The 4 rules to protect your muscle, bones, and brain health when using Ozempic and other weight loss drugs with Dr. Federica Amati

Ozempic, Wegovy and Mounjaro can help people lose weight. But what should you eat on GLP-1 drugs to avoid side effects, protect muscle, and maintain results long term?

In this episode, Dr. Federica Amati, ZOE’s Head Nutritionist and author of The Appetite Reset explains how these drugs work, why many people struggle with side effects, and why losing weight does not automatically mean better health.

You’ll learn why the weight lost may not be fat, why nutrient deficiencies, dehydration and muscle loss can become a risk, and what to eat before, during and after treatment.

Millions of people are now using GLP-1 drugs. But if these medications reduce appetite so effectively, how do you make sure your body still gets the nutrients it needs?

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Actionable takeaways

What are GLP-1 drugs and how do they cause weight loss?
GLP-1 drugs copy a hormone your gut naturally makes. They slow down digestion so you feel full for longer, help your body manage blood sugar after eating, and signal to your brain that you don't need more food.

What is food noise, and why does it matter?
Food noise is persistent, anxious preoccupation with food — not normal hunger, but intrusive thoughts that can take over your day. For many people, the reduction in food noise is the most life-changing effect of these medications.

Why does diet still matter on GLP-1 medications?
These drugs reduce how much you eat by 30–40%, so every bite needs to work harder. Poor diet quality on a smaller intake can lead to nutrient loss, low energy, and poor long-term health — even if the number on the scales is going down.

What are the best foods to eat while taking GLP-1s?
Focus on foods that deliver protein, fibre, and micronutrients in one go — like wholegrains, legumes, oily fish, and Greek yoghurt.

Can you lose muscle on these drugs?
Yes, particularly after the first few months. Resistance training (even simple exercises at home) combined with enough protein throughout the day is the best way to protect your muscles.

What happens when you stop taking GLP-1 medications?
Hunger usually returns, and without lifestyle changes in place, weight tends to come back. Stopping slowly, eating plenty of fibre, and keeping up resistance training give you the best chance of maintaining your results.

Jonathan: Can these drugs change your behavior beyond food?

Federica: Yes.

Jonathan: Do Ozempic or Mounjaro work for everybody?

Federica: Not necessarily.

Jonathan: Can taking GLP-1 drugs lead to muscle wasting?

Federica: Yes.

Jonathan: Do people need to be on these drugs for life?

Federica: Not always.

Jonathan: And finally, what one thing should everyone know before taking Ozempic or Mounjaro?

Federica: These drugs help to reduce your appetite, but they don't help to improve a poor diet.

Jonathan: These GLP-1 drugs, like Wegovy and Ozempic, have taken the world by storm. An astonishing 1 in 10 Americans have already tried them, and because of their popularity, we get a lot of questions from people worried about what to eat during treatment to get the best results and stay healthy, both for themselves and for loved ones. So I'm really delighted to have ZOE's head nutritionist, Dr. Federica Amati, with me today, and you have now just written an entire book, The Appetite Reset, which covers these exact topics because we've been having so many questions about them, and that book is available for pre-order now.

Federica: That's right.

Jonathan: So that's really exciting. Let's start with the basics, Federica. What are GLP-1 drugs?

Federica: So GLP-1 drugs are a group of medicines that basically acts like a hormone that our gut produces, so they're the same sort of structure. So if you imagine, we've sort of taken the shape of this hormone, copied it, and created a drug that acts in the same way on the receptor, but doesn't break down so quickly. The drugs have a much longer life in our body. So instead of being broken down within a couple of minutes, it persists for a week, so it's a much longer duration of effect.

Jonathan: Why do these drugs cause us to lose weight?

Federica: So these drugs literally switch on a system that already exists in us, but just makes it last longer, and they do this by reducing the speed at which your stomach empties, so the speed at which food travels down your gut. This means that your stomach is full of food for longer. And you know that feeling when you're like, "Oh, I'm full. I don't really want to eat anymore"? So that helps reduce food intake. It also acts on the pancreas. So the pancreas is the organ that's involved in making insulin after you eat sugars, and it does this in a really clever way, though. So it actually increases insulin secretion only when you have carbohydrates. So it means that you don't run the risk of too much insulin without the carbohydrates, which can lead to hypoinsulinemia, which could be very dangerous. So these drugs are really clever in the way they help the pancreas to create more insulin. And they also act on the brain, the hypothalamus, right? The hypothalamus is our central control system for appetite regulation, and these drugs go directly to the brain and go, "We don't need to eat. We're not hungry. We're full up."

Jonathan: Amazing. And so they are literally sort of just switching off the need for me to eat just with an injection.

Federica: Just with an injection, you have this massive powering up of our natural body's system that actually has evolved over thousands of years to help us feel satiated and help us go about our day with quite minimal amounts of food. Appetite physiology is actually built for us to feel satiated with quite a little amount of food because for most of our time on Earth, we've had quite scarce food supply. And so the way that this works is actually to be activated with just the right foods to keep us full for a long time so we could continue scavenging and hunting and building our dens and all this stuff. So when we realize that these drugs are just activating a system that's already there, I think that's where the interesting part is, and we can start to unravel, well, why have we got to a point where we actually even need these drugs if that system already exists?

Jonathan: Do they really work, and do you consider them miracle drugs?

Federica: They do work. There's no such thing as a miracle drug. They still have side effects. They don't work for everyone. They're the biggest revolution in metabolic medicine we've ever seen, so that's super exciting. We finally have a drug that can actually help people to improve their metabolic health at a time when metabolic diseases are the leading cause of disease, death, disability. You know, before these drugs, bariatric surgery was the intervention which saw really good results for metabolic disease and obesity, but now with these drugs, it's unlocked its accessibility to millions more people, predicted to be millions more in the next few years. But we know that over 90% of people who access these drugs do so outside of a complete support system, so they don't have exercise support, psychological support, and most importantly, dietary support. That is a problem. So we have this amazing drug. It works. People reduce their food intake by 30 to 40%. That's a big change, right? But without the correct framework around that treatment, you run a real risk of under-nourishing yourself and making the overall metabolic picture worse than when you started, and that's why I wrote this book. 90%, nine out of 10 people accessing the drug right now are doing so kind of flying blind.

Jonathan: And that's because we're mainly getting it a little bit like we might just get something delivered, you know, in a box from Amazon.

Federica: Yeah, and then there's also this sort of online market for the unregulated versions of these drugs, so it's an even bigger problem. So there's a black market of what we call compound drugs, so it's the ones that haven't been made by the big manufacturers. So if you add that on top, you see that there's this real potential for a very powerful drug that's just being accessed way too easy, so there's definitely issues here with how it's being regulated, right? It should be tighter, and they're seeing on TikTok, you can buy it online. You can go to an online pharmacy and fill out your details and never actually speak to a doctor and get the prescription in your post.

Jonathan: Even, yeah, to your point, a box arrives with the drugs with very little support around the dosage, how to increase it, when to stop, but more importantly from my point of view, how to eat, how your lifestyle needs to change, what to expect in terms of side effects.

Federica: You know, what we know now from trials and from real world data is that the best way to manage the gastrointestinal side effects, which are by far the biggest reason people stop, is through diet. It's the best way to manage them, right? So if we don't give people this advice, then we're not really setting them up for success, and by not setting up for success, what we see is this huge drop-off. Depending on which study you look at, it's about fifty to sixty percent of people stop taking the drug within a year.

Jonathan: Fifty to sixty percent of people stop within a year?

Federica: In some analyses, it's two-thirds of people stop because they can't tolerate the side effects or because they can't afford to keep paying out of pocket for it. And so we then have two problems. The side effects could have been managed with diet, right? And the second problem is if you're stopping because of access issues, cost issues, you're likely to just go from max dose to zero, so there's no tapering down, and that is a massive predictor of how much fat mass you're going to regain. So there's so many opportunities for us to make this drug more effective and more tolerated for the population that want to take it and need to take it. And the need to take it point is where as well we're not giving people enough information. I think to your point, Jonathan, these drugs feel like you might just be ordering some vitamin D. People are taking them quite freely, even when they're not in the populations that they're really designed for. We know that a lot of people already aren't eating enough of the right foods to support their health and their long-term goals. And so if they're also taking an appetite lowering drug that drastically reduces their food intake, we're putting their body at even higher risk of under nourishing themselves, and that is a real red flag. You know, if you're a nineteen-year-old girl with a BMI of nineteen, you can buy this drug online and inject yourself with it, and the long-term damage that can do is really quite shocking. And I think we need to empower listeners to understand these risks so they can make more informed decisions about what they're doing, and also really push for tighter regulation on how they're dispensed.

Jonathan: Thank you, Federica. I want to get into all of that. Could I just start with just a simple understanding maybe of what the drugs are and what you're supposed to do if you go onto them? And first off, there's a lot of different names, right? I'm thinking Wegovy, Mounjaro, Ozempic. Are they all the same? And if you start to go onto these drugs, what would the experience normally be that a doctor would take you through?

Federica: So it's important to note, I work with doctors. I can't prescribe these drugs, but of course there's lots of evidence now, so we know what the best practices are to improve success. So Wegovy and Ozempic are both semaglutide-based drugs, so GLP-1 receptor agonists. They're just licensed for different outcomes. So the Ozempic is for type two diabetes, Wegovy is for weight loss, a slightly higher dose. Mounjaro is a dual agonist, GLP-1 and GIP. They're like little mates. They act together in slightly different ways on those systems, on the pancreas, on the gut motility and your brain, but they sort of complement each other. So Mounjaro has more weight loss effect. You lose more of your body weight. Now the way that they're supposed to be taken is, the bit that everyone misses out, is a pre-drug phase where you're supposed to really think about your diet, really support your gut microbiome, because if you actually prepare your gut before you start the drugs, you reduce that risk. So the pre-drug phase, you know, ideally like a couple of months before, it really depends on how your diet already is and how your metabolic health is. So how is your liver functioning? Do you have fatty liver? How is your gut functioning? We'd want to target that and improve everything before you start treatment. The analogy I use in my book, The Appetite Reset, is to think about this like driving a Ferrari. These drugs are like a Ferrari in terms of medicine, but if you're taking a Ferrari on a really dusty, rocky track, it's not going to be a smooth ride. If you take them on a lovely freshly tarmacked road, it's going to be smooth. So prepare your surface.

Jonathan: I love that your Italian ancestry is coming out here with the Ferrari example, Federica.

Federica: You've got to prepare the surface, and we've got to do that by feeding your gut microbiome, feeding your gut the fiber it needs, feeding your liver with the lovely fruits and veggies and healthy fats that it thrives with, right? It will massively improve your experience of starting the drug. So there's a whole phase there. Once you start the drug, start at the lowest dose and titrate up. Every patient is different. Someone might be responding really quickly to the drug at quite a low dose, and then you stop there. Don't carry on going up for no reason, because that's when people come off the drugs and feel quite ill.

Jonathan: Could you clarify what the side effects are, and then are you saying the side effects are worse if I'm taking a higher dose of the drug?

Federica: Yeah, so because we don't know what people's lowest effective dose is until they go on it, if you go straight to the top, straight to the hero dose, then quite a lot of people will feel quite ill. So they'll have the constipation, the nausea. Those are the biggest two. Sometimes diarrhea, and that can be paradoxical, so where you have constipation and then diarrhea with it, which is uncomfortable.

Jonathan: Sounds unpleasant.

Federica: It is. Vomiting in fewer cases. And then there's more serious side effects that are rarer, but your doctor should tell you to look out for if you have very persistent pain. It could be due to your gallbladder or your pancreas struggling. And again, setting the scene in the pre-drug phase really helps to reduce that risk. But so if you imagine if you go to max dose and you're someone who's quite sensitive to the drug, you'll instantly feel really nauseated, like you might vomit. Your constipation's going to be really intolerable very quickly. Whereas if you titrate up from a small dose...

Jonathan: And when you say titrate up?

Federica: Yeah, so it's if you just increase your dose very gradually, maybe the lowest dose will be the most effective for you as a patient. You might be like, "Actually, I'm already losing weight. I'm already reducing the intake of the foods that I wanted to reduce. My food noise is already improving, so my mental health is improving." You stop there, or you just go up a little bit at a time until you get to that dose where your side effects are tolerable and you're seeing the metabolic effects of fat loss and reduced food noise that is going to be supportive of your health outcomes. So that's a really big one. Then the other one is, what we mentioned earlier, making sure that your GI symptoms are being managed with diet. So these symptoms of nausea, constipation, vomiting sometimes, diarrhea, reflux, these are all symptoms that can be managed with diet. There are ways to manage all these symptoms with dietary intervention.

Jonathan: We talked about some of the side effects as you start, but in a way we've almost jumped over, I guess, the thing that I hear from friends and family who are on these drugs, which is the transformation in how hungry they feel and what they want to eat. What is that experience for somebody who starts on these drugs?

Federica: So I'll never forget the first woman I was working with who told me this and that, and we were talking about side effects and potential risks, and she just said, "I'll take all of those risks if I can continue to have the amount of mental space I now have." So what's really interesting about food noise is that this wasn't a term or something that we looked at as clinicians until these drugs came to the market. Suddenly, lots of patients started reporting that their food noise had gone down.

Jonathan: And Federica, what is food noise?

Federica: It's not just like, "I love food. I'm thinking about what I'm going to have for lunch," in a nice way. That's not what it is. And it's also not, "I'm genuinely hungry, and therefore I'm going to think about what I'm going to eat as a snack." It's not that. Food noise is persistent, pervasive, and sometimes ruminant, so, like, going over and over and over in your head. Thoughts about food, where you're going to get food, how healthful your food is, whether you've reached your macros. The really interesting parallels with food noise is that patients with obesity that report food noise behaviors have a lot in common with patients with eating disorders and that describe how much it takes over their mental space. It's not a pleasant experience, and it takes over your day. So if you can imagine, Jonathan, from the moment you wake up to the moment you go to sleep, all you're thinking about is food, its effect on you, how you're going to get it, where you're going to get it from, is it good for you, and you have anxiety around that. And to have that completely switched off by these drugs is one of the most transformative effects of these drugs. And so this is why when you talk about GLP-1 receptor agonist or Ozempic, Wegovy, they're really brain drugs and fat loss drugs. Like, they're not cosmetic weight loss drugs. Their big effects are these two and then some of the emerging evidence on inflammatory effects, right? Anti-inflammatory effects. It helps us to really understand why certain individuals struggle with food so much, and it's nothing to do with willpower. It's everything to do with the way our brains are wired and the environment we live in, which actually makes that responsiveness worse. And it also does this, we're starting to see, for alcohol, smoking, and gambling addiction. So why these drugs offer such a window of opportunity is because they help to make space for dietary and lifestyle changes that that patient can then take with them for the rest of their lives. And we're talking here about the people who should be taking these drugs, so the correct populations. That food noise element doesn't apply to those who are microdosing or taking it for vanity reasons, but it's such a powerful additional benefit in terms of mental health for patients who really suffer with food noise.

Jonathan: And Federica, is this why people lose weight on the drug?

Federica: Certainly one of the main reasons, yes, because as we said, appetite regulation is really a brain exercise. So if we think brain is the control center, and the messages come from your gut primarily. There's a four-stage system that helps to regulate your appetite. The first one is cephalic, so in your head, and the cephalic system is seeing your food, interacting with it, so smelling it, tasting it, anticipating. This can only happen if you're actually preparing whole foods. If you are opening a packet or you are drinking your lunch, that is bypassed. So this is a problem in our current food environment, like ultra-processed foods everywhere. People literally do drink their lunch at their desk. So you're skipping one of the first steps in appetite regulation. Have you ever been really hungry and you're making lunch or you're making breakfast, and you start salivating?

Jonathan: Oh, yeah, for sure.

Federica: Your mouth is watering. Your tummy's rumbling. That's physiological effects of your brain being like, "Yo, there's food coming."

Jonathan: I'm now thinking about being a child and thinking about my mother preparing lunch, and that is definitely what's going on. She's like, you know, you're like, "Oh, can I have a snack?" And she's like, "No, because I'm making lunch," and you're getting hungrier.

Federica: That is part of the appetite response. It actually primes your pancreas to start secreting insulin. So there's actual physiological consequences to interacting and preparing your food. If there's one health hack that is unsung is preparing your own food actually helps with your metabolic health. Then you taste it. Your taste receptors, everything is having a party. It's great. Travels down to your stomach. Now, your stomach plays a really important role with appetite regulation because it's got stretch receptors, so this is a very physical response. When you eat foods that take up space in your gut, they stretch your stomach. And these send signals straight back to the brain to say, "Okay, we've received food." This is about 20 to 30 minutes after you've started your meal, right? So this is like minute minus two. It's cephalic in your stomach half an hour later, another round of satiety signaling from the stretch receptors. The drugs that slow the emptying of your stomach means that that stretch receptor activation is longer, because your stomach stays fuller for longer. It's also why people who have very high volume diets with things like broccoli, cauliflower, rocket, so these foods that take up a lot of volume tend to have better appetite regulation, because their stomach stretches more and they feel more satiated from their meals. We've got to try and distinguish fullness from satiation, because satiety is longer term and fullness is quite short term. We want people to help feel satiated from their meals. So your stomach's emptied, and it goes into your small intestine. This is the third phase now. In your small intestine, there are lots of these really clever cells that make hormones for us when they sense nutrients, and they send messenger signals to our brain, GLP-1, GIP, PYY, to say, "Hey, guys, we've got nutrients. We've got some cool building blocks we're working with." Now, this is like an hour and a half after you've eaten, maybe. It changes from person to person. I'm sort of generalizing. So an hour and a half later, you're still getting satiety signals because you've had a nourishing meal that has proteins and fats and vitamins and minerals, okay? Through the small intestine, right? Takes a while to go through. It's actually quite long, the small intestine. You get to the colon. If you've had a high fiber meal, you have plenty of fiber reaching your colon, okay? The first part of your colon has more of these cells ready to go. They're like, "What am I going to get? Feed me." They release GLP-1 and PYY from the same L-cells. They get released from the same cells, and they have amazing effects on your satiety. This is like two to three hours after your meal, okay? So you now have lots of fiber. You've eaten an 80-plus score on the ZOE app meal with loads of fiber, nuts and seeds, broccoli. It's great. And your gut is now saying, "There's still more nutrients for us here." Your gut microbes break that fiber down. They produce short-chain fatty acids and other fatty acids that interact with these specialized hormone cells in your gut that then send the signals up, GLP-1, PYY. Again, GIP getting released again. So whilst the drugs have this really prolonged time they act, so it's like burning a really long bonfire, yeah? If you eat a diet that is built to work with our appetite and satiety signaling, you will feel satiated from a meal for hours, even though the individual life of the molecules is only minutes. So it's like little crackles throughout instead of one massive bonfire that runs forever. So the magnitude of the effect of the drugs is like 1,000 times bigger than our own hormones we make. Some people are like, "Make your own natural Ozempic." You can't do that because our own natural Ozempic works very differently compared to the drug. So we have to be super clear. It's like thousands of orders of magnitude, okay? But if you have a diet that supports your natural signaling patterns, then you do have a much higher chance of being able to feel satiated and not having so much food noise from the internal stimuli.

Jonathan: I think what you're saying is that being full isn't just the period when there's like a lot of food in my stomach and that that's sending messages, which I think is how I've thought about being full. But that we now understand that as the food sort of continues its journey and goes into the small intestine and eventually into the colon where all the bacteria are, actually even when it gets to the bacteria there, they're saying like our body is able to sense, wow, there's all this fiber. I'm really happy. And it's then sending like our own GLP-1s up to the brain saying, "Hey, I'm still feeling satiated." To use the word you said, still feeling full. And you're describing this is the way that if everything is working inside us, that a traditional healthy meal would keep us full for many hours. And it's not just that I've stuffed myself, it's actually that my body itself is sending these signals to my brain two to three hours later saying, "Actually, everything's still good. We're full. I'm really happy with what you ate, and therefore I'm not having these really strong hunger cues." Have I got this right?

Federica: That's correct.

Jonathan: And am I right in suspecting that the sort of ultra-processed food that we generally eat doesn't do this same thing?

Federica: Yes. So the way I think it's helpful to frame it to understand is if we understand its evolution. So when we used to forage food, right, we would get plenty of very fibrous tough roots, seeds, berries, tubers. That was the majority of our diet. And so our body has evolved in a way that having that very high fiber diet, and you see this in the Hadza tribe today, where they have upwards of 90 grams of fiber a day, right? This very high fiber diet actually helps our body to feel like it's getting what it needs, and that satiety signaling continues even though compared to our modern Western diet or the SAD, standard American diet, SAD, in terms of calories, in terms of energy, we're eating way more with our modern diets compared to a hunter-gatherer diet, and yet we're starving, right? We feel hungry all the time in our modern food environment. Whereas that very high fiber diet helped hunter-gatherers and our ancestors to continue with their day, continue hunting, continue gathering with much fewer calories. Now, what's really cool is when you have a gut microbiome that's very dialed into this system, you produce even more of these short-chain fatty acids. So the higher your fibre intake from a diverse range of fibres, the more you produce short-chain fatty acids. Short-chain fatty acids have energy in them, which our gut microbes can use, and they can confer to our body to use. This is where it gets super interesting. Maybe 10% of our energy needs comes from the short-chain fatty acids produced from our microbiome. But if you amp that up to a really high fiber diet, it could be as much as like 30%. So you're now getting energy and satiety from your gut microbes, which means you don't need to then go out and look for more food. So if you contextualize it in that way and you compare it to our diet now where more than 96% of us don't reach the minimum dietary amount of fiber per day, where we are over-consuming refined carbohydrates, meat products, and massively under-consuming a variety of plants, you start to understand why that signaling system is not operating. Because the brain's there and it's waiting for signals, but our internal sort of fireworks are not being let off, so the actual signaling from our gut isn't happening in the way that it's supposed to help our brain. On top of that, you look at brain structure changes, so we know that children who are born in families that already have obesity, their hypothalamus is slightly differently wired, so they're actually less able to feel satiety. And then you add on top of that when you have increased fat mass, another hormone called leptin really interferes with the hypothalamus, can cause something called leptin resistance, which then means that even your fat mass tends to help you feel less hungry when you have enough of it, but if you're leptin resistant, even that doesn't work. And then you have advertising, the availability of food absolutely everywhere, you can't escape it. Everything is stacked against us in a way where it's actually harder to remain a healthy weight when you consider that entire picture of how we're supposed to eat and live and where we're actually living and eating, and the generational effects we're now seeing because we're sort of two or sometimes three generations into being overweight or having obesity.

Jonathan: A lot of your book is talking about practically what should you eat in order to get the benefit. For a lot of us, I think we say, "Well, you take this drug, and people lose a lot of weight, and it's obvious that they're feeling much better, and they seem to have more energy than they did before. So why do we even need to worry about what they're eating?"

Federica: Especially when you're taking these drugs, you have to eat the correct foods, otherwise you won't feel better and you won't be improving your long-term health. For patients living with obesity, there was a review published just last week. First three months of treatment mostly result in just fat loss, which is what we want. We know that 20 to 40% of weight lost can be from lean mass, your muscle and your bones. But actually, it's phased, so the first phase of weight loss is more targeted to fat loss, especially in this population of patients that have excess body fat. But then once that body fat starts to come down, you have this real increased risk of losing lean mass. When you have very rapid weight loss, there's this real risk of losing the lean tissues that you're trying to hold onto, which is why I think these drugs are correctly referred to as fat loss drugs, because that's what you're trying to lose. You don't want to lose your lean mass, like, at any age, right? You want improved body composition. Ideally, you want more lean mass, stronger bones, and reduced fat mass to healthy levels. Now, if you don't support yourself with the correct diet, there's a few main concerns. Micronutrient deficiencies, right? So we know that because of the diet we already have, many of us are living with micronutrient deficiencies already. So folate is a really good example, iron in menstruating women. So if you then have even fewer opportunities to get your nutrients and your diet quality is poor, I mean, it's not looking good. Micronutrient deficiencies are going to be an issue. So you might have heard the term nutrient density is very popular now because of these drugs. Nutrient density just means that each mouthful of that food is actually delivering a lot of nutrients. No prizes for guessing some of the most nutrient-dense foods we have are plants. So if you have a poor diet and you drastically reduce your food intake but still poor diet, micronutrient deficiencies are a big risk. The next one is protein. So protein's the one you hear a lot about. It's absolutely true. Because you're eating way less food, you have to make sure that the food you are eating contains enough protein. However, just eating loads of protein is not going to save your muscles unless you do resistance training. It doesn't have to be some crazy exercise. It can literally be some bands at home. You can start by lifting tins or bottled water. Like, start from where you are, but make sure you're using the muscles in a way that actually causes some sort of strain so that you're keeping that muscle mass and keeping it active, basically. As you'll remember from our ZOE protein principles, it's one of the only times when actually the recommended amount of protein, grams per kilograms of body weight, does go up. So we're looking at 1.2 grams to about 1.6 grams of protein per kilogram of body weight. It's hard to work that out. Like, I would struggle to work that out myself, and it's my job. So it's more about what foods do you need to include. Very high quality protein foods. You know, eggs, poultry, cheese, and yogurt, but also nuts and seeds, products like tofu, so soy-based products, beans and lentils as well. These all help to achieve enough protein in your day if you're making sure they're at every meal, basically. Hydration is often overlooked. When you have less of a drive to eat, you're also reducing the amount of fluids you're getting in your fruit, vegetables. They all contain water. Or if you eat soups and stews, they're all water-containing foods. So if you eat less, you also have less of a drive to actually drink, so your thirst response can be dampened. The result is, you know, constipation being a huge problem. Dehydration and constipation are not friends. You're going to make it so much worse, and also dehydration can make you feel really tired, give you headaches, make you feel sluggish. During treatment, there is a real risk of dehydrating yourself, so make sure you're drinking water. Things like smoothies and soups are really good, especially when you start to get used to that feeling of fullness. The fourth one is this nutrient density idea, so every single mouthful plays a role when you're taking these medications because you're eating so much less. One of the side effects of these drugs that is not often talked about, but can be very serious, is that when you have this reduced reward circuitry, it can lead to something called anhedonia, so you stop enjoying the things you used to enjoy. And for some patients I've worked with, that's stopped them taking the drug, because they stopped enjoying their lives. But you can help that energy and that mood by focusing on fiber, very specifically fiber, and it goes back to the role of our gut microbes. When I was researching the book, the amount of times I came back to the role of the gut microbiome in this picture, I was actually astonished. There's lots of evidence that shows how focusing on feeding our gut plays a pivotal role, and we see this a lot in the effects that fiber has specifically and diversity of fibers in the diet.

Jonathan: 90% of people are effectively self-medicating. Right? They're finding this online. They are overweight. They are self-medicating. What happens if they just continue to eat the poor quality diet that they were eating beforehand?

Federica: Let's look at the real world data, because we have it. So by some estimates, two-thirds of people stop taking the drugs because they don't feel well. They have GI side effects. Longer term picture-wise, one of the red flags and one of the worries is this yo-yo effect of coming on and off the drugs can be actually detrimental to long-term health in a way that if you imagine you've lost lots of weight, you haven't changed your diet, you haven't changed your lifestyle, you haven't done any resistance training, and you're in that group of people that have taken it for long enough where it's not just fat loss, it's now lean mass. If you then come off the drugs, you will regain the weight lost mostly as fat mass. It's much easier for our bodies to store fat mass. So there's a term for this, which is called sarcopenic obesity, and it's this idea that you have increased fat mass and much reduced lean mass. And this doesn't necessarily mean that your weight or your body won't necessarily be that much bigger, but the proportion of lean mass to fat mass is worse. And the real risk is that you actually end up with weaker bones, less muscle mass, and more fat mass than you started with, which then turns the picture back around to increased metabolic health risks. So increased risk of type 2 diabetes, increased risk of fatty liver disease, increased risk of hypertension, name it. So all these metabolic conditions that we're trying to reduce and that the drug is so effective at helping to reduce. If you have a good enough framework around these medications, there is a world in which you could come off them and not have that worse a health outcome in the long term. So we know a lot of patients come off them and don't go back on them. The majority of people who go back on them are those who then see a rapid increase in weight again, and they're like, "Okay, I'll give it another go." But there is a subset of people, and I have a few patients who have successfully reduced their dose and now don't take the drugs, and two years on have maintained their fat mass loss. I'm not saying that's for everyone. Some people will need to take these for life, but there's a world in which you personalize the approach and support people to have the best possible outcomes for their biology and their background.

Jonathan: So in your experience, you have seen people lose a lot of weight, come off it, and keep the weight off?

Federica: Yeah.

Jonathan: But you've also seen people, which I've definitely seen as well, lose the weight, come off it, get really hungry, and then find that inevitably they're therefore going to put the weight on.

Federica: They do, and often it's quite a big proportion of the weight loss comes back on within the space of six to 12 months.

Jonathan: Just before we come on to like, okay, what are all the practical things that you can do, what about people who are just going to stay on the drug? They're like, "This is magic. I didn't have side effects, so I've got through them. It's magical. I'm going to keep taking it, and I'm just going to keep eating the food that I was eating beforehand."

Federica: So I'd say it's quite hard to take these drugs long term and not eat in a way that supports your gut and your body, because you will get the side effects. If you have any intervention that restricts your food for very long periods of time, you always run into the risks of decreasing your resilience, your immune system really struggling, your brain health struggling, your lean mass, so your muscles and your bones struggling. There was a patient in the UK who had scurvy, so bleeding gums. People couldn't understand what was going on. He'd been taking these drugs without any support and just hadn't been eating fruits and vegetables, basically. I wouldn't say it's big numbers right now, but there was a case study of a patient who had started to have really severe brain health issues, and the case report described this patient as possibly having early onset of dementia. And then they found out he was just massively micronutrient deficient for his brain. And it's because if your dietary quality doesn't improve on these drugs, then you are definitely going to run into an issue of complete undernourishment. So when you take these medications, every single meal counts more than if you weren't taking them because you have fewer meal opportunities to actually improve your health.

Jonathan: And Federica, you talked about the food noise, but does it also change the sorts of food you want to eat?

Federica: It's a good question. So there isn't data that has quantified this, but anecdotally, some patients really do change the food preferences. They're like, "Oh, I can't even think about eating that." And the biggest group of foods for that is fatty foods. A lot of people report just not wanting to drink alcohol, or if they get a beer or have a glass of wine, they don't finish it. So it does actually change some behaviors and preferences for food. Hopefully, it will help you to be less attracted to certain food groups, but it doesn't automatically improve your overall food choices. You might remember Lucy, our participant from the documentary. Do you remember Lucy?

Jonathan: Yeah.

Federica: One of the big changes she reported was that she never used to eat chickpeas, and chickpeas were obviously recommended as one of the foods to incorporate, and within weeks she felt like she wanted chickpeas, and she couldn't explain it. She was like, "I never ate chickpeas. I didn't think I liked chickpeas." And that is a really beautiful example of gut microbiome-driven hunger. Gut microbes love the chickpeas, populated, really like, her abundance of these grew, and they send signals through the vagus nerve to your brain to tell you, "Eat more chickpeas so we can survive, please."

Jonathan: That's brilliant. So you could have your microbes start to help you to shift what you want to eat. If you eat the right foods to have fewer of the ones that love, you know, Oreos and McDonald's and more of the ones that love chickpeas.

Federica: Crowd out the Oreo noise, exactly.

Jonathan: So I would love now to switch to where you're going now, I think, which is what should you do when you're starting out on these GLP-1s to reduce the side effects? And then I would like to talk about the more longer-run changes.

Federica: Great. So we talked a little bit about the pre-phase and trying to really nourish your gut microbiome, reduce any kind of constipation before you start. So the pre-phase is very focused on fiber, and gradual increase of fiber because most of us are deficient in fiber. So how do you help people go from baseline, which is around 14 grams a day, to 20, 25, and 30 before you start the medication? There are some major groups of foods that have fibre, so like pulses, that includes chickpeas and lentils and beans. Nuts and seeds are really important as well, including those in your everyday diet. Fresh fruit, because it's hydrating. And then you want to try and incorporate whole grains. So whether that's barley, buckwheat, try and replace your white rice or pasta, not at every meal, but as often as possible, once a day, try and have whole grains instead. If you incorporate those foods into your diet and gradually increase, that will help to increase your fibre intake, help your gut, help to repair your gut barrier that might be a little bit leaky, as we say, and start to populate your gut microbiome with the guys that we want to see in there. Now, this is really interesting. This will also naturally increase that short-chain fatty acid production, and it will increase the nutrients in your diet that actually make the GLP-1 production, GIP and PYY production go up naturally. One of my patients was doing the pre-diet and decided she didn't want to start treatment because that pre-diet was helping her to lose weight, helping her to feel better already. So she was like, "I'm going to wait before I start the medication, because actually, this dietary intervention is already helping me." Great. That's fantastic. During treatment, prioritize protein, nutrient density. Making sure that you're getting enough hydration, and focusing on these micronutrients that we know. So the nutrient density and the micronutrients go hand-in-hand. If you're having nutrient-dense foods like broccoli, like cauliflower, like berries, like nuts and seeds and legumes... Legumes are anything that's kind of a bean-adjacent food, but also green peas, which are often really accessible to people.

Jonathan: And these are just helping you with fiber?

Federica: No, they help you with fiber and they also have excellent protein profiles, especially when paired with whole grains. So if you pair whole grains, say like a barley with lentils or beans with spelt, they then have the complete amino acid profile in the right amounts so that you're getting really good quality protein. Then during medication, you know that each bite counts and that you run a higher risk of dehydration, so you're prioritizing structured mealtime. So this is a framework that's in my book, which really helps you to keep on track, to making sure that you just give yourself enough planning so that you're not left guessing. Because when your appetite is reduced, it's quite easy to just be like, "Well, I'm not hungry. I'm just not going to eat." By giving our gut a clear idea of when food's coming, it helps to reduce the side effects. Our bodies love to predict when things are happening because they can't see what you're doing or thinking. So if you have a very clear breakfast time, lunchtime, and dinner time... Now, for some patients, actually, they prefer to spread things out with snacks too because their appetite is very reduced, and you don't want to eat past the point of fullness on these drugs. Very important. You will feel uncomfortable. But telling your body, right, breakfast is, say it's like 9:00 AM every day-ish, within the hour. That's also critical for your gut's motility. Gut motility is what helps everything keep moving, and we want that. We want to go to the loo regularly. We want to give our gut that stimulus to say, "Okay, it's the morning. Wake up. Start moving things along," and breakfast is the way to do it. So having your breakfast at the same time every day, then having your lunch planned and prepared, so that you know you're going to have something that's nutrient dense and that will make the most of that meal. So I often recommend bringing something with you because it is really hard to find nutrient-dense foods, like, in a supermarket or at a quick sort of lunch place, right? I know we talk a lot and we think a lot about how to help people snack better, and so having a very healthful snack with you, nuts, fresh fruit. Our gut health bar is literally made for this. Having that with you means that you have something that's nutrient dense, high in fiber, good quality protein, with minimal additives that's in your pocket that you can take with you.

Jonathan: If I am then going to be a bit hungry mid-afternoon, in this case you're saying it's actually good to snack.

Federica: Yes, another opportunity for nutrients.

Jonathan: Because actually I can take in something really healthy, and the danger is that if I'm not doing any snacking, I just might not be able to eat enough to get all the nutrients I need across these periods.

Federica: Yeah, exactly that. Yeah.

Jonathan: So it's almost like the opposite of everything we've been told.

Federica: Well, it's not the opposite of everything we've been told, as long as your eating window is reasonable. So I'm not recommending people just graze all day. But just be aware that it's better to stop eating as soon as you start feeling full and then having a healthy snack like a couple of hours, three hours later, than it is trying to either push past your point of fullness and then feeling really rubbish, or ignoring that window opportunity to get extra nutrition in. In this case, yeah.

Jonathan: Got it. It's important. And is that because if you overeat, there's side effects or?

Federica: The nausea will be, this is when the vomiting happens and the nausea, and really uncomfortable reflux, because you're literally taking a drug that makes that physiology happen. It's like that slowing down. So don't push it. And then dinner time, making sure again that you have an opportunity there during treatment. If you don't think you've hit enough protein in the day, this is a good opportunity to make sure you're getting good quality protein because most people are at home or they have some control over what they're having. And remember that with protein, the window is like a whole day. So if you feel like you didn't quite get enough protein at breakfast, don't panic. Your muscle's not going to start wasting away as long as you eat enough protein in the day.

Jonathan: And Federica, what types of food should you be eating to make sure you're getting enough protein? When I say that to my son, he's like, "Well, I need to eat a steak." Protein equals steak. Or maybe a chicken breast. Is that what you mean?

Federica: That's one of them. I think the ones to focus on, if you think about a protein pyramid, like what are the ones we want to get the most of. So majority of the combinations we're trying to do are the whole grains with the legumes. So protein is an opportunity to get other nutrients too, right? So if you're getting a lot of your protein from a legume with a whole grain, you're also getting fiber, you're also getting micronutrients, you're also getting other benefits. So try and have opportunities to have those combinations frequently. Nuts and seeds, another great one. And then soybean products. I have to say they are amazing for high-quality protein with amazing protein packaging. The fiber, the micronutrients, it's really good. Then you have fermented dairy, so cheese, yogurt, cottage cheese. Really, really great ways to get good-quality protein with micronutrients again, and fermented, right? So you're getting something good for your gut. Then oily fish comes next. So oily fish has omega-3 fatty acids in it. Really important for our overall health. Also very important for our gut health, liver health, and brain health. So just three times a week, oily fish. And these can make other dishes really flavorful, and you don't need to eat a lot of it to get really good amount of protein and omega-3 fatty acids. And above that, you have eggs and poultry. So eggs and poultry also play a role and can be eaten fairly regularly, I'd say like every other day or, you know, four times a week. And then above that, you then go to like the red meats. And red meat, if you want to eat it, and that's fine, it is micronutrient dense. You don't need large portions of it, but it's not necessary to have a good amount of protein in your diet.

Jonathan: There's been this spike in concern about getting enough protein if you're on these GLP-1s. People saying, "Well, you're not eating very much, so you've got to eat lots of meat. Otherwise, you're just not going to be able to get enough protein, and you are just going to lose all of your muscles, and in the long term, and then become like a jellyfish on the floor or something."

Federica: A jellyfish, yeah. Okay, let's go back a minute. We said if you have too much saturated fat intake, fatty foods worsen these gastric side effects. If you're eating red meat, that's really quite high in saturated fat, unless you're having filet mignon every time, which most people don't. So red meat is absolutely not the only way to do it, and neither is chicken, to be honest, or eggs. There's that whole pyramid of foods that's going to support your protein intake, and can I just be super clear again here that that protein intake is pretty pointless unless you're doing this resistance training. So think resistance training first, and then making sure you get enough protein throughout the day. There's a lot of foods to choose from in that protein pyramid, and they all contribute to getting enough protein. So if someone's increasing dose, sometimes they really struggle to get enough food. There is opportunity there to use a protein supplement, a simple like pea protein isolate, nothing fancy. That can be helpful for the days that you're increasing dose if you're really concerned, but you don't see like this wasting away with protein deficiency. It's usually a lack of physical exercise that's driving the lean mass loss.

Jonathan: And it sounds to me as though you are more concerned about sort of overall nutrient shortage than saying that your primary concern is not getting enough protein. Even here where you have said that this is one of the areas where ZOE's protein advice is higher than elsewhere.

Federica: Yes. If you hyper-focus on just the protein, then you miss out on the rest of the dietary picture, which is super important for overall health and for long-term success. So that's why I like to focus on the foods that provide multiple benefits, the protein and the omega-3s, the protein and the fiber, the protein and the ferments, because you have an opportunity there to then tick multiple boxes. So it's really about your food quality and the nutrient density. It's true. Nutrient density is a really nice way to think about it. Because for something to be nutrient-dense, you're ticking several boxes.

Jonathan: And basically, because I'm not eating so much, it's actually I really want to get sort of like it's a three-for-one offer is sort of what I want out of what I'm eating.

Federica: Yes, exactly. And lower volume. So really important here, Jonathan, we talked about the importance of volume for the stretching of your stomach, and actually, during treatment, you don't need any more help with that because of the slowing down. So you end up having smaller meals that are smaller volume, but really nutrient dense, so you can get the most out of every single bite, and that is very different to the advice for post-GLP-1. So for people who are now tapering off the drug, they've decided they don't want to continue taking it, or they can't afford to continue taking it, and they start tapering off, or they want to just see if they can continue their new lifestyle without them. That's where volume ramps right up. So then what you're trying to do is you change your diet again, and you start to really work with that internal signaling we've spoken about, and ramp up the high fiber, high volume foods that are actually still nutrient dense, but lower energy density that help you to feel fuller for longer with less energy in the foods, less calories in the food. And that is what I've seen in my clinical practice, is the way that with slow tapering off of the drugs and this ramping up of high volume, high fiber foods, you actually see success in people maintaining their fat loss, maintaining their energy levels, and getting back to a new lifestyle and a new diet that supports their health goals in the long term.

Jonathan: And so basically, they were eating one diet before they started taking these drugs. They've used these drugs to lose a lot of weight. They were living with obesity or overweight, lose a lot of weight, and then you're saying that while on these drugs, they were able to learn to eat a completely different way. And live too, yeah. And then after coming off the drugs, you have seen that if they then are ramping up what they're eating, but if they're ramping up and eating something that is very different from the diet they had before, in some cases, they've been able to maintain the fat loss.

Federica: Yes, and continue with their healthier lifestyle. So one of my patients, he drastically reduced his alcohol intake during treatment, and he was able to continue that reduced alcohol intake after treatment, too. The thing that seems to really set apart those who then go back on the drug after a while because their weight isn't stable, is the lifestyle elements and the diet. So resistance training, non-negotiable, but if you can also then start to incorporate more cardiovascular training, that seems to help with the fat loss maintenance after you come off the drugs. So taking up something like tennis or running or spinning or swimming, something that is just very cardiovascular in its nature, and then really focusing on these high fiber, high volume foods so that you actually feel satiated, but without drastically increasing the amount of calories you're consuming. Because, you know, when you come off these drugs, especially if it hasn't been that long, so if you've maybe taken them for six months, your body is like, "Wow, we've just come out of a famine." Like, you know, the signaling is there to say, "We have got to replenish our fat stores because that was a really bad famine, and there might be another one around the corner," right? So your hunger is going to go. Especially if you come off without tapering. So if you taper, if you come off quite slowly, you start to get used to your hunger again and you start to work with it. But if you go from your dose to zero, it's suddenly like floodgates, right? And it's a normal physiological response. And it's not to say that you won't put any weight back on, but if you are able to maintain the new body composition so that the fat loss you've seen, especially the visceral fat, so the fat around your organs that's really pro-inflammatory, that goes away. That tends to go down with these drugs. That's the stuff you want to keep off. Your weight might come back up a bit, it might fluctuate. But if you can keep it fairly stable after coming off the drugs, it's an absolute game changer, and it is amazing to see the patients who've had that success. I want to kind of just caveat that it tends to be patients who didn't have lifelong obesity. I think there are genetic factors and structural brain factors at play for those who have familial sort of several generations of obesity that might mean that this approach doesn't work, and they may need to consider taking their medications longer term.

Jonathan: Yeah, I was going to say, I think it's wonderful that you're seeing people who can come off. I think one of the things that I've definitely really realized through this is that obesity is a disease. We now understand the way that ultra-processed food is one of the things that plays into what happens to your brain and makes you so hungry, and that when that's out of control, like, there's nothing you can do, and just in the same way that it's clear this is not just about willpower at all, but I don't think that anyone listening to this who has tried to taper down the drugs or come off and realize the hunger comes straight back should feel bad. You know, you wouldn't expect to suddenly stop taking your blood pressure medication and magically, even if you've improved your diet, like have it all fixed. So I wouldn't want anyone listening to this to feel that it was bad to continue to use this if it is having all of these benefits. Is that fair, Federica?

Federica: It's fair, and it's also fair that what we're seeing in real world data is people take it for a while, come off for a while, take it again for a while, come off for a while. So as long as that is structured and supported, that might be the way people do benefit from these drugs. There isn't one right way to do it, and everybody's different. So it's about understanding what works for you as an individual and making sure you have that support network in place. The more they're used, the more they become part of medicine, hopefully, the more the framework is communicated and people understand what needs to happen alongside them. I think the big risk we have is that they are used in isolation. That's not going to have the desired effect, and that's not what we need to be doing to improve people's metabolic health, basically.

Jonathan: Federica, I think the book is great. I think it's incredibly timely because clearly we are seeing this enormous number of people using these drugs for the first time, and it's really exciting, right? That in a way it creates this opportunity for people to change their diet and have all the profound health benefits that, you know, many others have been able to access, but it's so hard if you're living with this level of hunger. So I think it's brilliant. I'm going to wrap up and try and do a quick summary. I mean, the thing I'm most struck by actually is you said, like, two-thirds of people who have taken these drugs have dropped off. So that's an enormous number of people who haven't actually managed to stick with this and make it work, and a lot of that is due to side effects. And the second thing I think I'm really struck by is this idea that if you don't change your diet, you could lose the weight but still have all of these long-term risks, and you said particularly like brain health and immune system. You know, you might have less weight, but you're not magically getting the benefits of a healthy diet. I thought on the positive side, I heard you say there's been a lot of fear about, well, actually all that's happening is you're losing, like, your muscles. But actually you're saying, like, in the first three months, the very new data says it's largely fat loss, which is good. After that, as you're continuing to lose weight, it's like a mix of fat, which you want to lose, and then what you called lean mass, which I now understand is muscles and bone, and obviously you want to minimize that. However, there's like, I guess two big issues. One is the side effects, and often the side effects are most intense at the beginning. And so a lot of people bounce straight off because the side effects are too bad.

Federica: And as you increase dose.

Jonathan: That's particularly, like, constipation and nausea. And if you can prepare yourself in terms of making some changes to your diet before you start taking the drugs, you can really reduce the risk of those side effects. You also, by being slower to increase the levels of the drug, give you more time to adjust to it. And then I think the final thing is you need to really think about what you're eating when you're on these drugs. You can feel like magically, "Oh, but I'm losing all of this weight. Everything is brilliant." But actually, there's a real risk that you're not getting enough of the nutrients you need. And so we talked about a number of different things that you should do. One of them, maybe the most moderate, is think about the nutrient density of your foods. And I think you loved all of these foods where they're combining fiber and protein and all sorts of micronutrients. This is like you're combining whole grains and beans, for example, and chickpeas and lentils, just all of this magic, but also, like, broccoli and berries, all these sorts of things which are incredibly dense there. That's because the protein does matter. You do need to get more protein, but it doesn't mean that you have to be eating sort of red meat all the time. You talked about all these other foods like beans and yogurt and oily fish and eggs, and indeed chicken, that can give you a lot of this protein. Red meat still has all of this saturated fat, which also the fat is triggering issues. But you can combine getting all of the benefit. And of course, the other benefit is fiber. We understand how much the microbiome is playing a role in all of this hunger and appetite control. And so you get this right, you're in a much better place. The other thing to be aware of as well is, like, eating all of this, you know, more fiber, is hydration. If you're a little bit constipated going in and you start these drugs, it's going to get much worse. It's another reason you're going to give up. And then finally, what you said is, well, you know, we talk about all this protein, but if you're not doing resistance training, then the protein's going in one end and out the other. It's not doing any benefit. So actually, you're going to be feeling better, hopefully, as you're starting to lose this fat. You need to add resistance training. If you can be doing that on top, then actually you're going to sort of keep up that muscle as you lose it and hopefully end up in a place where you feel wonderfully better.

Federica: Exactly, and where your metabolic health is actually set up for long-term success.