Welcome to Zoe, Science and Nutrition, where world-leading scientists explain how their research can improve your health. Today, we have something very exciting to share with you, a brand new scientific discovery only revealed within the last few days. We've been working for the past two years on a randomized control trial of Zoe membership. Participants use personalized nutrition advice to try to improve their health. If you stick around, you can find out their results, which are fascinating. I'm excited to have my scientific co-founder, Professor Tim Specter, and our chief scientist, Dr. Sarah Berry, on the show today. Tim is one of the world's top 100 most sighted scientists and a Professor of genetic epidemiology at Kings College London. Sarah is Associate Professor of Nutrition, also at Kings College, and one of the world's leaders in running very large scale human nutrition trials to understand how what we eat affects our health. Sarah and Tim, thank you for joining me today.

Great to be here, Jonathan.

It is a real pleasure.

Tim, you could sound more convinced.

Do you know what? It's bloody fantastic to be here today. All right.

I think both of you know the drill, so we're going to start with a quick, fire round of questions, and I'm going to alternate starting with Tim. So are you ready to go? Is my future health predetermined by my genes?

I used to think so, but now for most people.

That is not true. Sarah, if you and I eat the same things, will our bodies respond in exactly the same way?

No.

Tim, is there one best diet for everyone? No. Sarah, is your latest study a randomized controlled trial of a personalized nutrition program?

Yes, it is.

Did participants in the clinical trial who were given Zoe membership see improvements in their health?

Yes, sure.

And both of you, what's the most surprising thing about working at Zoe? You can have a whole sentence now.

How much fun work can be.

I wouldn't have thought I'd be doing all these podcasts, but that's for sure. It wasn't in my contract, but it is quite fun.

We actually started Zoe almost seven years ago. Tim and I have talked a few times actually about when we met, and he thought these crazy guys, myself and our other co-founder, George, came in and had this idea of doing this whole new idea of using AI and collecting this huge amount of data and doing tests to give people personalized advice. But I think we haven't talked very often about, Sarah, about how you got involved, and I think that's a good maybe starting point for today. Can you maybe share with us when you first met me?

Do you want the unedited version of my first impression? Go for it. I was actually first contacted by Tim, who, despite us working at Kings for many years at the same time, I'd never actually met. And he asked if he could have a chat with me about my muffins.

I was very interested in your muffins. Yeah, definitely. I'm in the room.

I went along to Tim's office, which, as you know, Jonathan is a beautiful office overlooking the Houses of Parliament. And I sat there to tell Tim about my muffins, but also educate him on everything that he didn't know about postprandial metabolism. During that meeting.

Tim- Which is what happens in your body after you eat food.

Yes. And during that meeting, Tim spent a lot of the time on his phone scanning his arm because he was wearing, for the first time, a continuous glucose monitor. And so I actually thought that was very rude. And I thought, Okay, I can handle this a couple of different ways. I can either walk out, I can just brazen it out, or I can just talk over the fact that he's being quite rude. And I thought, Actually, I'll brazen it out. I'll pause, I'll sit there quietly. And as I left the office, I thought, Well, that's quite sorry Tim, but rather typical rude male professor, I'll be on my way. Then I bumped into you and George, who were bouncing around, full of enthusiasm, told me all about these great ideas that you had. And I thought, My gosh, I've just met this rude professor and now I've met these two crazy guys who think they're going to pull off 1,000 people, post-prandial clinical trial in a year. I remember going back to the office and speaking to my colleague and just telling her, Oh, my God, I've just like these three people I've just been chatting to, they're nutters.

But you know what they say? There's a thin line between genius and madness. I now realize that Tim isn't rude that he can be charming when he wants to be.

I hope you were going to dig me out of my hole as well, but is.

That where you're going to start?

You're.

Still just crazy.

I said there's a thin line between genius and madness, and I realize there's a majority of genius in you and George.

That's very kind. I think no one's going to believe that now they're like, Oh, I have to overcommonize. But maybe not completely mad. Actually, we've done a lot of clinical trials since then. And the one that you're referring to was the first one we did 1,000 people, most of them twins, that led to the first two Nature Medicine Papers and gave us that first version of Zoe. But we've done a lot of different studies since then, and you've really been all of them, Sarah, right? Luckily, I think bringing that experience of doing these really large scale human studies. Now, one thing I know from the very beginning was that both of you always talked about the idea that once Zoe became mature enough, we needed to do a RCT, is the language you use, which I needed you to decode and is a randomized control trial, which I still needed you to decode. And you explained to me, This is what you do whenever you test a vaccine or a drugdrug. It's like the gold standard of how you determine whether something works, where you actually have this very formal process with two groups, one of whom gets the placebo, which you call the control, and the other one that actually gets the thing you want to test, whether that was the vaccine or the drug or in this case, you wanted to test Zoe, because for you, that's the real test as to whether something really works in science.

Is that a fair summary of what you were saying? Probably for almost seven years, right?

Yeah. I mean, I think that the first six years, the science that we conducted was groundbreaking. It was amazing. And I often talk about the pace of the research that we did as well as being something that's quite special. And I know I often say our research is like research on steroids. And typically in academia, we do our research so slowly that sometimes it almost outdates itself. And what's been really exciting is we've been able to do the research that would just be most academic stream, a scale and pace that's never been possible before. And then the icing on the cake is now let's put all of this to the test in this randomized controlled trial to see actually does Zoe really work.

Yeah, and the key is in the randomization. So epidemiology is just following people over time, and that's very good for big numbers or when you're doing long periods of time. But if you really want to dig into the detail of how important that intervention is, rather than just selecting people who want to go along with it, you have to do this randomized trial, which divides people into these two groups by tossing a coin, essentially. They could have equally been in the study, but you just arbitrarily say, Well, you're going to study, you're not. We're going to see the differences between you. This is the gold standard for most areas of medicine, but it's rarely done outside medicine, I would say. This is why it was so important. But the reason they're not done is they're hard to do. They cost a lot of money, they take a lot of manpower, it's hard to get the funds for it in academia, and it often takes years of people's lives. That's why they're not often done.

So there are actually quite a number of randomized controlled trials in the field of nutrition. I think, though, that like Tim said, they are very expensive. They take a lot of time. They're very burdensome. And where there aren't enough trials is looking at whole dietary approaches. So I spent my career before Zoe running randomized controlled trials, but looking really specifically at very specific nutrients, so specific types of fat, for example. And what's lacking is looking at whole dietary changes because we don't consume single foods, we don't eat single nutrients. We need to look at the diet as a whole, and that's really important to consider it as.

A whole. So I think what's exciting is we started two years ago saying, Yes, we're going to do this first randomized control trial. And so I'm very excited that basically two and a half years, I think, actually years later, we can finally share the first results, which have just been peer reviewed and presented at the leading nutrition conference called FENS, and we'll have the link to that in the show notes. Now I'm sure that everyone listening is probably now as excited as we were to find out the results. But we're going to tease a little bit because first we'd like to actually explain what those participants experience, because as we described, there are these two different groups. So what are you actually getting the results for? And I think one of the things that makes randomized controlled trials, I think the other reason why there's not so many is you test this one thing. So it's a bit different from many of the studies that we talk about on this podcast, where they look at people over a period of time and they can understand lots of different effects. Here you're really saying, Okay, we're doing this one thing compared to the control and actually really proving does it work.

So we could get both of you to do a long explanation of exactly what we gave to both groups. But actually, I thought it would be a little bit more fun if we talked about the process, lived through our own experience, because one of these groups actually became Zoe members for this period of 18 weeks, and we've actually just been going through that ourselves over the last few weeks. So I thought it might be quite fun to actually talk through a little bit our own experience of what it was like to be a participant in this arm. Before we go into that detail, though, maybe we could just start right at the top. So in a nutshell, Tim and Sarah, what is Zoe and how does it work?

What is Zoe? Zoe is a way of life. We used to think of it as a starting point of a test, but actually it's getting people to think about food in a completely different way. We do this through a series of both tests and then education to get people to alter the way they're looking at food, realizing the foods that are good for them, the foods that are less good for them, trying to change the composition of their plates every day, trying to think about not only what they eat in a day, but how they eat it, and doing things in a way that are sustainable, not only over months, but years and potentially decades. It's far more than perhaps some people think of it when they just talk about Zoe, Oh, that's just the app. That's just one of the many tools we have in order to make this real step change in someone's life that once they've participated properly and seen the benefits, they'll never go back to their old ways. They'll always be thinking about food in this different way, this new way that is a much more holistic approach to food.

We're using a whole series of techniques and educational nudges, if you like, to get people to eat in ways that is good for their metabolism, is good for reducing their hunger, improving their energy, their mood, but is also good for their gut microbes and their metabolism, their blood markers, for example, of future health. That's the broad overview. We can explain exactly how we do that through these series of tests and then recommendations that come from it.

I think of Zoe, if I was to describe it to my friend as being a way of living that's underpinned by the latest science, that's underpinned by us understanding who you are, so all of the details about your biology, your family history, and us giving you advice that you can implement as easily as possible about the food that's the healthiest for you, the healthiest for you as an individual without being restrictive.

And being fun, I think that's the other thing. So it's not only a question of not restrictive. I think I'd like to feel that everything we're doing is getting people to eat more different foods, enjoy that rich variety of eating, enjoy the social aspects of it, and not have any of these old taboo's and negative images of food. So in a way, nothing is off the table. You can eat anything you like, but you just realize what is a treat and what's a staple and getting people to really engage in food and understand it, where it comes from, what's behind those labels, hopefully how to cook a little bit more, what to pick in a supermarketmarket or an offer restaurant menu, be more adventurous.

I think it's really educational as well. People that I know that have tried Zoe, as well as learning about themselves, they say it's great. They learned so much that they just didn't know. That's really surprised them about food and about how it impacts their health. Because as well as teaching people about themselves from all of the tests they do, when they're on the Zoe journey, there's continual lessons and education that we impart based on what we already know, but based also on the latest science that we, as scientists at Zoe, are producing.

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Let's talk about maybe the steps that the participants in this trial went through. Maybe start, the first thing that we're doing is getting this big yellow box and doing these tests for the first couple of weeks. Could you explain a little bit what happens? And, Sarah, maybe you can help us to understand a bit like what's the science behind that?

Okay, so the participants who were randomized to the Zoe arm of the trial went through essentially the same experience that people who purchase the Zoe program and become a Zoe member. So it all started with them receiving the nice yellow Zoe box and then starting a two week test phase where we measure different parameters related to health. So they are given a continuous glucose monitor so we can.

Look at- And I can see one on your arm right now? Yes.

With a sticker upside down, as you told me off for earlier.

I could just tell you put it on yourself. Whereas I always rely on my wife to both put the CGM on and put the sticker on, because otherwise I always put it on the side of my arm and knock it off on the door before the end of the first week.

That's the difference between us. You take care over these things I just slapped on. So participants receive their test kit and there's various bits within their test kit that allow them to measure features of their biology. So one is the continuous glucose monitor that allows them for a whole two week period to monitor the blood sugar levels from a minute by minute basis. There's also a finger prick kit so people can look at what their blood fat responses are after a high fat meal. And then there's also this nice kit to people to use in the toiler in order to collect a poop sample that is then posted back for us to look at people's gut microbiome. And this is all done using the support of an app. And within the app, we also record lots of information about people's health history, about their dietary habits, about the foods that they're eating, and other questionnaire data.

So one thing you haven't mentioned is the cookies, Sarah. So could you just explain a little bit the cookies and how you then use these other measurements to actually get this data to personalize the rest of this OE membership?

That's because I'm upset that my muffins aren't in the box anymore.

Sorry. We'll talk about how your muffins suddenly disappeared.

So it's really important that we actually provide people with a standardized meal so that we can assess everyone compared to other people. So all eating exactly the same meal. So all eating exactly the same meal. And this is what we use in nutritional research often. If we want to look at people's responses to a meal, like their blood sugar responses, their blood fat responses, which we do in Zoe, we want everyone to be having the same meal. So over the last 25 years, in my research at Kings, I've been using these very high fat, high carbohydrate muffins, which is how Tim and I met over the muffins, but they are quite difficult to eat. They're really high calorie. They're really very dense in terms of the fat and carbohydrate. And so because it's always something we're always doing is trying to listen to our users, make the experience as comfortable as possible. Recently, we move from using muffins to using cookies. So in the yellow box, as well as all of these kits to test your biology, we also have these cookies. Now, the breakfast cookies contain quite a high amount of fat and a high amount of carbohydrate.

And these are eaten in the morning, having had an overnight fast. So you won't have had anything else to drink or eat. And then four hours later, we ask you to eat a lunchtime cookie. And these lunchtime cookies are this bright blue color. And the reason is because we want to look at something called transit time, which is the amount of time it takes from consuming, eating a meal to actually appearing in your food. This is because we know from our own research, it tells us something about the health of.

Your gut. And so why... Because I think people listen to this and saying, Okay, so you're going to make me eat a meal, but completely random. Why are they full of fat and carbohydrate? Have you just made this up 25 years ago and just convinced the rest of the world to follow on? Is there any logic behind why you're doing this?

There is some logic, yes. So what we know is when you consume a meal that contains any nutrients: fat, protein, fiber, carbohydrate, you have very short term changes in lots of chemicals in your blood. And we know that these short term changes that occur in your blood after you eat a meal actually underpin many of the long term changes that food and diets have on your health. So what we want to do at Zoe, is give everyone a standardized dose of fat, a standardized dose of carbohydrate, and look how they change the circulating levels of blood sugar and of blood fat. And the reason is, is because we know that if you have a very high level of blood sugar and a very high level of blood fat after eating a high fat or a high carbohydrate load, that actually initiates this cascade of downstream effects. So it initiates unfavorable effects if it's repeated at this high level, such as inflammation. And we know that this therefore underpins many chronic diseases such as cardiovascular disease and type 2 diabetes. So what we want to do is we want to assess what is the level of people's responses to a standardized meal in blood fat, in blood sugar?

So we can look at how it might be impacting their long term health.

And people don't all respond in the same way?

No, absolutely not. So we know from the very first study that we did back in 2018, there's anywhere between a 10 to 20 fold difference in the level of increase in blood sugar or.

Blood fat. 10 to 20 times different. So like enormous.

Difference between people. Hugely different. Yes.

And I think one thing you've mentioned quite a few times here, but I think many listeners will never have heard of before is blood fat, which I had never heard of before meeting you. But a lot of people will be familiar with things like cholesterol and can just help them to understand what blood fat is.

Yeah. So we have different types of what we call lipids that circulate in our blood. One of the types of lipids is cholesterol. So many people have heard of LDL cholesterol, which we also call our bad cholesterol, or HDL cholesterol, which we call our good cholesterol. There's also another type of lipid, which is called triglyceride, which I'm referring in this podcast to and generally referred to as blood fat.

What a measure of your overall fats in your blood.

So triglycerides come from two places. They're firstly produced by your liver, but they also come from the fat that you eat. So when you have a meal that contains fat, you have a short term increase in circulating blood triglycerides, or to keep it simple, circulating blood fat.

So you do these tests, you eat these cookies, you understand what's happening with your blood sugar and your blood fat, I think you also mentioned about measuring some of your poop. Tim, can you help us to understand why that's also part of the Zoe membership?

Yes. So we knew from the first predict study, and actually some of my research on twins going back longer term and other research around the world, that the composition of the microbiome had an influence over how you responded metabolically to certain foods. And we know that nearly everyone is very unique in their microbiome. Understanding, in a way, all the microbes you have there, lets us understand what chemicals are being produced in your gut, which ones might be, in a way, interfering with the way you dispose of sugars or fats. And so really important to understand the composition of those gut microbes so that we can factor that in when we're looking at your responses, and also give us a baseline to say what to work with. So it's as well as influencing how you respond to sugars, carbohydrates, and fats, these microbes are also pretty good guides to your gut health and your likelihood of getting other common problems. So in a way, a lot of the influence, we wanted to get a baseline idea of your gut health so that we can then start tailoring foods towards it to try and improve it. Because it's one of the most modifiable factors of our bodies that we can modify with things like diet.

And I think what's really important to highlight, Jonathon, is that we're looking at lots of different pieces of the puzzle that make us who we are, that also influence how we respond to food. So there's lots of kits out there, products out there that are measuring single pieces of the puzzle, but we're far more complicated than one piece of a puzzle. And this is what I think is great with the work that we're doing. So we're measuring lots of different pieces of the puzzle, like the blood fat, like the blood glucose, like the microbiome. But we're also asking a lot of people as well, lots of questions about themselves, because we can also learn a lot as well by using the information that they provide us from questions, and we do that in the app as well during that initial phase.

Amazing. So you've collected a lot of information from these participants who are just starting in the experience of the Zoe membership. All those tests go off, takes a few weeks, the results come back. Talk us through what now happens for the rest of the period in this study.

So I think after you've done all the tests, it's important just to step back a moment. After you've done all of your initial tests, you will still be for a whole two week period monitoring your blood glucose levels to different foods. You'll be logging the foods that you're eating so that we can really understand the timing of the foods that you eat, the types of foods that you eat, as well as the nutrients that you're eating. Then there's a period where, like you say, you're waiting to get your results back. But we help people and guide people through the whole journey. So even when people are waiting to get their results back, then we're also educating them about things that they might not have thought about relating to food and how. So we start the journey even before they get the results back. And then after a few weeks of having the results been sent away, the Zoe participants then get a report back that tells them about their puzzle. So it tells them about their blood sugar control, their blood fat control, their microbiome health. And it's all integrated together with all of the questions that we are trying to ask them as well in order to deliver their own Zoe score that can guide them on the best foods for their health.

So can you talk me through a little bit then about the continuing? Because this is now just a few weeks into what I think is an 18 week trial here, is that right, Sarah? Yes. So tell me what happens. They get the results. What are they then getting that is hopefully going to be something you can test and see has some impact?

So the participants on the trial, just like the Zoe members, once they've got their results back, they have access to our app. And by accessing our app, it means that for any food that they're eating, they can look up what their Zoe food score is for that so that they can be educated in how it impacts their health. So we give them guidance on whether this is the food that has maximum benefit for their health or whether it's a food that they might want to eat less frequently. They also have daily lessons and daily advice throughout this 12-week period that's educating them again and other aspects that we know are really important, such as the importance of sleep, the importance of physical activity, the importance of factors like fasting, for example, as well.

So every time I do this, I learn different things. And I'm struck by... When I first started, which is probably maybe three years into my Zoe journey with both of you and about four years ago, I was making my first big change, which was discovering that basically everything I was eating for breakfast that I thought was good for me was terrible for me. So that was my first really big shift. And I was very focused on my blood sugar in particular because my blood sugar control had been very bad. I was eating lots of highly processed carbohydrates, and it was like shooting through the roof. It was a bit scary, actually. And I'd also, in that case, I'd done this DEXA scan where they done this full body imaging, which is not part of this trial. And I discovered that I had all this fat in places that Tim was like, That's really not a good place to have fat. So that was my big focus. But what's interesting is each time I've done it again, actually, I've unpicked another layer. And I think for anyone who's listened to quite a lot of the podcasts, they can understand that food is very complex, and it's not just like one change or two changes.

There are all of these different things. So maybe you could both share something that when you've done this again or something in the last 12 months, what have you discovered and shifted?

Well, I've recently discovered that delaying my breakfast makes quite a big difference to me, my energy levels and my mood and things. I've started swapping around some of my lunch, for example.

And- What do you have for lunch today, Tim? This is always the number one question we get asked.

Putting me on the spot. Well, I actually made my own vegetable soup. I basically looked at the bottom drawer of the fridge, took out what was there, got some red onions, garlic, red peppers, then I added some mushrooms in there, some leftover other bits. I can't remember what they were actually, just some vegetables. Some kale, that was right. It was looking a bit worse for wear. And then I added some stalk and a large jar of Italian white beans, then some tomatoes, some herbs, spices, bit of paprika, brewed that up and then stick it in a blender. Twenty minutes later, I had my soup with plenty of leftovers, and it was great. I really enjoy doing that because it's different every time. I've learned that things like beans, A, score particularly well. The great source of protein and fiber, and I realized I wasn't eating as many beans as I should have been. And so I'm always trying to find ways of incorporating beans.

And this is one of the things that you've changed more recently, is it?

Yes. I try and get a whole variety of beans in jars and things. Some great ones out there, if you don't look, you don't see them and just think it's only baked beans or nothing. That's been a change for me, as well as adding fermented foods to many of my normal dishes. For people who know me, now I'm into my kimchi and my saucraats, and things, but I actually started adding them to salads and salad dressings and cheese and things. They're not an unusual thing to be eating, so you can have them more regularly. I'm finding that interesting as I'm experimenting with that. And all these things don't really affect my blood sugar at all. I know that there's no real downside to it. It's all good, and it's all going to be good for my microbes, which hopefully when I get my test, I'll be able to prove, but.

I.

Can't prove it quite yet.

What have I changed? Well, I've obviously been in nutritional research for 25 years, and as you know, Jonathan, to your frustration, I've had quite a relaxed attitude to the food I eat. And I'm a firm believer in listening to your body, listening to how it feels. But I've never self experimented. So when I first wore a glucose monitor, which actually wasn't that long ago, it was like almost a Eureka moment of putting two and two together that I often would get these slumps where I'd feel shaky, I'd get dizzy, I'd get really hungry. My poor kid-.

Never, Sarah. Hangry?

No. You've not seen half of it, Jonathan. I think Tim has occasionally, but I would feel awful. And I could never really work out what it was despite all of the nutrition research that I've done and all of the nutrition research in this postmeal, this postprandial area. And then when I wore a glucose monitor, what I found fascinating is when I looked back and looked at any time that I was feeling this awful feeling is when I was having a glucose dip. So blood sugar dip. I noticed what particular foods were causing me to have those dips. So the breakfast that I've always enjoyed, which is white bread, pan of chocolates, et cetera. That's one of the big changes I've made is to change the breakfast I have and to be a bit careful to avoid foods that give me that dip, because at the end of the day, I hate feeling like that. And so don't let Tim know. But I actually now have Tim's breakfast like a large proportion of the population do. So a bit of Greek yogurt, a bit of kefir, some nuts and seeds, and a little bit of dried fruit, but I don't want him to think he's educated me, okay?

Don't worry, it'll be our secret.

Well, I was thinking about what I... There's so many things I've changed, but one of the things I was struck by is one of the big changes in our family is that Justine did Zoe probably about a year ago now, and that was a really big difference because I changed a lot of the meals I was eating on my own, so particularly breakfast and lunch. But actually, dinner was a shared experience, really driven by what the two of us would eat. I've been sane and all these things for ages. I think when Justin was on the podcast earlier, she also said it was like, Well, who's going to listen to Jonathan? But then she got her own results. And I think this is one of the power of Zoe that we were able to test in this RCT. Suddenly, it all started to make sense. And so we changed our diet a lot. But interestingly, Justin has much better blood sugar control than me. So she's just generally better. And so we eat a much more similar breakfast than before, but she puts seeds on, which are full of lots of dried fruits in it.

And I refuse to put the dried fruit on because I know that basically my body treats that pretty much like sugar. It's like spiking up my breakfast. And I eat a lot of breakfast anyway, so there's definitely quite a bit of spike. So we have quite a similar breakfast, but we have these two different mixes to put on top. So it's like 90 % the same, 10 % different.

Your own sprinkles.

Exactly. I get to put my own sprinkles on. Exactly.

I think, Jonathan, though, it's really important for listeners to say that having an increase in blood sugar after milk is a normal physiological response. So I know we often talk about spikes and dips, but actually having an increase is normal. We don't want people to be obsessive about this and flatten the curve, but it's about looking at what is an excessive peak or a response that actually you don't feel great about. That's what we want to be mindful about.

I know everyone has them. I mean, we talked about your dips. We think about one in three women have these significant dips, but two out of three don't. So it is all about listening to your body, isn't it?

And I think that's a great example of what our Zoe Predict research is showing, just how different people are. So I get these dips to quite an extreme that I actually feel awful like I've said. And we find that about 25 % of people have these big dips, but 75 % of people don't have any. But the 25 % of people that do get these dips, we know from our own research that they actually eat about 300 more calories than an age match person that doesn't get these dips. They feel less energetic, they feel less alert, and they have lower mood.

And they get hungrier.

And they get hungrier a lot more quickly and eat their next meal at a shorter time interval than if they didn't get a dip. And I think that whilst I think we have to caution about over focusing on one piece of the puzzle, so although we measure blood glucose, it's just one of the many things that we look at. What I think is really powerful with the continuous glucose monitor is it's actually the first time that most people will have been able to almost take a look inside their body. So I think it's a really good way for people to see, wow, the food that I'm eating is actually impacting me here and now. Not in 20 years, not in 30 years, but here and now, and actually I can make changes to the here and now that in the long term will have a favorable effect.

And we create these scores, which combine looking at the blood sugar, looking at the blood fat, looking at the microbiome, understanding things like ultra-processed food, but then looking at you as an individual, right? So that they're quite different depending upon whether your blood sugar control is good or indeed risk factors that you might have had in the family. I think some people listen to this and saying that then suddenly you give them this fixed from day one that they just have to follow. But maybe just finish off by helping people to understand. So what happens? How are you guided through? Because these participants were... Well, who were these participants? What was their average starting diet? Let me just talk through a little bit how the app was guiding them as a program. And then I think we've teased people for long enough. Let's talk about how the study came together and what the results.

Look like. So the people that took part in our study were representative of the typical American?

Age 40 to 70, all slightly overweight, not particularly healthy, but not either very unhealthy either. So pretty generalizable to everybody in Western Europe.

Just talk us through what happens, because we talked quite a lot about the test. We talked a bit about that initial bit. Just help us understand a little bit how the app guides you from the point that you get your results through that rest of this period within the membership that was tested in this study.

So after the participants got their results in the Zoe arm of the trial, they were given their own personalized scores for each food, and they were given recommendations of menus and ideas they could use. They were given healthy swaps of ways they could improve their breakfast scores, for example, and their lunch scores, and they had access to coaches to enable them to do that. So over the next few weeks, they got more confident about out their foods for more healthy ones, knowing what to pick at the supermarkets, and sometimes downloading recipes and using those themselves. So generally, the idea was as time went on, they were getting a much better idea of what suited them and their health, and were consistently getting good scores, both by the meal, by the day, and then they would get a weekly score to check they were on track and they were able to log in with their digital coaches to see they were on the right track. At the same time, we were asking about all kinds of things like mood and sleep and energy and exercise and all these things that are very important to this idea of this being a long-term plan rather than just a short punishment, if you like.

We wanted to check that they were very much engaged, but also able to sustain it and.

Enjoy it. Tell us about the control.

The control group were individuals. These were randomized, randomly. And so where one group got the Zoe kit and the test and the program, the others were given the standard advice that all Americans are given through the American government, which are very similar to the UK Eat Well guidelines, which are used by government and NHS and GP surgeries and nutritionists around the country. Essentially, this is telling people to eat more fruit and vegetable. They're telling to have a balanced diet. They're telling them to generally eat less fatty foods, eat more starchy foods and grains, and eat low fat products, wherever possible, such as spreads, and to try and record their calories so that they are not exceeding the calorie limits for men and women, which usually around 2,000 or 2,500.

And you didn't mention calories before, but was there a calorie control in the people following the Zoe membership?

No. In the Zoe membership program, we don't discuss calories. We've discussed this at great length and researched and found there's no evidence that calorie counting is a useful, practical tool long term, and calorie restriction diets don't work for the vast majority of people.

Doing this. This is one of the important differences between the device.

This is a big difference between official guidelines in most countries and what the Zoe program is trying to teach people. And the calories, in a way, are, in my view, a very negative view because they're distracting people from eating high-quality diets. They're obsessing about one particular facet of it, which is this artificially measured energy measurement, which means rubbish food can have very low calories, but really bad for you, and some really good food can have high calories and be very good for you. This is why we're absolutely against it. But the people in the control group were told to do these things, some of which we agree with, like eating more fruits and vegetables, some of which we don't, like low fat foods and counting calories. But that was essentially the model that is used in the health care systems of most of the Western world. They had reminder leaflets and they had regular phone calls, emails from coaches, making sure they were still aware of those guidelines.

I was actually going to ask about that, Sarah, because were they just abandoned with this information? Because you're contrasting that with the Zoe membership, which has this app which is guiding you through.

So we actually spent a lot of time as a science team thinking about what we wanted the control to be. And it's something in nutritional research we spend a lot of time as nutritional scientists thinking about what we would want a control arm to be, because there's different approaches you can take. And what we really wanted to do was compare how effective the Zoe program was in improving health versus standard practice. So that's why we chose the approach that we chose, because this is the standard practice. The standard practices, you're given a leaflet by your healthcare practitioner, which contains these population based, my plate plate, USDA guidelines. Now, some people might be followed up with some consultations. So that's why we made sure that our coaches were reaching out to them at regular intervals, checking in, asking if they needed any help. They also.

Provided- I think it was on a weekly basis, right? So actually this is pretty intense compared to anything you're likely to get if you go and visit your doctor.

Yes. Although we intentionally made it not as intense as those following the Zoe program who have integrated within the program all of this information coming to them because we wanted to compare it with a real-life scenario. That's so important. They also had a video that I put together giving them advice as well along the way.

I'd like to share something exciting. Back in March 2022, we started this podcast to uncover how the latest research can help us live longer and healthier lives. We've spoken to leading scientists around the world doing amazing research, and across hundreds of hours of conversations, they've revealed key insights that can help you to improve your health. If you don't have hundreds of hours to spare, no need to worry. At the request of many of you, our team has created a guide that contains 10 of the most impactful discoveries from the podcast that you can apply to your life. And you can get it for free. Simply go to zoe. Com/freeguide or click the link in the show notes and do let me know what you think of it. Okay, back to the show. So we've got these two groups. People came in, they're randomly assigned between the two groups. One of them is the standard advice that you get from the healthcare system in the States or the UK, includes calorie restriction, has somebody checking in on you regularly. The other one is the Zoe membership. We've teased the audience for a long time. Can you tell us what the results were?

I can.

I.

Have to beg. Will you share the results?

Will you tell him or what was the lies for you?

I will tell you what some of the blood results were, and then I'm going to hand over to Tim, who's going to talk through the microbiome results. One of the key things that we're interested in looking at was how did it change some key risk factors related to long-term diet-related diseases. Risk factors such as our body compositions or our waist circumference, such as our blood fats, which we talked about earlier, the blood triglyceride levels. What we found was that people who were following the Zoe program significantly reduced their blood fat levels compared to the people following the control arm. They also significantly reduced their weight and their waist circumference. Also in people that were really adherent to the Zoe program, so followed it really well. We also found that they reduced measures related to their blood glucose control and their insulin sensitivity as well.

So it's like your.

Blood sugar and things. -yes, yes. And then what we're trying to do is also tease apart this whole question about adherence. So we know in the UK, one of the big problems, and it's the same in America, that actually only one % of people actually follow the guidelines, that it's actually quite challenging to follow these within our current food systems. And so what we did is we teased apart in our data, those people were very adherent to the UK dietary guidelines and those that were very adherent to the Zoe program guidelines as well. And what we found is even when we selected people that were really adherent to the control guidelines, to the population based guidelines, compared them to those really adherent to the Zoe guidelines, that there was still this big difference. So the Zoe program was still causing a big, significant improvement in the blood fat, in the body composition, like weight, waist circumference, and also blood pressure as well.

I have to say this is a huge relief to me because as someone who has never done a randomized control trial before, it wasn't used to be in academic science or I had done data science, privacy to this. The idea that we were going to do this test, which has very strict rules, which we haven't really talked about, but there's very strict rules about this because it's done for life and death, medicines, and things like this. So you have to put in advance onto this global website exactly how you're going to do the study. You have to commit how you're going to measure it before you do it. You have to commit that you're going to publish the results. So basically, it's a bit scary.

You were very nervous. I remember you took a bit of convincing that this was necessary pain because there's always some uncertainty.

And you can't hide. This is what I think is great about research is if you do it properly, like we did, where you register your trial on clinical trials registration, so everyone in the world can see that you're doing and you have an obligation to report the results. So even if we had found that the Zoe program didn't cause these significant improvements, we would, as scientists, be obliged to publish these for the world to see. So, yes, it was a big chance.

Yeah. I was like, Wow, we spent all of these years doing this. We might prove it doesn't work, and I guess we'll just have to shut Zoe down. I was a bit nervous. I mean, Tim, how many of the wellness things that are out there actually go through this randomized control trial and how much of advice that we hear about things that we should eat or take?

If you look in this space, in this wellness space of all the apps that are out there, everything from your smartwatch to these heart rate monitors and all this other stuff, nothing has a randomized control trial in it. So it really is extremely unique that we're doing this and putting our heads above the parapet, ready to be taken down. And in doing so, you are exposing everything you're doing to criticism, which companies that never do it, never publish results, or are never being exposed to.

I think as well, going back to the results, there's some other really quite novel results for me a nutritional scientist, that we never ask people in research, How do you feel? So we do all of these what we call objective measures, take blood samples, take blood pressure, that thing. But despite running 30 randomized controlled trials in nutrition science before joining Zoe. I've never actually said to someone, How did you feel? Which is.

Quite funny because that's actually how we live our life is how we actually feel, right? It seems odd that.

You've never did that before. I know, but I think we're so preoccupied with these very objective, clear cut, chemical measures. Gosh, we mustn't do anything wishy washy, like even ask someone how they feel. And so I've actually found it really exciting that one of the results that I think is most interesting for me, because it is quite novel, is we did ask people, What's your mood? What's your skin like? How energetic do you feel? How hungry do you feel? And we found that actually the differences in energy, in mood, in hunger, and many other of these self-reported feelings were a lot better in people following the Zoe program compared to those following the control. So, for example, we found that nearly 50 % of people following the Zoe program had improvements in energy compared to only about 10 % in those following the control. We found that sleep improved in 35% of people compared to less than 10% of people who were following the control. And we found that although people were reducing their weight slowly, but reducing their weight, reducing their waist circumference, which we know is really important in terms of our health, that actually they felt less hungry.

So lots of the Zori people are higher proportion said they feel more full, they're not that hungry.

Which the opposite you'd expect. So people on calorie-restricted diets generally will lose some weight but feel hungrier.

Which is why then they bounce back, because they've got these huge hunger signals saying, Well, I need more food. They might be able to resist it for a few months, but then after a few months, the hunger signals just become too much and lots of people bounce back.

And I guess that's exciting because this was an 18-week study because of how long it takes. Most people starting on Zoe are committing for a year at the beginning. And so would you hope to see better results at a year's time than what you're seeing at this point?

I think absolutely. The trajectory that we see in the results, because we actually took measurements halfway through as well. So halfway through the 18-week period, we took measurements. And what we saw is there was a slope where people were improving more and more some of the outcomes. We particularly saw this in relation to the microbiome. But one more thing I just want to touch on with regards to our results, I think it's also really interesting is we also looked at people who were more adherent.

So followed-Following the.

Advice more. Yeah. So we also looked at people who followed the advice more on the Zoe program than people who followed it less. And what we found is the more you followed the Zoe advice, the greater the improvements were. So we saw that if you followed the Zoe advice, you had even bigger improvements in your blood fat, even bigger improvements in your reduction in blood pressure, bigger improvements in your weight, in your waist, and also your glucose control as well. And I think that's really reassuring because when we do these studies, particularly in nutrition research, we always want to see if there's what we call a dose response effect, i. E, the more we give of that food, and it's the same in drug studies, the more you give of it, do you have a bigger effect? And the fact that we see this stepwise increase in favorable outcomes with people following it more shows that dose response.

Effect- Making you more confident that this is real and not some unlikely chance.

Of that? Or it's not a rebound because most diets will get a short-term benefit. People going on keto diets, nearly all get some... If they can put up with it, the majority will get some benefit and lose weight and maybe feel slightly better short term. But then if you follow them up for three months, you could start to get a rebound. And so by one year, most of that benefit has been lost. So you get this improvement and then a rebound. We're not seeing that at all. We're seeing a much more sustained benefits, which fits in really with the philosophy that this isn't just about changing one thing instantly. It's about educating people, about a new way of eating, about a new way of selecting foods, changing their old habits slowly. It's not easy, as you know. You were a big oats, porridge man, and probably ate lots of bagels and smoked salmon. I did. Yeah. It takes a while to start phasing that out. And similarly true even for Sarah.

Tim, I'm not eating your soup with all those beans yet for lunch. Give me a bit of time. Give me another five years.

We'll.

Report back. But I think we've all noticed in our journeys that we couldn't do all this in three months. Actually, a year or two later, you're improving and tweaking it and working out what suits you, what makes you hungry, what gives you more energy, what is best for you that also tastes great and is fun and doesn't restrict your lifestyle. And it is a journey very much. This is why it's so great to see these trajectories improving. And what Sarah didn't mention is what really I like and the long-term benefits of this are on your gut health. They do take longer to kick in.

Tell us.

About that. And so we've obviously measured the gut health at the beginning and at the end. And the measure we're now using is the ratio of the good bugs to the bad bugs. And this is a new measure that we're taking throughout Zoe. Now it's quite revolutionary, and this allows us much better to track gut health than we have in the past. And so we saw in the difference between the two groups, there was a significant difference in good bugs versus bad bugs between the two groups. As people were on the Zoe program, the longer they were on it, the more they were getting a higher ratio of good bugs and less of the bad bugs, the longer the study went on and the more compliant or adherent they were. So just looking at that graph, that's going to get even better at a year or two years as again, they start to understand the things that are improving. And I think it's really exciting now that we're starting retesting in our normal members, get a chance to actually see how they're progressing and give them milestones to hit, if you like, rather than going in the dark.

So these can be really effective tools for pointing us all in the right direction.

And because with this study, we did what we call in research a midpoint measure. So midway through the trial, we did measurements of the microbiome of weight and all these other outcomes. It allows us to see what that trajectory is. So like Tim said, what we saw was that there was some improvement in the at the midpoint, but it got even higher at the next measure that just shows that this slow increase. And we always want, I think, a slow change to happen that it's continuing to increase. And what was interesting, going back to the control group and what we were talking about with weight and the sustainability, we found that there was a very small reduction in weight in the control group at the midpoint measure, but then we found that it rebounded above their original weight in the.

Control group. So they lost a little bit of weight at the beginning and then they went back above.

And that's what you see. With all calorie focused weight loss trials, you see exactly that. You see an initial weight loss and it rebounds up. We saw exactly that. But what we saw with our trial is a small amount of weight loss, quite similar to the control group at that midpoint, but then it continued along that same trajectory.

At the end point. They're losing more weight at the end than at the beginning, than at the middle.

Yes, absolutely. That might be because microbes are improving as well. So they're giving off the good chemicals, they're helping the whole system, helping our energy management system work much better. And people are choosing foods rather than being low calorie, or actually helping them reduce the hunger pangs.

And it's a process, right? They're not suddenly switching to this perfect diet on day one. This is a process of adjusting what you're doing. So one thing I'm struck by is normally when you do these RCTs, it's on some drug, you prove it works, and that's it, right? Then you go out and you try and sell it as much as possible around the world and hopefully treat some serious issue. So is that the situation here? Is that great big checkmark this Zoe membership works?

Well, great big checkmark the Zoe membership works. And importantly, the Zoe membership works actually in a nationally representative group of people. Who hadn't heard of Zoe? Yeah. So these aren't our typical customers that are already really motivated to change their diet. So I think that's really worth to mention. But no, it's not, Jonathan. We are continually improving the whole experience. And that's what's really exciting for us on the science team. So how the program looks now versus how it was when we did the study, even though it only finished just over six months ago, is even better. So in the publication and when we presented this research, we talk about it as being our first version. Our first version of? Our first version of the Zoe program because it's continually evolving as we learn more from our own data. So there's loads of new features that are now in the program that I think make it even better and a lot better. And so what I want to do, actually, I'm going to ask you now because you can't say no in this situation. In a year, I'd like to repeat the RCT, which means a lot of money and effort, because I think that actually in a year with all the new features that are going into it, we will double the improvement that we've seen.

I genuinely believe that.

I think that sounds amazing. I think one of the things that we talked about, the excited.

Me coming from- Sorry. Did you say yes? You'll give us the money to do that. We would like the money to be able to repeat the RCT in a year.

Let's do it.

We got to hold them to that now, Tim.

Let's do it. And I think what I was going to say is one of the things that excites me is coming from a background in data science and technologies. We're just used to our technology constantly getting better, right? We all know that the is so much better than before that the experience of using Google search or whatever compared to when it first came out. And generally, that's not the way that we tend to do things in healthcare for some good reasons, but it's also part of what makes it, I believe, so slow and hard that you have this huge long period for many drugs is like 10 years and a billion dollars to do the RCT, and there's no mechanism to then keep learning and improving it. And I think what's really exciting with this approach where everyone in Zoe can choose to participate in the studies and give more data, and we can keep measuring these things all the time, is you can really continue to improve this dramatically. And I think that, for me, is the thing that really motivates me to come in every morning.

Yeah, and it's super exciting. You're absolutely right. And we're doing things that we couldn't do if we were a standard medical device company. We'd have to lock in whatever we found two or three years ago and sell it. And we know it was out of date and we could do much better, but the rules would be so limited. So this is a fantastic opportunity for people in this lifestyle space to make all the running stuff that the old traditional pharma and medical devices just can't do because the rules are just absolutely wrong for.

The technology. Absolutely. And, of course, we don't treat any disease. It gives us much more flexibility there. But I think it is this amazing opportunity ultimately to come up with something that is just so much better because of this ability to keep improving. So yes, I think it would be great to do it again in a year because I think the playback of everything you and the rest of the science team are learning should allow it to be much better.

Yeah. And I think what this study has shown us is that we're on the right path. We knew as scientists, we believe we're on the right path, but it's proven we're on the right path. But like Tim said, what's exciting is we're going to go even further on that journey. And the further we go on that journey and the more data we collect and the more features we add, and the more we learn about what is impactful and what isn't impactful, then we're creating a program and a way of life that people can follow that we know will have the maximum benefits for their health.

Brilliant. Well, let me do my quick summary. I think in this case, it's all very clear, but I will do quickly. The first thing is, I think we said, look, we've just done this big randomized control trial. It's really exciting. We've just announced it at this big conference. It's really extremely unusual to do something like this, but it's really important, we think. We ran with these two groups, one, having the same experience as if they were members of Zoe, the other one with this control, which is very representative of what's supposed to be the best advice that you would get in the States or in the UK. If you went and saw a doctor with actually probably quite a lot more support than you would generally get. And the good news is the results show that Zoe works. We saw improvements in lipids, which is the blood fat. We saw improvements in weight. We saw improvement in waist circumference, which you said briefly, but I think we know from a lot of the other podcasts, is directly related to health, which is why I think it's something that is so important. And then really excitingly, for people who are more adhered.

So there's a big range of how much people within the Zoe Armor this study followed Zoe. And for the people who actually really followed it quite closely, we saw significantly better results than the average. You saw bigger improvements in all of those measures. And you also saw a bunch of improvements in things to do with blood glucose control and insulin and these things which we know are very important for things like diabetes. And then amazingly, we also asked them how they felt and saw these really profound differences between the two arms, one of which which is all about calorie restriction, which we know is really difficult and not very sustained. One which is really about saying, Actually, nothing's off the table. And there I think you said half of the people, for example, said they had more energy who are following the Zoe arm. Is that right, Sarah?

That's correct.

Brilliant. And finally, we said we think the best is yet to come, and you sign me up on air to spend the money to launch another RCT in a year's time. So we will keep you posted. And I think the final thing to say is there is a full written paper that's in the peer review process that always takes a long time. So you start generally by having this peer review process with these conferences, which is out. There will be a paper that follows, and we will, of course, share that with everyone when that happens.

Thank you.

You've got it.

Amazing. Thank you both. Thank you, Sarah and Tim, for joining me on Zoe's Science and Nutrition today. It's been an absolute pleasure to have two great scientists share their incredible research with you today, and to give you the first glimpse at how Zoe's personalized nutrition program actually performs in a randomized controlled clinical trial. If after listening to this you'd like to see if Zoe can help you with your goals, then you can learn more about Zoe and get 10 % off by going to zoe. Com/podcast. As always, I'm your host, Jonathan Wolf. Zoe Science and Nutrition is produced by Yella, Hues, Martin, Richard, Willen, and Tilly Fulford. See you next time.