DR FEDERICA AMATI: How Weight Loss Drugs Can Rewire Your Brain

0:00Everyone, it feels like, is talking about what we call the skinny jabs.

0:03Dr Federica Amati: The most vulnerable population for this is girls in their late teens, early 20s. Reflux, vomiting, nausea, constipation. They've seen a huge increase in people taking these medication who developed an eating disorder. If you undernourish yourself, your muscles and your bones will suffer. The risk that they are undermining their long-term health is huge. Is it a miracle drug or is it a danger? Wow. Hi, I'm Dr Federica Amati and I'm in great company again. Leading nutrition scientist, Dr Federica Amati. GLP-1 receptor drugs, they are a medical breakthrough. The idea that we can now harness peptides and completely change metabolic health is wild.

0:45Dr Federica Amati: This drug is being taken as a lifestyle drug because we're obsessed with weight. I'm not pro-drug or anti-drug, I'm pro-patient. Reta tried, Reta, known on Instagram. It is not yet approved by the FDA. untested, untracked, unregulated, but people are accessing it on the black market. They're really for rats in labs. I'm not joking. I have like a million more questions. Weight loss is almost not the most interesting part of this drug. It also turns down your desire for alcohol and gambling. No. Yeah, it's a brain drug. I'm very angry about this. There are adverts that target postnatal women. Recovery requires a lot of nutrients, especially if you're breastfeeding.

1:26What are the long-term effects of taking these drugs?

1:29Dr Federica Amati: Everybody should know this.

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4:42She's back for a second episode. It's Dr. Federica Ramati. Federica is one of my favorite people to have ever been on the show she's one of the first people we had on the show one of the first experts today we're talking about so many different things but most importantly GLP ones and the side effects and the things that they do to their mind what I learned today is simply incredible now before we start if we can do one thing click that subscribe button it's completely free and keeps allowing us to make the show better for you guys every single week if you can do that one thing thank you so much okay enjoy this amazing episode of Great Company with Dr.

5:15Federica Amati. Federica, hi. Hi, Jamie. Do you know, we have, I think we've only ever done one other person twice on the show. So you are, you are the second person to come back. And if I'm totally honest, the first time you came on was so mind blowing and so wonderful. And you were one of the early guests on the show. and it kind of for some reason it put this sort of um footprint out there and so people went oh I really like this podcast I really like this show so I owe you a lot oh my gosh thank you allowing people to really enjoy what this show is about well I loved our first podcast I was

5:54Dr Federica Amati: actually I don't think I told you this but I was in quite a bad mood that day yeah I was I think I'd done quite a few podcasts for my last book and I was just like oh gosh I've got to do one more podcasts and your old studio was in Vauxhall which is quite far yes and I just remember being like come on pack up you know just you can and and I had the best time to this day I tell everyone that whenever they're like oh you know I've been invited to this podcast great company do it it's one of my favorite podcasts to record that is so good I honestly I loved it I had so much fun that day I came out bouncing did you really yeah but when I arrived I was like come on deep you can do this that's you in a bad mood yeah that's me on a bad day that was wonderful so thank you because i really enjoyed it and i'm so glad it helped because yeah i think i remember it was just launching so just launching and it was just incredible and it did amazing things and so much has changed since then i'm now a dad yeah i know i know that's a lot a big it's a big step it's a huge step because you have how many kids two you've got two babies and yeah it It changes your mind completely.

7:03Dr Federica Amati: Yes. Well, it actually does as well for mothers. It actually rewires your brain with each child. But also it changes your entire perspective on life, doesn't it? We were just talking about this earlier. It pivots all the priorities. Well, it did for me. And I think it's interesting because when you talk to someone who becomes a parent, there's so much more common ground now where you're like, oh my gosh, this and this. And as much as you can talk about the changes beforehand, but until you live it, it's just you can't, your brain just can't do it, that you can't actually imagine what it's going to feel like.

7:39That was my biggest shock is that it's exactly that way. You try and discuss it. Someone tries to say, by the way, get sleep now because you don't know what it's going to be like. Terrible advice. Terrible advice.

7:49Dr Federica Amati: You can't bank sleep. No. And you also, you can't comprehend what it's going to be like and how it's going to change your life. Yeah. And I think a big thing, and certainly my husband said this to me a few times, is that when you speak to other parents, you feel like it's not just you. It's not just you that's struggling with X, Y, Z. Or, you know, as your kids get older, it's not just you that's noticed that your four-year-old has become really defiant. It actually, you start to see that there's lots of patterns and there's lots of common ground. And that makes you feel like, okay, actually, it's not just me as a parent.

8:22Dr Federica Amati: So that's a really important part. It's hard. Oh, yeah, yeah. It's like a, you know, technically the most intense job in the world. It's 24-7. You don't get a break. And it's a big responsibility, depending on how you parent. Because I know there's different attitudes to parenting and different viewpoints. But certainly, I think where I stand and my idea of parenting is that you're raising the next generation. And so I want my kids to be good citizens. I want them to be a good contribution to humankind. and I want them to have a really good life. Part of our job as parents is to help set them up to be able to navigate life and not only have fun and have a great time and lovely holidays, but also be prepared to challenge, to take on challenges, know how to respond and hopefully be quite resilient.

9:14Dr Federica Amati: I think that that's the hardest part, isn't it? Because you can't protect your kids from everything. so what you try to do is give them the tools to know what to do when they are having difficulties because life's going to hit you around the head at some point anyway i do think that when when i hear people say you know he needs to toughen up a bit and it is usually about boys he needs to toughen up a bit i'm like life will do that like this time life will toughen people like make them feel safe that's the main thing is that the main thing to do oh i so i'm not a like child psychology expert but certainly what I think and as a parent and what I've read is that it's like like helping children feel like they have a safe place within the family and it might be your parents it might be your adoptive parents it might be your aunties grandmas it's different for each family for each child but having a very firm fixed safe person is so important for psychological safety.

10:10Dr Federica Amati: There is a study of what's called adverse childhood events, so ACEs. And when you look at predictors of health, ACEs are one of the biggest predictors for health outcomes. And there's a scale, basically. So the more ACEs, the more adverse childhood experiences or events you have in your life, the higher the likelihood of certain outcomes are. For example, suicide, for example, high blood pressure. So actually, it's fascinating when you start to look at this, just how much impact childhood events have. And this is things like your parents divorcing when you're young. It's things like surviving war.

10:49Dr Federica Amati: So there's some pretty serious ones, abuse, neglect. But when you start, you know, add them up if your parent was an addict, for example, while you were a child. So some of the children do have a lot of these exposures. And I think as a society, our job is to try and protect the most vulnerable children who are at risk of having several ACEs. And then as a parent is understanding that childhood exposures are really important and how do we create the best possible environment to help our kids flourish and have a good life and enjoy their life as much as possible despite the challenges. It makes me feel sorry for people.

11:30Firstly, it makes us realise that, which we all slightly know, is that childhood kind of is the roots for everything. within our lives, right? That's what makes our flower blossom to what it is. And it makes us feel so sorry, or makes me feel sorry for people. You know, you think of the amount of people who are probably incarcerated, right? Who are being put in prison, who may have made mistakes, done things. And yes, I'm generalizing here, right? But you kind of go, God, what happened in their lives?

11:54Dr Federica Amati: Well, you've touched on something here, because I think what I'm really passionate about at the moment in sort of wellness and health culture is that we talk about wellness and health and life outcomes as though it's an even playing field. It's not. But it's just not. It's totally not. So what I, and actually, interestingly, GRP ones have shown us this, but there's still this tension in wellness culture where I saw recently, I saw an influencer just yesterday, actually, someone sent me a video saying of an influencer saying, why would you take a medicine that's made synthetically to lose weight when you could just have the natural alternative?

12:29Dr Federica Amati: And this, this influencer is extremely slim she's extremely wealthy and no shade on what she's doing but that kind of story where it's like actually if you just tried harder and if you just like you know bought this supplement and it would be fine when we have to understand it's not sexy but when you have to understand that socio-demographic factors underpin the rest of your the rest of everything else so if you are someone we're lucky we were educated we were born into families that could afford to take us on holiday and do things. We both have homes. We have to appreciate that we're lucky and own that.

13:06So when people say, oh, you know, but do you think that these medications

13:11Dr Federica Amati: are bad or do you think that we should all just exercise and eat less? It's like, no, we live in an obesogenic environment right now where 60 % of adults are either overweight or obese. What does that tell you? It tells you that the environment is stacked against health, right? It's actually currently we're swimming upstream. We're all these little fish swimming upstream. So if you're one of the lucky ones, like us, that aren't suffering with a chronic condition and are not overweight, that's quite a lot down to luck, right? Partly genetic and epigenetic luck, because perhaps our parents and our grandparents didn't suffer with obesity, and down to the fact that we have access to make it easier for us not to be overweight.

13:53Dr Federica Amati: So we have to accept that it's not the same for everyone and it's the same with i mean aces especially children have no control over the exposures that they are generally exposed to so we do have to take these things into consideration and hope and help to build a way of looking after people and looking out for people that actually says okay here's your deck of cards what what can we do there's lots of evidence around what works what doesn't work what can we do to help you play that deck as well as possible you can't really change the deck of cards it's really hard to do but what can how can we help you give you the tools to change how you play it so that perhaps you don't end up spending the rest of your life in prison or perhaps you learn ways to make the most of the skills you do have and then flourish that way so there's it's just but you have to be compassionate and you have to think about where you sit in in that scale and be comfortable with the fact that perhaps you are a lucky one actually you have your new book the appetite reset how to eat drink and thrive before drawing and after glp ones so everyone it feels like is talking about this sort of what we call the skinny jabs yeah asempic jabs manjaro is another one is it a miracle drug or is it a danger they are a medical breakthrough so like the idea that we can now harness peptides and completely change metabolic health is wild it's something we've been waiting for for decades because the diabetes pandemic so diabetes type 2 diabetes and obesity have been rising steadily for decades and in terms of public health it's you know it's been watching a car crash like how do we slow this down what do we do that's because of different that's because the foods we're creating right As I said, it's an entire obesogenic environment.

15:50Dr Federica Amati: So it is the food. It is how we live, how we work. We're very sedentary. There's much less manual labor. It's also how much time we spend outside. It's a lot of factors. Food is definitely a massive one, don't get me wrong. but I think we have to realize that there's there's other pieces to the puzzle there's undercurrent disrupting chemicals in the environment there's lots of other things that all converge towards obesogenic environment right so having a medicine that can actually help because the problem is is that when we talk about obesity we talk about excess adiposity so it's not how much you weigh it's actually how much of your weight is fat tissue compared to lean mass okay if So you can be quite lean looking, you can be quite sort of small stature, but you can still have this real mismatch between lean mass and fat mass.

16:45Dr Federica Amati: And when we have increased adiposity, increased fat mass, that's when you start to see the metabolic health consequences of obesity. And type 2 diabetes actually goes hand in hand. So type 2 diabetes risk increases with obesity and type 2 diabetes has lots of consequences downstream. So living with either type 2 diabetes or obesity impacts your lifespan and it impacts the diseases that you're likely to develop. This is why we want to tackle it, right? We want to help people reverse that risk or at least reduce that risk. And here's the medicine that can do it. However, it's a powerful metabolic medicine.

17:23Dr Federica Amati: And it was actually initially licensed just for type 2 diabetes. And for many years it was only prescribed for type 2 diabetes. But then people noticed that it helped people lose weight. It's like, oh, my diabetic patients are also losing weight without really trying. And so here then we have, so for a medicine that was prescribed for, you know, GLP-1 receptor agonists were prescribed for 15 years or so without making any much noise at all. But as soon as the prescription moved to obesity and weight loss, it just took off. and a combination of celebrity endorsement, press, and not so much in the UK, although you started seeing it here.

18:02Dr Federica Amati: Just on my way here to the studio today, I saw a massive bus advert that had, because you know you're not allowed to advertise pharmaceutical products in the UK. So you've been to the US, you know you switch the TV on in your hotel room and it's like these really long adverts all about drugs. Now in the UK and EU actually, they're not legal, but I've noticed for the first time on a bus on the way here there was a big bus poster and it was a tiny pill held between two fingers didn't say the name of the drug it didn't say like weight loss and then it just said the I won't say who it was but it would say who the company was that can provide it what is that legal very borderline right so that I don't know if you saw the Eli Lilly adverts that were on the tube there's been a lot of complaints to the ASA about these adverts because it feels like it is advertising drugs.

18:52Dr Federica Amati: Point being is when you have a combination of celebrity endorsements from the likes of Oprah Winfrey, Serena Williams, right, to advertising in the US, then social media phenomenon, and then suddenly the demand for this drug far outweighed the actual clinical prescription for it. So people who absolutely don't need this drug, they don't have type 2 diabetes, they are not living with obesity, are trying to access the drug. and what happened here in the uk is that the nhs is really strict with which medicines it buys for the population in part for cost saving so like it has to be cost effective and in part because it has to be safe you can't start giving out a medicine on the nhs and then find out that it's damaging people's health so getting a prescription for glp1 receptor agonist on the nhs is actually quite hard work there's quite a serious clinical pathway you have to be assessed it has to be the right population.

19:47Dr Federica Amati: The cutoffs for BMI are really quite high. So it's not easy to get a GLP-1 receptor agonist prescription on the NHS. So what's happened instead is people are just buying it privately. So 95 % of UK adults that are currently using these drugs are buying them privately. They're not going through the NHS. What does that mean? It means that most of the time, And listen, different providers are better or worse at doing this, of this assessment and screening. But mostly the problem is that patients aren't assessed properly. You know, these medicines impact your brain. They're brain drugs. That's where most of the work happens.

20:27Dr Federica Amati: They impact your gut. They impact your pancreas. So having some sort of screening ahead of time is really useful to make sure that you're the correct patient to receive this drug. So screening is very poor with a lot of these providers because you fill in an online form and you can lie. So there's lots of stories of people who are very slim, doctoring images to upload it to show that they're overweight or just downloading an image off Google, frankly. So assessment, then prescription is made and then follow-up and screening. So there's no continuation of like, how's your side effects? What's going on with your weight?

21:06Dr Federica Amati: Like what is happening with your mood, your energy, your constipation? So the most common side effects are non-life-threatening. They're gastrointestinal. Okay, so that is... That's reflux, vomiting, nausea, constipation, right? Okay. All of them can be quite well managed with dietary intervention. Sure. But if you don't tell people that and you don't help them understand what to do, then a lot of them are turning to buying medicines. So over-the-counter antacids, for example, have shot through the roof. Absolutely. Because people are taking the drug and then going, while I'm constipated or my stomach hurts or whatever it is.

21:41And so then I need to take that.

21:41Dr Federica Amati: And then they're taking the antacid on top, right? So this journey, I've worked with a lot of people who went through that journey, had a terrible time. And these are patients who actually need the prescription. So they ended up going private, but they did have obesity or they did have type 2 diabetes. And actually type 2 diabetes, I have to say, access is easier. It's mostly obesity. So they come to me and they've just spent hundreds and hundreds and hundreds of pounds for six months on these drugs nothing it didn't work or the side effects were terrible and so they then came off the drugs and then desperate last minute last resort they come to me they're like i've tried everything i even tried the drugs they didn't work for me please help me and the psychological damage i've seen in these patients where they feel like they failed because the miracle drug didn't work for them and then i explained to them that actually non-responders is about 20 percent one in five people and it's not because you failed well just for weight just in one in five people you don't see a clinically significant weight loss so more than five percent of your body weight in about 20 percent of people but here's the thing these drugs are not just weight loss drugs so like these drugs are designed to help your metabolic health primarily it was type 2 diabetes so glucose glucose control it it tells your pancreas to release insulin when you eat carbohydrates, so it pumps more insulin into your blood.

23:05Dr Federica Amati: But also, it seems to have an anti-inflammatory effect. So people who have rheumatoid arthritis are reporting that their rheumatoid arthritis is better. Now, this does go hand in hand with weight loss. But just because the medicines haven't resulted in clinically significant weight loss doesn't mean they haven't had a benefit on your overall metabolic health. This is obviously given that you're actually a patient that needs them. so I think the way we framed these like the skinny jab it's like actually it's not just about weight loss weight loss is almost not the most interesting part of this drug and we have to be mindful that the way that the drug is evolving right now like the access to it the the sort of desire to try it out patient populations that shouldn't access this are accessing it it also makes it harder for people who actually do need it to navigate how to be successful on it and what to look out for.

23:57Dr Federica Amati: So there's so much. So the reason I wrote this book is because there's so much confusion about how to take them. There's literally no conversation about how to prepare for them. So the way I think about this, I did a BBC Panorama documentary for this like two and a half years ago, is these drugs are delivering the same level of weight loss and so change in body composition as bariatric surgery. That's huge, right? But can you go to your local wherever and just access bariatric surgery? No. So there's enormous amounts of screening and preparation. Now, of course, bariatric surgery is major abdominal surgery, but the physiological outcome on the other side after the surgery, in terms of weight loss, body composition has changed, even some of the gastric symptoms, quite similar, but you have none of the follow-up.

24:46Dr Federica Amati: You have none of the nutritional screening. So with bariatric surgery afterwards, you're closely monitored for micronutrient deficiencies because you're at higher risk. Why? Because you eat less food. And then what's the side effect to that? Well, if you have micronutrient deficiencies, then you run into risk of losing, being ill for other reasons. So for example, if you suddenly have a huge B12 deficiency, then you'll be exhausted. You'll start to feel like your hair might start falling out. There's other issues. If your iron levels are really low and you're a woman especially, and you're still menstruating, you can run the risk of anemia.

25:17Dr Federica Amati: So micronutrients are an important part of the picture. But because of the way we've set these drugs up, right, we don't follow people up. So if you think about bariatric surgery as the closest medical comparison, and the difference in care that you get. Can you explain what peptides are? So peptides are teeny little proteins. And we have hundreds of them in our body. So they're you need little proteins that act as messengers between tissues. So GLP-1 is a peptide. So peptides are often hormones. So they're just signaling molecules that happen between tissues. You have myokines from your muscles.

25:54Dr Federica Amati: You have adipokines from your fat cells. There's lots of different peptides. So what's happened is because GLP-1, which is a very specific peptide, which has got over 20 years of clinical use and was discovered in the 70s, So it's pretty, we've known it for a while. That's obviously now become a super popular pharmaceutical product. And it's used widely. And we have a lot of data on safety, efficacy, population data, who it's good for, etc. And that is used for? GLP-1 is now the prescriptions, so like the licensing is used for type 2 diabetes control. And that's what semaglutide is licensed for.

26:34Dr Federica Amati: So Wagovi, for example. and then you have tizepatide which is a dual agonist so two peptides in one drug and that's used for obesity so you use that to treat obesity and then there's future ones retatutride reta known on instagram everyone's going mad it's a triple agonist so there's three peptides and it is not yet approved by the fda but people are accessing it on the black market why because what's happened alongside the grp1 rise is that peptides everyone's like well that peptide works all these peptides will work so there are as i said hundreds of peptides we typically used to think of hormones as just coming from endocrine organs right so like we'd say thyroid hormones from your testes from your ovaries but what now so there's about about 60 hormones that come from like these typical places and endocrinology was based on those it was like these are the hormones is how they work since then so like in the past sort of 30 years we've seen that there are peptides released from your muscles, peptides released from your bones, peptides released from your fat cells.

27:35Dr Federica Amati: So we have way more signaling molecules than we thought, hundreds. At the moment, it's hard to know how many hormones, how many peptides that are signaling molecules we don't know about. But we do know that there are hundreds of receptors that we have in our body and we don't know what they're receiving. So instead of trying to find like what hormones are missing from our list it's like well what are these receptors doing what's going on here and when you look at all the proteins that are expressed in humans you know when you talk about um when we talk about dna sometimes you have this like junk dna we're not sure what it's doing dna codes for proteins right and when we proteomics which is a study of proteins essentially it's we know that there's about there's lots of proteins that we're not sure what they're coding for so this field of peptides and molecules is just blown up this is the beginning right so when you look at all the clinical trials that are happening right now in like phase two and three so so nearly done right um there's dozens of new drugs of different peptide combinations that are going to come to market in the next 10 years dozens so you can just imagine so when you look at this one of the reasons i wrote this book it's like okay we are literally at the precipice of an entire change to how we treat metabolic health and so the peptides that you see the peptide stacks the wolverine stack these are individual peptides that for now are only licensed for in-lab experiments or clinical trials they are not licensed for use by the general population or for prescription by a medical professional so you're not supposed to be using them you know they're really for rats in labs i'm not joking so what's happening but people are so what's happening now is this really strange situation where the clinical trials are here and and now they have started some clinical trials use looking at these peptide bcp-157 is one of the most popular ones right there's there's no human studies on safety or efficacy of bcp-157 but thousands of people use it maybe more like honestly i don't know what the numbers are now here's the problem clinical trials and pharmaceuticals haven't really kept up yeah with the adoption in the general in the mass population in america you can go to peptide clinics and i'm not sure how that works like in terms of law legally but they figured it out in the uk you start to see peptide clinics i have patients in the uk who take peptides right so it's happening and the biggest missing opportunity we have this like what we could do is say look we know you're taking these yeah we know you're prescribing these let's collect the data because we just aren't keeping up with the adoption of these peptides so i can stand here and be like don't take them we don't know about the safety we don't know what they do like one of the don't know what they do well we we have like we know from mouse data or from tissue data like this peptide is involved in this process but what we know about all hormones is that there is no single hormone that only impacts one system.

30:39Dr Federica Amati: So even though you think BCP157 might be helping with your joint pain, it's also going to be doing something in your brain, doing something over in your lung, probably, pancreas. So we just don't know, right? And so why don't we all come together and say, let's just collect the data? Because there's a huge population study you could be doing right now, just collecting data from people to say, okay, well, what are your side effects? How often are you taking it? When are you taking it? But the biggest problem here Jamie is that because these preparations are not for humans, they're not medicines they're not regulated so why do we care about FDA approval?

31:16Dr Federica Amati: Why do we care about EMA approval, HMRI, all these companies because when they approve a product for a pharmaceutical company to sell to you, it has to be produced exactly the same way with strict safety standards and every single time you buy a paracetamol that says 500mg it actually has 500mg of paracetamol in it yes correct whereas these peptides right now you don't know like so there's been some tests people have gone out and bought a bunch and tested them some of them had none of the peptide that it advertised some of them had like three times the dose some of them had very odd other compounds in it that aren't good for you so it's like playing it's basically like it's basically like cocaine on the market i mean uh yeah i can see how you got there but it's not it's just like you wouldn't you don't know what you're playing with you don't know what you're taking you don't know what you're taking and there are people that are like the cleanest the safest but imagine doing that and then instead of just playing around with one of them imagine stacking them and doing three or four or five which is what's happening with these wolverine stacks and other things you have five untested untracked unregulated peptides that you're taking if something goes wrong we don't know which one it was that went wrong because you don't There's five of them.

32:35Dr Federica Amati: So I'm very cautious about people trying these out. I've worked with people that have. And to be fair, luckily they're okay. But it's not a good idea. And also, it's this classic thing where you're trying to inject yourself with a stack of peptides. For what? Normally, it's for something that you could do and improve on with lifestyle. It's like people love a silver bullet. And so if this peptide is going to help me to recover faster from my workouts and it's going to help me to, you know, get leaner. So a lot of it is aesthetics. It's like, will it help me lose weight? Will it help me get leaner?

33:12Dr Federica Amati: It's never like, oh, this peptide is supposed to be really good for your heart health. It's never that. It's usually aesthetics. And they want to do it to like push that boundary as fast as possible. So it just harks back to the issue we have in general. And it's happening with GLP-1s as well. GLP-1s are regulated pharmaceuticals. They're a prescription drug. but people are taking it recreationally and and and honestly like it's it's wild to me how this has been allowed to happen because the regulatory body bodies are clear that it has to be prescribed for certain patient populations but somehow people can just go on tiktok click a link fill in the form never see a doctor face to face and receive a metabolic medicine in the post you could never do that with thyroid medication or with blood pressure regulation medicate you just you just can't you have to see a doctor and have be like examined so i don't know how that's happened but it's opened a whole pandora's box this is hannah burner from giggly squad opil is the first over-the-counter daily birth control pill available in the u.s let's be real getting a birth control prescription is not always easy and it's so much admin in fact about a third of women face barriers to access prescription birth control between scheduling appointments missing work class or just trying to exist it's a lot but now opil is putting birth control in our control opil is a daily birth control that's fda approved full prescription strength and estrogen free and 98 effective when used as directed grab it online or at most major retailers no prescription or doctor's appointment needed so if you're thinking about birth control check out opil to see if it's right for you.

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36:48What does it do to the mind? How does it change your mind?

36:50Dr Federica Amati: Yeah, nice. So GLP-1 receptors are found in the brain. And one of the ways in which these drugs actually change eating behavior is by affecting the brain, the hypothalamus, which is your central control for things like reward, pleasure, and drive. So there's agonists, there's receptor agonists on the brain. And when you take this drug, and actually what's really interesting is how many of those is genetic. so some people find the brain effects really strong and some people are like it hasn't changed anything for me and some one of the pieces of work that's happening now is to try and be able to map who is going to be a better responder to which agonist based on genetics which is cool so the future i think looks like personalizing these drugs so that you get prescribed the one you're most likely to respond to right so it affects your brain what does it do there's a neuron called POMC.

37:46Dr Federica Amati: And it basically helps us switch this on and off. If you take GLP-1 receptor drugs, agonist drugs, it dampens down your drive to eat. So the lack of appetite, the lack of food searching comes from the brain. That's what's really driving it. So your body, actually, most of your peptides that are involved in appetite regulation are there to help you feel satiated. So we have lots of lovely peptides like GIP and PYY that the drugs don't mimic yet. GIP, yes, that's what Monjaro is, GIP and GLP-1. PYY, they haven't managed to put into a drug yet, but it's a very interesting one because it mostly acts on the brain.

38:26Dr Federica Amati: These are all involved in helping you feel satiated. So our body is actually wired to help us feel full if we feed it the right things. And we'll get to that later. There's other hormones involved like leptin, which comes from your fat tissue that it's also involved in helping you feel full. Ghrelin is the one that helps you, that makes you feel hungry. And what happens is when you take these drugs, ghrelin is shouting because you're not eating that much. So, but thanks to the activation in the hypothalamus, can't hear, your brain can't hear the ghrelin anymore. So it's just gone to the volume, right?

39:00Dr Federica Amati: So that's what actually changes people's drive to eat or hunger, as you'd call it. Like that's what we would say, it just turns your hunger down. It also turns down your desire for alcohol and gambling and smoking. No. It turns down your addiction side of it. It does, yeah. Because it's a similar pathway as hypothalamus. So actually the trials that are happening now, and this is trials only, it's not in patients yet, this is trials. But the trials that are happening in addiction show that GLP-1 receptor agonists may be one of the drugs that we could help people to reduce their addiction behaviors with.

39:36Dr Federica Amati: Now, of course, addiction is super complicated and there's lots of other factors, but how amazing to have a drug that literally just turns that down. So it has those effects. Is that the positive? It is. I think that, again, it would have to be a different formulation because there's other considerations with physiology with addiction. For example, you certainly wouldn't want a heroin addict to lose a lot of weight because typically they're underweight. But it's about the dose. So I think in the future there'll be different dosages with different combinations that may help with addiction medicine.

40:06Dr Federica Amati: Breakthrough, we haven't had anything very successful for a while. So that's interesting. It does also change drive for other things. So depending on which paper you look at, some papers report that people have more sexual desire when they take these medicines, whereas others find that their sexual desire is dampened and it affects their relationships with their spouses, with their partners. Now, what's interesting there is that if you're a man and you are overweight, you have excess adipose tissue, excess fat, it changes your testosterone levels because there's an enzyme produced by fat tissue called aromatase, which literally flips testosterone into estrogen.

40:42Dr Federica Amati: If you lose a bunch of weight, a bunch of fat specifically, the aromatase goes down and your testosterone levels stay up. And so suddenly men have more sexual drive. So for me, there's a 50-50 split between the patients who seem to have increased sexual desire and those that don't, that actually have decreased and they consider coming off the medication because of the effect it has on their relationships. And for me, and I don't know if this is true, but this is a hypothesis, it shows you which patients have more of these receptors on their brain. So I think the ones who lose sexual desire are more responsive in their brain.

41:18Dr Federica Amati: so the reward pathway is so dampened that they start to feel the effects there's also reports of yeah it changes it changes people's mood so um what does it do to the mood it will i've worked with people who've had to stop taking it because they felt depressed on the medication so you know there's so much there's a brain it's a brain drug and i think that's often missed in the conversation so for people who are thinking about buying these medicines to take them recreationally or to take them because their mates are or because they want to lose some weight before a holiday or a wedding like just i would urge everyone to think twice because these they're not supposed to be used by you first of all second of all they have an impact on your brain so it's not you're not just losing weight um they also impact your pancreas so this stimulation of the pancreas to release more insulin actually if your blood glucose levels are fairly stable and you don't have any metabolic issues.

42:11Dr Federica Amati: We don't necessarily want to be doing that. And then, of course, there's the gut effects, right? So the way GRP1 changes your gut is that it slows down that lovely peristalsis, you know, the gut motility that keeps your food moving and your everything moving through. It slows it down quite a lot. In very rare cases, it can completely paralyze it, gastroparesis, which is a very serious side effect, and it's not very common. but that's how powerful it is so what happens is when you eat your food sits in your stomach for way longer than usual so you'll get full very quickly because actually our stomachs aren't that big and if they're not emptying then it's just going to sit there so it sits there so you've got the fullness in the brain and then you've got that uncomfortable like my food is right here feeling you stop eating and you really should stop eating so never eat past the point of fullness if you're taking these drugs.

43:03Dr Federica Amati: And that slowing down of the entire movement also, of course, changes how your gut environment is, because typically a healthy gut has a transit time of about 20 hours. So you don't want your food to be in your gut for too long. There's variabilities between people. So if you're really, really tall, your gut's probably a bit longer. And actually, gut length varies quite a lot. But generally speaking, you want things to keep moving. With these drugs, it slows right down. constipation risk is much higher. And one of the main things that I'm super passionate about is if these drugs are being prescribed for patients who already have some metabolic dysfunction, right?

43:39Dr Federica Amati: That's the point. Oftentimes they already have, not always, but they do already have like not great gut health. They tend to already suffer with some constipation or IBS or potentially reflux. And if you give them this medication without preparing their gut at all, so without doing anything to try and improve that, it's only going to make it worse. So that preparation before the drug, taking the drug, is so important for trying to make the whole journey a bit smoother for everybody and not make it such a hard ride. So the constipation can be really painful and uncomfortable. And then the nausea is often associated with the day that you increase your dose or your first day.

44:21Dr Federica Amati: and that's it's just to do with the with the gastric emptying being so slow in your stomach acid builds up until you have increased risk of vomiting and nausea so it's not um i think one of the other myths that i see is online it's like this is the easy way out you're such you're such a cheater for taking these drugs you could have just worked harder yeah i don't think so these they're not an easy ride these drugs um and there's listen patients who take them and see the results uh there's one journalist who i adore and she's written about her success story about on these drugs and she'll say oh i would do it again all day because it's just transformed her life and this is where the importance of the risk benefit so if you are someone who has metabolic dysfunction and has struggled with obesity all of your life obviously this is a benefit yes outweighs it so you so it's funny people are online they're like it's changed my life i would do it all again i love it i'm like great you're the right patient but if you're not someone who actually stands to have this really great benefit risk uh like ratio then think about it it's not an easy thing it's not an easy ride it's not there's a firstly you're so right and now what's happening i think a little bit which is where if someone looks skinny they're automatically being said that oh they must be on these skinny jabs so sophie my wife who she had a baby and then she worked hard lost the weight and she's naturally slim as well and she was criticized in a way for yeah for being on one of these skinny drugs right which is kind of sort of upsetting in a way i suppose but you know that that actually there's adverts targeting post like i'm very angry about this but there are adverts that target postnatal women with these drugs and let's be super clear the postnatal period is not one to start messing around with reducing your dietary intake, especially if you're breastfeeding, right?

46:19Dr Federica Amati: Your nutrient requirements are really important and they're high. Like postnatally recovery requires a lot of nutrients. So what we haven't spoken about is like what happens with these drugs is that there's all these cool effects on your brain and pancreas and gut, but the result is that you eat up to 40 % less than without these drugs. And that's a shock on your body. That's a lot. That's a lot less energy every day. And it's not just about the energy. All the nutrients that come with that food are also reduced, right? So the risk with these drugs is that if you're not guided through and the importance of nutrition isn't highlighted and you don't have a bit of a plan of what to do if you need to come off them and you don't know what things to look out for and how to manage your symptoms, all these things, you're running the risk of medical malnutrition because you're literally halving, nearly halving your food intake.

47:13Dr Federica Amati: And oftentimes, you know, if you haven't already established the kinds of foods that are important to keep, it's not always actually. I've seen people's food preferences change on these drugs. So that's a good thing. But the data tells us that generally speaking, it changes the amount of food you eat, but not the quality. So if you don't have a good nutrient-dense diet before you start these drugs, the risks are higher. So this is another thing. It's like actually taking these drugs means that you really have to double down on nutrition. You have to work harder to make sure you're getting the right foods than you did before.

47:48Dr Federica Amati: You have to be consistent with your exercise. If you don't resistance train, then your lean mass is going to suffer. Because you lose the muscle. And bone, yeah. You lose muscle and bone. And this is not unique to the drugs. So if you went on any massively restrictive diet, if you went on a cabbage soup diet, which is ridiculous but it was so popular wasn't it for a while um if you did that you would lose a ton of weight and you would also lose muscle and bone because your body runs out of nutrients it needs now we don't have a reservoir for protein so protein is essential for all your enzymes essential for all dna transcription it's essential for your immune system so if you don't get enough protein in your diet your body will get it from your muscles it'll just break it down and so this is not but this is it's a true finding so in some depending on which study you look at between 20 and 40 percent of weight lost is lean mass but this is true of any restrictive diet weight loss so it's not unique to glp1 i i see instagram posts where it's like they melt your bones no they don't it's just any kind of serious dietary restriction it's not unique to these drugs but if you undernourish yourself your muscles and your bones will suffer and the way to combat that is primarily resistance training so if you have to give your muscles and your bone that friction that pressure that signals the body that you that it needs to maintain it that it's working that it's needed so the resistance training does most of the work and then adequate protein makes sure that there's actually protein to go there and keep the strength

49:29What are the long-term effects of taking these drugs?

49:32Dr Federica Amati: This is a great question because also I think now what I'm seeing more and more is like people who have reached their target body composition and they want to come off. And they're like, what do I do now? How do I stop taking this? And so basically what the population data, so the real world data, not the trials, because the trials we have for these specific formulations, I mentioned earlier that versions of GLP-1 receptor agonists have been around for a long time. So there's about 20 years of medical practice where they've been used, and they're safe and effective for managing type 2 diabetes.

50:04Dr Federica Amati: What we don't know as much about is the long-term use for Monjara and the formulations and the drugs that are used for obesity. So we have about the longest... So Monjara is different? Yeah, Monjara is a dual agonist. So it's GLP-1 and GIP, and it causes more weight loss than semaglutide, which is the original sort of type 2 diabetes one. Xenpic. Xenpic, yeah. Xenpic and Wigovie. So we have about five years worth of clinical trial data for those formulations. So that's not really super long term. We don't actually know. What we know from the real world data is that about 60 % of patients stopped taking it in the first year for various reasons.

50:46Dr Federica Amati: Number one reason, do you want to guess? Don't know. Access. so it's expensive so they couldn't afford it couldn't afford to keep going okay love this the side effects is another reason for people to stop taking it yeah side effects are low mood no the gastric ones the gastric ones the vomiting typically it's reported as the gastric ones but it's side effects it could be low mood it could be a combination it's usually more than one so people stop taking it and then what happens is if you follow those people up a year later those who then start putting weight on again or feel their blood glucose is not staying stable basically not being regulated well come back on the job 50 of them go back on so we have this pattern in people who kind of go on it then mostly stop not necessarily because they want to but they have to then they see that they start to regain weight again or that their blood glucose isn't great again and they go back on it so at the moment it's quite cyclical right for a lot of people but then there are a minority of people who take it and as i said get to this point where they've pushed past so plateau you may have heard that term um all weight loss reaches a plateau at some point because our bodies are so clever do you remember we talked a lot about homeostasis last time yeah so at some point even with this massive calorie restriction our our metabolic system adapts to functioning at that lower calorie intake basically and so you reach a plateau so about 18 months in for most patients they stop losing weight sometimes it's earlier sometimes it's like six months and so they hit this plateau and they're not losing any more weight and they're like what oh my god this is so stressful it's normal it's a normal physiological response it's your body trying to keep you alive it's your body saying we need to yeah yeah okay so so people but people push past that then they sometimes increase dose or change medication at that point so they might go from wagovi to manjaro um and then they get to the body composition that they are trying to get to and we're talking about people who are losing you know 20 30 kilograms of weight so this is this is going from obesity to within normal range for and not just bmi bmi is a metric but it's bmi it's adiposity it's body comp so all these things waist to height ratio my favorite measure um and they get there and they're like okay now you can either stay on a very low effective dose to maintain the weight loss, which is certainly what the manufacturers would like.

53:09Of course.

53:10Dr Federica Amati: Because it's good business. And it is genuinely what some people will need, okay? Or many patients are like, I kind of want to tighten it off and they want to stop taking the drugs and see if they can maintain the weight loss as it is. Let's rewind to the beginning of the conversation where I say we live in an obesogenic environment. So having to stay on a lowest effective dose to maintain the new body comp may be necessary for some people. And that's not because they're a failure. It's because the environment we live in, unfortunately, drives weight gain. But for some people, and in my clinical experience, I don't know if there's data for this, but in my clinical experience, people who have lived with obesity all of their lives are typically the ones that may need some maintenance dose.

53:52Dr Federica Amati: Those who have more recent obesity may be able to come off entirely and weight will fluctuate. So it may rise back up a bit and move around as it should, but actually they're able to maintain the body comp, able to maintain a new weight range, which is super exciting. That requires work. The work doesn't finish there. But we don't know what happens to someone who's been taking this drug for 20 years because they haven't been around in this formulation for long enough. What the theory is, is that if you're helping someone to move from the risks that are associated with living with type 2 diabetes and with obesity, then it's going to be worthwhile so whatever the side effects or the long-term side effects are then if they're managed correctly it should help that person live a longer healthier life now that was that's the good side what happens when they're mismanaged so what could possibly go wrong if someone takes this medication and they're not as supported properly the biggest concern is what's called sarcopenic obesity which basically means that you have more fat mass and very reduced lean mass that puts you at risk of frailty.

55:03Dr Federica Amati: So this accelerated frailty, sometimes it's called in the headlines, is the risk of the other side of the story, where if you have somebody who is given these medications and they have rapid weight loss, they don't have supportive nutrition and they don't have supportive resistance exercise, then they stop taking the drug. 75 % of patients tend to regain weight and to about 75 % of the weight lost. So about three quarters of the weight. Some people regain 100 % of the weight and a minority regain it above. When you regain that weight, you're not regaining bone and muscle. You're regaining fat.

55:40Dr Federica Amati: Our body most effectively gains mass as fat, especially when you're exiting a famine. So if your body is in famine mode, which by the way, your body doesn't know if you're taking a medication or you're actually starving. So when your metabolism kicks back in to regain as much lost energy as possible, it will store this as fat. So the real problem here is that you could actually, and this is a warning for anyone who doesn't need to take these medicines. Say you take these medicines because you want to lose a stone. You don't have obesity. You don't have metabolic dysfunction. You take the medicine and you're like, I'm just going to lose some weight.

56:16Dr Federica Amati: I'm not going to resistance train. I'm not going to do the nutrition. I'm just going to do that for the wedding. what could happen is that you lose the weight but you haven't done any of the work to retain the lean mass and then when you stop the medication you'll regain the weight all as fat mass but you in the meantime you may have lost up to 40 percent of that weight from your lean mass wow so you'll you'll be you have no but you're not getting any more muscle your bone density has gone down and you're just gaining fat yes and so then sarcopenic obesity is where this this there's a real disparity between the fat mass and the lean mass.

56:50Dr Federica Amati: And that's the real danger. Why is that a danger? Because when you have even more reduced, first of all, your muscles are a metabolic organ. So they really help to regulate things like risk of type 2 diabetes. So if you have reduced lean mass, you're actually increasing your risk of type 2 diabetes. If you have reduced bone mass in, say, midlife, so this is happening mostly in midlife, then your risk of osteopenia, osteoporosis later in life is higher. And when you get into your 70s, 80s, 90s, falls and fractures are one of the biggest causes of frailty and death in older people you don't want to have weaker bones it's not it's not protective it's not in terms of longevity so it's really thinking about some thinking ahead if you want to have an independent older age you need to have a good lean mass you need to have a really strong good lean mass and the best way to do that is to protect it one of the best best ways to do that is to really go back in time and build it in your 20s and so where i also get quite worried there was a famous influencer who posted a video about the fact that she took glp1 receptor agonists for a while and just for aesthetic reasons and then she came off them and her doctor said you have osteoporosis she so she'd actually malnourished herself enough to get to that point now in your 20s is when you're you have max capacity to build bone and muscle mass right into your early 30s, right?

58:14Dr Federica Amati: And so the biggest warning for this, and it's interesting because talking to different healthcare professionals, where I sit sort of in the middle, so I get to talk to everyone, obesity doctors are like, yes, this medicine is everything we've been waiting for. Because it's one of the biggest killers, right? Yeah, because obesity is so hard to treat unless you have bariatric surgery. It's like such a hard thing to treat, right? And now we have a medicine that works. Then you speak to people who work in eating disorders and they are literally like, ah! I spoke to someone recently who works in a psychiatric unit in London and she shared with me that they've seen a huge increase in people taking these medication who developed an eating disorder or that the medication like re-sparked an eating disorder for them and they had to check themselves in.

58:56Dr Federica Amati: So the dangers of young people accessing these drugs on TikTok and often they're accessing compound drugs versions so what does that mean it means it's not from the pharmaceutical companies it's like some lab that's making knockoff versions and so we go back to the risks of the peptides where you don't know what's in there yeah so the fact that they're so easy to access and the most vulnerable population for this is girls in their late teens early 20s the risk that they are undermining their long-term health but like really long-term health with the loss of lean mass wow is huge. So it's short-term, they're looking short-term rather than long-term.

59:38Dr Federica Amati: Yeah, and it's very hard to build that back. So that's the kind of dangers, right? I think it's important to point them out. I think it's also important to point out that there was a paper recently that analyzed the weight loss patterns in people with obesity. And actually what it found is that the first three months of prescription, because you have excess adiposity, so this is critical, the right patient group that was taking Monjaro, they saw that the majority of weight loss in the first three months was fat. So if you have excess fat, as people with obesity do, they will lose that first. And then it will become more about the lean mass to fat mass balance.

1:00:21Dr Federica Amati: And it's around six to nine months where you really have to put the work in for the resistance training and making sure that you're preserving lean mass. So all these risks of increased lean mass loss are more pronounced in the populations that might be taking this recreationally who don't really have an excess fat mass to lose and it's really important that we underline that because as i said this drug is being taken as a lifestyle drug because we're obsessed with weight but anyone who thinks about taking this and doesn't need it i say to them would you do this with an anti-hypertensive Would you just take a blood pressure medication for kicks?

1:01:00Dr Federica Amati: Would you take insulin for kicks? Because this is the same metabolic health, right? And these are very important hormones that do important work. So would you do it? Or is it just because we live in a society where weight is such a focus? And actually, weight doesn't always reflect health. So that's another thing. So one of my friends, she's wonderful. and she said to me and I love this her name is Rose Stokes she's a journalist and she said you know health is not a meritocracy And people can work really, really hard and be really consistent and go to the gym and like eat really well and have worse outcomes than someone who barely makes an effort.

1:01:46Dr Federica Amati: And the problem with like pinning weight to healthfulness is that people who are just genetically more likely to be slim and find it quite easy may be attributed as being more worthy of health than someone who's trying really hard but just doesn't live in a very slim body. So we have to, yeah, I think we have to be really clear that these medicines work exceptionally well for the patients who need them. They can be transformative for people who have struggled all of their lives. And you hear so many patient success stories. And in the same breath, they can be really dangerous for someone who doesn't need them.

1:02:24Dr Federica Amati: And can even, you know, anorexia is already the deadliest psychiatric condition in the world. And what we don't need is to drive up that death rate with a medication because access is too easy. so there's always two sides to the coin so people say to me oh are you pro-drug are you pro-drug i was gonna ask would you would you take it for me no maybe you wouldn't no but it's not that you need it but if you did need it would you take it yeah so if i developed type 2 diabetes or if i ended up living with obesity then i would go to a doctor who could do all the screenings look at my liver look at my pancreas do a really good assessment uh look at my history of eating disorders like really get a good picture and then make a decision of course but it's it has to be thought of as carefully as that and so i'm not pro-drug or anti-drug i'm pro-patient like it's the person is it depends on the person it doesn't depend on whether the drug is good or bad right but tell me this so if someone's listening to this right now right and perhaps they're going shit shit because shit because i've been taking it okay and i've been taking it for aesthetic reasons or I've been doing it because I have a wedding coming up and I needed to feel that I wanted to fit into my wedding dress or perhaps a guy's done it because, you know, they're being bullied at school.

1:03:41I don't know. Loads of different reasons, right? But they're maybe young teenagers or in their 20s or whatever it be. And they listen to you and they go, oh, I want to change it.

1:03:49Dr Federica Amati: What steps do we do now to change it, to make it better? Yeah. So the first thing is don't just try not to, if you can. Don't just stop taking it. Don't just go cold turkey. try to titrate down. Now if you're not already under the care of a doctor who's responsible in prescription and I can actually speak to you so if you try and find someone who can it can be your GP it can be they may be able to point you to the right place. So speak to a healthcare professional don't just come off straight away and look to titrate down slowly so that you give your body time to readapt to essentially not having that really strong metabolic signal coming in.

1:04:33Dr Federica Amati: At the moment, it looks like titrating down is better for avoiding that rebound fat gain that we talked about. However, if your side effects that are bothering you are psychiatric mental health, so if you're finding that you're really depressed or it's affecting your mental health in a way that you can't be a good parent or you can't go to your job, then actually it might be best to stop. Now, the point is, I'm not a prescribing doctor for these medications, right? There should be a prescribing doctor who is looking after you. So whoever prescribed you the drug, speak to them and talk about your options considering your entire medical history.

1:05:11Dr Federica Amati: If there isn't a clear path for that, which there really should be for all providers, and I hope that there's more regulation for that, then find a GP, find a doctor that you can speak to and try and access that care as soon as you can. If you've bought them off the black market, so if they're compound drugs, stop. Because who knows what's happening there. And then try it like, I find that people who have side effects that stop them from taking the drugs, do it quite quickly. They like, no, it's not for them. If you've been feeling okay, actually, but now you're just worried because you've listened to this and you realize that you potentially haven't been looking after your nutrition, you may have under-consumed nutrients, you might be lacking is your hair falling out is that's one of the classic signs um of especially in women ferritin dropping so low that their hair falls out so have you had some symptoms some some signs that actually maybe you're not getting what you need from your diet skin cracking dry skin um then really start looking at nutrition if you haven't done this like make sure that every time you eat it's it contains lots of nutrient dense foods now one of the worst mistakes i've seen is that people will take this drug and then diet with it.

1:06:22Dr Federica Amati: So they, because, but that's diet culture is like, essentially the problem is that especially people over the age of say, I'd say like over the age of 35 now, they've grown up with this idea that the less you eat, the better. So actually, if you just don't eat, that's pretty good. That's a good thing. If you can survive on fumes or, you know, the famous Vogue diet of the cigarette, the steak and the glass of wine, then you're doing really well, right? So it's really hard as a mental switch to say, actually, on these medicines, I need to make sure I'm eating enough. Start to make sure you're doing that.

1:06:56Dr Federica Amati: If you need to take a multivitamin, you can. Don't fall for these GRP1 magic combinations. There is no such thing. A normal multivitamin is fine. There is no approved or tested GRP1 supplement that's been actually tested in GRP1 patients. So it's all marketing. and then and then resistance train so maybe you haven't done it so far maybe you've never done it but certainly if you've had this rapid weight loss or if you're taking these medications start and that might look like just doing own body weight squats it might look like lifting tins of baked beans in your house or buying you know those bands from amazon or wherever you like to buy your bands and just doing some form of resistance training it doesn't have to be in a gym or high rocks or any of these things it just need you need to put some pressure and feel some strain in your muscles start doing that three times a week for 20 minutes and build up from there and then as i said like please access a healthcare professional who can actually help you change the prescription titrate down change change the agonist or completely discontinue but again people shouldn't be accessing these medicines without appropriate care and we just haven't had the resource to grow the support around these drugs as quickly as they've grown in popularity.

1:08:16Dr Federica Amati: So the way that all of the guidelines live, they all say that every patient should have full nutritional support, that's me, full exercise physiology support, right? So like in an ideal world, you actually have someone teaching you how to do this stuff, and psychological screening. And so that's how they're supposed to be prescribed. So if that hasn't been the case for you, then know that there's missing pieces to your prescription. You've only been given like maybe half of what you're supposed to be receiving. And particularly with these medicines, nutrition plays a really big role because as we said, it just massively, drastically reduces your food intake.

1:08:57Dr Federica Amati: And just because you've reduced your food intake, it doesn't mean your body needs less nutrition. In fact, if you are living with obesity, typically people who live with obesity have higher micronutrient needs because they have a bigger body. So it's a balance that you have to maintain of nutrient-dense foods. What are nutrient-dense foods, I hear you ask? It's whole foods. It's fruits. It's vegetables. It's legumes like lentils. It's soy foods like tofu. It's eggs. It's oily fish. It comes back. It's funny, isn't it? Because it comes back to the Mediterranean diet as a really clear pattern of eating.

1:09:37Dr Federica Amati: Just be Mediterranean and eat. Just come with me. Just come with you and do that. Hang out in Italy for a while. No, but jokes aside, it doesn't have to be Italian food. But the Italians have it right. They surround themselves with family and great food. Well, Mediterranean diet is actually a lifestyle. It's more than the food. It's the conviviality. So if you look at the pyramid, it's the conviviality. it's cooking from scratch, it's sharing, it's spending time outside and playing. So there's lots of aspects to it. But what's really important here is that it doesn't matter if you're not Italian or Mediterranean.

1:10:09Dr Federica Amati: The Mediterranean dietary principles and Mediterranean lifestyle principles are translatable to any culture. It's a way of, it's a philosophy as opposed to being prescriptive with you have to like tomatoes and aubergines. You don't, right? So I think of this as the modern Mediterranean. It's like actually we can translate the pattern to any culture. So So it's accessible to everybody, but it does depend on whole food diets. And the difficulty here is that we live in this food environment, which just pushes non-whole food products. So you can buy bars that are made with no food. I won't name the brands, I'll tell you later.

1:10:47Dr Federica Amati: But you read the back of pack and none of the ingredients are a food. Not one. Not one. They're all additives pulled together. It's not all food. It's not all food manufacturers. There are some wonderful manufacturers. But as a whole, when you go into a supermarket, it's quite easy to see why people consume a majority ultra-processed foods. Because they're cheaper. They're sold. They're marketed. They've got really jazzy signs. There's two-for-ones. And also the marketing is so confusing. And with the GRP1 now, there's marketing directly to this population. Can I tell you how angry that makes me?

1:11:27Dr Federica Amati: Because can we talk again about the fact that GRP1 receptor agonists are prescribed to patients? These people are a patient population with metabolic dysfunction, and you're creating like a high-protein dessert for them. Shame on you, not you, Jamie. But do you know what I'm saying? Yeah, I know. How are we... It just blows my mind how you might create a food product that is fundamentally unhealthy. Slap a high-protein label on it, which, by the way, is so easy to get. 20 % of calories from protein. That's what you get in a glass of milk, right? It's not a hard bar to get a high protein stamp on the front of your food product.

1:12:04Dr Federica Amati: And people then buy it and they'll spend their hard-earned cash buying food products, because they're not actually whole foods, food products that aren't helping them to be micronutrient replete, to get the nutrients they need. So whenever you see a packaged product, now I've started to see nutrient dense on front of pack for this population. Because you know what? GLP-1s are changing the food environment. In America, it's going to happen here because America is just a bit ahead of us. But as we go, we've hit 2 million people taking these drugs. It's going to go higher. In the UK, yeah. Whoa. And that's the people that we only know, right?

1:12:39That doesn't even have the black market.

1:12:41Dr Federica Amati: So these are prescriptions. These are prescriptions. Yeah, yeah. Not NHS. This is prescriptions, NHS and private, but not black market exactly. So in America, they're a bit ahead of us. They're at like 11 million. So they, if you imagine like, it's now one in six Americans, I think, that take GLP-1 receptor agonists. Their food industry is changing because their alcohol consumption has dropped off a cliff. Because people aren't drinking because no one has the appetite to drink. Yes, you don't have the same drive. You don't have the same drive. And so then now the beverage companies are like, okay, what are we doing?

1:13:10Dr Federica Amati: So there's now, if you go to America, the fridge is of like adaptogenic drinks and this sort of like gut healthy pops and there's so many new drinks that are non-alcoholic. It's wild. So there's like teas and all sorts of things, right? And then you have a change in actual food preference. So crisps sales are going down. People don't want to eat crisps anymore. Because you're eating? Pastries. Well, very high saturated fat foods, so like crisps, for example, fried foods as well, donuts, will make your reflux fire right up. So people aren't consuming it because... Because it makes your symptoms worse.

1:13:47Dr Federica Amati: But actually, apparently, and we don't know if this is true, it's not just symptoms. So GLP-1s are changing the supermarket. They're changing. Yes. And you know why I love that? Because I've been saying for years that your purchasing power is power. So when people feel quite helpless in the face of the food environment, and they're like, oh my God, how do we change this? Because it really, policy is the best way to change it. If there are policies in place to restrict the amount of this food that's been made or how it's marketed, if you could just strip out the marketing and stuff, it would change the food environment.

1:14:17Dr Federica Amati: But until we get there, it feels hopeless for the individual. but actually every penny we spend on the food we buy changes the food environment if you don't buy it they can't sell it to you correct and so this and i say this and it's like yeah that sounds nice in theory but you know advertising is super powerful and so is marketing and but you see it's happening with glp ones people are genuinely changing what they buy so i can't work out if that's a positive or negative good thing it's a good thing so the glps are a bad thing but actually no no no the glp ones but for the population they're intended for it's a good thing so these people that are taking these medicines and have struggled with their weight and with eating healthily all their lives suddenly have a freedom to be like, actually, I'm not going to buy those.

1:14:57So the people who typically have a bad diet, the ones who are eating junk foods, that is now declining because people are not consuming it as much.

1:15:05Dr Federica Amati: Yes. So the purchasing power is actually making the food industry pivot. Now, the bad side of this is that... Well, you could predict... That's a powerful position to be in because you could predict the next wave of craze within a supermarket. Yes. You can start to see in the data already through survey data what people are buying more of. So you already know. So the food industry is already responding by being like, what do we make next? That is wild. So in some ways, it's good, I think, because it shows the power of purchasing at individual level and what happens. If everybody decided to stop buying, I'll give you a non-related example just to show it.

1:15:44Dr Federica Amati: if everyone decided to stop buying chocolate that was made using slave trade, because, you know, a lot of chocolate manufacturers enslave children to make chocolate. And everyone was like, whoa. That's the great thing about Tony's, right? Which is where they say their whole ethos. So there's good brands that have actually gone away from this. But if everyone was like, whoa, I'm not doing that, and stopped buying those chocolate brands, they would have to change something. They would have to stop using slaves, for example. So this is the positive. Now, the skeptical side is that the food industry will do something about this and will change something.

1:16:15Dr Federica Amati: So there are reports that there are some companies that are really looking at how they can bypass the satiety signal and create new ranges of foods that are hyperpalatable, even if you're on these medicines.

1:16:32Dr Federica Amati: So I haven't seen this work. I've been told by reputable sources that it's happening. but to be seen whether it like rolls up. But you can imagine that they'll find a solution. These are companies that need to make money. They need to make profit. So like, what are they going to do to do that? And we'll see what happens. Can I ask you two questions? One is, what is, and I remember you told me this step, but I want to remember, what percentage of the food in the UK is ultra processed? So what we have data on is the percentage of calories consumed from ultra processed foods by British people. And it's between 52 and 60 % on average.

1:17:05Dr Federica Amati: Now it gets worse for toddlers. teenagers it's up to 72 percent which is what is an italian and also older people um 14 yeah do italians live longer on average yeah we have a average life expectancy between 86 and 88 years which is about 10 years more and the uk is 78 and you think it's down to diet definitely it's definitely part of it right i mean a big a big part of a longevity is diet which is why i was furious when well when i see books on longevity that have like a page on diet i'm like are you okay diet is so important but and you know diet is important i think it's it's so important not because it holds like superpowers but because you do it every day so when you look at when you look at jamie the six things yeah that are well understood to essentially structure 80 of your chronic disease risks that's quite a big number yeah they are all free and they're all to do with what you do every day so we have diet and if i had to like encapsulate it into one sentence it's eat mostly whole plants that's that's the way to make it easy so it's a plant forward not vegan but plant forward diet mostly from whole foods great and then Mediterranean diet if you want to see the kind of food groups exercise and that doesn't mean going to like a Barry's boot camp every day although i used to love that in my 20s now i'm like it's very loud in here isn't it yeah I'm in a nightclub in the morning and everyone's topless.

1:18:33Dr Federica Amati: So, but it doesn't have to be like, you do what you like. The most important thing about exercise is that you do something where you can move your body every day and enjoy it. A walk, a run, a jog. Because then it means you do it. Dancing, it can be groups. Like it's actually, there is some nice evidence that if you do exercise in a group, it's really good for social cohesion too, which is number three. Not bad. So social cohesion is one that is hardly ever spoken about. I've not yet seen an influencer, a topless influencer in a supermarket telling you how important it is to look after your friends and spend time with them.

1:19:04Dr Federica Amati: But it's actually one of the biggest levers, right? This is my next LinkedIn post. That is so great. It's the six pillars of lifestyle medicine. And they are literally, so when we look at risk factors for chronic disease, these six pillars account for 80 % of risk. If you can achieve four or five of them, you reduce your risk. So what are the six I go through? So you've got diet. diet mostly plants whole foods correct exercise move your body every day throughout the day another thing that is really common unfortunately now is people who have eight hours a day at a desk and they do like a one hour berries or like one hour really stressful workout and they don't move throughout the day we our bodies actually do need to move so walk after lunch a walk to work if you can like find ways to move your body every single day several times a day not just once in the morning.

1:19:54Dr Federica Amati: Social cohesion, social connection. It's so important. So for my PhD, one of the things I put forward in my thesis was that we should be measuring social function as a health outcome when we look at patient success. Because disease cutoffs are interesting and they're useful, but actually if someone's social function improves, their overall health improves. So social function, and that means talking to someone you love, lots of data about, it's not about the number of friends you have, it's actually having like four or five really good friends that you can call up have a chat and they're there for you and when you spend time with them it recharges your battery then this one there's avoiding risky behaviors which are really this doctor in america who's got a book out at the moment he calls it don't be a schmuck but yeah it's basically like don't drink loads of alcohol yeah don't smoke cigarettes don't gamble don't like you know don't go out and take cocaine every weekend and expect it so there's risky behaviors that we know are bad for health and just reduce them as much as you can or avoid them if you can right um then so we've done diet we've done exercise social cohesion avoid risky behaviors sleep a big one so sleep is i think now we've moved away from this idea that like i'll sleep when i'm dead yeah when i was growing up that was definitely the narrative yeah yeah yeah you should yeah exactly don't sleep when i'm old terrible terrible james dean live fast die young what this is terrible things so it's like so genetically speaking very slow and sleep lots and it's interesting because there are what's known as um super sleepers it's a very small percentage of people and i would encourage everyone to think that they're not one of them so these are people who only need sort of maybe five hours of sleep and actually that's enough for them very rare not most of us are not like this so sleep seven to nine hours on average for most people look after your sleep.

1:21:43Dr Federica Amati: It's important for you. And then the last one, again, I'm very passionate about this as I nearly hit 40, Jamie. Stress mitigation. What does this mean? Stressful events will happen in your life. People will die. People get sick. You lose your job. All sorts of things happen. You can't really change that. Although I do like the influencers who are like, just don't let stress happen to you. It's like, you can't do that. But how you handle the stress has a huge impact on your life. So in the same way that you go to a trainer to learn how to exercise and you might go to a nutritionist and more about your diet, learning how to manage your stress requires a toolbox and there's no shame in learning how to manage it.

1:22:20Dr Federica Amati: Whether it's meditation, walks in nature, art, journaling, there's so many modalities that can help with stress management. Of course, seeing a good psychotherapist is a huge one too. So those six pillars alone explain like 80 % of chronic disease risk. And as I said, if you can get four or five of those in your life, you're actually doing really well and you're reducing your chronic disease none of them cost any money none of them are a supplement none of them are a specific diet or regimen and the thing about it is that it's simple but it's not easy so again if we live in the uk as we live trying to do all those six things if you live in an area where there's plenty of places to walk and it's safe and you have access to green space to exercise and you can afford to buy healthy food and you can afford to see your friends and hang out with them because you're not working 24 hours a day so therefore you sleep and you have access to tools then you can do it but there is also a disparity in access to these pillars in our society so whilst it's simple it's not easy for everyone but it should be it should be a human right to be able to do that

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1:25:10Okay, so we'd like to end our conversation with eight quick fire questions. What's a saying or phrase that you would like people to take away from this conversation with?

1:25:17Dr Federica Amati: Just take away that being healthy and staying healthy is actually something you have to put effort into. And so anything that is trying to sell you a quick fix or something that's a miracle cure is not looking after your health. And it can be harder for some people than others to be healthy. So don't blame yourself. That's a structural issue. Best compliment someone's given you about how you've changed the way you think about food. Yeah. So by far, it's when people say to me, thanks to you, I really enjoy food again now. And I know that it's good for me and it can help me feel better. Amazing.

1:25:51What's the scariest thing about people's knowledge or lack thereof when it comes to nutrition?

1:25:55Dr Federica Amati: The scariest thing is just how vulnerable people are to misinformation. Nutrition misinformation is rampant at the moment. What's your guilty food pleasure? There's no such thing as a guilty food pleasure. Food is great. One of the things, well, you know this because I've told you so many times, but it's not mine, but my girls love candy kittens is it candy kittens kitten candies i call them both they so we actually uh yeah we have them in my house and they love them and i'm just i like that they're made well basically i love dark chocolate which is not at all guilty i love food what i don't have any guilt about it what's one thing we can all do today to build a healthier relationship with food learn to cook yeah so if you i'm in that space at the moment if you because most of us aren't taught and if you didn't have a family that taught you which is quite common it's a really good skill to gift yourself so learn to cook and it will transform your enjoyment of food and your kids as well what's something that people are most embarrassed to admit about nutrition i think what people are quite embarrassed to admit that they don't know what to do next and that they feel lost and that they feel like they're doing everything wrong that's what i hear a lot what's one thing you've learned whilst researching your new book, The Appetite Reset, that generally surprised you?

1:27:11Dr Federica Amati: I think one of the things that really surprised me was in pregnancy, exposure to some of these hormones that are associated with appetite, it changes the hypothalamic structure of the baby, the baby's brain. What's really interesting is just the transgenerational effects of how our appetite has been handled by the food industry. Yeah, basically. Last one, what are you most proud of with all of your work? Anytime someone says that I've helped them in any small way. So I'm actually, I'm very lucky because I feel proud most days. If I can help someone feel like they can be healthier and happier and less stressed about their health, I feel like I'm doing my job.

1:27:53Dr. Federica, thank you so much. You are beyond great company. I really appreciate it. You are amazing.

1:28:05Do I want the diet, the diet, the diet?

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