Which supplements work — and which are a waste | Prof. Tim Spector & Prof. Sarah Berry
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Welcome to ZOE Science and Nutrition, where world-leading scientists explain how their research can improve your health. Since the late 1990s, supplements have become a part of our daily diet. Today, they're impossible to ignore. But can these pills and powders really help us to achieve better health? Because despite their clinical appearance, most supplements aren't subject to genuine scientific scrutiny, no matter what they might say.

Today, I'm joined by two ZOE scientists behind a groundbreaking new study to help us find answers. And they have exciting results to share and the promise of a brand new class of supplements. Tim Spector is one of the world's top 100 most cited scientists, a professor of epidemiology and my scientific co-founder at ZOE. I'm also joined by Dr. Sarah Berry, a world leader in large-scale human nutritional studies, a professor in nutrition at King's College London and chief scientist at ZOE.

She's led extensive research into how our bodies process different nutrients. You'll finish today's episode able to make informed decisions about taking supplements. Sarah and Tim, thank you so much for joining me today. Pleasure. Very excited. So I don't need to explain the rules, but we're going to start with a rapid fire Q&A from our listeners. Tim, are many people wasting money with the supplements they take? Sadly, yes.

Sarah, can vitamin supplements provide the same health benefits as getting nutrients from eating whole foods? Rarely. Tim, can supplements actually harm your health? They can. Sarah, do you see marketing claims from some supplements and think that's just nonsense? Yes, I often see a load of Nutribollocks regarding them. Tim, are there alternatives to synthetic supplements that are just as quick and simple? There are.

Sarah, have you done a brand new randomized controlled trial on a prebiotic gut supplement that you can tell us about today? Yes. Brilliant. And finally, Tim, what's the most common misconception about supplements? I think it's that if you take an excess amount of something that is good in tiny amounts, it's going to do you some good. And there's virtually no evidence that's true.

My earliest memory of supplements is watching my grandmother knock back a long line of pills in like different shapes and colors and sizes. And I think, you know, one for her bones and one for her skin and another for her heart.

And I do remember thinking, well, that's pretty convenient. What a sort of handy, simple way to stay healthy. And these supplements are just like medicine. Now looking back on it, I also see there's something quite strange about it. And it's very sort of clinical and almost a little dystopian, you know, like some future world where you don't get to eat any real food and you get everything in, you know, seven little colored... Star Trek style. Yeah, exactly. We've had so many questions about supplements. It's probably the biggest...

topic we've been asked to cover in the last six months. What exactly are supplements and why were they created in the first place? There isn't an official definition of supplement as far as I'm aware, but it's usually some chemical that you have as a pill or a liquid or a powder that will replace a deficiency and improve your health.

And this is why we have supplements added to foods all the time routinely and

Some of them by law, for example, in breads, when you strip out the normal bit of the wheat, you lose the normal vitamins that are there, the B vitamins. And so by law, you have to supplement that food again with what you're lacking. So that's the general remit, but it's a very broad area. And it's usually taken to be things that are in some chemical form rather than in a food form.

And traditionally, when we think about supplements, we think about vitamins and minerals. These are essential for our health. And at a time where there was deficiency, supplements were of value. But we're talking hundreds of years ago, for example, where there was deficiency in vitamin C amongst sailors, which we often talk about in nutrition, that led to something called scurvy.

It's almost eradicated now. As long as you're consuming a reasonably balanced diet, it's very difficult to be deficient in these essential vitamins and essential minerals. There are some people at certain stages in their life that may benefit from supplements. So for example, iron deficiency and pneumonia is quite a big problem amongst certain populations. But for the majority of people, we get the vitamins and minerals that we need from our diet.

And 100 years ago, was this very different? Because you mentioned scurvy. And I do remember this in history, you know, like sailors needing to eat lemons or something. It's not only scurvy that you're talking about in these deficiencies. Yep. So there were lots of different deficiencies. It depended on where you were living as well. And there still are some vitamin mineral deficiencies in other countries who are typically malnourished.

But in well-nourished countries like the UK, like the US, it's really unusual. But yes, there were deficiencies years ago, not just in vitamin C, but in many other vitamins and minerals as well. Ricketts, for example, you know, all these pictures 100 years ago in Glasgow of kids with bendy joints. This was a vitamin deficiency.

deficiency that now really no longer exists. We often talk about how the diets in the past were much healthier. So why was there this concern and actually this occurrence of deficiency? It generally happened during industrialization and the UK was at the forefront of the industrial revolution and people rapidly moved from the countryside where they didn't really have these deficiencies to big cities

and the food supply had to be reorganized and people ended up just for example eating bread or just porridge didn't get any fresh fruits vegetables any variety and so as soon as you lose that variety you go on to these staples you do risk having some of these vitamin deficiencies so it's

that was the cause of this. And this actually you see in times of war and displacement of people, that's when you get these vitamin deficiencies in things like thiamine deficiency, vitamin D, vitamin C. All

All these occur in major catastrophes. So that's why nutrition was actually set up as a science, really because of the two world wars, dealing with nutritional deficiencies at a population level. So that's why we've been obsessed with this idea that supplements are replacing these nutrients that for these geopolitical reasons have been a problem. And

And this legacy has carried on into the modern day. And we've still got this mindset that we're living in this post-war environment, which no longer is applicable for the vast majority of people. And I think when we think about supplements, it's thinking about deficiency, which very, very few of us are deficient in most of our essential nutrients, micronutrients.

We also think about insufficiency. So if we think about iron, for example, some people who aren't getting enough iron or aren't absorbing it well might have iron deficiency anemia. There is a place then to supplement with iron. Then there's other people that might have moderately okay iron stores, but might be quite fatigued and may benefit from some additional iron.

So that's in a phase of insufficiency. But this whole idea of adding extra nutrients or adding extra chemicals, vitamins, minerals in to then boost your health is

I think that's where we start to go into problems. So using iron again as an example, if you have sufficient iron stores, this idea that, oh, well, hold on, iron prevents us from feeling fatigued if you have anemia. Let's add more iron in to feel really this great boost of energy. If you've got enough, you don't need to add more and it's not going to make you feel more energetic. And if anything, it can actually be harmful. So is my analogy a bit like my car needs...

petrol and it needs oil to function. But as long as it's got enough petrol, enough gas and enough oil, like if I put twice as much oil, actually all I do is like pour oil at the car. I'm not making things any better.

Yeah. And I think as well, our bodies are so, so clever. Our bodies know how much we need of these different vitamins and minerals and other nutrients. So for example, with iron, we control the levels within really tight upper and lower boundaries.

And we have clever mechanisms to make sure we can control our iron stores, our vitamin stores, our minerals, et cetera. And by adding loads more in, we're making our body work harder. And sometimes they can therefore even be toxic because if we don't need it,

In many instances, we need to get rid of it to prevent toxicity and that can put extra strain on our kidneys, other organs, etc. Calcium is another great example. For the last 30 years, we've been told that we're all lacking calcium and that's why we're getting brittle bones and fractures are going up. And it was never actually true. And our body is brilliant at keeping our calcium levels exactly right.

And when they've done studies finally showing that when you give people calcium supplements as opposed to in food, you don't get any benefit on the bones because it doesn't get into them as it does when you're normally eating food.

And it can build up to dangerous levels and increase your risk of heart disease. So again, we've been misled from this old idea that vitamins and minerals were deficient in everybody. Even if you're not deficient, having extra is going to give you benefits. As Sarah's saying, it's across the board. This is this real misconception about this whole field. You're saying they've now done studies on taking calcium aminobutans.

as a pill and actually increases your risk of heart disease? Yes. So it doesn't help fractures, which is what it was supposed to be. That's what I used to prescribe it all the time, giving calcium to menopausal women, for example. It doesn't prevent fractures and it

there is increasing evidence that it's associated with heart disease. It hasn't been proven causally, but it's associated with increased risks of heart disease, possibly because it's increasing the hardness and thickness of your arteries. So these are just several examples, whether it's vitamin C or it's calcium, of this mindset that our body just needs minute amounts of these things, finely tuned, and there's no reason to have 10, 100 times more of it

there's never been shown that that is beneficial. I think, Jonathan, it's always important to caveat, and you know I'm always here to add that extra nuance, that I think, yes, in general, adding in these supplements, particularly high doses, is not necessary for the majority of the population who are having a healthy balanced diet.

there are certain groups in the population that will benefit. So particularly certain elderly groups who aren't consuming enough energy, who aren't consuming the right diversity of foods, who aren't consuming enough foods, they may benefit from having just a kind of broad spectrum multivitamin and mineral. Folic acid,

Absolutely for women of childbearing age who are trying to get pregnant in the early stage of pregnancy, supplementing with folic acid reduces the risk of neural tube defects between 30 to 75% in different populations. People who have iron deficiency anemia, yes, supplementing with iron in the right way. B12 works very well for vegans who struggle to get their B12 levels up. We talk about generalities here. There are obviously subgroups that do still benefit from it.

So if I understand this rightly, you're saying there are particular groups for whom supplementation makes good sense. And so being pregnant is a great example that you really believe in. If you're elderly and you're no longer probably really eating as much food as you should. Or you've got an eating disorder, for example, would be another one.

So in those particular cases, but in general, we're not in the world that these vitamins were invented for, which is just industrialization. And you're just basically getting plain white bread every day for months on end when you could actually be missing them. Even with the rather sad state of the diets that we eat today in the West, actually, vitamin deficiency is not a problem for most people. Yes.

For most people, the thing that annoys me the most when I think particularly about the Nutribollocks out there is that you go into some of these supplement aisles and you see these bottle supplements that are promising the world that you'll look 20 years younger, that these hair supplements, these menopause supplements, and they're just washed with all of these claims.

And, you know, everyone wants a quick fix. Everyone wants a silver bullet. They're not the silver bullet. And often they're marketed at 10, 20 times the price of a standard multivitamin and mineral just because it says whatever claim actually, you know, prays to someone's insecurity or concern that they might have.

People think if I'm paying a lot of money for a vitamin or a mineral supplement, it's got to be good quality. Well, that's not the case. Most surveys show that sometimes they don't even contain the chemical they say they do. Most of them are now made in China. It's the biggest producer of these in vast factories. And I think the majority are now made for

from genetic engineering of microbes. They ferment them in these big tanks. So people's view of what these are is very different to the reality. And they don't know that when they're taking these, it actually contains the products they think it does, or that they aren't going to have other additives in there that might make sure they don't work or get absorbed.

Now, Tim, what I see around me with supplements is not things that talk about solving my deficiency or the deficiency that my daughter might have, but making all sorts of health claims, right? So they say it's going to boost my immune system or my brain health, or it's like good for my children's health. I see that on all the cereal packets. What's going on there?

This is a throwback to the post-war years where they did studies of people who'd suffered famines or had major deficiencies. And the early nutritionists would discover that someone, for example, had hardly any zinc in their diet.

were getting lots of infections. So they had zero zinc, their blood levels were zero, and these groups were getting recurrent infections. If they're placed with zinc, then they got better.

That's been translated 50 years on to say that if you add zinc to anybody at whatever level, it's going to boost their immune system or aid their immune system. And is that true? It's rubbish. There's no evidence that additional zinc has any enhancing effects on your immune system once you've relieved the deficiency.

And zinc deficiency is incredibly rare if you're not in one of these extreme situations. So that allows any food manufacturer to add a little tiny amount of zinc to any food and they can then claim it boosts immune function. Makes me feel very angry.

because people are being misled. And this allows big food manufacturers to stick labels on foods that are blatantly unhealthy, contain 30% sugar with a healthy label saying enhance or boosts your immune system.

when the science really doesn't back it up. And we are prevented in many other areas from giving real advice of things that can actually be beneficial for your system. So Big Food has made sure that these really old-fashioned, out-of-date science stays there and that they can, just by adding tiny amounts of whether it's copper, manganese, zinc...

niacin, whatever, made artificially to bad foods can now give it a health claim. It's ridiculous. It should be stopped. So what I understand is that the sort of supplements that I'm likely to get on the supermarket shelf today are

are not likely to deliver sort of big health benefits to me unless I'm in one of these categories you've described before. And so I'm not suddenly going to be able to boost my immune system or my brain health with the supplements that we traditionally see. Is that a good understanding of what I've heard from you both? Yeah, I think that we need to move away from worrying about deficiencies and taking supplements for deficiencies, except in a few certain population groups.

And we need to be cautious about seeing these supplements and thinking that they're going to boost our health. That's where there isn't sufficient evidence. But I think the area of fortification and the area of supplementation are two slightly different areas. The whole reason for fortification is to try and target key minerals that at a population level we were struggling with some years ago. So Tim, if the problem isn't deficiency, what is the problem with our diet today?

The problem with our diet today is that high-risk processed foods dominate what we're eating. So over 50% of what we're eating has some element of risk to our health. It's lacking in nutrients. It's lacking in fiber.

It's making us sick. It's making us overeat. It's upsetting our gut microbes. And this is this new way of thinking. So it's not about individual chemical deficiencies. It's about the whole environment of our food that is rotten, that is making us sick, that is inflaming our gut microbes, which then inflames our immune system.

which then leads to this constant state of irritation in our bodies. So we get all these chronic diseases. And I think it's sort of a mixture of overnutrition with lower quality food. So we're sort of in this new era where we're getting fiber deficiency whilst being overfed. We're not getting quality food. We're just being bulked up with sugars and other chemicals. And this, I think, is the major problem we're facing today.

And it can't be cured with supplementation for these individual items as it was very effective after the war. That's the big difference. So we need to change the villain here. The villain is not the lack of vitamins. It is the whole food system, the food quality, and the fact that we're missing out on the whole plants that we used to be eating before big food got in there and changed where we eat. And

And I think, Jonathan, even though we've said, okay, if you have a balanced diet, you don't need these supplements, etc., we're getting what we need. We know that the current diets that we're having that are deficient, like Tim said, in fiber, in plants, in diversity, etc., and excessive in all of these unhealthy nutrients.

That kind of diet is accounting for one in five premature deaths. We know in the UK and the US that 20% of premature deaths are estimated to be from the food that we're eating, from having an unhealthy diet. And I think that's a really stark statistic because that means that 20% of premature deaths can be prevented by changing our diet. But it's hard. And not only that, it's also all those chronic diseases that...

And some estimates you could reduce that burden by about 80% if you transferred everyone on the current bad diet to an optimal diet. So I think realizing what the problem is and what a major impact it could have on every population in the world, I think is really important. And I think as well, at any point we can make a change in our diet. And I know we've talked about this often in the podcast. There's some great research showing that whether you're 40, 50, 60, 70 years of age,

there is still a huge benefit to making a change here and now. You both talk a lot about this on this podcast, as do many other guests, about the amazing ability to impact your health as you change your diet. And I think we know that many people find it really hard to make significant and sustainable, permanent changes to their diet. Why is that?

I think there's lots of reasons and I think the reasons differ for every individual. There's practical reasons such as accessibility to healthy, nutritious, fresh, whole food.

There's affordability. There's been lots of research that shows on average there's a 50% price difference between minimally processed food compared to the old processed, heavily processed equivalent foods. We've also got to remember how we live our lives has changed, that you have many households where both parents are working.

50, 60 years ago, typically very few women were working. Fortunately, it has changed. But one of the problems with that is then there's less time to prepare food. There's less time to menu plan. There's less time to think about it. And it's easy to take the easiest route. I think education is the other thing that's changed. Most countries no longer teach cooking in schools.

Many homes, when you're renting them, certainly in the US, don't come with any cooking facilities, only a microwave. So this is the other problem that...

Even if you had access to food, you wouldn't have the education or the facilities to cook with it. So it's a lot of grassroots problems as well, as well as these food deserts that every country has. Our needs have changed. So when supplements were really first becoming important was when we were deficient in micronutrients.

That's not the issue now. The issue is we're deficient in fiber. We're deficient in plant diversity. We're having excess of other nutrients. So the problem has changed. And so we need to think about a new generation of supplements and a new era of supplements. What are we trying to supplement for now? Because our needs are different to when, you know, 50, 100 years ago. So given that,

Problem that suddenly we need to supplement something completely different from what we had to supplement in the past I know that you came to me and said I need to do a new clinical trial Yeah, this happens quite often as listeners of the podcast may know and you said you want to try it like a new type of supplement right and you described it as a prebiotic gut supplement sort of plant-based

not powdered and you want to see whether it was actually possible to do supplementation against the sort of problems, the scarcities we have today. Can you explain for a minute, like,

Why that was and the idea behind it? Yeah, so amongst the science team and together with our head nutritionist Federica Amati who was really heavily involved in this as well We wanted to create something that was really tackling what we believe are the biggest problems their lack of fiber their lack of bioactive so chemicals like polyphenols that are in so many of fruits vegetables and other plants and

and also the lack of plant diversity. So as a population in the UK and the US, these are the biggest problems.

There's also other features that we wanted to tackle, like we're not having enough whole grains, we're not having enough legumes, pulses, beans, those sorts of things. And that's the root of, I think, the problem alongside overconsumption of other nutrients such as saturated fat or sugar, for example. And bearing in mind that we live these busy lives, bearing in mind all of the challenges that we just talked about,

We wanted to create something that would be a helping hand, a new kind of supplement, and a supplement that was also representative of the kind of way that we should be eating our food. So it's whole foods where the structure of the food is generally intact. And we've done whole podcasts on this, Jonathan, where I've talked about the importance of the food matrix. So the importance of retaining the structure of the food, because that plays also an important role in modulating the healthfulness of that food.

And Sarah used some very fancy words like modulating and matrix. Could you help to understand? Because I think you have this hypothesis that using these sort of synthetic supplements, which are all powders, might be less effective than

things that you would take from plants, but could you help to explain that better? Yeah, so let's take a step back. When I think about the healthfulness of a food, so how healthy a food is, I think of three core elements. I think of the nutrients,

So the very classical things that we talk about, how much protein, fiber, fat, carbohydrate, minerals and vitamins there are. Then I think of what we call the non-nutrient bioactives. So these are the thousands of other chemicals that are in food. And we know food has on average about 50,000 chemicals. So these are chemicals like polyphenols that we often talk about that have really beneficial effects mediated through the microbiome in our health. These are the sorts of things that...

feed the different good microbes in our gut? Yeah, they have wide-reaching effects. Many of the effects are mediated through our gut microbiome through essentially feeding, yes, our good bugs in very simple terms. And then we know that these bioactives and these nutrients are encapsulated within the structure of a food. Okay, every food has its own different structure. We call it the food matrix, but we're essentially talking about the structure of the food. And the structure of the food is

changes how those bioactives, how those nutrients are metabolized, how much they're metabolized, where they're metabolized, how much reaches the gut, and also our kind of sensory feedback mechanisms, like how full they make us feel, how hungry we are later, for example. And so when we're thinking of creating a new generation of supplements, I think we need to think of

the macronutrients that we're deficient in, fiber. 95% of the UK, US population are not consuming enough fiber. We need to think of all these bioactives, all of these polyphenols that we don't get enough of. Having more in our diet reduces inflammation, feeds the microbes, etc. And then we need to think about making sure that where possible and where relevant,

not just for the sake of it these are within a suitable structure of the food so for example if we're giving nuts don't grind the nuts down give little chunks of nuts if we're giving the seeds don't grind the seeds down give chunks of the seeds because that will change how we absorb it where we absorb it how we feel how we metabolize it

Another way of thinking about this is that in the past, we've been reductionist and we've tried to say, okay, well, rather than giving you lemons, we'll just extract the vitamin C from the lemon, that one chemical ascorbic acid, which gets added to processed foods and things.

Whereas you're ignoring the other 800 chemicals in the lemon so that if you just did a bit of dried lemon, you'd be actually getting the benefit of hundreds of other potentially beneficial chemicals. And that's the real philosophy here is in the past, it's been reductionist. We're thinking about supplements in their chemical nature and just let's get the best one from all of them.

Whereas actually, plants, as you said, have 50,000 chemicals or more. And we're trying to harness as many of those because most of them are likely to be beneficial for us and that we don't know yet exactly what they are. So it's taking a much more holistic view of how we should be supplementing with real plants. And Tim, you're a microbiome expert. This is one of the things which has obviously been the biggest change in our understanding of...

I guess not just nutrition but also human health over the last 20 years. How does that play into what Sarah's talking about, about this variety of different chemicals but also the desire not to smash things up into powders? There have been studies for the last 20 years on giving fibres to individuals and seeing how the gut microbiome changes. And so traditionally we would use

one or two fibers and the three commonest ones are something called goss and phos and inulin and when they were given individually in large amounts they would improve the gut microbiome but

Interestingly, they wouldn't have as much benefit as you would have thought. They would only feed a certain subtype of the community of microbes growing there. You didn't get the increase in diversity. So the next group of researchers then started combining five or six of them together. And then you saw a greater improvement in the gut microbiome.

But I don't think we should stop at five or six. We should be going for hundreds or thousands of different types of fiber, which would then have exponential effects. And that's really what the science is showing us. And as Sarah is going to explain, when we tested us in the gut microbiome, that's exactly what we saw. So the more diversity of fibers you put in, the greater the benefit you see on the gut microbiome. And we also know this is greater than probiotics.

The effect of fibres is a bit like a fertiliser rather than just giving little individual seeds, which is what the probiotics are doing. We've been talking about a prebiotic gut supplement. Can you remind people what the difference is between a prebiotic and a probiotic? Absolutely. They sound almost exactly the same. They do, yes. Biotic just means it's life-giving and it's healthy. It has a health benefit. A prebiotic...

means that it's like a precursor. So it's fertilizer for gut microbes that then allows them to proliferate and give health benefits. So it's like you're fertilizing your gut microbes to then go crazy and be healthy. A probiotic is a live microbe that you ingest,

and then that in itself acts as a seed and then has health benefits on the gut. And so both of them have been shown to be healthy in multiple experiments. So you had this idea that would it be possible to create a sort of prebiotic gut supplement and you definitely said you wanted to go and do a study and prove whether or not it could work. How did you come up with the blueprint for this, the recipe for this supplement? So I

I need to give credit to Federica Amati, our head nutritionist for this. She spent a lot of time thinking firstly about what are we trying to solve for? As I mentioned, lack of fiber, lack of diversity, lack of bioactives. What are we trying to make sure it's not? Just a powdered supplement given the importance of the food structure in this, given the important role that preserving that plays in some instances.

And she developed the recipe that we went on to test in an RCT. And this recipe is high in fiber. It's high in bioactive. So it has the amount of polyphenols, for example, that you'd get in the equivalent of a couple of portions of fruit from just a small amount of this particular gut supplement.

and it's high in plant diversity. So it's got 32 different plants, but importantly, 32 different plants from a whole variety of plants. So from mushrooms, from legumes, from whole grains, from fruits, from vegetables, from nuts, from seeds. And what it's delivering, as well as lots of fiber, as well as lots of biactors, as well as lots of polyphenols, is an estimated 54,000 different chemicals that are all going to have a role

in our body, in our health. And Tim, I know you spent a lot of time on this also. How did you figure out what to put into this recipe? Because you had sort of this one shot for the trial. You wanted to try and prove whether or not it's possible to come up with this whole new class of supplement, right? This privatic gut supplement.

So we sat down with the team and looked at the different possibilities that we'd be able to put into this and came up with a short list of different foods that have been shown in the literature to be beneficial for health or particularly for gut health.

And from that, we then refined it down to foods that you wouldn't be normally eating every day so that we had a variety of ones that we'd be actually adding to the chemicals that you wouldn't find in your normal diet. So it was this combination of factors based on theoretical knowledge and trying to work out what would be in addition to the average American British diet.

But of course, that was just the first step because we knew that just taking the theory isn't the same, particularly when dealing with a combination of foods that might interact with each other. We know that if you've got different chemicals in there like magnesium and zinc and iron, they interact with each other, so they stop each other working.

And that's why you have to study the whole thing together once you've got your shortlist. And that's exactly what we did. Yeah, and I think that's really, really critical. And that's one of the key reasons we did the randomized control trial, because it's all very well putting on the back of pack, backed by science, because it's got these 20 ingredients that there's these studies on the individual ingredients.

But because we know in nutrition science now that they do interact, that they do modify how one acts versus another acts when they're in combination, you can't take that evidence. I don't think it's an appropriate thing to do. You need to look at the product as a whole. You need to look at the supplement as a whole and see as a whole how does it impact your health.

So Sarah, you came to me and said, I want to run this experiment. Basically, I've got this theory that there might be an ability to sort of create a supplement that works. And you want it to be this thing called a randomized controlled trial. Could you tell me about that? Well, I went cup in hand. I said, Jonathan, please, can I have some more money? Yeah.

Because randomised control trials are very expensive to run, hence why so many supplements out there, the majority of supplements don't have randomised control trials because they're challenging, they're expensive. So a randomised control trial is the gold standard way to conduct nutrition research in order to look at how effective a given food, nutrient, dietary intervention is in terms of our health.

And we conducted a trial where we recruited over 300 people and we randomly allocated them to what we call three treatment arms. So a third of people were randomly allocated to consume for six weeks our prebiotic supplement.

For another six weeks, another third were randomly allocated to consume a probiotic. And we chose one of the standard probiotics that you can find in your grocery store that there is lots of evidence for its effectiveness. And so that's like a little pill that has some live bacteria in it. So this was a little pill containing live bacteria for which there's lots of evidence showing it's beneficial. One of the most popular ones that's been shown in multiple trials to have a benefit.

And then we chose a third control, which was what we call a functional control, because the real complexity of dietary interventions is that when you add something into your diet, often you're displacing something. And also we consume meals, we consume diets, we consume whole patterns, you know, dietary patterns. And so if we were going to add in this control,

prebiotic supplement that the goal is for you to sprinkle it on top of your food or add it to, you know, on top of your yogurt, your salads, et cetera. We wanted a control that would be used in a similar way. And why is the control group so important and why is this randomized control that you're talking about? Why is that important? So control group is critical in a randomized control trial.

It's critical because there's lots of noise in us. So if I was to give you a supplement that

There might be a change for the better or for the worse that could be random rather than due to the supplement itself. And so what we do is we compare your response to someone who is having a control. So in drug trials, we often call them placebos, where you might have an active pill versus a placebo, like a dummy pill that's got nothing in it. And it's so that we can see, is there a true, real effect of what we're giving you versus that control?

So that's why the placebo effect is real, whether it's a drug trial or a food trial, particularly when you're looking at some subjective outcomes like how does it affect your mood, your hunger, your energy levels, all these things, really important to have that. And we know from many, many published studies that people who are told that they're having diabetes

a supplement, whether it's a real or dummy, there is this placebo effect, this dummy effect. And people often say, oh yes, I felt healthier. I felt better. I slept better. When actually it's just due to them thinking that they're taking something. So that's why it's really, really important to control for that because then you have confidence that there is a real effect going on. Now, if you're only taking blood measures and

then there isn't that subjectivity, for example. But because in our trial, we were looking at multiple outcomes, including how people were feeling, it was even more important that we had those control arms. So these three groups, one was taking this prebiotic gut supplement, one was taking a probiotic, and one was basically taking sort of bread sprinkles? Yeah. So the third control was these kind of bread sprinkles, which can be used in the same way as the prebiotic gut supplement. Okay.

And what was the next part of the trial? Well, a trial is quite complex. So we have to go through quite a rigorous process of designing the protocol, deciding really important features of a protocol, like inclusion criteria, who are we going to recruit? How long do we want them to be on the trial for? What are our key measures that we want to look to show that there's a health effect?

What kind of dose are we going to give of the prebiotic gut supplement or the probiotic, etc.? Once we've made those really key decisions, we then have to go through a process of applying for ethical approval. And this is a painful process, but a really important process. And then we register our trial on a clinical trials database. It's a public database. It means, therefore, you are obliged to publish your results online.

and it's a really important part of the research process. It means we can't hide if we don't get the results that we want to see. And Sarah, I think, you know, I want to tackle sort of the elephant in the room here. You know, you're both research scientists. Obviously, I'm at Zoe, which is also a commercial company. Like, how is what you're describing different from what, you know, most of those companies that are selling a vitamin or a supplement might be doing? So I think there's two key differences. One is that we're doing an RCT, right?

is the main difference where many will use the term backed by science where they will lean on published research based on individual ingredients.

And then the second thing is, is the fact that we did a randomized control trial. There's many companies that will do what we call kind of longitudinal studies or consumer surveys. Or surveys. Yeah, we could call them. They pay a third party to survey 20 people. They give them the product and they say how much they improved. It's a bit like the cosmetics industry does the same thing for wrinkle creams. And

And so they say, you know, X percent of people said that they had more energy after, which is great, but compared to what? They don't have the control arms. So I think having the control arms is the most critical thing here, as well as the fact that we were doing on the whole prebiotic supplement.

You got these people to do this. What did you end up measuring? So we measured at the beginning and end of the six-week intervention when they're taking the different treatments, so the prebiotic gut supplement, the probiotic and the other control. We measured microbiome composition.

We measured gut symptoms, so everything from indigestion to bloating and so many more. We also measured how people feel. So we asked people, what's your sleep like? What's your energy like? What's your hunger levels like? What's your mood like?

And then we also looked at people's biochemical markers. So by this, I mean things like their blood fat. So like their bad cholesterol, like LDL cholesterol, their levels of inflammation, etc.,

And then we also invited a smaller group of participants to come back and do a sub-study called a post-prandial study. And this is a study where we asked people to consume a carbohydrate load, so 60 grams of carbohydrate on one day on its own and another day together with the prebiotic gut supplement.

to see if that modifies how we metabolize it and how we feel if we add that into a meal, because that's how it's intended use is, to add it to a meal. So what were the results? The key finding was that the prebiotic gut supplement significantly improved gut microbiome composition.

It significantly improved it compared to the probiotic and compared to the control. And interestingly, it improved species that we've previously identified through our years and years of research at ZOE that are associated with favourable measures of health, favourable measures of blood pressure, lipids, inflammation, et cetera, and so much more. That was one of the key findings. I'll just add, the detail is, you know, it was significantly greater, but

I was expecting a bigger effect of the probiotic. It was well proven, but this had 10 times the effect on shifting the good and the bad bugs compared to the probiotic. So yeah, it was sort of night and day. And this just goes to show that generally, you know, the attitude of giving fertilizer rather than seeds seems to be a much better approach for the gut microbiome. Can I interrupt you for just a second to share something that you might find interesting?

Because of the success of the clinical trial that Tim and Sarah are discussing here, we took this prebiotic gut supplement in the trial and we developed it into a new ZOE product. We've called it Daily 30 and it's available to buy now from our website, zoe.com. You see, after the trial finished, a number of the team, including me, immediately began using the supplement each day.

Now, I'm someone who tries really hard to eat a diet based on everything I've learned at Zoe, but ultimately, I'm juggling my busy job and my family life. And so I fail often. Adding a scoop of daily 30 to my yogurt each morning has been a game changer as it's enabled me to consistently hit that magic 30-plant number with effectively no effort. What I love is it has all of these diverse ingredients in it that I would never normally eat.

Lion's mane mushroom is one that springs to mind. We did a whole podcast on the incredible health benefits of mushrooms. Daily 30 has eight mushrooms in total that now I'm eating every day. Buckthorn is another.

a bright orange berry that grows in harsh Asian climates. It's bursting with polyphenols, which we know are there to boost your good gut bugs. I think it's working because I'm feeling great and that's because, sorry to overshare, but my bowel habits have become more regular. To me, that's definitely a signal of healthy digestion and happy bugs. I also feel fuller for longer, which means I'm snacking less than before.

And best of all, Daily 30 tastes great because it's not a synthetic powder. I feel great adding it to my breakfast. But don't take my word for it. Why not try Daily 30 yourself and see if you can feel the benefits? Just head to zoe.com, where for the next seven days, listeners to this podcast can get 10% off by applying the code FEEDYOURGUT at checkout. That's zoe.com with code FEEDYOURGUT at checkout.

And let me know how you get on with it. I think you're going to love it. And what was interesting is we measured the particular species that were in the probiotic, because it's always a good way of looking at what we call compliance. Did people actually take the probiotic?

And those significantly went up. So we knew that they were really taking the probiotic, taking the capsule. So you're basically measuring their poop at the end of the six weeks and you can tell they're taking the probiotic because you see the probiotic did work. There were these additional bacteria in their guts. But what you're saying is even adding a few of these special probiotic

is nothing like as effective as adding a whole blend. It didn't shift the good to bad ratio nearly as much as the prebiotic gut supplement. So that to me was a bit of a wow moment and changed my view of whether the future is all about

developing probiotics or actually this whole new way of thinking about prebiotics and looking after our gut that way. Were there any other results? Yeah, so we also asked people how they felt. And this is something we do in a lot of the trials that we do at Zoe. And I know I've explained before that we rarely do this in nutrition research, but actually how you feel ultimately is one of the most important outcomes we should be looking at. And what we found was that the number of people or the proportion of people who

who had improvements in things like happiness or in energy and these kind of self-reported outcomes was far greater in those who were taking the prebiotic gut supplement versus those taking either of the controls. And so we can say that with some confidence because we had that control group. It wasn't just because they felt that, oh, well, I'm taking something. So of course I have more energy, et cetera. They actually felt different. Yeah. So they had differences in hunger.

differences in their feelings of energy and also differences in their feeling of happiness. And Tim's far more familiar with this, but there's lots of evidence to underpin that actually if we can modify the microbiome, which we saw in our microbiome results, that that can bring about changes in things like our mood, in things like our levels of hunger, and also in terms of like our energy levels. And I think the other interesting thing is this happened

pretty quickly, didn't it? We didn't have to wait till the end of the study to see these actual self-reported changes. So you do notice quite quickly that these things are happening, particularly if you're having to fill out a form every day and do it. But I think it shows that changing your diet can have dramatic effects quickly on some of these

things that traditionally haven't been measured in nutrition science at all. Another finding that we had that I was particularly excited by is that in a subgroup of individuals who had slightly higher cholesterol and slightly higher levels of inflammation, we found that when they were taking the prebiotic supplement, there was a significant improvement in inflammation in

in cholesterol as well. So we saw a 0.22 millimole reduction in LDL cholesterol, which might sound small, but that's a really big reduction.

How much did they take of this gut supplement every day? So we asked them to have a couple of scoops a day. So it's the equivalent of kind of a small handful. And we asked them to carry on the rest of their diet as they would. So they could just add it to their diet. And something else we did is we did actually look at if their diet changed, if other aspects of their diet changed across the three treatment arms. Because that's really important to be able to say, well, hold on. The effects that we're seeing are due to

the prebiotic gut supplement and not due to the fact that they're making other changes. And we saw that their diet remained consistent across all three arms so that we could say again with more confidence it's due to what we're adding in rather than that we're taking something out.

So it's quite a small amount, like it is definitely still a supplement rather than here's an entire new meal that you're just giving people to eat. Yeah, and this is the idea, given what we said earlier about how difficult it is to change your whole diet, to start modifying your meals. The whole purpose is that it's just something to supplement your normal food. It's not to replace your food. We still want to encourage a healthy balanced diet, but it's a really simple way just to add that extra kind of boost to your health into your meals. ♪

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You've described all of this, you know, has this been peer reviewed and published? So the hard work doesn't stop once we get the results. We then write it up as a paper and we submit that to go through a very vigorous peer review process for publication in a journal. So the reason you wanted to do this was really to understand if it was possible to come up with a whole new like category, I guess, of supplements for 2025, not, you know, 1925.

What's the overall takeaway here, Tim? The overall takeaway is that we've succeeded.

that beyond our expectations, this approach by embracing all we've learned about gut health and nutrition, the new way of thinking, allows a whole new way forward of providing these supplements to diets. And at the same time, whilst we want to still encourage people to have as healthy a diet as possible, this is a way to enhance that simply and easily that everyone can do.

particularly when they've got busy lives. It's all very well saying this is the perfect diet, but we live difficult times and we need to be pragmatic as well. So I think we'll be seeing a whole range of other products based on these principles.

seeing how much more effective it is than chemical powders or even some of these individual probiotics as we've shown here. This is a whole new way of thinking about how we can enhance our gut and our health. And are there equivalent results for sort of these traditional chemical powders that you were talking about at the beginning? As far as I'm aware, there's nothing of this scale or significance in terms of result.

Most of these other powders haven't been tested properly. And if they have, they're more likely to be the survey type without a full placebo control or done over significant periods of time. But there are some companies doing it, and we do want to encourage others to do the proper studies. And when they do do these proper RCTs, they should be applauded.

And what does it tell you about other products? You also told me when you came away with this, that this does also tell you, for example, that probiotics do work and they do have an impact. Is that right?

Yes, our studies show that the probiotic, this is lactobacillus rhamnosus, which has been shown in other studies to have a beneficial effect on things like anxiety and depression, does have some benefit on the gut microbiome. But relative to the prebiotic supplement, it's a minor effect. So I think we need to be looking at combinations of probiotics to have anything like the same effect as we found with our gut supplement here.

The science is still developing in the probiotics, and we believe that future is going to improve as well. So I'm not ruling out combining probiotics with our prebiotics in the future as well. I think there's a whole new era that we can see that could really change the landscape of nutrition.

Brilliant. Thank you very much. I'm going to try and do a quick summary, and I think we covered a lot of different areas. I think we started with the fact that almost everything we're told about sort of vitamin supplements comes from this world of like, you know, little kids having rickets in 1900. And it's just not a match for the world we have today where we're all suffering from too much food that is sort of emptied of quality. Jonathan, and that is in the Western population.

micronutrient deficiency is still a problem in some countries. It's really important to caveat that so we don't underplay that. Thank you. Adding zinc is not going to improve my immune system. That's rubbish. Too much of some vitamins could even hurt me. So I heard that actually taking calcium supplementation

won't help my bones and it's actually associated with an increased risk of heart disease. So this idea that there's no possible downside isn't right. We need to be aware that taking super doses and things that our doctors don't suggest to us isn't necessarily going to help.

But on the other hand, today we have a completely separate problem, which is our gut microbiome is getting none of the food that it needs, that we're eating this diet that is all this high-risk processed food, completely different from what we grew up with. And therefore, there is a real gap that

that we need to understand how to supplement because it can be hard. You're in an airport, you're traveling, you go to the corner store and there's like nothing that isn't made by big food and has like 16 things in the label. And when I scan it, it says it's high risk. And hence you had this idea, well, what about if we could try a new supplement for the gut for 2025? And think about something that's going to be a prebiotic gut supplement with all the science we have today.

did this randomized control trial, had these amazing results that we really saw a big shift in the microbiome. We saw a shift in a whole set of measures about how people feel in a subset. You also saw a shift in these other measures.

Interestingly, we also saw improvement with a probiotic. So we saw benefit from that as well, again, showing sort of the way that it is possible to shift the microbiome relatively a small amount. And I think my takeaway is this is really exciting. It's just like the opening up of something really new, a whole new category of supplements that both of you could actually believe in rather than your normal response when I ask you about it and you say, well, that's all nonsense and tends to be in stronger language when we're off air as well.

Yeah, I think you've summarized it there, Jonathan. Now, if you listen to the show regularly, you already believe that changing how you eat can transform your health. But you can only do so much with general advice from a weekly podcast. If you want to feel much better now and be on the path to live many more healthy years, you need something more. And that's why more than 100,000 members trust Zoe each day to help them make the smartest food choices.

Combining our world-leading science with your Zoe test results, Zoe is your daily companion to better health for life. So how does it work? Zoe membership starts with at-home testing to understand your unique body. Then Zoe's app is your health coach using weekly check-ins and daily guidance to help you shift your food choices to steadily improve your health. I rely on Zoe's advice every day and truly it has transformed how I feel. Will you give Zoe a try?

The first step is easy. Take our free quiz to find out what Zoe membership could do for you. Simply go to zoe.com slash podcast, where as a podcast listener, you'll get 10% off. As always, I'm your host, Jonathan Wolfe. Zoe Science and Nutrition is produced by Julie Pinero, Sam Durham, and Richard Willett. The Zoe Science and Nutrition podcast is not medical advice. And if you have any medical concerns, please consult your doctor. See you next time.