behavior you can imagine seem to be dialed down with these drugs.

The trials to date have been mixed and the researchers who study reward are quite cynical that these results are going to endure.

And the way it's been described to me is so for a long time we know that if you make rodents hungry, they're more likely to have addictive behaviors like they're more likely to get hooked on cocaine or push the lever. So hunger has this overlapping pathway with these other motivated behaviors and it can increase the risk of addictive behavior it seems. And so one explanation is that once you've been on these drugs for a while and your appetite starts to normalize, you've lost the weight and your hunger starts to normalize again.

“Whether the results for addiction are going to actually endure after that, I think a lot of people think about these as clear treatments for these addictive behaviors.”

And that's where I think we don't have the high quality research we want to have to defend that. My assumption of why some people are getting an hedonia, some people were seeing, you know, lower desire for drinking that it was actually not necessarily to end up proving to be a clear treatment. But that it is messing with the system we don't really understand. I sort of think what's interesting about this whole conversation is we're basically saying, we don't understand any of the systems very well we don't understand the appetite system it's working in different way than we hypothesized the cardiac system is not doing what we thought it would be doing.

We don't know why the inflammation system is responding the reward system is changing I mean the human body is a very very very complex set of systems. It seems to be a complex change to them that at the population level is positive probably, but not in a way where we can precisely define the mechanisms by which it is positive or tell you for whom it will be positive for whom it will be negative and who will actually lose weight and who will won and how much. The word space actually. Absolutely and that's where I really feel this like there were just at the beginning of this.

After we ran this piece where we did the poll and talked about all these other surprising benefits people have experienced. I got lots of emails about weird like people who were on SSRI so they were on antigen presence and they start on a GLP one and they completely spiral and that's not something that I've seen show up in the randomized control trials are.

“The research but it's an experience that people have so I think we're going to have lots more of this at the scale that people are taking these drugs.”

We're seeing these these new drugs are coming down the pipeline. We're seeing that there's now oral forms of these drugs available the drugs are going generic we're going to see more and more people on these drugs and learn much more about them there's so much we don't know. What about all the drugs that are coming now so I know people who are getting ready to try from some compounding pharmacy in China or something and ready to try maybe you can explain it but. It's another Eli Lilly drug he also makes up on the trisepatide variant and this is in trials now and it's expected that it will be approved in the next some amount of time and it'll probably be a big deal but.

That and have full confidence in the way they're being manufactured like what's going on with reddit to try why is it both like around my community and all over my social media feeds.

Oh interesting this says something about are you in body building algorithms or. No this is. Already up X for me.

Oh interesting okay that's interesting so it's a research compound that's still under study it's targeting three hormone receptors so.

It's a magletied olzampica regovies targeting one and this is where at the beginning of the conversation we talked about how we had this a lot of research on these diabetes drugs over many years and we could be fairly confident in their safety profile. These drugs that have come on since like when jar or like to zip a tide and like ready to try they're targeting more than just the GLP one so they're targeting other hormone receptors and we don't have long term data on these drugs.

“And I think that's a really important thing that a lot of people overlook right so this one is still under study but in the research we have so far it looks like it's causing faster and more dramatic weight loss.”

And it's taken off and I think longevity and body building.

Well because the the argument I keep seeing about it is it increases energy use that it seems to have some independent effect on how much calories are burning. Yeah, I'm not sure what the mechanism but that could make sense that it's not just reducing appetite it's also increasing metabolism and maybe that's why people lose even more weight more quickly. But the point is we have this emerging evidence that it might be even more effective than what's already available and I think it just speaks to the frenzy around these drugs that people don't want to wait.

For the FDA to get the random highest controlled trials to approve the drug they're going directly to elicit sources and trying to buy the drug which is still a research compound. People I knew who used to order drugs on the internet they were doing fun drugs and how it's like. This is weird yes eat less and focus more. One thing I think is interesting about the glp one I mean for everything we've talked about here is for instance. You know the categories of who might want to lose a little bit of weight or even more so who might want to protect themselves from inflammation.

They speak to this reality that the difference between well and sick is not this like clear binary thing we now have these categories like pre diabetic and pre hyper-pensive and pre-menopausal and we didn't used to have them I mean we keep expanding the space in which you should worry pre you know we have like pre overweight pre obese kind of things and I think that there is an interesting dimension.

“People start looking for like chemical answers to wellness because the truth is for a lot of people get enough sleep and go to the gym regularly and eat whole foods is hard.”

If you could give yourself a shot or take a pill people want it and so how do you think about the the broader shift which is not new but it's happening with more force right now towards medicine as not a way of treating illness. But as a way of optimizing wellness. Do you see it as something new is that something old? I think it's more pervasive maybe but I think we have to be careful so if you think about the American public like most people aren't eating the minimum daily requirements of fruits and vegetables let alone personalizing or optimizing their diet beyond that.

Most people aren't getting enough sleep most people aren't getting enough physical activity and I think that's the majority right. I'm agreeing with that.

“Yeah, but then there is I think this minority that we pay a lot of attention to in the media that is interested in the longevity and the optimization.”

I don't think there's anything that new about wanting to use medicine to be more well as opposed to heal from illness and we've been doing that forever. And we've had health and wellness influencers forever but I think if you look around the media escape at this exact moment and you think about how big. Rogan and Huberman and Attia and then you have like Brian Johnson is one of the breakout media figures of the era this sort of former entrepreneur who's trying to never die and is like the you know has like ended up in this incredibly incredibly.

You know, OD the other day on a live stream is getting billions of views on his clips and I think there's something about the way like how dominant this is become in the media sphere. And it doesn't have checks that used to have on it. I mean you were talking I remember that coverage you would do a box of of doctor's. But one of the things happening on doctor's was like there was a network behind that I mean there were gatekeepers there were people who didn't want to see their stock price go down or something went wrong and now it's a complete wild west boosted by algorithmic interest.

“And I think it's going to push us into a real period of like a longevity and optimization focused system because like there's going to be money for it there's going to be attention for it.”

Yeah, I mean a lot of people in this country are very, very sick and what they need is treatment for chronic illness, but I think there's going to be a real push in the system to it's treating these people who what they are is not very sick what they are is well and they want to be weller. And really wild things to optimize their health, but the megaphone is so much bigger and more fragmented and it's so much more effective at creating this confirmation bias like I think about my mom who is diagnosed with osteoporosis and she was trying to decide whether to go on one of these medicines it's available for the condition and she ended up in a complete YouTube rabbit hole of doctors who were really skeptical of osteoporosis drugs.

And she became quite frightened and it took her like a couple of years to go on the medication and this is happening at a scale that we've never seen before right.

But this desire to optimize like in our book we found this wild example of after the first World War there was an ingredient in explosives manufacturing that sped up the metabolism and cause people to lose weight. And doctors at Stanford pivoted and turned it into a drug that was taken by hundreds of thousands of people and became one of the first targets of the FDA.

“And it had terrible side effects and killed people and caused eye problems and so I think we've always done these wild things in search of they had looking for the magic cure.”

The quick fix or bettering our health but the in your faceness of the messages and the way they're targeted with the algorithms this we've never seen so I think you're touching on something really important which is how this media landscape has changed. Not only around the blockbuster FDA approved drugs like the GLP ones but around this broader ecosystem of yeah wellness hacks and optimizers. I mean this goes to something that you wrote about in a piece of the time which is that these are the first blockbuster drugs to collide with our wellness obsessed algorithmic age.

And yeah I mean I must have clicked at some point on retitude tried content on X and now every time I turn on the system the platform. I get these videos from people like tell me how great retitude tried is and there's a huge boom and people just ordering peptides from places where they can't really tell what's in them.

We've never tested some of these and found a lot of them have led or impurities or things you don't want or they're not at the right dose.

There's something long we got these blockbuster drugs and you might expect to be really excited to be on them but it seems to have exploded into this bio hacking moment.

“And it's like if something like we go we could exist well then who knows what is out there and you should order it from China and inject it in yourself and find out.”

Like what do you make of it? I think it was it's sort of the perfect drug for this social media algorithmic age that we're in because it's visual right it's not like like you have the before and after photos you have. I've spent way more time than I did mid on tiktok and read it accounts where you see the videos and the before and after photos and how people's bodies are transforming.

And we were kind of living in this very appearance obsessed culture and now for the first time again we have this drug that does something that humans have questioned after for like a century or more.

And so it's meeting that moment I was doing a thought experiment when I was working on that piece of one pros that came on the market that was another blockbuster drug that was another drug where we had a cultural moment around it. But we didn't have telemedicine so you still had to go to your doctor to get a prescription the internet wasn't in widespread use so you can order a research compound from China there was no social media to compare your personal experiences and share them with the world.

I guess it does reflect but I've told my algorithm to tell me although not intentionally. I see so many people just posting about random studies that are not full randomized control trials are often not even in human beings and being like.

See look at this amazing mechanism and look at these early results and at least according to them they're getting them compounded in an ordering them.

I'm fascinated by this because there is some weird overlap between the community of people who are incredibly skeptical of vaccines of the FDA and at one point that was understood as a preference for naturalism. But there was a primitiveist impulse here and yet some of these same people who were so skeptical about she was was a very well studied class of drugs are now ordering completely unknown forms of peptides. But some of which are just to increase energy use sort of cure your tennis elbow or to try to improve like you know salary generation and they're stacking them in different formulations.

Like it's like a mistrust of the authorities but a belief in unproven technologies in a way that like that I find culturally very.

Interesting and I'm curious to somebody who's been around the space for a long time what you've made of it.

“Well I think it kind of goes together so we have I think since the pandemic we've had and maybe even it was brewing before the pandemic but we've had this.”

Optic in an appreciation an interest in health and health optimization and then we have these technologies now to spread information about health optimization podcasts in particular that are often sponsored by supplement makers.

The mistrustful of authority and a lot of people I think were left quite cynical after the pandemic of public health and the medical establishment.

And now we have this vehicle actually there was helped also in the pandemic with telemedicine where people can take their health in their own hands in a way that they haven't been able to before. And then this idea that you can just do it yourself it feels like that's almost the currency today of social media like you know you say there's this new study and this new I found this new use for something and now I'm going to promote it on my feeds.

“Or flex this way in which you have to trust something the world is simply too complex for anybody to have first hand knowledge of very much of it at all.”

So you can trust established authorities like the FDA and the CDC but if you lose trust in them you have to still find some way of deciding what to believe and what not to believe. A lot of people choose individual voices you know Andrew Huberman or Joe Rogan or Peter Kia or people further into the Mahal world. And I'm not even saying they're necessarily corrupt but if you're in media for instance and you run a podcast on health and wellness week after week you have to find new things to say. Just getting on the mic every week and saying here's another week when you should eat whole foods and try to reduce your stress and sleep well. It doesn't last even putting aside the fact that some of them are getting a cut of either supplement companies are advertising for it.

You have this huge bias towards the next new thing and it was always there right I spent a lot of time earlier in my reporting career with you at Vox like looking at Dr. Oz and I remember once interviewing a mirror's ago and he said you know that I think I said like why do you have the magic and miracles on your show like your cardiovascular assics surgeon you know this isn't. Research base of the question like that and he said you know if I didn't have the magic and miracles I wouldn't have a show.

There's also the very sound advice the very sound scientific foundation we have for how to optimize your health. It's so boring right it's what you said it's like sleep more have social relationships eat more vegetable stuff your mom has been saying to since you were in your high chair. And yeah.

“I will say before I make this next point that I think injecting yourself or taking poorly studied peptides it's a stupid idea and people shouldn't do it so I really want to say this very clearly.”

But I'm preparing this episode in reading what some of the peptide booster types are saying their argument is look people have a right to do this it is their body. They are doing it and it would be better if we let them buy them from domestic compounders whose processes we could regulate and oversee rather than these fly by night Chinese companies that we can't trust.

Like the government doesn't want you doing this and we're going to try to make it hard to get them and increase the you know the risk so more people don't try.

So that argument is how we got the supplement market we have you know do know that the history of how supplements became kind of this thing there was a big campaign push in particular help by supplement makers it was like a massive letter writing campaign on the part of the public. We had with famous actors and the thing was like don't touch my supplements I have the right to use these supplements and representatives who are from states with large supplement manufacturers really pushed to have this kind of lacks regulatory environment.

“But it was this argument that Americans have the right to use the supplements they want to use that's why we have this regulatory regime around supplements that we have today.”

I personally think the government has a role in protecting public health and protecting consumers which way does a supplement argument actually point you walk into whole foods or you walk into CVS and there's a lot of supplements and I don't think we see it as a national tragedy and a lot of those supplements have names I don't even know and it doesn't seem like they do that much when I look into it but maybe and some people seem to think so. So is that a bad thing or good thing right in my upset people can create the supplements tax I mean not really if you want to take it healthy and I know whatever go for it.

I think when people are being misled and using scarce resources on things that aren't going to help them I think actually it is a problem but it's a very sensitive topic and a lot of people especially in the American context it's this idea that you know you have the right to. Do what you want with your body and to access the products that you want to access and I guess I have a more conservative view on that but a lot of people definitely disagree with me. I mean my gut is that this is going to become a disaster my personal view is actually fairly conservative I'm trying to be the devil's advocate here. But it seems like people are taking a lot of things right now to increase cell growth which maybe is good in the short term but has really.

“I mean I think we might end up realizing that a couple of the things that people are starting to get excited about you know really not good for folks which has happened before I mean we were talking about fenfen and things like that earlier.”

We have had periods where people got really into something and it wasn't good for you used to put cocaine in Coca Cola.

If you know anything about the history of medicine it's littered with examples like this and that's also why I always come at this much more conservatively.

But I think we're definitely in this big experiment now where these different things are colliding right this interest in wellness and longevity and health optimization. The availability of these drugs it seems to do everything and then these over the counter variants that people are accessing and buying online or in the pharmacy it's a potential disaster waiting to happen.

“One thing that I think is just a deep appeal of these drugs of broader peptides and other things that are you know becoming culturally influential.”

Is on some of we all want it's control control of our bodies control of our health control over never getting the diseases that scare all of us.

And on the one hand if you are able to be given a real possibility for control if it's true that the GOP ones that low doses protect you against heart disease amazing. I've a friend somebody who I care about tremendously who's parent died young of dementia and I've been following all this Alzheimer's research on them you know very closely because if they're prophylactic against dementia like I want my friend to take them. I think that wanting to protect yourself as a bad impulse it isn't. On the other hand a desire for endless control over your own body and future can be mentally poisonous too because you can't control it.

The great inside of Buddhism is that you know desire and craving are the root of suffering and you know the more we trick ourselves into believing we can control what will happen to us. And then when things do happen to us we feel like we failed absolutely we live in food environments that are so game against making the right choices for most people right. So even if you are on the GLP one and I've talked to many of these people they're not losing the amount of weight they want to lose because they have other barriers to eating the way you're exercising the way they'd like to.

We've created these systems and food environments that make it literally impossible for most regular people to do the things that they know they need to be doing for their health.

And I'm not anti GLP one at all like I think they've been absolute game changers for so many people I've talked about for friends and family.

But we're doing this big experiment on the population because of diseases that really are preventable. If we do the things that we've long known we need to do like restricting junk food marketing to kids figuring out ways to make healthy food more accessible. Actually it encourages me as a person who struggled with my weight before like this realization that this was preventable. I didn't have to suffer like that and like the kids who are now going through this now they don't have to suffer like this.

I feel like I've heard this argument as long as I've been touching this issue which like as you know beginning of my career as a health care reporter. You know you debate food deserts and what would happen if we put you know good grocery stores and food deserts and we did this in a bunch of places and it didn't really work. I've become very cynical about this I mean yes it would be much better if everybody had was like wrapped around with you know more walkable places to live and better in healthy foods and I don't think you should be able to advertise junk food at all the children.

“I think it should be illegal to have pop patrol on kids cereals.”

I think this whole thing where we allow endless advertising children is completely insane and it makes every parent's life in the grocery store a nightmare myself included.

And for the society at large I think the problem is people want things that aren't good for them.

But we've never done enough but but people don't want you to do enough. But which people I feel like this is both like this happened in New York Bloomberg wanted to tax sodas. I think it was ran about a town on a rail. Okay nobody think things are the politics of this are changing. I think like more and more people are raising kids with diseases like diabetes and fatty liver and they're aware that this is caused by the food.

It's caused by the food environment and I feel like that the politics they're shifting but we've never done the inversion of our food environment that we need to do.

It's going to take many many levers to really see an impact and that really hasn't been done.

“I think you would need a level of paternalism for that that I guess what I would say about it is that there is not a single jurisdiction in this entire country.”

Where the politics of that have worked like we cannot point it one thing one place one state one city where we've been able to do that much. If it were there to do I would be the first one to say we should do it but I don't think it's there to do like the public health community. We try to get people to take vaccines in the like aftermath or the the math during a deadly pandemic. And it led to like the largest public health backlash in my lifetime such at RFK juniors now the Secretary of Health and Human Services.

People's sensitivity to paternalism is very, very, very high. It's a very potent political force. But I think one thing that I'm talking about and that we write about in the book it's not about taking people's fried chicken or their M&M's away. It's about making a food environment where the healthy options are as accessible as the unhealthy stuff. And so I'm living now in France and obviously the politics are completely different. There's no shortage of chocolate tears of places wrecked and by croissant we all like all these things that I know I shouldn't be eating every day.

But as accessible are the healthy options so they they've done things like fresh food markets in every district. And they minimize the size of grocery stores through land use planning since the late 1800s like using school lunches as a lever to feed children healthfully. And over time they've become more and more avant-garde about what that actually means they pull all these different levers.

“But what we're talking about I think is creating this regulatory environment around chronic disease like how do you protect the public from developing these diseases like obesity diabetes cardiovascular disease.”

And it seems like impossible now because it does involve these radical changes to the food environment. But America did this over a hundred years ago right when we started to protect people against acute food poisoning. It was just it was wild west they were putting calf brains in milk at this time and putting like. Brick dust to die food in a certain way and lead that's where the FDA came from that's where the median inspection program of the USDA came from after like the publication of updancing Claire's book.

But I hear you it's going to be very difficult. I do think the politics are changing so we're in a moment where like places like California and West Virginia are both looking at. You know doing things like reducing ultra-process foods in school lunches and banning certain negatives.

What they're saying about die cause diseases you can't tell who's saying it anymore.

“That's true but I've been extremely disappointed to see that even the parts of my heart that I thought made sense have made it nowhere right you will watch Kennedy now it like.”

Like eating his calo fried french fries and you know going to like these fast food restaurants that you know if they really wanted to make America the American food environment better like they could. Meanwhile, the president of the United States is like forcing North Carolina to eat McDonald's and photo ops. Like they're actual willingness when it came down to it to take on industry was extremely low. No absolutely like yeah like if you listen what they're saying it's fine. Have they done anything that will in a sustained way change the food environment for people.

I would love to have seen Mahabhan you know advertising kids they didn't.

“No the way I think about it is you know you had the new nutrition guidelines come out which had this great message eat real food right.”

But no one is doing anything to make it easier for the people who actually really struggle to afford an access real food to eat that food right it's like.

There's something like 3 million fewer people on snap the administration has made it more and more difficult for.

Yeah huge cuts were are continuing to go into effect there and there were programs to make local and fresh produce available to schools can teens available for school lunches and those have been cut. And then there's a lot of like tweaking at the edges of you know swap out high fructose corn syrup with king sugar or focusing on certain food out. There's such marginal problems in the greater system if you really want to help more Americans eat real food you're going to have to do a lot more than that and you're going to have to focus on the segments of society that we're on food stamps for example.

So I completely agree I think a lot of the rhetoric has been in the right place like this is the first time I've seen at that political level people talking about the food environment and saying. These diseases are preventable and they are caused by these environmental factors taking the pressure off individuals. But then a lot of the solutions that have been proposed to have also been focused on individuals like give Americans more wearable devices and continuous glucose monitors. It's not the intensity of the intervention that I think we actually need.

Then I was a final question. What are three books you recommend to the audience three books that really shape my thinking as I was writing my book one was behaved by Robert Sapolsky.

“He wrote another book determined about basically it's an argument against free will, but he comes at this I think from a really interesting and important angle.”

Another one is death blums poisons quad and this is like an excellent look through a biography of one of the former chemist at the USDA. To research that helped lead to the establishment of the FDA and a lot of the food regulations and other types of consumer protection laws.

We have I love that book and a third book that I really enjoyed was ultra-processed people by Chris Ventiliken and this is really a polemic and much more than where I ended up coming down in my book.

But I thought that was a really illuminating and fascinating book on ultra-process foods. Julie Blus, thank you very much. Thank you so much. This episode of this country is produced by Annie Galthin, fact checking by Michelle Harris with Mary March Locker. Our according engineer is Johnny Simon, our senior audio engineer is Jeff Gellbe with additional mixing by Johnny Simon.

Our executive producer is Claire Gordon. The show's production team also includes Jack McCordick, Roland Who, Marie Cassion, Marina King, Kristen Lynn, Emma Calbeck, and Yann Coble. Original music by Amin Sahota and Pat McCusker. Audience tragedy by Shannon Busta, the director of opinion shows is Annie Rose Strasser.