I’m happy to be interviewing Dr. Shoemaker with guest host Dana Howell. Dana’s introduced me to a lot of the CIRS (Chronic Inflammatory Response Syndrome) and mold research. I was really impressed with her story; now she has healed herself from CIRS and helps others to recover.
Dr. Shoemaker is a pioneer in CIRS research, has written several books, and has successfully treated thousands of mold patients.
I’m happy to be interviewing Dr. Shoemaker with guest host Dana Howell. Dana’s introduced me to a lot of the CIRS (Chronic Inflammatory Response Syndrome) and mold research. I was really impressed with her story; now she has healed herself from CIRS and helps others to recover.
Dr. Shoemaker is a pioneer in CIRS research, has written several books, and has successfully treated thousands of mold patients.
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Dana Howell: Welcome to SelfHacked, my name is Dana Howell. I’d like to thank Joe Cohen for inviting me to host this show and be the patient perspective of this podcast today. I’m so happy to be bringing two people together that have been so instrumental in my healing of CIRS or also known as Chronic Inflammatory Response Syndrome. After being exposed to a moldy building in Vietnam I experienced some really chronic and excruciating symptoms that truly baffled doctors and really caused me to dig into the depths of my heart and soul to try to overcome. It was Dr. Shoemaker’s knowledge of biotoxin pathways that really played a huge part in my recovery. He’s really changed my life. He’s written several books, including “Mold Warriors,” and also “Surviving Mold,” Joe calls that one my bible. Joe Cohen was a wonderful addition to Dr. Shoemaker’s work, and he’s integrated some other processes into the mix that have helped me to really get that much better. I’m going to start off asking Dr. Shoemaker a few questions, before handing them over to Joe Cohen. Dr. Shoemaker, it’s truly an honor to meet you.
Dr. Richie Shoemaker: Well the honor is all mine. I’m pleased to meet you via Skype because the phone connections weren’t doing well at all. I’m going to blame that on the rural eastern shore of Maryland. It’s interesting with the new stoplight on route 13 it can take me almost 3 minutes to get to my office. I mean these people that are just driving up and down the highway slowing me down, it’s terrible, but I figured that just applied to Skype as well!
Dana: Oh well, we’re just happy you joined us any sort of way. If we had to do it by owl we would have. So Joe Cohen, the prolific information guru from SelfHacked, welcome to you as well.
Joseph Cohen: Thank you very much I’m really glad to be on here. I’ve been reading Dr. Shoemaker’s information for the past year now. I’m just blown away by his brilliance when it comes to figuring out these things and really pushing the envelope in understanding the root causes and the biology of people with CIRS and chronic inflammatory conditions. So back to you Dana.
Dr. Shoemaker’s Biotoxin Discovery
Dana: Ok so Dr. Shoemaker, first can you please give a brief history on how you determined the relationship of the biotoxin that you discovered in Maryland, related to the fish and Pfiesteria, and how it’s related to other biotoxins like mycotoxins from mold, and spirochetes given off from Lyme disease, that can cause this chronic inflammatory response syndrome that often needs to be addressed in order to recover?
Shoemaker: Ok, we have about 20 hours for this discussion is that right?
Dana: I know! We almost took this question out but it’s just so interesting.
Shoemaker: When I finished medical school I had the idea that the very best trained physicians would be primary care docs. Out in the countryside or in the intercity or areas where they were called underserved. And the reason for that is I felt primary care docs could manage a host of problems far more competently than specialists in terms of the breadth of what we do far less expensively in times of need, and certainly far better in terms of continuity. That was the dogma I had set up a model for a rural healthcare system that I wanted to pursue, and sure enough a family practice residence in Williamsport, Pennsylvania provided that opportunity. We set up the idea of a spoke of the wheel where Williamsport was the center for patients from outlying clinics, and patients would be treated by local docs. Over 95% of the problems, of course, family docs can take care of, sending them in for studies and consultations as needed. But there would not be this common mechanism of a patient being sent to a cardiologist and then disappearing forever. The idea is that the specialists would be out-writers, they would go from clinic to clinic in addition to managing their own illnesses. That way we could provide a model of care that was inexpensive and rather intensive in personalized care. That was the background that led me to Pokomoke, it’s medically underserved. We are right on the Pocomoke river which flows into the Chesapeake Bay. Our town has 2300 people and when the people from Virginia come up..oh my god the traffic jams because they can’t turn left without doing something strange, but I’m sorry! Getting off track! The issue is that in a rural environment, I got a chance to play with wetlands, I got a chance to work with my darling bride Joanne for years on taking what had been a watermelon field and make it into a wetland paradise.
And that’s what I was doing when we started hearing about fish with funny behaviors, fish with funny lesions in all areas downstream from just where we are. These are areas where the salt wedge or the saltier water with the tide comes in from the Chesapeake Bay and meets the downstream flow. And where that mixing was taking place, we started to see some weird things. There were a few fish that died. The people that catch the fish, and harvest crabs, and oyy-sters, or that’s oysters if you’re not educated, is, we call them watermen, and they started telling me, whether I’m waiting in line in Walmart or in my office or somewhere else on a Saturday night, that they didn’t feel right.
So where was the answer?
And I’m supposed to be well trained from Duke, and I’m supposed to know all these things. Where was the mechanism to identify their illness? Where was the mechanism to identify the biomarkers of the syndrome and where was the mechanism to treat them? Well if you anticipate that the answer is all 3 were not known, welcome to my world in 1996/1997. And the question is, what would you do? I’m supposed to be the fella who can help out 95% of the problems. Gee, I have to refer these guys out, I don’t know what’s wrong. So I referred them out and guess what, the referral specialist didn’t know either.
So the question comes, what illness can cause a multisystem, multisymptom illness with cognitive problems, respiratory issues, rashes, and GI problems and much more all at the same time? It’s not in the textbook I’ll tell you that.
When one lady, as I got further along, and there were fish kills now and the news media was involved, one lady had terrible diarrhea. I mean she was just pooping up a storm every 20 minutes. So I said well I can’t fix the rest of your memory problems and your headache and all this other stuff, but I can stop this diarrhea with an old fashioned cholesterol-lowering drug that nobody uses because it’s 4 times a day and makes everybody constipated. It’s called cholestyramine (CSM). So I gave her cholestyramine and she called back 2 days later. I knew her diarrhea was going to get better, that’s simple. She said yep it’s better. And I said ok how’s the rest of you? And I almost fell off my chair when she said well my headache’s gone, my memory’s better, my cough stopped, I feel pretty good! I said you gotta be kidding me. Here’s a drug that’s not absorbed. It can’t possibly add anything and it’s treating headache, it’s treating cognitive problems. What’s the mechanism of this one? Well we can speculate until the cows come home but I started saving stool specimens because I figured if there was something that cholestyramine was binding, then it was going to be reabsorbed like things are like bile salts do and other kinds of toxic problems that can be fixed by cholestyramine, certainly fat soluble problems like DDT and dioxin and Kepone can be absorbed by cholestyramine. And it works by breaking up enterohepatic recirculation. So if this stuff is recirculating, it’s dumped out of the liver in the bile, dumped out of the bile in the intestine, and back in the body, we call those ionophores or amphipods. If we can show the mechanism of cholestyramine benefit is binding these things, well how can that be? It turns out there’s a structure-function relationship, where the positive side chains of cholestyramine are about the same shape and size of what are called the anion rings of these ionophores. And it all made sense but no one had proven one way or another, and that’s why I started saving stool specimens. I don’t think anybody else saved stool specimens the way I did, but I had a freezer full. Great conversation at parties. Anyway, the question Dana is if you found one person who got better with an insoluble illness with a problem that had been torturing you for 6 months, what would you do to the next 200 people that you saw?
Dana: Right, I would just try it out.
Shoemaker: Would you give them cholestyramine? Yea it was kind of overwhelming that it all worked. And I thought boy this is great, but these were acute illnesses, later shown to be biotoxin illnesses. And the fascinating issue in the education process is that there was a lot of political spin saying well what made the Pfiesteria dinoflagellate bloom was poisoning of the water with nutrients. And I’m going, well wait a minute that’s like the dead zone of the Gulf of Mexico. If nutrients are the problem, we all are part of that because we all make nutrients. But if there was a specific chemical involved then there is somebody that is at risk. So politically it was very easy to say nutrients are the problem, there will be no lawsuits here, no litigation here, and we need to go forward. Well turns out that was just dead wrong. The issue also comes back to, is there anyone involved in cutting edge medicine that doesn’t deal with the interface of science, and political opinion, and public relations, and now I guess we have to put in social media in that as well, because if you have access to a Twitter or something like that and you have an opinion online. But having said all that, the treatment with CSM for Pfiesteria lead to so many questions. Why did some people get sick and others didn’t? If there were some people who were sick longer they didn’t get better as quickly, and there were other things, and what were the biomarkers? The only biomarker we had was visual contrast sensitivity and that took a year for Ken Hunt now, who is down at the national institute of environmental health part of EPA, and Ken figured that out. We had a biomarker. The abnormalities in the visual contrast show the problem with neurological functions of vision. Well, that got better with treatment. So as we started moving forward, here we had a diagnosis, we had a pattern of a multisystem, multisymptom illness without lab abnormalities of standard labs that you learned about in medical school, that got better with cholestyramine that had problems with visual contrast, that got better after treatment, but only to relapse with re-exposure. So this was just something brand new.
And I started looking at blue-green algae problems down in Florida, problems with people sickened by exposure to where pesticides had been used in Florida. Then one guy had the same symptoms, same kind of findings, same response to CSM and all he had was exposure to a closet that was full of black mold in 1988. That was my first so-called mold patient and that’s occupied the last 18 years of my interest and my research. We have fast forward now gotten to the point, really probably ought to be talking about genomics and transcriptomics, because that’s where illness is, and that’s where the problems and the new arguments and the new political spins and the new social media spins and the new internet spins where we’ve got a lot of opinions, but we’ve got something that other folks don’t have, and that’s data. And I think that as we go forward data is mandatory.
Genes, & Diagnosing CIRS
Dana: You’re now starting to call CIRS genetically-induced CIRS. Joe you can talk a little bit about that now if you’d like.
Joe: Yea, so my first question is, what is the diagnostic criteria for CIRS. You recommend testing for 10 biomarkers or whatever it is, and the VCS test and other things. The question is, in some people, some markers are going to be high, and some markers are not going to be high. What is the defining characteristic of CIRS, from a diagnostic perspective?
Shoemaker: Fortunately that question was answered in 2008 by the USGAO in their report to the federal government on the federal agencies involvement with moly buildings. There must be the potential of exposure for any kind of CIRS, there must be the same symptoms found in those patients, same or similar, statistically, to those in peer-reviewed published literature. There must be the same lab abnormalities present in those patients as well, and interestingly, there must be a response to treatment. So it’s a little different from what the case definition our group published in 2003-we did not demand improvement with treatment so much as we looked at some other things. But the issue is that there is no one specific test that will give you CIRS. We look for cluster analysis of symptoms. Fascinatingly, I had no way, and in my mind, that you could take a subjective history from a patient, take it through the brain of a trained physician, and make it into an objective measurement that a statistician can convert into a number. For god’s sake that they can do that, it’s amazing. They could probably run this Skype machine without a problem too! But the issue is if we look at cluster analysis, we can sort out depression anxiety and fibromyalgia as possibly separate by individual symptoms from person to person, but they all will have clusters of symptoms, 8 out of 13, if they are a CIRS patient. And a lot of the times when we’re looking at folks who think they’ve got fibro, and there are people with chronic soft tissue pain. Do they have symptoms of CIRS? No. But when they do, and you’ve got a diagnosis of fibro be raising suspicion that they may actually have been misdiagnosed. The lab abnormalities, I would love to say HLA was all you needed, now that I know that transcriptomics combined with proteomics is the most sophisticated way, and the issue is that there is no one gene.
There is a grouping of 675 genes that we know are vitally important sorting out patients with CIRS with inflammatory processes, compared to say some with other issues that don’t. And it’s that sophistication that computers can bring and data mining can bring that may give specific answers. One gene, I doubt it, it’s usually the interaction of genes. But the other issue is that we’re looking at constant day-to-day and actually minute-to-minute variation of gene expression. And if you’ve got minute-to-minute variation separate in men vs. women, gender really does have a role here, race doesn’t have too much, age has a little bit, but the real issue is how can you pick out who actually is a control? Because we know that everybody is changing from second to second, and as we go forward with that, if you meet the case definition, then what we want is to identify a group of abnormalities, not a single one group, fix those, and then see do we now have the availability to say symptoms, labs, VCS, NeuroQuant, and genomics are equal to those of controls. That’s what we’re after.
Joe: I agree with you 100% as far as the genes. People will often focus on one gene, whether it’s MTHFR or specific genes, and I’m of the opinion that you need to look at thousands of genes to really get a good picture of what’s going on. And that’s actually what my program will be doing in the future; it’s going to be looking at thousands of SNPs and synthesizing that information with algorithms to see what’s going on.
So here’s a question with CIRS. Let’s say there’s a patient with high TGF-beta 1, high C4a, but passes the VCS test, but did not have a clear exposure to biotoxins. There were no clearly identified water-damaged buildings, but let’s say they lived in New York City or something, and we know New York City buildings are most of the time water damaged. Would you say someone like that would be categorized as CIRS?
Shoemaker: We don’t have the capability of making an assumption that just because you live in a Lyme endemic area you have Lyme disease, just because you live in a high rise looking out over Central Park, and I agree with you there’s an awful lot of moldy buildings in this world, that doesn’t equate to being diagnostic of a mold problem. And there are people that we are going to hedge on because if you don’t meet all the criteria you can’t come up with a secure diagnosis. But having said that, do we have to have a completed diagnosis in order to initiate therapy? And this goes back to some of the discussion of medical certainty. Are there times that you don’t know what’s wrong that you have to do something? For example, if you have a child with a fever of 102, and he’s got a red eardrum, having been in that situation thousands of times myself, I’ll frequently have used antibiotics thinking I have an ear infection. Were there times that there were an ear and a sinus problem? Yea. Were there times I treated viral infections with antibiotics? Yea. Were there times I said virus and I was wrong and I didn’t give antibiotics? Well you know you don’t have absolute certainty every single day of every single minute. One of the things we talk about now is the Zika virus and microcephaly. Well, have we really looked at chemical exposures of people with microcephaly? Because microcephaly can be caused by chemical exposure. I was raised on a fungicide that caused a lot of problems in Florida including on the brain. So if we’re going to blame one causative agent, you need to do a lot of epidemiologic work. So I hear you, if I have a high C4a and a high TGF-beta 1 and a multisystem multisymptom illness, I know that 8% of people with VCS will have a normal VCS. So that one doesn’t bother me. But if they don’t have a multisystem multisymptom illness, they don’t have CIRS. That is part of the case definition.
Joe: I really find it very interesting how you’re diagnosing a disorder like CIRS. When you look at conventional medicine, and you are part of conventional medicine, but the way that most doctors will really accept diagnosis is when there’s either a very specific infection or toxin, like hepatitis a-c, HIV, Lyme disease, or there are very specific defining symptoms like schizophrenia or bipolar, or there’s a very specific biomarker like Hashimoto’s and antibodies to the thyroid, or it’s so common it can’t be ignored. I’ve identified those as the 4 categories as to when a condition becomes accepted widely in the literature. If you compare that to CIRS, it’s very different, because there’s a lot of symptoms, and there’s no extremely specific biomarkers that you can pick on, or very specific infections or toxins. Are you trying to change how conventional medicine diagnosis diseases, or what do you think about that?
Shoemaker: Well I would ask the court reporter to read back the statements that you made because you strung together a lot of things that I’m objecting to as I heard them, just so as you know I’m not going to agree with you on a lot of what you just said. But what I’m trying to do with CIRS is simply find a way to solve a medical problem of what is wrong with folks that have now an increasing number of biomarkers. And that’s the path that’s led me to genomics. It’s kind of hard to find the folks that I used to have. All they had was blue-green algae exposure. I don’t get to see that anymore, fortunately, there’s probably a thousand docs using my protocols around the country. So I don’t see the easy ones anymore. I don’t see the Pfiesteria people that take CSM and are better in 3 days. There are those people, that’s for sure. But it was the search to see why does a person not get better that led to HLA, that led to MARCoNS, that led to VEGF, and MMP-9 and each one of these separate branches have led to additional information. Symptoms, I just don’t think you’re going to get much information looking at those. As far as Hashimoto’s goes, like all autoantibody illnesses, we’d like to know what the mechanisms of injury are. Now that we have a lot of genomic information, looking at retinoid acid orphan receptors I think we have to go back and revisit our thoughts of autoimmune disease. The fact that TGF-beta 1 can be important here, does not mean that’s the whole answer. But I’m quite content to not know everything.
When CIRS is an Underlying Cause
Joe: Right. If you look at cytokines that are elevated in autoimmune conditions, many are very similar cytokines, and I’m sure there are many conditions with elevated MMP-9. TGF– beta 1 is elevated in wounds, ischemia, hypoxia. So here’s a question for you. What percentage of diseases that are diagnosed with schizophrenia or bipolar do you think, have the underlying cause of CIRS? Or these diseases are really just symptoms of a chronic inflammatory state. So let’s say those two diseases, what percentage of those people do you think really has a chronic inflammatory syndrome going on?
Shoemaker: Well Joe, I need you to take your question and turn it around. What are the diagnostic criteria we use for schizophrenia? What are the metabolic biomarkers that are used? Are there any?
Joe: I think, to my knowledge, the way they diagnose schizophrenia and bipolar is simply through a symptom checklist. Do you have these symptoms? And the symptom checklist is usually pretty specific. So are you hallucinating, a certain kind of hallucination with schizophrenia, things like that. But we know that people with CIRS also develop a lot of symptoms that are similar to schizophrenia sometimes. So the question is, is CIRS let’s say brought on by mold, the root cause? I mean how often is it the case with a disease like schizophrenia or bipolar, or maybe if you’re not sure about those diseases, let’s say autoimmune conditions like MS? I know thyroid conditions, a lot of people with CIRS will develop antibodies. What percentage of the people do you think with let’s say Hashimoto’s are really having a mold-induced illness or CIRS?
Shoemaker: Well I know that there’s no difference, because I have looked at two different kinds of antibodies in Hashimoto’s, when I look at cases vs. controls, and I hope that you would do the same and record symptoms and lab abnormalities, you can look at say the incidence of auditory hallucinations in schizophrenics, compare that to nonschizophrenics, and the incidence of that one symptom will be pretty high in schizophrenics compared to non. So we can assign that one a relative risk. That number, the CDC wants the number to be 1.5, I use 2.0, but I think that number’s going to be a lot higher. But do you have a difference in schizophrenics, cases for controls for elevated levels of TGF-beta 1? Well, that would be an easy enough question to answer. We need a group of cases of thought to be schizophrenics, and then we look at nonschizophrenics, and we have to sort out are they sick from CIRS, or are they not sick, and we should have three different relative risks. The interesting feature along this line of argument, since there is no answer to the question that you pose, is we now know the incidence of C4a is quite high in established schizophrenics. There was a paper not too long ago in decent peer-reviewed literature. So is that just a comorbid condition, is it an association, or is it causative?
Joe: Well they think it’s causative based on that study.
Shoemaker: Can you share with me your definition of medical causation? I have a feeling we’re not talking about the same thing.
Joe: Well they think it’s causative because they see that C4a is able to interfere with the synapses in certain parts of the brain, and also I think because that study was looking at genetics, and people with schizophrenia were more likely to have genes that caused higher C4a.
Shoemaker: The issue is that medical causation is not simply an association and a putative mechanism. We can guess mechanisms until the cows come home. But testing those prospectively is really what we need to do. Good science really demands fairly careful thought, and it’s the rigor of thought that will lead to publication. So not every publication that you see is going to be as pure as what we want. But the issue is that if there is an association of C4a with schizophrenia that does not translate just because someone comes up with a mechanism into causation. We would have to find some people who had perfectly normal health and follow their C4a and look to see when their C4a goes up that schizophrenia can develop. That may not be the best example, but it’s one where prospective evaluation is very different, which is necessary for causation, is very different than an association study or a case control.
Joe: I agree. And that actually brings me to another question. With CIRS, have you studied people, before CIRS that had certain markers, let’s say low MSH, low VIP, and then see them developed CIRS? Because that is truly difficult for any disease, and the medical community struggles with that. Have you followed people pre-CIRS, then they get a biotoxin exposure, after which you were able to see their markers, TGF-b, C4a, MMp-9, MSH, VIP, and all that stuff?
Shoemaker: That’s an excellent question, and what we have done is to look at our control populations with 4-3-53, that’s the only haplotype of HLA we’ve looked at, and followed them sequentially looking for changes. This was done a while ago, so we just had MMP-9 and C4a. But we were able to show that there was an antecedent inflammatory event in a significant percentage of these people. The problem was defining what the inflammatory event was going to be, because we had some people get mono and their C4a’s did not go up until they got mono, and they did go up after mono. But unfortunately, we also found a small group of people who had C4a that was normal before mono, elevated after mono, who did not go on to develop the rest of CIRS. So you know the idea of following one biomarker, I abandoned, as quite frankly we have already talked about, no one entity that does it. But it’s a vitally important area. And here’s where the international registry of transcriptomics I think will come in, because we’re going to look at people who are well far more than just looking at HLA and follow them sequentially over time to see what genomic changes. These are changes that are expressed, very different than SNPs of course, but expressed genes are ones that are going to be associated with subsequent abnormalities, not just protein coding, but regulation of DNA. Your question remains an excellent one. How are we going to do that looking at one gene or one test? We have to look at a lot.
% of CFS that Actually Have CIRS
Joe: Ok yes, so now what percentage of let’s say people who claim to be CFS, Chronic Fatigue Syndrome, if you had to guess, (obviously there’s no way to know, that would take hundreds of years to figure out exactly), are suffering from biotoxin illness vs. some other cause?
Shoemaker: There are some people that diagnose CFS in mold patients, there are some people with Lyme disease that get diagnosed with CFS. I remember I gave a talk at the International Association of Chronic Fatigue Syndrome in 2009 in Reno. My talk was at 2 pm, Lenny Jason was right after me at 2:10 pm. And I talked about pediatric patients that met the case definition for CFS. The audience, as they responded to me, was excited to find biomarkers because they had a genetic susceptibility, and TGF- beta 1 was elevated, and C4a was elevated, and they had autoimmunity, and wasn’t this great to show that these CFS patients shown by case definition had a biomarker? And then with my normal lack of subtlety, I just said and as a matter of fact the 163 patients and 52 controls, all the cases were mold cases, every single one. Lenny Jason who wrote that case definition gets up after me and says I’m not quite sure I can follow that talk. That I thought, would be the turning point that CFS would be recognized in the role of mold. There was some initial discussion for at least a week. My paper was published in the CFS bulletin about mold patients looking like Chronic Fatigue, and there’s some discussion that now CFS had to rule out mold exposure. But no attempt was made to look at Chronic Fatigue Syndrome diagnosed by any mechanism. And we have the same problem with Lyme disease. Lyme disease can be diagnosed a whole series of different ways, and I’m hoping we can get some real rigor in there. But I can’t answer your question of what percentage of CFS is moldy.
Joe: So why are people, it seems that people are trying to suppress that mold is a cause of CFS? What reason, I have some theories, but what reason would you give why people aren’t willing to accept why mold is the cause of CFS?
Shoemaker: I’d be more interested in hearing your theories then possibly you hearing mine, but go ahead.
Joe: Ok my theories are conventional medicine, the way most doctors in the medical establishment works, is that they’re not interested in finding a relatively vague cause, such as mold. Mold can be any kind of mold toxin, or it could be contributing factors. It could be maybe environmental pollution in combination to mold, in combination with priming infections that you speak about. So when you get to a very complex area of multiple things that need to be required, and it’s not a specific infection or toxin, so the medical community will identify aspergillosis or something like that, but if you look at CFS patients, you’re not going to find a very specific mold strain. And the way I see the medical community is they look at very specific biomarkers, very specific infections, or very specific symptoms, CIRS or even CFS, is just like this multisystem multiple cytokines, multiple issues wrong, and the scientific and medical community like simple so that they can establish cause and effect, whereas CIRS is very hard to pin down a specific kind of toxin or something like that. What do you think?
Shoemaker: Well let’s take that one step further. Is there specific causation for a CIRS from water-damaged buildings, yes or no Joe?
Joe: I don’t think it’s specific enough, in the sense that it’s not a specific enough toxin in order for the conventional medical community to get on board easily.
Predisposing Factors: Lack of Sun, Priming Toxins/Infections, Diet/Lectins, Genes, Stress (sometimes), Circadian Rhythm Disruption
Shoemaker: Let me give you one more question. Is CIRS, WDB (water damaged buildings) caused by a toxin?
Joe: Now so, I think that when people are dealing with these multisystem issues with these multiple cytokines, multiple symptoms, I think that it’s either an infection or a toxin.
Shoemaker: Nothing else?
Joe: No I actually do think there are other issues as well. I think it comes from, well the biggest environmental trigger that I’ve seen is psychological stress.
Joe: Meaning that a lot of people that come down with it will say that a particularly stressful period preceded coming down with CIRS. I have noticed that. Have you noticed that?
Shoemaker: Dana were you stressed out in Vietnam?
Dana: He calls me the exception we actually argue about this.
Joe: Dana is the exception, and we argue about it, but every client I speak to, I ask them the question, did your issues start after a particularly stressful period. Dana’s answer was no. I didn’t say every single person, I say it’s a predisposing factor. And I study why stress is a predisposing factor. I think it’s a predisposing factor to heart disease and cancer and a bunch of other conditions.
Shoemaker: Ok so you can define stress for me then since it’s the source of man and woman’s mankind’s problems right?
Joe: Exactly, emotional stress. And everybody has it, to one degree or another. Some people are less susceptible to it, some people are more. The people with CIRS, I’ve noticed, are at a higher likelihood to have a particularly stressful period before they come down sick. That is one predisposing factor.
Another predisposing factor that I found is a lack of sun. Now, the modern world is living indoors, we’re not being exposed to sun, the medical community is telling us it causes skin cancer, and it does cause skin cancer to a degree, but we ignore all the other benefits, including increased MSH in the system, which we know will shut off inflammatory markers, and that UV and infrared in the sun and the light is a very powerful immunosuppressant. When you study what effects the sun has on our biology, you can connect it to, and then you ask people, were you getting sun before this happened? That’s a hard question to compare to other people because it’s possible that nobody is getting sun, or very few people are getting sun.
But I think sun is a predisposing factor, psychological stress, I think a priming event, like an infection, is a predisposing factor, and I think diet has a big role too. I had an interview with Dr. Gundry, who studied 800 people with autoimmune conditions, and in his study, he said that every single person with an autoimmune condition normalized their autoimmune condition when they went on a lectin avoidance diet. So I think there are lectins that are causing immune changes on the gene levels, and we know that lectins can change toll-like receptors and things like that. And I study which genes are predisposing to lectin sensitivity and factors. So I think lectins, lack of sun, psychological stress, and then I think circadian rhythm disruptions. So we’re living in an environment where we have tons of light at night and we don’t get enough light in the day. And we know in animal models, and now we’re conducting clinical trials and we have people with night shift work, they’re susceptible to autoimmune disease, cancer, and all that stuff. Why is that? Because their light cycles are out of whack. And I spoke to 2 top circadian researchers who agreed that if your circadian rhythm, one researcher from Stanford said circadian rhythms could control 90 % of the genes in our body. It’s obviously a really important system and it’s controlling inflammation. It causes a lot of immune disruptions, but the most significant is the TH17 arm, which you discussed and you know about. It increases TH17 cells and that immune response.
So I think circadian rhythm disruptions which includes not enough light in the day too much light at night, I think lack of sun, I think psychological stress, and then I think genes, whether it’s HLA genes, a combination of genes, and then I think obviously toxins or a priming infection is triggering this kind of inflammatory response in people. Now, can I prove that? To prove such a thing would be really really difficult for such a model to be accepted in the conventional scientific establishment. It’s just a hypothesis as to the main triggers.
Shoemaker: I would hope that you would partner with a physician or a Ph.D. so that some of your ideas could be looked at in kind of routine standard scientific inquiry if you have some good thoughts, and you can develop a hypothesis that can be tested. That would make a lot of sense and I would hope that you would be able to do that.
Joe: I have a lot of hypotheses, but it’s testing them and proving them that is really really difficult. I mean look at you you’ve been trying to prove your hypothesis since 1996 and you’re adding on information, you’re publishing studies, and even though you’re doing all that stuff, conventional medicine is not taking on your ideas wholeheartedly. There’s a big struggle. Now the question is, why is that? Again, I have my theories why that is, it’s not any kind of person on the top that’s suppressing people, it’s just the general, science is very specific, and they don’t like multisystem, multisymptom disorders, they just don’t. And it’s extremely difficult to prove causation.
Shoemaker: Yep, that’s for sure, but you know, there was a book by Kurt Vonnegut I often like to quote, and he used his writer Killgore Trout as the writer of venus on the hasshel. And his question that drives me is similar to what drives you, and why is man created to suffer and die? And Killtrout’s hero travels the universe and gets to the end of the universe, he’s immortal, and he finds on this planet a giant cockroach named Bingo. And Bingo runs the computer and he says why is man created to suffer and die, and he takes a big swallow of beer and he burps and says why not? And that’s the end of the book. There’s the nihilistic approach. But why not is an argument that can be translated into null hypothesis, and that’s what you’re dealing with, because I listen to you talking about stress, to lack of sunlight, circadian rhythms, and lectins not specifying what they are, the null hypothesis is something we have to deal with that says all our great ideas don’t have any diddly do with anything else.
Joe: I agree.
Shoemaker: Welcome to the world of Bingo, why not!
Joe: Right, so yea, I mean what’s your explanation for why the scientific establishment is shutting this down? Even though I look at your work and I see how you think, you’re obviously a very scientific thinker, you’re a very skeptical guy as well, and you’re not a part of any quackery communities or anything like that. Question is why is science not accepting your work with open arms?
Shoemaker: I’m not sure that I can answer why questions, my wife will tell you I don’t really like why questions, but I will tell you that at the end of doing 200 depositions in my legal career for mold cases, there were lots of green reasons people didn’t want me to be right, and those green things were dollar bills and lots of dollar bills. There is the concept that I alluded to earlier with Pfiesteria, you know what goes around comes around is that if nutrients are the problem we all are responsible and no one pays for it. If there is a chemical problem indicted by one then there is a liability. If you are a landlord and you don’t provide a safe workplace, or a school system doesn’t provide a safe school, they are negligent in the eyes of the law because you’re required to provide safety in your workplace and safety in schools. Same thing with housing construction.
Joe: But the science community isn’t as affected. In courts you’re right, the landlords and these kinds of people, the lawyers, they’re going to try to put it down. But the scientific community is generally not like that with regard to that conflict of interest. So the question is why is it not more accepted in the science.
Shoemaker: Well, I’m still not certain with how to answer the why question. The issue got to be how many people read our paper on NeuroQuant in neurotoxicology and teratology, and it was one of the most read papers that they had. And we had the same thing with the journal “Health.” How many people read the VIP paper, it’s one of the most commonly read papers that they had. The fact that you read a paper doesn’t mean that you agree with it, but it also says that you’ve read. Cynically, there are some physicians I’ve talked to that don’t spend a lot of time reading. They have other things that they have to do, and that’s understandable. It’s very hard when you’re keeping up with new things to know things.
But to go back to your ‘why’ question. One of the fascinating issues is that when we think about tumor necrosis factor alpha, TNF, I’m sure you’ve responded to TNF, nodding your head, the first paper on TNF was written about 1985, and it was unheard of. By the year 1995, there were 10,000 papers on TNF, and now 20 years later there are multiple drugs that we use with phenomenal improvement. Yea there are some problems maybe with TB and some things like that, but rheumatoid arthritis and cirrhosis are just two examples. And the TNF was a huge problem to get doctors to read about. Now the mechanism to bring new information to physicians at least in the US is primarily driven by sales techniques. And who was pushing TNF education? Well, it was the drug company that was selling the drug, whether it’s Embrel or Remicade or something like that, there was a financial incentive to teach doctors to things and the teaching was required to have acceptance.
When I look at the wonderful cold spring harbor symposium on innate immunity from 1979, you know, this is seemingly 40 years ago, but everything in this seminal lecture that the researcher from Yale told us was going to happen has happened. So when I say doctors need to know more about innate immunity, they’re being bombarded with innate immunity constantly. And when people are going to need to learn about genomics, I pick up the new “TIME” magazine, and there it was on page 2, Cancer Treatment Centers of America talking about genomics. That’s where the education’s going to come from. And unfortunately, in the US, it comes from someone that’s going to profit from a sale. So selling CIRS education is going to require an investment, and if you make it or I make it or Dana makes it, then people are going to learn quicker, but it won’t just be reading for reading’s sake.
Joe: I agree. Now, this is a post that I just published. It has to do with the 5HT2A, the serotonin 2A receptors. I thought you might find this interesting and I’m curious about what your take is. So these receptors cause fatigue, it’s associated with CFS, it causes sleep problems, it causes higher TGF- beta 1 when it’s activated, and it causes anxiety and depression. Have you looked into the 5H2TA receptors?
Joe: What do you think of something like that, do you think it’s something to look into?
Shoemaker: I’ve looked for specific causation forever. One of the challenges that I simply would leave for you is to continue your work from the perspective of the null hypothesis. And that is the studies are biased, the studies are animal-based, the studies don’t have any human correlates and not been repeated by anybody else. Start with those and see how your analysis goes forward. And that’s the kind of approach that I think will be of use to you, as you look forward with your enthusiasm and your passion that I think I see to find answers that other people haven’t. So I encourage you to continue but never forget the null hypothesis.
Joe: You mention people with Lyme disease are more likely to react to CSM. Why is that?
Shoemaker: When you say react can you share what your question’s referring to.
Joe: That people who feel worse after it.
Shoemaker: We know that there’s a subset of people who when they take CSM within a day or 2, dose 6 to dose 10, will have a marked worsening, globally, of their symptoms, that’s associated with a rise of MMP-9. So we know that TH1 cytokines are involved, MMP-9 is kind of a global marker, it’s almost impossible to measure TH1 cytokines individually accurately. But specifically they also have a fall in row E of the visual contrast score, so we know there’s capillary hypoperfusion. So those people with a TH1 driven capillary hypoperfusion are getting an association with cholestyramine.
Well, how can something that’s not absorbed be creating this cytokine storm? One hypothesis is yet unproven, is that this comes from Lyme patients, is that there is some inflammatory response that is altered by removal of compounds that normally are in equilibrium with receptors, and I’m glad you know receptors they’re very important. But the issue is has anyone ever proven that? The answer is, just as you said, I’m chasing after hypotheses, for which we’ve got really good experimental data and really good answers to the null hypothesis.
But do we have it in a bottle? Nope. I think that genomics will give us our answer, and we’re looking certainly at those pathways with great interest, and right now some really interesting results. So maybe in 6 months, I can give you an answer, I’ll try.
MSH & VIP
Joe: Ok so now this question is regarding MSH and VIP. A lot of people are having problems with trying to source the MSH and VIP, MSH is not something that’s available on the market. There’s an analog MSH pro 2, but it’s hard to get these hormones. There have been studies that showed exercise, fasting, glycine, and nicotine increase VIP, and we know that sun increases MSH. What would you think about these modalities? Do you think people should try them, or do you think we need to have more research as to if this clinically is effective?
Shoemaker: We know that sun exposure and light exposure does not increase MSH in CIRS patients. That was an idea back in 2001 when I was trying to get the FDA to let me use MSH, that was one of the things they threw at me thankfully for them. So if light exposure is helping drive MSH in keratinocytes…
Joe: It’s not systemic.
Shoemaker: It’s not driving it elsewhere.
Joe: Ok that’s an issue.
Shoemaker: The second issue has to do with what else would happen if we started a clinical trial and gave people MSH. As you know, and you’re right, it’s illegal for use in the US. It’s funny in 2002, there was a company formed called Zengen that was looking at MSH because there are countless opportunities: it inhibits candida, it inhibits staph, it’s anti-inflammatory, it restores circadian rhythms, so many things that you’re talking about MSH is vitally important. And they took their company public for 160 million dollars to develop a research fund. Nothing came out of it, and by 2008, I believe by that time, Zengen was sold to South Korea, for 500 million dollars, still no products. And so whether it’s pro 2 or any of the congenitors of MSH, the smaller sizes of MSH, hoping would have the magical benefits there, no one has cracked that nut yet. But if they’ve got 500 million dollars into it and they’re 10 years into the research, don’t you think we should have had something by now? I do.
Joe: So do you think MSH Pro2 is not going to have any of the effects, I mean it makes you darker so obviously, it’s having some of the effects of MSH, and that’s available on the internet.
Shoemaker: So you have any moles on your skin? Just a personal question. Dana do you have any moles on your skin?
Dana: I have a few yeah.
Shoemaker: You’re very fair featured. What would you say how you would react if someone gave you MSH and one of those moles got a lot blacker and bigger, do you think that would be scary?
Shoemaker: Would you think that you have melanoma?
Dana: I could possibly think that, sure.
Shoemaker: Yea I have never prescribed MSH, I never told anybody to take MSH, but I know people who have used it and just about everyone who’s used it has gotten blackening of these moles.
Dana: But do you know if they are actually just blackened moles? If people have these really debilitating symptoms, I’m sure they wouldn’t really care. If my mole got blacker, but my symptoms went away, then it would definitely be worth it. Or are you just worried that these people would get worried, going to the doctor…
Joe: You have that risk with anything you give, any drug is going to have risks for getting whatever. There’s the great unknown when you give any drug.
Shoemaker: Your job is to look at the null hypothesis before you tell others to go out and get sunlight. Your job is to look carefully at to those things that perturb circadian rhythms as you go forward.
When Depersonalization & Derealization is not psychological but caused by brain swelling/ microvascular cerebral edema in CIRS
Dana: You know I think a lot of people too, need to be heard and feel like there’s a place where there’s a lot of information available publicly, like sites like Joe’s, where you can make kind of your own decision on whether or not you want to try something. I know we touched on this before the interview, but this depersonalization and derealization symptom, actually one woman got the same issue after leaving my house in Vietnam, another woman got bipolarism, and I’m sure that a lot of these issues are stemming from the same exposure, mine certainly got much better after your protocol.
This is a little off topic, but when I was trying to figure out what was wrong with me, there’s depersonalization, I labeled what I have, ‘depersonalization what is this?’ It’s horrible, I feel out-of-body, I’m chronically hallucinating, I’m in my own world, and I noticed a lot of these people were getting this same symptom from smoking marijuana. And they’d have a panic attack and be stuck in this state. So I started to wonder well maybe they’re being exposed to moldy marijuana. But anyway, I’d actually love to know what you think about that, but also people like this who are absolutely completely annihilated from the medical system, until people like you Dr. Shoemaker who come in and starts putting these pieces together, and Joe’s certainly incorporated quite a lot of your protocols. People need to know there is help out there, and obviously, it’s a personal risk that you want to take, but when you feel so horrible, man I mean people are willing to do just about anything. Which is good in a way, because they can get better, and also a little scary because you don’t really know what you’re getting into sometimes.
Shoemaker: The book I published in 2001 was called “Desperation Medicine,” and one fellow was asking where in the world did you come up with that name? And here was this nice lady who was diagnosed with Chronic Fatigue Syndrome, and she had insulin resistance and leptin resistance and was as moldy as could be, but she said you know I would take dog manure and make it into a milkshake and drink it if it would help me feel better. And that was the source of desperation medicine. So I hear you loud and clear, but I go back to what I said to you earlier, and that is we know that changes in the hippocampus and the amygdala are associated with depersonalization. Be very careful when Joe says to go out in the sun.
Dana: Look how pale I am!
Joe: Well you have to ask yourself with each experiment, my approach is to experiment.
Dana: Dr. Shoemaker wait hold on I have to ask you one more question before you go. Before you strangle me as well. A lot of the people that I talk to, and work with to try to help them get better and find the help they need, some of them worry you know how do they know if they have a colonizing problem, or like what some people call a fungus ball in the sinus or aspergillosis. Usually, if someone is worried about that or if they have certain symptoms, then they go to the specialist and get this checked. Is there any way that you’re able to see signs beforehand? Because usually these things are overlooked anyway in the medical community, those things are also very hard to diagnose.
Shoemaker: Well I wish I could break your question down into fine little pieces that we could chew up and spit out one at a time. I do worry about aspergillus. Aspergillus fumigatus is a real big player in people who are on immune suppressor drugs, and nobody’s found a good mechanism to prevent infection from Aspergillus in the lung or Aspergillus in the sinuses. To date in having seen 12,000 CIRS patients, I’ve seen one who had a fungus ball in the sinus. I will just tell you, what does not work is to ascribe causation of illness to colonization of nasal passageways with fungi, because the sinus and the nose are very different, and you may not ignore defense mechanisms that sinus has, you have to look at the availability of water in mucous secretions to see whether the organisms are number 1 able to grow and replicate, but also make secondary products including mycotoxins. That’s not the case. That’s just bad science all the way around. But the issue for you, if you’re worried about sinuses, get a CAT scan. Sure there’s some radiation there. If you need a CAT scan of your chest because you’ve got mucous that shows 2 or 3 different hyphae, somebody thinks that there may be a fungus ball, you’re stuck, you gotta go through radiation. But is there any way that I know or anyone knows to detect a, what is going to be a fungus ball, before it’s a ball, the answer is no, I don’t know any way at all. So vigilance and all that.
Joe: Ok wow it’s been so great to have you on and I appreciate the insights and guidance.
Dana: Yes, thank you.
Before the Podcast
Dana: This is an excerpt of Joe, Dr. Shoemaker and I speaking before the podcast. We talk about some of the labs used for diagnosing CIRS, and in particular a computer program called NeuroQuant. NeuroQuant uses specialized software to take MRI scans of the brain and look at areas including the thalamus, forebrain, cortical gray matter, pallidum, hippocampus, caudate, cerebellum, putamen, and posterior gray. People with mold-related issues will have specific areas of the brain that are smaller, where others are larger. People with Lyme disease will have other specific variations in size. It’s also a tool used to diagnose other neurological conditions for early detection of brain atrophy in dementia and Alzheimer’s disease. It’s very exciting though for CIRS patients to see NeuroQuant results start to normalize throughout treatment. Enjoy!
Shoemaker: Dana before you start asking me questions let me just ask you if you are identified as having CIRS. Can you tell me how that diagnosis has been confirmed in you?
Dana: Yes, I had a 14,000 TGF-beta 1 after about 70% recovery already. Then I had a higher than normal, out of range C4a. I had an abnormal NeuroQuant for 8 of the 12 biomarkers of inflammation in the brain related to mold, 2 to Lyme disease.
Shoemaker: Because you mention a chronic hallucinogenic state, and my concern is that what we’re looking here is at multi nuclear atrophy as opposed to Lyme, or mold or both.
Dana: Ok, I had frontal lobe inflammation, and issues in the dopamine area, the caudate.
Shoemaker: You mention you have 8 abnormalities, that’s a lot.
Shoemaker: One of the things that concerns me, when folks are looking at some of the new information about CIRS, is that initially what we found with NeuroQuant, is that we could identify plain old CIRS, WDB in a pretty straight forward manner. We find enlargement of forebrain parenchyma cortical gray, that’s about half the brain, that’s a big deal, but it’s not an enlargement interestingly you can see on an MRI, it’s called interstitial microscopic edema, and that does resolve pretty nicely with our protocols. The enlargement of the palladium was far more commonly seen back with Neuroquant 1.4. When they changed it to 2.0 I think there may be some refinement either they need to make or we need to make, because enlarged palladium which was pretty obvious initially, is not quite as common now that we’ve got a different version. But what is striking is the atrophy of one of the small gray matter uncle the caudate that we see in mold patients and some Lyme patients and those 4 elements taken together are critical. With Lyme, you’ll have a reduction in the size of the putamen. And the putamen sits right next to the caudate, it’s separated by the internal capsule, it’s not a real big area at all. But in Lyme patients, over 98% of the ones we’ve seen will have small putamens, and then they also have enlargement of the right thalamus. Now it’s not the left thalamus it’s the right thalamus, there’s some specificity. So I see a lot of folks thinking they’ve got Lyme disease based on a western blot on a lab here or a lab there that are not supported by NeuroQuant. And we’re starting to look at now including Nanotrap in our Lyme evaluations.
But when someone has putamen atrophy, think Lyme or mold, when they’ve got caudate atrophy, think mold. But if you have thalamus atrophy and hippocampal atrophy and then amygdala atrophy, I really get worried because we’re looking at now a step up in severity of the illness. And when you described yourself as depersonalization, that really is common for folks with problems with the amygdala, especially with the basal lateral nuclei, something we can’t see in NeuroQuant. So it’s an important issue. It’s one thing to say CIRS. But, are your joints real flexible?
Dana: I don’t have that hypermobility.
Shoemaker: Ok, and the good news there is that there’s another condition that we see far more common in those with hypermobility and elevated TGF- beta 1, and hypermotility really does have a strong association with the higher levels of TGF-beta 1 like yours, but in those people we see impairment of tissue responses in inflammation, and we call this TH17/T reg imbalance, which is a separate entity than CIRS. It still makes people’s lives destroyed, but at the same time treatment is a little different compared to what we’re looking at. Ok looking at HLA, and looking at the first question, is how does treatment differ based on if you take away one test at a time. Well if you have a classic CIRS, the 11 or 12 step protocol that I use, depends if you give a separate step to MMP-9 and VEGF, works very nicely, the issue is that if you’ve got Treg deficiency, and Treg imbalance is really common as well, then we don’t get the same benefit early on but things like VIP make a real difference. Ok alright go on, I’m sorry to interrupt the interview, but that was critically important to answer some of your questions.
Dana: No, thank you. Thanks so much that was huge I really appreciate it. And you know my TGF-beta 1 is actually normalized now.
Shoemaker: Do you have a history of having had some dental problems in the past. Either wisdom teeth that didn’t erupt or root canals?
Dana: Actually yes, I had one tooth that had to be pulled down by a crank because it didn’t ever come in.
Shoemaker: And what tooth would that have been?
Dana: This one right here, it’s not a molar.
Shoemaker: So it’s the lower part of your jaw on the right-hand side.
Shoemaker: What we are finding, and here Dr. Ackerley has been one of the leaders in this line of inquiry, for folks who have non-suppurative osteomyelitis, which are problems with the maxilla and mandible, and yours would be the mandible where that tooth is, there is a grouping of organisms, some are anaerobic, but we find that just about every one of these folks has got MARCoNS that’s similar to what we find in the back of the nose. It’s a hot item of research and there’s some speculation that certainly underlies this, but these are biofilm forming organisms, very perfuse biofilm formers, that appear to be making compounds that are neurotoxins separate from what we’ve ever seen before. And Dr. Joe Musto is arranging for the mass spectrometry to look at this new player, but it has a lot to do with people with recurrent positive MARCoNs, people with unusual problems related to what looks like CIRS usually from mold, but is actually more than that as well. So just keep that in the back of your mind at some time you may want to look with a Galileo scan, it’s a 3D cone view CAT scan of your mandible.
Dana: Ok absolutely I’ll be doing that. I didn’t test positive for MARCoNS.
Shoemaker: A large number of people, especially those with medical exposure will have Gram-negative rods.
Shoemaker: Generally we see, in our controlled patient population, it’s been well reported in peer-reviewed literature, that for normal people walking up and down the street and playing football on Sundays or even baseball on Saturdays, the mean number of fungi found in their noses exceeds 3. For cases for presumed CIRS, it’s about 2.3. So you can disregard the significance of Gram-negative rods whether it’s Pseudomonas or Klebsiella or E. coli, those guys are along for the ride. Doesn’t mean if you’re picking your nose, that would apply to men of course, but at the same time, we have to worry about hand washing and exposures, especially if you have a dog or a pet.
Dana: Ok thank you so much.
TGFb1 – (remind lab technician to SHIP FROZEN) – Will help you determine if you have a biotoxin issue
MSH – an anti-microbial and anti-fungal
VIP (Vasoactive Intestinal Polypeptide) – regulates peripheral cytokine responses, pulmonary artery pressures, and inflammatory responses throughout the body. Low VIP levels are present in mold patients, leading to shortness of breath especially in exercise. Once levels are restored, many patients return to normal lives.
Complement C4a (Quest Diagnostics) – Will help you determine if you have a biotoxin issue and if you are actively being exposed… This will necessitate a different protocol… it needs to be processed fairly quickly, no significant lag time during the processing period.
MMP-9 – (remind lab technician to SHIP FROZEN) (Drawn in a serum (red top) tube but must be spun down immediately to avoid spurious elevation of MMP-9 from white cells in the buffy coat)
VEGF – a marker of hypoxia
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