EPISODE 238

[INTRODUCTION]

[0:00:02] ANNOUNCER: Welcome to the BetterHealthGuy Podcast, where we take a deep dive into complex chronic conditions and explore ways to build resilience, improve vitality, and achieve better health. To stay updated on Scott's work, you can sign up for his newsletter in the show notes, where you'll also find ways to support the show and help make more episodes like this one possible. If you find the podcast valuable, please subscribe, rate, or leave a review as it helps the show reach additional listeners exploring similar questions.

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[EPISODE]

[0:00:57] SCOTT: Welcome to Episode 238 of the BetterHealthGuy Podcast. If you are seeking new ways to find better health, I might just be your guy. Today, we explore Two Perspectives, One Mission: Advancing the Conversation on Mold Illness and CIRS. My special guests for this episode are Dr. Neil Nathan and Dr. Ritchie Shoemaker.

While they really need no introduction, Dr. Nathan is a leading clinician in the treatment of mold illness, Lyme disease, chemical sensitivities, and other complex chronic conditions, and is the author of several books, including Toxic and The Sensitive Patient's Healing Guide.

Dr. Shoemaker is a pioneer in the field of biotoxin illness and the developer of the chronic inflammatory response syndrome, or CIRS model. He is the author of several books, including Mold Warriors and Surviving Mold.

And now, a conversation with Dr. Neil Nathan and Dr. Ritchie Shoemaker.

[INTERVIEW]

[0:01:55] SCOTT: Before we begin our conversation, I want to personally thank both Dr. Nathan and Dr. Shoemaker. Each of them has had a beyond meaningful impact on my own recovery from complex chronic illness. I am deeply grateful for their contributions to our community and for the many lives that they have positively impacted with their important work. I first learned about Dr. Shoemaker's work around late 2005, reading the book Mold Warriors. At that time, I had been diagnosed with Lyme disease, but had never thought of mold, and that was really the first time that that concept entered my awareness. That book, Mold Warriors, 2005, and then subsequently extended my knowledge in different areas of this conversation with Dr. Nathan's book, Toxic, which I believe was 2018 for the first edition.

Today's conversation is not a debate. There will be no winner. The goal here really is for us to hear each of their perspectives on specific topics that we have previously agreed to talk about today. Each of them will respond to a given question, and then we'll move on to the next question, and you can then decide which perspective you resonate with the most. My guess is that ultimately, it will be a mix of each of their perspectives. While they may have some aspects of these conditions that they view differently, as you'll hear in this conversation, they share a common mission to help those who are struggling to regain their health and their lives, and I appreciate their willingness to come together for this conversation and also for the decades that they've devoted to advancing our understanding of these complex conditions. Thank you both for being here, and more than that, for your important work.

I have looked to each of you over the years for information about mold, about CIRS, or chronic inflammatory response syndrome, about biotoxin illness, and other key pieces of the chronic illness puzzle. My goal for today is really to give listeners a look at the lens through which you look at these conditions and how you view them, how you approach diagnosing, treating your patients, and also for listeners to see that while you might have two different perspectives, that there can still be one mission. I'd like to start by hearing from each of you about what you hope to achieve from the conversation today.

[0:04:25] DR. SHOEMAKER: I personally feel that today's discussion is going to be in a way a restart of what we've been doing for the last 25 years, and the experiences that we've had with Gordon's group and Ratna Ling and spending time in my office looking what Neil's doing, looking what I'm doing. The nice bound book of information from Santa Rosa in 2011 where Neil was doing the Shoemaker for Dummies.

[0:05:06] SCOTT: I was there.

[0:05:09] DR. SHOEMAKER: It was kind of neat to look at that. We've come a long way, and I've chosen a path that I think is different than Neil's. At the same time, when he asked me to write a foreword to one of his books, I accepted that and didn't really know what he was going to be saying. At the end of the book itself, I realized that Neil had been holding my hand and talking about life in general as an unknown discussant, and I was very impressed with that. I like Neil and feel we can be compatible. We may have to have a couple series of arguments, and I know they're going to be distinctive, but I've added a lot new stuff since I last talked with him. I did send a paper a couple of days ago. Did you get a chance to look at that?

[0:06:06] SCOTT: I did. I saw about the triple positives and Parkinson's and VIP.

[0:06:11] DR. SHOEMAKER: It's just incredibly exciting. Now we're looking at the worst patients of all having a recognizable diagnostic process and treatment protocol, and it's a happy day for some of the worst people before.

[0:06:29] DR. NATHAN: Yeah. First, I want to honor Ritchie. He was the one who brought me into the field. I went out to Pocomoke, Maryland to spend a little time with him in the beginning. We became friends. We lectured together for a while, and then we began to see this whole field through a different lens. I think that's what we're going to be talking about today. I'm hoping that listeners pay attention not to our differences so much as to some of our commonalities, which is we are both, I think, my number one goal is to raise the consciousness of my profession, our profession, that mold toxicity is a serious epidemic, and that we need to be looking for it and diagnosing and treating it.

There are millions of Americans going undiagnosed, untreated, and this is a travesty. Worse, they're being gaslighted by their healthcare practitioners and being told there's no such thing as mold toxicity, or CIRS. Again, this is a travesty, and it really sets them back a lot. I'd like listeners to be aware of the fact that both of us really want the public and the medical profession to understand that this is very real and it's epidemic. We agree on you can't treat patients if they're ongoingly being exposed to mold at work, or home, or in their car. For us, both of us, that's a key component to treatment. We both use binders to a certain extent.

There's a lot of commonality to what we do, and we're going to be talking about some of the differences today. I really want listeners to be aware of the fact that we may not be so far apart as it's been portrayed over the Internet. I'll put it that way.

[0:08:27] SCOTT: I personally actually find some comfort in the different opinions and perspectives that you each have. It would concern me more if we all agreed and still did not have solutions that worked for the vast majority of patients. The fact that you each are looking at different tools that we can bring to this conversation, to me is actually likely to lead to more advances than if everyone agreed and no one was still working hard to find better tools and better solutions.

Let's start with an overview for our listeners, kind of a 30,000-foot level. How do you think about the treatment of mold illness? We know it goes much beyond mold alone, or biotoxin illness, or CIRS. How do you see the key components, or drivers of these conditions, as well as the foundational pillars of recovery for these patients?

[0:09:23] DR. NATHAN: The underlying process with mold toxicity is inflammation, and the goal is to get enough toxin out of their body that the immune system reboots itself. Removing the mold toxin is key. It's a root cause. But we have learned over the years that mold toxin has triggered in many of our patients limbic, vagal, and mast cell issues. Many of our sickest patients, some of the ones most difficult to treat, have a limbic system and vagal system that has become dysfunctional.

Also, mast cell activation has been set forth in a lot of those patients. Often, we can't even begin to treat those patients until we first look at limbic, vagal, and mast cell dysfunction. At that point, I view treatment as threefold. First, removing the patient to the… as best as possible from the source in which they're getting exposed. Second, using binders that are specific for the toxins that we find in them. And third, using antifungals, because a large percent of our patients, I believe, colonize, particularly in their sinus and gut areas. I have found that if we don't treat the colonized mold, they often won't get better. From my perspective, that's my quick overview.

[0:10:47] SCOTT: We'll get more into the fungal colonization conversation a bit later as well. Thank you so much for that, Dr. Nathan. Dr. Shoemaker.

[0:10:58] DR. SHOEMAKER: When I first got involved with people exposed to water-damaged buildings was 1998. I had been working on biotoxins and dinoflagellates and Ciguatera and Pfiesteria and looking at blue-green algae and Microcystis and Cylindrospermopsis in Florida, Peridiniopsis in Florida as well. It wasn't until 1998 that we finally had a test, visual contrast sensitivity, that we could add to symptoms and then symptom clusters. It wasn't until 2001 and 2002 we were able to add HLA-DR by PCR, and the genetic basis of susceptibility to this day is in papers written about the CIRS and the different variations that comes with it.

These have been keepers. That MSH deficiency and MMP-9 increase and things we hear about and talk about were ones that I had stumbled upon mostly. I was about the only person doing this kind of work back in 1996. But others joined, and we had situations that there was disagreement. I was looking for inflammatory markers and symptoms that fit into a case definition that I made in 2003. That was replaced by GAO in 2008. What I've done is to add the approach of hypometabolism, or suppression of ribosomal activity, and we are looking at that it has manifestations, as well as mitochondrial genes that migrated from the mitochondria to the nuclei area for transcription.

We're looking at proliferative physiology with insulin receptor substrate 2 and aerobic glycolysis following along the pathway of Dr. Warburg years ago. The fourth of these entities that is now part of my daily life comes with metabolic acidosis, and we find if there's this metabolic acidosis that we usually do, there will be pulmonary hypertension, insulin resistance, gray matter nuclei atrophy in the brain, and T-regulatory cell deficiency. The fifth of these layers of causation, as I term it, are looking at HLA, especially with 4-3-53 and 11-3-52B. It's a tremendous tool for looking at progression within a family and relatives.

The sixth element is immune dysregulation, and we see this mostly in patients that we're worried about what their exposure could be, whether it's beta-glucans, or fungi, or actinobacteria, or endotoxins. What we're going to be looking at is specific causation. The seventh element is what I call T3, and this has been remarkable. It has a paucity of things from the first six, but it has the addition now of three separate immune markers with clusterin being one, with coagulation being another. It's not the same as what other people are thinking about coagulation. We'll get to that I'm sure. But then, we also are looking at dysfunctional passage of, of ions and nutrients in neurons.

The last, or the eighth is still in progress, is we're looking at neurosenescence as a general category, but now we're looking at a vascular source, so that each one of these has a part that must be recognized and treated successfully if we're going to have successful treatment overall. I'll be following up with, with Neil's comments, because I have some different things to talk about with autonomia and then mast cell activation syndrome as well.

[0:15:22] SCOTT: Those comments were very interesting to me, because I think what some people think of as the Shoemaker model that shows how much that's continuing to evolve, and even some of those newer concepts that maybe I hadn't thought as much about that you're now exploring in your protocol. Then we'll talk more about that T3, or triple positives later as well in some of your recent research.

You touched on HLA in your comments a moment ago. Can you talk about the role of HLA-DR testing in your clinical work? Historically, these patterns have been discussed in relationship to susceptibility, or propensity to developing CIRS, possibly influencing recovery potential as well. Many will be familiar with terms like mold susceptible, Lyme susceptible, multi-susceptible. In recent years, there's been discussion around the role of actinobacteria and endotoxins and beta-glucans, things beyond mold, which you've talked about for many, many years. How has this evolving understanding around specific causation influenced the way you think about HLADR today? Do you still see it as a clinically important tool? And if so, how are you using it with patients?

[0:16:40] DR. SHOEMAKER: The approach to HLA was a stumble and guess approach to medicine that I have accused myself of taking an advantage of in the past. Here we had 10 people on Williams Point on the Pocomoke River, who were water skiing during an outbreak of hysteria. The bloom was going on and fish kill was going on. But people were swimming along. Of the 10 people that were water skiing and falling into the water, seven got sick and three didn't. I thought, "Well, that's interesting." Just a guess and just another stumble and what could be going on? Well, Somerset County is not one that you want to guess about what kind of cigarette that is that they're having on the road. It might be what you want, or maybe what you don't want.

It was a whole situation of here was the first marker that it was associated with illness and routinely not found at all in non-illness. If we then look at what HLA has done over the years, it does not change, as opposed to things I'll be talking about of biomarkers. The HLA changes. But we know where mom and dad come from and brother and sister come from. If we have one person ill, or someone contemplating having a family, HLA might be present, helps understand whether you should be cautious about moldy buildings, or not. It's almost that simple. If you don't have HLA, it's 99% of the time you will, MSH deficiency comes in and with HLA not being 100%, but MSH accounting for the rest. We have now got two markers for who's sick, who's not. Neither one of these heals very well. We'll talk about MARCoNS in a minute. Specifically, if we think about HLA-DR testing, that's more for a family answer. Why did I get sick? If we look at why 24% of people, that number has stayed for nearly 30 years of who gets sick in a water damage building and who doesn't, it's 24% routinely. Not 25, not 23, but 24. That correlates with HLA.

As far as is it a useful tool? Absolutely. Do I make clinical decisions by changing HLA? No. I've already told you that it doesn't change. But it is a marker of what could be wrong and what else was wrong with hysteria in 1996 and 1997 that still is true in 2026.

[0:19:38] SCOTT: Maybe I am going to just clarify one point there. It sounds then like you're using that to assess the potential in the family system, so you then can take steps to minimize the potential of someone developing CIRS, but it doesn't sound like someone's HLA-DR is deterministic of their potential for healing.

[0:20:02] DR. SHOEMAKER: You're right. I didn't explain that well enough. 4-3-53 and 11-3-52B are the two haplotypes that I worry most about. The third is 14-5-52B. The language of HLA is part of what I've grown up with medically. But it is a situation that if we have the dreaded genotypes and the 4-3 and 11-3-52B are telling us that we want to be very cautious about saying what's wrong and what's going to get better, because some definitely are more, or far worse off than others.

[0:20:42] SCOTT: I happen to be a 4-3-53, for listeners. So, there is still hope if that's the situation that you're in.

[0:20:50] DR. NATHAN: I have a different experience with the HLA-DR work. Having started my training with Ritchie, I started using it on all my patients initially. What I discovered fairly early on was that I did not see a correlation between how patients responded to treatment and what their HLA-DR showed. In fact, again, as you'll hear in our discussion, given the fact that our patients' limbic systems tend to be compromised, because of mold toxicity, hearing that you have a 4-3-53, which was described as “dreaded”, scared our patients. Many of them took that to mean that they were basically going to be unable to heal properly, because of their genetics. I stopped doing it, because I did not see a connection between whatever their HLA status was and their clinical response. I had patients with 4-3-53s who responded beautifully to treatment, and I had patients who had no supposed genetic predisposition who were really sick.

I'm going to reframe this immune system thing through my lens here, which is I've come to believe as we look at families, or offices where people are being exposed to mold, and some people get sick and some people don't. I began to look at that from the lens of how robust their immune systems, not measured by HLA-DR, which I didn't find corresponded with that, but from a global perspective of if someone had a robust immune system, you could be and live in a moldy environment and be minimally ill. Now this is true for Lyme as well. But if the immune system took a hit, and for many people that hit was COVID, it could have been a flu, or a serious infection, it could have been a surgical procedure, or an emotional upheaval, some hit. The immune system lost containment, and now we were off to the races. I began to look at the process as intrinsically needing to remove enough toxin that the immune system could reboot itself, as my overall way of looking at it.

[0:23:26] SCOTT: What I heard, and correct me if I'm wrong, but I heard that you have different perspectives about the clinical utility of HLA-DR, but I believe that I heard that you both agree that even if someone has an HLA-DR that may be perceived as more difficult, they still have the potential and can be hopeful about healing when doing the right things.

[0:23:52] DR. SHOEMAKER: Yeah.

[0:23:54] SCOTT: Talk to us about how central the biotoxin blood markers are, C4a, TGF-beta-1, MSH, MMP-9 and others. When we're exploring CIRS today, which do you feel have the strongest clinical utility, or are supported by research, including potentially published case versus control data? Are you using these markers in practice? How much weight do you place on them in terms of diagnosis, planning for treatment, tracking progress? Then given the increasing logistical laboratory challenges in getting some of these tests accurately done, changes in methodologies and so on, how essential do you think these remain in clinical practice today? Do any of these biomarkers provide us insight into causation, or are they better viewed as non-specific markers of inflammation?

[0:24:51] DR. SHOEMAKER: One of the issues that remains important is to be looking at treatment and say, "I'm looking for successful treatment and return to standard health." The markers you put forth C4a, MSH, MMP-9 were ones that were in wide use by… in my practice by 2003. We had a case definition with all these. We added TGF-beta 1 in 2008. Specifically, what we saw is that the illness was multifactorial in that there would be abnormalities and deficiencies of regulatory neuropeptides, MSH, and later on VIP. Inflammatory cytokines, MMP-9 was the first. C4a was the third, looking more at complement. One thing was clear to me is that when we looked at symptoms and visual contrast as part of the case definition, we also wanted there to be use of labs that are seen in published peer-reviewed literature. I really need to go pretty hard and heavy about publication and peer-reviewed literature, because if we talk about the immune systems without talking about specifics, we haven't really done too much.

I made a list of biomarkers that I've published over the years, and people have used and reproduced in reproduction of science is what it's all about. We looked at groups of symptoms, clusters of symptoms, visual contrast. We measured anion gaps. It's remarkable how rarely people do that. We looked at TGF-beta 1 before and after treatment, MMP-9, C4a, VEGF, MARCoNS, ACTH and cortisol and ADH and osmo. These were all in wide use by 2008. When we started using transcriptomics in 2013, we had eight gene groups from molecular hypometabolism. IRS2 is fascinating in controlling about glucose transport.

Hypoxia-inducible factor 1A is important for pulmonary hypertension and hypoxia. TUBA4A and TUBB1 are looking at cytoskeletons. Again, before and after. We look at immune systems before and after. We have now a Parkinson's fingerprint with eight genes in it. We have clusterin coagulation. We have 10 genes for that. Apoptosis, especially defective apoptosis, is remarkable how important that is. Specific causation cannot be underestimated. The role of fungi and actinobacteria, endotoxins and beta-glucans, we can give specific findings to groups of genes, and we can watch them treat successfully and return to normal. This is huge.

I mentioned gray matter nuclei atrophy, but cortical gray atrophy, forebrain parenchyma and superior lateral ventricle. Neil and I were going to be doing a talk in Norway in 2015, and I didn't make it. Neil did. I presented the new data on NeuroQuant at that time. T regulatory cells, we know they have tremendous role as that. T cell synapse is looking at antigen presentation. Without antigen presentation, we don't get antibody production. Actinobacteria that we can isolate from skin, from blood. This is just spectacular. This idea that blood is sterile is wrong. Actinobacteria are in blood for all the time. Defensins, Lyme acute, Lyme treated, the molecular biology of Lyme acute and positive, coming from John Aucott and Charles Chiu in UCSF.

Cytokines, CD14, CD4, CD12, gliadin antibodies. The new players, and I'll get off the high horse, AKT, RELA, and toll 2. These are huge. These are now prodromes for illnesses that are going to be present that we can recognize before they become terribly important. That's part of what reason that Neil and I have differences is I use prodromes, and I don't think he does.

[0:29:45] SCOTT: I won't ask you which of those markers are your favorites.

[0:29:51] DR. NATHAN: Starting my training with Ritchie, I used visual contrast, have a visual contrast in my office. I used all of those markers routinely on every patient. In the early days, those were the only measures we had that would help us define people who had mold illness, or didn't.

Over time, when urine mycotoxin testing came about, that for me was a game changer. I know we'll be talking about that, because we have very different views on the value, or use of urine mycotoxin testing. From my perspective, that was the game changer. That allowed us to know exactly which toxins were in that patient at that time. It gave us the opportunity to be specific about which binders we were going to use to bind those toxins. When I began to apply visual contrast and TGF-beta 1 and C4a and all the other markers, what I saw was visual contrast would go back to normal long before urine mycotoxins were cleared. TGF-beta1 and C4a would normalize long before they were clear. I began to see that patients hadn't quite completed their healing journey perhaps at a different point in time than Ritchie has.

I want to comment on, for me, those markers are useful, but they represent a nonspecific measure of inflammation in the body. You can get those markers being elevated with Lyme disease and Bartonella, several other types of infection. Here I want to point out what I think is a super important distinction between our practices. One of the things that has struck me over the years is that patients choose us based on their perception of us. Both Ritchie and I have written books and done podcasts for many, many years, and I think patients are attracted to our energies, if you will, our way of doing something, our approach. I don't think we see the same patients. In fact, I think that's a research flaw in almost all medical research, which is to compare one practice to another is inherently difficult, because of that draw.

For example, I see a lot more Lyme patients than I think that Ritchie has. If I'm wrong, you can correct me. To me, that means that my TGF-beta1s and C4a weren't as useful. And visual contrast wasn't as useful, because visual contrast will be affected not only by mold, but it will also be affected by Lyme and by mercury toxicity, both of which I see commonly in our patients. I found those markers helpful, but not as definitive as things that we've come to work with later on in time.

[0:32:54] SCOTT: Dr. Shoemaker recently authored an excellent paper, I think we all would agree, discussing some of the challenges, some of the limitations surrounding urine mycotoxin testing. I know, Dr. Nathan, you find this, as you mentioned, to be very clinically useful in your work. What has your experience been with urine mycotoxin testing? Is it still a valuable tool? Do you have concerns about its accuracy, interpretation, clinical utility? How are you viewing its current role in evaluating patients with suspected mold-related illness or CIRS? Then extending the discussion a bit further, what are your thoughts on blood-based mycotoxin antibody testing and its potential role in clinical practice?

[0:33:40] DR. NATHAN: First of all, I was very impressed with Ritchie's recent paper, which basically castigated the industry of urine mycotoxin testing, because they have not done appropriate controls. He's absolutely right. They have not. His concern is my concern in that we are using a test that has never been validated appropriately. I agree with that. That doesn't mean that the information isn't useful, however. I have personally done tens of thousands of urine mycotoxin tests with all three companies. I've split specimens to all of the labs that we're talking about, and I have found fair correlation between them, keeping in mind that they use different approaches. ELISA technology by real-time, mass spec is used by both Mosaic and Vibrant Health. We're not looking at the same thing through the same lens.

My bottom line is, having treated thousands of patients, that the urine mycotoxin test is really helpful to make the diagnosis. For follow-up testing, I have found results to be inconsistent, and the lab that does the best job with that, in my experience, is RealTime. What I found is that those tests help me make the diagnosis, they give me information about which toxins are present so that I can treat that much more specifically with binders, and I can use that for follow-up testing, so that I know when the mold is completely out of the system.

What I'm looking for ultimately is a RealTime test that reads not present in any category for me to think that we've completed the job here. From my perspective, I think that the information inherent with Dr. Shoemaker's objections understood and agreed with. I've personally gone after several of the labs repeatedly and begged them to do the studies we need to do to really verify it. They have so far not responded, and that is a failing. I agree with that. We're not going to throw the baby out with the bathwater here. The results that I have seen, and not just myself, but I have a mentorship program for over 300 physicians, the whole group has seen the value of urine mycotoxin testing in both making the diagnosis and following the patient.

I think we’ll continue to discuss this as we go. I have more concerns about the blood testing, which is an antibody test, in that I think it is still useful. A positive test I do think is helpful if there's a positive IgE antibody test that has been associated with ongoing, or acute exposure. However, again, follow-up testing I found to be very random and not anywhere near as helpful. My perspective, all of those tests are extremely helpful. I really feel, Ritchie, that if you would add urine mycotoxin testing, I know you're not ready to do so, because it hasn't been proven for your… and I accept that. I think if you added that to your database, you would expand your appreciation of exactly where patients are in space and time in a way that would enhance your whole outcomes. But that's my perspective.

[0:37:26] DR. SHOEMAKER: Any kind of test done looking at causation, cannot forget what we learned with Koch's postulates in medical school. We can't just substitute, because we'd like to. We can't say, "Well, we don't have any controls, but we don't need any." The issue is that when we look at people who are making assumptions based on six or seven or eight mycotoxins found in urine, which may or may not have been treated properly in handling from home to the lab. When we look at treatments with antifungals for putative sources of fungi, when we hear that sinuses are the source of fungi colonization, and that's a result of the reality is that when we look at hundreds of patients and thousands of patients who have been treated without assumptions about mycotoxins, we find that it is indeed a biomarker that we don't need when we have all these others.

The first paper I published in 2019, it was going after mycotoxin users, there were 21 studies looking at mycotoxins in urine in healthy patients. 21 studies for 2,756 controls, none of them were sick. I don’t think Neil's seeing people and they're sick. But when we look at control groups that we should and nobody's sick, what are we missing? We looked at published literature on fungal contamination of foods. Where are the putative fungi coming from? Are they coming from a building? Are they breathing it in, or are they eating it? Then we look at people who are measuring urine mycotoxins constantly for food safety and the European criteria for safe consumption, as this is done quite frequently.

It is rare to find one person who doesn't have one of 50 different fungi. If we look at Dr. Michael Sulyok from Vienna, Austria, now he's publishing, looking at mass spec and all the different kinds of mass spec. He's finding 1,500 antigen formers in urine for people in water damaged buildings. 2,000 people, 500 people with mechanisms that are available. Yet, when he looks at mycotoxin testing, if you've got multiple mycotoxins in urine, the chances of having correct findings approaches zero.

If we sure had case control studies and validated control groups, that would be fine. But how about placebo-controlled studies? How about confirmation of active fungal infection? How about confirmation that urinary mycotoxins are not simply derived from diet in presence of sharp repudiation of CDC? Then we look at a robust literature demonstrating causation of the illness. The water damage building is inflammatory, not infectious. Along that way, I do want to speak about the failure of proper antibody formation.

It's fascinating that when we look at aflatoxin and ochratoxin A and DON and zearalenone, T-2 toxin and fumonisins, those are the ones that you get. Neil's probably got 10,000 cases. But each one is a low-dose low molecular weight hapten. You cannot use a hapten to independently verify IgG, IgE, or IgM without carrier conjugation. You can't do that. That's not how the immune system works. Here, if we look at IgG detection reflects assay artifact, or contaminant exposure, if we look at other low-dose molecular weight haptens, they're not immunogenic in isolation. They lack biological plausibility. They cannot generate class-switched antibodies. These mycotoxins are low molecular weight secondary metabolites that function as haptens, rather than complete antigens. Without covalent conjugation to a carrier protein, such compounds cannot elicit a class-switched IgG immune response. They just can't do that.

I've got 20 papers, and they all have the same level of shrillness, and no, you can't do that. That's bad science. We can do that another day. All I can say is that, with no control groups, you don't have a test. With haptens, you don't have a test either.

[0:42:54] SCOTT: What I heard from that conversation is we all agree that people should read Dr. Shoemaker's recent paper discussing some of the limitations and concerns around some of these tests, and we all agree that we need better tools and better tests in the future.

Beyond some of the more traditional CIRS biomarkers that we already talked about, are there any other labs, assessments, clinical tools that you find valuable when evaluating these patients? You touched on some of these. VCS we know is important, or can be helpful. NeuroQuant, GENIE, some people are using organic acids, other tools and tests as well. What other tools help to inform your clinical thought process, bring you insights that help with diagnosis, mechanisms, treatment direction, or monitoring patient progress?

[0:43:50] DR. SHOEMAKER: Well, of the, of the tests that we use looking for reliability, and I agree VCS is nonspecific, it's like saying, "Runners to your mark," doesn't say whose lane's going to come out first, but we know they got a lane and they're going to come out. We're not looking at specific versus nonspecific when we are looking at VCS and things, matters like that. But when we look at GENIE, and we've broken down GENIE into 19 different pathways, and we know full well there's more information that we can find. GENIE is under-underused. It's a sense that if we are looking at the mechanism of brain injury, GENIE and NeuroQuant go hand in glove together. Now that we can use GENIE to have specific causation, we can look at the pattern of NeuroQuant injury. We'll see cortical gray atrophy, or superior lateral ventricle enlargement in our endotoxin people, and they only have four or more findings of gray matter nuclei atrophy.

You can sort out in a heartbeat with looking at gray matter nuclei atrophy in Actinos versus endos. It is vitally important that these tests be done and not skipped. I had never ordered an organic acid test, and just for fun, I printed out, "Why use the microbial organic acid test? It's a convenient, effective way to monitor a patient's gut health by analyzing 21 organic acids." I thought, "Okay, I have fun with people talking about guts and microbiomes." I said, "How many people with microbiome testing have included actinobacteria?" It's in everybody's gut, and they don't test for them looking at these organic acids. Why? Why would you leave out one of the most important sources of bacterial interaction with fungi, with Actinos, and with gram-negative rods?

It's, it's just beyond me. This is science that we learned in medical school. We did not learn to ignore elements that we can't explain. We did not learn to make up things that we didn't know and try to give them causation. Having said that, I also then looked at the mycotoxins referenced with Matt, and I've forgotten Matt's last name.

[0:46:34] SCOTT: Pratt-Hyatt, I believe.

[0:46:36] DR. SHOEMAKER: This was published 10/23/20, and I have all these numbers, the PubMed numbers. I looked at every one of them, and I said, "This is food, this is food, this is food, this is food, this is food. This is cell culture. Oh, this is treatment, Dr. Hope with cholestyramine. 8, 9 and 10, Dr. Hope. Food. Three people, food. Then some metamorites, and some, some clay." When I looked at all of these, here's cell culture, cell culture, cell culture for nanosystem. You can tell what fungus, what mycotoxin they're after by the references they include, and they don't include doing anything with treatment. That was my addition to testing.

[0:47:30] SCOTT: For people that are interested in learning more about GENIE than we'll get into in this conversation, Dr. Shoemaker and I have had a prior episode deep diving into that. You'll find that very interesting.

[0:47:42] DR. NATHAN: Dr. Shoemaker is a pioneer in the use of GENIE, and I can't pretend that I understand how to interpret it with the skill that he has. I don't have anything useful to add to that discussion. I do find OAT testing of somewhat useful. I know that the Mosaic OAT test, the first component of it is called fungal elements. Typically, it looks at some of those are associated to a certain extent with the concept of colonization, and we'll talk about that more later. One of them, which is arabinose, is a metabolite of Candida, so that it is an interesting marker for Candida, one that I think is fairly accurate. I'll use my time with this.

I'd like to respond to Ritchie's comments, because I want to give a somewhat different perspective. When I began to embrace urine mycotoxin testing, the first papers that I read, which are published in peer-reviewed journals, were those of Joe Brewer, an infectious disease specialist from Kansas City. Joe in 2013 wrote a paper in which he took 112 patients with chronic fatigue syndrome and simply measured the urine mycotoxins. Shockingly, 92% of those were positive, which is an interesting way of looking at chronic fatigue may often not be correctly diagnosed. It may actually be mold toxicity for many of those patients. He then wrote a series of other papers over 2014 and 2015 in which he took 100 consecutive patients and treated them with different kinds of antifungal nasal sprays and found treatment-wise that 94% of them were treated successfully with amphotericin B as a nasal spray. There were also binders in that program. There were also oral antifungals. 89% responded to nystatin.

From my perspective, this was a truly scientific, well-done study that indicated to me that the urine mycotoxin testing was helpful, not just in identifying those patients, but in following their treatment along.

There's a couple of more papers that I want to refer to, and they will not meet Ritchie's criteria. There was a paper published in 2019 in a journal which is not peer-reviewed, called The Townsend Letter, in which Great Plains Lab, now Mosaic, took 82 controls and 112 patients with mold toxicity and compared their urine mycotoxin tests. To my knowledge, this was one of the more valuable papers that I've seen. It was well done, but unfortunately, it didn't ever get published in a peer-reviewed paper. Okay. Of the controls, the only toxin that showed up in their urine was ochratoxin. The other mycotoxins didn't show up. Compared to the patients with mold toxicity, the numbers were huge.

Particularly important, and I think this is especially relevant to our discussion here today, 51% of the controls had a small amount of ochratoxin, which would go along with… I know, Dr. Shoemaker, you wrote a paper with David Lark in 2019 in which you went over many publications, which showed the presence of mycotoxin in controls. But here's my point. The controls in this particular study, their amount of mycotoxin in the form of ochratoxin was 1.6 nanograms per gram. Whereas, the mold patients had greater than 18. What that shows us is, I think research which has not yet been done would need to compare controls with mold patients, so that we're really seeing a difference. Could there be a tiny amount of mycotoxin in people globally as controls? Sure. But if there's a massive amount more in their urine in our mold patients, this becomes a valuable test.

As a result of that particular study, Great Plains Laboratory changed what they considered an acceptable amount of ochratoxin from 3.7 to 7.5, which is their current standard. That means that basically, there's a very low statistical chance that anyone with an amount of ochratoxin less than that is a mold-toxic patient. One more small study that I just want to mention is the only one I know of. I did a study with Great Plains several years ago. It's a pilot project. It was not enough patients to really talk about. We took eight patients with mold toxicity, and we had them avoid all potential moldy foods that we all know about, foods like dried fruit, aged cheese, mushrooms, coffee, beer, wine, processed meats, tomatoes, fermented foods. They avoided them for 10 days. They got their urine mycotoxin test done. Then we had them pig out on those foods for 10 days. To our surprise, seven of those eight patients, their mycotoxin levels went down eating supposedly moldy food.

Again, study needs to be a larger study. It was not scientifically meaningful. We need an IRB for it. But these are the kinds of studies that I would like to see done to be able to address this issue in, as you would want, a more scientific way, and I'd want that information published in a peer-reviewed journal.

[0:53:43] SCOTT: Let's talk about MARCoNS and the broader sinubiome conversation. How important is MARCoNS testing in your work today, evaluating patients with mold-related illness or CIRS? When a patient has a positive MARCoNS results, how do you determine whether that finding is clinically meaningful and warrants treatment, particularly given some of our past discussions around polycyclic ethers and the idea that not all MARCoNS findings are equally significant? More broadly, what role do you think other microbial contributors in the sinuses may play, including potentially things like actinobacteria, or other bacteria, or even fungi, and is there a place for expanding the assessment to tools like MicrogenDX and some of their next-generation sequencing where we can look more broadly at the sinubiome?

[0:54:38] DR. SHOEMAKER: Well, MARCoNS has been one of my good buddies since 1999. Worked with Harold Butt and Tim Roberts out of Newcastle in Australia. They had done some work looking at antibody production that would lyse MSH and create MSH deficiency and were able to show that the toxins were made. They didn't know about polycyclic ether toxins when they were first publishing. But they knew that if you didn't eradicate a MARCoNS, the chronic fatigue patient did not heal.

When we started using MSH replacement, we ran into the FDA, says we couldn't do that, so we had to come up with a different way to eradicate MARCoNS. We used an antibiotic preparation, BEG spray at that time, had EDTA and gentamicin and Bactroban with it as well. That was an excellent solution to what do we do to get rid of MARCoNS. Until about 2015, we started seeing a tremendous increase, almost overnight spike in antibiotic resistance in MARCoNS between gentamicin and vancomycin. My God, vancomycin resistance, you're putting stuff in the nose. Well, it turns out what was being put into the noses were azole compounds, and they were getting these drugs from Hopkinton Drug primarily, and I couldn't persuade Dennis to stop using azoles.

Mayo Clinic had used a fungal player as well. 33% of people who used this antifungal developed intolerance to the compound. The horse was out of the barn. We had antibiotic resistance, and we had to come up with something else. Well, it turns out that EDTA at 0.25% at higher doses, 12 doses a day for a month, will help eradicate organisms, but a lower dose, two sprays twice a day of EDTA will activate biofilm formation by competitors and who will wipe out the organisms that were dependent on having absence of EDTA.

We found that other compounds might be used and tried this and that. It wasn't until Peggy DiTulio started treating to develop MSH resistance from MARCoNS that she was able to get MSH stimulation in patients evaluated with inflammatory response syndrome. The problem was MSH deficiency. If we didn't treat it, people didn't get better. If we did treat it in the old days when I was doing it, they still didn't get better. When Peggy comes along, she published a paper in Frontiers in Endocrinology in April of 2026. Clearance of multiple antibiotic-resistant coagulase-negative staph is selectively associated with higher circulating alpha melanocyte stimulating hormone. A problem that I've been working on for 23 years, she solves in 23 weeks. There's great hope that we can find MARCoNS at bay.

Now, Joe Musto answered my call of how can we find out what is it that MARCoNS are making that are keeping them alive, wiping out the competitors? Well, what he found is that when he grew MARCoNS in a well, assay what was in the well, polycyclic ether toxins were found in everyone with fungal antibiotic use. The mean number of antibiotic resistances for those antifungal users was 5.1 gray matter nuclei atrophy out of 6. It was one of the things that we wanted them to stop. Having said that, the polycyclic ethers had no known molecular library when the mass spec was done on them. We didn't know what kind of polycyclic ethers they were, but we knew that they were there and they were made by Actinos, and the Actinos genes had been incorporated into the MARCoNS themselves.

We found that if we look at the mitoribosome, both large and small, using GENIE, we've looked at those, if they were a Z-score of 0.94 or greater, the organisms would not make polycyclic ethers, and you did not need to treat with anything if the GENIE was on your side. If we can agree to use GENIE to say whether we should use it and not use antifungals, then we'll be in agreement.

[0:59:56] DR. NATHAN: When I started with Ritchie back in 2005, I was persuaded that MARCoNS were an important player as he's describing. We treated it back in the old days very aggressively. We actually used triple antibiotic treatment, along with BEG spray initially. I kept finding that many of my patients, I couldn't clear MARCoNS using this very aggressive treatment. More so clinically, aside from mild improvement in sinus symptoms, I didn't see any global improvement, or response to their treatment when we went after MARCoNS. I slowly stopped measuring MARCoNS and have not found that treating it has been helpful for my patients. It is possible, certainly, I use BE spray now and have for years. I took the G out, which is gentamicin, many years ago, because I began to see reactions. Some of the gentamicin was getting systemic and having effects on some of my patients. I've used BE spray for a very long time, and I find that to be helpful. It is possible that that is improving things from my perspective, not because of its effect on MARCoNS, but because its effect on the sinuses more globally.

We're going to be getting into this in more detail, but I think there are other things in the sinuses. I believe that mold colonizes. I know that Dr. Donald Dennis, who's an ENT surgeon, who's worked in this area for a very long time has found mold in the sinuses of many, if not most, of his patients. He's found using a special amphotericin B nasal washing process has been very helpful. A surprising number have got actually fungal balls in their sinuses which need to be surgically removed in order for people to make some progress. My perspective, I haven't seen the MARCoNS be as important a contributor to this as Dr. Shoemaker has.

Again, I'm looking at all of this as we take a step back from our various positions. Whenever we're looking at duality, in this case two different seemingly diametric positions on any given subject, I often find that there is a place of synthesis if you can take enough of a step back to look at it. I don't think we've done that yet. But it is my hope that others will be able to take enough of a step back that we can see that there is value in our different positions and find some way to synthesize that.

[1:02:46] SCOTT: What I heard you both say is that there is at least one or more organism that can live in the sinuses that potentially is impacting patients, and that maybe for different reasons, you both do have a component of your treatment approach that includes working on the potential microbial burden, or burdens in the sinuses.

Before we move away from the idea of testing, let's talk about evaluating the external environment. How are you currently having your patients assess their home, workplace, car, church, or any other space where they spend time? Where does ERMI come into the conversation, HERTSMI-2, other methods of testing the environment, testing the air? How are you using those tools to support your patients, and do you recommend working with indoor environmental professionals, or IEPs? If so, this is a sticking point for me, how important is it to find inspectors or environmental consultants who specifically understand medically hypersensitive individuals and the unique challenges that are faced by patients with mold-related illness, or CIRS?

[1:04:00] DR. NATHAN: Evaluating home, work or buildings you're going to spend a lot of time in is crucial. My approach includes using mold plates to start with, only because they're cheap and we can put a plate in every room in the house to get a feel of what area might be needing greater attention. Then ERMI testing is, for me, the most accurate thing we currently have. I believe that the HERTSMI-2 process that Ritchie developed is great for determining whose place is safe and who hasn't. I use it routinely, and I find it extremely valuable. Air testing, which is unfortunately a major component of the building industry, I find highly inaccurate. Your point, I think, was a lot of people who are licensed to do mold evaluations have 10 hours of training, which isn't even a drop in the bucket of what they need to do it correctly.

It is sometimes difficult to find an IEP who knows what they're doing, but it is essential. Because if there is mold, you need to know where it is exactly, so you can remove it properly. There's a lot of arguments about how that needs to be done, but I think you need to find the source of the mold and literally surgically excise it, so that it's out of the building. Spraying it with various things doesn't work well at all.

[1:05:29] DR. SHOEMAKER: When I think about treatment of CIRS, there must be an additional source of besides using medications from a physician. Unfortunately, I have been pleased to be able to work with a cadre of high-skilled indoor environmental hygienists, and we have a fantastic series of lectures before the CIRSx conferences. There are three or four layers of testing and training that can be done, and I encourage everyone who's involved with treatment of abnormal indoor environments to consider taking the time to get up to speed with state-of-the-art lectures on treating water damaged buildings.

As far as HERTSMI-2 and ERMI, and I agree, HERTSMI-2 is absolute best at can you re-occupy a cleaned-out house. ERMI, you get about 30% false positives, and HERTSMI-2 are less than 5% false positives for treatment. I think I can save us some time and just say that with current tools that we have readily available, we can make a big difference in cleaning houses and keeping them clean, so that we don't burn down houses, we don't tear down houses. We just go in and fix them.

[1:07:03] SCOTT: It sounds like, your perspective on this conversation is very, very similar, that there is value in doing an ERMI, even if we're not taking that ERMI score as the indicator of health of a building. There is value in the HERTSMI-2, and that algorithm has been particularly helpful. There is limited value in air sampling, and so I think that's a key message for people to get. If you're someone that's struggling with these conditions and you're needing to test your environment, please don't get someone who's just going to come air sample in the middle of the room, because that's not going to give you the right information, and chances are it's going to give you the wrong information.

How important is a patient's nervous system in terms of influencing the success, or failure of treatment when working with mold and CIRS? What are the impacts of the autonomic dysfunction, the limbic system impairment, vagal nerve function and regulation of the nervous system in recovery? Do you feel that unresolved traumas, emotional conflicts, chronic stress, or other factors need to be considered as part of a comprehensive strategy for approaching treatment of these patients?

[1:08:18] DR. NATHAN: Yes. That's the short answer. One of the difficulties we had in the early days was we were beginning to get a handle on how to treat mold and how to get it out of the body. A significant percentage of our patients couldn't take what we wanted to give them successfully. They couldn't take the doses of cholestyramine that Ritchie recommends. They couldn't take homeopathics. They couldn't take tiny amounts of charcoal, clay, chlorella, or things like that. It appeared, as we eventually learned more about it, that the work of Stephen Porges, which began in 1994 and eventually people began to embrace his work, was that the limbic system and the vagus nerve, which are 2 different parts of the brain which speak to each other, they're all about safety.

That both of those neurologically scrutinize the stimuli inside and outside of the body from the perspective of safety. If they don't think the body is safe, they will literally shut it down and not allow people to take the types of treatment they need. We began to discover that a huge percentage of our patients had some degree of limbic and vagal impairment. Again, in my patient population, I would put that at greater than 90%. Often, we needed to begin treatment not with binders and not with any other aspect. Yes, always looking at exposure, which always had to be considered. But getting patients' limbic and vagal systems rebooted was absolutely central to their ability to heal.

In 2016, with the publication of Never Bet Against Occam, Larry's book, mast cell entered the picture as well. It turned out there was a profound interaction between the limbic, vagal, and mast cell systems, and that these same patients often needed to treat mast cell activation as well before they could even begin to really respond to the right treatment. Short answer is absolutely, those are critical components triggered in a huge percentage of our patients by mold exposure.

[1:10:41] DR. SHOEMAKER: There's a nice discussion of dysautonomia from the Cleveland Clinic that I think probably should be considered to be offered to patients. Sometimes there's a lot of discussion about brain injury and limbic system injury when the problem is just MSH deficiency. The differential diagnosis of dysautonomia is something needs to be rigorous. One of the beautiful things that have come up since we wrote the textbook of CIRS Medicine in 2021 is a low-dose VIP protocol. We've been using that for people with drug sensitivity, chemical sensitivity, food sensitivity, but also extending it to dysautonomia. If we start with delusions of one to 10,000, or one to 100,000 and work our way up very slowly, we can treat the dysautonomia without much more intervention than just buying time.

We buy time with ability to give VIP. We then add in Welchol, or colesevelam. I don't use cholestyramine for much of anybody anymore, but especially if they're dysautonomic, we never use that. Here's where putting together a team approach that will include a coach, or someone who does spend a lot of time looking at some of the dysautonomic factions that we don't otherwise find. Fatigue and muscle weakness and difficulty performing physical tasks are oftentimes simply due to inflammatory problems when they're due to dysautonomia. A life coach is a good addition. What we found is that 40% of our patients were overproducing histamine because of a gene CCL5, or histidine decarboxylase. They were making histamine routinely and most commonly were diagnosed as having mast cell activation syndrome.

What we used to do with physical exam is draw a tic-tac-toe board on a patient's back, and it would turn red and you have an urticarial response, and we play tic-tac-toe. Usually, the husband was going second. I would go first. I don't like to lose at tic-tac-toe. The wife would be saying, "Oh, my God. What are you talking about?" We are reproducing mast cell activation syndrome, which is… I used it just to show how high C4A was. If you're going to diagnose mast cell, show me a normal C4A, show me a negative CCL5, show me a negative HDC. If you don't, then you don't have mast cell activation syndrome.

[1:13:29] SCOTT: How often do you evaluate patients with mold-related illness, or CIRS for hypercoagulation, coagulation abnormalities, fibrin accumulation? There's definitely an increasing discussion around fibrin formation and coagulation abnormalities, particularly in the era of COVID. Have you observed changes in the prevalence of coagulation issues in your patients with CIRS since COVID? When you identify coagulation-related abnormalities with whatever tools you each are using, how do you think about the significance of those findings and the approach to treatment of that coagulation issue?

[1:14:11] DR. NATHAN: Great questions that I might not be the right person to answer it. I started working with David Berg, who was big in coagulation back in the late 90s, and I began to use his testing and use his treatments on many of my patients. I was actually not very impressed that they did much. It pushed me away from looking at coagulation issues. They're coming up more and more now in many of our medical conferences. More and more people are writing about it. From my perception, I haven't seen it be as much of a player as some of my colleagues have. I will leave my comments at that.

[1:14:50] SCOTT: All right. Dr. Shoemaker, I know you talked about a coagulation section on GENIE, so how do you approach the coagulation conversation?

[1:14:59] DR. SHOEMAKER: Well, it's important to think about what's coagulating. If you're looking von Willebrand's profile, we have more acquired von Willebrand syndrome than anybody else in the world. That's a bleeding problem. Paradoxically, we also can have a clotting problem as well. That's one thing. If you look at factor V and factor V Leiden, I kept on saying I'd buy a pair of shoes for the first time I found one. It's one in 150,000. I usually look down my nose on people doing factor V.

If we look at the vascular theory of vascular hypothesis of Alzheimer's and Parkinson's, you will find GP6, glycoprotein 9, integrin B3, integrin 2B, platelet factor 4, SELP, thrombospondin, thrombomodulin. These are platelet-derived clotting factors that interact with white blood cells, that interact with clotting elements, including fibrinogen, interact in a way we didn't understand. It's one of the most important factors that there is looking at someone with T3, this very unusual problem. If you find more than two of 10 genes upregulated, you've probably got T3 with clusterin in the cytoskeleton abnormalities. These we now know are fixable. They never used to be before. But people would come in and have unusual coagulation problems, and the physician would just scratch their head and say, "Well, I've never heard of such a thing."

It is on the standard GENIE profile, and I would recommend that if you're not accustomed to using coagulation parameters, that you just take a quick course of lessons from Genis on surviving mold still, I believe. I'm not, but they are. There also is a significant abnormality looking at fibrinogen, where we have any tie to coagulation and Alzheimer's as we go along. We know full well that some of the coagulopathies in COVID were acquired, and we know that COVID is super acting on white blood cells, to they make a positive endotoxin foundation, as well as a actinobacteria moiety. Some of the COVID people you see are not ones that you might have thought, because nobody asks about water damage buildings anymore. But if you do, you will find the problem.

[1:18:01] SCOTT: You both use binders as part of your approach to mold-related illness and CIRS tools like cholestyramine and colesevelam, or Welchol have been important for many patients. Many practitioners also incorporate a variety of natural binders. Can you share your overall philosophy on the role and importance of binding in treatment? How do you think about the differences between prescription and natural binders, including the possibility that some natural binders may have mechanism beyond charge-based binding? How do you determine the right binder timing and intensity for a given patient? Do you feel like there are situations where some patients may benefit from remaining on binders long-term, or even for life, given the toxic soup that we all live within in our modern world?

[1:18:51] DR. SHOEMAKER: Well, that's a three-minute question if I ever heard one. I can remember how excited I was when I found Pfiesteria growing in the Outer Banks, and the Lumbee Indians lived along the bays of North Carolina, and they were using clay routinely. We would make fun of them at, the Duke saying that they were eating clay and what good did that run? I thought, "Gosh, maybe clay is what we need for Pfiesteria." I started using clay for Pfiesteria and found not a single problem, not a single bit of benefit at all. Just no nothing. I had found cholestyramine by luck, or by guess, I mentioned, I'd do some medicine that way.

One lady had terrible secretory diarrhea. Well, golly, if you've got secretory diarrhea, cholestyramine's your man. Most family docs know that, but other people wanted to use some things that didn't turn out to show statistically benefit. Using charcoal was not a great idea, and nobody that I used it got benefit from it. The biggest supplier of chitosan is just up the road here in Cambridge, and I went where they're making, taking crab shells, grinding up the chitin and making chitosan, which is a fantastic treatment if you can get the pH of the stomach to stay over 9. If you can't get alkaline, that alkaline in the stomach, the chitosan is not going to help you.

25 years later, Dennis Katz is trying to come back with a chitosan moiety that gets around the problem of alkaline urine, excuse me, alkaline stomachs, and we may have things come along different. Welchol has come along. It's not as many binding sites as cholestyramine have. It has more than others. Zeolite binds metals and positive charges, so it's not going to be your friend for a negative charge. I know Neil has come up with a different way to do those binders. It's just beyond me, and so it's no need for it, but I'm curious to see what he has to say.

[1:21:01] DR. NATHAN: When we first got into, first working with Ritchie, cholestyramine was the first binder we used, and it worked great for a whole lot of patients. When I started focusing on the work of Dr. Brewer, he had done a deep dive into the medical literature and found that certain mycotoxins were bound preferentially by certain binders, and that's been built on over the years. There's a table, eventually developed by Joe Mather, which is available on page 66 of my book, Toxic, which goes over all of the binders that have been shown in the literature to actually bind specific binders. It's a nonspecific table, and my clinical experience is that typically, I like Welchol, as Dr. Shoemaker has said. I like it better than cholestyramine. It has less side effects, and it generally works quite well.

Specifically, it works in my experience best for ochratoxin and zearalenone. If patients have trichothecene, or aflatoxin or gliotoxin, then they're going to need other binders, such as bentonite clay, activated charcoal, chlorella. Saccharomyces boulardii is a particularly good binder for gliotoxin and for zearalenone. I use whatever binders my patient needs based on their urine mycotoxin test. I have found a very close correlation between the effective use of those binders reducing urine mycotoxin test results, and that correlates perfectly with patients' clinical response.

I found when I don't use enough binders that are specific for what I'm seeing on their test, they often make limited response. The more comprehensive the binders are, the better I find the patients do. The longer I've studied this, the more convinced I am that the world we live in is incredibly polluted. It has now been determined that there are 350,000 new chemicals in our environment in the last 70, 80 years. Vast majority have never been studied in terms of their effect on human beings. I encourage people when they're done with treatment to continue to take light doses of one charcoal, one clay, and one chlorella forever just to help your liver deal with the toxic load. Honestly, my wife and I both do that.

[1:23:38] SCOTT: Let's talk about the concept of fungal colonization. Dr. Shoemaker earlier in the conversation has already expressed some concerns around the use of azole antifungals. We know that some HLA-DR patterns may create blind spots in the immune system related to antigen presentation in mold-related illness. Could those same immune patterns potentially make some individuals more prone to fungal colonization? How do you currently think about the role and clinical significance of fungal colonization in CIRS, in mold illness? How do you determine whether or not colonization is present, and do you feel that even non-azole, or natural approaches could have a role in addressing colonization, or in your experience, is fungal colonization less important clinically, or maybe not at all?

[1:24:33] DR. NATHAN: Well, in my patient population, I would say that 90% of my patients have colonized. It's not easy to make the diagnosis. It's almost a diagnosis of exclusion. As we mentioned before, OAT testing would give a slight hint that colonization has occurred, but that test is only somewhat accurate, and I would never base my diagnosis on that. What I typically base my diagnosis on is primarily response, or lack of response to binders alone. If patients are getting well with binders alone, they don't need antifungals. I don't see very many of those patients. In my patients, if I don't… after we've got them on binders, if I don't give them antifungals, the vast majority of them will not get better.

I don't use azoles alone. I'm increasingly inclined to use amphotericin B both nasally and orally. It's safe given that way, because it's not absorbed. Absorbed, as we know with IV, has tons of side effects, but taken that way, it's pretty safe. That's my go-to. But I do use quite a bit of itraconazole. As to whether fungal colons… fungal, if you get used to that, or the body is no longer responsive to that anymore, I don't see that almost at all. I mean, I've given antifungals to probably 4 or 5,000 people. I've not seen them become resistant, and I've seen the vast majority of them get well using it. I know that Dr. Shoemaker is adamantly opposed for a variety of reasons, which I view as theoretical. In actual practice, I find that patients often can't get well, unless they go on antifungals.

[1:26:19] DR. SHOEMAKER: It's a situation that the approach that we've seen with people using amphotericin B, or a fellow up at Mayo Clinic was using amphotericin and creating lots of intolerances. In the debacles of the literature on fungicides, where DuPont was making benomyl for years, creating just horrible mutations. Wherever we started looking at substituted benzimidazoles, we were asking for trouble, and itraconazole is one of those. It's not theoretical to see what it's doing to the voltage-dependent anion channel, and it's a way to impair delivery of pyruvate into the outer membrane of mitochondria. It's not a theoretical ill-illness.

When we look with GENIE at molecular hypometabolism, we're looking at the problems with delivery of pyruvate across bound to outer membranes, and we know that's a bad thing. Why are we giving them itraconazole as well? I still have not heard any good argument, any before and after studies done. We will look at what's in the nose, and when someone says, "Well, I'm, I'm checking it." It's a sinus culture. I said, "Oh, you are? How do you do that?" He shows me his nasal culture. What's in the nose is not what's in the sinuses. If we're looking at fungus balls in the sinus, okay, that's something that happens all the time. It's a cinch that using medications that are bioactive where they're not necessary is just not good medicine at all, in my opinion.

[1:28:16] SCOTT: Dr. Shoemaker, could you just comment then, is your position more that the antifungals are unnecessary, or is your position more that you have concerns with the type of antifungal that's being used?

[1:28:29] DR. SHOEMAKER: Both. There needs to be shown, this is not an infectious disease. This is an inflammatory problem. If we look at mucus in the nose, which is probably the best antibacterial and best antifungal approach that there is in the human body, we are ignoring what the good Lord gave us and making a mistake in doing so.

[1:28:52] SCOTT: For many years, Dr. Shoemaker has emphasized that what many people call mold illness is far more than mold alone, so that broader concept is not new, that soup in a water-damaged building. What is newer for many people is the discussion around contributors such as Actinobacteria and endotoxins potentially playing a much larger role in CIRS causation than many had previously understood. Some emerging data suggesting that mold and mycotoxins may represent a very small part, I believe 7% of the overall causation picture. How has this evolving understanding translated into clinical practice for you? Does treating mold and mycotoxins alone often fail to fully resolve CIRS in some patients? Have you seen meaningful clinical improvements when specifically addressing contributors such as Actinobacteria and endotoxins and not mold and mycotoxins? Do mold and mycotoxins still matter? How are you approaching these newer areas of focus in terms of your treatment approach?

[1:30:00] DR. SHOEMAKER: In 2015, 16, somewhere along in there, I ended up working with people in Finland looking at approaches to a remediation of wet buildings. We saw some fantastic remediation results. Fungi, or HERTSMI-2 was zero, or four, or eight, or heaven forbid, 10, and yet, people weren't better. What did we do wrong? What have we done wrong here? We started looking at something that I've been talking about since 2002, which is Actinos, and we started measuring Actinos and found out, aha, look at all the Actinos you've got there. These Actinos are motile. They move from place to place, so they're, more likely to be causing trouble from one room if they got it in another room.

Specifically, what they're able to do is to grow well in an alkaline environment and not in an acidic environment. With that in mind, we started treating for acidic conditions, and we had alkaline conditions, and we'd isolate one room and clean that and test that. That was fine. Waited a week later, and now it was re-colonized. This became a problem, and then we started looking to see that what else was wrong was endotoxins and gram-negative rods with you think of puppies pooping in an apartment building and all that kind of thing. We found out that plumbing problems, and we did more smoke tests than anybody, and I started finding places of water in the inner sanctums of the bedroom and the bathroom and the closet were all moist areas and were holding secondary organisms, not fungi.

It came into how do we measure what's doing it? If a person's sick and you eliminate fungi, can you guess that it's Actinos? No. We measured. The use of science, not guessing, remains a important part of practice these days, because we know full well that when we're now looking at some organisms that are Actinos that grow in skin appendages, like sweat glands and oil glands, and these organisms will be expressed after a shower. You get nice and clean, and you've re-layered your skin with Actinos. We're using shampoo and lava soap and find out that the first time that we have a shower, we don't get resolution of the problem. Second or third time, what we've done it now is mobilized these organisms from their inner sanctum, so that between that and then extracellular mycetes, which are small organisms forming from the skin being taken into the deep areas in these skin appendages and then getting into bloodstream.

The problem is that Actinos are nearly ubiquitous. Gram-negatives are close to ubiquitous. They're making illnesses 48%, 42% for Actinos, 28 percent for endos. Those numbers haven't changed over the past four years, but when we start measuring skin, extracellular mycetes, we're going to have more problem to pay attention to.

It's a cinch that we cannot ignore fungi. 7% is not 0. It's not unusual to find fungi and actinomes, or fungi and endos, but endos and Actinos are two together of the most commonly found. It's coming into clinical practice for me as every single patient that I've got to look at has got an 80% chance of having a non-fungal source of their illness. If we learn how to deal with Actinos, doing Actino skin, and Actinomycetes, or endos, we're finally able to get ahead of people and keep them healthy, them not relapsing when they go visit a neighbor with a wet building.

[1:34:34] DR. NATHAN: It's fascinating to me that Rich and I have treated thousands of patients successfully over the years, and yet, we have evolved a different way of looking at it. I've been looking at the Actinos and endotoxins more so since I listened to your podcast with Scott, actually, and trying to look at it. What I found clinically is that the mold issue, the mycotoxins specifically, are by far the biggest percent. In your research, it's 7%. In my clinic experience, it's 90%. We're seeing a different critter here. What I find clinically is if I clear out the mycotoxins using my urine mycotoxin test, the vast majority of my patients are well, that very few need to address the Actinos, or the endotoxins. Actually, because I'm using Welchol in most of my patients, which binds endotoxin, I'm treating that already.

In terms of the Actinos, I've followed, or helped to manage several dozen patients that have worked with practitioners that you've trained. I have not found that focusing on the Actinos has taken them where they need to go. But when we got the mycotoxins out, that's when they completely got well. We're just seeing this from different angles. I suspect that I'm not treating the Actinos as adequately as I should. I think that that's something I need to be looking at. One of my colleagues, Jill Crista, who I respect greatly, has found that she needs to treat the Actinos in 30% to 40% of her patients for them to respond optimally. I think I'm a little behind the times on that, but I do have a different perspective on what is the essential inflammatory process, that there is an inflammatory soup going on here with Actinos and endotoxins and mannans and proteinases. Absolutely, and we've agreed about that forever.

[1:36:41] SCOTT: What role today do peptides play in the treatment of mold-related illness and CIRS? Does VIP still hold the same place in treatment today that it has for many years, or how has your thinking around VIP evolved, or changed over time? You alluded to that earlier with the low dose, or microdosing of VIP in certain clinical applications. How has the clinical application changed, including the patient selection, timing, and prerequisites before use of VIP? How consistently does VIP help improve environmental tolerance, or resilience in these patients, and are there any other emerging peptides that you feel are, or may become important tools in the treatment of CIRS in the future?

[1:37:26] DR. SHOEMAKER: In 2016, I had to give testimony to the FDA to prevent them from taking VIP off a list that let pharmacies compound it. We argued back and forth, and I presented papers with documentation of VIP benefit and doing it right and all the FDA requirements, and they let the VIP stay on the “may compound” list. Now we're looking at a whole new group of peptides being espoused as being miracle drugs, just like, I guess, I did with VIP when it first came out in 2008. The issue was that there are people then using erythropoietin to help chronic fatigue, and it was a gorgeous drug, fixed C4A better than anything did, and yet, we started seeing allergy to a natural product.

Having a allergic reaction to VIP was not a good idea. The hematologists went button nuts. That was the reason that the FDA went after VIP, because erythromycin, erythropoietin was so bad. But it gave me strict lists of what must be done for a protein to be agreed to that by the FDA that it was safe to use for people. You can get the information from any of the papers I've written on VIP. My recent most paper, recent paper, we're using high-dose VIP. I put it again, satisfying the FDA, because the FDA is relentless. They'll go after you if you let your guard down once. Specifically, if you're going to use a peptide hormone, know full well that allergy is a risk, statement of a benefit's going to be run under risk, and you better have yourself covered before you use KPV, or B something else, or BCL 1, whatever it is. Because they might be miracle drugs, like VIP was, but there's a process that needs to be gone through for strict medical safety. You don't want to have a malpractice urine, malpractice lawyer saying, "Well, now tell me, what does the FDA say, and what did you do about what the FDA said? You didn't do anything? Well, how do you know Mrs. Jones wouldn't react with erythropoietin allergy?" Or however else a lawyer might ask questions. Don't screw with it.

[1:40:05] DR. NATHAN: We got into VIP through Ritchie, what was it, 2010, 2011, and we began to use it a lot in our patients. Originally, we weren't going to be using VIP if people still had MARCoNS present, or if they still were in the throes of mold toxicity. It was thought that it wouldn't respond well that way. I followed those criteria. I found it helpful in some patients, but not to the extent that Ritchie does. Is VIP helpful? I think it's a cornerstone of a lot of his treatment.

I've used in thousands of patients at this point, and I just haven't convinced myself that it works the way he sees it working. Whether someone can respond to a peptide, I think, has a lot to do with whether a patient is in the throes of whatever illness they have, be it mold, or Lyme, and they're in what Dr. Naviaux called cell danger response one. In cell danger response one, it's survival mode, and I don't find that patients can respond to peptides well in that state. In fact, it often makes them worse. As they get better, they are more apt to respond. Now, some of my colleagues are in love with the peptides at this point. GLP-1 has kind of exploded on the scene. Some of my colleagues find that it's helpful in every single patient in very low dose. I have found that in too many patients, it causes unacceptable side effects, especially if not taken at the right timing.

Other peptides that have been helpful later on in treatment include BPC 157, KPV, MOTS-C. I think they have value, but the patient has to improve to a certain point that they're capable of responding. Dr. Andy Heyman, one of your colleagues, Rich, has recently come up with some mitochondrial markers that he thinks enable us to know whether patients have gotten into cell danger response 2 or 3 and that they, at that point, might be more responsive to those materials.

[1:42:21] SCOTT: What tells you that a patient has been successfully treated and has reached a meaningful stage of recovery from mold-related illness, or CIRS? Do some of your patients need ongoing maintenance therapies, or longer term lifestyle modifications to remain well? Then after recovery, do patients still need to strictly avoid environments with mold, actinobacteria, endotoxins, beta-glucans, or other biotoxin exposures, or should treatment ideally restore a greater degree of resilience and tolerance to occasional exposures? Ultimately, do you view CIRS as a lifelong condition that must be managed, or do you view it as something that can be fully resolved, or even healed in some patients?

[1:43:09] DR. NATHAN: Well, I use urine mycotoxin testing as my final arbiter of when the mold is gone. Before that, how the patient is doing is what is of ultimate importance to me. If a patient's symptoms are completely resolved, that's what I'm looking for. What I found is that there is a very clear, direct association between a cleared urine mycotoxin test and being well.

Once someone has those criterias, which their symptoms are completely resolved, their urine is clear, from my perspective, they're cured. Having followed those patients for years afterwards, that means cured. Not just prone to illness, but cured. Meaning, they can do what they want. They can go into hotels that might be suboptimal from a moldy perspective. The world we live in is moldy, so you can't put yourself in a bubble and function that way. That's not just possible for these patients. The vast majority of them are able to get their immune system to reboot, as I've described before, in such a way that they are able to function in this world like they did before. Actually, many of the patients who go through limbic retraining and mast cell and vagal retraining find that a lot of old traumatic injuries have resolved, and they're actually healthier now once they've cleared the mold than they even were before they got sick.

[1:44:41] DR. SHOEMAKER: I used to not use the cure word. Didn't think that was appropriate. Didn't know we had all the manifestations of illness treated successfully. As time goes by and we've got more and more colleagues publishing papers, and we're looking at chart review and whole series of approaches that say, “Yes, we're on the right track.” We're at the point that we're probably at 95% are better to be at the point of being able to be functional. 85% be happy and kicking around. The numbers are still not good enough.

If we've got to do 20 doses of VIP to fix T3, which the recent paper is all about, 20 doses of VIP is $10,000. That's a lot. When you see people spending great quantities of money, you say, "Well, why don't we have just a little less, or not go to the antique shop and not go to the old newspaper section of the warehouse?" The answer is that we have adaptation of life to the badness. We have adaptation to doing something for the badness. If you do have something bad happen to you, don't gnash your teeth. Help is on the way. The Welchol that you packed with you, go ahead and start taking it now.

[1:46:09] SCOTT: Where do Lyme and co-infections fit into the CIRS landscape? Do mold illness and Lyme commonly co-exist in patients with complex chronic illnesses? How do you determine when persistence of symptoms could be driven by mold versus ongoing infections like Borrelia, or Bartonella, or Babesia, and when is it appropriate to treat both of them? How and when do you approach the treatment of vector-borne infections in the context of mold illness and CIRS?

[1:46:40] DR. SHOEMAKER: What we have to recognize is that more than today, where Neil and I are disagreeing a lot on things we knew we were going to disagree about, but if you want to get some real good arguments, talk to a Lyme person and say, "You don't need to use any more antibiotics." I left ILADS in 2002. I was frustrated that they didn't have any… pay any attention to how to diagnose Babesia. Nobody would look at Babesia under the microscope looking for a red cell inclusion. They try to come up with other things, and they ignored Sarcocystis, which is more from birds, Eimeria, which is pigs and chickens. Toxoplasmosis, which is found in kitchens and cockroaches and everything else. It's an apicomplexan. All these apicomplexans, including malaria and Babesia, have a GPI, or glycosylphosphatidylinositol as a toxin inducer attached to their cell walls.

So, that if someone says, "Well, I've got Lyme disease, but I've got co-infections. I've got Bartonella." I say, "Okay, how do you know you got Bartonella?" "Well, I didn't get a test on a Galaxy, but they're the only people that run it." Ed Breitschwerdt did at NC State says he's got 28 organisms that are testing positive for Babesia. Whether you got 28 Babesia organisms, how can you rely on one?

When Neil and I were going to Norway in 2015, we had done results looking at NeuroQuant and testing for Lyme. If Quest Western blot's positive, N was equal 10, IgM 9, NeuroQuant would be positive in 6. If Quest Western blot positive had 9 IgG, NeuroQuant positive in 6. If IGeneX had positive IgM, N was 42, NeuroQuant was 3. IGeneX found IgG N is 42, NeuroQuant was positive in 1. Atrophy nuclei 1.62 and CIRS WDB post-Lyme syndrome 2.38. That was never repeated. What we had back then, 13 controls, 34 base, looking at Tregs, post-antibiotics 29, post-CIRS 31. TGF-beta1 was 36, 21 in controls, 67, 82 in base, after antibiotics 89, 67, and after CIRS 48, 90.

C4a similar, same pattern. C3a, 124 controls, 1,284 for base, and after antibiotics 384, and then after CIRS 410. C3a is definitely doing something soon, earlier on. Inducible Tregs 466, 294, 302, 416. Treg cell deficiency is a problem. Then thymus-derived Treg was worse, 425, 244, 298, 396, 386. Now, I've never seen this reproduced by anybody in the Lyme community. Why are we not looking at TGF-beta1 and in thymus-derived Tregs and inducible Tregs? These are important in the inflammatory illness. When I hear someone's got Babesia, I want to see what a red blood cell looks like and what haptoglobins look before ordering an IgM, or some other tests that may not be what I consider to be right. It's a cinch that we've got a problem with Lyme. We don't have any answers to say just take an antibiotic, but it should be looking at inflammatory and innate immune responses in Lyme as critical and not stopping the antibiotics if they're there.

[1:50:50] DR. NATHAN: Your question, Lyme with its co-infections coexists in a huge percentage of my mold patients. I'm not surprised by that. Mold weakens the immune system, predisposing to Lyme and vice versa. What I tell most of those patients, most people who come to me have already been worked up pretty thoroughly. They've already got what I consider good testing from IGeneX. Quest is not a particularly good test at this point. Western blot isn't even done anymore. In most places, we're using the immunoblot, which can test for multiple species as you're recommending, Ritchie. It will pick up, yes, there is a lot of species of Babesia, there's a lot of species of Bartonella. Newer tests are picking up more and more of them, not all of them yet. Our testing's gotten better.

What I typically find in those patients is we need to treat the mold first, or they're not going to make any progress with their Lyme. You can also, once the mold is cleared and that inflammatory load is out of the body, they will respond infinitely better to shorter courses of antibiotics and make much, much better progress. One other hooker to throw in here is long-haul COVID. If I had to list the three most common inflammatory root causes that we look at, it would be mold, Lyme with its co-infections, and long-haul COVID, all of which give fairly similar symptoms. And so, it's a little bit tricky to tease that apart.

[1:52:27] SCOTT: What has changed in the COVID era relative to mold-related illness and CIRS? Can COVID itself act as the trigger for a CIRS-like illness, or can COVID be the specific causation for CIRS? How has COVID influenced your interpretation of inflammatory and immune markers, like TGF-beta 1? How do you currently approach the diagnosis and treatment of patients where CIRS overlaps with COVID, long COVID, persistent spike proteins, or other post-viral contributors?

[1:53:02] DR. NATHAN: One of the tests I've gotten most fond of most recently is Bruce Patterson's 14 panel cytokine test, which tells us a pattern of cytokines. Now, Dr. Patterson has clearly laid out in published papers, peer-reviewed journals that there is a particular pattern of cytokines that we see with long-haul COVID. You might have a lot or a little bit of spike protein, but the question is, did that immune system get triggered in such a way that we can now call it long-haul COVID, and we can tell by the cytokine panel. I find that test useful. He's also done the same thing for Lyme, which is a different pattern. Recently, he and I have been working together on the mold pattern, which just for edification, we find that RANTES and sCD40L are particularly elevated in our mold patients more so than the other conditions.

The beauty is we can literally look at what is the immune system considering to be public enemy number one here? What is it wrestling with primarily? In my hierarchy, I treat the mold first, then the long-haul COVID, and then the Lyme. What we found is a huge percentage of people were, I will use the term unmasked by COVID, meaning that the inflammation it triggered weakened their immune system to the point that the mold that they were harboring emerged full blast, or the Lyme that was in their body emerged full blast, and their immune system had lost containment. I think we see that commonly. In my experience, a lot of people who are diagnosed with long COVID really have mold toxicity, or Lyme disease, but sometimes both.

[1:54:55] DR. SHOEMAKER: We published a paper way back in 2021. Not that long after COVID started going. We looked at people that were fine, had COVID, got better with 3 weeks of antibiotics, whatever they were going to use, and then we had them stay away for three weeks. Six weeks after the COVID got started, they got better, they're feeling fine, and then they got worse. Well, what we had done is Don Cheney went on their first visit, looked to see what it was. No big deal, no answers, no arrangement. When we looked at them come back at six weeks later, then of the people that were sick, all of them had gene activation for Actinos and endos. It was 64%. 63% for Actinos and 54% for endos.

This coincided with time that people got worse. Well, they were diagnosed with long COVID. The answer is what happens now is we measure what's going on inside the house. The house was contaminated before you got sick, but you weren't sick from the house. HLA, maybe we can go back and talk about. Specifically, what happened is that there was now a relapse with a masking that had been taken care of, and that what we had was COVID that was induced by activation of cells that were benign before COVID, and then they turned out to be Actinos and endos. Now, our paper didn't get published in a big journal, but with all the brouhaha going on with COVID now, with what was done and what wasn't done in 2020, 2021, 2000 even, I think it'll come back. Post-COVID, we're going to find is primarily gene alteration.

[1:57:01] SCOTT: I think that term unmasker, the great unmasker for COVID, kind of fits with what both of you are talking about, that then we're seeing other things that we could tolerate previously that now we can no longer tolerate.

How do you balance creating treatment protocols that are grounded in published science and evidence, while also remaining open to interventions that could help patients clinically, but don't yet have strong research bases behind them? How do you decide when an emerging therapy, observational experience, or clinical outcomes are compelling enough to incorporate into your broader clinical approach?

[1:57:41] DR. SHOEMAKER: If there's an adequate database based on an experimental basis, or something different, something new, different dose, different species all the way around, then I'll keep it in mind. I remember the famous words of my grandmother is, "Remember, you're the doctor. You don't know everything." She was right. Specifically, if there's things that make sense, that look good, can be done at low risk for patients, then you can think about doing a study. The IRB focus of the late 2000 teens has eased off just a little bit. The FDA is not quite so, so picky. If you're going to do a study, you got to do it right. Because if you do it wrong and you publish it, then you've told the world that you did something wrong and you hurt a patient. There's nothing worse than that. Treatment protocols, everything should be published. If you got work that's so good, why not publish it, man? What's wrong with that?

[1:58:53] DR. NATHAN: Guilty. When I came to your clinic, 2005, I was really impressed at how you were at that point keeping reams and reams of data on your patients. A failing of mine, I'm not that organized. Had I done so, we'd be way ahead of the game at this point, and I'm just not wired that way. However, I am absolutely aware of the need to get the data that you're asking for and of its importance. I'm working right now with Jill Crista. We have put together a questionnaire similar to yours that we have just finished, and we have an IRB for it, and we're going to get it published in a peer-reviewed journal, showing that her questionnaire, which I contributed to, will be able to be validated as a way of documenting who has mold toxicity and who doesn't in the same way that Dr. Horowitz did the same thing for Lyme disease.

Once we have that in place, we're funded for it for the first time, our goal is with my hundreds of physicians that are in our mentorship program, we're going to have them do those questionnaires, add to the questionnaires so that every aspect of treatment will be cataloged, and we'll put it through our AI computations and begin to document which interventions work the best for which treatments and really begin to get that out there. I know it's necessary. It's a high priority of ours. Yes, we need to do that, so that I would love to add my data into what you are doing, so that we could begin to talk even more about how all of these things are interconnected.

[2:00:38] SCOTT: What are your current research interests in CIRS, or mold illness in terms of the overall landscape? What projects are you currently involved in that you feel have the potential to make a difference for patients? What do you see as the future of mold-related illness and CIRS? Are there emerging lab tools, treatment strategies, environmental assessment methods, or building mitigation approaches that you believe could significantly change how we understand, evaluate, or treat these conditions in the years ahead?

[2:01:09] DR. NATHAN: First of all, especially for patients who are listening to this, we've learned a whole lot in the last 20-plus years. I think for myself, and Ritchie would probably say the same thing, I'm much better at this than I was in 2005. We have many more tools. We have more things to do. We've got a greater understanding of the complexity of mold-related illness. It's not as simple as you used to think it was. We can approach it so that the majority, vast majority of our patients will heal whether they use Ritchie's methods or mine. The interesting thing is they both seem to work in the vast majority of patients, so there's got to be some synthesis here that we can look at.

In terms of the research, I mentioned the work I'm doing with Jill right now, work I'm doing with Bruce Patterson at looking at the cytokine panel that will help, I think, with the diagnostic process and make it a little bit more streamlined. I think simply collecting more data and getting better at what we do. We've been doing it all along. Both Ritchie and I have trained a large collection of physicians to do this work. We're getting old. The hope is that those folks will carry this work forward. My number one hope is that the medical profession will embrace this and not gaslight patients anymore and allow them to understand that, yes, you're ill. We know what you have, and we have an approach that will work. To me, that is number one. We need to get it out of the quasi-science into this is an absolutely important and very real diagnosis.

[2:02:56] DR. SHOEMAKER: What we've done over the last three years is figure out what a fingerprint for Parkinson's was, show the injury peripherally, then rising up into microglial cells with inflammatory responses, then taking that further to take the link between peripheral to central being a prodrome and come up with a mechanism to treat the prodrome. That paper's published. That's serious. Next, we are after the vascular hypothesis for Alzheimer's disease. Sidney Strickland from University of Rockefeller in New York has been after this for years. I think he's missing the wrong coag elements. I think I've got the right coag elements. We're looking at the link between peripheral injury, setting off inflammatory problems peripherally, going to central injury with an additional turmoil based on coagulation and inflammatory changing what goes on with beta amyloid. It's a big player. I don't know, I think maybe some days, I'm going to die before Neil does. We got to get working, Neil. This is crazy.

[2:04:27] SCOTT: I want to give each of you an opportunity to share any closing comments that you might want to leave our listeners with, or leave each other with.

[2:04:36] DR. NATHAN: Yeah. For me, for listeners, for physicians, for consumers, mold illness is real, it's diagnosable, and it's treatable. To me, that's the big message, my takeaway message to people. I think Ritchie and I have talked about a wide, wide understanding of the whole mold illness field, and I think there are pieces of that that need to be explored in more detail, and we need to learn how to incorporate them into what we do. Is more research needed? Absolutely. But we already know enough that we can help a whole lot of folks.

[2:05:17] DR. SHOEMAKER: Well, thank you, Scott, for your courtesy and skill. I'm getting goosebumps. It was very nice of you to offer your time, especially walking into potential minefield, like you did today, Scott. My applause for you, and may God bring you many more years. One of the things that you wrote here, "What are some of the key things you do on a daily basis?" It sounds trivial, but my first wife passed away. She died of breast cancer, and never thought I would be so lucky as to find someone else that would stand me, much less spend time with me, or in my case, much less marry me. I've had the best three years of my life as a lonely old codger, and now I'm a young man. What I do in every day is tell my wife how much I love her. That's how I start my day.

[2:06:14] SCOTT: Beautiful, beautiful. This has been such a powerful discussion with two of my personal mentors and true leaders and heroes in the field of complex chronic illness. While they may have different perspectives, they share a common mission, which is advancing the conversation around mold illness and CIRS, while improving the quality of life for those who have been impacted by it. Thank you both for your life-changing work, for your unwavering commitment to pursuing new understandings, new tools, new answers. Your dedication continues to move the field forward and brings hope for so many of us on our healing journeys. I honor you both, and thank you for being the yous that you are.

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[2:07:00] ANNOUNCER: Thank you for listening to today's episode of the BetterHealthGuy Podcast. You can learn more about today's guest, including relevant links and resources in the show notes. This podcast may provide community discounts and occasionally share links from affiliate partners. You can find this and other episodes on YouTube, Spotify, Apple Podcasts, Amazon Music, iHeart, and more. To learn more about Scott's personal journey to better health, visit BetterHealthGuy.com. Join us next time on the BetterHealthGuy Podcast.

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