Dr Shilpa Ravella: Para-inflammation is another iteration of hidden inflammation. Then you have inflammaging, which is the inflammation of old age. And these different iterations of hidden inflammation, they have commonalities between them. They are all hidden inflammation, they are all inflammation, but they arose from distinct research settings. So meta-inflammation arose from research in obese mice and inflammaging arose from research in ageing humans.
Dr Rupy: Hidden inflammation presents a unique dilemma. The idea that it may be a shared biological mechanism between diseases as distinct as obesity and ageing or depression and heart disease, fosters a new understanding of human health. It pushes us to consider preventing or treating these diseases in concert rather than in parts, taking into account the totality of a patient's body and mind, including the germs that live within and on top of us. The biomedical framework of the 19th century divided by organ systems and an understanding that a specific cause results in a specific disease is no longer effective for most health conditions that plague us today. That was from Dr Shilpa Ravella's book, Silent Fire. It's one of the most beautifully written books that I've had the pleasure of reading. Shilpa's eloquent writing style complements the wonder of inflammation as both a benevolent yet destructive force that weaves its thread through a multitude of conditions including autoimmunity, cardiovascular disease and obesity. Dr Shilpa is a gastroenterologist who treats a range of general GI ailments and has unique experience in managing complex rare cases including intestinal failure and intestinal or multi-organ transplantation. She's also an expert in the field of nutrition and is particularly interested in the interactions between lifestyle, the microbiome and the immune system. Today, we're talking about inflammation, cancer, immunity, dementia, cardiovascular disease, as well as the components of an anti-inflammatory diet and lifestyle such as spices, fibres, greens and exercise. In addition, we're also going to be talking about what inflammation actually is, the various terms like para-inflammation, meta-inflammation, inflammaging and why it's so important to control it. Remember, I've also got an inflammation mini-series that you can sign up for free right here in the caption, just click the link. There were plenty of issues with the recording on today's podcast, so unfortunately we had to cut it short, but perhaps some of you will find this shorter, bite-sized podcast a refreshing break from the regular longer length ones. We'll definitely have to get Dr Shilpa back in the studio at some point in the future where we can do it face-to-face rather than via online, which I really dislike. And remember, you can also watch the podcast on YouTube as well as all the other pods that we're doing. We're trying to invest a lot more time and energy into beautiful quality video that we're going to be doing right here in the Doctor's Kitchen studio. And you can download the Doctor's Kitchen app for free from the App Store. We are working to make sure it's accessible to as many people as possible and there is an inflammation health goal there as well that you can check out right there on the app. For now, on to my chat with Dr Shilpa Ravella. Shilpa, great to have you on the show. Let's start off with the top foods you should eat to reduce inflammation and heal your body.
Dr Shilpa Ravella: Well, one of the top foods I can say is just greens. So lots and lots of leafy greens packed with fibre, and some of those greens have the immune-modulating potential of our ancestral greens, like kale, for example. Greens are very, very important. They have polyphenols. Polyphenols are also immune-modulating. They are plant phytochemicals that can help to dampen inflammation. And then also whole grains and beans. These are foods that are somewhat overlooked, but we have so many randomised control trials showing us that the consumption of beans can actually dampen inflammation in the body. And overall, you want to just be eating a lot of fibre. We know that 90% of folks in the US and the UK have a fibre deficiency. We are failing to meet even the minimum recommended daily allowances. And fibre is one of our most anti-inflammatory nutrients. It can manipulate all arms of the immune system. And when we metabolise fibre, when fibre gets down into our bodies and the germs inside of our gut metabolise fibre, we are creating many wonderful beneficial compounds like short-chain fatty acids. And these compounds are active. They can dampen inflammation in the gut and also throughout the body. And they have so many wonderful effects inside the body. So eating tons of fibre is very important. And I would also say just don't forget about the spices and herbs because those are very, very important. And in my culture also, we use tons of spices in cooking, but even things like cumin and and cinnamon on your oatmeal, just adding a little bit of spice to your food is very easy, doesn't have to take that long, but it can really enhance the anti-inflammatory potential of a food.
Dr Rupy: Were there any spices or foods that surprised you when you were doing your research for the book, A Silent Fire, that you perhaps have started introducing into your daily or weekly diet?
Dr Shilpa Ravella: Well, I already cook with cumin quite frequently, but I was actually surprised to find that cumin contains salicylic acid, one of the highest concentrations of salicylic acid of any plant food. So when you're eating all of these different types of plant foods, it's kind of the equivalent of taking a baby aspirin. And spices and herbs, the salicylic acid is what you find in aspirin, was once extracted from willow bark. And when you're using those spices, particularly cumin, you are actually equivalent to taking a baby aspirin a day almost. So it's incredibly beneficial, but I was actually surprised to find that cumin was one of the spices that had the most salicylic acid.
Dr Rupy: I guess a lot of people will also say, okay, that's great, I'll get some spices into my diet, I'll increase my fibre, I'll have some greens. What are the kind of foods that people should be clearing or steering clear of when it comes to healing the body or even healing specific ailments like their gut, for example?
Dr Shilpa Ravella: I would say one of the most insidious types of foods that's come into our diet is just processed foods in the last few decades. And these are actually whole food derivatives, so they're made from whole food extracts, have an excess of not so favourable fats, excess of salt, excess of sugar, and lots of additives, and we're slowly finding out what the components of some of these processed foods can do to our bodies. And when I talk about processed foods, I'm talking about ultra-processed foods, so foods that don't look like anything that you would normally see in your grandfather's farm or grandmother's farm. And we have some types of processed foods that are just packaged, but I'm talking more about the processed foods that have been adulterated in many different ways. And we're finding out that some of these additives, like the emulsifiers, for example, are not so great for the germs inside of our gut, and they can change not only the types of species in our gut, but also their behaviours, which plays an important part in health and disease. And processed foods are addictive, and they tend to cause steep insulin spikes and then crashes, which is a stress on the body that can actually raise inflammation in the body. And companies profit markedly from these processed foods, but many processed foods are not so healthy for us. So I think that's been one of the most insidious changes over the last few decades. And in general, I think we need to have diets that are very high in plant foods. High in plant foods or exclusively plant foods doesn't really matter. I think there are different iterations of an anti-inflammatory diet that can still work depending on your culture and your preferences. But we do need to be focusing on eating as many plant foods as possible and conversely, trying to minimise some of the animal foods, particularly the processed meats and such.
Dr Rupy: Yeah, yeah. It's one of the sort of bugbears, I guess, of the modern food landscape that I have is just how sort of accepted it is that that's the norm. And I think challenging the norm with recipes and finding ways to still have convenience on our day-to-day basis but introducing some of those healthful attributes of the anti-inflammatory foods that you mentioned right at the start, is something that we should all be aiming for. I want to get into sort of the premise of the book and how beautifully it's written, for example, and how it gives a real, a fantastic picture of this common thread that runs through many modern diseases that we see as doctors. It's also told against the backdrop of quite, quite a, I wouldn't say sad case, but it was certainly a case that must have been absolutely distressing for you, but also your friend Jay, who suddenly had an inflammatory condition that wasn't initially diagnosed and was treated with what we currently use for immunotherapy and anti-inflammatories. I wonder if you could give us the backstory to Jay and how that framed the context of the book.
Dr Shilpa Ravella: Sure. Well, this was several years ago and this was a close friend who had gone to the gym just for a typical workout. He was in his early 30s and was a very healthy guy, had no prior conditions at all. And was just going to the gym for a workout one day, came back and had some pain in the back of his neck. We chalked it up to muscle strain. He took some ibuprofen, thought things would get better, but this actually devolved into something pretty horrific because he eventually over the next weeks ended up developing a complete head drop. And the human head weighs about 10 pounds and carrying it up, holding it up is actually a pretty seamless task and most of us don't even think about that too much. But when your head drops down to your chest, it requires a brace and he required a body brace at that time, a full collar and then also a body brace and started having other symptoms as well, like he couldn't swallow, he had trouble with some, with some weakness in his thighs, got short of breath. And doctors initially did not understand what was going on. We saw rheumatologists, neurologists, and at the end, we understood that this was actually a form of an atypical autoimmune disorder. And many, many people across the country, across the globe suffer with autoimmune disorders and they're on the rise as are allergies.
Dr Rupy: I had no idea just how diverse their research interests were. I learned from your book that Metchnikoff actually coined the term gerontology and was one of the first people, at least in Western medicine, to appreciate the good and bad bugs in our system and how we can tolerate pathogenic bacteria differently based on our internal ecosystem. Walk me through the process because it is fantastically well researched and and and like news to me for a lot of the chapters.
Dr Shilpa Ravella: Thank you so much for those thoughts and you know, I've just been very fascinated by historical medicine in general since I was a kid. And I think probably the best part of writing this book was just the process of discovery, being able to learn more about some of these scientists. And in a sense, it is a homage to all of these scientists past and present who really helped to define the role of inflammation in our lives today. And I was fascinated by Rudolf Virchow, you know, he's a 19th-century German pathologist, was one of the first ones to really see inflammation on a cellular level. But all of these men in general were somewhat Renaissance men. They had so many diverse interests. They were able to take advantage of that cross-pollination that comes with that diversity of interest. And Virchow is known for certain things in medical school, Virchow's node, for example, that portends a higher risk of gastrointestinal cancer. But we also know today that he was one of the first ones to say that inflammation can actually cause disease, can cause diseases like heart disease or cancer. And we know now, you know, over a century later, we know now that we have large-scale clinical trials to support this. So I was really fascinated by this arc, this narrative arc and then the story of discovery and rediscovery. I could probably spend hours in historical libraries or medical museums. I remember staring at old surgical tools and just being equally horrified and fascinated and staring at them for hours. And so I was very captivated by these folks and I think the history does have so much relevance to the present day and can help to teach us so many different things.
Dr Rupy: Yeah, and there are a number of characters that popped up that I just wasn't expecting in a book around inflammation. I mean, Edward Jenner describing the bony grit of a blocked coronary artery that you talk about. It seems that inflammation has sort of weaved its way through all of these people. And I imagine you can see why because inflammation, as we know now with hindsight, has afflicted or is the common thread across a number of different diverse medical disciplines. Before we get into perhaps those different areas, perhaps we should define some terms that I think people have heard. I mean, we've mentioned the word inflammation quite a bit already, but perhaps para-inflammation and meta-inflammation. Those are two other terms that are bandied around. So within the context of what we're going to talk about, maybe we should go through some of those definitions and how you describe inflammation and those other things to people.
Dr Shilpa Ravella: Sure. Well, there are so many different iterations of inflammation. One, the inflammation we typically think of is the overt type of inflammation. So for example, you stub your toe or something like that, and you see redness, heat, swelling, and pain. And these signs are a manifestation of what's going on inside of your body when blood vessels dilate, blood flow increases, and fluid and protein leak out of those vessels and put painful pressure on your nerve endings, and you have pain as well. So we have those four cardinal signs of inflammation, and there's also a fifth sign, loss of function. And that's acute inflammation. We can see the things that are happening to our body. And it's acute overt inflammation, meaning that it's very visible. Now, we also know that we can have hidden inflammation. And hidden inflammation is a type of inflammation that kind of swims through your body, but you don't know that it's actually there. This is low-level inflammation. And there are many different names for this type of inflammation that I discovered as I was researching this book. Meta-inflammation, for example, when you think of the type of inflammation in metabolic disorders, the type of inflammation that is spewed out by the tissue in your fat, essentially, that's meta-inflammation. And these came from distinct research segments, for example. And para-inflammation is another iteration of hidden inflammation. And then you have inflammaging, which is the inflammation of old age. And these different iterations of hidden inflammation, they have commonalities between them. They are all hidden inflammation, they are all inflammation, but they arose from distinct research settings. So meta-inflammation arose from research in obese mice, and inflammaging arose from research in ageing humans.
Dr Rupy: Yeah, yeah. And let's move to, as much as I really want to dive into a bit more about cardiovascular disease, I think there's so many topics that inflammation touches. Cancer and inflammation, this is, I think, a topic that has multiple parts, and we're going to get to inflammation and obesity, and you've talked about how obesity has a connection with cancer. What is going on with inflammation and cancer? And how are cancer cells essentially hijacking this system of inflammation to grow?
Dr Shilpa Ravella: Well, normally when you think of your immune system, you think of this idea that your immune system is trying to protect you, not only from germs, but also cancerous cells. And that is indeed what it tries to do. And the problem is that what tumours can do is that they can hijack the immune system. They can use inflammation for their own good. So inflammation, when you have low-level or overt inflammation in the body, in most cases can lead to an increased risk of cancer, whether it's overt or hidden. So for example, I have patients with inflammatory bowel disease in which their intestines are inflamed. So they have chronic inflammation in their bodies, it goes unchecked, and if it's untreated over long periods of time, they end up having a higher risk of cancer. And inflammation is actually a hallmark of cancer. It was added as a hallmark a few years ago. And this means that it can take part in every stage of cancer development from the initial epigenetic or genetic changes to the continued growth and the spread of cancer throughout the body. So whether it comes before or after a cancer, inflammation plays a very important role. And then also as an aside, this isn't to say that every part of the body with inflammation contains a higher risk of cancer because we know that when, for example, the joints are inflamed or you have inflammation in the brain, that actually does not lead to as high of a risk of cancer as when other parts of your body are inflamed. But inflammation, when you have a tumour, for example, inflammation is a very important part of the tumour microenvironment and can help the tumour to grow and spread.
Dr Rupy: I'm particularly interested in how you talk about in the book about how inflamed cells essentially ignore insulin signalling, leading to higher amounts of insulin being needed to be produced by the pancreas in order to have the same glucose-lowering effect. Can we talk a bit more about how there is this link between inflammation and obesity?
Dr Shilpa Ravella: So we know that when fat cells pad things like the thighs or the upper arms, it acts more like a sink and it's not as insidious for your body. It's when the fat pads the belly, that type of fat is actually a marker for the deeper fat that wraps around your abdominal organs on the inside of your body, and that's called visceral fat. And visceral fat is just highly inflammatory, spewing out inflammatory cytokines at all hours of the day. And inflammation may be one mechanism by which obesity is tied to a variety of chronic conditions. And we know that there is a complex relationship between insulin resistance, obesity, and inflammation. And we have animal studies, for example, showing that when you create inflammation in animals, that can actually cause insulin resistance. And we also have human association studies showing elevation of inflammatory blood markers tied to diabetes, for example. And I think that this is just a fascinating connection because we can sort of think of this as, hey, can inflammation cause insulin resistance, which leads to fat storage? And this is something that I think I was thinking about a lot when I was researching this book. And I was actually quite surprised at all of the different connections that were coming through. Now, when it comes to treating inflammation in a diabetic and treating that risk factor, I think that's somewhat more complex, particularly in humans. You can treat inflammation in a mouse or a fruit fly and reverse their diabetes, but in humans, the pathways are more complex. So we still don't have those types of large-scale clinical trials as we do in heart disease with the CANTOS study, but I feel like there are potentially lots of exciting things coming through in that field.
Dr Rupy: With dementia in particular, I think there is this understanding that inflammatory cells can now cross, or have always been able to cross the blood-brain barrier, but you mentioned Teresa Gomez-Isla from Harvard who essentially demonstrated that with some studies. What is the this connection now that we have an understanding of, or a better understanding of, with regards to dementia and inflammation? What is the story that's going on there?
Dr Shilpa Ravella: Well, we know that, for example, with Alzheimer's disease, there are a lot of genetic factors, but there are also environmental factors in up to a third of cases, you know, things like exercise and smoking and such. And we know today that inflammation in the body can indeed cross the blood-brain barrier. The immune cells can cross that barrier or they can relay signals through the epithelial cells that line the vessels. So inflammation that is going on in the body can affect the brain. And when you have inflammation in the brain, inflamed nerve cells, when that happens, the connections between those neurons are less adept at learning and at storing information. So inflammation can actually cause some of those problems in the brain. And we know that from autopsy studies, and this is the work of Teresa Gomez-Isla from Harvard, as you mentioned, we know from autopsy studies that the folks that build up the plaques and tangles in Alzheimer's disease, these misfolded proteins, the amyloid and tau, the folks that build up those plaques and tangles also seem to need inflammation as well in order for the clinical disease to manifest. She saw that the folks that did not have inflammation as much inflammation in the brain, actually did not end up developing the clinical signs and symptoms of Alzheimer's. It was the folks who had both those misfolded proteins and inflammation as well. So this may be akin to something like the relationship between the cholesterol plaques and heart disease as well. Do we need both? You know, do we need the blockages, you know, those misfolded proteins or the blockages in our arteries as well as the inflammation for disease to manifest? But we do know that inflammation is turning out to be a bigger and bigger part of this picture.
Dr Rupy: Yeah. I, you know, I get sent books all the time regarding food, medicine, lifestyle, and reading your book was super refreshing because you have this ability to narrate and this wonderful poetic language. I'll give you an example. I've got a whole like number of examples of some of your writing because it was just so lovely to read. The history of medicine, unlike classical history, is capricious and angular, bereft of the narrative framework provided by wars or shifts in political power. You were talking about that in relation to Virchow and these other pioneers of medicine in the 1800s and 1900s. Where, how long have you been writing in this way? Because learning about inflammation with through the narrative and the writing is such yourselves was was even more enjoyable than just, you know, spitting the facts and everything else. Is this, is this something that you've, you've, you've sort of fostered over, over your career? Because you also work as a gastroenterologist. I imagine you don't have too much spare time.
Dr Shilpa Ravella: Well, thank you so much for those comments. I really appreciate it and I'm grateful for your take and your feedback. And I, so the honest answer is that I probably have always wanted to become a writer since I was a little girl and I wanted to write fiction. And that was kind of the dream I had growing up in Indiana all those years ago. You know, but I love to read, I love to write and I, I love to, um, you know, I, I think over the years, it's, it's something that I just ended up doing on the side. I just write in my journal every day. I would write a lot of fiction stories and, and as I was going through my clinical training, of course, there's a lot to write about when you're on call for 30 hours straight and when you're seeing all of these different things in the hospital and having all of these different experiences. And in some ways, it was just cathartic to be able to put everything down onto the page. And I think there are many physicians who also feel like this, who, who feel like writing gives something of a catharsis to the clinical training that they're going through. And I've always felt like that. And as I came to my gastroenterology fellowship and learned a lot more about how food affects health, and I was very curious about inflammation, became kind of obsessed with the topic in some ways and obsessed with the history and really getting to the root of this issue, you know, what's the hype and what's the evidence? And I really wanted to answer that question for my patients and for my loved ones and try to find out more about this topic. And I wanted to blend the teaching with stories as well because I do feel like often times, and this is true of me too, if I'm taught something and I'm taught that thing in stories, I just tend to remember it much more so than if I get a list. And we memorise lots of lists in medical school and and throughout training. So I wanted to see if stories and also sharing some of my personal experiences and and my and my childhood and that of my parents and my family could could also help to shed some light on this topic.
Dr Rupy: Yeah, yeah. Um, let's go through some some quick fire questions, even though they're definitely not quick fire topics. Um, uh, there was this famous Lancet paper that you refer to in the book called The Only Good H. pylori is a Dead H. pylori. Um, is H. pylori the enemy or is it something that is innocuous unless we find it in certain circumstances?
Dr Shilpa Ravella: That's a great question. And as gastroenterologists, we are trained to absolutely eliminate H. pylori. And it's true that H. pylori can play a part in cancer, can play a part in ulcer causation, but there are very specific indications for testing for and then treating H. pylori. And what we're seeing is that, you know, a lot of these bugs, a lot of these germs in our bodies, they are not entirely good or entirely bad. They have some symbiotic properties as well. So if we go around the world and eradicate H. pylori in every single person in the world today, that probably wouldn't be such a good thing. We know that it does have some benefits, it does have some anti-cancer benefits as well. It does have some immune-modulating benefits. So as is with the case, as is the case with many other germs, we have to really think about why we are testing for and why we are treating this germ. And there are very clear clinical indications as to when you should test for H. pylori and get rid of it in your body. And I think, you know, it's absolutely necessary to do that in the right cases. But as with antibiotics, for example, we have to think about which germs are we eradicating and why before we eradicate germs that live on or inside of us.
Dr Rupy: Oils. So you mentioned corn oil in people's diets in Southeast Asia. Um, and we all know now that trans fats are terrible for us. Most of it is seemingly being taken out of the food supply. However, what about vegetable oils that a lot of people do have concerns with still? Where do you stand on vegetable oils that aren't olive oil?
Dr Shilpa Ravella: That's a good question. And I, you know, I would say in general, I think when you look at what someone is eating, you want to think about what it's replacing. So I would say if you have someone eating a diet very high in processed foods, very high in processed animal foods as well, and they are replacing those types of foods with vegetable oils, and hopefully some more plants along with those vegetable oils, that's a positive change. I think in general, you know, I, it's, it can be a good thing to keep in mind that there is this omega-6, omega-3 balance, they compete for space in our cell membranes. This isn't to say that you should, you should not ever have any other types of vegetable oils besides olive oil. Again, I think it's about what you are replacing the foods in your diet with. So it's a positive move, I think, when you do use those, you do use those vegetable oils to replace a lot of the, the, the animal-heavy processed foods or the typical Western diet.
Dr Rupy: You've seen patients who come to you with symptoms of celiac disease, yet every single test is negative for celiac. And when they remove the wheat-containing products or the gluten-containing products, they seemingly have resolution of their symptoms. Why is that? And what else could potentially be going on there?
Dr Shilpa Ravella: Well, this is a different entity called non-celiac wheat sensitivity, and we've just been learning more about this over the last few years. And in non-celiac wheat sensitivity, folks may have reactions to the products in wheat. It could be the gluten, it could be something else, another type of protein in the wheat. We're not entirely sure yet. And these folks often have various gastrointestinal symptoms or extra-gastrointestinal, extra-intestinal symptoms, which are not GI-related. And the important distinction between these two disorders is that if you have celiac disease and you have that visible inflammation or the visible changes on the endoscope and you are diagnosed with celiac disease, you need to avoid gluten 100%. This means that you have to avoid gluten in your medication, you have to be very stringent about avoiding gluten because we know that the chronic inflammation that you develop from eating gluten in this scenario can lead to other issues like cancers down the line. With non-celiac gluten sensitivity, we actually recommend avoiding wheat products as it suits you. So you are able to avoid wheat products on a more casual basis, just monitoring your clinical symptoms. And we know now that there is actually an immune activation in non-celiac wheat sensitivity as well, a different arm of the immune system that prevails in non-celiac wheat sensitivity as opposed to celiac disease. So I thought that was quite fascinating as well that you see, you see some immune activation in this disorder as well.
Dr Rupy: Is there a test for non-wheat, uh, non-celiac wheat sensitivity on the horizon that people could be looking out for? Because I think folks today, like you said, are really balancing their exclusion based on, you know, just eliminating it from the diet and monitoring clinical symptoms.
Dr Shilpa Ravella: You know, in the clinical setting, typically I get a lot of patients who come in and if they are having problems with gluten or wheat products in general, they will just cut it out of the diet. I think one, it's very important to get tested for celiac in that case. And and then make sure that you don't have the actual celiac disease. But we don't currently use the clinical test for non-celiac wheat sensitivity, though there is research going on in this area and I think it would be great to see something come out. We can actually test some of these folks and try to understand what is going on inside of their bodies and at least try to diagnose this disorder.
Dr Rupy: Shilpa, this has been brilliant. I think we're definitely going to have to do a part two, um, perhaps when maybe I'm swinging by Hawaii. Is that where you're based now? Is that?
Dr Shilpa Ravella: Hilo. Yes, yes. It's, it's on the big island and it rains a lot here and I work in a rural health setting here and it's, it's a beautiful place. So you should definitely come visit Hilo if you get the chance.
