What are the biggest mistakes practitioners make when treating autoimmune conditions?
The incidence of autoimmune disease continues to rise, with no signs of slowing down. The challenging side of practice is unravelling each patients’ unique triggers and guiding them through peeling back the layers whilst simultaneously implementing strategies to help build back in their quality of life so they can continue to function in everyday activities. It’s a delicate balance and something Dr Datis Kharrazian is all too familiar with both from a clinical practice and research stand-point.
Ahead of his trip to Australia to be a keynote speaker at the forthcoming BioCeuticals Research Symposium, Dr Kharrazian joins us to paint a picture of what we can expect to learn from him in 2020 from genetics, lifestyle, diet, the microbiome and beyond.
Covered in this episode
[00:33] Welcoming Dr Datis Kharrazian
[01:40] The challenges of treating autoimmune disease
[03:25] Autoimmune triggers
[05:59] Different scientific theories for the cause of autoimmune disease
[10:35] Explaining haptenization
[12:20] Managing autoimmune disease clinically
[15:28] Using artificial intelligence
[17:01] How autoimmunity patients present and delayed symptoms
[19:35] Foundations of treatment
[22:10] Testing for markers of flare-ups
[27:50] Exploring Treatment
[29:00] Struggles and side effects of pharmaceutical drugs for autoimmune diseases
[34:38] Mistakes to watch out for
[36:48] What reactions to supplements?
[40:44] Pathogens and autoimmunity
[44:13] Cross reactive proteins in food
[45:32] What to expect from Datis at the 2020 BioCeuticals Research Symposium
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. Joining us on the line today is Dr Datis Kharrazian. He's a clinical research scientist, academic professor, and a functional medicine healthcare provider. He's associate clinical professor at Loma Linda University School of Medicine, a research fellow at Harvard Medical School, and a researcher at the Department of Neurology at Mass General Hospital. Dr Kharrazian earned a PhD degree in Health Science concentrating on immunology and toxicology, and a Doctor of Health Science degree from Nova Southeastern University. He completed his postdoctoral research training at Harvard Medical School and Mass General Hospital, and Dr Kharrazian earned a Master of Science degree in Human Nutrition from the University of Bridgeport, a Doctor of Chiropractic degree from Southern California University of Health Science, and a Master of Medical Sciences degree in Clinical Investigation from Harvard Medical School.
Dr Kharrazian, I warmly welcome you to FX Medicine. How are you today?
Datis: Doing well. Thank you for having me on.
Andrew: It's our pleasure. Now, today we're going to be discussing why autoimmune disease patients just don't get better. So I guess we start off with, what's the real issue going on with autoimmune treatments?
Datis: Sure. I think the first thing that I think is a core in a sense for practitioners is that autoimmune disease for the most part is a disease that can go into remission, but it's not curable. No one has figured out how to actually cure autoimmune disease. So it's one of these chronic inflammatory diseases that flares up and a patient can go into remission and feel like they're cured at some point, however, there's always that susceptibility to flare up again.
But I think one of the frustrating things that a patient may not understand, or the practitioner may not understand is that it's an ongoing battle, that once the genes...it's turned on for autoimmunity, and there's multiple chains and multiple triggers that change the expression of the phenotype into an autoimmune disease, then there is this ongoing susceptibility.
So that's why, you know, the word "cure" is such a strong word, and it's so harmful to patients when they're trying to think that, you know, they're going to clear out their heavy metals and they're going to be cured, or they're going to fix their gut and they're going to be cured. Those things don't necessarily cure, they just decrease the immunological load on an individual. For some people, it can be helpful. For other people, it can have no effect.
So I think the real thing to first understand about why autoimmune disease patients don't get better is, you know, that's actually clearly an uncurable condition…
Andrew: Yeah.
Datis: …and these relapse or remissions are part of the disease.
Andrew: Can we talk a little bit about the variable triggers and initiation of the various autoimmune diseases? Like, you've got, you know, juvenile rheumatoid arthritis and then you've got lupus, and so many others obviously, but, you know, why is there such a vast variance in when the autoimmune disease is triggered?
Datis: True. So what we know about autoimmune disease in the research world is that there's multiple genes involved, that there's not one gene. So there could be an HLA-DQ gene, there could be a single nucleotide polymorphism, there could be some genes associated with specific T-cell responses. And it's a combination of these genes in combination with many variables that can include things like chemical exposure to pathogens, various things that cause immune dysregulation all happening together that's been shown to then turn on the onset of the disease.
So it's multi-factoral susceptibility and multi-factoral triggers that then turn on the autoimmune disease. Now, there are certain specific pathogens, then susceptible individuals have been shown to turn on different diseases.
Andrew: Yep.
Datis: There’s definitely chemical triggers, there's lifestyle triggers that play a huge role. And I think for most people, they kind of think of the last thing that was the final blow, but it's very clear that it's multi-factoral, multi-variant variables that turn on the disease, with multi-factoral genetic susceptibility. That's why it's so difficult to cure. It's also so difficult to clearly find one insult that does it.
Andrew: Is there any work on looking at the multiple insults that are needed or that are required to cause the perfect storm?
Datis: They are absolutely looking into those things. So what they can do now is they can say, for example, if you have a HLA-DQ genotype, you have a 20% increased risk for this autoimmune disease. But they don't know what all the variables are. So they can find individual variables that impact autoimmune disease, but they haven't figured out how they all stack up together. And to be quite honest, it's going to require machine learning, and it's too complicated…
Andrew: Yeah.
Datis: …unless we use equipment. We still need data to actually figure out what to put into the machine. So we're really, really far away from figuring that out in the world of research of that. But we do know people develop autoimmune diseases, we just don't know what all the variables are.
Andrew: Yeah.
Datis: And that's what makes it so difficult and frustrating.
Andrew: Talking about gut priming, I'm aware of, you know, the work by Dan Littman and others, Ivaylo Ivanov at New York State Uni in Columbia, I think it was, with regards to...and I do bang on about this, forgive me, Datis, in FX Medicine, that is, these segmented filamentous bacteria priming the Th17, and possibly priming autoimmunity.
Datis: Sure.
Andrew: Do you know of any work that's being done in this area in humans?
Datis: Yeah, of course. There's specific regions within the world of autoimmunity where people are doing research. So there's some people that are looking at molecular mimicry. There's people that are looking at what are called epitope spreading. There's people that are looking at what's called T-cell differentiation, which is what you're talking about.
Andrew: Yep.
Datis: There’s people that are looking at T-cell propagation. There's people that are looking at citrullination. So there's actually dozens of these models. What happens is sometimes when you speak to one of them you think that's the model for all of it, and it's really not. So there's at least 21 known mechanisms that cannot turn on autoimmune disease. Activation of the Th17 just falls under the categories of T-cell proliferation where your different T cells act inactive. And for some autoimmune diseases, the gut is really a big deal, and for other autoimmune diseases, the gut is not really the main issue. And this is what we also see clinically, that some patients that come in, they're gut is perfect…
Andrew: Right.
Datis: …and other people, it makes a life-changing clinical impact on them when they clean up their gut on their autoimmune disease. So I think that's a problem we have tried to do in functional medicine, is kind of ignore all the research, and then try to come up with a model of, like, it's really just leaky gut, it's really just a pathogen, it's really just dysbiosis, and it's not necessarily any one of those things, but it's all of those things, and it can be different things or different parts of those things for different people. So that’s what’s… and that's the reality of autoimmunity when you, kind of, really read up on to it and really read what's happening in the immunology world, if you go to an autoimmune scientific conference where different researchers speak. And I think what the difference is in functional medicine we try to cut it down to a few things that are a part of the picture, but it's not the entire picture. And it's definitely unique for each individual. So there could be some people that get pathogenic bacteria and that turns on their Th17 as part of it, that could be a trigger for an autoimmune disease, for example, in combination with susceptibility and other variables.
Andrew: So the most dangerous words are, "It's just that?"
Datis: Exactly. That’s the… for myself, that's what I see so frustrating with what people are talking about and doing, is they explain one model and they give reference for the model, and it's like, yeah, that is one part of the picture of the autoimmune world, but it's not all of it, and that doesn't apply it to all individuals. So, for example, one autoimmune process unrelated to the gut microbiome is called citrullination, and this is where arginine transforms to a new protein that then becomes a new antigen, or neoantigen, and they know that like a gingivalis infection, gum disease can turn on that process. And then that process is found to really express in joint cartilage, and it's one of the mechanisms for RA, completely unrelated to the gut microbiome, just from the gum, just from the oral mucosa. So…
Andrew: Wow.
Datis: And, again, that has happened with susceptibility for that person because not everyone with gum disease gets a citrullination process that takes place. So, once again, it's multiple genes plus finding that trigger...that has been shown to do it. So that's what's kind of interesting with autoimmune because in a clinical setting, that's what different about it. For some people, managing their gum disease maybe one way they can manage their autoimmunity, for other people, it will be working on their microbiome. For other people, they may have a process called haptenation where they can't clear chemicals out of their body well…
Andrew: Yeah. Yep.
Datis: …chemicals bind to proteins and they become new antigens. For them, biotransformation, liver cleanses could be a big part of how they go into remission. So that's the thing about it. It's fairly complex and it's not one variable, and it's different from one person. And the person coming in with an autoimmune disease, let's say RA or MS, doesn't tell us which way to go through it. Each and every one of those mechanisms are all possible to some degree.
Andrew: Yeah. Can you explain something for me about haptenization? Am I correct in this thinking that when people say, "I'm allergic to iodine," for instance, they usually not?
Datis: Yeah.
Andrew: I mean, you can't be allergic to iodine. But there's some degree of...am I correct here...haptenization there that is causing this link to an inert mineral or something?
Datis: Well, remember, you can only develop antibody to cause an immune response to the actual protein itself, that’s your protein. So different compounds can bind to proteins, but they can change the structure of the protein. And that's what's called haptenation.
Andrew: Right. Right.
Datis: Some of the research we published out of Harvard Medical School was looking into things like BPA plastics, and how plastics combine to albumin, which is the most abundant protein in circulation, and that creates a new antigen. And then we showed that that can directly be associated with development of a neurological autoantibody, and also associated with Parkinson disease development from an autoimmune perspective. So that's, kind of, haptenation. Now, iodine, you know that iodine is been shown to be a clear trigger for Hashimoto's disease, even though many people like to use iodine for thyroid disorders. But iodine also activates the synthesis of TPO, thyroid peroxidase...
Andrew: Yep, yeah.
Datis: And then the target protein for Hashimoto's is TPO.
Andrew: Right.
Datis: So one of the theories for some of these people that flares up, it's really the iodine that increases the TPO synthesis. It's possible that iodine can bind to different structures and change the protein, but I've never really read too much about that. I don't have a...
Andrew: So when we're talking about realistic prognoses for autoimmune disease, I mean, really what we're trying to do is thwart the accepted nomograph, if you like, I guess, of decline?
Datis: With autoimmune disease, I mean, the first question we always like to ask clinically is, where's the rest of it? Because usually when they have one autoimmune disease, they have other autoantibodies that they're unaware of. So, what we like to do in a clinical setting is to then screen for other tissue antibodies. Sometimes the history really gives us clues of what's going on, sometimes we just do a general screen. And then we really find that most people that have one autoimmune, like, for example, they have Hashimoto's, they have RA, they'll have autoantibodies to other target proteins that they don't even know is a potential for becoming an autoimmune disease. And then the next question is, what are the triggers? And you're ultimately left with dietary triggers, lifestyle triggers, pathogen triggers, and chemical triggers, and then just general immune health, which relates to the gut in T cells and B cells, and then you're trying to assuage all that through medical history, and their physical exam, and lab work, and then kind of figuring out the right approach. And a lot of times the patient will just tell you, like, they will tell you that they're autoimmunity flares up if they just don't get enough sleep. There's lots of associations between circadian rhythms and how sleep impacts immune cell priming and modulation.
Andrew: Yeah.
Datis: And for other people, it's very clear the protein exposure, and for other people, they've eliminated all foods and this made no difference in their autoimmunity, and it's not food. And for other people, it's a chemical exposure, a combination of multiple things. And that's what's makes autoimmune clinically so hard to manage.
Andrew: I'm imagining your intake form, and I'm imagining that it would be a small book.
Datis: No. I mean, I don't think it's any different than a normal person that has some history…
Andrew: No?
Datis: …and obviously we want to look at all those things, but there's a point where we want to look at, like I said, the big picture. So, yeah, I mean, we can use, I guess, some good intake forms. But, you know, it’s still… with autoimmune disease management in my practice when I work with my patients, I tell them, "We don't know. There's going to be lots of trial and error. We're going to try to go through the most common mechanisms that can be triggers from you, but we'll have to spend some time figuring out. And we'll have to work through your case and then try to figure out how to get you in remission, and then once you're in remission, how to monitor you, make sure you don't progress further…”
Andrew: Yeah.
Datis: “And then if you do have flare-up, which are inevitable, how do we put you on a protocol right away to have you recover as soon as possible?" And that's kind of the big picture, at least for me when I work with patients suffering from autoimmunity. I mean, it is a complex condition. I think it could be one of the most complex conditions. It's certainly as complex as cancer and other non-curable diseases out there.
Andrew: Can I ask, with regards to machine learning, which you mentioned earlier…
Datis: Yeah.
Andrew: do you think maybe the future might hold promise with, you know, managing autoimmune conditions by, let's say, different data sets? You know, you're mentioning sleep, you're mentioning gut, we've spoken about oral hygiene…
Datis: Yeah.
Andrew: If there was some way of collecting this data amongst...you know, do you concentrate on just one autoimmune condition or do you get it across the breadth, and maybe, you know, letting artificial intelligence in the future work out which has the most bang for buck?
Datis: Yeah, this is actually something they are doing at Harvard Medical School, they have a bioinformatics research division, and they're looking at doing these for multiple diseases, including autoimmunity where they can track weather, pollutants in an area where the patient's been in, they can look at their food intake, they can look at their trigger, and they can keep that data.
Andrew: Wow.
Datis: And then they have different algorithms where they can start to program and fine-tune to then look for flare-ups. They're already doing that with...the easiest example is asthma. So they already have apps which they can track where the patient is in relation to pollution and different pollutants in the air, and then start to be able to give them warnings when they know when they get a trigger, they start to get warnings when they get exposed to that. And that's already a part of personalised lifestyle apps with machine learning and algorithms, so that's pretty cool. So I think eventually in the future, that's what's going to happen.
Andrew: And I was going to ask also, how does a patient with autoimmunity present clinically? And I guess, alongside that, you were talking about earlier, you know, how patients say they don't get enough sleep, and then the next day their symptoms flare. What about delayed symptoms?
Datis: So, to answer your first part, how do autoimmunity patients present? The first part is they have a huge list of everyone they've seen. They see these listed talented practitioners. They've all thought it was one thing or another. Some thought it was their microbiome, some thought it was a leaky gut, some thought it was...who knows what. And they've all tried their interventions. They may have had some results here and there, patient continues to have good and bad days, and flare-ups. Some things made a difference for their life, and they're happy to have figured out those things, but they're still suffering. They usually have a huge list of supplements, countless supplements that they're just taking out of desperation. They usually have noticed reactions to foods, they’ve been limited a lot of foods, some are already on a very restricted diet. And many of them actually don't know they have an autoimmune disease. They just think they're, have this weird illness no one has figured out yet, but, in fact, they do. So there's a group of patients that don't know they have an autoimmune disease with that history, then there's some that finally know they have an autoimmune disease but didn't know the autoimmune disease attacking all the other symptoms that they may be having. So that's how they typically present. And what was the second part of your question? I'm sorry.
Andrew: With regards to delayed symptoms rather than immediate symptoms.
Datis: Yeah, that’s very true. So one of the things, depending on the autoimmune mechanism, you could have an exposure to a trigger, and then you may have response several days later. I mean, the easiest example is, I mean, a food…
Andrew: Yeah.
Datis: …immune food delayed issue is a delayed response, that could being exposed to food and not have the flare up until a few days later. And then there could be issues associated with other variables that combine together so it's even harder to track than one thing. So that's one thing. And some of the research that was published by Vojdani, he showed, for example, certain food proteins don't become antigenic until you combine them together.
Andrew: Right.
Datis: So he did a study where he looked at, let's say, cheese, wheat and sausage or meat, and then he found what percent of reaction was. And then he combined them together on a [inaudible] which is pizza, all cooked together. And then there was a significant trigger with a large population of the study that didn't respond to each of the triggers individually. So that's what makes it difficult.
Andrew: Okay. So then to try and treat that...I mean, you know, it's impossible to think about different combinations. I mean, you're into codes here.
Datis: Yeah.
Andrew: But if you went back to the gut and you said, "Okay, well, let's try and give the gut some resilience," is that a reasonable…
Datis: Sure.
Andrew: …you know, foundation of treatment?
Datis: Yeah. And I don't mean to...I don't seem like I don't think the gut has an impact. The gut has a major impact on autoimmune disease. And, you know, the more immunological tolerance a person has, the less reactive they are, for example, to foods or combination of food proteins. And the role of immunology in autoimmunity, there's a concept called oral tolerance.
Andrew: Right.
Datis: And oral tolerance is how active your immune system becomes to exposure to different triggers. So oral tolerance is specific to food proteins. So we know, for example, if a person eats a food protein, that protein can trigger an antibody response and then trigger the autoimmune response, but that food protein can only trigger it while it's a protein structure, and the antibodies bind to protein structures, not to amino acids. So if someone isn't digesting their proteins, they have inability to break down the proteins to individual amino acids, which tends to nonreactive, then their enzyme deficiency can make them much, much more susceptible to foods and immune triggers.
Something as simple as just taking digestive enzymes can be a huge impact for some people that have autoimmune disease because now they're breaking down that protein structures that antibodies can bind to individual amino acids more efficiently. The gut microbiome has a major impact on regulatory T-cell function, and much of the research being published right now on the microbiome shows the more diverse the microbiome is, the less reactive intestinal T cells are to food proteins.
Andrew: Yeah.
Datis: So there's lots of little, you know, things that happen in the gut, whether it's regulatory T cells in the gut or microbiome diversity, or enzyme breakdown, or dendritic cell activity. These things are all important. And as you do the work up for autoimmune disease patients, you have to go through each of these factors one-by-one, and see if a patient does respond to each of these individual variables. But it is an important part of autoimmune function, but there are definitely people that that is not the mechanism for their autoimmunity to go into remission. There's other things besides the gut that are factors.
Andrew: I'm going to ask a dangerous question because I'm not one given to excessive testing and wasting, you know, in some cases, hundreds and thousands of dollars in certain individuals on useless testing. But would there perhaps be...here we go, it's a wish for, say, in the future, would there be a test, or a simple array of tests where you could say, "Hey, listen, you're on a downward trend with your autoimmune disorder. You're starting to flare?"
Datis: There's definitely those tests, and the key thing is to do what's called a cytokine-stimulated test. And if you do a cytokine-stimulated test, what they do is they take a person's blood...we can do this in lab, they take the person's blood, you isolate out the T cells, and then we put the T cells in a dish, and then you activate it by antigen, usually something like pokeweed or something. And then that T cell releases cytokines, and then you can measure the cytokines with the different types of equipment, with the flow cytometry. And then when you measure those cytokines, you can see what the immune system is primed into.
So one of the most important ratios is this Th3 to Th17 ratio. So Th3 cells, which are regulatory T cells promote autoimmunity, and Th17 promote the inflammatory response. And then Th17 cells release things like IL-17 and regulatory T cells release things like TGF-beta. So there's ratios between these different cytokines, between Th3 and Th17, and they find that if a person has higher Th3 activity, they're in remission, and they're going to stay in remission. And if they switch to a higher Th17 and Treg, they're about to flare up.
Andrew: Right.
Datis: So that is one of the most sensitive markers. Unfortunately, there hasn't been enough commercial labs to offer this test. It's, kind of, still in the research world. But, you know, these tests are expensive, and I think, for the most part, they don't seem as marketable…
Andrew: Right.
Datis: …to the population. But that would be the most sensitive test. And you could literally do a blood draw and then figure out where you're headed.
Andrew: Yeah, yeah.
Datis: And if you're in a stressful period, you can look at your ratios and go, "Oh, my God. I'm about to have a flare-up."
Andrew: Yeah. Of course, then you have to have the appropriate management to coincide with that, to get them back on track.
Datis: Yeah. And if your regulatory T-cell function is great, then you know you're doing all the right things. So, you know, sometimes with autoimmunity, you just don't know because there's so many variables, you don't know if the things you're doing are some that get you to where you need to be. So you could have someone who figures out, what type of exercise they can do without crashing, and how long they can do it without falling apart, and then that really helps their autoimmunity. And then they find out that there's a few food proteins like gluten or nightshades, they can't eat, they get rid of those. Then they find out if they cut out a little bit, if they can get some sleep, that can be a big issue for them. And then those factors all add up and they're kind of starting to feel better, but not really sure. And then if they had that Treg measurement, and they start to see their Treg function go up, it would be a home run to know they're on the right path.
Andrew: Yeah. Forgive me for asking you to repeat this, but what were the ratios of, you know, let's say, good versus bad? I know this is very simplistic, but even if we could just have a guide, some yardsticks?
Datis: Yeah. So it's going to depend...I mean, the thing is you have to kind of…you can’t just, kind of, use a lab to measure IL-17 and TGF-beta randomly because they have to be done from the same T cell.
Andrew: Ah.
Datis: It can't just be secretion levels.
Andrew: Right.
Datis: What labs are doing right now is they're measuring the cytokines in blood, and you have to have extreme levels in blood to show an extreme cytokine activation to show these level high blood. That's why you have to do what's called that cytokine-stimulated test, or T-cell-stimulated test…
Andrew: Yep.
Datis: …and that way isolate to the cell in a dish. That's why it's expensive and it's why it's unfortunately unavailable. But they can bring that cost down and people can just do, like, a single prick with blood and send that in, that would be probably the future of looking...yeah.
Andrew: Wow. That would be really, really good.
Datis: But I think it will get there. It's just a matter of time.
Andrew: Yeah.
Datis: But also, what's been published in the literature already is they look at acute-phase reactants on blood work.
Andrew: Yep.
Datis: And acute-phase reactants like C-reactive protein and serum ferritin, and even ESR levels have been shown to start to elevate from baseline before a flare-up. So the key thing there is that it's not just outside the lab range, but, like, if you know what your baseline C-reactive protein is and you know what your baseline ferritin levels are, if you start to see them go up, that could be a strong indicator that there's about to be an autoimmune flare-up.
Andrew: Yeah. Obviously, CRP is used in, I'm going to say gross amounts, if you like, with Crohn's disease, for instance.
Datis: Yep.
Andrew: But what about hs-CRP? Would that be a more sensitive indicator of something's going to happen, or you just measure CRP?
Datis: Or a high-sensitive CRP I think, for most people, would be the preferred test.
Andrew: Gotcha.
Datis: And it's better technology. You know, some of the labs are just saying they're not distinguishing anymore between high-sensitive CRP and CRP because everyone's starting to use highly-sensitive CRP. Might be different in Australia, but in the U.S…
Andrew: Right.
Datis: …they are not making those clear on lab reports because they're all using highly-sensitive CRP now.
Andrew: Gotcha. So now we need to speak about treatment. Where do we go from here?
Datis: The key thing is you have to have a very proactive patient, and you have to have a patient that's very observant, and then you're basically trying to do one variable at a time. And, you know, the basic concept is for them to have more good days than bad days. And it's different if you're doing treatment in an acute flare-up scenario versus the, kind of, in and out of remission, and you can try to maybe keep them in remission for, let's say, several months, maybe even keeping them in remission for a month straight would be an ideal scenario.
If they are having RA and their joint pain is really active, and you figured out a combination of things clinically, or their joint pain goes away for the next eight weeks, then they get exposed to something, then the trigger becomes much easier to identify. So, and it can change from time to time. So that's what makes autoimmune disease so frustrating, because it's not caused by a single nutrient deficiency, and it's caused by multi-variables that impact multiple genetic susceptibilities, and it's dynamic and changing all the time.
Andrew: Datis, what about the effects of, you know, the new kids on the block? These are the blockbuster drugs of the age, the monoclonal antibodies. I've sometimes heard, for instance, a drug used in, again, Crohn's, Adalimumab…
Datis: Yes, yep.
Andrew: …some people say that the "effect" wears off. Do you find this is real, or do you find this is just part of the actual autoimmune disease?
Datis: Oh, there's definitely people who will take medications that block immunological pathway, or will take a monoclonal antibody and they will have a beneficial effect on their autoimmune expression. The issue with it for most patients is that they don't have a ongoing effect because it makes them...tends to outsmart the drug over a very short period of time.
Andrew: Ah, right.
Datis: So that's the difficulty with it. And some of the most aggressive drugs are also...one of the side effects that they make a person very immune-susceptible. So, in most of these trials that have been done for short-term and long-term studies really show that sometimes the immune system gets more activated, more inflamed, and then they try to go off those other side effects and other issues with it. So, in the past, you know, the basic thing, the CT steroids which shut down the whole immune system, and, like you're saying, now they're basically using different types of medications to inhibit subsequently T cells or B cells where they target specific B cells with monoclonal antibodies, or they specifically block TNF-alpha.
And there's some people that it really does help them. And what we find is the best use of those types of medications, people that have very serious autoimmune diseases like demyelinating MS where they end up in a wheelchair…
Andrew: Yeah.
Datis: ….they get a flare-up, is to use them in the acute crisis care, and then really focus on diet and nutrition lifestyle, you know, at other times, because there are other problems when there's immune system activation and flare-ups. Immune system can prime itself and wind up even further and further, and never recover back to baseline.
Andrew: Right.
Datis: And at times as they destroy tissues, surrounding tissues start to then develop autoimmune against them. This is what's called the bystander effect.
Andrew: Aha.
Datis: So you may, for example, have antibodies against, if you have MS, against myelin basic protein, but as the inflammation destroys myelin, it also starts to destroy the protein structure within neurons. Now you also develop antibodies to break down the synapsin, now you get synapsin autoimmunity. Now the autoimmunity is much worse and much more progressive.
Andrew: Right.
Datis: So, you know, for me as a person who, you know, practices functional medicine, and is definitely not primary pharmaceutical treatments or those things, I mean, an integrative approach, and especially in pharmacology, can be very helpful for some people with very serious autoimmune diseases. But at the same time, you can't ignore how diet and lifestyle impact autoimmune disease, I mean, it's a well-known mechanism. It's funny, I work with the Institute for Functional Medicine and they did a survey few years ago, and they asked how the physicians in that group got interested in functional medicine. And the number one answer was they or their family member got sick.
Andrew: Yeah.
Datis: And then they were looking for their own option.
Andrew: That's right.
Datis: And then, all of a sudden, they were willing to try some vitamin D, or want to, you know, try a probiotic for the first time, but they would never ever, in their entire career in practice ever recommend that, or read a paper on it. There's that total human characteristic that comes out, you know?
Andrew: Yeah.
Datis: It's different when it's you.
Andrew: But, again, I guess another aspect of this is you'll get people that, for instance, got sick themselves, let's say chronic fatigue, or Hashimoto’s…
Datis: Yeah.
Andrew: ….or Ehlers-Danlos syndrome, and then they looked into it for themselves, their family members. That's fine for EDS…
Datis: Yep.
Andrew: …or for whatever, the disease they have. But what about another one?
Datis: Yep.
Andrew: What about somebody with Hashimoto's, which they haven't got?
Datis: We really look at so many patients suffering out there because they don't have anyone to guide them, and they just, you know, don't really know where to start to get accurate information. And, you know, the internet is filled with, like, simple solutions to complex situations.
Andrew: Yeah, yeah.
Datis: It’s that simple. So it is a problem with research and studies, too, because when you look at, for example, with the most studies, they're done to be generalisable to the population as much as possible, and they're looking for one change, like a change in blood pressure or something.
Andrew: That’s right.
Datis: Autoimmunity is not that simple, and it's multi-factoral, and it's dynamic, and it's changing. So in the world of research, there's something called NM1 trials where you look at a patient, you measure certain biomarkers and you do a multivariate treatment, multiple things at once, which is what we do in functional medicine. And then you monitor them over time, and those things can change. And that's really the real clinical model and the real research model they can apply to autoimmunity.
Andrew: Right.
Datis: So it's like, it's the thing. So what happens with practitioners, you know, kind of, like, some practitioners, they, kind of, label themselves. They become the heavy metal leaky, you know, curator. They become microbiome expert. They become the adrenal exhaustion guru. And then they see any disease that way. And then those types of models don’t work for autoimmunity. I mean, they have a limited effect, I should say, in autoimmune.
Andrew: Yeah. So I guess this carries on to my next question, and that's, what's the biggest mistake that practitioners make who are working with autoimmune disease? And I guess we've already said it, that they over-simplify, that it's that, you know, one thing or another, or it's just that.
Datis: Yeah.
Andrew: What are the mistakes do you see practitioners making that we really need to wake up about?
Datis: One of the big mistakes is they do too much at once. I can tell you for myself working with autoimmune disease patients for over 20 years with a very comprehensive approach from day one, was the only thing I can be really proud of over the years is I don't make autoimmune disease as flared up as I used to. I mean, I'm really proud of that. That's a huge accomplishment for me as a clinician.
Andrew: Right.
Datis: Easy to, you know, give patients multiple supplements, multiple things, and they react against all of them…
Andrew: Yep.
Datis: …or react different for them. So I think the key thing with autoimmune disease management in a clinical setting is you have to, kind of, go work through step-by-step, and then create the environment for the patient to understand you have to do a multivariable treatment model, but you can't do all of them at once. You have to, kind of, filter through and see what they respond to, what they don't do. You, kind of, like, you know, you're pushing and pulling, tugging away different areas of the autoimmune web to seeing how you can untangle it. So I think one of the key mistakes is just being too aggressive at once and not looking into it slowly.
The other mistake is making unrealistic expectations. That can completely make a case fail if patient loses all trust and their spirit gets broken because they think that, you know, when their levels of mercury on their chelation conscience goes away, that they should be better, but they're not, you know? Or when their GI panel doesn't have a pathogen anymore, that they should be better, when they're not.
Andrew: Yeah.
Datis: So those are big mistakes, and that happens every single day. And I think for all of us that practice functional medicine, when we see an autoimmune patient come in, they all have huge files. They all have the list of things they've all done, and how they were treated, and it's very clear to see that these mistakes happen every day.
Andrew: Yeah. You were mentioning that, you know, patients often react to the supplements that they're given.
Datis: Yeah.
Andrew: When you see that there's a lot of immune cells close to the skin, and guarded by the very tough stratum corneum, what do you think there might be of the facility of perhaps doing, say, a scratch test with a multivitamin?
Datis: Well, I mean, when you're looking at the immune supplements, the main issue isn't always, like, an immune response in a sense…
Andrew: Yeah.
Datis: …from an antibody sensitivity. Remember a skin test is only going to measure an IgE immunity response…
Andrew: Right.
Datis: ….and the IgG then is not an issue. The biggest thing with supplements is that, like, sometimes you'll give someone...a supplement has 20 ingredients in them, and one of the ingredients in there is like maitake mushroom or Echinacea…
Andrew: Yep.
Datis: …which then stimulates their T cells, and they don't even realize that their T cells are being stimulated, and then they get a flare-up.
Andrew: Ah.
Datis: Or they'll take a supplement, and the filler in there, it says, "Modified food starch." And it's actually gluten is the filler in that supplement. So sometimes it's contaminants from poorly made supplements and sometimes there is immune-activating supplements in there. And there's also a lot of contamination in supplements in plant compounds that we know about. So we know, for example, in California, we have a proposition that was passed, Prop 65, which would single out any chemical compounds in any supplements here. And that's difficult to do because some plants typically have a little bit of naturally occurring chemicals in them. You know, there's some ingredients manufacturers can't even use anymore in California because of worldwide toxicity, you know, like rice, rice protein. If you test any kind of rice protein, doesn't matter where you get your source of rice protein, most of it will have some contamination with arsenic or lead…
Andrew: Yep.
Datis: …to some degree. Now, there's normal contamination in foods that we eat all the time just because of the environment, but for some people, the supplement will have some type of a...it could have a chemical, it could be an immune stimulant, it could have a filler that's an issue with them, or sometimes they just can't handle too much immune support at once, you know, and that…
Andrew: Right.
Datis: …becomes a problem from that.
Andrew: So it could indeed just be the facility of their immune system not handling it?
Datis: Yeah. I mean, even with the high-quality supplements. I mean, it's not always contaminators.
Andrew: One of the things that we're quite proud of in Australia is the due diligence and the surveillance of the Therapeutic Goods Administration, the TGA, which differs from the FDA, I understand. But what you're saying is that some of these issues, like, for instance, rice protein, it doesn't matter where you source it from, it's going to have some level of contamination with a heavy metal?
Datis: Absolutely.
Andrew: Right.
Datis: Sorry, if the guidelines are...it can only have enough contamination which is found in normally occurring rice, then some guidelines will allow that to be used, you know?
Andrew: Yep.
Datis: In every other state in the United States, that can be done in manufacturing. In California, it's not permitted anymore…
Andrew: Right.
Datis: …because they’re capturing, no levels, not even natural occurring, you know, levels of contamination.
Andrew: How do they eat rice?
Datis: Well, they can eat rice, they can eat rice, but now you have to have warnings on rice and food products in California, or you can't sell them.
Andrew: Wow.
Datis: So it's different than the rest of the United States. And there's also lots of manufacturers who completely moved out of California when they passed this, the law.
Andrew: Wow.
Datis: They can't manufacture. Many supplements in California will actually have to have warning labels on them because they're not following the guidelines that these may contain carcinogenic compounds or things on them, which makes it difficult for anyone buying supplements to want to take them.
Andrew: Yeah. Absolutely. Just along that molecular mimicry concept. I remember attending a talk by Professor Alan Ebringer where he was talking about the associational or the cross-reactivity between, I think it was Klebsiella and AS. Where is this going? Where has it led since then? Is that still true or has it moved on from there?
Datis: Yeah. Yeah there’s a whole list of… there’s many review papers now available on National Library of Medicine, PubMed, you know…
Andrew: Yep.
Datis: …scientific literature where they have definitely reviewed and linked many pathogens to various specific autoimmune diseases. And when a person makes an antibody against, let's say, a pathogen, the antibodies can be similar enough to the protein of the pathogen as a cell tissue, or the antibody for the pathogen binds to a cell tissue structure. And then that causes the autoimmune disease flare-up. So, we did some research where we purified 204 proteins and we found all the different cross activity with food proteins, 200 most common foods consumed with thyroid autoimmunity and with Type 1 diabetes. And we published that research. So that becomes the major clinical strategy when you're dealing with someone who's got Hashimoto's and they're already on an autoimmune paleo delay and they don't know what else to eat for their Type 1 diabetes.
So it's some sensitive research that I've done and published that I do put into clinical practice and use that I'd like to share with people. And it's the applications from other research on molecular mimicry is also important to do, for example, like you said, pathogens for specific autoimmune diseases.
Andrew: What about things like interstitial cystitis? And if an antibiotic knocks out the infection…
Datis: Yep.
Andrew: …does it knock out the priming or is the priming set now for life?
Datis: No. So, for example, if you had the pathogen that turns on an autoimmune disease, like interstitial cystitis, one of the target proteins for interstitial cystitis is tropomyosin antibodies.
Andrew: Right.
Datis: Tropomyosin is the antibodies to smooth muscles. And many people with interstitial cystitis have antibodies to their smooth muscles, and they could have had a different pathogen turn on that tropomyosin response. But once the pathogen is gone, there's antibodies that are produced against tropomyosin, and there's cross-reactivity or similarity between the protein structure of the pathogen and tropomyosin. So now there's B cells with tropomyosin. And then when things activate antibody production, you can have a flare-up. So, for example, shrimp has tropomyosin in there. So if you have interstitial cystitis, and also you have colitis, and you have tropomyosin antibodies, when you eat shrimp...if you have sensitivity to shrimp, you're making tropomyosin antibodies, which then flare up your interstitial cystitis.
Andrew: Right.
Datis: A pathogen to turn on antibodies, those antibodies can then cross-react with cell tissue and you can have foods that have those similar food proteins and you can have that reaction. So you get a bacterial infection, turn on interstitial cystitis. Now there's memory B cells, and therefore tropomyosin, and then you eat food that has a similar amino acid sequence, then you get a trigger. So that’s…
Andrew: Oh gosh. Yeah. So I guess one of the tricks with managing autoimmune disease would be working out which are the cross-reactive proteins, assaying them, and then working out which foods or which triggers contain those. And that's part of their ongoing management.
Datis: So we've mapped out...so we started with foods, so we sort of mapped out thyroid, with 200 food proteins, we published in Journal of Thyroid Research. We just submitted a paper to a journal where we looked at chemicals that we thought would have molecular mimicry with haptenation of thyroid. And there's already a long list of pathogens, but we hope to do a study where we look at multiple pathogens beyond what's been published already. And then the goal for us as researchers is to try to blueprint each autoimmune disease by their molecular mimicry. We're focusing on Hashimoto's first, it is the most common autoimmune disease, but in the future, when someone has an autoimmune disease like Hashimoto's, we can go, "Okay. Well, we've already done these lifestyle things, and you've already fixed your gut. You still have autoimmunity, and you're already on a restrictive diet, like, let's say an autoimmune paleo diet. But let's see if there's any specific molecular mimicry chemical responses in food proteins or any pathogens that could be triggering your immune response." So that's big picture. Big picture is to rule each one out and then go through each in more detail.
Andrew: Datis, you'll be coming to Australia…
Datis: Yes.
Andrew: …in early 2020 for the BioCeuticals Research Symposium. What sort of things will you be teaching practitioners there? Obviously there's a lecture, but then there's going to be some case study and some hard-core learning there. What sort of things do you want practitioners to walk away with?
Datis: Well, I think I want to really talk about a realistic model of practice. Too many times, you have patients, and they present and they show you a perfect case, and rainbows come out, and everything's perfect, and they're amazing, and they're awesome, you know, and I hate that. I'd like to really show people the difficulty and the realities of practice, especially things like autoimmunity. So I'm going to share with them real case videos of real patients, what they went through, the struggles, the ups and downs, and really talk about the real world working through a clinical case model.
At the same time, you know, I spend half my time in practice and half my time in research. I've done extensive amount of research in autoimmunity, and molecular mimicry, and cross-reactivity, and haptenation, and how we apply that in finding specific triggers for autoimmune disease, and, kind of, taking all the complex literature and simplifying it for people that don't read journals or they don't want to spend, you know, all their time learning about autoimmune research and all the new concepts, and just summarise for them very quickly, very simply for them so they can use it in practice. So, I mean, there's definitely a role where a researcher has to simplify everything so practitioners can have a clinical useful model, and at the same time, the clinician, you want to, you know, really talk about what's realistic. So my goal in that conference is to really share my research and also share real-world clinical scenarios, and not have any hype, you know.
Andrew: Yeah. Professor Datis Kharrazian, I cannot wait to hear from you and learn from you at the 2020 Symposium. There's so much to learn.
Datis: Yeah. But there's also so much to use clinically.
Andrew: I thank you so much for really opening our eyes on FX Medicine today. It's been great.
Datis: Thanks so much. I really appreciate.
Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook.
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