Using Peptides to Mitigate Immune Dysfunction

Cory Tichauer, N.D.

I’m doing great. Yeah, thanks so much, Matt, for having me, I’m really excited to talk about peptides, something that I’ve been using a lot for the last about three years and continue to do as much as I can to learn more for what we have available to us, anyway.

Matthew Cook, M.D.

Awesome, tell me just a little about, of your background in terms of complex illness and stuff, just so people get a sense of where you’re coming from.

Cory Tichauer, N.D.

Yeah, so I’ve been in practice for about 20 years. I originally started off with a goal of trying to work with the chronic illness population. The people who really had been sort of left destitute by the mainstream medical paradigm and, you know, the fibromyalgia chronic fatigue world and that, you know, exploration kind of led me down a rabbit hole that I described earlier to you as sort of representing what I sort of have these four bubbles in this chronic, you know, chronic illness venn diagram, so to speak. One is chronic infectious illness, like things that, you know, we all know and talk about things like Lyme disease or chronic viral illnesses, you know, fungal illnesses, parasites, all of that world. And then we have biotoxins. So that’s a world of mold and heavy metals and solvents. And then immune dysfunction, we’ll see like primary auto immunity, but there’s also a lot of just individual, you know, immune issues. And some people are just not geared well genetically or otherwise to deal with the environment or the organisms they encounter. And then the fourth thing which is probably the most recent addition to what I do and a lot of what I attribute to having a daughter with hypermobility, is the structural world in looking at things like you know, Ehlers Danlos and the connection or association of mass cell activation, or even traumatic injuries, like, you know, like TBIs and other things. So I’m always kind of trying to parse out what’s going on between those four bubbles and how to individualize treatment to get people to function again and function well, so yeah.

Matthew Cook, M.D.

That’s amazing, okay, a hundred percent. Well, so I’m just gonna dive into some great topics. And so then one thing that’s not a peptide but it’s sort of peptide to Jason, and it was the top of the list of stuff that we’re gonna talk about. And it’s something that I think is an evolving area that we’re interested in and a lot of people are interested in the anti-aging world, but I think it has some immune benefits also, is rapamycin. Maybe give us a little introduction to rapamycin, how you think about it and how you like to use it in clinical practice.

Cory Tichauer, N.D.

Yeah, so like you already sort of alluded rapamycin as I see it has two really distinctive roles and benefits. One is sort of for the general aging population and what we can see as far as its benefits in reducing overall you know, morbidity as we age. And the other one is it’s immune modulating effects and dealing with the, you know, the increased, you know, antigenic presence around us. We’re all exposed to a lot more chemicals, a lot more allergens. And then in the people that I’m talking about with things like biotoxins or chronic infections, a lot of these things aren’t gonna be completely eliminated from the body. So, you know, again, not to keep bringing up Lyme, but, you know, borrelia, but any of these intracellular organisms that we’re gonna think about borrelia, or bartonella, or coxiella, or brucella, you know, TB, all of these things go on and on. These are organisms that we can’t get rid of completely. So the goal of course, with antimicrobial treatment is to lower the infectious load to the point that the immune system ultimately can sort of quarantine those things away and manage it to prevent it from getting worse. This is a long winded answer, Matt, but rapamycin in this world, I use it after we treat people for that biotoxin or that infection to help bring back immune balance, or restore immune tolerance, I think is a good way of thinking of it. Rapamycin in large doses is used in the transplant community to prevent organ rejection, but in low doses, just like low dose naltrexone, it has wildly different effects without the same risk profile. 

It inhibits antigen induced proliferation of T-cells and B-cells and reduces overall antibody production. And so this can be really, really helpful in conditions where the biotoxin exposure a person is dealing with is due to the presence of a chronic latent, nonactive or carriage infection that like, can’t be eliminated completely. And so the idea is that by giving it for say, four to six months, you can break a cycle of immune activation and help the body reset its immunogenic sensitivity so that it has immune tolerance moving forward in the future. The other side of this of course, is into the mitochondrial world, which is a whole different side of rapamycin. And again, in the anti-aging world, this is where they’ve really talked about it, but like, what’s really going on? Like, what are we really doing with this? And I really find a huge amount of benefit for people in the chronic illness world as well, because of what I call damage done. This idea that a lot of the people who finally find me have been suffering for a decade or more and seen, you know, a dozen doctors and they haven’t really recovered. 

And so a lot of it is there structural damage that may have happened to joints or, you know, neuroendocrine issues, or ultimately you see this cell danger responses discussed by Dr. Navio which is really cellular senescence. And that basically means that the cells are basically in this hibernation state. They’re not metabolizing well, mitochondria aren’t being turned over, cellular function is impaired. So rapamycin inhibits a key regulatory protein called mTOR, that is what promotes that cellular senescence. And it upregulates NRF2 to increase mitochondrial autophagy or turnover and get that cell out of that senescence cycle. And so, you know, by doing this, we see the ability to improve the intracellular clearance of biotoxins, we see improved energy motor function, cell to cell or paracrine function, and ultimately a restoration of the cellular function that can then translate over into, you know, the ECM and improved you know, everything else in the body. And so, yeah, so it’s a really wonderful peptide and the fact that it’s not injectable is appealing to a lot of people, of course, as well.

Matthew Cook, M.D.

A hundred percent. Are you doing for those, on the immune side and sort of versus immune tolerance versus sort of an mTOR side, are you looking at similar dosing?

Cory Tichauer, N.D.

Yeah, you know, it’s actually an area that I’m looking at exploring a little bit more right now. It’s very dependent on the person. So a lot of the people that I deal with are really, really, really sensitive. So while it might make sense or in theory seem like, oh, we wanna use higher doses to reduce that sensitivity, the truth is it’s usually a better approach to start slow and gradually work up as we see improvement. So usually, I start off in the more sensitive people, at one and a half milligrams twice a week, sometimes we’ll go up to three milligrams and even up to five. But again, I sort of touched on this with you a little bit ago. It’s a project I’m working on because at some level we do have to watch and make sure that we’re not suppressing the immune system. You can do a standard CBC and just look at WBCs and your lymphocyte neutrophil counts. But what I’m actually doing is looking at the lymphocyte subsets and looking at your CD3, CD4, CD8, CD19 cells, and actually asking, are we actually truly suppressing things? Are we causing problems? Because, you know, we don’t want someone to end up with you know, bacterial pneumonia or something like that either. So I think that there’s a realm of functional addition into the sort of medical realm where we’re having to use higher doses and having to be a little bit more cautious about that. But ultimately, it synergizes really well with a lot of other things that help that as well. I think I talked already about it a little bit, but I’m, you know, I’m a big proponent of using low dose of naltrexone. I think it’s a huge asset for a lot of the people provided they do well on it. And it’s something I’ve lectured for the Naltrexone Research Trust before as well. And also using thymus in beta 4, using low dose immune therapy, using low dose allergy therapy, and in truth, even using helmets therapy, which is a whole new world of discussion because I’ve actually found some of the best benefit restoring immune tolerance. But in those cases I am actually using little bit lower dose of rapamycin to prevent colonization.

Matthew Cook, M.D.

So then, yeah. As the tool or as a concept modulating and regulating immune function is sort of what this whole conversation is about. And then as you hear, there’s not one exact dose, and then these are generally things that you cycle on and off of. And so then, we’re gonna have multiple tools and strategies of modulating on and off of those. To begin to deal with what was going on, you know, we were talking and I thought this would be an interesting trajectory of conversation for people to hear about. When you think about some of these complex infections, there’s a question of A, is there an infection that’s out of control that we need to fight and bring down? Or B, are we over here with an overactive immune response to maybe the remnant of an infection, but the infection is not really the priority? And when you said that, I was like, “oh, awesome.” So then we have to, let’s dive into that because I think hearing about this is gonna be an intriguing thing for people to begin to help them understand sometimes what’s a diversity of how they feel based on the two of those paradigms.

Cory Tichauer, N.D.

Yeah, it’s a huge topic, and ultimately, you know, there’s this idea that just because we have a test that shows antibodies to some organism doesn’t necessarily mean that it’s something that needs to be treated. In the functional medical world, I think we jump a lot towards the idea of, “oh, we’ve gotta treat this, you know, infection. “Or we’ve got, you know, an early antigen for Epstein-barr, “we’ve got high CMV levels, or we’ve got, you know, “IgG positive results to borrelia or bartonella.” But a lot of those IgG in particular results are really reflective of exposure, you know, or past treatment. And it’s a whole discussion into the world of like, what does that exposure mean and it’s sexual transmission in a topic. And I know we’re not here to talk about testing, although I will put in a little plug for doing more on the T-cell based testing because I.

Matthew Cook, M.D.

Like Infectolabs.

Cory Tichauer, N.D.

Yeah, yeah, I deal a lot with Infecto and had the privilege of going to meet Carsten in Oxburgh in 2016 at the lab there and really have been using that testing more since then. Because with the T-cells, we’re looking at a cycle that really represents the last 60 days, right? So we really can assess whether something is active versus just present. But ultimately like in this world of infection or biotoxin, like, there’s sort of this chicken and egg phenomena that happens. And this is basically what I describe as the difference between treating disease and restoring health, right? Because ultimately there’s always some toxic insult that affects cellular function and that can be infectious, toxic, or traumatic in nature, but it all affects the immune system, right? And so when we have a source of the problem that we can’t completely resolve, we see this sort of cycle of dysfunction that happens. And it’s characterized by, you know, the inability of the innate immune system to eliminate this toxic insult, which often causes an amplification of the adaptive immune response which increases cytokines and inflammation, which further impedes the shift towards an improved innate immune response, which, you know, just continues to increase this cycle. So generally in this kind of chronic fatigue world, that goal is trying to find the right balance between eliminating the antigenic source of the problem by restoring innate immune function and, or providing, you know, detox support antimicrobial therapy, or whatever, some metabolic for like ozone or naltrexone or you know, hyperbaric or whatever. 

Or, the other side is promoting immune tolerance like we said. So this is a topic that I have a lot of fun talking about and spent a whole lecture just describing this nuanced idea of, you know, the idea that every microbe in the body that’s established itself, is either a commensal or a pathogen has a unique threshold at which the immune system reacts. And I actually think that there’s two thresholds that happen, I don’t think there’s one. I think there is an infectious threshold which is what we learn in medical school, right? And that infectious threshold is what load of that in antigenic material, that infection, or that toxin is required to trigger an immune response to guard against damage from that pathogen, right? But there’s also what I call an immunogenic threshold. And this is the idea that the immune system is trying to prevent dissemination of something out of an area where it shouldn’t be, whether that’s in a cell or whether that’s, you know, with quarantined borrelia or whether it’s, you know, a commensal organism, like clostridia that lives in the gut or stuff that should stay in certain areas. But there’s two sides to that. I guess I’m rambling a little bit on this topic right now, Matt. But yeah, the idea…

Matthew Cook, M.D.

So tell me those two sides.

Cory Tichauer, N.D.

Yeah, so, you know, it’s an interesting thing, and I’ve got a bunch of graphs but again, the goal of treatment is either to you know, treat the infection and bring it below the infectious threshold, right? So that the body isn’t like seeing there is a perceived threat, or it’s to raise the immunogenic threshold, because for whatever reason, the body became more sensitized to the presence of the biotoxin or the infection itself and now it’s reacting at a level that it shouldn’t anymore. And so I kind of described there being four categories of pathogens if we’re talking not in the biotoxin world, we’ve got our commensal organisms like I talked about staph, and cleptial, and H. Pylori, and clostridia. And these are things that have high infectious and immunogenic thresholds that permits their presence in the body unless they breach barriers, right? Or become really overgrown. And so almost all of the hyper reactive responses to these are localized, like things like acne or ulcers and the tonsils or cross reactive, like we see with PANDAS, or reactive arthritis or rheumatic fever, right? And so the commensal organisms is one, the other three categories with, you know, I can go into detail, but there’s invasive pathogenic organisms that are gonna have both low infectious and immunogenic thresholds that’s, you know, gonna be stuff like cholera, or strep pneumonia, or pertussis, or meningitis. And we’ve got our parasitic and viral organisms. You know, Epstein-barr, ascaris, blastocystis, herpes, and these have low infectious thresholds but high immunogenic thresholds. 

And that kind of ensures that these things stay localized or latent in the body so that it doesn’t get overloaded or depleted nutritionally or metabolically while also preventing, you know, a chronic inflammatory response to a persistent organism that we’re not going to get rid of. And then the fourth organism is the one I think that we see a lot of focus on right now in the functional medical world, which is these intracellular and cell wall-deficient organisms. So that’s gonna be, you know, again, borrelia, bartonella, chlamydia, mycoplasma, mycobacteria, coxiella. And these likely have high infectious thresholds, but low immunogenic thresholds because of the unique ability of these organisms to persist. You know, I’m of the belief that we’re not gonna get rid of these things. So, you know, the reactional type we see is characteristic of the body’s attempt to prevent dissemination into other cells while minimizing inflammatory damage to already infected cells. So those are kind of the, you know, the ideas that I at least have. You know, biotoxins are an entirely different thing, of course, because biotoxins have direct and indirect effects either, you know, due to their direct impact on fatty structures like, you know, the neuroendocrine system or cell membranes in particular, or due to their effects indirectly on, you know, on the body and you know, the pituitary gland, the hypothalamus and their effects on changing those neuroendocrine hormone, like melanocyte stimulating hormone and VIP and, you know, and how that pulled downstream cascade happens.

Matthew Cook, M.D.

Okay, good. So then let’s take a little walk into MIC toxins as a biotoxin and VIP ’cause that’s one of our topics. And this is a topic that is sort of near and dear to our hearts so I’m interested in your thoughts.

Cory Tichauer, N.D.

Yeah, okay. So again, like combining peptides with either IV or oral detox protocols, right? It’s kind of what we’re talking about if we’re talking about detox, we’re not talking about the tolerance side of things here. You know, and with the assumption that we all kind of know this idea, there’s two sides to the toxin. You know, one is a direct impact on the fatty structures and the cell membranes. And when you have a toxin that gets into a cell membrane, it creates scarring. But that scarring, as I describe it, it’s not like we think of on the skin, it’s basically the addition of long chain fats and odd-chain fats that basically impair membrane fluidity. So you get these sort of wax plugs. I sort of describe it as like what coconut oil is like in your cabinet, it’s not fluid, right? And so when you get these longer chain, longer carbon chain fatty acids, we see an impairment of that happening. And then sort of like what you were asking about is this neural endocrine effect, and you know, how the biotoxins affect cytokine production by binding the leptin receptors and reducing melanocyte stimulating hormone and VIP and affecting all the downstream things from, you know ADH, and endorphins, and melatonin production and you know, the clotting cascades and all of that. So with all of that in mind, the peptides, it’s kind of nice ’cause the primary neuroendocrine hormones that are impacted or peptides that are available to us. Melanotan, VIP, and epitalonthal, and frankly, and really KPV should be discussed if there’s a way to get it anymore, I don’t know. You asked a little bit about VIP specifically. 

So vasoactive intestinal peptide been written a lot about in the shoemaker world. Obviously it functions as a paracrine mediator, as a neurohormone. It’s been promoted for its ability to heal atrophy or damaged areas of the central nervous system, but it also helps to limit inflammation and regulate the immune response. So it can really be helpful because it does correct some of those inflammatory markers that we see. In particular, I like it when we see high TGF beta 1, which is a, which in of itself is something I really have fun talking about ’cause TGF beta 1 is sort of a weird conundrum of a protein marker because it has both anti-inflammatory and pro-inflammatory components to it. You know, but we know that ultimately chronic elevation of TGF pushes towards that Th17 immune response, which is characterized by chronic inflammation and allergy or loss of immune tolerance and autoimmunity. So it really focuses and fundamentally addresses like what we’re talking about right now for these people. And there are other ways to lower TGF of course. And assuming that someone’s not still in a moldy house, you can use VIP and bring TGF down. 

It works for MMP9, it works for C4A. I’ve seen it help address, you know, steroid hormone levels in younger people who are clearly, you know, affected when you see a 35 year old with a testosterone level of you know, 250 or 350, you know, you know that there are more toxins affecting it. So it can be really helpful in those cases as well as, you know, the vitamin D pathway, which is a really fun topic for me to talk about as well with COVID around. Like, I really spent a lot more time looking at vitamin D and the conversion into calcitriol. And frankly, the use of prescription calcitriol in a lot of these immune topics, which I’m going off track here. But anyway, VIP, it helps to correct T regulatory cell effects and definitely helps to regulate both the innate and adaptive immune response. And so, you know, if we’re thinking about all of how these biotoxins affect these, you know, the pituitary and the hypothalamus and everything downstream is being affected, there’s sort of a temptation to say, “I’m gonna treat all the downstream things”, right? And that’s kind of the sum of the parts is greater than the whole. But why I like using the IP and MSH and epithalon, is ’cause you’re working more from that top down approach. You’re saying, “I’m gonna treat and correct “the neuroendocrine deficiencies “and everything below that should correct.”

Matthew Cook, M.D.

What dose are you doing, what dose are you doing for VIP?

Cory Tichauer, N.D.

You know, I used to start lower actually Matt. Anymore, I’m usually starting off at like 25 micrograms QID, four times a day dosing, but I’ll go up to the full 50.

Matthew Cook, M.D.

Are you doing a nasal spray?

Cory Tichauer, N.D.

I’m doing it as a nasal, yeah. I’m still using it nasal spray. I don’t know if there’s any injectable forms of doing that at this point. I will say that one of the things I see and maybe it’s more melanotan specific is, you can get sort of a sympathetic neurologic reaction to some of these when they’re used injectably, maybe you’ve noticed that as well. Melanotan in particular, I’ve really found it to be super, super helpful because I mean, melanotan is alpha MSH, it’s basically the primary hormone that we see affected in that shoemaker cascade. But I think it probably does trigger histamine reactions in a lot of people, which is why I said to you, you know, whenever we’re talking about the use of peptides in the biotoxin world, I think KPV needs to come up because KPV is basically melanotan minus that carboxyl terminus. And so it has an oral availability and it doesn’t trigger the histamine reaction that I do see with melanotan. And not to say I don’t use a lot of melanotan, ’cause I do.

Matthew Cook, M.D.

And I think KPV probably also has some antihistamine calming effects also, right?

Cory Tichauer, N.D.

It does, it has quite a bit of it actually. Not quite as much as like amlexanox which is another one that we, as far as I know, can’t get right now. You know, I think it’s all kind of esoteric as far as where, and you know, I think I know all the sources and then, you know, I’ll talk to a colleague, I’ll be like, oh, you know, like there’s, think about this place as well. So, you know, it’s something that I’m trying to keep my eye on and you know, what’s available to us. But yeah, KPV does have antihistamine effects as well.

Matthew Cook, M.D.

Do you ever see people react? How, how often do you see negative reactions from VIP?

Cory Tichauer, N.D.

VIP, if you start someone really high, you can definitely see negative reactions. I mean, there’s no question. You know, some of the reality is you do need to monitor you know, pancreatic lipase in particular, like if, so VIP is primarily gonna be produced by the pancreas and then secondarily by, you know, in the brain, in the pineal, I mean in the pituitary, but because of its ability to affect pancreatic function, I have seen upper left quadrant discomfort happening or GI issues. So I do tend to screen primarily for people who have had a history of chronic alcoholism or pancreatitis and watch them and maybe start a little bit slower. But other than that, I usually don’t see too many negative responses to it.

Matthew Cook, M.D.

And then tell me in kind of parallel to those things, your thoughts on epitalon and in terms of this side of the conversation.

Cory Tichauer, N.D.

Yeah, I mean, epitalon is an interesting one. You know, I describe epitalon as a peptide that you don’t usually see a lot of subjective you know, benefit or noticeable outcomes with it. Typically it’s something you kind of have to trust is working in the background. And at least that’s been my experience. Maybe you’ve seen that it’s something I’ve taken for quite a long time and I don’t, maybe I notice some things. But it’s a pineal peptide and it’s one that we know decreases with age, and so typically by about age 40 we see you know, a pretty significant reduction in epithalon as the pineal gland is not working anymore. And I think it’s just not known very much because we don’t really think of the pineal as doing much more than producing melatonin and being a surrogate marker on an MRI you know, because it typically calcifies in western populations. But you know, epitalon has known benefits with metabolism with increasing sensitivity of the hypothalamus to hormonal feedback. It helps to normalize function of the anterior pituitary and it regulates gonadotropin levels, melatonin and serotonin in particular. In the immune world, it’s something that you know, there’s just not a ton of data on it, but there is some information that shows helping to normalize T-cell function. Something that’s a little hard to measure, honestly, reducing uric acid and possibly improving pancreatic function. But generally as one of the sort of upstream neuromodulators or bioregulators in this sort of biotoxin pathway. I think it synergizes really well with MSH and VIP as well, frankly, as some of the thymic peptides to help support long term recovery for people who’ve dealt with, you know, biotoxin.

Matthew Cook, M.D.

What dosing are you doing?

Cory Tichauer, N.D.

Yeah, so I’m trying to think, so, 0.3 MCGs every three days or 0.1. I wanna say, I have to look, I wanna say it’s a 3000 micromil. So I wanna say we’re looking at about 300 micrograms daily or 900 every third day depending on you know, patients’ willingness to stick themselves.

Matthew Cook, M.D.

Okay, good. And the alpha MSH, are you getting alpha MSH? And how much are you doing with that? Or tell me about that.

Cory Tichauer, N.D.

Yeah, so I mean, alpha MSH is melanotan, right? And yeah, you know, melanotan is, I mean, it’s a synthetic alpha MSH.

Matthew Cook, M.D.

Okay.

Cory Tichauer, N.D.

And I mean, Yeah, so, I mean it’s, you know, melanotan-II anyway. And, I will tell you, there was melanotan-I for a while which didn’t have the greatest success with ’cause the histamine response. You know, and we can go into the whole details of MSH or melanotan, but the primary, the primary issue with melanotan is it causes tanning, it increases melanin deposition, which is not always desirable in everyone. So a lot of times what I do, I’ll start off with you know, something like 200 mgs daily and maybe even increase up to 500 micrograms per day for somewhere in that six to eight week zone. I kind of think of it as like priming the pump, right? You’re kind of getting the effects of melanotan and ideally, sort of opening that pathway to all those downstream issues. And then usually I’m gonna try and reduce doses down to somewhere around a hundred to 150 mgs every day or you know, 250 micrograms twice a week, which tends to work pretty well from a maintenance standpoint without like continuing to darken the person. You know, the biggest, I think concern that we hear about melanin is are we increasing risk of melanomas or, you know, skin cancer or actinic you know, issues. And it doesn’t really seem like there’s any data to support that issue, but it does take a while for someone to kind of come back to you know, their normal skin tone after discontinuing it. But I mean, I found it to be huge. I mean, melanotan increases in interleukin 10, which is kind of a cytokine I focus a lot on and you know, whether, again it’s in the HELTH world or in the, a homeopathy world or in the you know, in the peptides or whatever, because IL-10 increases T reg cells. 

It kind of has that opposite effect with IL-17 and that Th17 pathway due to its inhibitory effects on IL-23. So there’s kind of like a crosstalk that happens at that point, but it does up-regulate IL-10 and there is some really cool data on melanotan anti-inflammatory effects. And you know, they’ve shown in models of IBD or RA, or even LPS induced, you know, fevers and inflammation where in lab models where they’re finding, you know, melanotan has anti-inflammatory effects similar to prednisone without the side effects of immune suppression. And we also get that improved immune tolerance by upregulating IL2, or I mean, IL-10. So it’s pretty cool stuff, you know, and you know, I tend to like using it especially when we see high MMP9 levels along with low MSH and you know, and we know there’s not a histamine component in there. You know, the corollary of course, to this is KPV. And so, you know, if someone’s MSH level is measured and it’s less than eight, which is undetectable, then I’m usually gonna go for a melanotan, I’m gonna recommend it. There’s this sort of gray zone I kind of describe between 15 and 25, where sometimes it helps at lower doses. But once we get above say 20 ish, I’m more, I was, I don’t again, know how to get KPV right now now that you know, Dr. Holtorf from the Integrative Peptides doesn’t have it. This is my plug to you, Ken. It is you know, I’d use KPV as an alternative because it still has all that anti-inflammatory benefit without the full neuroendocrine effects of melanotan. So we still see suppression of NF kappa B and TNF alpha while upregulating IL-10. And it’s kind of like you mentioned, KPV also has anti histamine effects, but it also has some interesting antimicrobial effects as well. So in cases where we’re thinking that the offending issue might be the presence of again, some carriage infection or a latent organism, KBB might be a better choice in fact, than in the mold world.

Matthew Cook, M.D.

A hundred percent, and then explain, can you explain the MSH mold idea, the idea of why that goes, MSH goes down in the presence of microtoxins?

Cory Tichauer, N.D.

Yeah, for sure. Okay, so MSH. So MSH is basically produced in response to leptin binding to leptin receptors, right? So when we have biotoxins, we tend to see those biotoxins binding to those leptin receptors as well. So when it basically blocks the ability of leptin to bind, which inhibits infect the production of MSH. So when we see MSH reductions, it basically, again, it has sort of this whole downstream effect on, you know, everything from hormone production to you know, adrenal function and sleep disorders and chronic inflammation and chronic pain and vasoconstriction. But yeah, I mean, basically, so I guess what you’re probably wanting to know it, I’m trying to think of like, how best to explain this. So certain people have, they lack the receptors to recognize biotoxin. So I kind of a alluded to this earlier, when I said that biotoxins have direct and indirect effects. So in the indirect world, biotoxins are normally going to be sort of phagocytosed or consumed by our innate immune system in our antigen presenting cells. 

Then those APCs are gonna need to present that biotoxin to a naive CD3 cell, right, a T lymphocyte. But what they found, at least if you look at shoemaker’s work, is certain people lack the HLA proteins on those CD3 cells to basically recognize that biotoxin, right? And that might be an over simplification and I mean, a lot of that data is relatively dated at this point but it still seems like there’s some good data on it. So when you have the inability to create antigen specific CD4 cells, because that CD3 cell can’t recognize that biotoxin because it lacks that HLA receptor, you see that biotoxin basically persisting and being reliant on the innate immune system. And it basically will bind to that leptin receptor. And so these toxins an innate immune inflammatory cascade by binding the toll like receptors, which are present on all the body and because of its inability to produce antigen specific recognition, you get chronic cytokine productions that, you know, further disrupt this whole hypothalamic pituitary issue you know, aside from the, you know, binding of the biotoxin into the leptin receptor. Is that kind of an answer to your question?

Matthew Cook, M.D.

A hundred percent, that’s awesome. So then, So thematically then if we were to kind of go through this conversation, and I’m glad that you brought up, you know, Infectolabs and all of that stuff, I love them.

Cory Tichauer, N.D.

Yeah. 

Matthew Cook, M.D.

I’m glad we’re talking about testing a little bit and because clearly what you should, your takeaway from this is this is nuanced and complicated. And sometimes there’s this upstream thing where maybe we have the lack of some proteins that creating downstream inflammation. Like for example, MSH. There could be infections that we’re having an immune reaction to, there could be biotoxins that we’re having an immune reaction to or not. And it is really, and our immune system may be active or not active enough. Appropriate too active or not active enough, and then within the things are in us, there’s these sort of four categories. And then probably a lot of people have a little bit of all of those categories of infections. Because we have a virome, and a microbiome and getting exposed to all of these things. And even I find in my practice, a lot of times you have two people that live together, and one of ’em, but they have the same testing and one of them has a lot of symptoms and the other one doesn’t.

Cory Tichauer, N.D.

Yeah.

Matthew Cook, M.D.

And it’s all intimately associated with how your gut’s working. So then basically then the idea is to have a thoughtful way of working your way through, trying to diagnose what’s going on, and then trying to work on treating these biochemical pathways. And then we’ve got supplements, peptides, and other things. But then basically, almost the most important thing, I think is building a clear model of what you think is going on at a high level, and then strategically working your way through these things.

Cory Tichauer, N.D.

Yeah, I completely agree with you. And I think that better testing is helping a lot. You know, you kind of mentioned you know, the world of testing for infections and like the T-cell tests which are really great ’cause they really do help to delineate that issue. And you know, I have a lot of pet peeves around some of the provider and I shouldn’t say pet peeves, it’s really not that. I shouldn’t say judgment either. But it’s a around like treatment of you know, like, do you really need to treat something for three years or five years or seven years? And like, what are we doing when we do that? And I mean, I’m guilty of it. Like, I mean, I’ve been doing this for 20 years and I’m not gonna sit here and say I haven’t had people on IV antibiotics for you know, a year or more, or I haven’t done this for some of this. But having reflected on things at this point, it’s really not what I tend to do anymore. And so some of the testing really helps A, to identify that, and B, to find out like if it’s not working, it’s probably not that you don’t have enough antibiotics on board. If you have, you know, a few things or you’ve got a bunch of herbs, it’s usually that the immune system is probably not working the way it should, or there’s some associated biotoxin, or maybe there’s some structural issue, maybe it’s related to, you know, again, a hyper mobile issue or maybe it’s an emotional or you know, something that happened in the past that affected the limbic system that’s creating all these, like, you know, other issues downstream. So yeah, the T cell tests have been helpful at distinguishing resolving infections versus active ones. But in the immune world, there’s some really cool tests that have come out as well. And COVID, I think has frankly been a huge asset, both towards the, you know, more mainstream acceptance of T-cell testing, as well as our ability to further look into the immune system. 

I mean, I talked to you a little bit about lymphocyte subset, which is really about as far as we can go with quest other than looking at total immunoglobulin levels, which is valuable. Certainly you’ll find people who are low, but what are you gonna do? What do you do with someone who’s like a 500 on their IgG? They’re lower than that 610, but they’re not gonna qualify as CVID so you’re not gonna give them subQ Ig levels, right? So there’s this whole gray zone in that you could test natural killer cell function as well, which is helpful if you live near the lab, right? Because as soon as that T-cells outta your, or those NK cells are outta your body, they’re kind of withering. But like I said, there’s better tests. You know, I don’t know if we should, you know, if we wanna mention specific labs or vendors, I guess we’ve already talked about Infecto, but Cyrex has a great lymphocyte map that I found to be somewhat helpful at identifying TH1 and Th2 and looking at Th17, which is, again, you kind of heard me, like, I’m really kind of obsessed a bit about that topic, as well as, you know, looking at natural killer cells and all of that. And then Bruce Patterson, who I think you’re gonna be talking with here coming up, you know, he’s done a lot with IncellDX too in the long COVID world and looking at this monocyte polarization and all of these, you know, individual cytokines. And it’s an area that I’m, it’s kind of literally the cutting edge of where I’m looking at right now, trying to assess like the utility of doing those tests and how good are they? Because, you know, as you know, Matt, like cytokines in your knee are gonna be different than cytokines in your blood and gonna be different than cytokines in your CFS. Like, so it kind of depends on what we’re looking at. But it’s certainly providing a clue in terms of how to direct treatment and what to do in addition to doing, you know, clinical interventions.

Matthew Cook, M.D.

Yeah, a hundred percent. What’s been your experience with long COVID and the IncellDX testing and what are your thoughts?

Cory Tichauer, N.D.

Yeah, I mean, honestly, I haven’t done a lot with it. We’re just sort of starting into that world. With long COVID, I would be remiss not to mention Mark Cooper up at University of Washington, a professor emeritus up there, who’s done so much work on this topic and really, you know, developed a really neat model. And I think you heard me talk a little bit about vitamin D and I could easily get off topic on this.

Matthew Cook, M.D.

Oh, go ahead, it’s okay, that’s a good topic.

Cory Tichauer, N.D.

Yeah, ’cause one of the things we see, I mean, we know about this monocyte polarization, this idea that we’ve got sort of like monocytes full of spike protein that aren’t dumping their load and remaining in this you know, M1 state and how do you convert them back again? And there’s also this observation with COVID that we’re seeing a lot of reactivation of chronic viral infections in particular Epstein-barr. It’s really interesting because vitamin D, like, it’s one of those things you learn in medical school and you kind of got, oh, that’s simple stuff. Take your 5,000 IUs of co calciferol or D3 every day, but it really doesn’t stop there. ‘Cause D3 as we call it, which is really called the calciferol that we take gets converted in our liver to calcefediol, right? And that’s like really transitory, it doesn’t last very long. And then that gets converted into calcitriol or 125 dihydroxy vitamin D in the kidneys. And all we’ve been taught as providers is like, “hey, look at this in cases of chronic kidney diseases, “look at this in, you know, in transplant patients “and maybe in some of these really severe osteolytic cases.” And because of calcitriol regulation for calcium. But what’s interesting is COVID and Epstein-barr upregulates something called 24 hydroxylase. 

And 24 hydroxylase is this enzyme that impairs conversion of calcifediol and the calcitriol. So instead of making 1,25-dihydroxyvitamin D, your body produces 24,25-dihydroxyvitamin D, it’s sort of like reverse T3. It’s an inactive form of vitamin D and the only lab that’s testing is Mayo Clinic, and you can totally do it. It’s really cool actually. And you’ll start to notice in these cases where you like, see this profound fatigue in these probably long noted cases. You know, and the lack of recovery and you assess not just 25 hydroxy vitamin D, your standard vitamin D, but you look at the full vitamin D profile. You look at the 1,25, the 25 and the 24,25 levels. In addition to say, a chronic viral panel, you know, with whatever, lab core, or vibrant, or something like that, you’ll see that often there’s a match with this. You’ll see that there’s an upregulation, that 24,25 hydroxy D, there’s an imbalance because you’ll see a low level of 1,25 active calcitriol and you’ll see high viral levels. And so something like I said that I don’t see anyone talking about, actually, and that’s why I wanted to give full credit to Dr. Cooper, is the use of prescription calcitriol in treating long COVID. And I have really, I can tell you I’ve had great success, you know.

Matthew Cook, M.D.

what dose are you using?

Cory Tichauer, N.D.

Yeah, so it depends. So for acute COVID, we’ll go up to a milligram a day for, call it seven to 10 days. And there is more data on the ability of either calcifediol or D2, or calcitriol in preventing, you know, serious, you know, death or progression to ventilators in acute COVID, right? Tons of really interesting data on that, a lot of it coming, a particular case in the Spanish literature but I, I literally have a, a library of this now. As far as the long COVID world, I’m usually doing 0.25 micrograms BID for eight to 16 weeks. You have to really be careful. It’s not something that I would advise be like, just you cavalierly do it because you can create hypercalcemia and we know there’s a lot of things that go into calcium regulation, especially in the cardiac world. So if you do something like that, you need to measure parathyroid hormone, you need to measure phosphate, you need to do 24 hour urine calcium levels, you need to look at your metabolic panels, and you also need to make sure you’re not suppressing conversion on the other side. So you’re usually having to do both. And then there’s the other side of things which is like this whole topic that we’re having, Matt, which is on, you know, these patients who have persistent chronic viral issues or persistent borrelia, or whatever. And you’re like, “I need to upregulate “your innate immune system.” So, I’m actually finding that using 0.25 MCGs of calcitriol with calciferol or calcifediol, one of the two. 

And getting those numbers matched you gotta, with all the lab testing, I said, has been hugely, hugely useful because zinc and vitamin D, in my opinion, are probably the two most important co-factors involved in supporting a healthy innate immune system that’s designed to eliminate a persistent infection or put the genie back in the bottle as I call it, when we think of things like EBV, or CMV, because I don’t know if you’re like me, Matt, and you’ve tried every antiviral in the world. You know, if you’ve tried, I mean, I’ve tried IV cytovene, like, I mean, you know, and nothing works long term in my experience for EBV or CMV. You know, I think there’s some, I think there’s more to be said in the world of treating the immune system, and Paul Chaney really had it down years ago when he was dealing with chronic fatigue syndrome and using, you know, kutapressin and things like that to up regulate that same immune in issue. And I think that’s really what we should be focusing on because the world we live in now with, you know, all the biotoxins and all the things we’re releasing and the recognition of mold toxin, and who knows? This is electrosmog and things like that affecting all of this. I think in terms of sort of 21st century medicine, the focus needs to be moving more towards supporting healthy immune responses in terms of preventing cancer, in terms of reducing the likelihood of neurodegeneration, in terms of all of these things. That’s what I believe the focus should be.

Matthew Cook, M.D.

I would 100% agree. And the interesting thing, that’s the thing it’d be like, if you said that there was somebody knew how to fix EBV in Africa, I would get on a plane right now and fly there and cancel my week to figure that out. But basically the only thing that I’ve ever seen be very helpful is regulating and fixing and balancing immune function and basically raising the C level of health. And then that basically, and that C level of kind of a tide that is actually coming in and out, but to the extent that you balance immune function. And so then the immune supporting peptides, I think have been helpful in that category as well.

Cory Tichauer, N.D.

I agree in, you know, the two peptides I use in a lot of these cases where I still see residual active infection, thymus and alpha-1 and LL-37. You know, I love thymus and alpha-1, but I mean, you’re talking to a guy who’s been dealing with, you know, the treatment of tip 1 illnesses for a long time and you know, its ability to upregulate the innate immune system and T-cell function and improving Th1 conversion to sort of reinforce that cell mediated response is the important part in dealing with these types of infections. So, you know, personally, I find TA1 can be really helped to improve cellular membrane detox, as well as treating active infections that the body hasn’t been able to clear, like in Lyme or EBV, or C pneumonia. I’ve seen it work at improving NK cell function like we talked about. It augments antigen presenting cells, signaling. And so it can really be useful in particular in combination with other antimicrobials, whether that’s, you know, Western prescription medications or, you know, herbal therapies, I find it really helpful. And in the immune modulation world TA1, I’ve seen it really helping in some of these sort of Th2 dominant conditions like, you know, chemical sensitivity, or lupus or chronic fatigue syndrome, or that sort of atopic triad that you’ll see with eggs and asthma. I’ve definitely seen benefit from that as well. 

And then LL-37, LL-37, another one, I mean, again, I talked about this but it’s really interesting. If you’ve ever gone to even just Google Scholar or PubMed and typed in LL-37 and COVID, really, really interesting stuff there. Because there’s a lot on LL-37 being the primary or one of the primary focuses on the cell mediated immune system’s ability to get rid of these things. Because, you know, LL-37 is naturally stored in neutrophil granules as inactive precursors, and it’s released, I mean, its active form when neutrophils are stimulated, and what’s really interesting is production is stimulated by vitamin D, which is really cool. We’re all the way back into this discussion around how do you have support an effective innate immune system? And so we just created this really cool cycle. So yeah, I mean, and in these, you know, in these active COVID cases or these chronic viral things, I do like using TA-1 and LL-37 in these cases with prescription vitamin calcitriol and you know, and sometimes other things, right? Of course, like you know, all the armament of things like, you know, major auto hemotherapy or herbs or whatever it’s gonna be. So yeah.

Matthew Cook, M.D.

I had this great lecture that I went to years ago from a Hopkins professor that was talking about an analogy for, and I mentioned this in another, but an analogy for neurologically Lyme was drug resistant TB. And so then the idea is that for drug resistant TB, there was an antibiotic model which would be like four antibiotics.

Cory Tichauer, N.D.

Yep.

Matthew Cook, M.D.

And so then I said, well, technically, we’re kind of having the same conversation but like two antibiotics, is the LL-37 and TA-1. You know, and then the, you know hypothetically, you know, ozone could be one and then vitamin D from a certain perspective is almost one. And so then we have all of these others. And then herbals, maybe you have a couple of herbals, but combined that might add up to be one. And, you know, there’s people who really believe a chance to kill is a chance to cure. And so then that would be more of on an antibiotic side. But then if I was to put the whole conversation together, I think the you’re managing that thought process with the immune regulation process. And I would agree at a high level, you know, the epitalon, and you know, there’s both some injectable and oral versions of kind of the bioregulator peptides. And, you know, one idea that I just wanna maintain, like a long term conversation with you around, is the, from a pineal peptide, you’ve got pineal and epitalon and corgens and another sort of neurological bioregulator. But so then to begin to think about them as a possible alternative to VIP particularly for people who are reacting to VIP. So I had this whole conversation with Holtorf and interestingly putting KPV in there. And so then what I think that there’s going this next year or two is gonna be an interesting sort of journey of regulating in and around MSH and those pathways in the brain, which are basically to some extent, at a epigenetic level, putting that genie back in the bottle in the sense that from a transcriptome perspective, we’re printing kind of inflammatory genes. And that may be because MSH is low. And yet if we could start to balance that. And the nice thing about KPV is it’s easy to take, you know the melanotan does cause nausea.

Cory Tichauer, N.D.

It does, and sweating, right? Yeah.

Matthew Cook, M.D.

Yeah. But KPV makes people feel better. And so then kinda strategically there’s, and this goes back to kind of the overall arc of the conversation, we have all of these levers to pull and COVID is involved, chronic viral stuff is involved, these self infections are involved, actual third killer infections are involved and kinda managing all of that and managing symptoms and then doing things that help people feel good just to get them on the journey.

Cory Tichauer, N.D.

Yeah, I’m curious, do you have a source of KPV these days? ‘Cause I have about a hundred patients that would like claw their way to you right now if they knew that there was something.

Matthew Cook, M.D.

There’s, it’s challenging, it’s challenging. But there are probably some options, there are probably some options.

Cory Tichauer, N.D.

All right.

Matthew Cook, M.D.

Are you, tell me, are you using CmaX a lot?

Cory Tichauer, N.D.

I am, yeah, I do use CmaX. I’ve mostly been doing CmaX as a nasal spray and have somewhat recently started to explore a little bit more on the injectable which I actually feel like is helpful, but yeah. I mean, it’s another melanocortin peptide, right? So it’s sort of in that same category of KPV and MSH. And you know, especially, you know, when there’s cerebra vascular issues or know there’s some concern around impaired circulation to the brain, I think it can be really helpful. I think one of the issues I encounter with CmaX, is I wanna use it in higher doses ’cause I tend to find that more often, you know, especially in these neuroinflammatory scenarios, it can be really helpful. And I really encounter a price period for a lot of that for many people ’cause you know, doing, you know, say six or eight sprays a day, I think works great for a lot of folks and they really notice the benefits of it in reducing inflammation. I mean, one of the big topics, I think, in all of this is like this blood brain barrier, right? Like we have like getting things into the brain, whether you’re trying to treat an infection in the brain or you’re trying to remove something, it’s like a very protected area. 

And you know, even like you’re going back, you know, when you were just discussing neuroborreliosis or the, you know, the Lyme and the brain piece that you just had the analogy to it, to track resistance TB. One of the interesting things I found, and I found this data from, you know, Brian Fallon, one of his publications from, I don’t even know, probably over 15 years ago from Columbia. And it just came up again with, tolane, I think, where they talk about dead bacteria or dead borrelia being much more antigen than live ones, right? And so again, you know, kind of bringing this full circle to you what you were saying, like asking yourself, like, “what really is the priority here?” Is it really that there’s still an active infection or is it just that you’re dealing with a need to reduce that antigenic load and, or restore metabolic or neuroendocrine function to the brain, you know? And, you know, and so that’s where we get into phospholipid exchanges and kinds of other things. But yes, CmaX and like.

Matthew Cook, M.D.

Along, along those lines, I will find that sort of the phospholipids and you know you can, you know, whether you’re thinking from an IV perspective is kind of an interesting one.

Cory Tichauer, N.D.

Yeah, I mean, we do it both ways, you know, orally, as long as, you know, it’s well tolerated and you know, depending on how much you can absorb, but intravenously, we’ve seen a lot of benefit, there’s no question. You know, it’s kind of like the plaque X model or essential, or phosphatidyl choline. But yeah, using it with glutathione and using it with phenylbutyrate sometimes and you know, Luca Warren and all of that.

Matthew Cook, M.D.

Have you, are you doing phenylbutyrate IV? How’s your experience with that?

Cory Tichauer, N.D.

I think it’s huge, I think it’s awesome, It works great. I mean, butyrate is another one of the, like, I’m really focused on the gut these days, right? So like, you know, in terms of my sort of Genesis through medicine, you know, I sort of like look at the infectious world as like, okay, I don’t know that I can learn much more on antibiotics or antimicrobials anymore, so what else are we we looking at? And so the immune piece is really the bubble that I’m focused on, which brings us, you know, into the gut especially, and dealing with that. And so prebiotics and postbiotics are a big one. along about way of saying phenylbutyrate, right? So butyrate and just orally, probably is one of the most important things in supporting the T-regulatory cells ’cause 85% of our T-cells are in that gut associated lymphatic tissue. But IV, which is what you’re asking about, phenylbutyrate has great penetration into the CNS and a lot of the best data on that is on looking at ceramides or this idea of long chain fats that we talked about or odd-chain fats that form as these sort of wax plugs in the brain, you know, and the evidence that the phenylbutyrate is actually breaking down these long chain fats and helping restore membrane fluidity. And we definitely see improved cognitive function and, you know, we’ll do mocha tests or we’ll do promise 19 tiers here to sort of assess for, you know, the chronic fatigue world or the cognitive function piece. And we’ll definitely see improvements just by doing IV phospholipids with phenylbutyrate and, you know, we can get into fairly, fairly high doses in some folks. So yeah.

Matthew Cook, M.D.

I find those, you know, it’s interesting a lot of people will say, “oh, all of a sudden the world “has just becomes a little more clear, almost crystal “with the phosphatidyl choline and then word combining for the phosphatidyl choline also with, with other, you know, IVs. And that brings me back to, I think both of us, we’ve never met each other, but we’re doing very similar approaches and very similar with a lot of things that are just balancing and supporting immune function. Like my entire, I have about 18 things that I drink every morning during all of these podcasts, which is amazing, ’cause they just bring one thing after another, but it is all gut health oriented, you know? And so I like to tell people I’m just gonna project manage the gut as a thing that we do that is just something. And in a way project managing the neurological pathways, project managing these biochemical pathways and optimizing and supporting them. We’ve got antimicrobial, we’ve gotta kind of balancing things, we’ve got regulating things. But it delights me to listen to you because I agree with everything that you said, the long COVID pieces are interesting. And so then basically, just for people to know, I got a list of things that I was supposed to talk about and we only covered like 20% of it, which means in the next month, I would love to have you come on the Bioreset Podcast and we’re just gonna start a little regular conversation about some of the stuff and then try to keep making the world a better place. Thank you for being who you are, you’re an amazing doctor and I’m super impressed and grateful to talk to you.

Cory Tichauer, N.D.

It’s been really great being able to talk with you, Matt. I’m happy to share all this information and you know, I’m of the belief that, you know, not just what I can do for the people who come to see me, but as much I can help to educate other providers and help to sort of shift people in the right direction. I think we’re doing good medicine and gonna help a lot more people that way. And I think this is all just knowledge that should be shared. So I’m grateful that you’re doing these podcasts and these summits as well ’cause I hope this starts to change some of the paradigm in medicine and how we deal with chronic issues in general.

Matthew Cook, M.D.

Yeah, this just, this is that you’re listening to the future, so welcome to the time machine. Thanks so much, have a wonderful week this week.

Cory Tichauer, N.D.

Thanks Matt, great talking to you. I look forward to coming back for sure.