- Full Text Transcript:
- How Steve, the New RHR Host, Came to Be Here
- The Latest Study Showing the Concrete Connection between Chronic Stress and the Immune System
- Can Arguing with Your Significant Other Trigger Inflammation and Cause Disease?
- Recommendations for Benchmarking Your Inflammation from Chronic Stress
- The Latest Fasano Paper: Could Healing the Gut Prevent and Cure Autoimmune Disease?
- Why Fixing Leaky Gut Can Stop and Reverse Autoimmunity
- Will the Latest Intestinal Permeability Drug Trial Lead to Celiac’s Eating Gluten Again?
- How to Overcome IgG Food Sensitivity to Eggs and Milk
- The 3-Step Process for Figuring out the Right Diet Changes That Work for You and Your Body… Once and for All
The podcast is back! Only now it’s not a podcast, it’s a radio show (Revolution Health Radio), and we have a new host: Steve Wright. Everyone say “hi” to Steve!
We had a few growing pains on this first episode, so the audio is not quite as good as it normally is. We’ve got it ironed out now, though, so expect studio quality sound from here on out.
In the first episode of Revolution Health Radio (RHR), we cover:
- 1:17 How Steve, the new RHR host, came to be here
- 5:13 The latest study showing the concrete connection between chronic stress and the immune system
- 10:38 Can arguing with your significant other trigger inflammation and cause disease?
- 16:51 Recommendations for benchmarking your inflammation from chronic stress
- 21:18 The latest Fasano paper: could healing the gut prevent and cure autoimmune disease?
- 27:02 Why fixing leaky gut can stop and reverse autoimmunity
- 36:59 Will the latest intestinal permeability drug trial lead to Celiac’s eating gluten again?
- 44:12 How to overcome IgG food sensitivity to eggs and milk
- 54:07 The 3-step process for figuring out the right diet changes that work for you and your body… once and for all
Links We Discuss:
- Study: Chronic Stress, Immune Dysregulation, and Health
- Study: Leaky Gut and Autoimmune Diseases
- Diabesity: The #1 Cause Of Death And Disease
- 9 Steps To Perfect Health: Manage Your Stress
Full Text Transcript:
Steve Wright: Hello, everyone and welcome to the Revolution Health Radio Show. I’m Steve Wright from scdlifestyle.com and with me is Chris Kresser, health detective and creator of chriskresser.com. How’s it going today, Chris?
Chris Kresser: Well, to be honest, I’m a little bit sick for the first time in a long time and this will be a good segue into one of the papers we’re going to talk about which is Effect of Stress on the Immune System but Sylvie’s been teething, she started teething pretty early. She’s only four months old but she is starting to get a tooth and for those of you who have kids, you probably what that means. I’m not sleeping very much. She’s just really kind of out of sorts during the night.
And then, my family was out visiting. I have like nieces and nephews and three or four of them were sick so both Sylvie and I got sick because I’ve been really run down and not sleeping and so I’m a good case study for this stress paper we’re going to talk about. Steve, why don’t you introduce yourself, tell everyone where you’re coming from, how you came to be here on this show and just let everyone get to know you a little bit.
How Steve, the New RHR Host, Came to Be Here
Steve: First off, again, I want to thank you Chris for allowing me to have this chance to be your host. I think it’s going to be a great friendship that we’re going to build here and a great show. A little background on me, my friend, Jordan and I, we run a blog, scdlifestyle.com and the blog is dedicated to digestive problems and people who suffer with them.
Everything from bowel disorders, IBS, celiac disease, all those types of things. Jordan had celiac disease and I used to have IBS and we used a specific carbohydrate diet and supplements to really turn our lives around and our health around. And we feel really passionate about this subject and helping people and so we went ahead and created an E-book about how we did it and how people like us could turn their health around as fast as possible using this specific carbohydrate diet.
Chris: Right. Let me jump in and say, for those of you, actually one of my patients the other complained to me that we throw all these acronyms around and talk about these diets and we just kind of assume that everyone knows what they are and a lot of people do but for those of you who don’t know, some of you may be familiar with the GAPS diet and the GAPS diet is very similar to the specific carbohydrate diet but they’re, they’re like Paleo but they completely remove starches so you wouldn’t eat sweet potatoes or plantains or things like that and there is more of an emphasis on fermented foods and bone broth particularly in the GAPS diet. So how long have you been doing that for, Steve?
Steve: I started in January 2010 and previous to that I’ve been sick for five or six years. So since then, like you said, the GAPS diet and the SCD diet are very similar and Jordan and I have found out that along with Paleo and the starches that like you prescribe too, there’s no one diet for all. And so our take on the SCD diet really goes to the next level we think where we embrace the different things that the GAPS people have an emphasis on as well as some things like we’re not poopooing, no pun intended, starches or anything like that. But that we take the opinion that everyone needs to find their own diet. They need to test all foods and that everything should be subject to a test.
Chris: Yeah, great. So we’re glad to have you, Steve and Jordan is our behind the scenes genius helping with producing the show and making sure everything’s running smoothly and so I’m really glad to have you both on my team. So why don’t we dive in? We’ve got some interesting stuff to talk about today. Actually, one of the studies we’re going to cover is related to the gut as most of my listeners know; it’s one of my favorite subjects, too.
So I’m going to talk about the stress paper that I mentioned especially because it’s front and center on my mind right now. The connection between stress and the immune system and then we’ll talk about the new leaky gut paper by Alessio Fasano who is one of my favorite researchers and real pioneer in the field intestinal permeability in autoimmune disease research. And if we have any time after that, we’ll get to some questions. I know I did a Facebook post listing questions but I decided that I really want to talk about these two studies. If we don’t get to some of the questions, we’ll get to them on a future episode. Sound good?
Steve: Sounds great, man. I can’t wait to hear what you think about these studies.
The Latest Study Showing the Concrete Connection between Chronic Stress and the Immune System
Chris: Alright. So let’s talk about this paper, the title is Chronic Stress, Immune Dysregulation and Health. I can’t remember where I came across, somebody sent it to me. Last week is all kind of a blur. Let’s start with the definition of stress. That’s actually the first line of this paper and I really like their definition of stress. I think it will people understand what I mean when I talk about stress because I mentioned it several times on my blog and the Nine Steps to Perfect Health series on the podcast.
I’m really trying to encourage people to take a broader view of what stress is because most people hear of stress and they think of psychological and emotional stress like financial problems or problems in a relationship or anything like that and of course, that is stress but stress is actually much more inclusive. The definition these researchers used was, “stress occurs when environmental demands exceed the individual’s capacity to cope.” So from that perspective, anything that throws the body out of its natural balance or homeostasis being the more technical term is a stressor. So an injury could be a stress, a chronic gut infection could be stress. You know, over training especially the wrong kind of training can be a stressor on the body which means you could have no cares, you could be independently wealthy and laying on a beach in Thailand with absolutely no psychological or emotional stress whatsoever but if you have a gut infection, you’re under stress. And I think that’s really important to understand when we talk about addressing stress.
The other thing is when you look at it from this perspective; there are two different types of stress. One is called eustress and the other is called distress. Eustress is the kind of stress that is actually beneficial which is the stress that encourages an adaptive response. So an example of that would be exercise if it’s done properly. Like if you go and you lift weights, that weightlifting tears down your muscles. But when your muscles grow back, they grow back a little bit bigger so that they can handle the next challenge and that’s an adaptive evolutionary mechanism. So that kind of stress can be beneficial because it helps us to grow and expand our capacities.
Distress is often chronic stress and this is the type of stress that directly affects our immune function via neuroendocrine and sympathetic pathways and over time, consistent activation of those systems can cause wear and tear on the body that researchers refer to as allostatic load. So you know often mild acute stress especially when it’s adaptive like with exercise is beneficial but it’s that chronic stress that can be so harmful to the body.
And in the paper, they review a number of impacts of chronic stress but one of the main impacts is inflammation. And that’s something of course that we talk about a lot as well but studies have shown that even acute psychological stress can reliably increase interleukin 6 levels, that’s a type of inflammatory cytokine and C-reactive protein which is an acute phase reactant, a type of protein that’s elevated in the inflammatory response and it’s pretty well known and pretty well established in the literature now that chronic stress is associated with chronic low-grade inflammation and that’s the type of inflammation that’s associated with nearly every modern disease like cancer, cardiovascular disease, diabetes, autoimmunity, obesity, etc.
And one of the best models for studying this, one of the most frequently used models in the literature is they look at caregivers. You know, people who are taking care of a partner who have Alzheimer’s or dementia or other degenerative disease because that’s just so, so stressful. And when they study the caregiving population, they find that they have often double or even triple the risk of mortality than age-matched non caregivers. And you know, they’ll study circulating inflammatory markers and find that they’re higher. Their CRP is often higher and this is just more evidence of the toll that chronic stress takes on the body.
Can Arguing with Your Significant Other Trigger Inflammation and Cause Disease?
There was an interesting section in the paper where they were talking about conflict and even arguing with your spouse or partner can wreak havoc on your immune system and there was this study on couples who engage in frequent hostile negative interaction, that’s the way they put it. These couples had much higher levels of interleukin 6 that inflammatory cytokine than less hostile couples.
And then another study showed that people with a frequency of interpersonal conflict in their daily life had higher levels of interleukin 6 and higher levels of CRP. So you know, the lesson there of course is be nice to your partner. You know, the interpersonal conflict which can affect us emotionally is affecting us physiologically. And most people know this already intuitively, right. It doesn’t feel good in your body when you’re angry or really upset but I think it’s helpful to have the mechanisms pointed out where people can make a concrete connection between emotional and psychological stress and real physiological mechanisms that are affected by that and that was kind of the point of this paper.
Because a lot of times when I talk to people about stress, I think what happens, everyone has kind of an idea and a real direct experience that stress causes physiological problems you know even just on a simple level, if someone has a fear of public speaking or even if they don’t and they have to you know get out in front of a group of people, they’re going to probably notice some kind of fluttering in their belly, you know. Some people actually experience pretty severe gastrointestinal symptoms if they have to speak publicly. There’s a really strong clear connection so people aren’t really surprised by this.
But I think now that we have a better understanding of the actual mechanisms involved and people can really understand what those mechanisms are, I mean, personally I’ve found that that’s helped me to take stress more seriously and to really pay attention to it and really elevate it to the same level and sometimes in some cases even higher than nutrition and a lot of the other things that we talk about because it’s really difficult in the modern world to work with it and it’s a lot easier to change the diet and to take supplements I think for most people than it is to really address these stress mechanisms.
So there were a couple of interesting things about this paper. We’ve talked previously on the show I think when we did gut-brain access podcast about the connection between chronic inflammation and depression and in fact, some researchers now think that there is a model of depression or study of depression called the inflammatory cytokine model of depression and some researchers really believe that depression is primarily mediated by inflammation.
But this paper was saying that there’s also evidence that it work the other way around that depression can cause chronic inflammation which in turn leads to immune dysregulation and the evidence for that is that among clinically depressed patients, treatment leads to a reduction of circulating inflammatory markers and then initial levels of depression like when they do prospective studies of people with depression, people who start out in those studies depressed end up having higher levels of circulating inflammatory markers.
And you know, prospective studies are observational in nature and they can’t really prove anything but it’s an interesting correlation and when you put it together with the fact that treating depression reduces inflammatory markers, there’s quite a lot of evidence to support that connection.
And then the last thing I want to talk about in this paper is that most of you know, I think, that cortisol is one of the main antiinflammatory hormones in the body. It’s part of the fight or flight distress response. When we’re under stress, the body makes cortisol and cortisol suppresses inflammation. That’s how it’s supposed to work, at least but studies have show recently that persistent exposure to high levels of cortisol during chronic stress actually down regulates cortisol receptors on cells. So this leads to cortisol resistance where the immune cells become nonresponsive to the antiinflammatory effects of cortisol. In a way, this is just like insulin resistance only it’s working with cortisol.
So the takeaway is that when somebody is under chronic stress, they’re almost certainly going to be chronically inflamed and if someone is chronically inflamed, they’re almost certainly going to have a poorly functioning immune system and that can manifest as increased susceptibility to infectious disease like cold and flu, case in point for me this week. Or it could manifest as autoimmunity which we’re of course seeing a huge rise in over the past couple of decades and there are a lot of reasons for that. I think nutrition certainly plays a strong role but we’d be kidding ourselves if we didn’t acknowledge the role that I think increasing stress of modern life plays in the rising incidence of autoimmune disease.
Recommendations for Benchmarking Your Inflammation from Chronic Stress
Steve: So Chris, I’m guessing as someone who wants to try to maximize their health, you wouldn’t want us to be rushing out and getting our IL-6 or CRP test that we should just assume then based on this paper that we all have some stress if we’re living in a modern world that we should probably be taking some steps.
Chris: Yeah. Maybe you’re hearing Sylvie’s sound effects in the background there. She’s having a rough morning with this tooth coming in. Yeah. I think, I mean getting CRP measured can be useful. IL-6 is not very often tested in the clinical setting. You might have a hard time getting your doctor to order it. But CRP can be useful if anything else as a benchmark, you know, to see where you’re at. But if you’re under chronic stress, you can pretty much assume that you’re dealing with some inflammation and for all the reasons that I just mentioned. I don’t think it’s necessary to get a test to confirm that and yeah, I think it’s just a question of taking some steps to reduce the amount of stress that you have in your life if possible. It’s not always possible but there are some things you can do, even if you can’t really change the circumstances of your life, you can change the way you relate to those circumstances and that has a net effect of reducing stress.
And then you can also do things to increase your stress tolerance so that the stress that you are experiencing in your life doesn’t impact your body in the same way. And I outlined several of these things in the article on managing stress in the Nine Steps to Perfect Health series so if you go to chriskresser.com/perfecthealth, there is an index of all those articles and it’s the one titled, Manage Your Stress and there are several recommendations in that article for some of the things that you can do.
But interestingly enough, one of the most negative impacts of chronic stress and this is in the literature as well is that people who are under chronic stress will tend to adopt behaviors that can be damaging to their health or discontinue behaviors that could have protective health effect. So it’s one of those chicken and egg things or vicious cycles really where in someone who’s really stressed out says, “I’m too stressed out to do stress reduction.” No. or I’m sure you’ve all had the experience of we’re like really, really stressed or really upset, we might have craving for food that we wouldn’t normally eat or our diet kind of falls apart or whatever but that’s another reason why taking specific steps to manage that stress can be helpful because it puts us back in a kind of upward spiral instead of the downward spiral that chronic stress can often involve.
So I think that’s it unless there’s anything else you want to say about that, Steve.
Steve: No, I would say that I know from personal experience that if I spend too long outside of the gym that I can almost feel that anxiety kind of creep back into my life and that I’ve also tried your recommendations and I really like the rest and digest program. I use some of those exercises on like a daily basis, like you know, five minutes here or there during the day and that seems to really help so…
Chris: Yeah, I like that too. I think that you’re referring to the Rest Assured program, right?
Steve: Oh yeah, the Rest Assured program.
Chris: Yeah. Rest and digest might be a better name now, I like it. Yeah, so the Rest Assured program, you can get it at soundersleep.com, you can download the mp3s and it is really helpful. One of the things I like about it, in particular is that, like you said there are some techniques that can be done and as little as four or five minutes throughout the day and that really can just help keep the edge off even if you’re busy. Most people can find a few minutes during the day to do that.
Steve: Four or five minutes? I only do it for two and I feel it.
The Latest Fasano Paper: Could Healing the Gut Prevent and Cure Autoimmune Disease?
Chris: So there you go, there you go. Well, cool. Let’s talk about, let’s dive into the Fasano paper. Yeah, like I said, he’s really one of my favorite researchers. I’ve read, I think, everything that he’s published and I was really excited to see a new paper come out, it just came out, I don’t know, 23rd of November, I think. It’s called, “Leaky Gut and Autoimmune Diseases” and it was the clinical review of allergy and immunology. I just posted a link to it on Twitter, twitter.com/chriskresser this morning because I tweeted about it yesterday.
But, as I said before, Fasano is a bit of a pioneer in the field of leaky gut and autoimmune disease. He’s the one who’s really established in the scientific literature, at least, this connection between leaky gut and autoimmunity. And we’re going to talk about this more in more detail but I also wrote about this in my series on diabesity and the connection between the gut and diabetes and obesity.
But his view is actually that you can even develop autoimmune disease without a leaky gut and I’ll explain more about that in a second but first, I want to talk about some of the more conventional theories about autoimmunity or maybe I should say more traditional or recent views on autoimmunity because I don’t know that they’re actually conventional.
But early on after autoimmune disease was discovered, most people thought that they were associated with viral and bacterial infections and in fact there is a school of thought still today that believes that there is no such thing as autoimmunity and that all autoimmune diseases are actually infectious disease and infections that we may not be able to detect with our methods of testing it at this point.
Yeah, so there’s a whole group of people who believe that autoimmune disease does not exist and that all autoimmune diseases are actually infectious diseases and they may be infections that we can’t detect with our current method of testing. I think there’s a microbiologist named, Paul Ewald, I might be getting his first name wrong but I think that’s what he believes and there are a number of different groups that believe that.
But the connection between a non self antigen like bacteria or virus and autoimmune disease is often explained by a mechanism called molecular mimicry and it works like this, a microbial like virus or bacteria or a food antigen like gluten enters the body and then the immune system mounts an attack against it and produce antibodies but since the chemical structure of those non self antigens can be similar to proteins found in various tissues in the body, you get a cross reaction where as the body is attacking those non self antigens, it also starts attacking itself and it can attack the thyroid like in Hashimoto’s or Graves or it can attack the joints in rheumatoid arthritis or the myelin sheath in multiple sclerosis or the gut in inflammatory bowel disease and animal studies have confirmed that molecular mimicry is part of the autoimmune process.
But here’s the interesting thing, in human studies, it appears that molecular mimicry might be the effect rather than the cause of autoimmunity. So in other words, that molecular mimicry process that I just described is only a factor in the progression of preexisting autoimmune diseases. So that’s one theory, the molecular mimicry theory. And I would say that’s probably the most popular theory at this point.
Another theory of autoimmunity is called the bystander effect and it’s just similar to molecular mimicry. In this model, those non self antigens like bacteria or viruses directly damage the tissue in the body and the exposed parts of the tissue that shouldn’t otherwise be exposed and then the body attacks those parts of itself, of the tissue as if they were not self.
So I think the important thing to understand about both of those theories, the bystander effect and the molecular mimicry is that the idea is if you, even if you remove the trigger which could be a bacteria or virus or gluten, according to those theories, the autoimmune process will continue because the antibodies have already been produced and the body’s has already started attacking its own tissue and because of the way the immune system works, once the body starts producing antibodies then it won’t ever stop and that benefits us because for the most part, like if you get exposed to chicken pox when you’re a kid and you get exposed to that virus again later in life, you’re not going to get it.
And there could be 30, 40 or 50 years that pass but the body always remembers. But according to molecular mimicry model, that backfires on us when we’re dealing with this autoimmune process. But Fasano is proposing an entirely different theory of autoimmunity that involves leaky gut as a crucial element and he says that three preconditions have to be present for autoimmunity to develop and I covered this again in that article on the connection between the gut and diabesity.
Why Fixing Leaky Gut Can Stop and Reverse Autoimmunity
Number one is that you have to have a genetic predisposition to autoimmunity. So some people have asked me, why my friend eats a really crappy diet even worse than I ever ate and doesn’t really exercise and is really stressed and he doesn’t have autoimmune disease but I have three autoimmune diseases, you know, what’s that about? That’s probably about genetics. There is a genetic predisposition to almost every autoimmune disease that has been studied.
Number two, there has to be an environmental trigger. So even if you have the genes, the genetic predisposition to autoimmune disease, without an environmental trigger, it won’t get activated and that’s, that can explain why even though our genes haven’t changed that much in the last 100 years, very little if any, there’s been this explosion of autoimmune disease. that’s because even though the genes haven’t changed that much, the environment has changed quite a lot and the environmental triggers now are happening all around us both in food and then in air and water, you know, by chemical toxins and those are triggering these genetic tendencies in the way that didn’t happen 100 even 150 years ago.
And then number three and maybe most important in Fasano’s model is that, you have to have a permeable intestine or a leaky gut or more specifically abnormal function of the tight junctions. So the tight junctions or TJs as they’re called, if you take your hands and you interlace your fingers, that’s what kind of what the tight junctions look like. I mean on a much smaller level. then if you open and close your hands so that you can create a little bit of space between your interlaced fingers and then you close so that’s there’s no space and nothing can get through, that’s kind of how the tight junctions are supposed to work. They selectively allow molecules to pass into the bloodstream that should be in the bloodstream like nutrients that we need and then they’re supposed to selectively prevent things from entering the bloodstream that we don’t want in our body like antigens, pathogens or large molecules that would provoke an immune response.
But what happens with leaky gut is that those tight junctions stop being able to make that distinction and they just permanently become a little bit open so things start passing through the gut like a sieve and that’s a big problem because one of the main purpose of the gut is to serve as a barrier that keeps things outside of the body that shouldn’t be in the body and lets things in that should be in.
So Fasano introduced us this trinity a while back and a lot of research supports it. we know that celiac disease and type 1 diabetes, MS, rheumatoid arthritis, Crohn’s and several other autoimmune diseases have all been associated with leaky gut that allows the passage of these antigens from the intestinal flora into the bloodstream and this then challenges the immune system to produce a response that can target any organ or tissue in people that are genetically predisposed. So the significance of this is pretty huge because if it turns out to be right, it implies that contrary to those popular theories of autoimmune disease like molecular mimicry and bystander effect, the autoimmune response can theoretically be stopped and then even reversed if the interplay between genes and environmental triggers is eliminated.
Let me use an example to explain what I mean. Celiac disease is actually a perfect example of this because we know what the genetic factors are, the HLA-DQ genotype. We know what the environmental trigger is which is gluten and its many subfractions and then we know that celiac is characterized by a leaky gut. So I just mentioned gluten and its subfractions.
I want to take a little side tangent for a second and talk about that. one of the sections in the paper that really stood out to me and I talked about this in my first article in the Nine Steps to Perfect Health Series, Don’t Eat Toxins but you know, it used to be thought that it was just pretty much gluten that caused problems and now we know that the repertoire of gluten peptides that are involved in disease is a lot bigger than we previously thought and in this latest paper, Fasano says there are at least 50 different toxic epitopes in gluten peptides that have been shown to destroy cells, dysregulate the immune system and cause leaky gut.
So when we’re talking about the proteins in wheat, we can talk about gluten, gliadin, deamidated gliadin and then even with gliadin, there are different epitopes like alpha, beta, gamma and then we have wheat germ agglutinin or WGA. There are just a number of proteins that can cause problems like destroying cells and destroying tissue in the gut.
So back to what we were talking about before, zonulin is a protein that was recently discovered. It regulates the tight junctions and Fasano has talked a lot about this in his research. And we know that zonulin is overexpressed in people with autoimmune diseases like celiac so the more zonulin they have, the more leaky their gut is.
It basically works likes this, if someone with celiac eats gluten or gluten intolerance and then they get an increase in zonulin production and then that increases inflammation, inflammatory cytokine production and then tight junctions in the gut open, you know like those interlaced fingers open and allow passage of antigens from the gut into the blood and then the body mounts an immune response and then you get an inflammation in the gut and everywhere else.
But as Fasano explained, this process can be completely reversed in people with celiac if you remove gluten from the diet. So when you take out the environmental trigger which is gluten, you see a decrease in zonulin levels, you see that the intestinal barrier function which is supposed to keep things out and let the right things in is restored. Antibodies drop and the whole autoimmune process shuts off and then even after that, the intestinal damage, if you take away gluten for long enough, repairs itself completely.
It kind of leads to the question, is this a cure? Does this mean that autoimmune disease can be cured? I guess the answer to that depends on what you mean by cure. It doesn’t mean that a person with celiac can go eat you know a pizza and get away with it but it does mean they can live a normal healthy life if they order that interplay of genes and environmental triggers.
Unfortunately, in the case of other autoimmune diseases, the trigger isn’t quite as clear. We know that gluten can exacerbate and even trigger other autoimmune diseases by making the gut permeable in that framework that we’re talking about. If you have a genetic predisposition, environmental trigger like gluten and then leaky gut, you can develop autoimmune disease and not just celiac, a bunch of the other ones that I mentioned.
But, what I can say, you know, in my practice, in my experience working with patients is that removing gluten often helps but it doesn’t always completely resolve the condition as it would in celiac, you know, where you see that decrease in antibodies and repair of tissue and everything else. And in some cases like in Crohn’s, the trigger is not something that can just be easily removed because the trigger in Crohn’s is thought by a lot of people to be the commensal gut flora or the normal gut flora and the body is essentially mounting an autoimmune response to its own gut flora and it’s pretty hard to remove that since it’s a normal part of the body. You can’t really fully sterilize your gut unless you live on antibiotics and there are obviously a lot of reasons not to do that.
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Will the Latest Intestinal Permeability Drug Trial Lead to Celiac’s Eating Gluten Again?
But one interesting thing in this paper and I’m always naturally skeptical of drugs until I really see research that shows that their safe because do no harm is always the first principle of medicine even though that’s often forgotten but there’s a drug that they’re trialing right now. It’s in phase 2 clinical trials, it’s called larazotide and this is a zonulin inhibitor so, you know, zonulin as I mentioned is the protein or the substance that interferes with tight junction function.
So larazotide, they’ve done a proof of concept inpatient study. It was double blind, placebo controlled. It took two groups of patients with celiac and they gave them gluten. I mean, I’m wondering who signed up for this study, like, I have a lot of celiacs and man, when they eat gluten, it’s painful to watch what happens and the reaction can go on for a long time. So bravo to whoever signed up for this in the name of science or maybe they gave them a good financial reward or something.
But they took these two groups and they gave them gluten and one group was on a placebo and the other group was given larazotide. And in the control group, as you would expect, there was a 70% increase in intestinal permeability with the exposure to gluten so no big surprise, right? You give a celiac gluten and they get a leaky gut. But the big surprise was that in the larazotide group there was absolutely no change at all in intestinal permeability.
So they fed these celiacs gluten and the people that were taking larazotide did not develop leaky gut and furthermore, although they had some GI symptoms from eating the gluten, they were a lot less than the control group that was taking placebo. So you know my philosophy on medicine is whatever works and causes the least harm and in most cases that’s not a drug but in some cases like low-dose naltrexone which I’ve talked about a lot and thyroid hormone medication that can sometimes be, it can sometimes be a drug and perhaps larazotide will be that for autoimmune disease, I don’t know. It’s certainly worth following and I’ll be following it over the next couple of years.
I don’t think it will be, if they’re only in phase 2 trials, it’s probably going to be a few years before that medication would make it to the market and there have been a lot of drugs that have never made it out of phase 2 or phase 3 trials because of unanticipated side effects because you’re messing with function of the body that we don’t completely understand. We still don’t really fully understand zonulin and what it does and how it does what it does. So it’s still to me a little bit scary to be taking a drug that inhibits zonulin production without fully understanding that but I will mention that in the study, there were no adverse effects compared to placebo in the larazotide group. So it seems to be well tolerated at least in the very small study.
It was, I think, where is the sample size? I don’t remember the exact sample size but it was small, I think 14 patients or something like that. So we definitely would need to see a bigger study that was powered to better detect whether there would be adverse effects versus placebo and whether the drug effect was real or just, you know, consequence of chance.
Steve: That’s really encouraging. I just feel bad for the people who are going to be involved in the next phase of the, 200 to 300 people that are on the placebo.
Chris: Right. I mean, it certainly does present an ethical problem. I mean, it’s not as serious as some of the studies that were done in the past, you know, where they, and even recently where you had studies continuing where you know part of the drug treatment arm is you know, they’re dying at a much faster rate but yeah, that’s some serious discomfort. I don’t have celiac but I have a lot of patients that do and I guess you would know, Steve, that that’s not fun.
Steve: Yeah. From the people I’ve talked to, you’d have a hard time signing up anybody who’s lived in a symptom-free life to try that study so…
Chris: Yeah. So I guess there are people that probably haven’t found the GAPS study or the specific carbohydrate diet and they’re probably pretty desperate.
Steve: Do we know anything yet as far as what increases or decreases zonulin like stress or supplements or anything?
Chris: I mean gluten certainly increases it but, no, not that I know of at least. And I think probably inflammation is likely to do it. I mean, we know that inflammation causes a leaky, contributes to leaky gut and that chronic stress contributes to a leaky gut and we know that zonulin mediates the tight junction function so we could surmise that chronic stress and inflammation probably have an effect on zonulin which in turn causes the intestinal permeability but I’m not aware of any papers that have directly studied that. Nor do I know about any supplements that have an effect on zonulin one way or the other.
But interesting line of thinking, I have to look into the larazotide and what exactly it is and what it does and it will be interesting to think about other ways of accomplishing the same thing without using a drug.
But certainly, the basics that we always talk about are the starting place. Take out the toxins from your diet, eat nutrient-dense food, manage your stress, you know, make sure you’re doing all the things you need to do for a healthy gut like eating fermented food and possibly taking probiotics if you need and then making sure you’re getting enough sleep and you’re exercising and you’re having a good time in your life. That’s always the starting place, you know, and this stuff that we’re talking about here is for the people who’ve already done all that stuff and they’re still struggling and the same is true for low-dose naltrexone when we talk about that. I never suggest that someone just goes right to low-dose naltrexone and without doing all the other stuff that we’ve been taking about first.
So I think that’s it. It didn’t take quite as long as I thought so we may have time for a couple of questions.
Steve: Well, I’m looking at a question here that I think might really follow up those studies well and give you a chance to talk for a little bit longer if you want to go into one of those.
Chris: Let’s dive in.
How to Overcome IgG Food Sensitivity to Eggs and Milk
Steve: This one comes from Lana from Facebook and it’s, “how can one overcome IgG allergies, for example, eggs and milk? Thank you.”
Chris: Yeah, I think this is related for sure. First of all, I think a lot of people who have been listening to this show for a while know what my opinion is about IgG food allergy testing. I think it’s not ready for prime time. It’s been shown in experiments like my colleagues and I drawing our blood, labeling two different vials with two different bogus names and sending them to the same lab and getting completely different results. If you look into the scientific literature, there’s not really any support for IgG food allergy testing.
However, if you have an IgG food allergy and it says you’re allergic to eggs and you eat eggs and you feel horrible, well, that’s, you know, I’m not going to debate that but I’m more into paying attention to the symptom that you have when you eat eggs. Let’s just assume that someone has, well, let me step back again. I assume by IgG allergy they mean intolerance because if it’s a true allergy where, you know, you eat eggs and you have an immediate hypersensitivity reaction or anaphylaxis or something like that or the type of allergy that you can have to shellfish or peanuts or strawberries in certain people, I’m not sure that there’s that much that can be done about that.
If we’re talking about food intolerances where you eat eggs and you feel bad but you’re not like headed to the hospital, you know, with your life at stake, then I think this really falls into what we’ve been talking about all along. I think most food sensitivities are caused by leaky gut. That’s why I’m always a fan, an advocate of healing the gut and instead of, you know, continually removing more and more foods from your diet until there’s nothing left to eat because that’s just dealing with the symptom. The symptom is the intolerance to these particular foods but the cause is the leaky gut or the gut dysbiosis or gut infection or some combination of all three of those which is usually the case.
So, milk is a little, it’s a little more complicated because are we talking about pasteurized milk or raw milk? Are we talking about actual milk or are we talking about fermented dairy? Are we talking about full-fat dairy like cream or butter or ghee? As I talk about in the Personal Paleo Code, there’s a really, really big difference in all of those dairy products and if someone is sensitive to dairy, you have to ask are they sensitive to the casein which is the protein or are they sensitive to the lactose which is the sugar or are they sensitive to both?
If they’re only sensitive to the lactose then they should be able to tolerate dairy products that have very little lactose like ghee has no detectable lactose. Butter has very, very little lactose and if the ratio of fat to protein and sugar and butter is like 80 to 1. And then if you do homemade fermented dairy like they recommend in the specific carbohydrate diet and in GAPS where you ferment your own yogurt for 24 hours, you can pretty much get rid of the lactose in it. If you make kefir, you ferment for long enough, you can get rid of the lactose almost entirely so even people who are lactose intolerant can often deal with long fermented dairy and some of the full fat dairy products.
If someone is sensitive to casein, the casein protein then they’re going to have problems with nearly all dairy except for maybe ghee because ghee in theory doesn’t have much detectable casein either and whether somebody can overcome that or not, I would say that depends. Some of the most recent research about the effect of probiotics suggests that the real benefit does not come from restoring or repleting the number of probiotic organisms in our gut because really, most orally consumed probiotics are only putting a tiny little dent in the total number of probiotic organisms that we have in our gut.
But the recent thinking is that the probiotics are modulating the microbiota, the intestinal flora and they actually change the milieu in such a way that we can begin to digest foods better and we can even begin to digest certain foods that we haven’t been able to digest before and that explains why, and so our gut flora is somewhat adaptive and like for example we know that people who live in coastal areas in Japan, they have different gut flora than people who live maybe in the mountains in Europe. And they have different gut flora because they eat different foods and they require different bacteria to break down those foods.
So for example, there’s a type of bacteria that’s really helpful in breaking down the nutrients in seaweeds that the people in coastal Japan eat a lot so they’re bound to have a lot more of that bacteria and maybe if you took someone who is living in the mountains in Europe and they went in coastal Japan and tried that much seaweed, they wouldn’t be adapted to eat it. They wouldn’t be able to process it as well as someone who has that genotype or that, in this case, the intestinal microbiota to handle that.
Art Ayers who writes a blog called Cooling Inflammation has posted some interesting research in the past and theorized that some people who eat fermented dairy can cure themselves of lactose intolerance over time because they can change the gut flora in such a way that they become able to process fermented dairy or just dairy in general. But I don’t know if that works the same way with casein. Most people in my practice who are casein intolerant pretty much stay casein intolerant. You know, maybe other people have had other experiences but that’s just been my experience so far.
Steve: I know that I used to have a big problem because I tried making the SCD yogurt, the 24-hour fermented yogurt when I first started the diet and I did it with goat’s and cow’s and either of those were raw milk. They’re just store bought organic stuff. And it took me a really long time. I had this postnasal drip for a really long time and it wasn’t until I had seen an allergy specialist who was like, have you ever tried just not doing any dairy for seven days or something like that?
And so it turned out that’s what it was and so doing that. And then I did have a Candida infection that I got rid of but after that, I am able to eat dairy again including, you know, even the crappy kind, not the raw stuff.
Chris: Right, right. So I mean, it’s hard to say what you’re reacting at that point but I definitely think that that’s possible and I think that that’s probably mediated to some extent by the way that the bacteria in the dairy are modulating your own intestinal microbiota. And I do see that a lot. I mean that’s true in my experience, too. When I first started the GAPS diet way back, I’m not doing it anymore, but this is during my more therapeutic phase, I could only tolerate like a half a teaspoon of kefir and I would notice it, I would really feel it. And then it was a teaspoon. And now I could drink two pints of it and feel great and not noticing any negative effect at all. So there’s definitely some change that happens in the gut with that but usually you have to go, start really with a very small dose and proceed really slowly over time.
And it’s still optional. It’s only if you want to eat dairy. I think it’s a healthy food when it’s well tolerated and it’s got a lot of, you know, fat-soluble vitamins and things that can be hard to come by otherwise but there’s certainly no rule that you have to eat dairy. If you’re happy without eating dairy then proceed.
Yeah. I think we’ll stop there. There are several more questions but I’m going to give my voice a little bit of a break this week and we can come back to these questions in another episode.
The 3-Step Process for Figuring out the Right Diet Changes That Work for You and Your Body… Once and for All
Steve: Okay. Well that brings us to the end of this week’s show, Chris. Do you want to tell us a little bit more about the Personal Paleo Code launch and how that’s been received?
Chris: Oh yeah, sure. So I finally got that out. I see it was a couple of weeks ago now. Personal Paleo Code, for those of you who don’t know about it is a program designed to help you discover your own ideal diet instead of following a canned approach, you know, this is designed for everybody. And it was borne out of my experience working with patients, most of whom were totally confused about diet and even within the context of the Paleo community; there are a lot of disagreements. I don’t think they’re big disagreements but you know, Robb Walsh might say this and I might say that and Mark Sisson says that and you know, somebody else says a different thing.
The whole premise of the Paleo Code is just to stop listening to all of us and follow this three-step process that I use with my patients in my practice to figure out what works for you and your body once and for all so you don’t have to spend your evenings with Paleo hacks trying to figure it out anymore.
You can go to personalpaleocode.com. It’s been really well received. I had a lot of great feedback which of course feels good because I worked really hard on it. The meal plan generator in particular has been really popular. That’s a web app that allows you to generate highly customized meal plans using only the ingredients that you want. So for example, if you’re on the GAPS diet, you can just hit a button and it will bring back only GAPS recipes or if you’re on autoimmune Paleo diet, you can exclude nightshades and dairy and eggs and get a meal plan that only has recipes that don’t contain those ingredients.
It’s been a lot of fun and yeah, if you’re interested, go check it out, personalpaleocode.com.
Steve: Alright. I want to thank everyone for listening this week. Keep sending us your questions at chriskresser.com and you can use the podcast submission link to do that. If you enjoyed listening to the show, head over to iTunes and leave us a review.
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