Best of 2024 – Part 2

Let’s dive into the second part of our 2024 recap. We’re taking another look back at all the best nuggets of wisdom from ZOE episodes this year. 

In this jam-packed episode, we’ll hear how your second brain affects your mood, why fasting doesn’t actually have to be difficult, and how to prevent the disease you probably don’t know much about – but can lead to hospital time. 

As you consider your New Year’s Resolutions and new habits, this episode will ready you with some great ideas. Why not share with a friend who is also trying to make positive change?

Make smarter food choices. Become a member at zoe.com – 10% off with code PODCAST

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Transcript

Jonathan Wolf: Welcome back to our two-part recap of 2024, taking a look back at all the best nuggets of wisdom from ZOE episodes this year. In this jam-packed episode, we’ll hear how your second brain affects your mood, why fasting doesn’t actually have to be difficult, and how to prevent the disease you probably don’t know much about, but can lead to hospital time. Let’s get into it.

If you’re anything like me you’ve probably heard a lot about intermittent fasting but maybe aren’t completely sold on the idea. Well, this first episode might just change your mind. Intermittent fasting can spark some serious health benefits. But how to get started? 

In this episode, I talk with my ZOE co-founder Professor Tim Spector and I heard from Gin Stephens, an intermittent fasting advocate and best-selling author. 

And it’s the first time that I tried intermittent fasting and transparently, I absolutely hated it. And so I did follow, I did the required week and I could not wait. The day I stopped, I was so happy. 

But before we get into that, I’d like to just start at the very beginning, actually with you, Gin. What is intermittent fasting?

Gin Stephens: The word sounds so scary, you know, the word fasting makes you think that you’re going to like 40 days and 40 nights wandering in the desert.

But intermittent fasting, the word intermittent is key. You are having periods of fasting and periods of eating, which every single person who is listening or watching already does that. It’s just changing the balance of that. You know, you go to bed, you sleep, you wake up in the fasted state. Probably everyone listening has had fasted blood work before. So, our bodies are already fasted every single day. 


If you live an intermittent fasting lifestyle, the difference is you just extend that period. Instead of most people having this much for your feeding time and this much for fasting, we just switch it. And so, you’re fasting for a longer period of the day, intentionally.  


Jonathan Wolf: This is obviously on a 24 hour cycle, so very much focused on this idea there’s a time of day when you should do things and a time of day when you shouldn’t. It seems like that’s played in quite a lot into this idea of thinking about eating in particular parts of the day on a sort of regular 24 hour rhythm. 


Gin Stephens: Well, I would just like to point out that y’all know from your research with ZOE, bioindividuality is a big component of what you’re doing. It’s the whole thing that y’all are doing. And I think that also applies to circadian rhythm. 

I work with intermittent fasters from all around the world who live intermittent fasting as a lifestyle. I’ve worked with hundreds of thousands of members of my communities over the years, and you figure out what works for you over time. 

There are people who tend to have an earlier eating window or a midday eating window, but most of us tend to gravitate towards afternoon, and evening, just as a practical way of living our lives, but we’re not all the same. 


Prof. Tim Spector: That said, within that, there’s variation, but I think what you’re getting at is the fact that all humans have a circadian rhythm which means their body has to do stuff, active stuff in a certain time, and then rest stuff in another time, and all our cells are geared up for that. 

So, it’s become clear that eating needs to be done at the same time as your body is in activity mode and not in total rest mode. 


I think this is also being linked to the circadian rhythms of our gut microbes that are having to deal with the food we’re eating if it’s at weird times. And this also goes to this idea that shift workers and people who are doing stuff out of sync have poorer health because of it. 

So I think it’s more and more we’re realizing we have to Go back to our origins, and this means eating in times when we would normally be active rather than very late at night, particularly. 


Gin Stephens: Exactly, yep. But everybody figures that out over time. You find out where your body prefers, what just feels natural to you.  


Jonathan Wolf: And in this episode we also revealed a world exclusive: our brilliant team of ZOE scientists completed the world’s largest study of intermittent fasting. 

Could you tell us firstly about the study? What happened? And then what have we found?  


Prof. Tim Spector: The Big IF, it’s not a question mark, it’s IF, study of intermittent fasting. And it came out of a big health study we were running in the U.K. called the ZOE Health Study and there were 246,000 people that were eligible for this. 


We told them what it entailed, which was just monitoring what you eat for a week, so we actually could document what the normal eating windows were. And then the idea was to eat within a 10 hour eating window. 14 hours of overnight fasting and 10 hours of eating, which isn’t a very strict one, but it is one that has been shown across a range of animals and humans to be effective. 37,000 of them completed the study. 

Jonathan Wolf: How long did they have to do the fasting for?  


Prof. Tim Spector: They did it for two weeks. 27,000 were highly engaged and continued it for many more weeks after that, some of them up to about 16 weeks, and a proportion of them are still going, so that we got people hooked on it. 


At baseline, they weren’t too bad. Their eating window was about 11 hours. So, for many people, they only shifted it by about one hour. The people that did complete it, they lost on average about 1.1 kilograms. That’s just over a couple of pounds in weight. But importantly, we saw that people who reduce that eating window most, change most. 


We got increases in energy levels of 22%, mood improved by 11%, and interestingly hunger, which most people thought would have gone up, actually slightly dropped. 

Jonathan Wolf: So hang on, I just want to make sure I got that right. You’re saying that for the people who did this, even though they were eating in a shorter time than before, they were actually less hungry than they were before they restricted their eating. 


Prof. Tim Spector: That’s what they were reporting, yes. Sounds, like, counterintuitive.  

When we looked at the people who weren’t doing this consistently, so they were having one day of doing it, another day not, we found that actually things reversed. Those people were more hungry and they had less energy. So clearly you do need some sort of stability to this to get these benefits. 


And we also saw the people that benefited most had an eating window that was largest at the beginning. Those people that maybe were eating over a 14 hour window, they benefited the most from this and the people that were marginally, near it when they started. 

Jonathan Wolf: It’s been a bit of a shock to me, because I was definitely brought up with this assumption that you have to have breakfast, it’s really important, before you go and do something else.

Prof. Tim Spector: I think also the other misconception we were brought up with is, you’ve got to have food inside you before you undertake any activity. Otherwise, whether it’s walking to school or going for a jog or going on your bike, you’ve got to have carbs up there, you know, to be ready for it. And now we know that’s not true.  


Jonathan Wolf: In fact, doing exercise when fasting can be beneficial for your health – so get out of bed and go for it!

Tim also shared some of the science around time restricted eating. 

Prof. Tim Spector: That’s the one thing that stood out of all the studies is, on average, you’re getting reduced inflammation from giving your gut a rest. And you are improving your gut microbes. 

This has this effect all across our body and this is why it’s important for energy and mood and our immune system in general. 


Small amounts of weight loss are a bit of a side effect for some people. They’re not the main reason for doing this modest time-restricted eating, because it is very modest. We’re only shifting people, a lot of them, just by one or two hours in a day. It’s not a huge difference compared to these trials, which have often combined this with calorie restriction. 


Jonathan Wolf: This study was quite short-term, right? So it was two weeks. And I think one of the things we talk about all the time on ZOE is the only thing that really matters is a long-term sustained change in life. So this is clearly like a test of something as scientists often do, right? These short term to then learn about some long term. 

So if people had stuck to this shorter eating window based upon all the other sciences out there, what health benefits might they expect and you mentioned something about inflammation.?

Could you maybe help us on some of that and elsewhere? What would that actually mean for someone if they want to make this as a permanent change to their life?

Prof. Tim Spector: If we see this reduction in inflammation and we assume that’s going to continue no reason to think any otherwise, then you would see small changes across a wide area of health. 


So that means that your immune system is working better, that it’s reacting better, that your gut microbes are in a better state, they’re producing better chemicals. It means your mood is going to be heightened, you’ll get less depression, less anxiety, you will feel more general energy, less tiredness. You will have some small changes in perhaps your mood, response to sugars, minor changes in your fat levels, reducing your risk of heart disease, et cetera, et cetera. 

So you won’t suddenly change your risk in a few weeks from being high risk to low risk.

Jonathan Wolf: It’s not like the silver bullet that cures all ills and you’re going to live for another decade, healthy life, just because of the time-restricted eating. 


Prof. Tim Spector: Absolutely not. But if you multiply that small difference in inflammation over years. 

Gin Stephens: That’s when it adds up.  


Prof. Tim Spector: Which is what we want people to do. There’s no point doing this for three weeks and then stopping. You’ve got to find something that suits you and then do it for a long time. 

Realize how important it is to give your gut and your body a rest. And if you can just prune your inflammation levels down, that will have huge effects on your risk of virtually every disease. 

Jonathan Wolf: One of the main takeaways of this episode that did really surprise me was that you can and should tailor intermittent fasting to your own lifestyle and body. 

Find the full episode here: The truth about intermittent fasting Spotify | Apple

Jonathan Wolf: Now I’ve always been a fan of mushrooms. Mushroom stroganoff is a go-to weeknight meal for me, but I had no idea just how brilliant mushrooms are when it comes to our health. Turns out they could be a promising treatment for depression, and their chemicals might be protecting us from other diseases. 

For this mushroom tour, we chatted to Dr. Merlin Sheldrake, a biologist and the author of the best-selling book, Entangled Life: How Fungi Make Our World. 

Jonathan Wolf: If there were no fungi, would we be alive today?

Merlin Sheldrake: No.

Jonathan Wolf: Do plants rely on fungi as much as we rely on gut bacteria? 

Merlin Sheldrake: At least as much. 

Jonathan Wolf: Brilliant. Well, we’re going to go into that in a bit more detail. Now, Tim, do all mushrooms have the same health benefits? 

Tim Spector: No, but they’re all good. 

Jonathan Wolf: Are dried mushrooms as good for our health as fresh mushrooms? 

Tim Spector: Usually and sometimes more.

Jonathan Wolf: And finally, do psychedelic mushrooms have the potential to revolutionize medicine? 

Tim Spector: Absolutely. 

Jonathan Wolf: It came as a surprise to me that mushrooms aren’t plants – so what actually are they?

Merlin Sheldrake: Fungi are a kingdom of life, so that’s as broad a category as animals or plants. So there’s lots of ways to be a fungus, just like there’s lots of ways to be an animal and lots of ways to be a plant.

But they’re not plants and they’re not animals. Mushrooms are the reproductive structures of a small group of, well, a large group, but a small, proportionally small group of fungi. So mushrooms are the places where fungi produce spores, which help them disperse themselves over potentially large distances.

So when we think of mushrooms, we’re just thinking of a small part of the overall life of a fungus, which is usually in the form of a network. Most fungi live most of their lives as networks of branching, fusing cells called mycelial networks. 

Jonathan Wolf: And so that means I should think about mushrooms as a bit like a fruit. So it’s like a tomato or a pear within this thing that isn’t a plant. 

Merlin Sheldrake: It’s analogous to the fruit of a plant, except that the tree, say the apple tree that produced the apples, is underground. And the mushrooms you see usually are sticking up through the ground and you’re not able to see the rest of the tree.

Jonathan Wolf: Why aren’t they a plant? Because it feels like, they’re not an animal, and then they’re not a bacteria, so in my very simple view of the world, they’re a plant, aren’t they? 

Merlin Sheldrake: I think perhaps the most important difference is that plants on the whole, photosynthesize. So they produce energy from the light coming from the sun and from carbon dioxide in the air. And it’s a really fundamental process on the planet, photosynthesis. It’s kind of like they’re eating air and eating light to produce the energy they need to grow and do the things they do. 

Fungi don’t photosynthesize. So, like us, as animals, we have to find food in the world ready-made, as it were, and put it inside us. Fungi have to find food in the world and consume it. They can’t make their own energy-containing carbon compounds like plants do.  

Jonathan Wolf: For an ingredient that seems so unassuming, there are some really cutting-edge discoveries being made. Tim and Merlin shared how the humble mushroom can fight disease and protect our bodies.

Merlin Sheldrake: in Japan, there’s a chemical from shiitake mushrooms, which is used very widely for treating cancer alongside more conventional cancer treatments and also a compound from turkey tail, which is used very widely in quite conventional medical context.

So the research, the science is unequally distributed and some of the reasons why those are not used so widely here is because it’s not totally clear how they’re working, although it seems to be very clear that they work.

Jonathan Wolf: So psychedelic mushrooms have these amazing potential effects for mental health and cancer. But what about the edible kind, what might they be doing for our health?

Tim Spector: As well as being super tasty, there’s a lot of water in them, so once you’ve got rid of the water, they have huge amounts of protein, 25% protein, pretty good amounts of fiber as well. 

All these chemicals we’ve been talking about that have a whole variety of these effects. The source of selenium, they’re actually a source of vitamin D, and they sunbathe like humans.

Jonathan Wolf: You mentioned this before. Is it really true that if you leave them out in the sun before eating, they have more vitamin D? 

Tim Spector: It is. I mean, it depends slightly on the variety, but some of them are really good at converting natural steroids in them to vitamin D, which is a steroid, and basically you can get half of your vitamin D amounts from eating portions of mushrooms.

Merlin Sheldrake: I think there’s lots of things that fungi can do for us chemically that plants can’t. Because they’re so chemically ingenious, because they produce all these different compounds to do all these different things, in fact, lots of the chemicals that you’ll get by eating a plant have originally been concentrated or even made by a fungus.

Jonathan Wolf: So whether magical or not, mushrooms of all kinds really do seem to have these fantastic benefits for our bodies. Merlin and Tim left us with the key tip to eat mushrooms at least three times a week.

Find the full episode here: Mushrooms as medicine: Uncovering the health secrets of fungi Spotify | Apple

Jonathan Wolf: When I want to liven up my cooking, I tend to reach for the cumin, or maybe sumac. Spices are a staple in most kitchens. But spices are about more than just flavor, they’re a form of medicine too. My guest for this episode was Kanchan Koya, a molecular biologist turned food scientist.

Kanchan Koya: The formal definition of a spice is that it’s the root, the bark, the bud, the fruit, and the leaf. Although that can get a little tricky sometimes because leaves are more herbs than spices. 

Usually dried, those parts of the plant, once dried, constitute a spice. They’re often used in small amounts. for flavoring in food and hopefully, as will inspire people today, also to boost the health properties of food.

But yeah, that’s traditionally the formal definition of a spice. 

Jonathan Wolf: And it’s obviously started as something that just tasted really nice in our food, right? But I think now, and this is where your own research started, we understand they’re high in these things called polyphenols. Can you explain what those are?

Kanchan Koya: Yeah, so I would actually say that thousands of years ago when spices were first discovered, people did love how they made food taste. But actually, our ancestors also recognized that spices had additional properties like the ability to preserve food in the absence of refrigeration thousands of years ago.

So I think there was an understanding as evidenced by the fact that people waged wars and conquests were undertaken for the spice trade, that there was more to it than just flavor alone. But now we obviously have science catching up to some of that ancient kind of intuitive wisdom. 

Polyphenols are essentially a group of naturally occurring compounds that are highly prevalent in the plant kingdom, and for reasons that we’ll hopefully discuss, really enriched in herbs and spices, and highly concentrated. Phenols are just a type of chemical structure, and polyphenols just means that a lot of these compounds have multiple phenolic kind of units. 

But if you wanna just simplify it, they’re essentially chemicals, phytochemicals found in the plant kingdom that happen to play a role in plants but also have some beneficial effects in our bodies 

Dr Sarah Berry: And Kanchan, I always think that all of the chemicals that are in plants have magical functions because they’re there to preserve the plant itself. So if we take seed oils, for example, they’re enriched with so much vitamin E because it’s a natural antioxidant. So it kind of protects the plant. 

And this is the same with polyphenols in plants. They’re there as a natural defense for the plant itself. 

Jonathan Wolf: So we know that spices are fantastic flavour enhancers, and they contain these brilliant polyphenols. But how exactly do they work on our bodies, to support our wellbeing? 

Kanchan Koya: Yeah, so I’m gonna approach that question in two ways. One is I’m going to talk about the specific antioxidant potential of a lot of these polyphenols. 

So going back to this idea of oxidative stress, every time your cell divides, every time you undergo any cellular process, there is a production of free radicals.  These are just radicals that have a free oxygen on them that can then interact with proteins or DNA and sometimes cause damage. This is just a normal part of cellular metabolism. And polyphenols and spices can neutralize these free radicals. So they have this antioxidant capacity. So that’s one way in which they help us when we ingest them.

And the second way is actually something that we call hormesis in biology, which is a little bit of stress is good for you. So exercise is a great example. When you look at the effects of exercise on the human body in the short term, you actually see a lot of things go up in the short term that seem like they wouldn’t be a good idea. Like blood pressure goes up, a little bit of inflammation goes up, and you think, well, that can’t be good. 

But then what happens is once the stressor has been removed, you actually have greater cellular resilience. Now you have lower inflammation and lower blood pressure. So spice polyphenols…

Jonathan Wolf: This is what my trainer tells me all the time during the training session, it feels really painful and it hurts, but in the long run, it’s good for me. Which is what I always tell myself as I’m in the middle of the session wondering why I’ve done this to myself and you’re saying there’s something sort of similar with eating this food.

Kanchan Koya: Yes, so fasting is an example. In the short term, it can feel a little stressful and intense, but then long term, we know it can build some cellular resilience, help metabolic health. blood sugar control, that sort of thing. 

So spice polyphenols can be thought of as this short-term stressor, which is why they work as this defense compound against predators. And in our bodies, they also act in this way. They actually act as a little bit of a stressor, which then activates our own cellular antioxidant pathways. 

So a great example would be, and I don’t want to get too technical, but there’s a pathway that is the master regulator of antioxidant status called the Nrf2 pathway. And a lot of these polyphenols will activate our own cellular repair pathways because they are creating a little bit of stress through this mechanism of hormesis just like exercise or fasting.

Dr Sarah Berry: And I think the polyphenol research that’s coming out now is fascinating. It’s quite an exploding area of research, Jonathan, in the nutrition field. We know that people are having high polyphenol diets, whether it’s from herbs or spices or other foods. 

So, for example, polyphenols are found in very heavily pigmented kind of berries and vegetables, it’s polyphenols often give their color to fruits and vegetables. 

Jonathan Wolf: Is that sort of eat the rainbow? 

Dr Sarah Berry: Yes. You know, the dark green leafy veg, the berries, you know, et cetera. There’s so much research, isn’t there Kanchan, coming out now showing that polyphenols are linked to all sorts of improvements in health, whether it be cancer, whether it be type two diabetes, cardiovascular disease, you know, any inflammatory-related disease.

And I think this is because there’s evidence emerging around polyphenols beyond oxidative stress, around inflammation, about blood sugar control. 

Jonathan Wolf: We got creative in this episode. Kanchan actually brought in a spice box to show us. 

Kanchan Koya: The spice box in India is really an integral part of our ‘farmacy’, F-A-R-M, ‘farmacy’. And it’s rooted in the ancient Indian medical system of Ayurveda, which growing up I sort of rolled my eyes at and thought it wasn’t serious science. 

And then only when I became a Ph.D. student and my lab began to study curcumin and turmeric for breast cancer was I reminded that maybe some of this ancient wisdom is actually proving to be correct. 

Jonathan Wolf: I just want to be really clear here, right? So you are not saying, hey, any of these spices are replacement for modern drugs. You’re saying, however, there are some real properties in them, and we can learn something from that.

And I guess that a lot of modern drugs are sort of refined versions of compounds that are available in the natural world, aren’t they? I think about aspirin is the thing that I remember learning about when I was a kid. 

Kanchan Koya: Yeah, absolutely. So shikimic acid, which is the starting point in the synthesis of Tamiflu, which is one of our most successful antiviral drugs, actually comes from star anise, which is in my spice box. 

Jonathan Wolf: Amazing. So Kanchan, you just sort of pulled out a metal tin with, I think, what is our sort of six or so compartments that look beautiful with different colors and it sort of a bit looks like the bits of plant. Could you just talk us through what you’ve got in front of us? 

Kanchan Koya: So I have two different varieties of cinnamon, star anise, cloves, ginger, and ground turmeric.

Cloves are really interesting because they are thought to have some of the highest antioxidant potential amongst all spices. They’re also thought to have some antiseptic and analgesic properties, which means that they can relieve topical pain.

So if you’ve ever been to the dentist and they put clove oil on a painful tooth, that’s because clove has some topical pain-relieving properties. 

Dr Sarah Berry: There’s actually science behind that. It’s not a myth. 

Kanchan Koya: No, it’s not a myth. And when I have a sore throat, I just pop a whole clove in my mouth and just kind of keep it there like a lozenge almost. It’s not the most lozengy or sweet taste. It’s a little bit potent, but it really does seem to help.

Dr Sarah Berry: Does it alleviate the sore throat? 

Kanchan Koya: Yes, I think so, because of its topical pain-relieving properties. At least in my N of 1 experiment, I don’t know that there’s been a trial looking at a whole clove popped in the mouth for a sore throat.

Jonathan Wolf: But it works for you. 

Kanchan Koya: Yes, there have been some studies looking at clove oil, for sure.

Jonathan Wolf: Spices easing a sore throat or toothache? I was completely sold. But I was left wondering how exactly to integrate more spices into my everyday meals.

Kanchan Koya: So my biggest recommendation is to take the foods that you’re already eating, that you already enjoy, that your kids already enjoy and start to challenge yourself to add at least one spice to that dish. 

So if we just take some examples, people might typically eat avocado toast, you mentioned sumac, you could add some chili peppers, if you like heat, you could add a little bit of cumin and coriander.

Dr Sarah Berry: What about snacks? 

Jonathan Wolf: Oh, I was going to go exactly the same place. Exactly. 

Dr Sarah Berry: So you know, snacks account for 25% of our energy intake in the U.K. and the U.S. So I think it would be a great way if we could get some spices into our snacks. It would be fabulous. Any ideas?

Kanchan Koya: Yeah. So I would suggest a yogurt-based snack because we know yogurt is a fermented food, it’s great for microbiome diversity and inflammation. 

So, two options with yogurt. You could go in a sweet direction, where you take some Greek yogurt, you throw in a bunch of different berries for those wonderful polyphenols. You throw in some nuts, like walnuts, pistachios, almonds, and you sprinkle on some cinnamon, a little bit of grated nutmeg, and cardamom.  

And you almost have a pudding of sorts because it has all these luxurious flavor profiles from the spices. You get the benefit of potential blood sugar balance with the cinnamon and these additional polyphenols. Really easy way to spice up sort of a yoghurt snack. 

And then you could go in a more savory direction and prepare a yogurt dip for a plate of cut vegetables. So you can have your carrots, cucumbers, radishes, tomatoes, and your Greek yogurt with a little drizzle of olive oil. Some crushed garlic for that allicin, which is another great bioactive found in garlic. And to that I would again add salt, a little bit of sumac, chili, cumin, coriander, mix it up, and it’s almost like a Middle Eastern type of dip for your cut veggies.

Dr Sarah Berry: Great. And any ideas for snacks on the go? 

Kanchan Koya: Yeah, I actually love home-popped popcorn. So just get some corn kernels, do this with your kids. It’s super fun, a little bit of avocado or olive oil in a pot, throw the kernels in, let them pop. It’s really fun to hear them popping, the kids can get involved, and then just toss it with a spice blend that you love.

It can be garam masala, which is an Indian spice blend. It can be the baharat blend or a curry blend, you know, with a little bit of olive oil and salt. And now you have a spiced-up polyphenol-rich popcorn snack. 

Dr Sarah Berry: Great idea. 

Jonathan Wolf: That I have never tried. So it’s like curried popcorn. I’m going to be trying that one. 

Kanchan Koya: So I think there’s so many ways to take existing dishes that you already make, you already know how to do, and just add spices to that instead of sort of starting from scratch, which can be way more intimidating for people.

Find the full episode here: The medicines in your spice rack, with Kanchan Koya  Spotify | Apple

Jonathan Wolf: One of our most popular episodes this year took a deep dive into our second brain. That’s right: our second brain. It stretches from your mouth to your bum. It has more than a hundred million nerve cells. And it impacts your cravings and mood. That second brain is of course, your gut.

I was thrilled to speak with Dr. Karan Rajan on such an exciting area of emerging science. He’s an NHS surgeon, senior lecturer at Imperial College London, and hugely successful health and science communicator, with over 10 million followers across social media.

When we talk about the gut, we’re not just referring to the stomach, are we? 

Dr. Karan Rajan: No, and in fact, if you’re thinking about the gut, you think about digestion, and if you think about digestion, it would also be wrong to think about the stomach because no digestion actually really takes place in the stomach.

There’s some mechanical and maybe some chemical digestion. It also happens in the mouth. But actually, digestion begins in the brain. 

So, when you’re even thinking about an ice cream, a plate of food, the brain actually triggers that whole cascade of digestion. The signals get sent to the gut, to the salivary glands in your head, and all these juices are starting to be secreted. And that’s all linked with also your circadian rhythm, that biological clock. 

You see, I like to think of the gut as this orchestra. And that orchestra, the maestro of that orchestra is the brain, the circadian rhythm, because it determines when you feel hungry, when you want to go to the toilet, so it really all starts in the brain.

And then the bulk of the digestion, the kind of real mechanical digestion and the chemical stuff that we think about, then occurs in the small intestine, that’s where the bulk of it happens. 

So really the stomach is such a small player in the grand scheme of things of gut health and digestion. Even beyond the small intestine, where I’ve just said digestion occurs, it’s really, if you want to dig down into the granular detail, the colon, where the bulk of the ecosystem of our digestive activities takes place, and that’s where the microbiome lives.

I’ll be a bit biased when I’m talking about gut health, and if you ask any general surgeon or colorectal surgeon or any GI [gastrointestinal] surgeon, they’ll tell you that guts are the most important system of organs there is, and if you speak to a cardiologist, they’ll say it’s the heart, naturally.

Really, when it comes to it, it’s the foundation of everything. Actually, when microbiome research went from fringe hippie science into mainstream science, and that’s probably the most popular health topic right now, that’s opened our eyes into actually how powerful it is. Because we know your first question is, is our gut just there for digestion?

We know it’s far more than that because we know the gut has its own nervous system, the enteric nervous system. The immune system is also very highly active in the gut as well. It has a role in building our immunity and it’s interacting with the outside world. 

Jonathan Wolf: Can you help us to understand what are the most common ways in which we are irritating our gut?

Dr. Karan Rajan: I think it’s worth bearing in mind that whilst for specific things like gallstones or cancers, there’s a significant genetic component there we need to be mindful of. 

There’s also, with any number of gut issues, there are lifestyle factors at play, which people can modify, which doesn’t make them immune to these things, but can lower their risk of certain things. 

So for example, there are a number of irritants in our lifestyle that has a role to play unquestionably in our guts, some which we can’t change. Environmentally, we cannot change. 

We know that air pollution can have an impact on our microbes. And if you’re living in a polluted city, beyond moving from that city somewhere else, there’s not really so much you can do about that.

Other things; we know that antibiotics, especially broad-spectrum antibiotics, and chronic use of those antibiotics can have a role to play. I think there was a recent study on about 14 and a half thousand NHS nurses. So the national healthcare system in the U.K., the healthcare system, they looked at 14 and a half thousand of those nurses and they found there was a clear correlation and association between chronic antibiotic use of over two months and lower scores on memory tests, cognitive tests, focus, reflex, etc.

Is it because of its impact on the microbiome or something else? We don’t know. But clearly, it has some sort of detrimental effect there. And especially when the microbiome is evolving and growing in the early stages of life in the first few months and first few years, that’s particularly when antibiotic use can have a role to play, impacting the good and bad bacteria. 

Other things like even the food we eat, a lot of them are enriched with antibiotics and pesticides. There’s a lot of talk about ultra-processed foods. Again, the science is growing on that. I don’t think it’s right to say that ultra-processed food directly and causally affects your health directly. But we don’t have enough consistent strong evidence to say that. There may be a role to play for sure because that’s the change in the last few hundred years, one of the changes.

NSAIDs, nonsteroidal anti-inflammatory drugs, things like ibuprofen that can also have an impact on the guts. For example, I quite often operate on people who have got ulcers, burst ulcers because of chronic ibuprofen use, for example.

A lot of the other medications we can take can have an impact on the gut as well. Alcohol, that’s another potent irritant for the guts. And we also need to bear in mind that all of these things can influence the microbiome in a way, especially in early stages, that influences the immune system.

We know a bulk of GI conditions are autoimmune in nature. Things like Crohn’s, ulcerative colitis, and beyond. So there’s a number of irritants, some in our control, some out of our control. One of those things in our control could be things like smoking habits, alcohol, the diet, the fiber, as we mentioned, we know that has a role beyond just roughage as you suggested was the kind of dogma a few years back.  

So yeah, there’s a number of things modifiable and non-modifiable. 

Jonathan Wolf: So what changes can we make to keep our guts happy?

Dr. Karan Rajan: I think it does start with food, a lot of the at least easy options. That someone can make a change from right now, listening to this podcast from tomorrow, from today, even making that change.

We know the gut microbiome is quite adaptable. It bounces back, relatively well, and it’s very responsive to change. So even within 24 hours of eating a certain food, you can begin to see some changes in the microbiome. 

If you look at most of the literature that’s out there, the meta-analyses, and the systematic reviews when it comes to eating for better gut health, it’s nothing very complicated.

We talk about fiber and prebiotics, they’re essentially the fertilizer for the bacteria, allowing them to thrive. So plant-based foods. Now, it doesn’t mean you need to have a plant-based diet full stop and cut out every single piece of meat or fish. That’s not the case, you can have a perfectly thriving microbiome, with meat, but the majority of the diet, if it is plant-based, that’s good.

Jonathan Wolf: I can tell you’re definitely not very keen on people going down to the local grocery store and popping a probiotic. 

Dr. Karan Rajan: I wouldn’t be. I’m optimistic in that we will get to that point in science where actually that’s a viable option, where we have tailored probiotics and we have, or even generic probiotics which actually do work.

But I don’t think we can actually say, just like we recommend vitamin D in winter months, actually, yeah, we recommend probiotics for general health. I think we could get there in the next few years, maybe, but right now I don’t think it’s worth it because there are so many other low-hanging fruits.

Find the full episode here: Simple ways to improve your gut health with Dr. Karan Rajan Spotify | Apple

Jonathan Wolf: There’s one disease that leads to more time spent in hospital than many other major diseases, but most people aren’t aware of it until it’s too late. That disease is osteoporosis, which causes fragile bones. One in five men over 50 will break a bone because of osteoporosis. And for women over the age of 45, it means more hospital time than breast cancer, heart attack, or diabetes. 

But here’s the thing, osteoporosis is both preventable and treatable. For this episode we spoke to two leading experts on osteoporosis, Professor Cyrus Cooper and our own Professor Tim Spector. 

Prof. Cyrus Cooper: Osteoporosis is the commonest bone disorder worldwide, and it’s associated with reduced bone density, a disruption of the microarchitectural content of bone, and an increased risk of fracture. 

The fractures that typically arise from osteoporosis are fractures of the hip, the spine, and the distal forearm or wrist. Those three fracture sites account for about half of all fractures in older people, and the other half are from all the other sites combined around the skeleton. 

Jonathan Wolf: The places you are talking about feels to me not the most common places that people tend to break their bones when they’re children or in their 20s or 30s, is that…?

Prof. Cyrus Cooper: So that’s exactly correct. In their 20s and 30s, trauma plays a much bigger role than bone density. 

Jonathan Wolf: So this is like falling out of a tree or…

Prof. Cyrus Cooper: Or having a road traffic accident.

Prof. Tim Spector: Breaking a nose. 

Prof. Cyrus Cooper: Yes. Whereas as you get to later life, particularly for women above the age of 50, up to the average age of menopause, and men more so after age 70, low trauma or in fact, absent trauma is associated with many of the fractures and those truly are ones due to bone fragility.

Jonathan Wolf: So what does it mean to break a bone without trauma? I think of it always being like you…

Prof. Tim Spector: It means just rolling over in bed, for example. You can actually trigger a vertebral fracture.  

Jonathan Wolf: Wow. 

Prof. Tim Spector: Just by doing that or twisting in a certain way. 

Prof. Cyrus Cooper: Most of our vertebral fractures present on an incidental finding on a radiograph.

Jonathan Wolf: And just help me out, vertebral fracture, where is my, where are my vertebrae? 

Prof. Cyrus Cooper: Your spine. And typically, the bones that break in your spine. The spine contains small vertebral bodies all the way down. The mid-thoracic, which is the middle part of the back, and the lower lumbar, which is down towards the pelvis. Those are the main sites at which osteoporotic vertebral fractures occur. 

Jonathan Wolf: If you’re listening to this, and you’re worrying about yourself, or maybe you’re worrying about a loved one, is there a way to find out if you have this osteoporosis? Because you’re saying it’s hidden away inside the bones inside my body. 

Prof. Cyrus Cooper: Absolutely. So the assessment of future fracture risk has become a very topical area in the last 15 years. Before, we understood that age and a previous fracture were definite markers of a future risk of fracture, and those people, particularly those with a past fracture, needed to be evaluated even before 15 years ago.

In 2008, we developed a global tool that mixed risk factors for osteoporosis just from a questionnaire, height, weight, and a DEXA scan to derive for an individual patient the 10-year risk of a hip or any osteoporotic fracture. And that 10-year risk is now incorporated in multiple rules, which are often dependent on different healthcare systems in different countries, but the principle of which is to target treatments according to people’s fracture risk. 

Jonathan Wolf: And if you were a woman listening to this, at what point would you start to… because I think I’m hearing nobody, almost no one in their thirties would this make sense. When do you start to worry about this?  

Prof. Cyrus Cooper: A person who had a 20% chance of having a major osteoporotic fracture, or a 3% chance of having a hip fracture, meet the criteria for the cost-effectiveness of drugs that retard their future risk of fracture.

Prof. Tim Spector: So it’s a bit like the statin story. So in a way, what the osteoporosis world have done is come up with a table of risks, proportional to your age and sex, to say, at this point it’s worth worrying about it.

Each country’s got its own levels, but it really varies a lot with age. So, exactly the same risk factors, but just 10 years older, you’re much more likely to have a fracture. It’s much more important to get some intervention. 

Jonathan Wolf: And so if you’re a man or a woman listening to this, I guess my question is, at what age would you say, I think I should have a conversation with my doctor to discuss this? Because it sounds like this is something that is changing a lot with age.

Prof. Cyrus Cooper: Absolutely. Ever since the development of DEXA scanning, there has been discussion about when we should use that bone density measurement. And early on the most discussion was directed to, at the time of the menopause, at age 50 say, in women. 

Of course, that’s actually an inappropriate time to undertake mass screening. It’s much better when age has caught up, the fracture rates, to around 70 to 80 years for individuals on a large scale to benefit from knowing what their bone density is. 

Jonathan Wolf: So what be done about osteoporosis, and what are the treatments?

Prof. Cyrus Cooper: So, the first line of treatment would be a drug class called the bisphosphonates. And examples of bisphosphonates are alendronate or risedronate. Those are taken in tablet form once per week.

With adjunctive, as I’d mentioned before, calcium and vitamin D as part of the trial regimen. And those drugs will reduce over a three to five-year period, and indeed longer with follow-ups of the trials by 50% the number of fractures.

Jonathan Wolf:  Oh wow, so you can just take a tablet once a week and you can actually halve the number of fractures.

Prof. Tim Spector: That’s right, but only while you’re taking it. So that’s the caveat. We used to think, oh, if you treat people for five years, you’ve pushed everything five years away. It doesn’t seem to be true. It’s only while you’re taking it are you protected.

And that’s sort of the problem because you’re actually slowing the bone down while you’re on it. So that’s why we have these drug holidays you go on, and so every five years you have a little break for a year, let your bone recover, and then you go back on it. 

Prof. Cyrus Cooper: Indeed. That’s the regimen that would be the first line.

Then you can use intravenous therapy. of the same type of drug, zoledronic acid it’s called, but it’s a bisphosphonate, given once a year. And that allows the bone resorption to be reduced in a much more marked manner than the oral bisphosphonates. 

Then the next line would be the last of the resorptive agents, which is called denosumab and that it is given once every six months with a subcutaneous injection. Those will reduce by 50 or 60%. 

Jonathan Wolf: I feel if you’re listening to this and you’re concerned, you would definitely want to know your state. 

Prof. Tim Spector: And perhaps I should also mention HRT, which we mustn’t forget about. Which was the first one before bisphosphonates. 

Jonathan Wolf: So this is hormone replacement therapy. 

Prof. Tim Spector: Or estrogen replacement therapy in the U.S. 

Jonathan Wolf: What does that do? 

Prof. Cyrus Cooper: Above the age of 60, 65, there’s been a sort of discussion that perhaps the risks of heart disease become prohibitive on general use of HRT, but in someone who’s had a fracture they are going to be benefiting from their bone density’s point of view.

Jonathan Wolf: Now, I think one question a lot of people will be saying is, is there anything specifically, however, that I should be thinking about adjusting? So, imagine that maybe I’m going through perimenopause, or going through I’ve been through menopause. Is there anything that we know about, that I might want to think about changing my diet? Or is this just overall, I need to care more about the quality of my diet, perhaps than when I was younger?

Prof. Tim Spector: I think the number one message is care more about the quality of your diet. Try and get more plants now, because they are all these sources of other minerals.

As you said, there are 100,000 different chemicals in food. So the more diversity we get, the more we are going to get a balance of these things. And so that’s why a rich balance of particularly plants is going to give you all these, whether it’s zinc or magnesium or phosphate, in exactly the right amounts that your body needs.

We’re evolved to take it up and absorb it in those ways. That’s more important than any saying, okay, I’m going to forget all that. I’m just going to take some vitamin D capsules and drink a pint of milk. So I think in a way that’s where we’ve got it wrong in the past. 

We’ve said, well, there’s one quick fix here where actually it’s going back to there isn’t a quick fix. It’s this holistic idea. Again, it comes back to food quality.

Find the full episode here: What to eat to avoid osteoporosis, with Prof. Cyrus Cooper Spotify | Apple

Jonathan Wolf:  Thanks so much for listening to our round-up of ZOE’s best episodes this year. We’re committed to bringing you actionable tips from the cutting-edge world of nutrition science; and we really heard some fantastic insights throughout 2024. 

We hope you will leave today feeling empowered to take a personalized approach to your own nutrition like figuring out what intermittent fasting schedule makes sense for you, understanding your own gut health, spicing up your life (literally), and strengthening your bones are all within your control.