How inflammation could age you

Inflammation has become a hot topic. Scientists have shown that it’s an important factor in a range of conditions, including obesity, type 2 diabetes, and dementia. 

What’s perhaps more surprising is that inflammation isn’t always a bad thing — it evolved to protect us.

In this episode of the ZOE Science & Nutrition podcast, we’re joined by Prof. Philip Calder, who helps unravel the complexities of inflammation. 

Philip is a professor of nutritional immunology at the University of Southampton, in the United Kingdom, where he’s also the head of human development and health.  

Today, he outlines the links between inflammation and health. He also explains why inflammation happens after you eat and how to reduce it. 

What is inflammation?

Inflammation is the first part of your immune response. If you cut yourself, get bitten by an insect, or develop an infection, the surrounding tissues become inflamed. 

This inflammatory response is what causes the pain, redness, and swelling.

Inflammation is your body’s way of keeping you from getting injured further — it’s an important protective mechanism. 

But if it goes on for too long, or it happens in a place where it’s not needed, inflammation can cause trouble in the long run.

Why doesn’t inflammation stop?

Some medical conditions, like rheumatoid arthritis, cause long-term inflammation. In this case, the immune system mistakes healthy tissue in the joints for an enemy. 

Another example is type 1 diabetes, which is sometimes triggered by a viral infection. The body misreads what’s going on and attacks the pancreas' cells, creating long-term inflammation.

In conditions like arthritis, inflammation is high-grade: It causes pain. When inflammation is low-grade, people generally don’t feel it.

What’s low-grade inflammation?

Low-grade inflammation is associated with many common conditions, such as heart disease, obesity, type 2 diabetes, and dementia. To explain the link, Philip describes how inflammation affects blood vessels.

Over decades, inflammation can damage blood vessel walls. Compounds like cholesterol build up in these walls, gradually narrowing them. 

The immune system recognizes this as a threat and sends in specialized immune cells. These cells consume the buildup, but then they just sit there, adding to the blockage.

Meanwhile, smooth muscle cells move into the walls. They release proteins to cover the buildup with a fibrous cap, helping to keep it in one place.

However, if this cap ruptures, all the compounds beneath can enter the bloodstream and cause a blood clot, which can lead to a heart attack or stroke. 

Inflammation can weaken the cap, making it more likely to burst.

So, inflammation helps trigger the initial buildup, helps the buildup grow, and can weaken its cover, ultimately triggering a significant cardiovascular event.

Inflammation and aging

Certain lifestyle factors can speed up the aging process, like smoking tobacco or drinking alcohol to excess. Over a lifetime, this causes more and more damage — each factor triggers inflammation.

This is why older adults have slightly higher levels of C-reactive protein, a marker of inflammation, compared with younger people.

Meanwhile, as we age, we tend to lose muscle mass. This process is called sarcopenia, and inflammation is involved, possibly due to accumulated muscle damage over time.

How does food cause inflammation?

Philip explains how what we eat can trigger inflammation. In this case, it’s called postprandial inflammation

Over many years, a diet that causes pronounced postprandial inflammation can increase the risk of heart disease.

What are the main causes? Simple sugars and total fat.

As ZOE’s research shows, there’s a huge variation in metabolic responses from person to person. For instance, around 1 in 3 people struggle to clear fat from their blood after a meal.

To make matters more complex, what you eat in one meal can affect your response to your next meal. This is called the second meal effect.

How can we curb the response?

Your metabolism is supposed to respond to the food you eat. Damage only builds up if problematic responses go on for a long time or happen too often.

Philip gives us some simple tips to help control these postprandial responses. For instance, replacing saturated fats with extra-virgin olive oil can help.

To reduce inflammatory responses, you can also add these to your diet:

What about controlling ongoing inflammation?

Omega-3s from oily fish, called EPA and DHA, help resolve inflammation

According to Philip, tightly controlled clinical trials and large-scale epidemiological studies have produced “very strong” evidence of this. 

High levels of EPA and DHA can help reduce arthritis pain, for example. And regularly consuming omega-3s may also reduce your risk of heart disease and dementia.

This is partly because your body uses EPA and DHA to manufacture compounds that dial down inflammation.

Farmed vs. wild salmon

Finally, Philip wades into a divisive debate: Is wild salmon healthier than farmed salmon?

Like humans, salmon need EPA and DHA to survive. In the wild, they get these by eating other fish. 

Salmon farmers need to feed their salmon supplemented DHA and EPA. In fact, the salmon farming industry uses around 75% of the world’s fish oil, an expensive commodity.

To cut costs, the industry discovered that farmed salmon still do well if farmers replace some of the fish oil with vegetable oil. 

Because of this switch, farmed salmon contain less omega-3s than wild salmon. But, as Philip explains, farmed salmon is still a good source of omega-3s.

There are other options. Philip suggests mackerel, which is always wild-caught and has more EPA and DHA than wild salmon.

Also, sardines are cheap, widely available, and rich in omega-3s.

Show notes

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. 

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Is there a nutrition topic you’d like us to explore? Email us at podcast@joinzoe.com, and we’ll do our best to cover it. 

Episode transcripts are available here.

Transcript

[00:00:00] Jonathan Wolf: Welcome to ZOE Science & 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, Prof. Philip Calder joins us to help us 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 U.K. 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. 

[00:01:21] Philip Calder: Thanks for having me. Great to be here.

[00:01:22] Jonathan Wolf: It's a real pleasure. So we have a tradition here at ZOE, 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?

[00:01:45] Philip Calder: I'll try my best to stick to the rules. 

[00:01:47] Jonathan Wolf: Alright. Could inflammation make me age faster? 

[00:01:52] Philip Calder: Yes. 

[00:01:53] Jonathan Wolf: Can long-term inflammation cause serious diseases?

[00:01:57] Philip Calder: Yes. 

[00:01:58] Jonathan Wolf: Are inflammation and immunity the same thing?

[00:02:02] Philip Calder: No. 

[00:02:03] Jonathan Wolf: Can the food I eat cause inflammation after meals? 

[00:02:06] Philip Calder: Yes. 

[00:02:07] Jonathan Wolf: I'm nearly 50. Is it too late to change my diet to lower my inflammation? 

[00:02:14] Philip Calder: No. 

[00:02:15] Jonathan Wolf: That's good. I was going to get really upset if you'd said 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?

[00:02:26] Philip Calder: That inflammation is always harmful, I think is a misconception, because inflammation is there for a purpose. 

[00:02:34] Jonathan Wolf: 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 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.

[00:03:06] Philip Calder: 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, 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. 

[00:04:35] Jonathan Wolf: Got it. So a little bit is good, and in fact, necessary. So 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. 

[00:04:49] Philip Calder: 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.

[00:05:29] Jonathan Wolf: It's like a lot of things in life, a little bit might be good, but lots is not so good. 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?

[00:05:46] Philip Calder: 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. 

[00:06:55] Jonathan Wolf: 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 the sort of alien invaders you were describing when you cut yourself and you get bacteria.

[00:07:14] Philip Calder: 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. 

[00:07:43] Jonathan Wolf: Can that be triggered by the fact that you have a lot of this long-term inflammation from other causes, and then that makes it more likely that you end up having the arthritis? 

[00:07:52] Philip Calder: 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 one 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.

[00:08:30] Jonathan Wolf: I'd love to talk about… before we sort of 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 is the risks as a result? 

[00:08:57] Philip Calder: 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.

[00:09:25] Jonathan Wolf: So this is, you can measure the inflammation of somebody with a blood test, that gives you a real answer.

[00:09:32] Philip Calder: 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. 

[00:09:40] Jonathan Wolf:Is there one particular thing you look at, or is it a set of things?

[00:09:44] Philip Calder: 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, but not at this really, not the sky-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, 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.

[00:11:01] Jonathan Wolf: So just to make sure that I've got this, you're saying, okay, you can have this sky-high level of inflammation, and that you see, for example, with people with arthritis or multiple sclerosis. But actually, quite recently, scientists are now seeing that 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 the diseases that most of us are most worried about, whether that's heart disease or dementia or diabetes.

[00:11:28] Philip Calder: 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, 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. 

[00:12:32] Jonathan Wolf: 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, they're really tiny. What does that mean for there to be inflammation in the blood vessel? 

[00:12:49] Philip Calder: 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 is 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. Okay, 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 part and parcel of what increases the risk of heart disease.

[00:14:04] Jonathan Wolf: And so what happens in that wall as a result of that inflammation? Can you like, paint me a picture of what sort of…

[00:14:09] Philip Calder: 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 transcript the blood vessel wall. Now we shouldn't have that. 

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, 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 it's again, the end result is, is damage. Part of that damage is this narrowing that we mentioned. Cholesterol is involved in this narrowing as well. 

[00:15:24] Jonathan Wolf: 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. 

[00:15:31] Philip Calder: 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 into the blood vessel wall, some of these cells actually engulf the cholesterol. 

Okay, so these cells are called macrophages. That's a Greek word that means big eaters. ‘Macro’ is big, ‘phage’ is eat, okay? 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 and they become very large and full of cholesterol.

Okay, so the narrowing is the buildup of these fat-filled cells in the blood vessel wall over many, many years. 

[00:16:20] Jonathan Wolf: So I'm listening to this, I'm thinking a bit like when I cut myself, I get a scab over that. 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. 

[00:16:44] Philip Calder: 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. 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. 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, 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, okay?

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.

[00:19:14] Jonathan Wolf: But it takes a long time, you’re talking about 20 or 30 years in this example with the heart disease.

[00:19:20] Philip Calder: 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. 

[00:20:03] Jonathan Wolf: 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 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?

[00:20:31] Philip Calder: So of course the clock is ticking for all of us. So we are all aging. So 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 progressively. 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. And some of them, you know, seem to be prematurely rather old so that, you know, they're more like 75 or more.

And, you know, 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 lifestyle is really important. So 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. You know, 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, you know, 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. 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-0eactive 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, you know, 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. 

[00:23:56] Jonathan Wolf: Because of this constant level of inflammation. 

[00:23:58] Philip Calder: 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. 

[00:24:13] Jonathan Wolf: 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 analogous a bit to like somehow you're using a really cheap and dirty fuel or something like that, and it's not gonna 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 this really clean fuel, you might have made 100,000.

[00:24:42] Philip Calder: I think that's a reasonable analogy, yeah. So you just get this, uh, slow build-up of damage, and inflammation is part of that, and you don't really notice.

[00:24:51 Jonathan Wolf: This is all the cells all over your body that are affected by this inflammation?

[00:24:56] Philip Calder: So 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 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. 

[00:25:35] Jonathan Wolf: 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?

[00:25:51] Philip Calder: 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. 

[00:27:11] Jonathan Wolf: That's the fat tissues. 

[00:27:12] Philip Calder: Yeah, yeah, into the fat tissue. Yeah. And actually, these cells are 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, and this seems to amplify, make the inflammation worse. So, if you look in the fat tissue of somebody living with 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, okay? 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 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.

It 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. 

[00:28:31] Jonathan Wolf: 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 another example you're describing where…

[00:28:42] Philip Calder: Yeah this is just a cascade mechanism. So there's one other thing. When we started talking about aging, 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 this sarcopenia. It's loss of muscle mass, okay? And it turns out inflammation is also involved in loss of muscle mass. 

[00:29:07] Jonathan Wolf: Is that right? 

[00:29:07] Philip Calder: 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 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 a buildup of fat tissue. So there's this new sort of clinical phenotype that's emerged, you know, 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.

[00:30:14] Jonathan Wolf: 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 it 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.

[00:31:15] Philip Calder: So actually, it is possible for things we eat to trigger inflammation. There is this phenomenon of, people call it post-prandial 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. A little, you know, it's not massive, this is, 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 fat tissue. 

And then, you know, after some hours that goes away 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. Okay. 

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. 

[00:32:49] Jonathan Wolf: Yeah, we're very familiar with that at ZOE because everyone who does ZOE actually eats this standardized meal. It’s now cookies, but it goes all the way back to what Sarah Berry originally exactly designed with our first study. Which sort of challenges our metabolism in this standard way that we, you know, did originally with twins with both this fat and this sugar. 

Because I think one of the things that's really interesting, which you haven't, I guess touched on yet, Philip, is there's huge variation isn't there in this response.

[00:33:16] Philip Calder: Yeah, so you, you can use sugar and fat to challenge people's metabolism if you like, challenge their resilience. And part of the 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. Okay. 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. 

[00:34:28] Jonathan Wolf: 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? This isn't just in the first hour. One of the reasons we do these tests in ZOE and some of these are like sort of six hours after you eat, is there's a sort of process that means that one person and one meal, you might be fine and another person or another meal you could start to cause this inflammation. 

[00:35:09] Philip Calder: So you are 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 and 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 the 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 this sort of carryover effect into later meals.

[00:36:50] Jonathan Wolf: Maybe to share a little bit of some of the science that's come out of ZOE, because I think it's really, to me, fascinating. So, we 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, 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, very wide, 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…? 

[00:37:48] Philip Calder: Yeah. 

[00:37:48] Jonathan Wolf: 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.

[00:37:57] Philip Calder: So I think 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. You know, 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. 

[00:38:32] Jonathan Wolf: And one of the things we're hoping to see over time with ZOE members, as 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.

[00:38:48] Philip Calder: I’ve 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 you know, maybe part of that is just slowing down the process of digestion. So you, you know, you're letting stuff come into the bloodstream more slowly, so you're better able to handle it.

[00:39:12] Jonathan Wolf: 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, that'll solve my inflammation like a pill from the doctor? Is it as simple as that? 

[00:39:26] Philip Calder: I wouldn't 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. 

[00:39:58] Jonathan Wolf: People know what extra virgin olive oil is. They know what nuts are. That was really clear. And I know your own research, you've done a lot of your own research around omega-3.

Could you just tell us what omega-3 is, because I don't see that on the shelf, like I see olive oil. 

[00:40:13] Philip Calder: 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. They are, as I mentioned, sort of uniquely linked with fish and other seafood. They seem to have quite pronounced anti-inflammatory roles. 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. 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, the 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. 

[00:43:40] Jonathan Wolf: 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? 

[00:44:01] Philip Calder: For me, the evidence is very strong. 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 in some mice is one thing. 

But we need human evidence. 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 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, you know, 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 controlled 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. 

[00:45:56] Jonathan Wolf: 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 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? 

[00:46:27] Philip Calder: 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, okay? 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, okay? 

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. Okay, it's a commodity. It's much more expensive than vegetable oil, for example. 

[00:47:48] Jonathan Wolf: And that's because it actually comes from other fish, is that where the fish oil comes from? 

[00:47:51] Philip Calder: 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 farm salmon now will have less EPA and DHA than a farm salmon did twenty years ago.

[00:48:27] Jonathan Wolf: Okay so farmers have figured out ways to make this more profitable. 

[00:48:31] Philip Calder: 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 farm 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 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.

[00:49:19] Jonathan Wolf: 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?

[00:49:35] Philip Calder: 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.

[00:49:54] Jonathan Wolf: We've 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 would you say? 

[00:50:12] Philip Calder: Simple sugar. 

[00:50:13] Jonathan Wolf: Simple sugar meaning? 

[00:50:14] Philip Calder: Soft drink or whatever, but you know, also people add sugar when they're making stuff. So I think that would be one thing. 

I think saturated fat, red meat, you know, fatty meat, but also, you know, there's a lot of saturated fat for example, in the form of palm oil, you know, even things like pastries, for example. So I think sources of saturated fat, be they animal or plant sources would be a second.

[00:50:39] Jonathan Wolf: And that can really make a difference to your inflammation, therefore it really can, it's not just about your weight here you're talking about. 

[00:50:47] Philip Calder: 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, 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, you know, plant sources and plant alternatives of these fish-sourced omega-3s.

I think that's going to be a big area of future research. 

[00:51:13] Jonathan Wolf: We are definitely 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 cut our hand and swelling and redness, but interestingly 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's 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 a sort of long-term, sort of low-grade, chronic inflammation. 

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, you know, 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. 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, 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 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 I'll 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, you know, 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 elsewhere, sort of supporting the microbiome and helping to reduce this inflammation. 

And then I think we have 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, are in particular known to have these anti-inflammatory roles. 

And uniquely, you know, 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? 

[00:57:25] Philip Calder: That’s a perfect summary yeah.

[00:57:26] Jonathan Wolf: 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, you know than even a few years ago. So it feels as though this is an area where a lot of research is happening fast.

[00:57:43] Philip Calder: Yeah, for sure. Yeah. 

[00:57:45] Jonathan Wolf: 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. 

[00:57:55] Philip Calder: Yeah, I'd love to. 

[00:57:56] Jonathan Wolf: It was a real pleasure. Thank you so much for taking the time with us. 

[00:57:58] Philip Calder: Yeah, thanks for having me. It's been great. 

[00:58:00] Jonathan Wolf: This was wonderful. 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, visit zoe.com/podcast. There, you can learn more about ZOE and get 10% off your membership.

I'm your host, Jonathan Wolf. ZOE Science & Nutrition is produced by Yella Hewings-Martin, Richard Willan, and Sam Durham. As always, the ZOE Science & Nutrition podcast is not medical advice. If you have any medical concerns, please consult your doctor. See you next time.