Episode 2 with Dr. Philip Calder
Professor Philip Calder describes when inflammation is helpful and when it is not. Omega-3s as pro-resolvins and their role in immune function, as well as matters of background diet, balance, and genes are discussed. After listening to this podcast, you will welcome the omega-3 fire brigade.
- Difference between immunity and inflammation (2:17)
- Cardinal signs of inflammation (3:15)
- Benefits and harmful effects of inflammation (4:42)
- Role of omega-3s in inflammation (9:31)
- Treating inflammation with omega-3s (16:10)
- EPA & DHA in controlling inflammation (17:13)
- Differentiating responses to omega-3 (20:58)
- Plant omega-3s (24:31)
Resources Mentioned in this Episode
- Dr. Philip Calder
Any statements on this podcast are the opinion of the scientific guest and/or author and have not been evaluated by the FDA. The information we may provide to you is designed for educational purposes only and is not intended to be a substitute for informed medical advice or care. This information should not be used to diagnose, treat, or prevent any health issues or conditions without consulting a health care professional. If you are experiencing a health issue or condition, we suggest you consult with your health care professional.
Going back to my analogy about the burning fire of inflammation. This would be akin to a fire brigade, putting out a fire. And it turns out that omega threes actually can drive that process. omega threes can drive the resolution of inflammation.
Hello, and welcome to the science and the story behind omega three, a podcast brought to you by Wiley companies, where we explore one of the most researched nutrients on the planet. Listen in as global omega three experts and researchers translate the science, reveal personal insights and share their stories of discovery while navigating the sea of omega three science. Thanks for joining us today. Now, here’s your host, Greg Lindsey. Ah, yes,
welcome back to another episode of the science and the story behind omega three, where we talk with experts from all over the world. And my guest today is certainly no exception. He is the professor of nutritional immunology in the Faculty of Medicine at the University of Southampton, an internationally recognized researcher on omega three fatty acids in the influence of diet and nutrients on immune and inflammatory responses. And his work has been cited over 37,000 times to discuss the important role of omega three has an inflammation and the immune system. Please welcome to the program, Dr. Philip Calder. Dr. Carter, thanks so much for being with us today.
Oh, thanks, Greg. It’s great to be here with you.
So I’d love to jump right into omega threes. It’s often said that omega threes are anti inflammatory, but also here, they support immune function. So I’d love for you to explain this.
Yeah, Greg, I’d like to do that. But I think maybe First, we need to sort out what’s meant by immunity and what’s meant by inflammation? Are they the same thing? Are they different? How do they relate to one another?
Well, that’s perfect, then will you please explain the difference between inflammation and immunity?
Yeah, sure, sure. So the immune system is what the body uses to protect itself against pathogens, things like bacteria, and viruses, and so on. So immunity is really our host defense mechanism to prevent infections. The immune system also helps us deal with foods and other things in the environment. So it’s pretty sophisticated in its actions, and involves many different components, many different cell types. Now, it turns out that inflammation is actually part of immunity. It’s not the same thing. It’s one component of immunity. And inflammation, helps us defend ourselves. But also, I think we’re probably going to go on and talk about some other aspects where inflammation is involved as well. So one way to think of it perhaps is, inflammation is a part of the immune response. But it’s not the entire immune response.
So when does inflammation occur?
Yeah, so when inflammation is acting the way it should, the way it was designed to, it’s part of the very rapid response to infection, or to some other insult. So people might think about, oh, if I get an insect bite, or if I cut myself, or you know, I bang my thumb, when I’m hammering a nail or something, inflammation kicks on, straightaway, it kicks him actually within seconds. And the things associated with those unfortunate incidents that I’ve talked about the redness, the swelling, the pain, the loss of function, those are the cardinal signs of inflammation. Now, they’re designed to protect us. But immediately, you see, inflammation happens very quickly. And if things are working well, it will go away again in time, often, again, within minutes, but it may take hours or maybe even days of it’s been abandoned. So but that’s the timeline for inflammation when it’s behaving as it should, kicks in quickly, helps protect ourselves. For example, if we cut our skin, there could be bacteria around. And then when things are meant to return to normal, inflammation goes away again.
So I think people hear inflammation and they automatically think harmful, but I’d love for you to dig in a little bit more. Is it helpful? Is it harmful? It sounds like it can be both?
Yeah, yeah. So yeah, that’s right. Great. So inflammation is really it’s a double edged sword. It has its helpful side, and it has its harmful side. And I think when we talk about omega threes, we can try to see how they fit in with that picture. So so far, I’ve presented the idea that inflammation helps us deal with harmful incidents, like cutting ourselves getting infected, stuff like that, where the inflammation is there as part of the immune response to protect us, as I mentioned, inflammation should run its course and then go away again. So that’s the good side of inflammation. Now, inflammation can become harmful if it continues for too long, okay? Because inflammation is really about creating an environment, which is dangerous to bacteria, for example. And that means it can also be dangerous to our own cells. So when it runs its course it should go away, that’s called resolution of inflammation. If inflammation doesn’t resolve, in other words, if it just carries on, it can become harmful. So there is the good and the bad of inflammation. So one way to think about is, if inflammation is present is occurring, when it doesn’t really need to be, then it can be harmful to us. And in fact, there are some diseases that are caused by inflammation happening when it shouldn’t happen.
And I’m not trying to take the conversation in a pessimistic way. But when inflammation goes bad, I think is what I want to know a little bit more about. Yeah,
yep. So as I mentioned, great inflammation is designed to help us defend against bacteria, other insults in the environment, and therefore, so inflammation isn’t passive, it’s active, and it sets out to be destructive. So for example, part of the inflammatory response involves the generation of chemicals which are toxic, things like reactive oxygen species, hydrogen peroxide, noxious chemicals, histamine is another one, which people might have heard of, in allergic responses, which are also inflammation. So those chemicals are designed to be dangerous, as I mentioned, they can be dangerous to us as well. And what that means is inflammation in the wrong time, in the right place, can be damaging to our own cells. So it can actually create pathology. So we can damage our own cells, we can cause pathological changes, some of which can be rather severe.
So maybe we can swing back to omega threes. And are they anti inflammatory? Or maybe you can explain how omega threes react to this?
Yeah, yeah, I will do that. Great. But I realized I didn’t fully answer your last question. Fair enough. So rheumatoid arthritis, for example, where the inflammation is destroying the person’s own joints, for example. So that’s inflammation gone bad target against the joint, inflammatory bowel diseases, that’s inflammation targeted against our own gut wall. So we get pathology on the gut wall. I mentioned allergies, the allergic responses inflammation. So you might imagine skin swelling, lip swelling, those sorts of things. Asthma is an allergic reaction in the lungs. And in 2020, of course, we’re familiar with the COVID-19 problem, and people will have heard of the cytokine storm in really severe COVID-19 patients. cytokines are proteins produced by inflammation. So the cytokine storm of COVID-19 is actually an really severe inflammatory response, targeting the lungs of those patients. We call this high grade inflammation, something really bad was going on. But there’s also what people call low grade inflammation. So I prefer to think of that as silent inflammation. And this is where inflammation is low level, that can happen over a very prolonged period of time and also becomes pathological. So for example, heart disease involves inflammation in the blood vessel walls, taking place over a period of years. cognitive decline, involves low grade inflammation in the brain destroying neurons, for example. So we have this high grade inflammation, which is really pathological, like arthritis. And then we have the low grade, slow burn inflammation, if you like, like heart disease and cognitive decline. So this allows me to move on to your next question, which is omega threes. So one of the first discoveries with omega three is going back decades was they help to dampen inflammation, and they do that because they can reduce the production of many of the chemicals that are involved in the inflammatory process. And that’s where this idea of omega threes being anti inflammatory comes in. So people describe these effects as anti inflammatory. So omega threes are acting against inflammation. They’re actually helping the body to control inflammation to dampen inflammation. And if you imagine inflammation as a fire, for example, burning in the joints of someone with arthritis or in the lungs of someone with asthma, omega three sort of help to put out the fire a little bit. So they dampen the inflammatory response. And that’s through their effects on chemicals that are involved in inflammation. But Dr. Carter,
thank you. So a mega three can actually turn off inflammation, then can you say a little more about that and why it’s so important.
Yeah, yeah. So thanks for picking up on that, Greg. So I just mentioned the role of omega threes in dampening inflammation. So that was sort of the calming of inflammation, through the ability to decrease the production of some of the chemicals involved in inflammation. These chemicals are things like prostaglandins, for example, some cytokines, these are sort of fancy names, but these are chemicals involved in inflammation. So that’s the sort of the classic anti inflammatory role. But something perhaps even more important has been discovered in the last few decades, which your question is bringing to the fore. And that’s the ability of omega threes to actually turn off inflammation. And I mentioned the importance of inflammation running its course, and then settling down again, and I use the word resolution. So the resolution of inflammation is the turning off of the inflammatory response. And going back to my analogy about the burning fire of inflammation, this would be akin to a fire brigade, putting out a fire. And it turns out that omega threes actually can drive that process. omega threes can drive the resolution of inflammation. And this comes about because there are very special chemicals just discovered in the last 20 years that are produced from omega threes that produced from both EPA and da j that are the chemicals, perhaps amongst the most important chemicals in the body, that turn off inflammation. And these chemicals have been given the names like resolvent, because they resolve inflammation, that is they turn inflammation of protectant because they protect from inflammation and Bresson’s. So these are pro resolution chemicals, these are the fire brigade of the inflammatory response, they put out the burning fire of inflammation. And the really important thing to keep in mind is these chemicals are produced from omega threes EPA, MDA J.
So a question of has in how I guess, have people been tested with inflammation as it relates to omega three?
Yeah, yeah. So I mentioned earlier on, Greg, that the anti inflammatory effects of omega threes were amongst the first biological actions that were discovered for omega threes, and the doctors involved in Rheumatology, the rheumatologist were very quick to get on to the omega three story. And that’s because they knew in the early 1980s, late 1970s, early 1980s, that chemicals produced from omega six fatty acids. So the other omega family, the Omega six fatty acids, some of those chemicals were actually involved in causing inflammation. And they knew that omega threes could decrease the production of those chemicals. So in other words, some sort of re-balancing between the Omega sixes and omega threes, they thought could be important in controlling inflammation. So American rheumatologists actually did the first trials of omega threes in patients with rheumatoid arthritis. And typically, they use rather high doses of omega threes in clinical trials of patients with arthritis. And many such trials have been done since the mid 1980s. Right up to date. And these trials often have shown that omega threes at pretty high doses can help in let’s call it the treatment of rheumatoid arthritis. So they they can reduce the pain of arthritis they can reduce some of the problems like stiff joints, particularly when people get up in the morning and feel very stiff. omega threes have been shown to reduce that. So arthritis is one disease where omega threes are pretty useful. We’ve done some recent studies ourselves in arthritis with omega threes, inflammatory bowel diseases another where again, there are positive signs arteries, although there’s also some inconsistency in the literature, there are trials and asthma. And of course, I mentioned silent inflammation. And we know that omega threes are really important in protecting against heart disease. And I think some of that protective effect could be because of the dampening of the silent inflammation. So certainly, there are plenty of clinical applications of the anti inflammatory and pro resolving actions of omega threes.
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I don’t know if this is a question that you’re able to answer. But I think it’s a question that people may have is how much omega three Do you think people need to help control inflammation?
Yeah, yeah. This is a question. People often ask me, what’s the obvious one. And I already alluded to the fact that these trials in patients with Frank, chronic inflammation have used high doses. And typically they’ve used several grams of EPA plus tha per day, I think, to control inflammation. Certainly, you need at least a gram a day. I think, maybe you need more than that. I mean, people haven’t done good dose finding studies. But I think we’re talking about gram a day or more. I mean, the trials and arthritis, some of them have actually used three or four grams of EPA plus tha per day, which is courses, a dose you can use for treating triglycerides, even now in 2021. So somewhere in this, this range of a gram or more per day, I think is needed. Okay. You reference EPA and da j, is one more important in controlling inflammation? Yeah, that’s a good question, Greg. So if you’d asked me that question. 20 years ago, I would have said EPA is the anti inflammatory omega three fatty acid. And that’s because EPA is very good at reducing the production of chemicals involved in inflammation, such as the prostaglandins produced from omega six fatty acids. So EPA, certainly as anti inflammatory. But these pro resolving chemicals I mentioned, the resolvins, the protectants, the Morrison’s some of them are produced from EPA. And some of them are produced from VHA. And they’re both the EPA derived ones and the VHA derived ones are both bioactive and are both effective, at least in model systems. And so what that tells me is probably both EPA and VHA are important in the body’s battle with adverse inflammation. So I don’t think I would swing one way or another anymore. I think they both have their roles. And they’re both important. If that makes sense. That’s helpful. We also heard that omega threes have a role in immunity. So I guess the question, do they? Yeah. So people have been this idea of omega threes, controlling inflammation and the pro resolving effects and so on, that have been investigated really intensively over decades now. So we know a lot about the roles of omega threes in inflammation, the effects on the other parts of immunity, by which I mean things like how lymphocytes function, how well vaccines work, whether omega threes have a role in reducing infections have been rather less explored. But there are human trials in this area. So certainly omega threes can control how different lymphocytes work T cells, B cells, people might have heard of how they work. And there is some nice data on omega threes and infections. And remember, the immune system mainly is protecting us against infections. So there are some trials often done on children because children, one group of the population who can be at risk of infections, of course the other group is older people. So there are supplementation trials of omega threes in children. There’s one in Thai and Thailand. There’s one on South Africa. They’re also trials of omega threes and infants. And these trials have shown in these are placebo controlled trials. So you have one group of children taking omega threes and another group taking some sort of placebo that might be, you know, corn oil or something like that. And these trials have demonstrated reduced numbers of infections. And these are usually respiratory infections. So reduced numbers and shorter duration of respiratory infections in children receiving omega threes compared to placebo. I’m not aware of such trials in older adults. And I think that’s a gap in the literature. But I’m pretty convinced that omega threes do have a role in supporting the immune response in its action to deal with organisms that threaten us. Alongside this, well describe the effect on on inflammation.
I think another question that our listeners will have, because all people are different. Do you think the effects of omega three autoimmunity and inflammation might be different in different people?
Yeah, I think that’s a good question. So we’re talking about the role of omega threes and protecting people against disease, maybe using them in times of increased susceptibility. And I think not everyone is going to be responsive to the same extent, or the same dose of omega threes may have slightly different effects in different individuals. And I think one of the reasons for this is other aspects of the diet. So I mentioned, for example, that chemicals produced from omega six fatty acids are well known to have roles in inflammation. And in effect, the way omega threes are working is to sort of rebalance the Omega six to omega three availability in the body. So you might imagine, in people who have a very high omega six diet, omega threes may struggle to have their effect. Whereas in people with a low omega six, diet, omega threes might have their effect more easily. So I think when I talk about background diet, I would want to think about the Omega six content of the diet, maybe other fatty acids, maybe saturated fatty acids, which are known to be pro inflammatory, the game saturated fatty acid and take omega threes may have a different effect against that. Maybe antioxidants could be important in determining how omega threes are working. So certainly other aspects of diet, maybe something to do with genes, because we know that people’s genes predispose them, obviously, to different illnesses, but also, their genes control their immune responses, their inflammatory responses. And interestingly, people’s genes also control how well they respond to dietary factors. So this is described for some vitamins for minerals, but also for omega threes. So we and others have actually published research, where we look at whether people with different genetic makeups responded the same way to omega threes in the context of inflammatory responses. And we found there was a we call it an interaction, that is omega threes work a little bit differently, depending upon the person’s genetic makeup. So these are the sorts of things that you know, lead us to think, you know, a dose of omega threes is not going to be the same in every different person. Of course, that complicates things. When people think about what should I eat? Or, you know, should I use a supplement or not? Those, you know, dietary recommendations and the way supplements are formulated are sort of a one size fits all. And I think people probably realize that, you know, life is more complicated than that, that different people have different requirements. I think this is some of the future great, maybe a bit more. It’s called personalization of nutrition. But certainly, I wouldn’t say you know, if one gram of EPA plus da che was effective in one person, that exactly one gram would be effective and another person, you know, they may need 1.5 grams, or they may actually only need half a gram, because of these variations that we’ve been talking about.
Very helpful. Dr. Carter. So what about plant omega threes? And what role do they have?
Yeah. So this is, this is the perennial question, because in our diet, we know seafood, especially what we call fatty fish, or oily fish is the main source of EPA and DOJ. And most people don’t eat enough of that sort of fish. They don’t like it. They can’t afford it. They weren’t bought up with it. So they’re not used to it. They live too far from the sea. So if they get it, it’s not fresh. So most people Don’t eat enough fish. And therefore most people don’t get enough omega threes and many countries have recommendations for omega three intake, including the US the UK, most people don’t meet those recommendations. Okay. So if we’re thinking, of course, they can meet those recommendations if they use omega three supplements. So that’s one way to do it. But there is a, there’s always this question that actually plants make omega threes as well. plants don’t make EPA and bH chain, we have to get those from fish or from lb. So lb can make EPA and VHA. Both plants, the sort of plants we’re thinking about land plants, they don’t make EPA nbha. But they make other forms of omega three, so the most common one in plants is called alpha linolenic acid. And in our body, we can make the plant omega three alpha lipoic acid into EPA, we can do that in our own bodies. But in as far as we know, most people are actually not very good at doing that. So and they certainly are not very good at making the HA, which is further along the metabolic pathway. So what I’m kind of saying is the plant omega threes are not very good at acting as a substrate for us to produce our own EPA and D ha, that’s the first point. The second point is okay, do the plant omega threes actually have health properties in their own right? Can they control inflammation in their own right? And I think the answer is if they can, they’re not very effective. And you know, on another day in another context, you know, I might say actually, they’re not that useful at all. So I think the genuine answer, Greg is the plant omega threes can’t substitute for EPA and DOJ, they may have a role in helping control omega six levels, but as a sort of a direct anti inflammatory role as a precursor for EPA and DOJ. They’re not really so useful. So I think GM, you know, preformed EPA and D ha, are what we really need.
What a timely and intriguing topic and subject matter today. Dr. Carter, it’s just been fantastic. I want you to come back on because I really want to dig in more on the plant based and versus fish base versus supplements. Unfortunately, we’ve hit the end of our time today. But I did want to give you the opportunity because I’ve been asking all the questions. Is there anything else you’d like our listeners to know about omega three in inflammation and immunity?
Yo, yo, thanks so much, Greg, it’s been great talking to you. So you know, our context has been inflammation and immunity. But I’m going to go outside of that. Because omega threes are really important, right across the breadth of health and right across our life course. So from infancy to old age, EPA and VHA are really important in maintaining health, heart health, brain, health, immune health, all of those things. So you know, my main message would be people really need to think about ways to take onboard pre formed EPA and DHS to maintain their health. Well, thank
you so much again, Dr. Carter, thank you to our listeners today. What a great program can’t wait to get Dr. Carter back on the show. As always be healthy, be well in fight the good fight.
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Any statements on this podcast or the opinion of the scientific guest and or author and have not yet been evaluated by the FDA. The information we may provide to you is designed for educational purposes only is not intended to be a substitute for informed medical advice or care. This information should not be used to diagnose, treat or prevent any health issues or conditions without consulting a health care professional. If you are experiencing a health issue or condition we suggest you consult with your healthcare professional.