Which supplements work, and which are a waste? With Prof. Tim Spector and Prof. Sarah Berry

Can pills and powders really improve our health? Despite their clinical look, most supplements aren’t tested with the scientific rigour we expect from medical treatments, and many don’t live up to their promises.

Tim Spector is one of the world’s top 100 most-cited scientists, a professor of epidemiology, and ZOE’s scientific co-founder.

He’s joined by Prof. Sarah Berry, a world-leading expert in large-scale human nutrition studies, Professor of Nutrition at King’s College London, and Chief Scientist at ZOE.

By the end of this episode, you’ll have the latest science to help you make informed decisions about supplements and understand what your gut health really needs in 2025.

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Transcript

Jonathan Wolf: Sarah and Tim, thank you so much for joining me today. 

Prof. Sarah Berry: Pleasure. 

Prof. Tim Spector: Very excited. 

Jonathan Wolf: 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? 

Prof. Tim Spector: Sadly, yes. 

Jonathan Wolf: Sarah, can vitamin supplements provide the same health benefits as getting nutrients from eating whole foods?

Prof. Sarah Berry: Rarely. 

Jonathan Wolf: Tim, can supplements actually harm your health? 

Prof. Tim Spector: They can. 

Jonathan Wolf: Sarah, do you see marketing claims from some supplements and think, that's just nonsense? 

Prof. Sarah Berry: Yes. I often see a load of nutribollocks regarding them. 

Jonathan Wolf: Tim, are there alternatives to synthetic supplements that are just as quick and simple? 

Prof. Tim Spector: There are. 

Jonathan Wolf: Sarah, have you done a brand new randomized controlled trial on a prebiotic gut supplement that you can tell us about today?

Prof. Sarah Berry: Yes. 

Jonathan Wolf: Brilliant. And finally, Tim, what's the most common misconception about supplements? 

Prof. Tim Spector:  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 that's true. 

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

I do remember thinking, well, that's pretty convenient. What a 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. Like some future world where you don't get to eat any real food, and you get everything in seven little colored… 

Prof. Tim Spector: Star Trek style.

Jonathan Wolf: 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? 

Prof. Tim Spector: 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.

This is why we have supplements added to foods all the time routinely. 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 are 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. 

Prof. Sarah Berry: And traditionally, when we think about supplements, we think about vitamins and minerals. These are essential for our health. 

And at a time when there was a deficiency, supplements were of value. But we're talking hundreds of years ago, for example, where there was a 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 are 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 lives who may benefit from supplements. So, for example, iron deficiency anemia 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. 

Jonathan Wolf: A hundred years ago, was this very different, because you mentioned scurvy, and I do remember this in history, sailors needing to eat lemons or something. It's not only scurvy that you're talking about in these deficiencies. 

Prof. Sarah Berry: 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 U.K., like the U.S., 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. 

Prof. Tim Spector: Rickets, for example, all these pictures a hundred years ago in Glasgow of kids with bendy joints. This was a vitamin deficiency that now really no longer exists. 

Jonathan Wolf: We often talk about how the diets in the past were much healthier. So why was it that this concern and actually this occurrence of deficiency? 

Prof. Tim Spector: It generally happened during industrialization, and the U.K. 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. 

People ended up just, for example, eating bread or just porridge. Didn't get any fresh fruits, vegetables, any variety. As soon as you lose that variety, you go onto these staples, you do risk having some of these vitamin deficiencies. 

So 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 thymine deficiency, vitamin D, and vitamin C, 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.

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.

Prof. Sarah Berry: 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 and 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 are other people who 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, 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, you know, this great boost of energy. 

If you've got enough, you don't need to add more in. It's not going to make you feel more energetic. And if anything, it can actually be harmful. 

Jonathan Wolf: 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, if I put twice as much oil, actually, all I do is pour oil into the car. I'm not making things any better. 

Prof. Sarah Berry: 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.

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, et cetera. 

Prof. Tim Spector: 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.

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 a real misconception about this whole field. 

Jonathan Wolf: You are saying they've now done studies on taking calcium as a pill, and it actually increases your risk of heart disease. 

Prof. Tim Spector: Yes. So it doesn't help fractures, which is what it was supposed to be. It's what I used to prescribe it all the time. 

Giving calcium to menopausal women, for example, it doesn't prevent fractures, and 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, you know, 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, a hundred times more of it. 

It's never been shown that that is beneficial.

Prof. Sarah Berry: I think, Jonathan, it's always important to caveat, and you know, I'm always here to add that extra nuance. 

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, 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. 

Prof. Tim Spector: B12 works very well for vegans who struggle to get their B12 levels up. 

We are talking about generalities here. There are obviously subgroups that do still benefit from it. 

Jonathan Wolf: 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 and… 

Prof. Tim Spector: Or if you've got an eating disorder, for example, would be another one. 

Jonathan Wolf: 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. 

Prof. Sarah Berry: Yes. For most people. 

The thing that annoys me the most when I think particularly about the neu nutri-bollocks 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.

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 plays to someone's insecurity or concern that they might have.

Prof. Tim Spector: People think if I'm paying a lot of money for a vitamin or a mineral, you know, 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 from the 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.

Jonathan Wolf: 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 good for my children's health. I see that on all the cereal packets. 

What's going on there? 

Prof. Tim Spector: 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.

They had zero zinc, their blood levels were zero, and these groups were getting recurrent infections. If they placed them 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.

Jonathan Wolf: And is that true? 

Prof. Tim Spector: 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 are 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.

It 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 boost your immune system. When the science really doesn't back it up. 

We are prevented in many other areas from giving real advice on 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. 

Jonathan Wolf: So what I understand is that the sort of supplements that I'm likely to get on the supermarket shelf today are not likely to deliver 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? 

Prof. Sarah Berry: 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. 

Jonathan Wolf: So, Tim, if the problem isn't deficiency, what is the problem with our diet today?

Prof. Tim Spector: 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 are getting fiber deficiency whilst being overfed. We are not getting quality food, we're just being bulked up with sugars and other chemicals. 

This, I think, is the major problem we're facing. 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 are missing out on the whole plants that we used to be eating before big food got in there and changed where we eat. 

Prof. Sarah Berry: And I think Jonathan, even though we've said, okay, if you have a balanced diet, you don't need these supplements, et cetera, we're getting what we need.

We know that the current diets that we're having are deficient, like Tim said, in fiber, in plants, in diversity, et cetera, and excessive in all of these unhealthy nutrients; that kind of diet is accounting for one in five premature deaths. 

We know in the U.K. and the U.S. that 20% of premature deaths are estimated to be from the food that we are eating, from having an unhealthy diet.

Prof. Sarah Berry: 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. 

Prof. Tim Spector: And not only that, it's also all those chronic diseases, 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. 

Prof. Sarah Berry: 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, or 70 years of age, there is still a huge benefit to making a change here and now. 

Jonathan Wolf: 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? 

Prof. Sarah Berry: I think there are lots of reasons, and I think the reasons differ for every individual. 

There are 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. 

Prof. Tim Spector: I think education is the other thing that's changed. Most countries no longer teach cooking in school. Many homes, when you're renting them, certainly in the U.S., 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 these food deserts that every country has. 

Prof. Sarah Berry: 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 are deficient in fiber, we are 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 50, a hundred years ago.

Jonathan Wolf: 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. This happens quite often, as listeners of a podcast may know, and you said you want to try 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 why that was and the idea? 

Prof. Sarah Berry: Yeah, so amongst the science team and together with our head nutritionist, Federa 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; the lack of fiber, the lack of bioactives, so chemicals like polyphenols that are in some many of fruits, vegetables, and other plants. And also the lack of plant diversity. 

So, as a population in the U.K. and the U.S., these are the biggest problems. There's also other features that we wanted to tackle. Like we are not having enough whole grains. We are not having enough legumes, pulses, beans, those sorts of things. 

And that's the root of, I think, the problem alongside over consumption 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, as 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. 

Jonathan Wolf: And Sarah, you used some very fancy words like modulating and matrix, could you help to understand? Because I think you have this hypothesis that using these 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? 

Prof. Sarah Berry: Yeah, so let's take a step back. When I think about the healthfulness of a food to how healthier 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, they 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. 

Jonathan Wolf: These are the sorts of things that feed the different good microbes in our gut. 

Prof. Sarah Berry: Yeah, they have wide-reaching effects. Many of the effects are mediated through our gut microbiome to 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. Every food has its own different structure. We call it the food matrix, but we are essentially talking about the structure of the food. 

And the structure of the food 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. 

So when we are 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 U.K., U.S. populations 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, et cetera. 

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, and how we metabolize it. 

Prof. Tim Spector: Another way of thinking about this is that in the past we've been reductionist and we've tried to say, okay, well let's, 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, you know, supplements in their chemical nature, and just that, 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. 

Jonathan Wolf: 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, this variety of different chemicals, but also the desire not to smash things up into powders? 

Prof. Tim Spector: There've been studies for the last 20 years on giving fibers 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 GOS and FOS, 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've 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 you know, 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's going to explain, when we tested this 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. 

We also know this is greater than probiotics. The effect of fiber is a bit like a fertilizer, rather than just giving little individual seeds, which is what the probiotics are doing. 

Jonathan Wolf: We've been talking about a prebiotic gut supplement. Can you remind people what the difference is between a prebiotic and a probiotic, because they sound almost exactly the same?

Prof. Tim Spector: 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. 

So both of them have been shown to be healthy in multiple experiments. 

Jonathan Wolf: So you had this idea that it would 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 the recipe for this supplement? 

Prof. Sarah Berry: So 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 that, the food structure in this, given the important role that preserving that plays in some instances.

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. 

What it's delivering, as well as lots of fiber, as well as lots of bioactives, 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. 

Jonathan Wolf: 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 supplements. This prebiotic gut supplement. 

Prof. Tim Spector: 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 had been shown in the literature to be beneficial for health, or particularly for gut health.

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 would 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. 

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. 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. 

Prof. Sarah Berry: 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 are 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. 

Jonathan Wolf: 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 create a supplement that works, and you want it to be this thing called a randomized control trial.

Could you tell me about that? 

Prof. Sarah Berry: Well, I went cap in hand. I said, Jonathan, please, can I have some more money? Because randomized control trials are very expensive to run. 

Hence, why so many supplements out there, the majority of supplements don't have randomized control trials because they're challenging, they're expensive.

So, a randomized controlled trial is the gold standard way to conduct nutrition research in order to look at how effective a given food, nutrient, or dietary intervention is in terms of our health.

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 a consumer 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.

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Jonathan Wolf: And so that's like a little pill that has some live bacteria.

Prof. Sarah Berry: So this was a little pill containing live bacteria for which there's lots of evidence showing it's beneficial for… 

Prof. Tim Spector: One of the most popular ones that have been shown in multiple trials to have a benefit. 

Prof. Sarah Berry: 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 are displacing something. And also, we consume meals, we consume diets, we consume whole dietary patterns. 

And so if we were going to add in this prebiotic supplement that the goal is, 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. 

Jonathan Wolf: And why is the control group so important, and why is this randomized control that you're talking about? Why is that important? 

Prof. Sarah Berry: So a controlled 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, 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.

Prof. Tim Spector: So that's why the placebo effect is real, whether it's a, you know, 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. 

Prof. Sarah Berry: We know from many, many published studies that people who are told that they're having 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. 

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 are only taking blood measures, 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. 

Jonathan Wolf: 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.

Prof. Sarah Berry: Yeah. So the third control was these kind of bread sprinkles, which can be used in the same way as the prebiotic gut supplement. 

Jonathan Wolf: And what was the next part of the trial? 

Prof. Sarah Berry: 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 at 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, et cetera? 

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, 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. 

Jonathan Wolf: And Sarah, I want to tackle sort of the elephant in the room here. You are both research scientists, obviously, I'm at ZOE, which is also a commercial company. 

How is what you are describing different from what most of those companies that are selling a vitamin or a supplement might be doing?

Prof. Sarah Berry: So I think there's two key differences. One is that we're doing an RCT. It's 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. 

Prof. Tim Spector: 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.

Prof. Sarah Berry: And so they say, 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 it on the whole, prebiotic gut supplement.

Jonathan Wolf: You got these people to do this? 

Prof. Sarah Berry: Yep. 

Jonathan Wolf: What did you end up measuring? 

Prof. Sarah Berry: 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, et cetera.

And then we also invited a smaller group of participants to come back and do a sub-study called a postprandial 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.

Jonathan Wolf: So what were the results? 

Prof. Sarah Berry: The key finding was that the prebiotic gut supplement significantly improved gut microbiome composition. It significantly improved compared to the probiotic and compared to the control.

Interestingly, it improved species that we've previously identified through our years and years of research at ZOE, that are associated with favorable measures of health, favorable measures of blood pressure, lipids, inflammation, et cetera, and so much more. That was one of the key findings. 

Prof. Tim Spector:  Can I just add, the detail is, you know, it was significantly greater, but I was expecting a bigger effect of the probiotic. That 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. 

Prof. Sarah Berry: 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 weren't really taking the probiotic.

Jonathan Wolf:  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 can see the probiotic did work. There were these additional bacteria in their gut. 

But what you're saying is even adding a few of these special probiotics is nothing like as effective as adding this whole blend.

Prof. Tim Spector:  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.

Jonathan Wolf: Were there any other results? 

Prof. Sarah Berry: Yeah, so we also ask 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 had improvements in things like happiness or in energy, and these self-reported outcomes were far greater in those who were taking the prebiotic gut supplement versus those taking either of the controls. 

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. 

Jonathan Wolf: They actually felt different. 

Prof. Sarah Berry: 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 our energy levels. 

Prof. Tim Spector: And I think the other interesting thing is this happened pretty quickly, didn't it? It wasn't, 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 we traditionally haven't been measured in nutrition science at all.

Prof. Sarah Berry: 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 gut supplement, there was a significant improvement in inflammation, 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. 

Jonathan Wolf: How much do they take of this gut supplement every day? 

Prof. Sarah Berry: So we ask them to have a couple of scoops a day. So that'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. 

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 are taking something out. 

Jonathan Wolf: 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. 

Prof. Sarah Berry: 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 to add that extra kind of boost to your health, into your meals.

Jonathan Wolf: You've described all of this, you know, has this been peer reviewed and published? 

Prof. Sarah Berry: Yeah. So the hard work doesn't stop once we get the results, we then write it up a a paper, and we submit that to go through a very vigorous peer review process for publication in a journal. 

It's now in press, in Nature Communications Medicine, to be published really soon.

Jonathan Wolf: So, the reason you wanted to do this was really to understand if it was possible to come up with a whole new category, I guess, of supplements for 2025, not 1925. What's the overall takeaway here, Tim? 

Prof. Tim Spector: 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. 

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 in 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. 

Jonathan Wolf: And are there equivalent results for sort of these traditional chemical powders that you were talking about at the beginning, or… 

Prof. Tim Spector: 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.

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

Prof. Tim Spector: Yes. Our study showed 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. 

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The science is still developing in the probiotics, and we believe that the 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 that's a whole new era that we can see that could really change the landscape of nutrition. 

Jonathan Wolf: 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 vitamin supplements comes from this world of 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 emptied of quality. 

Prof. Sarah Berry: 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. 

Jonathan Wolf: Thank you. 

Adding zinc is not going to improve my immune system. That's rubbish. That too much of some vitamins could even hurt me. So I heard that actually taking, you know, 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, you know, 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.

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 nothing that isn't made by big food and has 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.

You did this randomized control trial, had these amazing results, and 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. 

I think my takeaway is, this is really exciting, as just 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. 

Prof. Tim Spector: Yeah, I think you've summarized it there, Jonathan.