ZOE Science & Nutrition - How inflammation could age you with Prof. Philip Calder

Episode Date: May 16, 2024

Inflammation is a complicated topic. Short-term inflammation plays an essential role in fighting infections and healing injuries. But too much inflammation can be a catalyst for chronic ailments, like heart disease, type 2 diabetes, autoimmune disorders, rheumatoid arthritis, and obesity. What we eat can influence our inflammatory responses and contribute to chronic, low-grade inflammation. In today’s episode, Prof. Philip Calder helps us understand the science behind inflammation, how it impacts our health and what food has to do with it. Philip is head of the School of Human Development and Health, as well as a Professor of Nutritional Immunology, in the Faculty of Medicine at the University of Southampton. He’s also an internationally recognised researcher on the metabolism and functionality of fatty acids. His work focuses on the roles of omega-3 fatty acids and the influence of diet and nutrients on immune and inflammatory responses.  🌱 Try our new plant based wholefood supplement - Daily 30 *Naturally high in copper which contributes to normal energy yielding metabolism and the normal function of the immune system Learn how your body responds to food 👉 zoe.com/podcast for 10% off Follow ZOE on Instagram. Timecodes 00:00 Introduction 01:20 Quickfire questions 02:55 The role of inflammation in immunity 05:30 Chronic inflammation and disease 08:30 How to measure inflammation 09:53 Low-grade inflammation and disease risk 12:30 What causes blood vessel inflammation? 15:23 What creates the narrowing of blood vessels? 17:20 How inflammation can cause blood clots, heart attacks and strokes 19:15 Inflammation and aging 21:40 Inflammation and lifestyle factors 25:07 Obesity and inflammation 28:45 Muscle loss and inflammation (sarcopenia) 30:52 The impact of meals, sugar and fats on inflammation 33:35 How diet could reduce inflammation 34:42 Why we all respond to food differently 38:42 Dietary choices to manage inflammation 40:00 What are omega-3s? 41:17 Anti-inflammatory foods 43:40 Health benefits of omega-3 fatty acids 45:55 Challenges with farmed salmon 📚 Books from our ZOE Scientists: Every Body Should Know This by Dr Federica Amati Food For Life by Prof. Tim Spector Mentioned in today's episode: Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology? in the British Journal of Clinical Pharmacology Omega-6 fatty acids and inflammation in PLEFA Omega-3 fatty acids and inflammatory processes in Nutrients  Another relevant study: Health relevance of the modification of low-grade inflammation in ageing and the role of nutrition in Ageing Research Reviews Have feedback or a topic you'd like us to cover? Let us know here Episode transcripts are available here.

Welcome to ZOE Science and Nutrition, where world-leading scientists explain how their research can improve your health. Today's topic is inflammation. It's a word we often hear, but what does it really mean? And how does inflammation relate to what we eat? Some inflammation in the body over a short time frame is necessary for us to function well. It's a natural response to infection or injury. But long-term or chronic inflammation can increase your risk of serious health conditions, including heart disease, liver disease, type 2 diabetes, obesity and even dementia. Today, Professor Philip Calder joins us to help understand how we can lower inflammation

to avoid diseases and improve our health. Philip is a professor of nutritional immunology and the head of the School of Human Development and Health at the University of Southampton in the UK. He's a highly cited research scientist with over 800 scientific publications and an expert on how our diet influences our immune system and inflammation. Philip, thank you for joining me today. Thanks for having me. Great to be here. It's a real pleasure. So we have a tradition here at Zari Philip, and the tradition is that we always start the podcast with a quick fire round of questions. And we have some very special rules that professors always find really difficult. You can say yes or no, or if you absolutely have to, you can have a one sentence answer. Are you willing to give it a go?

I'll try my best to stick to the rules. All right. Could inflammation make me age faster? Yes. Can long-term inflammation cause serious diseases? Yes. Are inflammation and immunity the same thing? No.

Can the food I eat cause inflammation after meals? Yes. I'm nearly 50. Is it too late to change my diet to lower my inflammation? No. That's good. I was going to get really upset if you'd say something different, so that's good. And finally, and you can actually have a few sentences, what's the biggest misconception about inflammation that you often hear? That inflammation is always harmful, I think is a misconception because inflammation is there for a purpose. I've been talking about inflammation with scientists for seven years now since I first got involved with Zoe and I still find it really hard to understand. I know it's something to do with our body's defense mechanisms. I understand that the food we eat can influence it. And I'm really excited to have you here to help me and the listeners sort of to understand more. Can you explain in simple terms,

what exactly is inflammation, how it's different from immunity, and why you're saying it's not necessarily always a bad thing. Yeah. So immunity, our immune system, is the way we defend ourselves against harmful things in our environment, particularly things like bacteria and viruses. Now, immunity is very complicated, very complex, it's very sophisticated, and it involves many different things happening in the body, many different cell types and events occurring. Inflammation is the first little part of the immune response. So immunity is sort of like an umbrella of very complicated but joined up events, and inflammation is just part of what's under that umbrella. So we shouldn't mix up inflammation and immunity. Now, because inflammation is part of immunity, it's actually

designed to help us. It's designed to be part of our protective mechanism. So inflammation is really the first thing that happens when we get exposed to something harmful. And that could be an infection. It could be an insect bite. It could be, you know, a paper cut. So the things that people experience when they get a paper cut or even a more serious cut, you know, the pain, the redness, the swelling, that's inflammation. So that's designed to help us.

So it's something that happens in a helpful context, but it turns out if it's not regulated properly or if it's happening in the wrong place at the wrong time, that's when it becomes harmful to us. Got it. So a little bit is good and in fact necessary. So I can, you know, obviously if you cut yourself and you don't stop bleeding or anything, you will eventually die, I guess, but it needs to cut out. If you imagine you cut yourself, and I use paper cut as a really simple example, but any sort of cut, a more serious cut, you have a problem with bleeding. So you have to turn bleeding off, but also you have the possibility of getting exposed to bacteria that might be living on your skin, for example,

or on the thing that cut you. So you need to be protected against those. That's what inflammation does. But as you say, it has to turn itself off. And we call that resolution. So the resolving of inflammation, the turning off. And lots of problems happen, for example, when we age or in certain diseases, if inflammation doesn't turn itself off. So we don't have this resolution of inflammation. It's like a lot of things in life, a little bit might be good, but lots is not so good. Correct.

And in theory, it should be getting switched off. And I guess that sort of raises the question. So what's going on, therefore, that we can end up with this sort of bad inflammation where it hasn't been switched off? So I think there's two things. One is if you get continuous exposure to the thing that initiated the response in the first place. So a good example of this would be a disease that's known to be driven by inflammation. So something like arthritis, for example. So arthritis is where inflammation is attacking the person's joints and you get all the hallmarks of inflammation. You know, you get the redness, the swelling, the pain, all those things. So what's happening there is actually the inflammation is responding to the person's own body. You know, that's not going to

go away. So you get this continuous exposure. So you never get the opportunity to turn the inflammation off because it's always being driven forward. The other is a loss of the signals that turn inflammation off. And this is actually where some dietary components, which we're probably going to talk about later on, come into play. We need to actively be able to turn off the inflammation. And if we lose the capability to do that, obviously, it just keeps going. It's like a runaway car, if you like.

Got it. And so, I'm guessing your first example with the arthritis, you're saying that your body is actually attacking itself. It's actually sort of being triggered in that situation. So it's feeling like actually your own body is like one of these sort of alien invaders you were describing, you know, when you cut yourself and you get bacteria. That's right. It's called an autoimmune disease, but it's actually an inflammatory disease, like arthritis, multiple sclerosis. There are others that we know inflammation is central to actually causing the disease. And it's because your body's actually made a mistake. It's seeing itself as somehow harmful,

and it shouldn't do that, of course. Now, there's a genetic predisposition to that. So, you need the combination of the genetics and something else to trigger that sort of response. Can that be triggered by the fact that you have a lot of this like long-term inflammation from other causes and then that makes it more likely that you end up having the arthritis? It could be. So if you have a series of events that can trigger one of these autoimmune inflammatory diseases. So a good example of that actually is type 1 diabetes,

which is believed to be triggered actually by some sort of viral infection of the pancreas. So you get an initiating sort of trigger from something that is foreign, that does need to be dealt with, but then the body starts misinterpreting what's going on, and the body starts attacking itself, and that of course destroys the pancreas, and you get type 1 diabetes. Not type 2 diabetes, type 1 diabetes. I'd love to talk about, before we talk about the food, just other things that this chronic inflammation can do. So you were saying if it's switched on permanently, it can start to have a lot of negative effects. What does that actually

mean given that I understand most of us living in a sort of Western lifestyle today probably have higher levels of inflammation than we should? What's the risks as a result? Yeah, I think we have to think of different levels of inflammation. So I've used some examples already like arthritis. I mentioned multiple sclerosis. I mentioned type 1 diabetes. These are diseases that clearly involve inflammation gone wrong. And if you measure chemicals in the blood of people that are indicators of inflammation, in those patients, the levels of those chemicals are very high in the blood.

So this is, you can measure the inflammation of somebody with a blood test. You can. That gives you a real answer. There are chemical readouts in the blood that are elevated, that are higher in someone with an inflammation in the joints, for example, like arthritis. Is there one particular thing you look at or is it a set of things? So the most common marker is a protein called C-reactive protein or CRP. That's a very good indicator that someone is inflamed, but there are others as well.

So in these disease scenarios, we would consider that to be high-grade inflammation. So the levels are very high. But we also have other conditions where there is elevated inflammation, so too much inflammation. So the levels are very high. But we also have other conditions where there is elevated inflammation, so too much inflammation, but not at this really super high level. So we call that low-grade inflammation. Of course, the inflammation in arthritis and so on has been known for decades now. But this phenomenon of low-grade inflammation has really only been known for about 20 years, I guess, now. And it turns out low-grade inflammation is part of many common diseases that people wouldn't think of as inflammatory diseases. So things like heart disease,

for example. Heart disease. Heart disease, obesity, type 2 diabetes, even dementia. So these common diseases are linked with this low-grade but persistent inflammation. So that's part of the risk profile, if you like, for these conditions. At this point, we usually remind you about getting 10% off Zoe membership with the coupon code you can find in the show notes. Though I would love for you to do that, I'm actually here to tell you about a common request we receive from people like you. It goes something like this. I've just discovered the show and now I listen each week, but I don't have time to go back and listen to all the previous episodes. Could you share some of the key things I need to know how to improve my health? The team has gone back through hours of recordings to find 10 of the most impactful tips led by science and put them into a free guide that you can download right now. To get yours, simply go to zoe.com slash free guide. when you have this raised level, not sky high, but higher than it should be, so not switched on,

then actually that's really increasing your risk of, I guess, the diseases that most of us are most worried about, whether that's heart disease or dementia or diabetes. Yeah, that's right. The conditions where inflammation is really high, those patients will be feeling or seeing all the things that are the hallmarks that I mentioned, swelling, redness, pain, all of those things. You know, someone with arthritis has very painful joints, for example. But this low-grade but chronic, so sort of persistent inflammation in the blood vessel walls, for example, underlying heart disease, in the brain, underlying dementia, in fat tissue, underlying obesity. That's not associated so much with these hallmarks. So you don't feel

the pain. Maybe that's because the level isn't as high, but it is persistent and ongoing. So this has really opened the doors to interest in inflammation, a wider interest, but also what are the factors that maybe are causing that inflammation and what are the factors that can be used as interventions that would mitigate the inflammation? And, you know, diet and other aspects of lifestyle are part of that picture. When we're thinking about inflammation,

you're giving these examples of sort of these cuts on the outside, and I can definitely imagine, you know, we've all hurt ourselves and you see it go red and swell. But blood vessels, you know, they're really tiny. What does that mean for there to be inflammation in the blood vessel? I'll use heart disease as an example. So heart disease is really a disease of the blood vessels, I think, as people will be familiar. So you get what people will call narrowing of the arteries,

for example. So the arteries are a type of blood vessel. And that narrowing, so that's actually a physical reduction in size, is caused by things that are happening in the blood vessel wall. So if you think of the bloodstream as like a drain, this is the drain pipe we're talking about, okay? And what can happen is these same cells that are involved in arthritis in someone's joints can also get into the blood vessel wall, and they will produce the same chemicals in the blood vessel wall that are being produced in the joints of someone with arthritis or the lungs of someone with asthma. So you have exactly the same inflammatory processes happening in the blood vessel wall. Now, people will already have gathered that when inflammation

is happening in the wrong place or at the wrong time, it's damaging. It causes damage to the tissue. And this happens in the blood vessel wall over many years because this is low-level inflammation. And this is low-level inflammation, and this is part and parcel of what increases the risk of heart disease. And so what happens in that wall as a result of that? Can you paint me a picture of what sort of… Yeah, so cells go into the blood vessel wall, and they shouldn't be there because there's nothing happening there for them to be interested in.

But one of the things that makes them do that are other things that people might be familiar with, like high levels of blood cholesterol. The problem with cholesterol is not that it's in the bloodstream. It's actually that the cholesterol also goes into the blood vessel wall, and it starts building up fatty tissue in the blood vessel wall. Now, we shouldn't have that, okay? Maybe a way to think about this is the body sees that as, well, that's not right. I need to do something about it. So, the body starts sending in these inflammatory cells. So, now you've got these inflammatory cells in the blood vessel wall. They shouldn't be there, but they start doing what they think they're meant to do.

So, over time, and this is a very slow process, I mean, this process occurs over decades, but you get this inflammatory buildup in the blood vessel wall, cholesterol is associated with that, all sorts of things are happening. So actually, you start getting damage in the blood vessels. So again, the end result is damage. Part of that damage is this narrowing that we mentioned, cholesterol's involved in this narrowing as well. I've heard quite a few people both on this podcast and elsewhere talk about ultimately narrowing these blood vessels or making them stiff is a problem. Yeah. The inflammation is part of the response that causes narrowing, yes. Because what happens is in an attempt to protect the body against this

cholesterol that's gone onto the blood vessel wall, some of these cells actually engulf the cholesterol. So these cells are called macrophages. That's a Greek word that means big eaters. Macro is big, phage is eat. So these are cells that actually eat cholesterol, but when they eat it, they don't do anything more with it. And they become- They just sit there. They just sit there and they become very large and full of cholesterol. So the narrowing is the buildup of these fat-filled cells in the blood vessel wall over many, many years. So I'm listening to this and thinking a bit like, you know, when I cut myself, I get a scab over that, right?

Which sort of protects me and that's my body's response. And eventually that falls off and I've got like my fresh skin underneath. And if I understand rightly, there's something a bit analogous happening. But the difference is like the scab never leaves inside my blood vessel and I'm sort of slowly building this thing up over years. So I really like this analogy. Okay. And I like it for a couple of reasons. So firstly, I'm going to just divert a little bit.

So the scab formation that you mentioned, inflammation, normal inflammation actually is part of scab formation because it's actually involved in healing. But again, we know if there's too much inflammation, you don't get that healing. Okay. So one of the problems in type 2 diabetes is wounds that don't heal. So this is things like ulcers, foot ulcers, for example, that don't heal. And part of the reason they don't heal, again, is too much inflammation going on. So the body's response, not working properly. Now, I mentioned these fat cells that just sort of get stuck in the blood vessel wall

and contribute to the narrowing. What the body does to protect itself is actually a little bit like the scab formation that you mentioned. Other cells called smooth muscle cells, they make their way actually from the other side of the blood vessel, so not the blood side, but the tissue side, into the blood vessel wall. And one of the things they do is release proteins that try to put a cap on this thing that's growing in the blood vessel wall. The process is different, but it's exactly the same as a scab formation. And it's a bit like a netting, trying to keep this growing thing in. A really big problem is if that fibrous cap breaks. Okay. Because what happens then is all the stuff that's underneath that it's trying to keep in

is now exposed to the bloodstream. And that actually can cause a massive blood clot. The body is attempting to keep everything under control by making this fibrous cap. And if that cap breaks, that's called rupture. If it breaks, that's called rupture, if it breaks, you get clot formation. So that actually is one of the causes of a heart attack. It's also one of the causes of stroke. Now, the really interesting thing is if you get inflammation in the fibrous cap, that weakens it and promotes this rupture. So inflammation underlies this whole process of buildup, but inflammation also underlies what might be the end result, which is the rupture, the breaking of this fibrous cap.

So if you like making a hole in the net, so everything just spills out and then you get a blood clot. But it takes a long time. You're talking about 20 or 30 years in this example with the heart disease. So we know that if you look in some children, you can already see evidence of the buildup of this fatty material in the blood vessel walls. But we know heart disease in most people isn't diagnosed until they're beyond middle age for most people. So this might have been building up for 60 years in some of those people. One of our problems in public health, if you like, is for people to understand that things they do now could have an effect in 20, 30, 40, 50 years time. So, you know, they need long-term buy-in if they're going to do anything about it. I'd love to follow up on the aging point you mentioned at the beginning, because

I think lots of people will be really shocked to hear that inflammation has anything to do with aging. And in fact, lots of people listening to this, I think will have the same view that I had a few years ago that like aging is just something that happens, but it's just a sort of a fact of life. And here you are saying, well, actually, no, your inflammation can affect your aging. What does that mean? So, of course, the clock is ticking for all of us. So, we are all aging. So, we have, you know, people call this chronological age. You're just moving forward progressively. But I think, you know, people will be aware that some people seem to age more quickly than others. In other words, they show the effects of aging sooner. So, you know,

you might take 10 people who are all 65, for example, and some of them seem to look and behave and have the attitudes of a 35, 45, 55-year-old. Tim Spector. And some of them seem to be prematurely rather old, so they're more like 75 or more. And some of them will have some conditions already and might be on medication and others won't. So we have to differentiate between your chronological age, so 60, 61, 62, whatever, and your biological age. So people's biological age can be quite different from their chronological age. And part of the reason for that, of course, is there may be some genetic aspect to it. So some people might be genetically programmed to age more slowly than

others. But also, you know, lifestyle is really important. So, you know, I think it's obvious that things like cigarette smoking, very high use of alcohol can be damaging to the individual, and that actually hastens aging. And part of that actually is probably inflammation. But diet is also important. Being overweight is important. Physical activity is important. Probably sleep and stress are very important. Inflammation is part of the process of making aging faster. And the reason for that, remember, inflammation is there as a response to insults. We talked about simple insults like cutting your skin. We talked about more serious insults.

So if you have a lot of insults, I'm talking about physiological insults, physical insults, over your lifetime, you will accumulate, if you like, more damage in the body, and you will accumulate sort of the net result of this inflammation, which is triggered each time something happens. You know, it may not go away. So what we know is two things. One is if you look at markers of inflammation in the blood, so we mentioned C-reactive protein before, but there are others, and we just take a whole lot of people who are, let's say, age 70, and a whole lot of people who are age 40, let's say, and just measure CRP. All other things being

equal, the older people have higher levels, not massively high unless they have a condition like arthritis or whatever, but they have a higher level. So aging is considered to be a state of this chronic low-grade inflammation. So we've already talked about the importance of low-grade inflammation in increasing the risk of heart disease, and in passing, we mentioned type 2 diabetes, dementia, and so on. So one of the reasons some people are more likely to get some of these diseases than others probably is they have a higher level of this low-grade inflammation. And one of the drivers, one of the reasons they might have this higher low-grade inflammation is just the accumulation of damage that's occurred during their lifetime. Because of this constant level of inflammation.

Yes. And some of that will be aspects of bad lifestyle, including diet. So you're just continually driving the process and that process is sort of continually eating away at your bodily systems, like the blood vessels and what have you. I'm trying to think of an analogy here

and I'm thinking a bit about like maybe driving with a petrol car over many years. And is this analog thinking a bit about like maybe driving with a you know like a petrol car over many years and is this analogous a bit to like somehow you're using a really cheap and dirty fuel or something like that and you know it's not going to break the car right away but it's like steadily sort of wearing away and therefore this collapses at 50,000 miles whereas if you put it all with like this really clean fuel, you might have made 100,000. I think that's a reasonable analogy, yeah.

So you just get this slow buildup of damage and inflammation is part of that. And you don't really notice. This is like all the cells all over your body that are affected by this inflammation. The answer is in general, yes. But the nature of the insults might make it more likely that that inflammation is in particular locations than others. We also

know that obesity also increases low-grade inflammation, and actually people's fat tissue can become very inflamed. And again, that's actually similar to what we were talking about in the blood vessel walls, where you have inflammatory cells going into the fat tissue to try to, they think they're going to protect, but things kick off. You get spillover of these chemicals into the bloodstream, and then they can have effects in other places. So obesity can be part of the problem. And just to make sure I understand that, because I think a minute ago, you said also that obesity can be a disease that's caused by the low-grade inflammation. So is there a sort of vicious cycle here where you're saying it both

starts to cause it and then it's also increasing the inflammation and making it worse? Yeah, actually I do. But I don't think inflammation is the initiating factor for obesity. But I think once we get an increase in body fatness, inflammation becomes very important and it makes the likelihood of an even greater increase in body fatness increase. And the reason for that is inflammation can induce what we call insulin resistance. So that means people don't respond to insulin properly anymore. Essentially, what it means is your metabolism gets messed up. Your sugar metabolism, your fat metabolism, actually your protein metabolism all get messed up. And inflammation causes that messing up. And as a result of that, you're actually driven to

accumulate more body fat. So that's a sort of a causal role of inflammation and obesity. I don't think it's the primary cause to start with but what happens is exactly the same process that we talked about for the blood vessel wall. The body senses something that's going on in fat tissue that's not entirely normal, and it sends in the troops. And again, the same cells that I talked about in the blood vessel wall, these macrophages, they also go into the adipose tissue. That's the fat tissues. Yeah, yeah, into the fat tissue, yeah. And actually, these cells involved in inflammation and the fat cells, because fat tissue is made of cells and those cells are full of fat, start communicating with one another. So they send signals to one another obesity and look for inflammatory cells,

but also inflammatory chemicals, they have more inflammatory cells and they have more inflammatory chemicals than the fat tissue of someone of normal weight. So the tissue is definitely inflamed. So you've got inflammation within the fat tissue, but some of that inflammation is exported because chemicals will leave the fat tissue and go in of that inflammation is exported because chemicals will leave the fat tissue and go in the blood, and then they can actually have effects elsewhere in the body. And this, I think, is one of the reasons why being obese makes it more likely that people will get heart disease, more likely to get fatty liver disease, more likely to get other, maybe even some cancers could be important because cancer

seems to like an inflammatory environment as well. So I think this exporting of inflammation from fat tissue explains why being obese increases the risk of lots of other diseases. And I guess another story about how if you do end up sort of, as you said, living with obesity, it just gets harder and harder to get out of that this is like another example you're describing where this is just a cascade mechanism yeah so there's one other thing we started talking about aging and and i sort of went off a little bit and talked about obesity which i think is relevant but the other really interesting things that can happen as people age is they lose muscle people call the sarcopenia. It's loss of muscle mass. And it turns out inflammation is also involved in loss of muscle mass.

Is that right? So this is inflammation in muscle. So again, this could be accumulation of damage over time. And again, you can think of it as like a slow eating away. So you get the slow eating away of muscle tissue. You asked a question before about whether inflammation was everywhere. And again, you can think of it as like a slow eating away. So you get the slow eating away of muscle tissue. You asked a question before about whether inflammation was everywhere. And I think it is, but it might manifest itself a little bit differently in different people, depending upon other factors. But certainly in older people, I think inflammation in muscle is one of the drivers of why they lose muscle. That's really,

really bad. And you could have a person, which has become more common now, where they have obesity, but they also have not enough muscle. So people call that sarcopenic obesity. So sarcopenia is loss of muscle, and obesity, of course, is buildup of fat tissue. So there's this new sort of clinical phenotype that's emerged maybe in the last 20 years of some older people who have this curious mixture of too much fat tissue and not enough muscle tissue. It's really interesting. I mean, Philip, you're painting a slightly terrifying picture about the way in which this sort of low-grade, long-term inflammation

can affect almost everything that people are worrying about, that interestingly can really affect aging, which I think many of us care a lot about, because I think all of us, I think, are really aware now that it's not how long you live, it's how many healthy years you have. And I think anyone listening to this podcast, anyone who's a member of Zoe is really interested in trying to make sure that they have as many of those healthy years as

possible. So I think you've painted this picture that inflammation is this huge, really enemy, I guess, of trying to achieve that. I'd love to switch to food, which of course I know is your passion in terms of how it fits into inflammation. how can the food link be causing this inflammation? And then I would love to end up talking about, okay, let's talk about all the some actionable things we can do to hopefully reverse this tale of misery and people can go away feeling positive enough to face the rest of the day. So actually, it is possible for things we eat to trigger inflammation. There is this phenomenon of

people call it postprandial inflammation. So inflammation that happens after you eat a meal. So again, if you measure these inflammatory chemicals in the bloodstream, an hour or so after you eat a meal, you see a rise. It's not massive. We're not talking arthritis levels, but you get a little rise in these inflammatory markers in the blood so that's telling us that there's some inflammation happening this is probably some little inflammation of the blood vessel walls again it could be stuff happening in adipose in fat tissue and then you know after some hours that goes away and and people have demonstrated that there's an association between repeating this inflammation

in response to meals and risk of heart disease, for example. That's been quite well described. So what are the things in meals that cause this inflammatory response? So one of them is simple sugar, okay? So if you have a high simple sugar meal, you have more inflammation than if you have the same meal with less simple sugar. Another one is total fat. And of course, fat could come in many forms, but I'm using it in a general sense.

So a high fat meal causes this inflammatory response following the meal. And in fact, in research, people typically use a high-fat challenge to cause this process to try to understand about it and how it can be mitigated. The show you're listening to right now that's providing you the latest evidence-based health and nutrition information from the world's top scientists? Well, making it takes a lot of time. We think it's well worth it, all in the name of improving your health. All we ask in return is this, send a link to this podcast to someone you think would benefit. And if you haven't already, click follow this podcast wherever you're listening right now. Okay, let's get back to the show.

Yeah, we're very familiar with that at Zoe because everyone who does Zoe actually eats the standardized meal. It's now cookies, but it goes all the way back to what Sarah Berry originally designed with our first study, which sort of challenges our metabolism in this standard way

that we did originally with twins with both this fat and the sugar. Because I think one of the things that's really interesting, which I haven't, I guess, touched on yet, Philip, is there's huge variation, isn't there, in this response? So you can use sugar and fat to challenge people's metabolism, if you like, challenge their resilience. And part of that challenge is to their inflammation. So I think this inflammatory response we're talking about is part and parcel of an adverse metabolic reaction to a meal. As you might imagine, there's been a lot of interest in can we tweak what's in the meal

to try to reduce this inflammatory response that occurs after a meal. And you'll be relieved to know that there are a lot of things, at least in experimental settings, that can mitigate this response. So I mentioned fat causes this postprandial inflammation. If you replace saturated fat or a source of saturated fat with extra virgin olive oil, for example, you don't get such a big response. If you include nuts in the meal, you don't get such a big response. If you include vitamin C with the meal, you don't get such a big response. So maybe oxidative stress is part of this as well. If you include omega-3 fatty acids in the meal, you don't get such a big response. What you're saying, I think, is that it's not just like how much fat or how many carbs you

eat that is going to cause whether or not you have this inflammation. Actually, you're getting down to the type of food is having a very different response. Just before we talk about this specifically, could you just link through for a minute between what happens when you eat this meal like this isn't just in the first hour one of the reasons we do these these tests in zoe and some of these are like sort of six hours after you eat is there can be like there's a sort of process that means that one person and one meal you might be. And another person or another meal, you could start to cause this inflammation. So you're right that there is a lot of variation in the metabolic response to a meal. There's also actually quite a lot of variation in the inflammatory response to a meal as well.

So you could give a whole lot of people the same amount of fat, and actually they will all show an inflammatory response, but it is quite variable. So I think part of that is, you know, what is the condition of those people beforehand? So I think if you do it in someone who's generally more healthy, they might be able to deal with it better. So they will show a smaller response. But there are also, as you mentioned, there are these more long-term effects. I mean, we think of a meal having an effect in a couple of hours after you eat it.

But actually, there are these longer-term effects. I mean, we think of a meal having an effect in a couple of hours after you eat it, but actually there are these longer term effects. And there's interesting work showing that what you have in one meal can actually affect your response to the next meal. And people have struggled to really understand how that can be. So we have cells that line our gut wall and they're involved in the uptake of the products of digestion and passing them out into the bloodstream. And some years ago, researchers actually at University of Reading did a study where they were able to trace what happened with things that were in the first meal. And of course, most of those things passed into the bloodstream, but they didn't all. And when you had a second meal, some hours later, you actually got things that were in the first

meal coming out into the bloodstream. So they interpreted this to be actually the gut cells hang on to some of the stuff from a meal and release it later on. So I think there might be mechanisms to explain the sort of carryover effect into later meals. Maybe to share a little bit of some of the science that's come out of Zoey, because I think it's really, to me, fascinating. So you had a lot more than 100,000 people now do these tests. Everybody who becomes a member starts by doing these tests to help to personalize. And what's really interesting is we see like roughly a third of people really

struggle with the fat in a meal, which means that, you know, it's sort of six hours later, for example, you can still see these raised levels of fat and about two thirds of people, even with this lot of fat, clear it all away. And so in my case, for example, I clear that all away, which is great. And then we look at the blood sugar responses to this meal and we see this very, very wide, like 10 amazingly wide variation and interesting for example some people like me whose blood sugar control is very poor despite the fact that like their ability to deal with the fats is quite high and what i understand in that case is where people are struggling to deal with this this can lead to more inflammation over time is that yeah and therefore that that's like sort of

saying to you quite directly you need to change the way that you're eating if you want to lower this level of inflammation so i think from from what i've said you might gather that both this prolonged or even a short elevation but a prolonged elevation of blood sugar is harmful to inflammation, but also too much elevation or prolonged blood fat after a meal is also bad for inflammation. So both scenarios would be bad, but I don't think we know why different individuals can be so different. Some of it obviously is how well do we respond to insulin, but also how is our system adapted to us having a lot of fat? And one of the things we're hoping to see over time

with Zoe members is you can see that if by shifting your diet, you may actually start to see sort of long-term improvements in some of these. And we definitely see already some improvements. Let's talk about what you can do if you've listened to all of this. I mentioned some things, extra virgin olive oil, omega-3s, having nuts, having vitamin C,

all help control, at least in an experimental setting, in a group of people, but also fiber in a meal. And maybe part of that is just slowing down the process of digestion. So you're letting stuff come into the bloodstream more slowly, so you're better able to handle it. And is it like one magic pill? Like if I take, you know, we often talk about extra virgin olive oil as being very good for you. Does that mean if I'm taking a shot of extra virgin olive oil three times a day, like that will solve my inflammation like a pill from the doctor? Is it as simple as that? I would prefer to think of it like that. I mean, I would prefer to think of a long-term dietary shift away from things that are considered to be less healthy. And I mentioned in general what they might be in the context of this

postprandial inflammation and a move towards things which we think are more healthy. And, you know, olive oil, particularly extra virgin, would be part of that. More micronutrients, I mentioned vitamin C, that would be part of that. More omega-3s would be part of that. More fiber would be part of that. People know what extra virgin olive oil is. They know what nuts are. That was really clear. And I know you've done a lot of your own research around omega-3. Could you maybe just tell us what omega-3 is? Because I don't see that on the shelf like I see olive oil. Yeah.

So you do see it on the shelf. It's just you have to go to a different shelf because you'll find salmon on a shelf in the supermarket. So when I talk about omega-3s, I'm mainly talking about the fish-sourced omega-3s, EPA and DHA. So omega-3 is a general term for a group of fatty acids. EPA and DHA are a type of omega-3. Okay.

They are, as I mentioned, sort of uniquely linked with fish and other seafood. They seem to have quite pronounced anti-inflammatory roles, both if you put them in a meal, they will help to mitigate this meal-driven inflammation. If you have this inflammation already going, be it high grade, but that's a disease like arthritis, or this low-grade persistent inflammation associated with aging, are there dietary components that can dampen that inflammation? More importantly, are there dietary components that can help you resolve the inflammation? There's lots of things in the diet that are anti-inflammatory. They include omega-3s, which I'll come back to shortly, but also some of the vitamins, vitamin C, vitamin E are

anti-inflammatory. Lots of the polyphenols from plants, so the things that give fruits, vegetables, berries, and so on, their colors, they're also anti-inflammatory. Things in nuts are anti-inflammatory. Gut microbiome is also a driver of inflammation, but also could be anti-inflammatory if you get it right. So there's lots of things in the diet that we can use to mitigate ongoing inflammation. I think these omega-3s, EPA and DHA that come from fish, and they're also in fish oil supplements, by the way. So people can go to a different shelf and get some EPA and DHA. And we might want to consider that in the context of people who choose

a vegetarian or vegan approach. We've been working on EPA and DHA for 30 years now. They are anti-inflammatory. Okay, that's clear. Lots of experiments show that. But the really interesting thing has been discovered in the last 15 years or so. This process of resolution of inflammation, the turning off, you know, flicking the light switch off, if you like, involves chemicals again. So everything in the body is involving chemicals, sending signals. Researchers in Boston discovered that some of the key chemicals in resolution of inflammation are actually made from EPA and DHA in the body. So EPA and DHA are the substrates, the starting point for making chemicals that turn off inflammation. People have studied omega-3s, EPA and DHA, and arthritis

actually since the 1980s. And it's well described that high levels of EPA and DHA as a supplement can help people with arthritis in terms of painful joints, tender joints, stuff like that, morning stiffness. And everyone always said this is an anti-inflammatory effect. But actually, if you think these are people who've already got high-grade inflammation, I think what's happening is EPA and DHA are acting to resolve the inflammation, so actually to take that high-grade and bring it down a bit. And that's why people with arthritis benefit from EPA and DHA. Imagine someone's listening to this and saying, I want to understand how to make some shifts to my diet in order to reduce this inflammation.

Maybe starting with the sort of omega-3 and oily fish i know that's your big focus how strong is the evidence in your opinion that you know yes if you're willing to eat fish you should be adding oily fish to your diet will it make a difference for me the evidence is very strong okay okay yes we have animal studies we have all sorts of studies but you know i'm mainly interested in human evidence, right? Because, you know, doing something in a laboratory and some mice is one thing. But we need human evidence. Yeah. And in human research in nutrition, we really, in general, we have two types of research. One is where you look at diets, foods, nutrients, levels of nutrients in people's blood, and you track what happens to those people over time. So, you know, we call that epidemiology. The epidemiology of omega-3s is extremely strong. In other words, people who eat more fish,

or people who eat more EPA and DHA, or people who have more EPA and DHA in their blood have a much better long-term health outcome. Less heart disease, less dementia, some cancers, less cancer, less metabolic disease, all that stuff. So the epidemiology is very strong. The other type of study we have is treating nutrition a bit like a pharmaceutical, so a randomized controlled trial. Typically, these are smaller in size and shorter. So they might involve tens or hundreds of people. But I think if you step back and look at the really important things like heart disease, for example, even from randomized control trials, there's pretty good evidence that higher intake of EPA

and DHA reduces risk of heart disease and mortality from heart disease. And certainly, they impact beneficially lots of the biomarkers that tell you about risk. So I think for me, the evidence is quite strong. And I personally would recommend that people should incorporate these sort of fatty fish in their diet if they can. I've been part of quite a few conversations with Tim and Sarah talking about the fact that a lot of oily fish today would come from salmon, which is now factory farmed and very different from the sort of fish that we would have got in the past. And I know that Tim is quite skeptical about this because he feels that like there might

be a lot of other reasons to feel that this is not really so good. How do you think about sort of the sort of factory farmed salmon that you would actually probably get if you went to the grocery store? Yeah, I think that's a great question. And salmon, I think, is a really good example, because salmon farming is a massive industry, and probably most of the salmon that's available in the supermarkets is farmed salmon. People will be familiar with fish oil, which is, you know, they'll think of an omega-3 supplement that they can get from a chemist shop or, you know, a supermarket or online. And, you know, fish oil contains EPA and DHA, these really important omega-3s. Now, in the wild, salmon eat other fish and they get EPA and DHA from their

diet by eating other fish. So if you farm salmon, traditionally, you had to give salmon EPA and DHA in their food. Otherwise, they didn't grow well and they didn't stay healthy. And the biggest user of fish oil is the salmon farming industry. That uses something like 75% of global fish oil is actually used in salmon farming. Now, first of all, that is a limited resource. And you could argue, if it's so important, why don't we give it to people instead of the fish? But the fish need it if we're going to farm them. So it's a limited resource and it's also expensive. It's a commodity. It's much more expensive than vegetable oil, for example. And that's because it actually comes from other fish.

And that's because it comes from fish. So you've got to invest in the production of fish oil. The research behind fish farming has been trying to find out what happens if we give salmon less fish oil and replace it with vegetable oil. So it's well described that salmon can still grow and do well if you give them less fish oil than they used to be given. And you replace that with vegetable oil. The consequence of that is farmed salmon have less EPA and DHA in their flesh than wild-caught salmon. A farmed salmon now will have less EPA and DHA than a farmed salmon did 20 years ago. Okay, so farmers are figuring out ways to make this more profitable.

The industry has found out a way to reduce its reliance on EPA and DHA and therefore reduce the cost of farming salmon, I guess. So one interpretation would be the overall health benefit is less from a farmed salmon now than it used to be, let's say 10, 15, 20 years ago, and less than a wild salmon. However, farmed salmon still is a good source of EPA and DHA. It just doesn't have as much as it used to. Salmon and other fish are not just about EPA and DHA. They do bring other healthy nutrients, and they are, I think, a good replacement for red meat, which red meat has its place, I think, a good replacement for red meat, which, you know, red meat has its place,

but we shouldn't have too much red meat. So I think there are other things in there. But if you're focusing just on EPA and DHA, I think this argument you're making is a viable one. And so if someone was listening to this and they weren't saying, hey, this is my swap for red meat, but more I'm thinking, do I need to add fish into my diet, which maybe doesn't have a lot of it otherwise?

What would you be saying to them? So I think there are a lot of other fish around, like mackerel, for example, which is all wild caught, actually has more EPA and DHA than salmon ever had. Sardines, very rich in EPA and DHA and very inexpensive and very easy to prepare. So I think there are other alternatives that people could choose. We talked a lot about what you can add in. If you were saying what were the three things that people should be looking to sort of try and reduce in their diet to reduce this inflammatory impact what what would you say simple sugar simple sugar meaning soft drink or whatever but you know also people add sugar when they're making stuff yeah so i think that that would be one thing yeah i think

saturated fat red meat um you know fatty meat but also but also there's a lot of saturated fat, for example, in the form of palm oil, even things like pastries, for example. So I think sources of saturated fat, be they animal or plant sources, would be a second. And that can really make a difference to your inflammation, therefore really can. It's not just about your weight here you're talking about. No, it would have an impact over the long term. And I think, you know, replacing those things with more plant sourced foods that will bring vitamins and minerals, you know, these polyphenolic compounds that are in plants. But also, you know, I do still think that the omega-3s are really important. And we need to think about plant sources and plant alternatives

of these fish-sourced omega-3s. I think that's going to be a big area of future research. We are definitely at time. I would like to try and do a little summary of what we've gone through. And please correct me where I have gone wrong. So I think today we've had this fascinating explanation about the way that inflammation sort of affects all parts of our body, that it's a good thing. Basically, if we had no inflammation, we would die. So you need it in this response, but we seem to be in this modern world where it's not getting switched off. And you talk quite a lot about that, that what happens is that cells create chemicals that sort of trigger this inflammation. It's very much what we think of when we like cut our hand and swelling and redness, but interesting that can

happen anywhere. And you talked about examples where when this inflammation goes sort of sky high, you end up with these diseases that we talk of as sort of autoimmune diseases, because it means just your body is attacking itself. You talked about arthritis and multiple sclerosis, and you're saying, you know, we can measure this inflammation in the blood with something called CRP, and you can see that sky high. But interestingly, what you see for people who don't have those diseases is many of us have higher levels of inflammation than we should do. And this is this sort of long-term, sort of low-grade chronic inflammation.

And what's new is the realization that this increases our risk for many of the diseases that actually end up taking away our quality of life. You mentioned heart disease, which has come up on these podcasts quite a few times, but interestingly, you said dementia, for example, is also related to this inflammation. Diabetes and that obesity can both be increased through this, but that obesity itself is also one of the causes of this inflammation. So there's this terrible sort of vicious cycle that can happen. You explained how this inflammation happens. And I thought that the example that I found

like most straightforward is in our blood vessels, this idea that you have this high cholesterol because you're probably not eating a diet that's very good. It ends up stuck in the wall of this blood vessel and your body's like, well, that's not right. It triggers this inflammation. And then there's this sort of cascade of actions where your body's trying to protect you a bit like when I've cut myself on my finger, but it's not good. And I love this. I'd never heard this word before, fibrous cap. It seems pretty clear to me that you don't want your body to be stuffed full of fibrous caps everywhere if it's supposed to be this nice, smooth tube.

And interestingly, you explained that the inflammation itself over time can mean that those fibrous caps are more likely to break. So it's sort of like it's the full story. It both creates the problem and then makes it more likely that ultimately you have the stroke or the heart attack. You then explained how this ties also to aging. And I think this was really new for me and I think for most people. And that, I think you said, aging is a state of chronic low-level inflammation. Is that a fair? Which is not, I think, how we think about it. I think I always thought about it as just what happens every birthday, but actually it helps to

explain why you can see people look so different, you know, as they age, or even identical twins look so differently as they age. And again, the point is we will have inflammation, but for some reason, you know, we're not getting this inflammation to switch off. And then you did the sort of grand reveal, which is, you know what, the diet that we're eating is having this profound impact on our inflammation. Because every time we eat, you can cause a very low level. That's normal. We're designed to deal with it.

But the sorts of foods that we're eating time after time, year after year, start to have this impact where this inflammation is just getting raised constantly. The good news though, is that there is something you can do about it. And just as the food is a big, important component, by changing what we eat, we can do something about it. And maybe if I start with what you can reduce, I think you were very clear. So food with added sugar in it. So the Coca-Cola's, all these things like that, the sweets and all these other sorts of, particularly ultra processed foods,

I guess that have lots of sugar in it. Red meat, because you said it's not just the sugars here, it's also these sorts of saturated fats. You mentioned a lot of pastries that have palm oil in it. I think you said it was also bad. So again, you sort of see the overlap with these sorts of more ultra-processed foods. But then I think much more positively, because rather than saying what you take out,

what can you add in? Extra virgin olive oil, nuts. You talked about fiber in our meal and polyphenols from plants, which we didn't spend a lot on today, but we talked about where it's sort of supporting the microbiome and helping to reduce this inflammation. And then I think we had this really fascinating conversation about omega-3, which I know is a big area of your

research for a long time. And you explained that it's not just generally omega-3, it's like these particular things, EPA and DHA, in particular, are known to have these anti-inflammatory roles. And uniquely, we only get them normally in our diet through these particular sorts of oily fish, that you can also get them as fish oil capsules, that there are just starting to be, I think, some vegan alternatives, if I understood. And then we had a discussion a bit about what is the pro and cons today of factory farmed salmon, because there is this debate about, as always, what changes when we start to make something that's very manufactured.

And you said, well, there's still quite a lot of EPA and DHA in it. And it's true that it's less than there was before. And I thought, interestingly, you said both mackerel and sardines actually have significantly higher levels. So this is not the only place you can go. Net-net, I think you are clear if you were advising me on what to eat or what I should be asking my children to eat, you would be saying, put these oily fish in my diet.

Is that a fair conclusion? That's a perfect summary. Yeah. Wonderful. That was a lot that we covered today. I think it's really interesting. And I think one of the things I noticed is just how much the science is moving really fast here. I feel like many of those things are much clearer than even a few years ago. So it feels as though this is an area where a lot of research is happening fast. Yeah, for sure.

Yeah. I hope we can get you to come back again in the future and update us on your latest research as we continue to sort of unravel all of this. Yeah, I'd love to. It was a real pleasure. Thank you so much for taking the time with us. Yeah, thanks for having me. I hope you've enjoyed learning about inflammation from Philip as much as I have today, especially regarding how important what we eat is to keeping inflammation in check. If you want to go one step further and get personalized advice and support on how you can eat the best foods for your body to help you feel better now and live healthier in the years to come,

then you can learn more about Zoe and get 10% off your membership. Simply go to zoe.com slash podcast. I'm your host, Jonathan Wolfe. Zoe Science and Nutrition is produced by Yellow Humans Martin, Richard Willen, and Sam Durham. As always, the Zoe Science and Nutrition podcast is not medical advice. And if you have any medical concerns, please consult your doctor. See you next time.