Are We Making Our Children More Allergic? | Prof Adam Fox

0:00Dr. Karan Rajan: Our gut and our skin teaches our immune system what's dangerous and what isn't. Understanding this is crucial if you care about allergies. I'm diving into this with allergy expert Professor Adam Fox. We've seen a trebling in the number of visits to A &E with anaphylaxis, a severe allergic disease. This isn't more adults having allergic reactions to penicillin, it's small children reacting to food that is driving these numbers. I'm Dr. Karan and in this podcast I speak to the world's most foremost experts in science and medicine to cut through the BS of modern health advice. Thanks as always to Throne Science for sponsoring the show.

0:35Dr. Karan Rajan: It's the world's first continuous tracker for getting personalized insights about gut health, hydration, and prostate health with every flush. And thanks to Loam Science, the world's first invisible fiber blend with clinical trials. You are an expert in allergies. And what I want to know is that, and this is probably a question you're asking yourself, we've seen food allergy rates double over the last decade, severe allergic reaction treble over the last 20 years. And we're also seeing things like hay fever go from medical curiosity to something affecting 20 to 30 % of people. What is driving that?

1:11Dr. Karan Rajan: And why is that disproportionately affecting children? I wish I had a simple answer for you. Hopefully you'll give me a little bit of space to give you the more complicated answer. I think if you asked us in the 1980s and the 90s, we thought we knew. There was an observation from epidemiologists that the older child in a family seemed to be differently affected to the subsequent children in the family. So there was what we called a birth order effect. So the idea was is that the older child is born into an environment where in modern Western living has very limited pressure on their immune system.

1:48They're not dealing with typhoid and cholera and all these nasty diseases anymore. So that child's immune system under very little pressure would look for trouble and would develop inappropriate immune responses, because that's what allergy is, an inappropriate immune response to things that are actually harmless. Pollen, house dust mite, peanuts, milk, things like that. And the studies suggested, the big birth cohort studies suggested that the older child was more likely to have hay fever than subsequent children. However, over time, it would appear that lots of studies showed that the older child didn't always have a high risk of allergies.

2:24In fact, it was pretty evenly distributed and that there were big holes in the theory. And so we started moving away from this idea, the clean child theory, the hygiene hypothesis. Although for reasons that I'm not sure I understand, that theory has absolutely entered the public consciousness. So for most people, if you say, why do you think there's more allergies? It's because we're cleaner. But that doesn't really stack up. In fact, if you look at the data around the world, you'll find that in places like Switzerland, so lowest infant mortality probably in the world, certainly not, you know, very limited exposure to any of these nasty diseases, but actually not a particular high rate of allergy.

2:59So, you know, another hole in that theory. But it's when you look at these different rates of allergies around the world that you start finding other really interesting stuff. and one of the most interesting things for me is if you get a league table of where allergy prevalence is higher and there's not many league tables the uk's top of anymore but allergy is one of them and who's up there with us australia new zealand canada u.s geographically very disparate places but culturally very very similar so it seems that there's something in the culture that's somehow driving allergic diseases well that's obviously a little bit strange we know there's a huge genetic component to this.

3:39But there's loads of other things that are part of our culture, weaning practices, how much antibiotics we use, how likely we are to do a cesarean section on a delivery, a load of other dietary factors, lifestyle factors. And in fact, the thread that runs through all of those things seems to be our gut microbiome. And that seems to be something that's happened in westernized societies. And we've seen this happen in real time in places like Hong Kong, where initially there was a very big difference in the way of living in Hong Kong versus mainland China, where you had almost genetically very, very similar populations, very, very close geographically, but very different lifestyles.

4:18And as we've seen the westernization of China, you've seen the mainland really catch up in terms of the rates of allergy there with what was happening in Hong Kong.

4:26Dr. Karan Rajan: Yeah, I've seen, you know, whilst I can't quantify it with data and statistics and you know maybe you've seen this data but anecdotally when i'm comparing people that i know relatives and family friends and colleagues in india for example where in the 90s and probably early 2000s i would barely know anyone in my family or friends over there who had allergies who had autoimmune diseases who had any reactions or sensitivities to things and i compare that to their children or their grandchildren now, there is definitely a notable increase, again, anecdotally, of people who've got various allergies to common food items, who've got autoimmune diseases, who've got gut problems.

5:10Dr. Karan Rajan: And historically, they didn't have that. And the only change that I could see is the westernization of Indian culture. People are eating more fast food. There are more McDonald's and Burger King chains in India than there were when I grew up there in the early 90s. So probably a change in the gut microbiome affecting their immune system and then their predisposition towards these immune problems. Yeah, there's a lot of evidence. And I think it's worth mentioning a bit of context. Prevalence data for allergies around the world is pretty rubbish. It's going up. No, no, we just don't have good data.

5:45And we don't have good historical data. So it's really hard to compare then with now. and even for now it's really hard to get accurate data about just how much allergy there is around so there's always a risk that because of that anecdote because i agree i mean i've you know i i've noticed certainly you see that when families come from other places to live in the uk they very quickly take on our pattern of allergic disease and prevalence but um my indian colleagues that i speak to i've spent a fair amount of time speaking to the indian pediatric association for example, and there's so much more allergy noise coming from them than there was a few years ago.

6:20They're very clearly saying we're seeing this now in a way that we weren't previously, but then part of that could well be that, well, they're looking for it now. It does feel like when societies westernize, you do start seeing more allergic disease and what data there is seems to support that. So the UK data, which is as robust as you'll get pretty much, does strongly suggest, as you alluded to at the beginning, that we've seen over the last 20 years a doubling in food allergy over the last 20 years or so we've seen um a trebling in the number of visits to a and e with um anaphylaxis a severe allergic disease and when you dig into that data this isn't more adults having allergic reactions to penicillin yeah it's small children reacting to food that is driving these numbers pink panther us here coach and spotify are teaming up to bring music and style together and they want you to be part of it grab your friends and head to the Tabby Tour, hitting cities around the country with live performances from special artists, exclusive experiences, and personalized products.

7:19And discover custom playlists on Spotify, built just for you based on who you are and how you listen. Live your story with Coach. Learn more at coach.com.

7:31Dr. Karan Rajan: Sierra has all the best active and outdoor brands you need. From athletic stuff, like a full court pickup game swish to athletic stuff like a half mile stroll get those steps in and for morning hikes up the mountain trail good pace it's a nighttime ghost choice from the camping chair what a twist whatever level of active sierra loves it all head to sierra or sierra.com for the brands you want at the prices that let you do it all from athletic to athletic sierra's got it So obviously we don't know the discrete answer as to why that's happening. We've got ideas. And one component we're focusing on is the gut microbiome.

8:12Dr. Karan Rajan: People traditionally think about the gut as just this, you know, factory that churns out poop and digestion, but we know it's far more about that. it's the largest immune organ we have in the body, the layer of tissue there that's actually training our immune system and the interaction between the gut, the immune system, the skin, there's so many components which trains our immune system. So what is actually going on in the gut microbiome that is so linked to the immune system? Like why is that such a huge component of why we're seeing disease prevalence go up when it comes to immune related diseases?

8:47Dr. Karan Rajan: What is it specifically in the gut that has influenced all of this yeah so I think two things to set a bit of context so the first is is that the systems involved here that we're talking about are insanely complex and understanding them measuring them studying them is really hard and we are absolutely not infancy of this so the other thing is that we can't really think about especially when it comes to allergies think about the guts microbiome in isolation because we also have a microbiome up our nose in our skin in respiratory tract there's a number of these microbiomes going on so it's not just gut bacteria although certainly that seems to play the dominant part and certainly when we're thinking about food allergies it seems to have a really important role to play in what as an allergist and immunologist we refer to as tolerance so this is this incredible ability of our immune system to identify something and say do you know what we're going to ignore that because it's nothing to worry about and that's what we want our immune systems to be doing when it comes to things like food.

9:48And so this is where what becomes really important is which part of your immune system sees harmless things like food and when. And our current understanding, what's often referred to as the dual allergen hypothesis or the lack hypothesis after a colleague of mine, Gideon Lack, who came up with all the studies that led to our better understanding of this, is the idea that if you can get an infant's gut exposed to large amounts of an allergen very early on, it quickly recognises because the immune system knows it's in the gut. And so what it's seeing is food. It will usually recognise that thing as nothing to worry about.

10:27And it will say, right, to everyone else in the immune system, just ignore this. Don't worry about it. But what can sometimes happen, especially if your skin barrier isn't working properly. And what that means in practice is you've got eczema, which we now know is predominantly genetically programmed. If you've got eczema as a small baby and other people in the household are eating peanut, kissing and touching the baby, so that before that infant has ever eaten peanut and its gut immune system has never had a chance to see what peanut is and know that it's food, it's nothing to worry about. Instead, through the angry skin of the eczema, the immune system in the skin sees peanut, hasn't got any signal from before from the gut to say don't worry about this, thinks it's something new and potentially worrying because it's seeing it through the skin, there was a risk that that child's immune system will make a mistake and think, okay, this is something we need to react to and worry about.

11:21And you get an inappropriate immune response so that when you eat it subsequently, you then react to it. Now, on top of that, overlay the fact that the chances of you making these sorts of mistakes also seem to be related to the bacteria that populate your gut and your skin and not so much which bacteria but what they're producing yeah and there are certain bacteria which we consider some friendly bacteria the bifidobacteria the lactobacillus the sort of things you hear about in the yogurt drinks that everybody wants to put in your food that produce short-chain fatty acids and called butyrate which creates an environment that tends to tip your immune system away from being allergic and inflammatory in nature as opposed if you're not producing much of it or you're producing other certain chemicals that tip your immune system in a different direction towards that so i think

12:05Dr. Karan Rajan: yeah that's it's a good reframe for people to think about the immune system as not just an attack organ but actually something which is training your immune system and actually of being able to recognize what is harmless versus harmful and i guess to your point about the the gut is that processing layer where there's the interaction between the immune cells of our body but then this sort of external colony of organisms, the microbiome, which is also involved in that training process. And, you know, you mentioned about the sort of a weakened skin barrier with eczema or other similar conditions where that can predispose someone to, you know, more allergies.

12:44Dr. Karan Rajan: I guess once a child is weaning from breast milk or formula onto solid foods, that's when you've got the chance to further train the immune system and the gut microbiome. And I assume, unless you tell me otherwise, a diversity of colors, foods, dietary fibers, consistencies, food groups is key to decrease the risk of all of these tolerance issues. Yeah, absolutely right. So there's a couple of really important things are coming through clearly as strategies to minimize the likelihood of food allergy developing. And the one that's got the best evidence behind it is around early introduction of allergenic foods into the weaning diet.

13:25So the idea that you don't delay, as used to be the advice, foods like peanut and egg and sesame, because actually the sooner the infant's gut has seen that food and knows that it's nothing to worry about, you take then the risk away of the infant's skin inappropriately making a bad decision about it. But alongside that, there's loads of emerging data looking at dietary diversity and showing really clearly that there's an association between an increased dietary diversity in the mum and an increased dietary diversity in the infant in the weaning diet and having a lower chance of developing allergic disease.

13:59So we've got to think really holistically here when it comes to allergy prevention and the messages that I try my best to sort of get out to the pregnant mums who are worried about this are firstly, don't worry so much about whether you do or don't eat peanuts or egg or milk or whatever in your own diet because eating a lot of it or a little bit doesn't seem to make much difference. In fact, the best advice is a broad, healthy, diverse diet. That's the best you can do. And when it comes to the infant, not delaying the introduction of allergenic foods, ideally breastfeeding exclusively initially, and then at around six months introducing those allergenic foods, but not delaying peanut, eggs, sesame, tree nuts, things like that.

14:40but then alongside that also paying attention to trying to have as diverse a diet as possible because all of those things i think apart from anything you're if you've got a an eye on the diversity of the diet you're more likely to be including more allergens anyway so i think the

14:52Dr. Karan Rajan: two things go hand in hand so you know obviously in the first thousand days people talk about the first thousand days being so important for seeding the microbiome for young children and that's when the microbiome is going to be most malleable as it will be at any point in someone's life So once that microbiome is established, is there anything we can do? Is there any data to suggest that we can do as an adult to continue to influence the immune system? So say someone has a risk of autoimmune disease risk from a family history or even has established IBD or another autoimmune disease. Is there things they can continue to do even as an adult for their microbiome to manipulate their immune system that way?

15:31Well, my experience comes as a pediatrician and allergist. So our experience has been is that whilst you've got a great window of intervening early, that window doesn't completely close, but it gets harder. And your ability to manipulate your microbiome, it requires larger interventions. And if you look at the most extreme fecal transplants, we many years ago were very keen to do a study where we were looking at peanut desensitization, which was an emerging treatment at the time, and alongside it, a fecal transplant. And needless to say, it went brilliantly until we actually tried to consent the patients and told them what a fecal transplant was.

16:11And that was sort of the end of it. Because once they realized that, you know, we were going to get someone else's poop and put it down a nasogastric tube into their own gut, they were so keen. So that didn't quite happen. But there's been some really interesting work in Australia in particular, sort of harnessing the sort of manipulation of the microbiome using probiotics alongside oral immunotherapy. has shown more interesting results than just oral immunotherapy on its own, but the studies do have their own, their limitations. So this is still an area we're looking at closely. And I think still that there's a frustration that after many years of trying to show simple interventions with microbiome related things, I'll give you my experience.

16:51So I was involved in a study some years ago where we had a huge number, I think there was something like seven or 800 kids around the world, multicenter trial with milk allergic kids. These will children who had for whatever reason were no longer breastfeeding. So they were on hypoallergenic formula. So essentially milk that's been broken down in small bits so that it doesn't upset their immune system because of their milk allergy. And half of them got the regular formula and the other half got the formula that had added to it pre and probiotics. And what we were hoping to demonstrate was that we would, with the pre and probiotics, enhance butyrate production in their guts and, you know, get, get, get a more diverse, happier group of bacteria in their guts.

17:30and that would consequently help them outgrow their milk allergy earlier, reduce the likelihood of them developing other allergic diseases and all other good things. And it didn't make much difference. We did actually demonstrate on the stool samples that you can change the microbiome in what appeared to be a meaningful way, but actually when it came down to, well, was it meaningful clinically, did it actually make a difference? We didn't really show any differences and that's really, really disappointing and frustrating. But then as soon as you're involved in research like that, It makes you realize that when you're thinking about interventions relating to the microbiome, just because your intervention didn't work, it doesn't mean that had you have done it at a different time with a different strain of bacteria or a different amount or frequency of giving that bacteria, that it wouldn't have had an effect.

18:17And that's when you start realizing the level of complexity you're dealing with.

18:20Dr. Karan Rajan: I want to talk about something that's quite personal to me and about some medical conditions that I suffered from. I used to have high cholesterol and fatty liver disease, and that primarily stemmed from a severe lack of fiber in my diet. And on my quest for finding the perfect fiber supplement over the last few years that could help me add more fiber into my diet, I couldn't find one that ticked all the boxes that I wanted and the high bar that I set for myself. So I built Loam Science. What I'm most proud of is not the product. I know that's great, but it's the fact that we've run two clinical trials on it, two randomized controlled trials, which is far more than the vast majority of supplements on the market will ever do.

18:55Dr. Karan Rajan: And we've got even more coming because I'm a doctor first and foremost and a scientist. And I wanted to build something that I could actually stand behind with data and not just rely on good branding. So if you want to understand what's inside Loam Science and why, the science is all on the website and the link is in the show notes. You know, fundamentally, the immune system is the control guard for inflammation, systemic inflammation, as well as localized inflammation. And when you think about the crossover between the microbiome and gut bacteria and dietary fibers, for example, and other dietary components like polyphenols and other antioxidants, they are anti-inflammatory in themselves mechanistically.

19:36Dr. Karan Rajan: They also, as you were saying before, feed certain gut bacteria, which then produce anti-inflammatory short chain fatty acids, which can dampen down and turn down that inflammation and also have a direct interplay with the immune system. And as I've seen in some dietary fiber intervention studies that I've done, but also other published evidence as well, you see interventions with prebiotic fiber supplements or interventions where they've had higher fiber in their diets. not only the objective reduction in interleukin-6, TNF-alpha, high sensitivity CRP, those inflammatory markers go down, but they've been paired with subjective measures, whether it's, you know, quality of life scores or specific inflammatory validated tools, you know, whether it's joint pain or knee pain or anything like that, they've also seen a reduction in that.

20:30Dr. Karan Rajan: So you can almost triangulate the intervention, the objective outcome with the inflammatory markers, and then the sort of clinically meaningful translation, you do often see a significant triangulation of that. So I guess there is something there, but to your point, it's so individualized as well. It is, absolutely. But what's really exciting is I think we're beginning to see the beginnings of what's clearly a paradigm shift in the way that we start to understand disease. And we've certainly, in the allergy space, we've moved away a little bit from seeing asthma and eczema and food allergy and rhinitis as isolated conditions and thinking more in terms of paradigms such as type 2 inflammation, this sort of commonality of underlying mechanisms that involve similar pathways leading to inflammation that have an impact for some people on just one system like the skin but actually for many many people who have got eczema for example they very commonly also have rhinitis or asthma or food allergy.

21:27And likewise, there's a lot of interplay between all of those different conditions. And when we start thinking a little bit more holistically around inflammation, both in terms of diet, which is, you know, we increasingly understand that potential for intervention through the microbiome, but also other avenues as well. And you know, if you speak to big pharma at the moment, you know, these companies that what they're really excited about is the opportunity that if you can identify what's going on in these pathways of inflammation and get in the way of it, this is where biologics are coming in.

21:54And we've seen this huge change in the way that we're managing a whole range of inflammatory disorders over the last few years. It's been a real revolution, which I think maybe we haven't felt in the UK in quite the same way as they felt in Europe and the US because of access to these biologics. But if you run a clinic for severe eczema or a clinic for severe asthma, I can't imagine there's been a 10 years, you know, in history where there's been a bigger difference in what we're doing now compared to 10 years ago. And a little frustratingly, when you speak to patients who come from overseas, whether it's the US or Southeast Asia, places like that, when you hear what's on the table for them pretty much straight away for their inflammatory conditions, it feels a long way away from where we were very recently.

22:41Dr. Karan Rajan: We spoke about children seeing an uptick in all of these allergies and allergic reactions, but we're also seeing unusual and even new allergies developing in adults, you know, be a hay fever or something else entirely is the gut driving that as well and our chronic fiber deficiency dietary changes increased consumption of ultra processed food that's you know high in certain additives which could be changing the gut barrier layer what is what is driving that is it gut related do you think um i i really don't know and i don't think we've got any good data to inform that because um you're absolutely right we we have always seen what we refer to as the allergic march which is people have a history of often eczema and food allergy in early life they've got allergic genes as they get older they start to develop respiratory allergy.

23:26So we've always seen things like hay fever as being conditions that don't develop until you're a little bit older but I think the evidence is pretty clear that we're not seeing any the exponential rise in respiratory allergy that we're seeing in food allergy at the moment. I think the big rise in respiratory allergy has happened and now it's at a very high rate So you're still talking about 20 to 25 % of UK adults having hay fever. This is not a small issue. This is something that affects large swathes of the population. But our understanding of how that relates to diet and whether there's the opportunity for intervention in diet that would then make a difference to that.

24:03We're not anywhere near that yet. Yeah.

24:05Dr. Karan Rajan: And, you know, when we last spoke, you know, about various factors that can influence, you know, the microbiome and also just influence the robustness of a child's immune system. There were so many factors that we mentioned and alluding back to the hygiene hypothesis that you first brought up and how that was dismissed somewhat, but still, I guess, carry some molecule of truth in that we don't want an overly sterilized environment to train the immune system. We want to live a normal life. And to that point, you see possibly differences in how kids are raised in different cultures. There's a video going viral on social media where I saw this Scandinavian nursery where the kids always are playing in the mud.

24:50Dr. Karan Rajan: And presumably they're playing in the mud, but then washing their hands, coming inside. And, you know, that to me says volumes about, you know, the culture over there, but also how it's probably going to be overall a net positive for the microbiome if I had to guess. And I've also been thinking now about my own child. You know, last time we spoke, I didn't have a baby. Now I do. And I'm also trying to apply some of these principles I'm learning about. And that's published in the literature about the microbiome, about immune system. So he's only two and a half months. But as soon as possible, I'm going to start introducing those allergens.

25:23Dr. Karan Rajan: eggs peanut as soon as they're weaning but also you know i live in the countryside now so i've got this non-urban environment which in some epidemiological data suggests it's nurturing the microbiome yeah i've got a dog as well which is again furry animals having furry animals in the house and this is yeah this runs with it's a theme that runs through so many studies that having a dog at home when you're born seems to reduce your risk of allergies yeah so you know i wonder like you know all of these different things the hygiene hypothesis is not the whole picture but there is some truth there that we should still apply to this day where we should not focus on making this immaculate environment where we deny and deprive our children's immune system the ability to learn the ability to work hard and we should provide stimulus not pathogenic stimulus Like, you know, don't give them exposure to dogs, feces and whatnot.

26:20Dr. Karan Rajan: But I think a little bit of normal life, if I can put it that way, is good. Yeah, completely agree. And we often talk about what's called the old old friends theory. So this idea that there's these bugs that we've lived alongside for millennia and they've provided a really helpful synergistic value to us. And, you know, they help modulate our immune system to make appropriate responses. us, yet suddenly over the last 30 or 40 years, we're distancing ourselves from them. Kids are all being born in hospital rather than having always been born at home. Way more antibiotic use, ultra-processed food, changing weaning practice.

26:57All of these things are creating this perfect storm that are changing that relationship we have with these bugs that have always otherwise been there and helped develop to long siders. And now suddenly we're not quite interacting in the same way and to our detriment.

27:10Dr. Karan Rajan: You mentioned before that obviously, you know, we've clearly seen a rise, especially in Western countries of C-section deliveries, whether it's as an emergency or whether it's, you know, voluntary C-section. Yeah, there is obviously a difference in how a child's microbiome will develop, whether their vaginal birth or C-section. But there are more people now advocating for vaginal seeding where they're taking some of the, you know, mucus layer from the vagina and then wiping it on the child as they're born. I can't see any conclusive high quality data about that. But mechanistically, I understand how that could potentially work.

27:47Dr. Karan Rajan: Do you have any thoughts on that? Yeah, I mean likewise, interestingly, and there was a really, really large scale review of risk factors for food allergy that was recently published and notable by its absence was cesarean delivery actually. It's not a major factor. And I think that's the thing is that there's so many potential factors involved and none of them in isolation are that big. They're all little nudges and all of those little nudges one way or the other in terms of your risk of getting allergy have to be overlaid on top of your genetic predisposition. You know, there are some people that you could do absolutely everything wrong in terms of allergy prevention and your child will sail through life with no allergies because they simply don't have the genetics to give them allergies.

28:33Whereas there's other people who, and I have a lot of them in my practice, do everything that modern science tells them they should be doing and they still end up with a child with multiple food allergies and severe eczema. And that's because you can't change your genetics.

28:45Dr. Karan Rajan: Well, that's what I'm trying to rely on here because I think we've got such an abundance of data and evidence and people giving you advice on optimizing this and that. But I'm looking at my family history. Neither of my grandparents and even my wife's grandparents didn't have any allergies. Neither of our parents had any allergies. Neither of us have any allergies. And we're hoping that's mostly good enough to make sure that he won't have any allergies. And on top of that, we layer in all these other things that we've spoken about. Now, something I wanted to ask you, because I genuinely don't know the answer, and I don't know if you have any thoughts on this.

29:15Dr. Karan Rajan: A lot of people use medications like antihistamines for symptom control. They have got a particularly bad allergy or reaction. They use some antihistamines to provide relief for runny nose, teary eyes, and itching and whatnot. That is obviously providing short-term relief, and it's reducing inflammation and the release of mast cells and whatever is driving that symptom initially. but longer term is a reliance on that and dampening down the immune system is that a good strategy long term and is there any long-term risk with that pink panther us here coach and spotify are teaming up to bring music and style together and they want you to be part of it grab your friends and head to the tabby tour hitting cities around the country with live performances from special artists exclusive experiences and personalized products and discover custom playlists on Spotify.

30:05Book just for you based on who you are and how you listen. Live your story with Coach. Learn more at coach.com.

30:14Dr. Karan Rajan: From athletic stuff like a full court pickup game, swish, to athletic-ish stuff like a half mile stroll. Get those steps in. Head to Sierra or Sierra.com for the brands you want at the prices that let you do it all. From athletic to athletic-ish, Sierra's got it. Really good question and I get asked this a lot And, you know, there's a cautionary tale here. There was some data from Scandinavia some years ago that suggested that long-term use of first-generation antihistamines, so things like puriton, chlorphenamine, which we absolutely haven't recommended for some years, but long-term use of those appear to be related to an increased likelihood of dementia further down the line.

30:53So just sort of reminds you that although medicines can be over-the-counter, that doesn't mean that they can't have potentially long-term side effects and somebody needs to be keeping an eye on this. Now, actually, in the same studies, they were able to keep a, you know, have a similar look at long term use of second generation antihistamines like satirazine and loratadine and found none of those links at all. And actually a very, a very reassuring safety signal. But you're absolutely right. Whenever we're treating hay fever, for example, and for some, you know, for many people, hay fever is a slight irritation for a few days a year.

31:24But for an important minority, hay fever has an enormous impact on quality of life. And there's a group of people who pretty much lose their whole spring and summer and cannot operate properly. There were studies some years ago looking at the difference between exam performance in mock exams at Christmas time and public exams that of course, for reasons that remain unclear in UK with the highest rate of hay fever in the world holds its main public exams at the peak of the grass pollen season. So what the study showed is that if you had hay fever, you were 50 % more likely to drop a grade from your mocks to your public exams.

32:00So this is something that has a life impact because people aren't able to, you know, aren't managing it effectively. And in fact, for people who are using the wrong sort of antihistamines like the first generation pyrotons, which we would never recommend for hay fever, they're sedating. They were 70 % more likely to drop a grade. So you can make things even worse for yourself by using the wrong medication. But the whole approach of which is the mainstay of conventional medicine, nasal steroid sprays, over-the-counter long-acting non-sleepy antihistamines will be very effective for most people, but you are just suppressing the effect.

32:32All you're doing is sort of knocking out the impact that the downstream inflammation is having on your cells. So if your symptoms are mild and not overly troublesome, I've got no issue with that because the medicines do appear to be safe. You're not using them that much and the alternatives are much more interventional. But for patients who've got the real deal, people whose hay fever is really unpleasant and recurrent and every year it's getting progressively worse, as it often will do through childhood as their immune system gets more potent. Then increasingly as allergists, we're looking at different ways of trying to manipulate the underlying immune response to do better than just relying on those medications.

33:13And that's where we've spent a lot of time focusing on what we refer to as disease modifying medications. So immunotherapy, otherwise known as desensitization, it's got a lot of names. But the joy of desensitization or immunotherapy is that you're actually genuinely getting to the root cause of the problem. You're trying to change the way that your immune system sees grass pollen or dust mites or cats, and we do a lot of it for food now as well, and reduce that sensitivity so that you don't get that inflammation and release of chemical mediating your immune system in the first place. So you consequently get less symptoms and require less medicine.

33:54Dr. Karan Rajan: Quick one before we continue and something I've been genuinely nerding out on in my chief of science role at Throne Science is poop and pee. You see, most of us are completely blind to what's happening in our guts and urinary health day to day. We often wait until something is wrong, but your body's actually constantly churning out data in your urine, in your bowel habits, in those patterns that most people never track. I'm proud to say that at Throne Science, we're building technology that captures exactly that. Passive, consistent biomarker monitoring of your gut health, your hydration status, your prostate health markers, without you even having to think about it.

34:29Dr. Karan Rajan: From a clinical standpoint, the shift from reactive to continuous monitoring is really important because that is where the early signal detection happens and that's when you can change your habits and hopefully outcomes as well. I've been deeply involved from the science side because I think the research here is serious. And with rising rates of colon cancer, poop talk is no laughing matter. So if you're curious about what that data could tell you, the links in the show notes. I mean, given that we understand a lot of the mechanisms around that and we can plug in medicines at certain points in that sort of, you know, chemistry flow diagram of how allergy and how reactions are forming and how the immune system functions how close are we to making sure that allergies are prevented in the first place from even forming well there's a lot of interest in looking at exactly that at the moment so you look at the big clinical trials at the moment and often they're using things like the approaches that we know help us treatment so the immunotherapy I've just mentioned for example for dust mite allergies if you've got bad dust mite allergy will either inject you or more likely give you tablets made out of dust mite allergen go under your tongue every day have a send signals to your immune system that eventually sort of dampen down the responses and people are thinking well wait a minute why wait until somebody's got bad dust mite allergy why don't we find a load of infants who are at high risk of developing dust mite allergy and asthma and all the things that go with it and do the treatment to them and at the moment recruiting in Southampton and the Isle of Wight and Imperial College is a study doing exactly that.

36:02And it's essentially an asthma prevention study looking at sublingual immunotherapy, which is where you sort of try and get dust mite drops under the tongue.

36:10Dr. Karan Rajan: Why wouldn't that be effective for all infants rather than just high risk? I mean, every child would technically have a risk of developing a dust mite allergy, whether it was, you know, minuscule or higher risk. So wouldn't it be valuable if the side effect profile was virtually nothing to give it to everyone. And layering on top of that, having a pill which had microscopic amounts of every common allergen and giving that as like a sort of panacea almost. Yeah. Well, I guess to the first point, this is a proof of concept. And you're going to have to have a hell of a lot more people in your study if you want to prove it on an unselected population and a much smaller, much more manageable population.

36:47If you get really high risk people who you know that if you didn't make an intervention, 30 % of them are going to get asthma as opposed to 5%. So it's always going to start in these populations. And similarly, you know, the work that looked at food allergy prevention focused on really high risk kids. But then, of course, you have to question, well, can you generalize that? And look, there's been companies that have started suggesting, you know, we're going to make baby food that has a little bit of peanut, a little bit of tree nuts and a little bit of shellfish coming out. But you still need the evidence to justify whether that's going to make a difference because there was a danger here of, I guess, you know, mission creep of suddenly we're starting to medicalise something that shouldn't be medicalised like weaning and early life where with the best intentions we can have, we can lead to unintended consequences.

37:34And, you know, as you all know, medicine is littered with great ideas that somebody thought, well, this is going to be a really good idea. Let's do this as a large scale intervention to everybody. And then it turned out not to be

37:45Dr. Karan Rajan: such a great idea for parents of young children what would be your top advice to reduce their risk of allergies number one would be a bit of education simply you know understand a little bit about the area there's some really good stuff on websites with the big allergy charities allergy UK and Aflaxis UK simply because I think a lot of people worry about things they needn't worry about there's a lot of families where there's absolutely no history of allergy at all they have an infant has no eczema and they put an enormous amount of effort into worrying about weaning their child when actually the baseline risk is really, really, really low.

38:18And that seems a shame because it's such an important time of life to be enjoying and not worrying about, you know, minutiae of what your child's eating. Whereas there's other families where they simply aren't supported to realise that their child, because of their early onset and significant eczema, has a really high chance of developing food allergy and would very much benefit from a more interventional approach. but then beyond that it would be if there is eczema speak to your doctor get some support because increasingly and i don't think we've you know i don't think i could look you in the eye and say we know this definitively but there's very good and emerging evidence that good eczema control during early infancy is a strategy at reducing the risk i mean there is certainly data support that but there's large-scale studies going much more focused on proving that that if you've got significant eczema treating it will reduce your risk of developing food allergy so i'd always advised that's a good idea but also speak to somebody that knows get you know get get more information if your child has got eczema in early infancy because that's where the age of weaning becomes much more important and intervention will have much more value and if there's a signpost if I'm if I'm allowed will be towards the British Society of Allergy and Clinical Immunology so that's my sort of specialist organisation they produced a really nice guidance leaflet for parents that explains the science behind why sometimes we say you You know, yes, you know, if you if you look at the very sensible and evidence based Department of Health advice here, it's exclusively breastfeed ideally, and then around six months, introduce solids and do not delay the introduction of allergenic foods that sometimes in certain children it might be a good idea to be go a little bit further than that and deliberately even earlier introduce these allergenic foods, because it would enhance, it seems to improve your likelihood of avoiding food allergies.

40:05So I think that sort of awareness around the value of early introduction of allergens, thinking carefully about how aggressively the eczema is managed, all worth bearing in mind.

40:15Dr. Karan Rajan: Yeah, I think there are so many easy levers that we can probably do. The number one thing is exposure and diversity, whether that's diversity of environments, diversity of people interacting with the child, diversity of foods. I think that's like the common denominator. You know, diversity generally is good for the body and exposing it to things. And, you know, again, going back to that hygiene hypothesis, it's not quite, you know, your immune system is going to go wild if it is bored, but kind of, you know, it's kind of true. Shepherding it in the right direction. There's no harm in doing that.

40:49Yeah. And a little bit, I think what my grandmother would have said, you know, everything in moderation, a little bit of everything, I agree, is probably a sensible approach.

40:58Dr. Karan Rajan: Well, I'm going to be using my son as an N equals one experiment. Make sure you publish it. Yeah, exactly. But Adam, thank you so much. Yes, again. Thank you. Thank you for being here.