Steven: Yeah, sure. So, before defining that, I guess, to provide the context as a reminder, you know, what is this concept of so-called leaky gut, or intestinal hyperpermeability, right? So, the intestinal barrier wall is a gatekeeper, right? So, in a healthy person, in a physiologically healthy gut, this barrier should selectively be allowing macro and micronutrients and water through the gut wall and into our bloodstream, so that these components can be sent to the organs and tissues that need them. So we could say that the lining of our gut wall should be selectively permeable, right? So, it should only be letting through what needs to go through, and it should not be letting anything through that shouldn’t be found in circulation, right? So, microbial toxins, bacteria, metabolic waste, etc. And the structure of the intestinal barrier wall is like this three-layered membrane, right? So, the first layer is the single-celled, semi-permeable layer of epithelial cells, held together by tight junctions. On top of this is a double layer of mucus on top of these cells, and the gut bacteria reside on top of that mucus layer. Due to various factors, what can happen is that the tight junctions between those epithelial cells on the first layer can degrade, gaps can form in the lining of this wall, subsequently increase the barrier’s permeability, leading to what we call intestinal hyperpermeability, AKA leaky gut.

So, the loss of integrity in the health of this barrier, AKA leaky gut, has been suggested for decades, you know, if not longer, to supposedly lead to, or be a contributing factor to, a variety of symptoms and conditions, like, not just digestive, but metabolic and neurological and autoimmune and all these things. And what the research on this area called metabolic endotoxemia is highlighting is that it appears that, okay, it looks like everything really does start in the gut, or is driven by a leaky gut, so to speak. And the mechanisms of metabolic endotoxemia explains this very well, at a very specific kind of biochemical level. And yeah, the research is confirming there’s a lot of truth to the concept of so-called leaky gut.

Which is amazing, because, considering the wisdom of ancient traditions have held this perspective for centuries, right? In Ayurveda, you know, they’ve always taught that the Agni, or digestive fire, is the key to optimal health. In TCM, spleen and stomach chi are fundamental to overall health, and they are a fundamental component of the digestive system. And Hippocrates said that “death sits in our bowels,” and Henry Lindlahr said that, you know, the accumulated morbid matter and systemic poisons that are reabsorbed are what drives disease. So, yeah, it’s kinda cool that this field of research on metabolic endotoxemia is starting to confirm all this, right?

So, with all that, right, so, with endotoxemia, the simple definition of it, which I’ll expand upon, is a condition where there are excessive levels of something called LPS, short for lipopolysaccharide, in the bloodstream. And so, the term “endotoxin,” which is what LPS is referred to, it comes from the Greek word “endo” meaning “within,” because LPS is a molecule found within the outer membrane of specifically gram-negative bacteria. It’s what differentiates gram-negative bacteria from gram-positive bacteria. It is this LPS that is housed within the outer membrane. And, you know, LPS inherently shouldn’t be an issue. And, you know, while a healthy gut wall can handle a small amount of LPS getting into circulation, and be appropriately handled by the liver, to be cleared from the body, it shouldn’t, this LPS endotoxin should not be getting through that gut wall in large amounts. If excessive levels of LPS do get into systemic circulation, due to the gut being too permeable, this essentially triggers the innate immune system, leading to this chronic low-grade subclinical inflammation. And as we know, you know, the chronic inflammatory state is increasingly recognized as a key driver of most chronic diseases. So we have to step back and go, okay, well what’s driving chronic inflammation in all of these chronic diseases? And we have repeatedly been brought back to the gut, and specifically this endotoxemic mechanism is a very common explanation, linking all these conditions together.

So, you know, we’re essentially looking at the downstream effect of specific types of dysbiosis or bacterial imbalances, and a hyper-permeable gut wall. So, if someone has LPS-producing bacteria dominating their microbiome, and their gut wall becomes too permeable, this is essentially gonna lead to metabolic endotoxemia. And so, the excessive LPS endotoxin in the bloodstream, it triggers the innate immune system in some very specific ways, which we’ll get into. Because the immune and kind of subsequent inflammatory chemicals that are triggered as a result of this can interact with and impact such a wide variety of tissues and organs in the body, which is why so many conditions are being linked back to endotoxemia, which is so interesting. And so, the term “metabolic endotoxemia” is simply a term researchers came up with to describe when this excessive LPS in the bloodstream was observed to directly kind of be the beginnings of metabolic disorders, such as insulin resistance and obesity and that kind of thing.

Andrew: So, just, there’s so many questions floating around about LPS. Firstly, let’s talk about that “leaky gut.” So, first things first, it was Brad Leech who basically helped to dismantle that syndrome issue. There’s no leaky gut syndrome. It’s not a syndrome.

Steven: Yeah.

Andrew: That’s kind of like saying there’s a pain syndrome, or a breathing syndrome. But there is leaky gut, and there is excessive leaky gut.

Steven: Yeah.

Andrew: But it’s not a defined syndrome, if you like. So, thank you, Brad, for doing that, and I’ve watched Brad’s career blossom over the years, which is great to see. One of my questions, though, is that kids and the elderly have naturally more leaky guts, even leaky brains. How does this tie into function versus dysfunction?

Steven: Yes. Love your work, Brad. And I agree, you know, like, I’m very careful when, with clients, when discussing these topics of leaky gut, gut dysbiosis, SIBO, etc. I don’t like to refer to them as conditions or diseases, so to speak. Even though when you read about things like metabolic endotoxemia in the research, it gets referred to as, like, a condition, so to speak. But, you know, the danger there with, particularly with clients who are desperately looking for a reason for why they’re so unwell, and what’s kind of the “root cause” of their illness, I’m very careful with my language these days to make sure people understand that, you know, leaky gut is certainly not a syndrome or a condition. It’s just something that, it is the downstream effect of a variety of upstream contributing root causes, you know. I’m very careful to…I say, “Look, leaky gut, sure, it’s become a contributing factor to perpetuating a disease related to chronic inflammation,” but I wouldn’t say it’s the root, cause because what can happen is people can become a bit too reductionist about it. And they’re just looking for the next antimicrobial protocol and the next probiotic. And it’s not to say those interventions are not useful and helpful, but it’s, like, one-tenth of the picture, you know. So, while it is helpful to get reductionist about it, and get into the mechanics of it, at the end of the day, to address all this, you kind of actually just have to zoom out and address someone’s overall health, really, you know.

Andrew: Yeah. I totally agree with you. I think it was Dr. [inaudible 00:10:30] who saliently pointed it out about this kill-kill mentality. And he said what happens, particularly with extremely sick people, chronic fatigue people, multiple chemical sensitivity, etc., is you kill everything off in the gut, and they’ve got nothing. So they become what’s called the mashed potato and peas brigade, and they end up cycling at a lower ebb. They never revitalize their system. So, I love what you say about we’ve gotta dig down, or, you know, to the root causes. So, let’s start with those causes. Stress, anyone?

Steven: Yeah, yeah. And to your point, like, for example, just recently, you know, very recently in the past number of years, you know, there’s a lot of awareness around, you know, one of the conditions…it’s…a new study came out just a few weeks ago, I think, on, an LPS-producing bacterial overgrowth being commonly associated in women with endometriosis. Okay, cool. It’s another study looking at this LPS endotoxemic link, with endometriosis. But then what I see and, you know, this is just in the online world but, like, what I see from the general public, and even some practitioners, you know, following from that, which is, like, “Cool. There’s this research here confirming this link with endotoxemia.” But then what can happen is people go, “Okay. Cool. The solution therefore is gonna be, how do we kill this bacteria? What are all the things to get this bacteria…” Like, it becomes this very almost, like,  germ theory kind of discussion.  and its relationship [inaudible 00:12:18] endometriosis, but  the dealing with the bacterial overgrowth is just one piece of this puzzle. It’s almost like a damage control kind of style of treatment. Cool, we wanna get on top of that, but, like, in the longer term, to get on top of this and educate people about how to, you know, truly reverse LPS, kind of endotoxemia and leaky gut, we have to zoom out and go, “Cool, but what led to that type of bacterial overgrowth?” Right? And to your point, yes, stress, nervous system dysregulation, circadian rhythm disruption, and poor sleep. It was huge, like, bit more longer-term to consider and address, but, like, toxicant exposures. The amount of environmental toxicants, and medications people being exposed to, which, you know, are perpetuating this on a deeper level long-term is huge. Yeah, we’ve got…there’s so much to consider, so to speak. But that doesn’t mean under, at least in the short term, we can get very hyper-focused on the gut environment, and begin to reduce that LPS load. That’s still important, like, particularly at the beginning. Just start getting that chronic inflammation down.

Andrew: Just to point you, mate, that dysbiosis and endometriosis paper, was that, that wouldn’t have been written by Justin Sinclair, would it? I think he’s paper on it. I think he has.

Steven: Oh, really? Cool.

Andrew: And I also take your point. There was an author, one of my favorite microbiota authors, Catherine Lozupone, who, years ago now, and she used the analogy of a garden and things like that, which, you know, some people don’t  But in there, she spoke about…now, she mentioned the American spelling acetaminophen, which in Australia is paracetamol, and paracetamol overuse leading to increased amounts of p-Cresol, which is a metabolic byproduct which can…is one of the byproducts which can affect heart function, particularly in those people with kidney disease, when they can’t get rid of it. It’s just amazing that… So, you’re talking about this whole, it’s not just there in the gut. It’s the gut, things that affect the gut, and then the gut obviously flows out into the rest of the body, has to be handled by other tissues, not just the liver, but the kidneys, etc., da, da da, da da.

Steven: Yeah.

Andrew: So, you really have to treat the patient in a holistic manner.

Steven: Yeah. And, like, I love to explain to clients that if you look at the etymology of the word dysbiosis, it’s a Greek word that means “wrong living.” So, it’s like, [inaudible 00:15:05] it’s, you know, dysbiosis is the manifestation, or, again, the downstream effect of many different things that, an accumulation of those things over a lifetime, right? I know some people have this kind of, this typically, like, a catalyst of an event that, you know, started everything, so to speak, like an antibiotic, or gastro, or something, but I don’t know. I kind of feel like that’s usually the straw on the camel’s back, so to speak. But yeah, you know, again it’s just, I really, really… It can take, if people have never thought about it like this, it can take them a while to kind of get it, but it’s just cause and effect. Like, yeah, dysbiosis is perpetuating, and has now been left untreated for so long it’s led to a state of a permeable gut and endotoxemia, but there were things contributing to that dysbiosis over time.

Andrew: I… You are so insightful, Steve, I’ve gotta say. Even the word dysbiosis, “wrong living.” We think wrong living of the bacteria within us. It’s our wrong living that’s caused this.

Steven: Yeah. You know? And…

Andrew: So poignant.

Steven: Yeah. I mean, when I first heard that, I went, “Wow. But that wasn’t even explained to me in my training.”  said, “Oh, well, bacteria become imbalanced, and it’s just something that happens,” and blah blah blah. When you look more deeply into… Because, you know, again, we’re, like, the medical, conventional medical model is very germ-phobic, let’s say. Like, very hardcore germ-phobic. And, you know, the opposite of dysbiosis is symbiosis, so we should be living with these organisms. We should not be afraid of them and phobic of them. And they’re always, you know, even if they’re “imbalanced,” they’re always trying to serve us. So, you know, I think, again, there’s this kind of, in terms of supporting people who’ve got intense degrees of permeable gut and LPS getting into their bloodstream and driving endotoxemia, like, yes, we want to as quickly as possible reduce that endotoxic load, and heal and seal that gut, and reduce the populations of certain organisms in the gut that are perpetuating that. But not in this, you know, kind of black-and-white warfare mentality of, “Oh, I just gotta destroy all the bacteria.” And we have to really step back and try and get people on to say, “Cool, but, like, why did this happen in the first place?” And that’s, you know, there’s a lot to unpack there, over time. Yeah.

Andrew: Yeah. So, I guess much of your treatment phase, if you like, must be psychology, teaching people how to address the psychology that’s affecting their stress, that’s affecting their physical aspect.

Steven: Yeah. That has become pretty huge for me. Like, you know, I have people walking in, predominantly, to help with a gut issue. And I don’t know, but I think a lot of people are expecting a prescription of all this kind of what I would call gut-centric supplements. Probiotics and prebiotics and, you know, all the…”supplements for their gut.” But I rarely actually do. Like, when I first meet people, and, you know, usually send them off for some testing, in the meantime, oh, look, I’ll usually whack them on some PHGG. But outside of that, I’m pretty much just supporting their nervous system and their stress and their sleep, because that is one of the major contributing factors to dysbiosis and leaky gut, and why these imbalances are showing up in the first place. And, you know, the gut just won’t heal, so to speak, in a state of nervous system dysregulation. So I am, you know, hugely focused on that from the get-go.

Andrew: Can I ask, Steven, what sort of assessments do you favor to check leaky gut? And I’ve got a second part to this question, sort of, and that is, what you mentioned before about working first on these areas that affect the endotoxemia, or the leaky gut.

Steven: Yeah.

Andrew: And yet, people very often want a quick, not bang for buck, but a quick effect. So, how do you balance the longer-term issues with getting them feeling a little bit different? And, you know, I think that the term is different, not necessarily all well.

Steven: Yes.

Andrew: As long as they can feel a change, is that… Do you find that, or do they need to feel well now?

Steven: Yeah, look, I guess that’s, as a clinician, like, you know, we obviously have this overarching theme of we wanna treat the underlying causes, right? But, you know, some people are in significant pain and distress, and we absolutely wanna give them symptom relief too, right? It’s a bit of both. So, you know, when I first meet people and, you know, we’re discussing testing, if we are getting testing while we’re waiting for that testing, you know, like I said, we do want some symptom relief. And so, if appropriate, I try not to impose strict elimination diets on people, unless they’re pretty debilitated with symptoms, you know, and I see a need for them to establish a bit of a baseline, like, we need to calm all of your symptoms down, to establish a baseline of, you know, what it can feel like, like, how is your body functioning when you remove the variable of all these foods coming in and perpetuating your symptoms? So that people aren’t just chasing the next supplement when, you know, because of their state of chronic inflammation and leaky gut, their diet is unfortunately making them very symptomatic.

So, look, I will get into the elimination style diet area if appropriate, but some people, just based on what else might be going on, I may not see a need to take them that far, and I will just, you know, give them some supplements to improve their sleep and support their nervous system, or some, you know, just some herbal medicines to improve their gut function, like bitters or liver support. Yeah, it’s kind of dependent on the person. But while I’m trying to get them some symptom relief and give them some foundational support at the beginning, with tests, with the testing question, look, on paper… So, there’s two areas to this, right? It’s like, if you have a dysbiotic gut, with a dominance of LPS-producing bacteria, combined with a very leaky gut wall, that is gonna lead to significant endotoxemia.

So, you know, on paper, it’s like, okay, well, to see if someone truly does have a leaky gut, I’d go to the lactulose/mannitol test. Now, in clinical reality, just to save people some time and money, if we need to prioritize testing, I will go with microbiome testing as a big priority. Just because I say to them, “Look, whether or not it turns out you truly have a very permeable gut wall, all the style of treatments we need to do anyway are going to treat a leaky gut. It’s going to improve that. So, I’m happy to safely assume, because it’s not gonna change what I need to do for you to begin with. If you wanna check, cool, we can check. But at a minimum, let’s check that in six months.” Make sure it’s, you know, actually gone, so to speak. And so, the reason I wanna prioritize the microbiome testing is, like, cool, if our treatment’s gonna take care of a leaky gut anyway, I’d rather see what the entire microbial environment looks like, and what your type of dysbiosis is, so to speak. You know, are there significant LPS bacterial overgrowths and/or hydrogen sulfide overgrowths? I’d rather have the information that’ll help direct their treatment, if that makes sense.

But if people want all the data, cool. We’ll get it all. And, you know, I’m always, yeah, outside of gut testing, I’m, again, zooming out and looking at someone’s overall health, so I’m always getting the appropriate pathology done, so to speak. And, you know, because, again, well, what contributes to dysbiosis and leaky gut? Well, nutritional deficiencies, and, you know, maybe some undiagnosed conditions that haven’t been found, like Gilbert’s syndrome and all that kinda thing. But that, yeah, that’s generally my approach with testing.

Andrew: Yeah. You’ve just turned what I used to do on its head. I used to favor the lactulose/mannitol test, and I totally get you.

Steven: Yeah.

Andrew: I totally get you. So, I used to favor the lactulose/mannitol test because it’s relatively inexpensive versus the microbiome testing, but I totally understand what you’re saying. So, thank you for that. That’s great. That’s actually really good. Gives you a lot more information about what’s going on, because the other stuff’s gonna improve the lactulose/mannitol test anyway, so it’s like, “eh.”

Steven: Yeah. Because some, I know it’s, like, “test, don’t guess.” It’s like, but, again, it’s not gonna change my treatment too dramatically

Andrew: Yeah.

Steven: Let’s just get into it.

Andrew: Yeah.

Steven: You know?

Andrew: Hmm.

Steven: Yeah.

Andrew: Love it. Love it. So, can we dive into a few conditions at all? You mentioned, for instance, you know, your metabolic, neuro, autoimmune. Can we start with those? I know that this is more than a broad brush stroke. But…

Andrew: …can we start with maybe those sorts of types of conditions? Patients that come and see you with those?

Steven: For sure. So, I guess, to preface that, what I’ll just briefly explain is, like, what happens once the LPS endotoxin is in circulation in excessive amounts? Because this is understand this, it’s like, okay, well, how does endo, how does PCOS, how does insulin resistance relate to metabolic endotoxemia? It’s, like, the same pathway. It’s the same chain of events. And then will just manifest in a different way, depending on the person. So, if LPS endotoxin is in the circulation in excessive amounts, there’s this very specific cascade of events, where…and this can get super dry and complicated, but if people wanna… There’s this is awesome paper, 2021 paper in “Frontiers of Immunology,” called “The Role of Metabolic Endotoxemia in Systemic Inflammation.” You know, that’s the paper you’d give to anyone, especially, like, a healthcare practitioner who’s, like, still living under a rock, and is skeptical about all this, that explains it so well. But essentially, you know, LPS gets in the bloodstream and binds to something called LBP. There’s this LPS-LBP complex. It attracts the attention of CD14, so, protein made of macrophages. It’s part of the innate immune response. And so the LPS-LBP complex gets transferred by CD14 to something called toll-like receptor 4. So, when you start looking at all the research on metabolic endotoxemia and, oh, what’s going on with endotoxemia and endo, and endotoxemia and Parkinson’s? It talks about many things, but particularly this TLR4.

So, with toll-like receptors, they are the principal inducers of innate immunity, and it’s why sometimes you’ll see, “Oh, what is endotoxemia?” They define it as a chronic state of innate immune activation, due to toll receptor activation, because the job of toll receptors is to detect the presence of microbes in circulation, or their components. And so, different types of TLR receptors are responsible for detecting specific types of microbes and components. TLR4’s job is to recognize LPS. And so, when it finds LPS in circulation, it binds to this, and there is this subsequent release of a myriad of inflammatory cytokines. So, TLR4 activation activates NF-κB, NFKB, which then leads to production of, you know, TNF-a, interleukin-1, interleukin-6, etc. So, you know, a cool way to think about it is, like, TLR4 detection of microbial components is considered the first line of defense against bacteria. The most extreme example of this being sepsis, right? It’s the same thing. It’s, like, it’s just a much more end-stage version of endotoxemia, if it gets bad enough. So, when bacteria translocate into the gut, and it overwhelms our immune system to the point that the inflammatory cytokines triggered by TLR4 lead to tissue damage and organ failure, right? So, I think I was reading in that paper, you know, the LPS levels observed in sepsis are about 15 times higher than those seen in individuals with what we call metabolic endotoxemia, this lower-grade endotoxemia.

Andrew: Wow.

Steven: But it’s the same thing happening on a lower grade, subclinical level. But obviously, people aren’t, you know, having organ failure. But it’s the same mechanism

Andrew: Wow, that’s… That’s huge, what you’re saying there, Steven, because, with sepsis, it gallops along. You know, the early signs are so weird, like, they’re more delirium and things like that, that you would not associate with “an infection.”

Steven: Yeah.

Andrew: And yet, just imagine… Forgive me. Sorry. And their treatments for sepsis are not, let’s say, optimal.

Steven: Yeah.

Andrew: You know, there was Paul Marik, trying to use his TAP therapy. That’s the, what is it, thiamine, ascorbic acid, and prednisolone, or prednisone. Knocked on the head, if you like, by Monash University, or poo-pooed by it. But nobody is looking, certainly in the orthodox world, about changing or treating the gut. Imagine, just imagine if people presenting early enough with sepsis were treated with quite innocuous things, given orally, like, I’m gonna say it, this serum bovine immunoglobulin complex, which I love, or probiotics, like Saccharomyces boulardii or, you know, lactobacillus coagulans, whatever, rhamnosus, LGG, whatever.

Steven: Yeah.

Andrew: Imagine if orthodox therapists started to embrace this in a hospital situation.

Steven: Yeah.

Andrew: Oh, my god.

Steven: Yeah. And, you know, just, and again, to the layperson, or maybe even practitioners and people in healthcare, it’s, again, it’s just a subtle use of language now, that is important, but it’s, like, you know, sepsis isn’t just an overnight random event of a bacterial invasion. It’s like, there was a sequence of events leading up to that, you know.

Andrew: Yeah.

Steven? It’s, yes, once they got in, in, to that degree, cool. You’re gonna need the damage control level of, you know, acute emergency treatment. But yeah, there’s this huge in-between gap in… But, you know, even, like, I was reading a paper, a 2024 paper, this year, August, in “Oncotarget,” a cancer journal, talking about how, in post-operative patients treated for colorectal cancer, it discussed the importance of gut barrier integrity in preventing bacterial LPS endotoxin translocation into circulation after surgery, because they’re acknowledging that, due to the damage to the gut barrier post-surgery, if that gut wall is still quite permeable, it’s the translocation of LPS compounds which increases their risk of local bowel and systemic cancers post-surgically in the future. So I thought that was really cool to read, that they’re looking at that.

And, you know, LPS trans…because of this TLR4 activation pathway, and the subsequent immune and inflammatory events, I mean, if you just pop Google, PubMed, a type of cancer, LPS endotoxemia, all of them are being connected to this. Like, it’s starting to be acknowledged, you know, whether it’s prostate or colorectal, you know, like, helicobacter and the risk of gastric tumors is a classic example as well. But, yeah. So, once we understand that pathway, it’s like, okay, cool. How does this relate to metabolic issues, you know, with atherosclerosis, obesity, type 2 diabetes? You know, the atherosclerosis one is a really interesting one, because, you know, when… LPS is essentially transported from the lumen into circulation via chylomicrons, right? So, and there are different sizes of all these lipoproteins, right? Got LDL, VLDL, small dense LDL. And LPS can bind to all of them. And, you know, so, the ability of the lipoproteins to bind to LPS, it’s, again, the body does everything very intentionally. That binding of LDL to LPS is considered protective, you know. The LDLs are trying to prevent sepsis. They’re like, “Oh, shit. There’s LPS in the system. Bind to that, get it, recycle it through the liver, and get it out.” The issue, and, you know, in studies, this is partly how statins appear to work, too, because statins increase LDL receptors, which increases recycling of LDL and LPS from circulation. The issue, though, is that, you know, not all lipoproteins get recycled. The smaller, denser LDL particles don’t get recycled, so LPS remains in circulation. And so it’s like, okay, well what happens then? Again, we go back to this kind of TLR4 activation. So, the LPS triggers the innate immune system, and that forms a foam cell, like, soft plaque at the endothelium, and that is the beginning of atherosclerosis.

Andrew: This is so interesting.

Steven: Well, there’s a huge topic.

Andrew: Can I… Oh, look, it’s a massive topic. Can I ask, though? At some stage, we’re talking about interventions. Right? So, when do you intervene with, you mentioned it, partially hydrogenated guar gum, PHGG. Even probiotics, we’ve spoken about the bovine serum immunoglobulins.

Steven: Yes.

Andrew: When do you institute those things that heal the gut, versus other things like, you know, NAC, calcium D-glucarate, other detox regimens, liver/gallbladder herbs, that might clear toxins? Do you work on, obviously, stress and psychology in that first diet, and then what comes in? Soothe the gut?  When do you start clearing?

Steven: Yeah, look, I do begin immediately. The main, I mean, pretty much, these days, assuming, again, there’s safely assuming there’s a degree of permeability to deal with, and everyone’s got a bit of dysbiosis going on in the end, from all the testing I do. Everyone gets a very high dose of a, you know, purified, third-party-tested omega 3. That’s really important. There’s research on the omega 3 for, you know, reducing LPS translocation, and a dampening of TLR4 signaling, and it’s, you know, crucial to the nervous system, so the omega 3 is up there. The bovine-derived immunoglobulins is a really nice one I’ll use at the beginning, for some people. And/or once that result’s now confirming things. It’s really nice to, again, come in with that, you know, initial damage control. Like, okay, we’ve gotta get this inflammatory load down as soon as possible, by trying to neutralize and clear LPS, like, to start that process. So, the immunoglobulins are really good for that, as is the fish oil.

As is, you know, prebiotics, right? Particularly the polyphenol variety,  let’s call it, right?

Andrew: Oh. Oh.

Steven: So, I mean, yeah. They act as prebiotics, so to speak.

Andrew: Yes. Yes.

Steven: So, you know, like, dietary, all our kind of, like, rich-colored plants, so to speak. Pomegranate is a pretty incredible one. May sneak that into someone initially, but if not always… Like, pretty much everyone gets pomegranate, for a variety of reasons, but in the context of LPS endotoxemia, you know, there was, for example, there is a really cool human trial, was a randomized controlled trial. Pomegranate polyphenols given to overweight and obese people with hyperlipidemia, over three weeks, and it showed a significant decrease in plasma LPS, binding protein, CRP, while increasing butyrate-producing bacteria, and decreasing pro-inflammatory organisms, like methanobrevibacter. So, polyphenols, particularly pomegranate, are kind of like the ultimate intervention for reducing LPS load, likely via feeding bacteria that reduce gut inflammation and heal a leaky gut, and decreasing the bacteria that are perpetuating that issue. Yeah. the immunoglobulins. Look, some people, I will get them straight onto a curcumin, just because it’s, the research on that for reducing gut inflammation and for permeable gut is just, yeah, pretty awesome too.

Andrew: Yeah. Cool. And sorry, I mentioned things like, you know, your calcium D-glucarates, your NACs, your clearers, your phase twos.

Steven: Yes, yes.

Andrew: Can you give us a dose guesstimate, a dosing range that you might use? And perhaps, if you might, you know, start off a little bit sheepishly in some people?

Steven: Yeah, yeah. So, yeah, to your point there, like, something I haven’t mentioned I should have is, when we’re getting a bunch of testing done, I make everyone do an at-home transit test, right? So, they consume, corn or sesame seeds first thing in the morning, write down what time they did that, and what time they first see it in their toilet bowl. Because bowel movements, this observation of bowel movements are notoriously not reliable, to tell, for someone to say whether or not they’re constipated, so to speak. And having optimal transit time, between 16 and 24 hours, is crucial, because otherwise you’re reabsorbing compounds, right, and that dramatically perpetuates and worsens a leaky gut LPS issue. So, in that context, hence, it’s kind of another win for PHGG, but in that context, particularly in a female who has super obvious relative estrogen excess issues, I will very regularly put them on calcium D-glucarate, to help the liver and the gut along. That, I’m usually doing, like, it’s about a 1000-milligram dose, kind of higher-end dose, but that works so well. And NAC does have some very cool research on reducing, kind of, LPS endotoxin load, and helping with tight-junction protein regulation. That, and we know it has, again, that one, I might pull out particularly if on top of the gut issues, I’ve got a client who has got some pretty intense nervous system dysregulation and, you know, anxiousness and, because of its kind of glutamate-modulating kind of properties. I think you only need about 600 milligrams a day of that, I find. It seems to do the job, and it’s super cheap. Yeah, so, so many options to support all this, right? This really depends on the person.

Andrew: Oh, yeah. Diabesity. Let’s move on to that. Disorders, I mean, diabesity’s so huge. You were talking about somebody, I think with, was it you was talking about somebody with polycystic ovarian syndrome?

Steven: Yes.

Andrew: No, you were talking about women with estrogen problems. That was it. That was all

Steven: Ah, yes.

Andrew: …your wording. Yeah.

Steven: Yeah.

Andrew: So, can we talk about that hormonal regulation, then?

Steven: Yeah. So, with, you know, addressing insulin resistance, I mean, like anything, there’s many factors to consider, right, like sleep, diet, macronutrients, stress deficiencies, etc. But, you know, I do see a lot of women with, PCOS, and people on a weight loss journey, and many things. And, you know, typically, I wouldn’t say most of those people have a chronic gut issue at the same time, so they’re not thinking about leaky gut. But the research is pretty strong on this point that, you know, metabolic endotoxemia may actually be the primary insult, beginning the pathogenesis of something like type 2 diabetes, due to its effects on insulin resistance, right?

Andrew: Wow.

Steven: So, I think it’s, like, the American Diabetic Association have been researching this since, like, 2007. And, you know, in this paper, you know, first of all, they showed if you took that CD14 innate immune system protein out, mice with it, you know, injected with LPS didn’t have any immune activation, right? So just kinda clarifies one of the mechanisms. But, again, once this TLR4 activation occurs, due to excessive LPS, there’s so many mechanisms to back up that LPS may be the primary insult, like, you know, the TLR4 activation reduces insulin sensitivity by inhibiting insulin receptor activities, and the inflammatory cytokines increase liver glucose production and subsequent chronic inflammation. It decreases GLUT4 translocation, which prevents proper glucose uptake. So, this idea that the metabolic endotoxemia piece is what begins to make someone, not so resist…sorry, not so sensitive to insulin, is compelling, you know, because there’s this big question when we talk about all this, like, well, was it chicken or the egg, right? Who knows? Maybe it’s different depending on the person. But I think at the end of the day, because of the TLR4 activation induced by LPS endotoxicity, it needs to be considered. And I think it’s a really smart approach to say reducing insulin sensitivity in people who, whether it’s PCOS or obesity, and/or, right? It does, you know, it’s not really gonna change my approach.

And, you know, with obesity, as well, you know, there’s interesting research on that, you know. Many people… I know association isn’t causation, but in studies, they do observe people with obesity have much significantly higher populations of the LPS-producing bacteria, gram-negative bacteria. And once there is… What the research shows, like, particularly on, like, the effects of diet on LPS endotoxemia, is that if you give, a “normal weight” versus an overweight individual a very endotoxic meal, it’s a very high in, say, processed saturated fats and refined sugars, they both have a very similar endotoxic response. But if you give that same meal to an obese person, their endotoxic response is significantly more toxic. So it’s kind of like once someone is obese, and because the TLR4 activation that’s on overdrives kind of perpetuates fat storage and increases inflammatory cytokines, they’re, an obese person’s endotoxic response to food is a lot stronger.

So, taking an approach of investigating and addressing metabolic endotoxemia in that patient group is really important. And, yeah, like, really educating people on how to reduce, you know, a strong endotoxic response in their diet. And again, there’s this question of what came first, you know, a higher endotoxic response to food due to being obese, or was it, you know, weight gain due to high metabolic endotoxic responses to food? And, you know, I mean, you could argue on both sides, but there’s some interesting research suggesting the metabolic endotoxemia preceded the obesity, just based on studies showing that people who had more potent endotoxic responses to food had a significantly increased risk of developing diabetes and obesity down the track. So, you know, are some individuals pre-programmed with a certain microbiome, to have more significantly endotoxic responses to food and therefore be at higher risk of developing metabolic issues, is the argument.

Andrew: Steven, can I ask, just, to give us an overview of, I mean, this would be an overview of your mind, obviously, but give us an overview of what sort of journey these patients have? You know, if you can just try and think about a few patients that you’ve treated recently, around this concept of metabolic endotoxemia, can you give us an example of how they improve over time? What sort of conditions you’ve treated?

Steven: Yeah. Look, I do see a lot of endometriosis. And so, for example, if I can think of some people recently, and, you know, these clients, [inaudible 00:47:08] they’re not well. You know, they’re in a lot of pain and distress, and they’re desperately seeking solutions, right? And so they’re absolutely a group who, while I’m begging on about treating the cause, I wanna get them some symptom relief ASAP, right? Especially with these people, I love me some PEA. And, yeah, similar, I guess, similar to the story I was, what I was trying to say earlier, it’s like, because people are so unwell, and really, really want a solution, and find out about this link with the gut, you know, again, a lot of these clients come in very focused on the gut, and it, you know, I make sure I explain to people really well, yes, we’re gonna treat your gut, but requiring that actually, sorry, treating that actually requires us to zoom out and really support your overall health too. It’s not just gonna be a gut protocol or probiotics.

And it’s a mix, you know. Some people, that really hits home, and they get it, and they’re up for it, looking at their overall life and health, and the sleep and the stress, and all the things. And others, not so much. But I’d say the overwhelming majority of people, once you get that point across, they get it. And, you know, their treatments are similar in some ways and different in others, just depending. But yeah, look, endo, I have really good results. I don’t know why. It’s just, once you and they all, for example, they… This, endo has this big link with histamine as well, right?  it’s like, cool, here’s a low-histamine diet. It’ll give you some relief, but it’s not a solution. So, with the histamine conversation, everyone’s like, “Oh, I wanna find out if I’ve got histamine bacteria in my gut.” Honestly, 90% of them don’t. But, 90% of them do have, like, in my experience, significant overgrowths of E. Coli, right? Kind of classic LPS-producing microorganisms. So, I don’t know. With endo, I find, if you really get on top of that endotoxemia and, you know, get gut-centric, and cool, reduce E. Coli populations and all that kind of thing, like, they get significantly better.

Andrew: Can I ask what dose of PEA do you use?

Steven: I’ll go pretty high for the first month. Like, that 600 milligrams twice a day, for a month, and then ideally reduce that back to a 300 to 600 maintenance dose. But awesome, awesome for pain relief, right? Because, right, and when someone’s in that degree of pain, it’s like they don’t care about the multiple variables of dysbiosis that they need to address over, you know, years.  Like, yes, but we need to get people symptom relief, so the PEA is pretty incredible for that. Like, yeah.

Andrew: And do they take the PEA every day through their cycle, or just when they’re experiencing pain?

Steven: No. I get them every day.

Andrew: Every day.

Steven: Yeah. Yeah. Most people need that

Andrew: It’s such a huge issue. So under-treated, poorly managed, poorly diagnosed. Yeah, oh. It’s a travesty

Steven: Yeah. I mean, you know, when we talk about medications, and, okay, what contributes to leaky gut, dysbiosis, and LPS? Okay. What medications? It’s, the anti-inflammatories are shocking, you know? They are very well-known to perpetuate, okay, well, what actually leads to these bacterial population? Balances and a leaky gut wall Some people are surviving on those meds, and it’s like, cool.

Andrew: Yes.

Steven: We have some good alternatives.

Andrew: Yeah. In desperation, I’ve seen one woman taking the high-dose ibuprofen, that’s the 400-milligram tablets, just popping them.

Steven: Yeah.

Andrew: All day, trying to get relief, because there was…she couldn’t get relief from a doctor who was hesitant about using opioids. And so she was popping these ibuprofen during the day, and had a gastric bleed.

Steven: Yeah.

Andrew: So she was done either way. She…you know?

Steven: Yeah. Yeah, yeah, yeah. And, you know, again, a lot of this comes down to lifestyle and diet and, you know, what’s the saying? Outcomes are generated by habits. But most, you know, people in chronic pain, that they know what they need to do, but they can’t deal with it, you know. So, the symptom is really important, at the beginning, right?

Andrew: Yeah.

Steven: And that’s the challenge about being a clinician. It’s like, cool, we wanna treat the cause, but we also wanna get you feeling better as soon as possible, without ignoring the root cause, you know, so PEA is just a total winner for that.

Andrew: And also, I have to ask about omega 3 fish oil. You said that you put a decent dose in. What dose do you use?

Steven: Yeah. Usually about, I mean, I’m using fish oil with a very high ratio of EPA to DHA. So, if someone’s pretty inflamed, some pretty serious gut nervous system issues, I’ll go about two to three grams total omega 3, with about a 3 to 1 ratio of EPA/DHA. Yeah, I go pretty high-dose with that. They may not need to take that much forever, but again, just to get as much impact on that inflammation and endotoxemic stuff ASAP. Yeah. Really fish oil to begin with. It was very helpful.

Andrew: Beautiful. We’ve learned so much from you, Steven. Just one last quick question. Where can we learn more? Now, you’ve given us some great papers throughout this. I hope we’re gonna be putting these up on the website, and in the show notes. We’ll definitely do that, not “I hope.” Anything else? Any other seminal works? Have you got any courses, for instance?

Steven: No. They’re in the works. You know, because I’ve been talking a lot in this chat about, you know, symptom relief and damage control treatments for LPS and, but there’s a much bigger picture to consider, right? That’s kind of what I’m in the process of developing a course on, because it’s just, it’s not sustainable for me or clients, like, legit time or money, to get through all of, like, okay, what are the things I have to consider? To get, figure that all out in appointments, it’s just not sustainable for anyone. So… And I’m a bit all-or-nothing, so, like, I don’t wanna, I’m gonna make something which kind of covers everything, all these variables, and, you know, here’s the phases to go through. And that is in the works. It’ll be out eventually.

Andrew: I look forward to that mind map.

Steven: Oh, my gosh. It’s, yeah, it’s been a process. But, yeah. So, until that is out, you can just find me rambling on my Instagram. Steven Judge [crosstalk 00:54:40] my website. Yeah.

Andrew: I love your work, Steven. I love your mind. And I love that you don’t just focusing on the problem at hand, but look at what’s causing the problem. You can see if you’re… It’s pretty evident that you’ve got a lot of love and care that you give to your patients, and it’s not just in about a little bit of poking it with a symptom relief. You really want to get them well. You want to get them vital. I really applaud you and what you do. Thank you so much for your work.

Steven: No worries, Andrew. It was a really cool chat.

Andrew: And thank you, everyone, for joining us today. We’re going to be putting up a heap of information for you in the show notes. And remember, you can catch up on all the other podcasts on the Designs for Health website. I’m Andrew Whitfield-Cook. This is “Wellness by Designs.”