Build a better brain: The 5 foods you need to protect your memory and mood and reduce dementia risk with Prof. Felice Jacka and Prof. Tim Spector

Can food improve brain health, memory and mood? 

In this episode, Prof Felice Jacka and Prof Tim Spector explore how diet, the gut microbiome and fermented foods may affect your mood, brain function and dementia risk. Drawing on clinical trials and research involving more than 10 million people, they explain why what you eat could have a much bigger impact on your brain than most people realise, and what the latest science suggests you can do about it.

Felice, who helped create the field of nutritional psychiatry, explains how food influences the brain through the gut microbiome and inflammation. She and Tim explore why some foods change brain function, which support brain health, what the evidence says about ultra-processed foods, and why diet is becoming an increasingly important part of research on brain and mental health.

If the food you eat today helps shape your brain tomorrow, what small change could make the biggest difference over the next year?

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Actionable takeaways

What's the link between diet and mental health?

Higher diet quality is consistently linked to a lower risk of depression and anxiety across countries and age groups.

How does food actually influence the brain?

What we eat shapes our gut microbes, which produce chemicals that send signals to the brain. The brain can interpret these signals as a threat, triggering inflammation and low mood.

Can changing your diet really treat depression?

In a landmark trial, people with moderate to severe depression who received dietary support were far more likely to go into remission than those who received social support alone, and the improvement closely tracked how much their diet improved.

Why are fermented foods important for the brain?

Fermented foods like yoghurt appear to support a brain region called the hippocampus, which is involved in memory and mood. They also may help calm inflammation, which is increasingly linked to depression and dementia.

What's the problem with ultra-processed foods?

The majority of negative health outcomes studied, including depression, anxiety, and dementia risk, were linked to higher intake of ultra-processed foods. This is likely due to a lack of fibre, nutrients, and beneficial plant compounds.

What's one simple change to start with?

Focus on a variety of plants, whole grains, legumes, and fermented foods, rather than worrying about strict rules. Small, consistent shifts towards whole foods can meaningfully support brain health over time.

Jonathan: Can eating fermented foods lead to measurable changes in our brain?

Felice: Yes. We wanted to do a controlled trial with yogurts. We randomly assigned 40 healthy women, and we did brain scans on them. This part of the brain called the hippocampus that is really key into learning and memory had an increase in the volume.

Jonathan: Just because they were having yogurt?

Felice: Yes.

Tim: But also the more ferments you were taking, the greater chance you had of having a significant improvement in mood and energy.

Jonathan: And finally, what fermented foods should I focus on? Felice Jacka is a professor of nutritional psychiatry and director of the Food and Mood Center at Deakin University in Australia. Her work has been cited in more than 100 policy documents for organizations such as the World Health Organization. Tim Spector is ZOE Scientific co-founder and is a leading light on the links between gut health and brain

Felice: health. People always think that that link between diet and mental health must work through body weight. You eat badly and you have a higher body weight, therefore you become depressed. Now, that's got nothing to do with it.

Tim: What's going on in our choice of food is changing our gut microbes. They're then producing these chemicals which send signals to the brain. The brain then interprets that as being unwell.

Felice: 70% of the health outcomes that we studied, like major depression, dementia, and anxiety, were linked to a higher intake of ultra-processed foods.

Tim: And it looks like diet is the number one thing that we can intervene on and make a huge difference.

Jonathan: If someone is saying, "I need really cost-effective ways to be able to improve my diet," what would you suggest? Felice, can some people with depression be successfully treated by changing their diet?

Felice: Yes

Jonathan: Are supplements necessary to maintain brain health?

Felice: No

Jonathan: Should we avoid eating all ultra-processed foods?

Felice: No

Jonathan: And finally, what's the biggest myth that you hear about the links between food and mood?

Felice: This is up to the individual. It's their responsibility to eat well, and if they don't and they're depressed, then it's their fault. That's a really big myth that's really problematic

Tim: I think it's the myth that it's the mood that influences what food you eat, rather than the reality that it's the food that is the major driver of your mood.

Jonathan: I think most people listening to this can remember a time when they've eaten something delicious and it's made them happy.

Felice: Yeah.

Jonathan: And before I met you, Felice, I would have thought about a piece of birthday cake or perhaps a nice glass of wine as a thing that would make me happy. But when you came on the podcast a few years ago, you told me I should really be imagining a can of beans.

Felice: Yeah. Hopefully cooked in a nice way.

Jonathan: Cooked in a nice way. And honestly, when I heard that, I thought that it sounded crazy, right? Like, who would swap, you know, birthday cake for, like, a meal of beans to actually make you happy? But after a lot of personal experimentation, I've actually come to the conclusion that you're right. Now, I don't think I should be surprised that what you were telling me made sense, because you've almost single-handedly invented this field of nutritional psychiatry. And so it's a real pleasure to have you alongside my co-founder, Tim, because over the last few years, Tim has become more and more focused on this question of the role of the microbiome on mood and brain health. So I think having the two of you here is like a powerhouse. Felice, could you maybe just start by telling us how you first became interested in what seems sort of crazy that there's a link between food and mood?

Felice: So I came into psychiatry research pretty accidentally, sort of by the back door. I did a psychology undergrad, and then I became really interested in statistics, and so I made my way to a newly established psychiatric research unit. And they had some data. And they said, "Would you like to analyze it?" So these were psychiatric data. And I burst into tears and said, "Yes, please." I was in my undergrad then. So I went on, and I did a number of papers using data from this really big cohort study. And I became aware that there were all these dietary data there, as well as the clinical interviews to assess depressive and anxiety disorders. When I came into psychiatry research, I was fascinated to realize that there just wasn't an evidence base that had linked food to mental and brain health. But at that same time, so this is, like, the end of the 1990s, early 2000s, there was an increasing focus and interest in psychoneuroimmunology, and that's basically how your immune system and your mental and brain health are linked in a bidirectional way. And of course, you know, what you eat is a really powerful driver of your immune function, and I knew that- And around the same time, there were all these data coming out of animal studies, neuroscience in the States from a particular group, showing that this newly recognized area of the brain that could grow new brain cells was very important in learning and memory, but also seemed to be important in mental health, could be modified by healthy or unhealthy foods. Manipulated. So here was another piece of the puzzle. And then of course, understanding that epigenetics, you know, your genes weren't just set in stone. They could be turned on and off by environmental exposures, and diet was one of the exposures that switched your genes on and off. So there were all these parts of the puzzle where I knew that bits of your physiology that are firmly linked to mental and brain health were influenced by diet. So why weren't we looking at it? You know, and it was really just that, that whole paradigm in psychiatry where nothing that happens below the neck is of particular interest. And we really hadn't started looking at the gut or any of those sorts of factors. So I set out to try and understand this better, and everyone thought I was a bit, you know, woo woo. Luckily we had really, really good quality data. I mean, they were observational. They were... It's not an experiment, you know, we're just collecting data from people. But really importantly, we had the data that we needed to properly test the hypothesis because we didn't just have very good quality dietary data and very good quality psychiatric assessments. But we also had very good data on socioeconomic status, you know, people's income and their level of education, their body size, their other health behaviors. All the things that we need to take into account if we're looking at this relationship. So then I was able to actually go and test this for my PhD, and it ended up being a very high-impact study. And so from there I was able to build the evidence base around how diet quality was linked to mental and brain health right across the life course from the very start of life to the end of life, across different countries. So it doesn't matter whether in Brazil or Norway or Japan or where have you. Higher diet quality, you know, a healthier diet that's got more of the whole foods in it tends to be associated with about a 30 to 35% reduction in risk

Jonathan: A 30 to 35% reduction in what sort of condition?

Felice: In the risk for depression. There was some evidence for anxiety as well, just hadn't been studied as often. But this was, again, independent of all those other factors we talked about. Really importantly, it's not explained by body weight. People always think, this is another one of the myths, that that link between diet and mental health must work through body weight. You know, you eat badly or too much and you have a higher body weight, therefore you become depressed. Now, that's got nothing to do with it. We see this link at every single level of body weight.

Jonathan: So this isn't just about the fact that you're living with obesity or you're overweight and that's making you depressed?

Felice: No, that's right. It seems to have nothing much to do with it at all. And then, of course, we went on and we ran the SMILES trial, which was the first experiment to see whether we could actually alleviate even severe major depression by improving diet quality. And in that study, the average body mass index was about 30, so it was in the obese, overweight category right at that point. That didn't change. People didn't lose weight, and the improvements we saw in their mental health, which were really large, that didn't correlate with body weight change.

Jonathan: And Felice, can you explain simply what that SMILES study was? Because I know that this is viewed as a sort of rather breakthrough study. Up until now, everything was just observational, and you said, "I'm actually going to do, like, a proper randomized controlled trial." Yeah.

Felice: I was a crazy post-doc in the first year of my post-doc thinking, "Well, we've got the evidence now from the observational literature from all these populations, from children up to older people across countries, but we really need to know if this is a causal relationship." That means does diet not just correlate with mental health, but does it affect mental health? So I developed this protocol for a randomized controlled trial. And basically what that meant was we recruited people with moderate to severe major depression. Now, many of these people had been sick for a very long time. Like, they were very, very unwell, a lot of them. Most were on other forms of treatment already, it just hadn't worked, and half of them were randomly assigned to get social support. The other half saw a dietician. So in the SMILES trial, what we did was we measured their depression severity. That was their main outcome. And at the end of the trial, we saw that there was a very large difference between the two groups. So about 8% of the people who got social support, their depression went into remission And roughly a third of those who got the dietary support, their depression went into full remission, which is really remarkable for a group who'd been sick for a long time very often.

Jonathan: So that's a huge difference. You're saying like 8%- Yeah ... got the sort of the social support. Yeah. But like a third of people actually came out of depression as a consequence of changing what they- That's right ... ate but nothing else.

Felice: That's right. The degree to which they improved their diet quality correlated really tightly with the degree to which their depression improved

Jonathan: Tim, I'd love to hear your thoughts on this

Tim: Felice's trial was one of the reasons that, you know, it's got me really interested in the brain again. And I think what we're seeing here is how potentially important food is as a brain medicine, and this is like, you know, the elephant in the room in psychiatry and psychology that nobody is trained in metabolic health, in nutrition. They don't even think about it. Patients with, you know, brain or mental health disorders often have the worst diets because people looking after them are not trained in any way in nutrition. They don't even make the link that there's any connection there at all, and yet this is one of the most powerful interventions that they can do. And the science is catching up now with the observations. So we've had these rather crude observations. We had the science that's, you know, from my point of view, the microbiome science has been there for a while, and a lot of that has been in mice. How you can produce anxiety or depression in mice just by swapping around their gut microbes from one to another. You know, in a way, a bit like mental health problems being an infectious disease, which I think is kind of a bit freaky sort of viewpoint, but that's what these mouse models show. But until you've shown it in humans, it's never really real. And so linking all that stuff with the changes in the SMILES trial really to me makes it much more concrete that we have here you know, a real reality that we know that now food improves your gut microbiome and that then improves what's going on in your brain and those signals to the brain. And it's so important because we know that the gut is the major source of information to the brain. So I think it's, you know, the most exciting area in science at the moment is this gut-brain connection that we're re-evaluating all the time and it's bringing in all this new neuroscience, particularly on inflammation, which we've talked about on this show a lot, how important it is to keep inflammation levels low. And we know that people with depression and mood problems have raised inflammation levels on average, and all of us actually, you know, in the Western world have raised inflammation levels compared to people in other countries. So this link that what's going on in our choice of food is changing our gut microbes. They're then producing these chemicals which send signals to the brain. That brain then interprets that as being unwell And then we go into this cycle of depression behavior, which is a protection for the body. So there's ... The other way of thinking about it, you know, we know that inflammation is a protective response. What's happening is inflammation in the brain is also a protective response. It's just inappropriate. It's just doing it at the wrong time. But it is incredible there's so few studies out there because this whole field, particularly the clinical area, has been cut off from the rest of medicine. You know, why do we put people in mental hospitals? Why are they separate? The worst diets are in mental hospitals and in some surveys, they've shown that long-term psychotic patients, about 70% of them have type 2 diabetes and the doctors looking after them are not trained-

Felice: in looking after diabetes or metabolic health at all. And the whole thing is just perpetuating everyone being made worse by their environment rather than better. And we know that the drugs we've got, unfortunately, they help a few people, but they have really failed to live up to our hopes and they haven't really changed in the last 50 years

Jonathan: I sort of wanna wind back sort of quite early where you talked about, like, what we've discovered in mice, and you sort of mentioned in passing, Tim, is mental health an infectious disease? But I think you were saying that they've done tests in mice where by changing the microbes inside the mice, they were actually changing-

Tim: They're transplanting them from one mouse to another. So using this model of these sterile mice, you can implant microbes from a stressed, anxious mouse into a sort of neutral mouse with no microbes, and that new mouse will then display the same anxious brain symptoms as the initial one. So I was being a bit joking about infectious disease, but normally if you've got microbes from someone else and it causes a brain effect, you know, you could call it infectious in some ways. Just like we've talked about obesity potentially or type 2 diabetes being infectious 'cause microbes are responsible for it. I mean, it's not in that sense.

Felice: Did you know that you can do it with humans too? So if you take poo from people with major depressive disorder or with schizophrenia and you put them into mice, compared to poo from healthy people, you can induce what's called the behavioral phenotype. Basically, you can make a mouse behave as if it has depression or schizophrenia. You can see some of the biochemical changes. No. Yes. You could do this with hypertension. I find it really wild that you could take poo from someone with high blood pressure and give it to a mouse and induce hypertension in the mouse. So what this is suggesting is that there's a causal effect happening here, that the microbes are causing this condition or phenotype if you're talking about animals.

Jonathan: You're saying you could take, like, the poo from somebody who has a mental health issue, like a serious one like depression or schizophrenia, you can give it to mice that don't have any microbes, and they basically become schizophrenic or depressed?

Felice: The mouse version of it. That's exactly right.

Tim: Or display, yeah, symptoms that were in that direction.

Felice: And some of the changes in their blood as well, which is also really interesting when you think about ... Like, we did a really large systematic literature review. We looked at all of the data, all of the studies that had taken someone with major depressive disorder or bipolar disorder or schizophrenia and compared their microbes to somebody without those conditions. Now, as you would expect, there's differences between the microbes of people who do and don't have a serious mental illness. But what I was really interested in was whether there were some commonalities. Were there some common features about the microbial profiles of people with serious mental disorders? And that's exactly what we saw. What we saw was consistent reductions in the microbes that produce butyrate. Now, butyrate is a really powerful anti-inflammatory molecule, and you'll often see that the people with some sort of an illness will have reductions in these butyrate-producing bacteria. But they also had increased levels of lactic acid producing bacteria. Now, in people with serious mental disorders, you will see increases in lactic acid in their blood and in their brain. And it's complicated, but there's something around the way that your body produces lactic acid, the way the bacteria does. It suggests that there's something about the microbial profile that's producing too much lactic acid that's feeding in potentially to the disease profile. The third thing we saw was differences in bacteria that produce these neurotransmitters called GABA and the glutamate pathways. Now, these are really dysregulated in people with serious mental disorders. So again, we don't know if it's cause or effect, but the fact that these bacterial differences mapped on to the biochemical changes that we see in people with serious mental disorders is really telling, I think.

Tim: I'd add another one to that, is that the other consistent message you get is that you get microbial patterns that are pro-inflammatory.

Felice: Yeah.

Tim: So they're driving the immune system to produce protein markers that you might see in the blood of things that we've talked about, CRP in the past, that are just slightly high, not, you know, clinically really high, but just above the surface. And so this is a consistent pattern across all brain disorders-

Felice: Yeah ...

Tim: is that there's something going on in the guts of these people that must be sending messages, you know, up to the brain-

Felice: Hmm ...

Tim: to say, you know, "Be on alert here. You know, you got to work harder." Yeah. There's something going on that isn't right in addition to the changes you've suggested.

Jonathan: And could you help our listeners just to piece this together? Because we started with a small study saying that if you change what you eat, then actually you can have this profound change, even on somebody with very serious mental health issues. And now we're talking about how these microbes in our gut seem to be really important.

Tim: We're linking the two together. We now know that, yeah, if you improve your diet significantly from the poor diet that most people with brain disorders are on, that will shift your gut microbes, and those microbial shifts are in a certain direction that it can produce these healthy chemicals like butyrate, or they're gonna produce anti-inflammatory compounds that are gonna counteract the inflammation. And these then have effects on the brain and can improve a lot of the symptoms. That's essentially what we're sort of summarizing from all kinds of different evidence, although no one study has done it all. But the other exciting thing is effect size of, say, a diet, a healthy diet on brain symptoms are not trivial. We're seeing effects, just to put it in context, that are bigger than you would get with starting an antidepressant on average. So we know that some people do well on antidepressants, but many people don't. If you take the average, you're gonna do better with a diet alone than an antidepressant. And obviously, everything, it's all personal, and your study didn't directly show that because it was in addition to an antidepressant.

Felice: Yeah, that's right.

Tim: But there are other studies out there suggesting that these effects are really big.

Jonathan: I know that everyone listening to this is like, "Okay, I want to start talking about the actionable advice about what I can do." But before going to there, I'd like to talk about some of the really interesting science that both of you have been involved in that I think underpins the advice that you might give. And I think what's already come through from what you're talking about is that you seem very clear about this big picture link between, like, the food you eat and microbes improving your mood. But, like, exactly how that works is a lot of challenging work that, you know, you and other scientists are doing to pin it down. The team said you've done a recent study involving fermented dairy.

Felice: Yeah, yeah. It's a pretty cool study. We teamed up with one of our big dairy companies in Australia, and they have a product on the shelf which is a yogurt. It just has an added probiotic bacteria. It's one of the really common ones that you'll see in a lot of yogurts. We wanted to do a placebo controlled trial. Now, of course, if you're having yogurt, it's not just got the flavor, it's got the texture, it's all sorts of things, but they made a really great placebo. So what we did is we randomly assigned 40 healthy women, so these weren't women with depression or anything else, they were healthy women, to have either the yogurt drink or the placebo over a period of eight weeks. Now, this wasn't a large amount, just a little tiny sachet, 130 mils, that you got from the supermarket And we did brain scans on them, and we also measured other things like microbes and their blood and things like that. But keeping in mind they were healthy people, so we didn't expect to see huge change in those things. But what we saw at the end of the eight weeks, and we worked with neuroscientists who know much more about this than we do really, and they were kind of blown away. Because if you remember me mentioning this part of the brain called the hippocampus, that is really key. It's really key into learning and memory. It seems to be really important in mental health. We think it's one of the main ways in which antidepressants actually work, is by increasing the size and the function of the hippocampus. So the hippocampus is a tiny little... Well, it's actually two structures, and it's got a bit of a shape like a seahorse, and the Latin word for seahorse is hippocampi or something like that. So that's where it gets its name. We used to think that your brain just lost all its brain cells, or not all of them, but, you know, lost brain cells as you went along, and you didn't get any more new ones. And then neuroscientists started to spot this area that seemed to actually grow and shrink, so it actually would grow new neurons. Particular proteins would help to grow the neurons. I think about them like manure for the brain. The hippocampus is important in certain types of memory, particularly the short-term memory, and it also seems to be important in mental health. Because when you look at the way SSRIs work, antidepressants, one of the things they seem to do is to increase the proteins that grow the new neurons, so they increase the manure for the brain. It's also involved, the hippocampus, in satiety, the sense that you've had enough to eat. And the studies that were done previously in the healthy adolescents when they were just given these junk foods for a week, or even just a few days, and they showed that there were impairments in these cognitive tasks that are linked to the hippocampus. They also showed these impairments in satiety. So people weren't feeling full. They wanted to keep eating. And I think maybe the hippocampus is part of that story, so it's something we really are focusing on now We've already shown, and others have now shown the same thing, that people with unhealthy diets have a much smaller hippocampus. Which is really key, 'cause as you get older your hippocampus shrinks. And because it's so important to learning and memory, this we think is involved in part of that, you know, loss of cognitive ability as you get older. Now what we saw in this dairy trial was that after eight weeks of these small sachets a day, that the women who got the real stuff, they had an increase in the volume of their hippocampus. It actually grew. This is what we saw after eight weeks- Okay ... of them consuming this. We didn't see that happen in the placebo group. We also saw that the there was more connectivity between the hippocampus and the frontal lobe. So this is the bit of your brain that sort of guides your higher order thinking and planning and this sort of thing. So it's suggesting, you know, improvements in brain function. And then what we saw was in the microbes an increase in the bacterium that was the probiotic bacterium in the yogurt, which is what you would expect. But that correlated really clearly with that increase in connectivity between the hippocampus and the frontal lobe. And we also saw suggestions of more glutathione in the brain. Now glutathione is your brain's natural antioxidant, so it helps to protect your brain. And it looked like the women who got the real yogurt compared to the placebo had higher levels of glutathione in their brain as well.

Jonathan: And so what is that glutathione going to be doing for me?

Felice: Well, it protects your brain. It's your body's own antioxidant.

Tim: It'll protect you against inflammation and sort of immune irritation of it.

Jonathan: You actually could see a real difference in terms of things that are going on inside the brains of people who are eating this yogurt versus this sort of fake alternative.

Felice: Yeah.

Jonathan: And that was both that, this important part, the one part of your brain that can, like, create more connections and everything, the hippocampus was actually more connected, but also is creating this chemical glutathione?

Felice: Thione.

Jonathan: Glutathione. Glutathione, which is good. Helps to protect my brain.

Felice: That's right. So it looked like there were aspects of the brain that you would expect would result in better brain power were there. So a larger hippocampus, more connectivity with the frontal lobe. Also more glutathione, which protects your brain from oxidative stress. So these are all good things. Now we need to do it in a much larger sample, because that was a small sample and it was also women who were really healthy. So there wasn't this remarkable difference that you might see if you were looking at it in a group of women, say, with major depression. Because we know that when people have major depression or another serious mental disorder, on average they'll have a smaller hippocampus. If they are successfully treated, the hippocampus grows again. But as I said, diet really affects the size and the function of the hippocampus. So does physical activity

Tim: But it could also be, you know, having written a lot about fermented foods, it could be it's acting on the immune system. So we know that people who aren't used to it and suddenly get fermented foods, like we've done this big ZOE trial where we had 6,000 people taking fermented foods and in the first week or two of taking it, 50% of them who were taking three or more a day fermented food portions, 50% showed an improvement in mood and energy-

Felice: Yeah

Tim: in that time. And, you know, this is in huge numbers of people.

Felice: Mm.

Tim: Whereas the people who only managed one fermented food got less, so it was a dose-response effect, which means that the more ferments you were taking every day or the more regularly you were taking them, the greater chance you had of having a significant improvement in mood and energy. And energy is very much this fatigue or energy is very much a brain symptom. We now know that. We used to think it was something to do with our muscles or, you know, it was something to do with, you know, the menopause or whatever. But it all comes back to the brain about our perception of our environment. And we believe that most of these fermented foods have a major impact on the immune system through... We don't understand all the mechanisms, but we do know that it reduces markers of inflammation. So it's quite possible, in addition to this specific effect on this little seahorse-type- Bit of the brain

Jonathan: Yeah ...

Tim: it could have a general calming of- 100% ... inflammation in the brain, which we now know is really important. So it brings in this whole other idea of, you know, anti-inflammatory effects being good for things like depression. The more we discover, the more complex it gets.

Felice: Yeah.

Tim: That's definitely the story of nearly everything in science, but particularly the brain. And I think it's, you know, we may want to just go back a notch and just say, "Okay, a healthy brain is one that has, you know, no, hardly any inflammation in it. It's getting the right signals from the rest of the body. It gets its main signals from the gut. The gut gets, you know, it's healthy signals if it's eating the right foods and the microbes are converting that into the right chemicals." So that, I think, to me, is the crucial link. And I think once we make this link between how that affects mood, and we're seeing this in lots of trials, whether it's the ZOE trials, whether it's, you know, your studies, I think we're getting this consistent message that we have to look after our guts if we're gonna look after our brains. And it's not just limited to depression, anxiety. Everything I've looked at, every mental health disorder has an element that you can link back to gut and diet or inflammation.

Felice: So there've been many, many, many studies now from all around the world showing very consistently and comprehensively that the diet during pregnancy is linked to child emotional behavioral outcomes over the first few years of life. It's linked to language acquisition, and it's linked now to ADHD and autism. Now, we've worked a lot in this space, and we work with colleagues all over the world. Those findings are very clear. What we think is going on, or at least part of the story, is that mothers who are eating an unhealthy diet during pregnancy, they have a less diverse or a less healthy microbiome. That we see is linked to emotional behavioral outcomes. But what we're also seeing is that those mothers have higher levels of inflammation, so higher levels of something called GlycA. So GlycA is a marker of inflammation, and what we see is that mothers who have unhealthier diets during pregnancy, more Western foods, ultra-processed foods, they have higher levels of GlycA, and that in turn is linked to slower brain development or slower language acquisition in infants.

Jonathan: You're giving this example about, you know, pregnant women and their children. But listening to you, I assume that's just an example. Like, that if I'm- Yeah ... eating that diet as a, you know, a 50-year-old man, or I'm eating that diet as a 14-year-old child, this is gonna be having these effects on my microbiome, and then my brain, and then my mood. Is that correct?

Felice: We've done many, many studies looking at, for example, adolescents. That's about the age of where really critical vulnerability in teenagers, particularly girls. And we know in young adolescents there are dose-response relationships again, so more of one leading to more of the other, between the level of unhealthiness in their diets and their mental health, independent of their family backgrounds, their, you know, family functioning, socioeconomic status, all of these things. And we see this whether it's in very early childhood, in adolescence, in adulthood, in older people. Very, very consistent findings. We're consistently seeing these links between the aspects of the gut microbiome and people's mental health across the age range. But again, going to the start of life, we're seeing it involved in neurodevelopment. And if you go back to the animal studies, we certainly see that that's the case. So all of these signals are pointing in the same way, which is the food we eat is critical to our microbiome and all of the molecules that it produces. This has a very important effect on inflammation, which is really important in virtually every chronic condition that you can think of, including mental health problems. It has an impact on the brain, whether it's the blood-brain barrier, the hippocampus. All of these other systems, including the way your genes are turned on and off, how your mitochondria function, the little energy generators in your cells. All of these different things are affected by your microbes.

Jonathan: Tim, we've been obviously talking a lot about mental health issues. Obviously, Felice focused a lot on depression. I know that you've talked to us about anxiety and all these sorts of things. Let's say someone's listening to this and they're not worrying about that, but they are worrying about brain health more broadly. Is that something completely different in terms of, like, is brain health outside of mental health or is it the same?

Tim: I think it's all part of the same spectrum and I think we need to stop seeing mental health issues as 360 separate symptoms and start seeing this as one organ. And equally for, you know, for depression or dementia, the brain is reacting in a way that is inappropriate for our age and the genes and risk factors for all these are very similar, which tells us there must be common ground and therefore in all of these studies you see diet, poor diet, as always there every single time. And the data is just as strong for avoiding dementia as it is for avoiding depression.

Felice: Yep.

Tim: And it's all been backed up by the science. The genetics has not shown there are separate diseases. They've shown at most there are two types of brain disease genetically. We're susceptible to all these things, but it needs another trigger and it looks like diet is the number one thing that we can intervene on and make a huge difference. You know, it's no surprise that, you know, one of the big risk factors for dementia is type 2 diabetes and type 2 diabetes is totally preventable by diet. So everything is keeps coming back to the same, same message that just hasn't got through to, you know, the medical community.

Jonathan: Could I come back to something that you've both touched on, but I feel like we've sort of like not addressed head-on, which is ultra-processed food. What are you seeing?

Felice: Well, ultra-processed food is food that if you look at the packet, it has a very long list of ingredients. It has a substrate that might have once been food, but it's been heated and extruded and changed to be completely unrecognizable We believe, we hypothesise that there's something about the actual processing itself that might be problematic, or the level of processing that might be problematic. We published this huge umbrella review a couple of years ago in the British Medical Journal, created news all over the world showing that 70% of the health outcomes that we studied were linked to a higher intake of ultra-processed foods. 70%? 70%, with particularly strong evidence for death, any cause of death, for cardiometabolic diseases, so heart and diabetes diseases, and common mental disorders, depression and anxiety. 70% of the health outcomes that we looked at were linked to a higher intake of ultra-processed foods.

Jonathan: Could you help me to understand what that means?

Tim: Epidemiology. Yeah So it's moving from little trials to big observational studies and compilation of multiple trials. That's what-

Felice: Putting them all together. So, you know, our study was what's called an umbrella review. So we brought together all of the meta-analysis that had already been done. So when you get small trials and you put them all together and you come up with a summary statistic, like a number that tells you something about how one thing is connected to another. We took all of the meta-analysis and brought them together. So we had data from more than 10 million people in this large umbrella review. And in our umbrella review, we looked at a whole heap of different health outcomes, and we saw that 70% of them were linked to higher intake of ultra-processed foods. So when, for example, you looked at individual cancers, you might not see that all of the cancers were linked to ultra-processed food intake, but quite a number were. So that's the sort of when we talk about health outcomes and the number that we looked at, 70% of them were linked to higher ultra-processed food, and the ones with really strong evidence, where there were just lots and lots and lots of studies saying the same thing, was around any cause of death, so life limiting, cardiometabolic diseases, so that's heart diseases or metabolic diseases like diabetes, high blood pressure, et cetera, and common mental disorders, depression and anxiety. Some people in the science community don't believe that ultra-processed foods that don't have unhealthy nutrient profiles should be demonized. What they say is if the food has a healthful nutrient profile, then it should be considered as food So we set out, again, tiny little study to test this hypothesis. Now, a really good example of a nutritionally balanced ultra-processed food are the meal replacements, the shakes and the bars that people are often going on when they need to lose weight quite quickly. Basically, these meal replacements become their food. We know that they're really helpful at helping people to lose weight. But we think that as a really good model of a nutritionally balanced ultra-processed food, they could be used in science because they've got low levels of sugar, 'cause they've got artificial sugars. They've got added vitamins and minerals. They've got added protein. They've got added fibre. They're low in fat. So they're nutritionally balanced, is what they're called. We compared them to very low calorie real food diet, so legumes and vegetables primarily. So we recruited nearly 50 women living with obesity who needed to go onto these very low energy diets, and for three weeks they got either the packaged, pre-cooked food, which was primarily legumes, vegetables, whole foods, or the meal replacements, the Optifast What we saw after just three weeks was that the women who had the real food, with the legumes and the vegetables, the diversity of their microbes really increased. Whereas the ones who got the Optifast, the microbes, there was evidence of a decrease in their microbial diversity. Now critically, both groups lost weight, so it wasn't about... They lost the same amount of weight. But it does suggest that even when they're nutritionally balanced, your gut microbes are interpreting them differently. If you have real vegetables and legumes, so plant foods, what you're getting as well as the vitamins and minerals and the protein and the fibre and these, you know, carbohydrates, these macro and micronutrients, you're getting them in a way that nature has provided them. So you're getting them within their own food matrix, which we think is really important, in the combinations that nature has intended, which we think is really important. But we're also getting the phytochemicals. So phytochemicals are things like people have think about them as antioxidants or polyphenols. There may be as many as 150,000 of them. Now it's likely that we coevolved to have receptors to these phytochemicals in plant foods, and we're not getting them at all when we're getting ultra-processed foods. There's no phytochemicals in those. The food matrix is lost, and we're not getting the fibre and the vitamins and the minerals in the form that nature has provided them.

Tim: Yeah, 'cause the difference is in these ready-made supplements, they might have one type of artificial fibre. Mm. Whereas if you're having a range of plants, you're getting hundreds or thousands of different types of fibre. So it's not giving the gut microbes the same food. It's like going to a zoo and just giving all the animals the same food, whereas in the natural way, you're giving a mix of 1,000 different foods.

Jonathan: And so bringing this back to my brain health, you're saying this experiment was a way to sort of demonstrate that the issues for my brain are not simply that I'm eating food which has got, like, lots of sugar in it or lots of salt. It's actually that the ultra-processed food itself is worse because it's missing a whole bunch of things that, like, my microbes and my brain need. And so we need to start thinking not only about, like, improving your diet in the sense of having less sugar, but, like, directly the ultra-processed food may be playing an important part of it. That's

Felice: right.

Jonathan: Am I understanding that right?

Felice: That's right. And, I mean, obviously it's early days. This is one small study. It's a proof of concept. There's so many aspects to ultra-processed foods because apart from in this study it was nutritionally balanced, but then we're talking about what it doesn't have. But in many ultra-processed foods, in fact pretty much all of them, and even in non-ultra-processed foods actually, we're getting a huge number of things that we think are detrimental to the gut. So one of them is emulsifiers. And if you look on any packet nowadays, you know, emulsifiers of different sorts, sometimes they've got a number, but they are in everything. And the animal science suggests that what they do is they impair the gut lining, which we know is really important to keep healthy.

Tim: People have known about cancers and obesity, and that's hit the press. What hasn't really hit the press is how important these foods affect brain diseases.

Felice: And putting it into a big context too, we've just had the latest study on mental disorders being published in The Lancet from the massive international Global Burden of Disease study. So this study looks at health data from right across the world, and it looks at the burden of different health conditions and as well as looking at risk factors for those health conditions. And what it's concluded yet again is that mental disorders account for the leading cause of disability across the globe. So it doesn't mean that they necessarily cause early death, although in some cases they do, but it's that disability where people can't engage in the world in the way that they would like to in education or work or in family activity, whatever. And when you look at mental disorders, by far the majority of that burden is accounted for by depression and anxiety.

Jonathan: I'd love to talk about, like, okay, somebody's listening to this, now they're really convinced that this can really make a difference to their brain health and mental health. So if I was trying to reduce this but also not become terrified of everything that might be in the supermarket, what should I focus on?

Felice: Well, for me what I do as a shorthand is to just look at whether there are emulsifiers present in the food. And I tend to avoid the ones that have got emulsifiers. Now that's a really simplistic way, but it's a, it's something that is really useful when you're rushing and you're really busy and everything else

Tim: I use my ZOE app if I'm in a store to just look at the barcode and tell me what is the rating for that. Because nearly all food is processed to some extent. And you can score into four categories. And I'm only really worried about the top two categories. So low processing risk doesn't really worry me. I'm not obsessed with it. And all of these foods, you can have them occasionally, it's not a big deal. But if you have it regularly, as many people do as part of their diet every day for breakfast or for lunch, they're getting meal deals, they're in this rut. So I would tell to everybody the first thing is get out of that rut. Change your breakfast, change your sandwich. You know, think about your evening meal and try and cut out ready meals. Avoid anything that has a massive health claim on the front. You know, you look, and if you look at children's yogurts or most breakfast cereals, and they're full of health claims. And that is a big red flag. They're trying to get you to buy this rubbish, and it's gonna cause inflammation, glucose spikes, and mess up your brain.

Jonathan: And so we talked about ultra-processed food. Are there any other foods that you would tell somebody to focus on if they're trying to improve, you know, their mental health and their brain health in terms of stopping?

Felice: Processed meat and sugar-sweetened beverages are associated with increased risk, and fiber and whole grains associated with decreased risk.

Jonathan: I would love to talk now about what you add in. Let's start briefly with something that isn't food, which is supplements.

Felice: There's some very weak evidence for some supplements alongside other treatments in mental disorders, but they're not incredibly strong.

Jonathan: Do you take any- No ... supplements?

Felice: I don't take any supplement. I take vitamin D in wintertime in Australia, 'cause we live in the south. That's all.

Jonathan: And Tim, what about you?

Tim: I'm interested in Omega-3. And it has been shown that in people with low levels it is beneficial to take Omega-3 supplements, but I always prefer to take the food. So I take sardines and anchovies and measure my blood levels. Now, the other thing I've started taking recently is folic acid, which we know works very well in pregnancy in protecting the baby's brain and development. So we know it has a major effect on the brain. And there's number of studies now showing that is preventive for depression and potentially other brain diseases. And the third thing that I've sort of dabbled with, I'm not quite convinced yet, is creatine. And we've talked about this on the show. Whereas there's some evidence, well, there's pretty good evidence that it builds muscle not very much, but it does build it, and there's weak evidence that it might prevent against dementia. So I'm looking at the evidence, but I haven't yet jumped in to say I'm gonna take this regularly

Felice: You know what I did as not a supplement, but to prevent dementia? I had my shingles vaccine

Tim: That's a great point. Vaccines have been shown to reduce dementia. So you say, "What should we take?" Well, you should definitely take the shingles vaccine if you're offered it, and you should also take your annual flu jab because that has been shown to reduce dementia. Amazingly, no one really understands why, but it's a bit like fermented foods. Your immune system is being tickled by these vaccines.

Jonathan: Let's move on to food and what you should add into your diet. Now let's take it in turns. What would be your key prescription for this?

Felice: Well, based on the emerging evidence from the studies that we're doing, I would've said legumes before, but now I'm saying whole grains. So whole grains come up again and again and again as the strongest correlate of better health outcomes, whether it's physical health or mental health.

Jonathan: And what's a whole grain?

Felice: So they're things like oats, not the really processed ones, the very unprocessed ones. Barley, rye, spelt, quinoa. You know, these types of things.

Tim: Well, I don't like to pick out one food 'cause I don't believe in super foods. So I would go back to our sort of mantra, let's eat the 30 plants a week. Yeah. And vary it and, you know, I'm finding I'm now getting up to nearly 50 plants on many times. So that will naturally incorporate things like whole grains- Exactly

Tim: et cetera. So the more diversity, the more likely you are to get all the nutrients your brain needs.

Felice: And fermented foods.

Tim: Fermented foods comes in a close second. Yeah And I think we should all be having some fermented foods in our diet 'cause it works in a different way on the immune system. And they're probably the two key fundamentals we should be all doing.

Jonathan: If someone is listening to this and they're saying, "This all sounds great, but I need really cost-effective ways to be able to improve my diet, and one of the reasons that I, you know, am eating lots of this ultra-processed food is that it's cheap and it sort of can, you know, it lasts," all the rest of it, what would you suggest?

Felice: Food has to be accessible, it has to be easy to prepare, and it has to be affordable. What I do is I do on the weekend a big Crockpot. I change the grains every week, but often it's things like barley in there. Legumes of different sorts. I'll put in different dried legumes. These are super cheap. Barley is super cheap. And then I can use frozen vegetables. They're really cheap and they're often frozen really just after they're picked, so they can maintain actually their nutritional density. Plus the whole grains, plus the legumes. And I think that that's a really simple, extremely cost-effective way of having super fast food available to you for the week.

Tim: I think it's a great question. How do you get people who are on a bad diet with some mental health issues to eat better? And that's why actually I've come up with a cookbook of over 100 recipes and tips about what to keep in the larder, how to batch cook, how to use frozen foods, frozen vegetables that canned things that cost very little. And when you do that and you start thinking about it more rationally, you actually reduce what you're spending on your food. You've just got to plan it right. You've just got to say, "I've got to change some of my habits. Let's have a new look at this." So hopefully people who want more detail, you know, can go and get some new ideas on how they can change what they're eating on a regular basis in ways that's really going to improve their mood and their brain. We want to change people's habits for a lifetime, and so it doesn't matter it takes time to get there. It's, that's not important. It's just making these permanent changes.

Jonathan: So to finish, Felice, if someone is listening to this, but maybe they feel a bit overwhelmed by, you know, where they are and the challenges in their life and how busy they are, what would you maybe recommend as one small change that they could sort of start with tomorrow that might really make a difference?

Felice: I think I'd suggest a mental change because when you think about the incredible complexity of the brain, it's the most complex thing that we know about, the incredible complexity of food, plus all the misinformation that's flying around as well as the really good information, the complexity of the gut microbiome and the science there, all that complexity could just blow your brain up and you could just think, "Well, I'll just give up and walk away and keep eating the chips." What I'd say is that's all complicated, but what you need to eat to feed your gut microbiome is super simple. So it's just lots of plant foods of different sorts. I think probably throw in some fermented foods. You don't have to be a vegan or even a vegetarian. Just try and avoid the foods that are in packets with lots and lots and lots of different ingredients, if you can, and focus on the ones that are whole. And they can be frozen, they can be tinned, they can be dried, they can be cheap.

Jonathan: Brilliant. I would like to try and do, I don't even call it a summary, but maybe pick out the highlights that have rested here in my mind, and maybe try and focus on particularly on the actionable advice at the end. The thing that immediately comes to mind is you can give mice something like schizophrenia and depression simply by giving them the gut microbiome of a human being with those. And I think it does really break this whole idea that I grew up with that these are things that are just in your head and they're not like- Yeah

Jonathan: in your body. And it really tells you also just how important your microbiome is, and therefore your food. So I think that's crazy. It also, I guess, makes you realize that people with these mental disorders, like, they have a very different gut microbiome. The second thing I'm really struck by is something you said, Felice, that mental disorders are the largest cause of disability in the world today. So this isn't just like a niche thing. That's huge, and that's before we even talk about people who are maybe high-functioning but feel anxious or stressed. And then the other thing, Tim, that you said, which is that mental health and brain health, like dementia, are really the same thing. The impact of food on our mental health is huge, that you can basically give people a change in diet and a third of them can stop having depression symptoms, you know, is remarkable, and that works as well as, you know, all the drugs and things we have The other thing I think that came through really strongly is ultra-processed food as an issue is really real. And you said you did this massive new study, and 70% of bad health outcomes, including mental health and cancer and heart disease, are linked to an increase in eating ultra-processed foods. You just see what a big deal it is. But I think the good news is then you said, like, there's a lot you can do. So this also isn't something that you're just stuck with. On food, I think that, you know, the rules are the same things we talk about all the time. Think about 30 plants a week. Particularly think about these plants that are gonna really feed your microbiome, whole grains, barley, quinoa, unprocessed oats, legumes like chickpeas and beans, fermented foods. But also think in this case about specific foods that you want to reduce or try and keep really low, so particularly cut out the worst ultra-processed foods. You know, Tim says, "Don't worry about all of them, but, like, the high risk and the medium risk you really want to take out." Felice says, "You know, you turn it over and say, 'Does it have an emulsifier?' Okay, I'm gonna try and avoid." Then on other things, cut out ready meals. Cut out sugary drinks. Processed meat, sausages, salamis, these hams, it's a really big deal. And Tim finally he said, you know, any food with a big health claim on it for you is a really easy way to say like, "I just wouldn't eat that." And then finally to finish, Felice isn't taking any supplements. Both of you are trying to eat a lot of oily fish to keep your omega-3 levels up, so that's a sort of food as supplement. Tim has started taking folic acid. And you both said, actually, just amazingly, think about vaccines. Shingles vaccine, flu jab, that might be the biggest thing you can do actually to, like, protect your mental health, which is amazing. I never would've thought about

Felice: it. Protect against dementia specifically. When you think about mental disorders, there are so many risks that we have very little control over. Now, the fact that something that 100% of the population does several times a day is actually a modifiable factor in the risk for these common mental disorders, which account for this huge global burden, this is critically important. So this is actually really exciting. It's something that we do have some control over, but it should not be up to the individual. We need to change the system. We need to change our environment so that less healthy foods are not the default.

Tim: Just a final note, I think if everyone realizes the link between what they're eating and their mood, they would actually be really motivated to change what they're eating.