The Peter Attia Drive - #277 ‒ Food allergies： causes, prevention, and treatment with immunotherapy ｜ Kari Nadeau, M.D., Ph.D.

00:00:00.000 Hey, everyone. Welcome to the drive podcast. I'm your host, Peter Atiyah. This podcast,

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00:00:53.260 of the subscription. If you want to learn more about the benefits of our premium membership,

00:00:58.080 head over to peteratiyahmd.com forward slash subscribe. My guest this week is Dr. Keri Nadeau.

00:01:07.600 Keri is the chair of the Department of Environmental Health at Harvard's School of Public Health,

00:01:12.360 a professor of climate and population studies, and the interim director of the Center for Climate

00:01:16.620 Health and the Global Environment. Keri's research focuses on the study of immunologic mechanisms

00:01:22.980 involved in the causes, diagnoses, and therapy for allergies and asthma. Keri earned her MD and PhD

00:01:29.760 from Harvard Medical School in 1995, completing her doctoral work in biochemistry and immunology.

00:01:34.740 She's a member of the National Academy of Medicine and has co-authored the book,

00:01:38.400 The End of Food Allergy, the first program to prevent and reverse a 21st century epidemic.

00:01:45.260 In this episode, we talk about how the immune system works when it comes to fighting bacteria and

00:01:51.940 viruses. Now, you might think, well, what does this have to do with food allergies? Well, of course,

00:01:55.400 it's because the same immune system that correctly helps us fight off bacteria and viruses incorrectly

00:02:02.100 gets wound up when it comes to food allergies. So unfortunately, you do need to understand how the

00:02:06.980 immune system works in the correct way to understand how it can go rogue. So from there,

00:02:11.680 we deep dive into food allergies and we distinguish them from food sensitivity. So I think many people

00:02:16.880 listening to this will have some sort of food sensitivity. And of course, that's also potentially

00:02:21.080 mediated by parts of the immune system. We'll talk a little bit about that. But really what we want

00:02:24.840 to focus on are true food allergies. And this can range from mildly inconvenient to outright life

00:02:30.880 threatening and debilitating. It's really that latter area that we want to focus on. So we talk about

00:02:36.740 early exposure. We talk about what sort of immunotherapies are available. Many people, for

00:02:42.500 example, listening to this will understand that there are certain people that have peanut allergies. If you

00:02:45.860 have a peanut allergy and you don't carry an EpiPen, you can end up losing your life. Well, I wanted to

00:02:50.360 understand why that's happening. I want to understand what parents might be able to do to

00:02:54.860 reduce the risk of that developing in their kids. And of course, for those who already suffer from

00:02:59.960 those things, I want to understand what are the immune-based therapies that can effectively take

00:03:05.620 a person who, in the presence of even microscopic quantities of those allergens, produce a lethal

00:03:12.940 anaphylactic reaction. And how can immunotherapy make those people safer in that presence? And this is

00:03:18.280 the kind of work that Carrie has been doing. And for that reason, I've wanted to have Carrie on for 1.00

00:03:22.540 some time. We also talk a little bit about air pollution, which was a real bonus for this discussion

00:03:27.600 for me. Because when I reached out to Carrie initially, I thought we would only talk about

00:03:31.420 food allergy. But as you may have heard me talk about on previous podcasts, I have a real interest

00:03:35.640 in getting deeper down the rabbit hole of air pollution, specifically PM 2.5s. We go into all of that

00:03:41.600 in this episode. So be sure to stick around for that part as well. So without further delay,

00:03:46.040 please enjoy my conversation with Carrie Nadeau.

00:03:53.920 Carrie, thank you so much for joining me today. I don't remember the last time we were together

00:03:58.280 in person, but I feel like it's been probably eight years or so. Is that possible?

00:04:03.580 I think so. It's been eight years and lots has happened, Peter, especially COVID. So it's nice to

00:04:08.800 see you again.

00:04:10.120 Yeah, yeah. I've always appreciated the amount of time you used to make for me when I used to

00:04:14.640 wander into your lab at Stanford just to pick your brain. Again, I've always thought that the

00:04:19.120 work you were doing was so exciting. And I know that it ties into so much about what people are

00:04:23.500 interested in around food allergies, even to some extent food sensitivities. And I think also even

00:04:29.820 based on your current role, you've now left Stanford, you're at Harvard. I think it's also very

00:04:34.260 interesting to discuss air pollution. I think this is probably something that isn't getting enough

00:04:39.000 attention with respect to health. I know it's something I feel woefully deficient in my

00:04:43.960 understanding, though I try to pay attention to my PM 2.5s. I'm not sure what to do with the

00:04:49.760 information sometimes. So with all that said, let's maybe just give people a really quick

00:04:53.900 background on why you're the person to be talking about this. So you're an MD, PhD. What did your PhD

00:04:59.520 dissertation focus on?

00:05:01.360 Yeah, I was really excited to do my PhD in biochemistry. So I learned a lot about toxicology

00:05:07.700 and biochemistry. And I did my PhD in parasitology, actually. I worked on an enzyme and a parasite

00:05:15.060 called the trypanosome, which causes African sleeping sickness and another disease called

00:05:19.720 Chagas disease. And I loved my work there because we were able to go to the very minute levels of

00:05:26.180 understanding of a chemical entity to be able to create a drug to target that entity to help people

00:05:32.660 with that disease. So it was a great PhD. I loved it. And I also did that at Harvard under Chris

00:05:37.600 Walsh. So that's what my PhD was in. And then I did other work in immunology and animal models as

00:05:43.000 well.

00:05:43.980 And then you're a pediatrician by training clinically as well. What led you then to study

00:05:48.620 the field that brought me to you as a matter of interest a decade ago around the field of food

00:05:54.960 allergies?

00:05:56.080 It's all a build, Peter. And we think of our careers, all of these things mesh, but there are certain

00:06:01.520 nexus points in our careers. And I believe that typically for me, it's been a patient and it's been

00:06:08.000 an inspiration to be able to move forward in a field like food allergy. So I did my MD training also at

00:06:15.000 Harvard and then trained in pediatrics at Children's Boston, as well as at Stanford. And with that, I had

00:06:22.320 the opportunity to become a fellow in a field that I loved, which was allergy, asthma, and immunology. And I

00:06:27.640 had done a lot of immunology work when I did my PhD in parasites because parasites are killed by the

00:06:33.060 immune cells. And especially this little molecule called IgE that tends to kill parasites, but it's

00:06:40.060 not so great for allergies. So this yin and yang of this molecule in biology as an immunologist for me

00:06:46.760 was also really interesting. But fast forward, I was a fellow on the wards and I was about to see a

00:06:55.080 patient that I was being asked to consult on for milk allergy. And he was in the ICU and I was told

00:07:01.580 that he had just drank a cup of milk and had had a bad reaction. And by the time I arrived there,

00:07:07.900 the unfortunate event of his death had already occurred. His parents were already being asked to

00:07:13.800 give consent for him to be a liver donor. And so I took care of the person that was the liver recipient

00:07:20.780 who also had a milk allergy. That really gave me pause. And number one, inspired me and really

00:07:29.580 initiated my efforts in food allergy to understand the role of this molecule called IgE, the role of

00:07:36.480 the immune system, how food allergies get started in the first place. How in the world did a child with

00:07:42.660 food allergy who died then give his same food allergy to the recipient of his liver? So all of these

00:07:49.340 things really started to catalyze my curiosity. And I felt very blessed and lucky at the time to be able

00:07:55.780 to be in a lab. And when you're a person that has this training, I feel that we're obligated in a way

00:08:02.420 to be able to use that training to best help mankind and to best help those questions that parents ask us.

00:08:10.380 And so at the bedside of this particular young child that had died, unfortunately, due to a milk

00:08:16.620 allergy, I'll never forget his father trembling, asking why the EpiPen didn't work at the time.

00:08:24.260 What can we do to help children in the future never have to die again? And so I promised that

00:08:30.820 father that I would do the absolute best to prevent further deaths in children and adults with food

00:08:37.900 allergy, as well as help really make sure that we educate about the use of injectable epinephrine

00:08:44.240 and how to best use them to prevent deaths to food allergies. So that's my why. And ever since

00:08:52.360 then, I've always wanted to really help out in this field. It would be impossible, I think, for us to

00:08:57.020 have this discussion at the level of depth that I hope we can have it without the listener understanding

00:09:01.640 how the immune system works under normal circumstances. You've already alluded to one of

00:09:07.080 the immunoglobulins, IgE. Does it make sense, you think, to talk about the family of the

00:09:13.060 immunoglobulins, what they're there for, how we acquire them, and how they normally serve us well?

00:09:18.680 Sure. So we have certain proteins in our blood that help protect us. And that's what they're meant

00:09:27.540 to do. And that's great. And they exist in different concentrations. Just like in a milkshake,

00:09:33.780 you have different proteins that exist in different concentrations. And they're all there for

00:09:37.540 nourishment purposes, sometimes for taste too. But in our blood, the proteins in our blood that

00:09:44.440 constitute immunoglobulins are really helpful. We learned a lot about how important immunoglobulins

00:09:49.700 were to protect against COVID, for example. Everyone wanted to know their quote-unquote titers. And what

00:09:54.540 that means is immunoglobulin. So the main class, IgG immunoglobulin, those are very protective. Those

00:10:04.240 are proteins that are in high amounts, and they float in our plasma. And in order to be really healthy,

00:10:12.080 when we are healthy, we have healthy amounts of immunoglobulin to protect us. The minute that

00:10:16.960 someone is maybe what we call under a drug like steroids or under other drugs that could affect your

00:10:23.820 immune system, that also reduces the amounts of these immunoglobulins. So we know that these

00:10:30.120 immunoglobulins are really important. It's important to have good concentrations. Not too high,

00:10:34.860 but good concentrations. And immunoglobulins in general help protect us against infections,

00:10:39.680 and they also help protect us against allergies. Then there's another complementary immunoglobulin suite

00:10:47.800 that doesn't just stay in our blood. It also gets into our organs, because you want to protect

00:10:54.400 all of the surfaces around your organs as well, not just in your blood. The blood is great. That's the

00:11:00.100 highway into so many organs. But in addition, it'd be nice to have some immunoglobulin protective

00:11:05.000 molecules that actually sit around your organs and help. So for example, that class is called IgA.

00:11:11.900 The other class was IgG. This class is IgA. And we call that the secretory class. And that's also

00:11:18.660 helpful in our saliva, in our gut, especially women who are pregnant, they secrete it after pregnancy in 0.99

00:11:25.780 their breast milk. So these are things that we've learned as immunologists that really help protect

00:11:30.140 and enable health. When people are missing IgA, for example, if they don't make any IgA, they actually

00:11:36.820 have allergies. And the other immunoglobulin class that I'll talk about is called IgM. And IgM is what

00:11:45.840 I call the marines. That is the type of immunoglobulin cell, IgM, that goes out their first call. They're

00:11:54.540 there to fight infections, but then the immunoglobulin G proteins come in afterwards and they stay for much

00:12:00.900 longer. IgMs don't stay for very long. The final class is IgE. So IgE, unfortunately, in the past, 0.97

00:12:09.540 when we were in the field and fighting animals and being out there in the wild, IgE was very hopeful

00:12:18.060 to fight parasites, for example. It was very specific to parasites. And now, unfortunately,

00:12:25.040 IgE still exists in our blood. It represents 0.005% of all the immunoglobulins in our blood. So of all

00:12:35.500 those classes, the IgE is the least represented. It's the least concentrated, but it is unfortunately

00:12:43.100 the most potent. And I call it the match that lights the fire behind allergies. And you think,

00:12:49.320 well, why do we have such a skewed response? Why do we still have this prehistoric molecule

00:12:54.780 floating around in our blood that truly all of us consider a bad actor? And we think it's because

00:13:01.020 of that prehistoric need to fight parasites. But importantly now, fast forward thousands and

00:13:06.920 millions of years, it's still there. And it unfortunately has a skewed response in allergies.

00:13:13.800 So maybe just explain a little bit more about what the immunoglobulin does. Let's just talk about

00:13:18.660 through the lens of an infection. So what happens when you get a bacterial infection? And what happens

00:13:24.400 when you get a viral infection? Those are two sort of different things, but yet they both kind of still

00:13:28.520 involve immunoglobulins, even though we think of one of those threats, the viral illness being more

00:13:34.480 dealt with through the cellular immune system versus the humoral. Maybe even you can explain what

00:13:39.080 cellular versus humoral immunity mean. So in general, what I'll explain today is how our immune system

00:13:45.120 fights a virus or a bacteria or a fungi. But there's always some exceptions to the rule,

00:13:51.080 but I'll just talk about the general pathway. And that, I think, helps people conceptualize what

00:13:55.960 happens. And I'm always amazed at the immune system, and there's a lot we still don't know.

00:14:01.020 So in all humility, as an immunologist, I learn every day what I don't know about the immune system.

00:14:06.660 But what we do know is that when something attacks us, like a virus, like a bacteria, like a fungi,

00:14:13.140 that enters into our lungs, our gut, our nose, those unfortunate microbes, they know how to get into 1.00

00:14:22.160 our body. So they get into our body, and they go through either the skin, or they go through other

00:14:29.520 organs. And then on the other side is waiting for them a whole panoply of immune cells ready to attack.

00:14:38.040 And so if a virus gets in through the body, now typically it doesn't. We try to fight it right

00:14:45.340 away, but sometimes it does. And so let's say a virus or a bacteria or a fungi gets into the body,

00:14:51.480 gets through our typical first layer, like a skin barrier, and it gets through. Then right away,

00:14:59.280 we have these cells called macrophages, and they literally just eat up things. So they bind on to the

00:15:06.240 virus or the bacteria or the fungi, eat it up, and then eat it up into small little bits. And then

00:15:12.100 they expose those small little bits on their surface. And then with those small little bits

00:15:17.640 on the surface, they actually then become the educator pieces for another group of cells called

00:15:24.540 the T cell. And that's what we call the cellular system, macrophages, antigen presenting cells,

00:15:31.500 these little bits are called antigens. And then the T cell comes along and says, huh, that's

00:15:36.900 interesting. I'm going to teach myself the T cell. I'm going to teach myself how to operate within

00:15:43.780 these little antigens. What are these things? How do I train the immune system to get rid of this thing?

00:15:49.740 So then the T cell says, all right, I'm going to start to understand what this new organism is that

00:15:54.500 just attacked my body. And I want to fend against that. I don't want that bacteria or that fungi or that

00:16:01.000 virus in this body. So the T cell becomes what we call a memory cell. A memory T cell then teaches

00:16:08.140 another cell called the B cell. The T cell interacts with the B cell. The B cell then starts to make

00:16:16.380 immunoglobulins. And that B cell makes the immunoglobulins thanks for the teaching cell to

00:16:23.200 train that B cell to make the immunoglobulins for the exact little antigens that that virus made or that

00:16:30.720 bacteria made or that fungi made. So you have this little B cell. B cell makes these immunoglobulins

00:16:37.420 and then they bind to the antigen. Now you have specificity in your cellular and your humoral immune

00:16:45.760 systems. So the humoral comes from these antibodies that float in the blood. And that's what we call the

00:16:52.120 humoral immune system. It's not attached to a cell, but it was made by a cell. So those humoral related

00:16:58.300 antibodies attached to the antigen and then another cell, again, back to that macrophage eating

00:17:05.900 cell, that macrophage then recognize this whole system. And we call it antibody dependent cell

00:17:14.040 killing. So now that the antibody recognizes this virus and it recognizes all the viruses that maybe

00:17:20.380 you had across your whole gut or across your whole lung for that one specific virus, it recognizes as foreign.

00:17:26.660 And then these other cells called the macrophage come back again and they chew the whole virus up and

00:17:34.240 eliminate it from your body. So that's a long system. I just talked about things that take days to respond

00:17:43.120 to, months to respond to. And it took many years of science to figure that whole pathway out. This is not

00:17:50.980 something you learn at the bedside with some story your mom tells you. This is a lot of science. And that

00:17:57.740 science has allowed us to understand the immune system to, number one, provide vaccines to people.

00:18:04.800 Because of the same system, we now know how to make immunoglobulins because of our vaccines. And we know how

00:18:11.000 long they can last for. These memory T cells, for example, can last up to 100 years. So I love the cellular

00:18:17.880 humoral part of the immune system because it's very instructive to fight microbes. Unfortunately,

00:18:23.960 it doesn't fight all microbes. Some microbes need a little help with antibiotics, with antivirals. So

00:18:31.200 the story that I showed you today isn't perfect. So that's why you need to see the doctor. You need to

00:18:36.920 have other medicines, for example, to try to help your immune system fight infections because there's

00:18:41.740 holes in the immune system and we need to help it. Why do you think our immune system is on balance so much

00:18:48.080 better at fighting viruses than bacteria, at least in terms of the clinically relevant ones? In other

00:18:53.020 words, very few people will take an antiviral drug in their life outside of, you know, a handful of unusual

00:18:58.880 circumstances. Most people will go through life with their immune system doing a very good job of lopping off the

00:19:05.980 head of two to three viruses a year that actually reach the threshold of clinical significance. And yet most

00:19:12.380 people don't go more than two or three years without actually requiring an antibiotic to aid in the

00:19:19.660 destruction of a bacteria. Do you have a sense even teleologically why that's the case?

00:19:25.960 This is an excellent question teleologically as well as from an evolutionary point of view,

00:19:30.880 as well as really understanding how did viruses start in the first place? How did a bacteria start?

00:19:35.980 What do they need to grow? From the perspective of the virus, why do they need us? From the perspective

00:19:41.720 of bacteria, why do they need us? Same thing for fungi. So when you think about a virus, they kind of

00:19:47.600 flit from one organism to the other. They sometimes can exist out in the wild. They don't necessarily need

00:19:54.040 us. But sometimes, like HIV, it needs some of our cells to be able to live inside to be able to keep

00:20:01.120 proliferating. So I'd say in general, there are some viruses that are, of course, very severe and they can

00:20:08.820 cause fatal disease. So on the spectrum, like you said, Peter, typically though, viruses aren't as bad

00:20:17.180 as bacteria. We don't typically need an antiviral because we can fight viruses. It's a great question

00:20:23.820 though, because viruses can mutate in our body like we saw with COVID. And then all of a sudden,

00:20:28.880 we can't fight them as well. But our body, because we make things like mucus, that we have fevers,

00:20:37.980 that we have these immune cells that are really programmed to attack quickly, they can chew up

00:20:43.940 the viral proteins much better and much more easily to destroy a virus. Because a virus is really,

00:20:51.440 relatively speaking, compared to a bacteria, it's very simple. So it doesn't take a lot for the immune

00:20:58.860 system to say, listen, didn't take me a lot of energy to wipe that out because that virus is made

00:21:04.420 out of simple things. It's basically like made of really simple Lego blocks. But then you have the

00:21:10.040 bacteria that's made of an enormous amount of Lego blocks. And it is much harder to destroy that.

00:21:16.500 Same thing with fungi. They are much more complex organisms. They're made of many different

00:21:21.940 materials so that it's harder for our immune system to kill every piece of the part and get

00:21:27.240 rid of it. So there are certain viruses though, that we still get infected with, but that they don't

00:21:33.320 cause fatalities. So they've learned to kind of use us and then move on because they want to just

00:21:38.960 keep proliferating, but they don't necessarily stick around for our immune system to kill it. They just

00:21:44.120 keep being contagious. So viruses are much easier at hopping from one person to the other. Whereas

00:21:50.340 bacteria, that's not so easy because they're heavier. It's harder to take a bacteria and give

00:21:56.060 it to another human. With bacteria, I also think that we have this bimodal relationship. And I want

00:22:02.420 to make sure all your viewers know that there are some bacteria that are actually really good.

00:22:06.660 We don't know any viruses in particular that are actually good and beneficial for us,

00:22:11.120 but our body lives with bacteria. So I think our immune system has a little tougher time to know

00:22:17.860 what is this? Is this a good bacteria or is this a bad bacteria? So that's maybe also why it's easier

00:22:24.420 to kill viruses than bacteria. We've learned to be tolerant to certain bacteria, but not others.

00:22:31.280 And some of them escape our immune system if they are bad bacteria, because they know

00:22:35.840 that we have this tolerance to other bacteria that are in the same class. But it depends on where that

00:22:41.560 bacteria is. It's totally fine if this bacteria is in your gut. But the minute it gets into your blood,

00:22:47.480 if it's the same bacteria, it's actually really dangerous. So that's where our immune system has

00:22:52.380 to figure out, is this a bacteria in the gut? I'm okay with that. Or is this bacteria in the blood?

00:22:58.020 I'm not okay with that. And bacteria tend to divide so fast, just like viruses, that for both

00:23:04.680 virus and bacteria, these are difficult. But when we talk about vaccines, we luckily have used science

00:23:12.260 for both bacterially-mediated diseases as well as viral-mediated diseases. So it's really thanks

00:23:19.200 to vaccines that we've enabled the immune system to get boosted for both types of infections. But it's

00:23:25.680 always hard to predict mutants, to predict different infections that one would have. But I think that

00:23:32.540 your question is an excellent one. I don't have all the answers.

00:23:35.580 It's funny. I think there's an analogy there with cancer, which is what makes cancer so challenging

00:23:40.060 for the immune system is that it's basically self. And it's very good at masking its non-self

00:23:47.480 entities. So even though it's genetically distinct from a non-cancer cell, it's very good at hiding

00:23:54.120 the neoantigens. Sometimes they're not even coding proteins. In other words, sometimes the mutation

00:23:59.780 in the cancer cell doesn't lead to the generation of an antigen, and therefore it can go completely

00:24:04.520 undetected, masquerading as self. Exactly. And that's the sad part about cancer,

00:24:10.360 that our memory T cells that are supposed to be there to protect us and monitor and make sure that

00:24:16.440 any cancer cells could be killed right away. Sometimes it's faked out in a way. And that's where I think

00:24:22.980 the CAR T cell therapy, a lot of the T cell mediated, immune mediated therapies now can enable and better

00:24:29.500 instruct our immune system, but that's not perfect either. So you're absolutely right, Peter, this

00:24:33.860 yin and yang of having the immune system do all that it can, but we can't expect so much. And one of

00:24:42.420 those areas in order to help our immune system, we found in COVID, for example, people that slept

00:24:49.480 better, people that ate a healthy diet, people that exercised in general, their immune system was

00:24:56.740 healthier. So I think when we talk about these public health issues and COVID kind of was the

00:25:02.140 x-ray into our soul of public health and public health processes, but in that we learned a lot about

00:25:08.160 what it takes to be healthy and what it takes to have a healthy immune system to better fight viruses

00:25:13.220 and microbes. I'd like to actually come back to that because it's such an interesting topic.

00:25:17.240 Like it's one of those things where it seems obvious and self-evident that all of those things

00:25:21.560 are true. I think I would also add stress to that. I think it's hard to understate the harm

00:25:27.760 that hypercortisolemia and a ramped up sympathetic system have in the immune system. If we have time,

00:25:33.720 I'd like to come back to that and probe a little bit about what the mechanisms are for that.

00:25:38.080 But what I really want to get to is now pivoting to this idea of what a food allergy is.

00:25:42.900 And I think it would maybe be a good idea to differentiate between a food sensitivity

00:25:47.320 and an allergy. Is that the right terminology that you would use?

00:25:51.780 Yeah, that's excellent. So for a lot of my patients, this comes up all the time. And I am

00:25:58.320 inspired by how much knowledge my patients have. They come to the table or they don't come to the

00:26:03.120 table with knowledge already that they received from the internet or podcasts such as yours and others,

00:26:09.040 as well as just reading in general. And finally, asking questions is so important. If you don't

00:26:17.800 know something, feel free to ask your doctor these questions. This is critical or a healthcare provider

00:26:22.740 or anyone. But I've always been really interested in this difference between food sensitivity and

00:26:28.340 food allergy. So food sensitivity means that you can bite a food and you're typically going to react

00:26:36.780 to a chemical in that food. Perhaps a protein, but it's mostly a small molecule, maybe a sugar,

00:26:43.460 maybe a fat, maybe a spice. And with that, people can get headaches. People can get bloating.

00:26:52.280 Typical food sensitivity is lactose intolerance. When you drink milk, for example, one of the sugars

00:26:57.840 in the milk is called lactose. And if you don't have an enzyme in your gut and in your body called

00:27:04.200 lactase, you can't break down that sugar. And so that's why people take lactaid milk, for example.

00:27:10.780 And there are some ethnicities that don't have that enzyme. So there is a bunch of people that

00:27:15.800 in a certain population really can't drink cow's milk because of that lactose sugar. So that's a food

00:27:21.320 sensitivity. People get bloating, people get headaches, but they're not going to have a fatal reaction.

00:27:27.900 And just to be clear, Carrie, the immune system is not reacting at all in that state of a food

00:27:35.380 sensitivity.

00:27:36.880 It can react. When you have enough lactose and you keep drinking lactose and your body says,

00:27:42.640 I don't like this sugar. Why are you keeping giving me the sugar? I can't break it down.

00:27:47.520 What happens is it sends its immune cells to try to break it down and that causes inflammation.

00:27:53.380 So some people, when they take preservatives as well, certain emulsifiers, these chemicals,

00:28:01.500 they can get into the body and our immune system doesn't like it. It's foreign. A lot of our

00:28:07.560 preservatives and unfortunate emulsifiers, it hasn't been seen by the body before. It's not

00:28:12.440 something that's natural. So for some people, their immune system does react, but it reacts with a

00:28:19.020 different pathway than an allergic pathway. It reacts with sometimes immunoglobulins,

00:28:25.500 IgGs. It reacts with something called a cytokine that isn't great because it causes chronic

00:28:32.680 inflammation. So we do have some chemicals that are associated with food sensitivities that can

00:28:39.360 activate the immune system in a way that's not great for the human body. And so that's why if someone

00:28:47.000 does have bloating or headaches, or they can still have rashes for food sensitivity, you can still

00:28:53.020 have rashes in your skin with certain chemicals that you eat in foods. And if that's happening to

00:28:58.240 you, then get yourself tested because we want to make sure it's not a food allergy. But importantly,

00:29:03.800 as we don't have cures or therapy for food sensitivities, we often will tell people,

00:29:08.520 please avoid that food. Like I have someone that has terrible bloating with mushrooms because it's a

00:29:13.500 certain chemical in the mushroom that bothers her immune system. Why? I don't know. But the minute

00:29:19.780 she even smells the mushroom, she gets this immediate reaction to her gut that causes her to vomit. But it's

00:29:28.140 not a food allergy. It's an intense reaction of the nervous system to that food chemical.

00:29:34.680 Sometimes we see people who have kind of a low-grade elevation of their C-reactive protein.

00:29:40.320 And we really like to see the very sensitive version of that below one. You'll see these

00:29:47.180 people that otherwise seem reasonable, but their C-reactive protein is somewhere between two and

00:29:51.740 three. So it's two to three times higher than it should be. And it lingers in this state for a very

00:29:56.740 long period of time. There's clearly no infection that's been brewing for that long. You query them a

00:30:02.120 little bit more and you sort of realize that it might be attributed to food. And I would say in my

00:30:06.320 experience, the two foods that far and away account for the majority of this, as determined by simple

00:30:14.260 elimination and watching this go away, are first wheat-related products and secondly, dairy. So

00:30:21.320 when I say wheat, I don't mean celiac disease, which I'd like you to explain as a contrast, but rather

00:30:27.400 some sort of low-grade sensitivity. And so what you're saying is there's nothing going on in the IgE

00:30:33.320 pathway, but there is something going on in the IgG pathway. And again, C-reactive protein is made by

00:30:39.780 the liver as basically a calling sign to the immune system. You're sort of seeing, for lack of a better

00:30:44.740 word, you're seeing the sirens going constantly, which is CRP.

00:30:48.920 We can measure what we can measure. And CRP has been around in our doctor's handbag for a while. And

00:30:55.280 it's actually a really good beacon, like you analogized, because it does tell us something's

00:31:01.240 going on there. And it is a window into what's going on chronically in the immune system. So yes,

00:31:07.780 when I test the CRP levels in my patients with food sensitivities, and they're not able to eliminate

00:31:13.900 that specific chemical, then I see the CRP in that range where I call it simmering immune

00:31:21.120 inflammation. It's not a fire, but it's simmering. And the problem with food sensitivities is I don't

00:31:26.800 have a great way to diagnose them. I don't have a skin test. I don't have an IgE test. I have to do

00:31:32.840 elimination. And then I follow that CRP level until it can try to get to zero. But that's not easy

00:31:38.000 because some of these chemicals are so systematically in our food supply that it's hard to get rid of. So

00:31:44.320 that's food sensitivity. And I agree with you. Milk and wheat are some of the most associated

00:31:52.480 culprits in food sensitivities, especially in the U.S. And that might be for a lot of different

00:31:56.680 reasons in terms of how we process and how we have detergents in our milk. And the same thing

00:32:00.360 with our wheat products. It isn't necessarily the same wheat that we ate when our ancestors ate it

00:32:04.920 originally. So maybe there's a lot of reasons for that. But let me bring it to wheat. This triangulation

00:32:10.880 of food sensitivity, celiac versus food allergy, and we'll get to food allergy. But let me just

00:32:17.180 transpose this interesting comment you made about food sensitivity versus celiac. So celiac is a very

00:32:24.180 specific type of food sensitivity. And it has a very marched out pathway of immune reaction to that

00:32:33.280 wheat. And that wheat protein and specifically is the gliadin, which is a part of the wheat. And celiac

00:32:40.420 also has genetics associated with it and other autoimmune disease with it, as you know. But that

00:32:48.180 reaction is to a very specific part of the protein of the wheat. And not everyone with a food sensitivity

00:32:53.760 to wheat has celiac. And certainly not everyone with celiac will have the same type of reactions to

00:33:00.260 wheat as the food sensitivity people do. Now celiac we take extremely seriously because it can result

00:33:07.900 in long-term problems with your gut. It has its own special category. But you shouldn't call yourself

00:33:16.240 someone that has celiac just because you have a food sensitivity to wheat. There's a specific diagnosis

00:33:22.400 that needs to occur with a professional that specializes in gastroenterology or in celiac to be

00:33:30.140 able to know if I truly have celiac disease. And if you do, then it's important to test family members and

00:33:36.420 to really get under the care of a good doctor. Are we seeing any increase in the prevalence of celiac

00:33:42.340 disease? Or are we seeing any increase in the prevalence of food sensitivities? It certainly

00:33:47.940 seems like it as a non-epidemiologist who pays attention only to the world around him. But it seems

00:33:56.300 like more and more people are saying, boy, I'm really struggling to eat. Fill in the blank.

00:34:02.220 On one side, I think that people are becoming more knowledgeable about this. And they also feel

00:34:09.600 they have agency, as they should, when they come to the doctor to be able to say, I think I have a

00:34:14.720 sensitivity to this food. And people take them seriously. And that's good. And we need that because

00:34:20.160 these symptoms are serious. They're affecting someone's quality of life. We need to help. And in the

00:34:26.240 past, maybe they were poo-pooed and said, oh, I can't help you. So I can't do anything about that. 0.99

00:34:30.980 But now people like you and I can say, well, let's test that CRP. Let's see if we can be better

00:34:36.640 detectives and really try to help you. Because in the end, we want to help quality of life.

00:34:41.420 So yes, people, I think, are feeling more and more like they can talk about it as well as celiac

00:34:45.580 disease. But importantly is we have better diagnostics. So I think that we as a community have gotten

00:34:52.780 better at really diagnosing celiac. So I think that's another good reason why there might be

00:34:58.620 more people with it. I think people also are seeing an increase in food sensitivities and celiac

00:35:03.860 because of the different ways that weed is processed, because of the different detergents now

00:35:09.240 and unfortunate chemicals that are put into our foods. So I think we have to be careful about that.

00:35:15.120 And hopefully the food industry and agriculture will think carefully about those chemicals before they

00:35:20.340 put them in because I've seen an increase. And when I tell people to not eat foods with those

00:35:26.900 chemicals in them, they tend to not have food sensitivities. So I think that perhaps, and I'd

00:35:33.200 be interested in your comment too, Peter, that might be one of the reasons why there's more food

00:35:37.460 sensitivity, although I can't put my finger on it. I feel like there's something going on. And I know

00:35:41.440 we're going to talk about this also on the food allergy side, where I think we can probably speak with

00:35:47.580 more clarity. Let's now talk about that because I think this is the area where, let's just start

00:35:52.460 with some statistics. Do you have a sense of how many people in the United States die in a year as

00:35:57.820 a result of a food allergy? Like the tragic story you told? Yeah, thankfully it is extremely rare.

00:36:05.380 The reason why I hedge is because nowadays with the codes and the emergency rooms and understanding if

00:36:12.000 someone died from a food allergy, some emergency rooms, some intensive care units, they're able to

00:36:17.420 ascribe or attribute a certain reaction exactly to a food. Sometimes it's a little blurry. So it is

00:36:24.680 very rare. There are people around the country in Michigan, as well as in Chicago, that are

00:36:30.120 epidemiologists. I am not an epidemiologist, although I love to work with epidemiologists.

00:36:35.060 So it is very rare. People have claimed that it's one of the reasons why people can have a fatal

00:36:42.120 attack is because they don't have access to an epi device or they don't have anticipatory guidance for

00:36:48.520 what to do during a reaction. So in my mind, any fatal reaction could have been avoided. And that's

00:36:54.400 what I learned from that case. Even though the fatal reactions are rare, and that's good, they can be

00:37:00.940 avoided. And when we learn about them, and I learn about one per month in the U.S., and it's very sad,

00:37:07.700 every one of those stories comes with a tragedy that's heart-wrenching. But it compels me to keep

00:37:16.140 training my patients on making sure they have two injectable epinephrine devices at all times,

00:37:21.260 making sure they know how to use it within a minute, making sure that if it doesn't help their

00:37:24.860 symptoms within a minute, that they use another right away, that it's okay to use an injectable

00:37:30.320 epinephrine device, because that's the only thing that can actually prevent the unfortunate death.

00:37:35.640 And so I think the numbers right now in terms of death rates are getting lower, which is good,

00:37:41.900 because people are understanding more about this disease, and the communities understand that, why

00:37:46.480 we don't want to expose people unnecessarily to foods that could kill them.

00:37:51.020 But in addition, there are increasing incidence and prevalence of food allergies in general in the U.S.

00:37:57.840 So, for example, my colleague Ruchi Gupta out of Chicago, she published data that one in every 12

00:38:05.400 children in the classroom in the U.S. has a doctor's diagnosis of food allergy. And we used to think that

00:38:13.100 children would lose their food allergy, especially those with milk and egg. So it used to be thought,

00:38:18.600 even when I was training, that children with milk and egg allergies, if they were under the age of five,

00:38:22.760 there was like an 80% chance that they would lose these allergies by the time they were teenagers.

00:38:27.520 But if it was peanut or any kind of tree nut or shrimp or fish, they had an 80% chance of keeping it.

00:38:34.400 Now, unfortunately, if you have a milk or an egg allergy and you're under the age of five,

00:38:38.540 you have a 50% chance of losing it. So now we see more and more adults having food allergy.

00:38:45.540 And the other unfortunate thing, Peter, is that more adults when they get to adulthood are getting food

00:38:53.440 allergies. That's presumably about one in 30 adults will have some type of food allergy when they're an

00:39:03.840 adult, whether or not that's because they had it when they were children or because they gain it newly

00:39:10.160 when they're an adult. So the numbers are rising. Luckily, the death numbers are not,

00:39:16.760 but someone needs to do more research on that. But this compels me as a food allergist to really

00:39:22.740 make sure that both children and adults understand this disease and how to manage it.

00:39:27.460 So let's talk about how this occurs. Unless it varies by food, can we just pick a very specific

00:39:32.580 example like a peanut? That's great. We talk about peanuts in the U.S., Peter. I also want to get

00:39:38.800 back to your original question about the incidence and prevalence of food allergy. It's occurring

00:39:42.080 throughout the world. It's not just a U.S. problem. So peanut is also not just a U.S. problem. It's

00:39:47.760 the U.K. and Australia, but not in Italy, for example. In Italy, hazelnut is number one in terms

00:39:54.580 of the sheets. In Japan, it's fish. In China, it's milk. So we can talk about peanut today because it's an

00:40:01.620 example of how our immune system reacts to something, but it's a very similar immune reaction to

00:40:06.360 a child in Japan who has fish allergy or a child in China who has milk allergy or an adult in Italy who

00:40:13.440 has hazelnut allergy. I've seen a spectrum of allergies. I've seen people that have allergies

00:40:18.420 to cinnamon. I've seen people that have allergies to orange pit seeds. All of these have proteins in

00:40:24.200 them, so people can actually become allergic to these proteins. People have allergies to the tannin

00:40:29.180 proteins from grapes in wine. So I'll tell about the story of the peanut, but I want people to know

00:40:35.880 that it's not just about peanuts. And many people that have allergies to one food have allergies to

00:40:41.220 other foods. So people also need to know that if they have a child with a food allergy, expect that

00:40:48.380 it's highly likely that that child will develop another food allergy as well. So be super careful,

00:40:53.800 but also super vigilant about taking your child or yourself to the doctor to keep on getting managed

00:41:00.360 and diagnosed. So you have a peanut. And we think that one of the reasons why people start to have

00:41:08.160 food allergies, it's not genetic. 70% to 80% of the time, it's environmentally related. It's not related

00:41:15.160 to genes in the family. So when a baby is born, perhaps their skin is a little rough and a little dry,

00:41:24.520 dry. And there might be microscopic holes in that skin. And that happens a lot now. A lot of children

00:41:30.560 have dry skin, and we can talk about that another time. But with that little dry skin, that means the

00:41:36.000 cells, my two hands here are cells called epithelial cells. They're skin cells that typically are connected

00:41:42.380 and then with a nice, beautiful barrier. But unfortunately, the dry skin, they kind of separate.

00:41:47.940 And our body doesn't know how to deal with this separation too well. It thinks it's like a mosquito

00:41:54.620 bite. It's like, what the heck's happening? I have a little hole in there. And so it reacts to these

00:42:00.600 types of holes as if it was a mosquito bite. So all of a sudden in the air, you have dust that might

00:42:07.820 contain hazelnut protein, or in this case, peanut protein. And that comes settling in, and it goes

00:42:14.360 through this hole. And our body has a very prehistoric way of dealing with this, back to

00:42:20.920 those parasites. So it comes in by just passive aeration. It drops down on the skin. The body

00:42:29.820 tries to pick it up, and it tries to sense this, just like I explained in terms of the immune system.

00:42:34.720 Those macrophages are like, what the heck is this? Is this good or bad? And then it says, wait, this is

00:42:39.920 bad. I'm not supposed to have food through my skin. I'm supposed to have food through my gut.

00:42:44.980 So the cell takes it up and activates the allergic pathway because it thinks it's a parasite. It thinks

00:42:53.880 it's a mosquito bite. So what happens is it takes it up and makes this molecule called IgE from that

00:43:02.780 B cell. So the food gets taken up, gets processed. It teaches a T cell to interact with that food

00:43:11.240 antigen. And then the B cell starts to make IgE against that very same food antigen. So the next

00:43:18.000 time that baby eats that peanut, even if it eats it through the gut, that little IgE molecule will have

00:43:26.420 been made by the B cell. And it's sitting around in the blood. And then it will bind to the peanut

00:43:32.260 protein that the baby eats. And when it does, even though, like I said before, the IgE is a very

00:43:39.080 small percentage of the concentration of proteins in the blood, it is such a potent molecule. And what

00:43:46.780 I call it, it's the match that lights the fire behind allergies. So you have this peanut that otherwise

00:43:53.120 for you and me, Peter, we would be able to eat and we view it as nutritious. But in a person with a

00:43:59.100 already given allergic reaction to peanut, that IgE binds to the peanut, and then this part of the

00:44:07.980 IgE molecule, my arm, that sets into another part of a cell as a receptor. So it docks into the receptor

00:44:18.120 after it binds to the peanut. And then that receptor on the cell surface activates histamine release of the

00:44:26.940 cell. And that occurs within minutes. So the histamine goes through the body and within six

00:44:32.940 minutes causes swelling, can cause mucus. And that mucus can be in your lungs, can be in your eyes,

00:44:40.380 can be in your nose. And it also releases histamine. That cell releases histamine. And that histamine can

00:44:46.420 cause itching on your skin. Very similar. So what would happen if you got a mosquito bite? You want to

00:44:51.800 itch. You want to get rid of that mosquito. In the same way, the body's trying to get rid of that food.

00:44:57.480 But unfortunately, you've already eaten it. It's already in your body. And so you see these reactions

00:45:03.400 via IgE, and they release histamines. And in my mind, it's a very skewed reaction. The body's trying

00:45:11.780 to do something that it was meant to do prehistorically, but it doesn't help the person at all. In fact,

00:45:18.320 the histamine becomes so high that it can cause sometimes death. And within minutes, if you

00:45:25.560 already have asthma, if you already have lung issues, that mucus can become so strong that it

00:45:32.380 clogs up your lungs. And that's what oftentimes can lead to those very rare fatal reactions.

00:45:38.820 Or there's another chemical called bradykinin that is released by these cells once that receptor

00:45:45.400 docks. When the IgE docks into the receptor, once that receptor tells the cell to release,

00:45:51.720 it releases histamine and it releases something called bradykinin. That's another bad actor chemical.

00:45:57.460 The bradykinin can affect our blood pressure system. That can lead to dizziness and can lead to heart

00:46:03.300 issues. That's the second reason why people have fatal reactions. So you can imagine when you take

00:46:10.820 epinephrine through an injectable epinephrine device, that helps both the lung clear the mucus

00:46:16.760 and it helps the heart and the blood pressure stay strong so that you don't have one of these

00:46:23.300 near fatal or fatal reactions. But it all is linked to the immune system and how it reacts.

00:46:29.700 And it's a very fast reaction.

00:46:32.320 Is my memory correct that the cell that's releasing the histamine is a mast cell? Am I remembering that?

00:46:36.960 Good. I was hoping you'd ask that. So again, you're seeing both sides of the story for the

00:46:42.480 immune system. The humeral response, which is IgE, and now the cellular response. So once that

00:46:49.260 receptor gets docked into by the IgE, the cells that have that specific receptor on them are called

00:46:56.900 mast cells. They're also called eosinophils. And for those of you sort of listening, there's another

00:47:03.360 type of disorder called eosinophilic disorders, which that's a different type of food allergy,

00:47:09.080 but also related. And then those mast cells exist in tissues, but they're not in the blood.

00:47:15.960 Eosinophils are in the blood. The other third type of cell is called the basophil. That's in the blood.

00:47:21.920 So this is such a potent system because it's got these cells ready to go in the tissues,

00:47:27.840 the mast cells. Mast cells are in the skin, they're in the gut, they're in the lung,

00:47:31.100 in the eyes, in the nose. And then you also have these other cells floating around the blood

00:47:36.680 that are also secreting histamine and bradykine. And they're like the messengers across the whole

00:47:42.200 system. And then you have the mast cells embedded and the mast cells can live a very long time in

00:47:47.180 tissues. So these basophils and eosinophils are in the blood. These mast cells can live a long time

00:47:53.320 in the tissues. And that's why someone's reactions can build up over time sometimes, because every time

00:47:59.440 they eat that food or have that allergen exposure, their mast cells are going to remember because of

00:48:05.840 the immunoglobulins that bind to them. Is the implication, Carrie, that each successive

00:48:10.680 exposure gets worse? As a follow-up to that question, how often is a person's first brush

00:48:18.920 with a food allergy a fatal one? So we're only as good as our data. We're only as good as epidemiological

00:48:24.740 studies as well. So typically, and this is again typical, there's always exceptions. If you learn

00:48:31.360 about your allergies before the age of two, those food allergic reactions are typically vomiting and

00:48:37.640 hives. They're not typically related to lung and heart. So babies, for example, although there are rare

00:48:46.840 exceptions, toddlers and babies typically do not have fatal reactions to their first ingestion of food.

00:48:54.200 But there's a lot behind this. So if you actually dissect out who dies and who doesn't die from a

00:49:00.300 food allergy, it's typically people that already have a heart problem, already have a lung problem,

00:49:05.100 or didn't get to the EpiPen fast enough. So it would seem logical, like you're inferring that with every

00:49:14.200 dose that you take, your reaction could get worse and worse with the same dose. But it depends. It depends,

00:49:21.000 for example, if you're at elevation. It depends if you already have a cold. It depends if you have

00:49:29.120 aero allergies and you're allergic to a dog and a dog came by you that week and you also ate a peanut.

00:49:35.060 So there's a lot that changed that. But yes, in general, if all things being equal, each time you

00:49:40.940 ate it, your immune system would remember more and more and would boost up that response.

00:49:45.900 Now, luckily, with therapy, there's a way to retrain your immune system. But that takes regular

00:49:52.640 interaction with the food every day, not every week. If you take it every week, it actually boosts

00:49:58.300 your immune system to become more allergic. Take it every day. So there's something to the circadian

00:50:03.760 rhythm and the diurnal cycle, which we haven't talked about this yet. But what I love about the immune

00:50:09.960 system is it can be trained and you just need to know how to train it. And you can train it away from

00:50:15.560 becoming allergic and train it into becoming more protective. I absolutely want to focus on that

00:50:21.160 because it's, I think, the most hopeful aspect of all of this. But I want to kind of go back and

00:50:25.180 understand more these environmental factors that are predisposing children and adults to these

00:50:31.600 factors. So you mentioned one, which was dry skin. I can only imagine after listening to this,

00:50:37.820 everyone is going to be lathering up themselves and their children. And we're going to make L'Oreal

00:50:43.320 or whoever makes nice skin lotion very, very happy. Are there any other factors that we've

00:50:48.400 identified that seem to be predisposing people? There's some factors if they're lacking,

00:50:53.100 they also predispose people. So people have talked about having good microbiome, good dirt,

00:50:58.480 and that helps decrease the likelihood of food allergies. Children who grow up on farms, for

00:51:03.220 example, have a really good exposure to animals. They tend not to have as many food allergies,

00:51:08.140 interestingly enough. So I call that the dirt hypothesis. Also growing up with a lot of animals,

00:51:12.940 like dogs, also helps reduce the likelihood, and that's probably due to the microbiome.

00:51:18.120 But importantly is vitamin D seems to also play a role. So having enough vitamin D in your blood

00:51:23.460 also decreases the risk of food allergies. Being around too much detergent, that's what I call the

00:51:29.740 dry skin hypothesis. Unfortunately, a lot of our clothing being washed in detergents, our dishwashers

00:51:37.060 having really potent concentrated detergents these days. It's not getting rinsed away enough so that

00:51:42.600 the skin in babies, it heals so well, but it is somewhat more sensitive than let's say adult skin.

00:51:49.080 And so because of that, they tend to have dry skin due to all these other issues and let alone

00:51:56.100 detergents, but also any time in life, whether or not you're a child or a baby or an adult. If you have

00:52:03.780 pollution or tobacco smoke, that also causes dry skin and itchiness, and not just the skin on the

00:52:11.440 surface, but also in your bodies. Anything that touches the air has skin cells. So that means our

00:52:18.500 lungs, that means our gut. So all of these features that I talked about can affect the skin. We think that

00:52:25.320 through the skin, allergies can begin. It's not the only hypothesis. We also think that it's really

00:52:31.820 important to make sure that when you look at your overall diet, that you diversify that diet really

00:52:38.900 early and often so that if you can take certain proteins and feed that to your children when they're

00:52:46.100 young and have that diversity in the diet, that that can actually prevent the advent of food allergies

00:52:52.960 later on in life. So we talked about dirt, we talked about dogs, we talked about detergents, we talked about

00:52:58.360 vitamin D, and we talked about diversity in diet. So I call that the Ds. But importantly, that dry skin

00:53:05.340 does seem to be a conduit by which food allergies start. But what I didn't say was DNA. And that's

00:53:12.140 important because a lot of parents, a lot of people will say, oh, my parents gave this to me, or this is

00:53:18.460 in my genes, so there's no way I can do anything about that. And that's not true. So there are certain

00:53:24.440 allergies that can be passed on from one generation to the next. But even those diseases, if you change

00:53:31.920 your behaviors, that can also improve and decrease the likelihood of having food allergies. So I hope

00:53:38.500 that was helpful. When people do listen, I hope when they do try to improve their skin barrier,

00:53:44.920 if there is an emollient you can buy, try to stay away from the emollients that are based 1.00

00:53:50.260 with petroleum products or paraffin products or Vaseline. Because what science has now shown us

00:53:57.540 is that because those are not natural to the skin, our skin doesn't really like wax or petroleum

00:54:03.980 products. Vaseline is a petroleum product. That tends to increase the bacteria on our skin. And that can

00:54:10.980 make overall the skin inflammation worse. So try to choose products that have natural lipids that give

00:54:18.880 the skin back what they're missing. How does one look for that on the label? What would be the signs

00:54:23.860 of that? The natural lipids are like ceramide. So I don't work for any companies. I don't really know

00:54:30.800 which companies have ceramide, but I know one company, Cereva, has ceramide in it. So try to look for those

00:54:37.200 emollients that actually replete the skin with what it is depleted from, which are its natural lipids.

00:54:45.500 And then also try to rinse things. Now we are in a water shortage and we have to be careful too

00:54:51.400 with not using too much water. But if you can choose ecologically friendly detergents, because

00:54:58.580 eco-friendly detergents, eco-friendly foods tend to be better for our own bodies. And I'd love to know

00:55:05.580 your own opinion about that, Peter, but that's what I typically tell my patients. Try to avoid detergents

00:55:11.020 that are not eco-friendly because they're probably not so friendly to your body.

00:55:14.980 I wanted to ask a question about this. Any relationship with breastfeeding? You mentioned

00:55:18.220 it earlier with respect to IGA. Does a child who's breastfed or not breastfed, do we see any

00:55:24.160 difference in the incidence of food allergies? There have been a lot of my colleagues in Europe

00:55:28.640 that have tested this. Now, because breastfeeding is now so much the standard that it's hard to do these 0.96

00:55:34.800 studies now because the World Health Organization has recommended breastfeeding, which is wonderful. And that's

00:55:40.240 really important to start feeding infants other types of foods between four to six months of age.

00:55:46.100 But in general, breastfed infants do do better in terms of their overall gut health, in terms of their

00:55:53.360 overall health in general. But it has not been shown definitively that by breastfeeding, you can prevent

00:55:59.820 food allergies. But it is very helpful towards creating an overall healthy immune system. So I, in general,

00:56:07.300 tell all my families, if you can breastfeed, please do. But the ulterior, unfortunately, is that some

00:56:14.760 children, it's very rare, but they can have an allergy to a protein in the mom's breast milk. So if your child

00:56:21.520 does start to have issues with your breastfeeding, go see a doctor and then see and make sure that they don't 0.81

00:56:27.500 have an allergy to your own milk. But that's very, very rare.

00:56:31.740 And nowhere in that discussion of the D's did I hear, I guess you talked about diversity of diet,

00:56:38.000 but I want to talk specifically about the antigen. So what is the case for and against early exposure

00:56:44.040 to nuts as a vehicle to prevent the onset of one of these allergies? I think about the last 15 years,

00:56:52.060 I feel like I've heard pediatricians go in various directions on this. At first it was,

00:56:58.200 and I think about this through the lens of my kids. So it's like, sometimes we were told,

00:57:01.720 absolutely don't let them see a nut. Don't have nuts in the house for the first two years

00:57:06.020 to, hey, make sure they're eating nuts and peanut butter. So where are we today on that?

00:57:11.400 I agree, Peter. It's been confusing. There's been a lot of flip-flopping. And unfortunately,

00:57:15.600 there were well-meaning people 20 years ago that made guidelines based on not a lot of data. I think

00:57:22.440 that people were seeing there was an increase in food allergy throughout the world, and that's

00:57:27.380 probably due to many different things. But they reacted in a way to say, oh, we don't have enough

00:57:33.540 science, but we're really worried. So let's just tell people to avoid those foods. And hopefully

00:57:38.160 that can prevent this epidemic from increasing. And unfortunately, the minute those guidelines came

00:57:45.300 forward, and it was also during the time that I was raising my kids, the minute those guidelines

00:57:50.120 came forward, you started seeing a hockey stick in the epidemic. It actually started to increase.

00:57:56.700 In those countries that did not follow those guidelines, it stayed flat.

00:58:01.780 That's a very telling case, even though it's not a randomized intervention, that says when you avoid

00:58:08.380 foods at a young age, you paradoxically predispose to the allergy.

00:58:13.820 Exactly. So let's talk about that. The importance of guidelines. I agree, they're very important. And

00:58:19.580 oftentimes guidelines are made by people that really think hard, and they use the data that's at hand.

00:58:24.960 But we're only as good as our data. So fast forward 20 years afterwards, the world had different data.

00:58:33.200 The world said, wait a minute. We now think that through the skin, allergies begin. Through the diet,

00:58:40.000 allergies can stay quiet. We now know that the gut is really important for tolerizing to those

00:58:45.500 antigens. The immune system in the gut is meant to tolerize. The immune system in the skin,

00:58:51.560 in our lungs, and in our skin skin is actually meant to be activated and react. So when you think

00:58:59.080 about that dry skin hypothesis, of course, it's going to be promotional of allergic pathways. But when you

00:59:04.220 think about taking things through the gut, it's going to be promotional of tolerogenic pathways. So we learned

00:59:09.940 a lot in the last 20 years. So when the same people came together and wrote the guidelines 20 years

00:59:14.520 afterwards, they said, wait a minute, it's very clear now. And many guidelines have changed, Peter, now to say,

00:59:20.220 we need to diversify the diet. We need to tell our country's population to start having children eat 1.00

00:59:28.960 foods in small amounts, like tree nuts, like fish, like milk, like egg, like peanut, and to be able to

00:59:37.440 have that early and often and regularly so that we can try to prevent food allergies. So that's the

00:59:43.920 general mantra. The guidelines have now switched. Same thing for people who are pregnant. It used to be 0.96

00:59:49.600 thought women who are pregnant, based on a very small study, only 20 individuals, but that was the only

00:59:55.400 study that was available 20 years ago, that those pregnant women should avoid peanuts and tree nuts. But

01:00:01.760 actually, fast forward 20 years after, there was a much bigger study done. And that showed that

01:00:07.560 definitively, it's okay to have peanuts and tree nuts when you're pregnant. It's actually healthier with

01:00:12.800 omega-3s. Of course, people who already have food allergies shouldn't be eating these foods when

01:00:18.420 you're pregnant or if you're a child. But in general, it's a way to prevent food allergies now, among many

01:00:24.460 other things like we talked about. But it does seem to be important, and it goes back to those

01:00:29.480 instrumental recipes of the immune system. If the immune system can probe the antigen, know that it's safe,

01:00:36.880 know that it's not going to harm the immune system or the body, it then becomes tolerant.

01:00:43.760 But in order to give it that instruction sheet, in order to give it that recipe, you need to feed and

01:00:50.280 you need to get exposed regularly. And we think regularly means every day to every other day. And

01:00:57.240 you'd say, well, wait a minute, why? My grandmother didn't have to feed me these foods, or my mother didn't 0.98

01:01:02.480 have to feed me these foods regularly. What all of a sudden changed? And we think that the environment is

01:01:08.520 changing. We know the environment is changing all around us, unfortunately, with different detergents, with

01:01:14.060 different emulsifiers, with different chemicals in our food, with different pollutants, with different

01:01:18.920 viruses. It's changing. So now we take the science and we have a better instruction sheet for patients, and I'm

01:01:25.260 grateful for that, but it is all based on evidence.

01:01:28.220 Do you think the genie ever gets back in the bottle? Do we ever get back to the levels we had 30

01:01:32.280 years ago? Or do you think that even if we can get dietary practices to where we were, which is to

01:01:38.300 say we're at a place where parents are encouraged to liberally and diversely sample food for their

01:01:44.740 kids, these environmental issues, the detergents, the dryness of skin, all those things, the low

01:01:50.320 vitamin D, presumably because kids are playing outside less these days and they're indoors more,

01:01:55.280 and all of the things that we understand, that it never quite gets back to the level it was when I

01:01:59.180 was a kid. Like, I got to tell you, when I was a kid, I did not know another child that had a food

01:02:04.300 allergy. All through grade school, middle school, high school, there was not another child in my zip

01:02:09.680 code that had a food allergy. Today, my kids can't take nuts to school. You can't have nuts on an

01:02:16.300 airplane today. So I can't tell how much of this is overreaction. There's clearly a log fold change,

01:02:23.100 but I can't tell how much of it is also just a disease of the brain, if that makes sense.

01:02:29.640 No, but you're right to ask that. And lots of epidemiologists have now tested it. It's real.

01:02:35.520 I mean, this is not just people thinking they have allergies. And when you and I were growing up,

01:02:40.280 they didn't. This is real. There were people very rarely that had a milk allergy, peanut allergy, but

01:02:45.820 the allergists never really focused on them. Now, the typical allergists, and we have allergists that

01:02:51.860 have worked in the community for 80 years, their offices have shifted from being offices where

01:02:56.920 aero allergens were what they took care of all the time, to now it's foods. And that's not because

01:03:03.120 someone thinks that they're allergic to food. This is a real diagnosed food allergy. And I think

01:03:08.900 your question is a good one, but I don't think we're ever going to get back to 30 years prior,

01:03:12.880 because we have different practices where we have different ways of processing food, different

01:03:17.700 environmental exposures. Because this is mostly environment, if I have identical twins

01:03:22.840 born to the same mom and dad, I can have one twin develop a food allergy and the other one doesn't.

01:03:29.880 And typically that's in adulthood. And the one twin that develops a food allergy, they're the ones that

01:03:34.820 have been out in pollution more. They've eaten not such a healthy diet. They have a lot of preservatives,

01:03:39.840 or they smoke, or they eat a lot of fast food, or they are under a lot of stress,

01:03:45.020 and they don't get a lot of sleep. So genetics being equal, exposures in early life being equal,

01:03:52.040 there are certain behaviors that now we're seeing are more associated with food allergy,

01:03:56.160 like air pollution. I don't think we'll ever go back, but luckily science has helped us

01:04:01.900 so that we know what to do now and how to change our behavior so that we can try to prevent

01:04:07.660 food allergies from worsening.

01:04:10.460 So let's now talk about the work that you've been, well, I'd like you to put the context around

01:04:14.700 your role. I mean, of course, I think of you as pioneering this work. I'm sure you'll elucidate

01:04:19.260 us all with how many people are pioneering this work. But you and I met, like I said, about a decade

01:04:23.640 ago through a mutual patient of mine who at the time was being treated by you. Quite frankly, I was

01:04:29.680 just sort of blown away at the fact that a person who once had an anaphylactic reaction to nuts was going

01:04:37.300 through an immunotherapy-based sensitization program with you at Stanford and then all of a sudden

01:04:43.620 didn't have an anaphylactic reaction to nuts. This was mind-boggling to me and I'm forever in

01:04:50.480 your debt for graciously letting me wander around your lab and sitting around chatting with me over

01:04:55.460 coffee. So can you give us a bit of a sense of what this revolution is about? It's sort of hard to wrap

01:05:01.280 our head around when you consider the lethality of these conditions. We take this so seriously and

01:05:06.960 that particular family has been so engaged, like so many other families, that this is a disabling

01:05:12.920 disease. My colleague Kim Yates has done so much work in this area as well as other families to be

01:05:19.360 able to educate and organizations like FAIR and others have really moved the needle forward.

01:05:24.800 So when you think about food allergies, it comes in a child's mind or an adult's mind something they

01:05:30.980 have to live with and it's not fun and it can affect their social lives or quality of life.

01:05:36.480 So they come to the table often wanting to know what's the best therapy now and compared to when

01:05:42.100 we started with your patient, we have a lot more therapeutic options and that's always good in any

01:05:48.080 field to have options, especially for our patients. So any of these decisions that I'll talk about today,

01:05:53.540 they're really personal. They're really something that the doctor, the healthcare provider should talk

01:05:57.980 to the patient about and see what's the best for me. But in general, again, getting back to that immune

01:06:03.820 system, getting back to the regular eating of foods so that you can start retraining it to

01:06:09.160 tolerize to those foods, to see them as natural and not unnatural. This has been going on for about 100

01:06:16.260 years. And even though to us and to many others, this is something new. And we did work at Stanford,

01:06:23.620 but actually other work at other institutions in the country and other work in Europe had already

01:06:29.600 been done. So what I was doing is building upon other evidence and clinical trials that had been done.

01:06:36.740 And I worked very closely with the Food and Drug Administration, the FDA, because you don't want

01:06:42.520 to do anything that's not safe and that you wouldn't want to do for your own children if they

01:06:47.260 had the disease. So with that in mind, I learned a lot about the immune system. What you do in

01:06:53.580 immunotherapy at the very basic level is give the person back the very same thing that they're allergic

01:06:59.480 to. And this was done a hundred years ago with dog allergies, with cat allergies, with grass allergies,

01:07:06.980 with mold allergies. People would actually start to take these things, but inject them.

01:07:11.200 A lot of your patients might've done allergy shots when they were little. But those are ways that

01:07:16.640 we've learned as immunologists that, oh, you can retrain the immune system. You can train a body so that

01:07:23.400 they are no longer allergic to cats, for example. But you need to keep taking those allergy shots in

01:07:28.200 general. So the same thing for food. You don't want to give a food allergy shot because the food in and of

01:07:34.640 itself is very potent. And because it's a very specific IgE-mediated disease, foods, if injected

01:07:42.660 into you, can be extremely dangerous. So we don't give it via injections.

01:07:48.340 Just to be clear, the allergy example, let's say it's cat dander or whatever, is the shot giving you

01:07:55.660 a little bit of that dander? Is it sensitizing to you a little bit? And how frequently does the patient

01:08:00.180 need that to achieve a symptom-free existence? Initially, you need to take it almost daily,

01:08:06.160 daily to a week. And then once your body starts to build up that immune muscle, you only need to

01:08:11.700 take it about once a month. But you will do that for life.

01:08:15.140 Well, some people do it for life. Some people do it for five years. If you stop it after five years,

01:08:20.140 you have a 25% chance of regaining your allergy. Another 25% chance of having it just be less,

01:08:27.560 but there. And then you have a 50% chance of having it be resolved for the rest of your life. But you

01:08:34.960 need to be on five years of immunotherapy, depending upon the aeroallergen. And we're talking environmental

01:08:39.920 allergies. Yeah. And is the reason that you can get away with doing that because it does not induce

01:08:46.020 anaphylaxis in the way that the food does? So it's just the severity of the IgE mass cell reaction.

01:08:52.060 Exactly. And we still are trying to understand why that is. Why is grass allergy not as bad as

01:08:58.880 peanut allergy? So people are still trying to figure that out. Why is dog allergy not as bad as

01:09:05.580 peanut allergy? But given that it is for immunotherapy, like we said, you give small amounts of that

01:09:13.680 specific allergen back to the patient, whether or not it be a shot for environmental allergies or

01:09:19.480 whether or not it be orally for a food allergy, you give it back in small amounts. You start with

01:09:25.900 a small speck that you can hardly see. And then you increase that dose by 25% every two weeks,

01:09:32.200 but you're giving it every day. And then you increase it step by step. Every two weeks, you

01:09:37.760 increase the dose, but you're giving it daily. And you want to do that in a doctor's office. You want

01:09:42.700 to be really careful about that. So we did it in our clinical trials. Over time, you readjust the

01:09:49.200 immune system. Now it takes a while, right? This person has had their allergy and it's been quite

01:09:53.720 severe for them. So to retrain the embedded memory aspect of the immune system takes time.

01:10:01.560 And what happens over time in the immune system is those little T cells start to be taught that,

01:10:07.520 oh, wait a minute, this antigen, it seems okay. I'm getting it every day. Boy, I need to

01:10:13.500 readjust myself. I need to reframe my mindset. And instead, T cells start to reframe their mindset.

01:10:22.140 You start creating another whole layer of memory T cells that become tolerant to that antigen. And then

01:10:30.120 they teach the B cell to forget making IgE. In fact, we want you to make more IgA. We want the 1.00

01:10:38.800 B cell to make more IgG because that's protective. And so that's what happens over time. During the

01:10:45.340 first year of immunotherapy, you're slowly going up, you're slowly readjusting. And in our patient's

01:10:50.560 case, that's exactly what happened. That person was readjusting their immune system, readjusting their

01:10:56.120 immune muscle, to then switch from an IgE-mediated bad reaction to instead creating protective molecules

01:11:06.160 that could protect the patient against the allergy. The IgE can still be there, but you have this huge

01:11:15.160 amount of protective, what I'm going to call blanket, so that that IgE doesn't have anywhere to go. When it 1.00

01:11:20.960 wants to bind to the receptor, that blanket of immunoglobulins don't allow it to bind to the

01:11:26.880 receptor. We all have IgE. All of us do. But some of it works and some of it doesn't.

01:11:32.860 In the case of the person with the anaphylactic reaction to peanuts, do they ever go above the 0.005%

01:11:40.620 IgE concentration? How high does it go, just for comparison?

01:11:44.700 IgE is typically specific. You have to have an IgE to a specific food to be able to have that reaction.

01:11:50.320 And yes, typically some people with peanut allergies will be over that 0.005% or anyone with allergies.

01:11:57.380 Their IgE is higher. And just so you know, a virus can also increase IgE, non-specifically.

01:12:04.280 Your body just starts making IgE, probably against the virus. It's a very prehistoric type of reaction.

01:12:10.420 But importantly, Peter, for every IgE molecule, we can make 100 IgG molecules that protect against that

01:12:20.300 IgE molecule circulating and becoming potent. And that's what's happening during the time of

01:12:25.980 immunotherapy. You're making a huge amount of IgG molecules to bind against that IgE becoming

01:12:34.820 what I call pathological. So it's a ratio thing.

01:12:39.220 Just give me a sense of scale. So on the very first cycle, that first two-week cycle,

01:12:44.640 what fraction of a peanut is being given in the capsule? How small is it? I'm sure it's less

01:12:50.880 than a single peanut, obviously.

01:12:53.100 Yeah. It's about one two hundredth of a peanut. You start very low and you go very slow because in

01:13:05.020 the end, you want to retrain that immune system, but you don't want to activate it too much. Now,

01:13:09.880 during that retraining, sometimes your muscles get sore, right? Sometimes you will see some hives,

01:13:14.100 sometimes you will get a little itchy throat. Your body will have these little reactions,

01:13:18.760 but I call them simmering reactions. But you do need to take it every day. And then you start to

01:13:24.320 see this switch from IgE to IgG. And again, the T cells are responsible for that. Many other cells are

01:13:33.340 too. But in general, if you stop the therapy, this beautiful pathway of tolerance then starts to go back

01:13:42.420 to the original pathway. So it's really protection. It's very rare that a person completely flips and

01:13:49.940 becomes non-allergic. Does that make sense? It's really what you're doing in the immunotherapy is

01:13:54.380 changing your threshold and creating more protection molecules around you and creating

01:13:59.900 more protective cells around you.

01:14:02.040 And when does that switch flip?

01:14:04.940 If you're on the typical immunotherapy regimen, it flips at around nine months to a year.

01:14:10.460 And again, just to give people a context of the doses we're talking about,

01:14:14.760 someone comes in with an allergic reaction to peanuts. For two weeks, they're going to take

01:14:20.180 a capsule that contains one two hundredth of a peanut. That goes according to plan. They will increase

01:14:26.060 that by 25% for another couple of weeks. A month into this thing, they're still basically taking

01:14:32.560 one two hundredth of a peanut. But you will continue to do that. They will not hit the threshold of a

01:14:38.240 full peanut by the end of the year. They're really, really microdosing this in the true sense of the word.

01:14:43.860 Well, you're super smart because you do the math. But in general, we've worked it out. Thanks

01:14:48.800 goodness to the science where we know the steps. There are going to be certain steps of this where you

01:14:53.480 don't have to increase by 25%. So once you get up to about 40 to 60 milligrams, and that's only

01:14:59.780 after a couple of weeks, we start to go up those steps. You start to skip and then you can go even

01:15:06.500 higher. You can go steeper. Then we double, we can quadruple. So that by the end of the year,

01:15:10.380 you are at about a peanut to two peanuts worth. And that was done with science. There were dose

01:15:16.080 finding studies. There were maintenance finding studies. And we do this for milk and egg and tree nuts

01:15:21.920 and peanuts all at the same time. That's the other thing, because I told you a lot of people have

01:15:26.960 more than one allergy. We had to work this out scientifically to go low and slow, but within

01:15:32.880 reason so that we could eventually within a year, make sure that that flip was happening in the

01:15:36.960 immune system and make sure that by the end of the year, if they didn't want to continue anymore,

01:15:40.560 we at least needed to get them up to an accidental ingestion of that food. So we were very careful to

01:15:46.300 design this. And that's in essence, why this needs to be a drug, because all that science,

01:15:52.220 you can't do this at home. All that science enables you to know, when do I push the immune

01:15:57.760 system to go quadruple? When do I not? And what are you using? Are you looking at the IgE, IgG level?

01:16:05.560 Are you simply doing this based on the absence of symptoms in the presence of the administration?

01:16:10.840 Thanks to a lot of pioneers who were in those trials, including our patient,

01:16:14.660 we were taking blood every two months, every three months. We were using blood biomarkers to

01:16:20.560 let us know, oh, look at that. The cell immune system has started to switch. Oh, look at that.

01:16:26.520 Isn't that interesting? The humoral immune system has switched. So that's how we knew to change our

01:16:32.300 protocol. That's how we knew it shouldn't take 10 years to do this, because there was this natural

01:16:38.080 switching that was happening underneath in the blood. So we use those markers to then

01:16:44.440 readjust and recreate our regimen so that you could go low and slow in the beginning.

01:16:50.240 But then by about three months, we knew that the muscles were starting to change. So we could hike

01:16:55.860 up the dose a little bit more. By six months, even more. By year, we knew we had it because by that time,

01:17:03.180 the immune system had switched. But that took a lot of time and effort and blood draws from those

01:17:07.880 original pioneer patients to give us the science by which we could perfect this regimen. It's not

01:17:13.420 perfect yet, but it's much better than where we were 10 years ago. If at the end of a year,

01:17:19.220 you kind of alluded to this, a patient says, look, I can't handle coming in here every day to do this

01:17:22.960 anymore. I'm sort of done with this. Is it on average safe to assume that they may never be able

01:17:27.880 to just go out willy-nilly and eat nuts? But if they accidentally ingest a nut here and there,

01:17:33.420 or there's dust from a nut in a food, and you refer to it as an accidental ingestion,

01:17:38.240 that they're going to be fine? Is that directionally trying?

01:17:41.680 You're absolutely right. On one side, we want to make sure that we reach the goals of the patient.

01:17:47.860 Typically, a patient wants to get up to accidental level ingestion. And because of that,

01:17:53.120 we say, okay, we'll try to get you up to 600 milligrams by the end of the time. We also know

01:17:58.900 that 600 milligrams is what the FDA also thinks is the appropriate threshold. So we're grateful for

01:18:05.360 that knowledge across many other communities and institutions. So we try to get it up to 600.

01:18:11.420 But you're right. Oftentimes people say, well, I'm done. I really don't want to have to do this every

01:18:17.800 day. Can you please tell me if I could take my dose weekly or if I can take it every other day?

01:18:23.120 And what dose is safe enough? For maintenance, for example, we try to get them up to two peanuts a

01:18:29.260 day. But sometimes they go off to college. They don't want to have to take a nut every day. But

01:18:34.960 we tell them that you kind of have to, because we don't know what will happen if you stop.

01:18:40.980 And that's what we told them five years ago. Now we have some long-term follow-up. Now across

01:18:47.720 many countries, people are sharing data and saying, what makes sense for patients? Can you predict

01:18:53.740 who can stop therapy and who might not be able to stop therapy? Who can go down on their dose during

01:19:00.500 long-term follow-up and who might not be able to go down their dose? So we're learning. But in general,

01:19:06.040 it's much better to take about one nut or two nuts a day every day after you finish your therapy

01:19:12.840 with a doctor. And just to be clear, do they ever transition to the point where they can do this

01:19:17.820 as outpatients on their own? Or do they always have to do this in a doctor's office?

01:19:22.120 After about a year, even after six months, if people get up to that one to two peanuts a day or

01:19:28.080 hazelnuts or glasses of milk, you can say, all right, you're done now. And you can go home and

01:19:34.480 do this at home and then let me know how you're doing. So yes, after you've got to that threshold,

01:19:39.300 we definitely let you go home. And that depends on the clinical trial though.

01:19:43.740 But nowadays in the clinic, that's what we do.

01:19:47.260 Are people undergoing this therapy outside of clinical trials yet?

01:19:50.640 They are, Peter. And that's been going on for a while. We were very careful to say that if you do

01:19:55.280 decide to do it in an outside clinic, try to get your health insurance to approve. We want to

01:20:00.460 democratize this. We don't want it to be only available to certain populations because everyone

01:20:05.700 gets food allergy and sees no boundaries in terms of ethnicities or socioeconomic status,

01:20:11.140 especially people of color have a much higher rate of anaphylaxis, unfortunately, because of

01:20:15.720 access to healthcare. So that's a whole nother topic for social determinants of health. But yes,

01:20:21.400 there are clinics that are offering this. And there are clinics, for example, Latitude in New York City

01:20:26.400 and San Francisco now that offer specific regimens that are based on science and evidence to be able to

01:20:32.980 offer therapy. So there are unique clinics out there that are specializing in food allergy care

01:20:39.400 to be able to help patients based on scientific methods.

01:20:43.600 What fraction of patients who continue this protocol get to the point where

01:20:47.060 they completely shed the allergy altogether and at some point will go on to eat as many peanuts as

01:20:53.940 they want?

01:20:54.820 I always like to start any conversation with the patient that this is possible. Some patients just

01:21:00.940 want to be able to eat one to two peanuts for the rest of their life and just know that they're not

01:21:04.560 going to have an actual ingestion. They're willing to do that. And they believe that is the word cure.

01:21:08.680 But for me as a doctor, I kind of push my own standard a little bit higher. Like cure should be eating

01:21:13.400 ad lib and not having to worry at all. So in that definition of cure, if you take the dose for at least two years,

01:21:22.360 you have a 20% chance of being in the cure category. 20% after stopping after two years.

01:21:29.580 After five years, you have a 60% chance. So time on dose matters as well. And again, it's all

01:21:38.100 recalibrating, re-educating the immune system. And many people ask me, well, are there some people that

01:21:45.540 are refractory? And you'll know that term because of people that are refractory to cancer therapy.

01:21:51.620 But in allergy, there's no refractoriness per se. If sometimes people have too much abdominal pain,

01:21:58.060 or they have too many hives, or their asthma gets worse every time they have the dose, that's where

01:22:03.860 I'll say, hey, it might not be worth it. There's too many side effects here. This bothers you too much.

01:22:10.060 We try to decrease the dose so that we personalize it for them. But some people just say,

01:22:14.760 hey, this is too much now. I really don't want to go through it. So those people will stop doing it.

01:22:19.920 But in general, if you stay with it, you'll get the benefit from it.

01:22:23.640 What percentage, if any, of people going through the clinical trials

01:22:27.480 required epinephrine during the administration of the immunotherapy?

01:22:31.120 Nowadays, because we go so low and slow, it's a very rare percent. So about one in 10,000.

01:22:38.000 In some clinical trials, one in 100,000. It's rare.

01:22:40.700 Is there any allergen that is not amenable to this type of therapy? As you said, you mentioned a few

01:22:48.020 others, right? Shrimp, other fish, non-shell fish. Is there anything that we've uncovered which this

01:22:55.220 therapy does not work?

01:22:56.640 It's again, back to that very elemental nature of the immune system. Proteins, any protein you can do

01:23:04.020 this with, which is great. Very carefully, if you're allergic to a protein, which is what we're

01:23:09.240 talking about today, you can do this. There are very rare allergies where you're allergic to a

01:23:15.180 sugar. It's called alpha-gal. And we don't think you can do this type of regimen with alpha-gal

01:23:21.120 allergies because that's a sugar. So with proteins, the immune system has this very elemental way of

01:23:27.840 readjusting and recalibrating and become tolerant. But with sugars, it's a little different. But

01:23:32.940 luckily, sugar-mediated food allergy, it's one of a kind. It's called alpha-gal, and it's very rare.

01:23:39.400 But it is occurring more in the southeastern part of the United States because it's associated with

01:23:43.860 a tick bite. So that's another whole area maybe in the future, Peter, for you to look at. But right now,

01:23:51.100 there is nothing that we have not been able to desensitize a patient to with food allergies that

01:23:58.900 we've tried to. Going back to sort of the environmental allergies, here in Austin, we have

01:24:04.060 this thing called cedar fever, right? So the cedar trees give off a ton of pollen and knock on wood,

01:24:10.420 unfortunately, it hasn't afflicted me. But I know so many people here who for a period of, gosh,

01:24:17.280 I think it's sort of December, January or November, December, January, where they can't function

01:24:22.420 without Benadryl and Zyrtec. I've asked around on behalf of friends to see if there are immunologists

01:24:29.840 and allergists here that have an immunotherapy regimen. And to my surprise, nobody does.

01:24:34.660 Would this be an easy thing to address? Cedar allergies are interesting because the cedar

01:24:39.840 protein itself is something called a protease sometimes. So it can start to grade proteins.

01:24:44.780 It's a little weird. But cedar allergies are very serious. And yes, there are people that

01:24:49.820 have developed immunotherapy for cedar. It's interesting that I can't find them in Austin.

01:24:54.900 I'll have to connect with you offline for this. There are a lot of people here who I know would

01:24:58.340 be interested in that. Yeah, it's the same rubric. You can desensitize to it, although it takes

01:25:02.680 a lot of care. Maybe that's why. Importantly, cedar allergies are something just like other tree

01:25:08.260 allergies. They're really to be cared for and they can give you lots of mucus and asthma. So

01:25:14.000 I hope that those individuals you take care of can get some benefit. But immunotherapy,

01:25:19.400 so I call it proactive therapy and reactive therapy. Reactive therapy are all those antihistamines

01:25:24.660 people need to take. Proactive therapy is the immunotherapy to readjust your immune system,

01:25:29.380 but you need both. I want to now talk a little bit about air pollution just for a moment.

01:25:34.580 Tell folks what's a PM 2.5 and why should somebody care?

01:25:37.760 10 years ago, I didn't really understand all of the PM 2.5 jargon either. So I want to just make

01:25:44.040 sure in all humility, this is something that we all need to learn now, every single one of us,

01:25:49.360 even if we're in a research station in Antarctica. Because air pollution, unfortunately, is rising.

01:25:56.520 We need to know that there are no boundaries. When wildfire smoke happens in Australia, it can

01:26:01.840 circumnavigate the world within four days. And PM 2.5 is a way that we as a society have given a

01:26:10.940 measure to air pollution. But it's not everything in air pollution. It's particulate matter. It's the

01:26:17.500 particles in air pollution that are 2.5 microns in size. Now you think, well, what in heaven's name

01:26:25.800 is that? Like 2.5 microns. What does that mean to me? Well, if you think of like a little red blood

01:26:29.860 cell, that's a micron. So you think about particles that are basically about twice the size of a red

01:26:36.000 blood cell. And those are floating around in the air. And why do they do that? Well, that's because

01:26:41.040 partially combusted fuel, combusted fuel from our cars, if you don't have an electric car,

01:26:47.420 combusted fuel from industry, when it breaks up petroleum, when it breaks up any kind of product,

01:26:54.180 wood fire as well, little particles escape into the air. And those particles are not what you see

01:27:00.820 as soot on your car. They are not what you see as brown dust on your house. These are particles that

01:27:09.260 are so small, they continue to be aerated and they can float in the air around the whole world. And

01:27:16.360 they're so small that they can penetrate into our lungs. And why do we care about that size,

01:27:21.800 2.5 microns? That's because it can get through our lungs and into our blood. It's dangerous also

01:27:29.180 because PM2.5, as a defined measure of air pollution, has about 200 different chemicals in it.

01:27:37.520 200. And of those 200, some of those are what we call volatile organic compounds. These are compounds

01:27:44.900 that you smell when you smell like markers, like xylene, or in the old days, mothballs,

01:27:51.160 naphthalene. So these are chemicals that are not good for the body. They are from combusting fuel.

01:28:01.040 If any one of your listeners is a chemist, these are what we typically called six-membered rings.

01:28:06.360 They're organic chemists, sort of nightmares because they smell horrible. And I didn't like them when I

01:28:12.200 was doing organic chemistry when I was a student. I don't like them now because now I know what they

01:28:17.200 can really do to your body. They can cause cancer. They can increase asthma. They can increase

01:28:25.000 cardiovascular disease, stroke. And wildfire smoke is even more potent as an air pollutant than PM2.5.

01:28:33.180 We also measure PM2.5 for wildfire smoke because wildfire smoke basically is biomass burning.

01:28:38.980 But unfortunately, wildfires aren't burning just trees anymore. They're also burning commercial

01:28:46.020 buildings. So what goes up in wildfire smoke compared to, let's say, just diesel from the car,

01:28:51.140 which is bad enough. But in addition, with wildfires, you're burning up your upholstery. You're burning up

01:28:57.580 your paint thinners. You're burning up your detergents underneath your sink, your shampoos.

01:29:01.580 That's all going up in the air. And that's also measured as PM2.5 because all those particles

01:29:07.260 are so small. They're also going into your lungs. So with wildfire smoke, we also have to be super

01:29:12.520 careful. So for any person that's getting exposed to any PM2.5, you can look on websites. You can go

01:29:19.100 look at AirNow. You can go look at the NOAA website and know in your region what air quality index you have

01:29:26.400 that day. If it's in the green zone, great. If it's in the yellow zone, please start wearing a mask,

01:29:32.900 basically a mask that you used to wear in COVID because those masks are very important to reduce

01:29:40.040 the risks of those exposures to your lungs, especially for children and elderly patients.

01:29:44.960 So that's what PM2.5 means. And I want people to really understand that it's measurable.

01:29:51.040 It means something biologically that's important. It means something medically,

01:29:54.900 but it also can be measured by well-meaning agencies like the EPA, like we use in California,

01:30:04.540 something called Purple Air. And you can actually look on the web. The Purple Air monitors can

01:30:09.960 actually tell you what PM2.5 measurements are in the air. Not all countries have that. We're lucky in

01:30:15.420 the U.S. that our U.S. agencies measure PM2.5 on a regular basis so that we can map that to our zip codes.

01:30:23.100 Do you recommend that people, because there's a lot of PM2.5 monitors that you can buy for your

01:30:29.180 own home, is it necessary? Or do you feel that if you are just looking at these databases,

01:30:34.360 you get a good enough sense? Because I can't tell which problem they're solving for. Are they

01:30:38.600 basically trying to say, you need to make sure you don't have particulate matter in your home?

01:30:42.840 Because if you do, by the way, it might be that you have a leaking stove, or I mean,

01:30:47.140 that would probably turn up as carbon monoxide or something else. Versus, no, you just need to know

01:30:51.940 what the level is outdoors, because that might be the day you choose not to do your 10-mile run,

01:30:57.240 if it's a red day.

01:30:59.140 All those things. So first of all, if you know that you have to be outdoors, and you're an immigrant

01:31:03.920 farm worker, and you have to be out there for eight hours, no matter what, and the air quality

01:31:09.340 index is 100, like it was yesterday here in California, and we had people out in the fields,

01:31:14.300 they should know that they should wear an N95 mask.

01:31:18.100 And N95 will sufficiently prevent PM2.5s from getting in? 1.00

01:31:23.620 Not perfectly, but at least it reduces the risk. No mask completely reduces those small

01:31:30.560 organic molecules, those six-membered rings from getting through the mask, but at least it's

01:31:34.880 better than nothing. So typically, that's what I'll say. And I'll definitely say to my patients,

01:31:40.440 please don't exercise during any air quality index that's greater than, let's say, 50.

01:31:45.520 Because even though they might not feel it during the hour that they exercise outside,

01:31:49.380 it definitely affects their immune system. There were studies done in London, for example, where

01:31:54.180 people would exercise out in the streets that had a certain air quality index. And in London,

01:31:58.800 you can actually do this because there's micro PM2.5 measurements in Hyde Park versus in

01:32:04.340 Broad Street. So they did this research, and they knew that even if people exercise out for one hour,

01:32:10.140 in clean air versus polluted air, their immune system changed for a whole day based on that one

01:32:16.640 hour of exercise. Be careful. And yes, indoor air is very important. Our lives are spent indoors

01:32:24.860 for more than 90% of them. That means 90% of the time that we're on this planet, we're spending it

01:32:30.760 indoors. That's typical for the average US citizen. So having a purple air monitor indoors is actually 0.83

01:32:38.200 helpful, especially if you live in a place with lots of wildfire smoke or air pollution, because you can't

01:32:43.460 assume that your air pollution is being filtered appropriately. And you can't assume that you're being

01:32:50.200 protected, because oftentimes you can't smell this and you can't see it. It is so small that you need a special

01:32:58.860 detection monitor to know if it's there. Now, if you do have bad indoor air, you can buy a MERV filter, you can buy a

01:33:07.000 filter in your air conditioning or central air, or you buy a stand-up filter to reduce the exposure. So

01:33:13.660 all these things are available to people. And in certain states, they are available freely for

01:33:19.800 families that can't afford them. So just to be clear, let's say you do this exercise, you buy the

01:33:24.880 purple filters, you figure out that, hey, actually, either A, I live in an area where there's enough

01:33:31.000 pollution outdoors, and of course, it's easily able to get indoors through windows and doors,

01:33:34.740 or just for whatever reason, there's something in the house that's producing these compounds.

01:33:39.000 Option one is you just get stand-up HEPA filters for the house. But you're saying option two is

01:33:43.700 there are certain filters you can put in your HVAC that will do the same thing. And what are those

01:33:48.800 called again? They're called MERV. They're MERV 13 or higher. Don't buy a MERV 7 or 8. MERV 13

01:33:55.080 reduces all of the major PM2.5, as well as pollens, as well as other chemicals. But you need to

01:34:02.540 change them often because they're getting clogged up. I don't work for purple air, but you can buy

01:34:08.100 any of these monitors that can monitor external outside air and indoor air. And you can buy them

01:34:14.760 and get to know the difference. It's good to ventilate your home. So you don't want your home

01:34:21.320 to also, like you said, be collecting its own toxins. And that can happen if you have a gas stove

01:34:26.660 or a wood stove. So yes, in general, knowing and measuring your PM2.5 is going to be helpful to

01:34:35.480 your health because you can manage accordingly. Do you have a sense, because I've never been able

01:34:40.160 to get a great answer to this question, Carrie. It's actually one of the reasons I did not include

01:34:44.040 this in my book. I wanted to include a section on air pollution in the book. And in the end, I didn't

01:34:50.220 for a couple of reasons, but biggest reason was I couldn't get a really clear sense of the mortality

01:34:56.580 impact. I couldn't quantify it the way I could quantify it for smoking, obesity, and some of

01:35:02.320 these other things. So coupled with the fact that the book was already about 50% longer than anybody

01:35:06.920 wanted it to be, do you have a sense of the magnitude of this? And for example, like what's

01:35:13.520 the difference between even quantifying the exposure is a little difficult. It's not like a pack

01:35:18.320 years of cigarettes where we can say 40 pack year history versus zero pack year history translates

01:35:22.880 to this much difference in outcome. Yeah, actually now, Peter, you can. So the WHO just put a report

01:35:29.840 out. The AQLI just put a report out from University of Chicago. I'll send it to you. I want to make sure

01:35:35.740 you have this because you have such a wide, amazing opportunity to influence people through your

01:35:44.560 bandwidth. And Peter, I feel like you are in this incredible position to make this impact with

01:35:50.400 others. You are a trusted voice. And because of that comes the privilege of being a trusted voice,

01:35:56.120 but also that accountability and responsibility of knowing all the science. And so what I'll do

01:36:00.980 is send you this report because it has now been put into exactly those terms. And it's more dangerous

01:36:07.740 than tobacco smoke because it is so prolific. And I'll give you this report because in the first page,

01:36:13.460 it shares with you the context of how pollution has killed about eight to 10 million people a year

01:36:22.320 now. And that's attributed directly to air pollution. What is the final common pathway? Is it

01:36:28.800 majority through cardiovascular disease, cancer? Where do we think the actual mortality comes from?

01:36:35.020 Exactly. Especially in low to middle income countries, it's cardiovascular disease and lung disease.

01:36:41.000 In quote unquote, more westernized countries, it's more associated with stroke, long-term cardiovascular

01:36:48.280 disease and cancer. So I'll send you this. I think it's important for you to know air pollution has now,

01:36:55.960 thanks to a lot of science, that you can disaggregate what deaths are due to air pollution versus what

01:37:01.420 deaths are due to tobacco smoke. There's a multiplicity of effect here. But now the epidemiologists really

01:37:06.700 have the data right. And you can sink your teeth into this data and know that it's accurate.

01:37:12.000 Well, Carrie, this is very interesting. I know we were a little bit short on time today. So I'll

01:37:15.020 kind of just ask you one final question. When you go back to the child who died in the ICU,

01:37:19.980 the child who was kind of your patient zero, you alluded to it, but we never really got to it. Tell me,

01:37:24.800 why did the EpiPen not work? When that father asked you about that, what happened there?

01:37:29.600 They hadn't renewed the EpiPen. It had expired. They hadn't gone to the doctor for at least five

01:37:36.880 years. And they assumed that their child had grown out of a milk allergy because that's what people

01:37:42.720 told them would happen. But they never got their IgE retested. They never went back to their allergist.

01:37:48.740 And so they still had the EpiPen that had been given to them five years prior, and it had expired.

01:37:53.980 In addition, it was for a different weight. It was for EpiJr. And he had gained and, of course,

01:38:01.020 grown. So if he were to even get an Epi that was not expired, he should have gotten a different dose.

01:38:07.200 So it interlaid all these aspects about the fact that you cannot know just what typically happens

01:38:14.860 to a patient if that happens to you. You need to actually go to a doctor and get your own set of

01:38:19.720 data to figure out how to best manage your disease. It also taught the lesson of you've got

01:38:25.740 to keep updating your EpiPen and making sure that it's renewed and not using an expired chemical or

01:38:32.920 any expired drug. And then lastly, that as you grow, you need a different dose.

01:38:39.040 Wasn't there a big controversy a couple of years ago when a company that was selling EpiPens

01:38:43.880 decided egregiously for no apparent reason other than just malicious greed to jack the prices up?

01:38:51.000 Has that resolved? And are EpiPens now relatively inexpensive again?

01:38:55.640 That's right. That company was Mylan and they were making EpiPens. And that's why I called it

01:38:59.320 injectable epinephrine device because now there's a lot of them. Thank goodness the FDA, other agencies

01:39:05.120 got involved and said, okay, this is not right. You cannot keep charging that enormous amount of

01:39:10.400 money. And so then what we call generic epinephrine devices started to be made. Other companies started

01:39:16.440 to hit the road. There's other devices now that can be used called the AvaQ. So I think luckily now,

01:39:23.360 thanks to many industries involved in this, there's also potentially a nasal Epi that can be used. So yes,

01:39:29.920 that company was seen as providing methods that were not ideal at all. And that was stopped,

01:39:37.880 thank goodness, because no one should be charged that amount of money for a life-saving drug.

01:39:43.040 What were they charging for EpiPens?

01:39:45.500 Oh, it was like 400 up to 600 for some of my patients. That luckily now is being covered by

01:39:51.440 insurance. But again, third-party payers also need to make sure that they can reimburse for these

01:39:56.700 life-saving medications.

01:39:58.400 Well, Carrie, this is really interesting stuff. Look, I've learned a lot today, certainly getting the

01:40:03.260 differences in some of the immunology here. Also, I think the PM 2.5 story is something that I look

01:40:08.860 forward to digging into a little bit more, especially as someone who does spend a lot of

01:40:13.120 time outside. Maybe no more than 10% of the time like anybody else, but it seems like I spend more

01:40:17.960 time outside. So I'd certainly like to be aware of that. Anyway, thank you very much for most of all

01:40:22.600 your work. I've seen firsthand the impact it has had on people's lives. And I know that there are

01:40:27.360 probably a lot of people who are hearing about this for the very first time today. There are people who

01:40:30.120 are listening to us or watching us who know somebody who suffers from a devastating anaphylactic

01:40:36.520 reaction, who probably at this point in time are completely unaware that such a therapy exists.

01:40:41.800 I guess my final point is, what would you suggest for those people, someone listening or hearing this

01:40:46.940 who is being blown away by what you're telling them, where can they either find a clinical trial or

01:40:53.120 find a non-clinical trial provider who's able to walk them down this pathway?

01:40:57.760 Well, first of all, thank you, Peter. Thank you for your excellent questions as always. I'm really

01:41:02.060 excited to be on the show and thank you for your curiosity and your care on this podcast.

01:41:07.080 For people that are learning about this newly, what's wonderful is you can get on your computer,

01:41:12.780 do a search on clinicaltrials.gov, look under the category of food allergy, and you can find out

01:41:18.900 what clinical trial nearby you is actually ongoing for food allergy therapy. And there's a lot more than

01:41:24.240 there were just five years ago, so that's good. There's like 17 companies in this space now.

01:41:28.080 I'm really excited about the future. There is a lot of hope and promise. Within that hope and promise,

01:41:32.860 there are more clinics around the country as well that are specializing in food allergy. I gave you

01:41:37.880 one example of latitude, but there are others as well. And so with that in mind, I would go to your

01:41:42.380 healthcare provider, ask them questions. If you feel like they don't have time or they haven't really

01:41:47.200 answered the questions in the way that you learned about today, go online and find out those clinics

01:41:52.940 that specialize in food allergy therapy. And again, not everyone fits with everyone, so give it a test,

01:41:58.900 see if you like that structure, and then you can try. And I hope the best because that possibility is

01:42:05.080 there, that reality is there, and I hope everyone tries to undergo therapy.

01:42:09.760 Carrie, thank you so much. This was absolutely fascinating.

01:42:12.260 Carrie. Thank you. Thanks for your great questions.

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The Peter Attia Drive - October 30, 2023

#277 ‒ Food allergies： causes, prevention, and treatment with immunotherapy ｜ Kari Nadeau, M.D., Ph.D.

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