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REPLAY: Multiple Autoimmune Syndrome with Lisa Costa-Bir and Daniel Sipple

Lisa Costa-Bir's picture

REPLAY: Multiple Autoimmune Syndrome with Lisa Costa-Bir and Daniel Sipple

Functional Naturopath Daniel Sipple and fx Medicine Ambassador Lisa Costa-Bir discuss Multiple Autoimmune Syndrome (MAS). With autoimmmune (AI) diseases developing in clusters it’s important to understand that management takes a multi-pronged approach.  

Join the two naturopaths in a clinically rich discussion that takes you through educating and onboarding patients in the management of autoimmune disease and taking care of the 25% who will experience MAS. They discuss how to recognise possible signs and symptoms connected to MAS, the three types of MAS and what to look for when undertaking functional tests.  

Understand how patient care involves not only treating the area impacted but importantly, addressing the root cause of immune dysfunction itself and various treatment options to implement using herbals, nutrients, probiotics, lifestyle (addressing stress and sleep) and diet for management of MAS.  

Covered in this episode

[00:33] Welcoming Daniel Sipple
[01:40] Hashimoto’s as a common autoimmune condition seen in clinic
[04:03] Increasing rates of multiple autoimmune diseases
[05:32] Educating clients on predisposition to multiple autoimmune conditions
[09:30] Categorising autoimmune diseases into clusters
[11:42] Common findings in blood pathology
[14:02] The role of Naturopathic medicine in managing multiple autoimmune syndrome
[19:40] Stealth infections and cross reactivity 
[23:13] Stress and vagal nerve dysregulation
[25:14] Modulating the immune system
[31:08] Therapeutics to impact autommunity
[35:02] The importance of lifestyle
[37:35] Connection and fun
[39:26] Thanking Dan and closing remarks

Key takeaways 

  • Autoimmune disease tends to develop in clusters with about 25% of patients with multiple autoimmune syndrome (MAS). Educating patients on the possibility of this is important, however care must be taken to reduce undue stress by providing holistic support, early intervention, and other avenues that traditional western practices can overlook. 
  • Focus on the issue of immune dysregulation/dysfunction, the impact of sleep/stress etc, and not only where the tissue is being attacked. Getting patients on board via education is also critical not only for understanding the health picture but to shift patient thinking to a “solutions focused” one rather than feeling helpless. 
  • Awareness of rogue symptoms can assist with better management I.e., sore joints, headache, fatigue, any symptoms that seem unrelated but exacerbate inflammation and warrant a deeper look. 
  • Although not well known, MAS Types can be classified (see paper in resources): 
    • Type 1 – Presenting with myasthenia gravis, thymoma polymyositis, and giant cell myocarditis. Rarest type 
    • Type 2 – Presenting with any combination of Sjogren's syndrome, RA, primary biliary cirrhosis, scleroderma, and autoimmune thyroid disease. Most common. 
    • Type 3 – Autoimmune thyroid, myasthenia, Sjogren's, pernicious anemia, thrombocytopenia, Addison's, type one diabetes, vitiligo.  
  • When screening Anti-nuclear antibodies (ANA) and extractable nuclear antigens (ENA) the naturopath's role is to see the trend in decline of results and intervene to work toward homeostasis earlier rather than wait for the clinical criteria to be met where health may be severely impacted. 
  • Pathologies and testing for MAS may include but not limited to full blood count where a focus on T-cells can aid with tracking immune health. GIT and microbiome testing can assist with underlying inflammatory drivers (dysbiosis, gut permeability and dietary antigens). Mold toxicity must also be considered as an underlying environmental driver. 
  • The use of remission stories can help shift a patient’s outlook on their health and provide them with hope. Revisiting initial consult data and checking in on their current status can help to show progression. 
  • Rebuilding healthy sleep and lifestyle patterns can positively impact the immune system’s T-cells and their individual circadian rhythm, ultimately influencing the maladapted immune system in MAS patients. Lifestyle supportive aspects include time in nature (grounding, sunlight exposure). Nurturing through nature supports activation of anti-inflammatory genes, exposure to phenolic acids, essential oils, exposure to a diverse soil microbial, social interactions can all positively impact immune health. 
  • Investigations into common dietary antigens can be helpful in reducing exposure to molecular mimicry effects that can further trigger autoimmune pathways.  
  • Improving vagus nerve tone for improving gut and brain communication, which can assist with managing stress reducing the likelihood of further disease developing.  
  • Novel treatment with peptides show promise. New compelling research using peptides (regulated for use by approved practitioners in USA, but not TGA approved in Australia) to support autoimmune mechanisms is emerging.  
    • The class of peptides thymosin alpha-1, thymosin beta-4 or TB500 may alter thymus gland function where atrophy or involution are present. Thymus atrophy differs from involution. Thymus atrophy is typically due to nutrition status, hormonal levels, adrenal health. Thymic involution is typically age-related and non-reversible.  

Nutritional support for MAS 

  • Vitamin D alone may not be enough. Vitamin-A is also required for optimal vit-D binding and activity to the retinol dependant VDR, RXR receptor complex. The optimal ratio to support this mechanism is that of 10 to 1 - cod liver oil naturally contains this ratio. 
  • Medicinal mushrooms and their beta-glucan content may assist with (underlying stealth) infections 
  • Glutathione for use mid treatment modulates T1, T2 and T17 cells, supports detoxification while supporting antioxidant pathways. Begin at 5ml/d up to 20ml/d in divided doses for flare ups. 
  • Herbal support with immune modulatory, immune boosting, adaptogenic and nervines can be considered. 
  • Microbiome support with L. Paracasei LP33 and lactobacillus rhamnosus GG (LGG) shown to support T-regulatory cell function and modulate TH17. 
  • EGCG (Epigallocatechin Gallate) can also act as a dietary antioxidant support 

Resources discussed and further reading

Daniel Sipple

Website: Daniel Sipple - the Functional Naturopath

Multiple Autoimmune Syndrome

Research: Multiple autoimmune syndrome. (Maedica Bucur, 2010)


Prescribing time in nature




Lisa: Hi, and welcome to fx Medicine, where we bring you the latest in evidence-based, integrative, functional, and complementary medicine. 

FX Medicine acknowledges the traditional custodians of country throughout Australia, where we live and work, and the connections to land, sea, and community. We pay our respect to their elders, past and present, and extend that respect to all Aboriginal and Torres Strait Islander peoples today.

With us today is naturopath Daniel Sipple. Dan is passionate about the areas of autoimmune disease, gut microbiome modulation, hormone optimisation, stealth infections, immunity, and anti-ageing medicines, and he's also an avid researcher, too. Daniel has a very successful clinical practice near Mollymook on the south coast of New South Wales. And as a result, his personal health journey, combined with his clinical expertise, he has a unique ability to recognise where to begin with every individual he works with. 

Welcome to fx Medicine, Daniel.

Daniel: Thank you. Thank you for having me, Lisa. I'm excited to be here.

Lisa: Yes, I'm very excited to chat with you today. 

So, let's talk about autoimmune disease. If we look at the statistics, we know there are more than 80 different autoimmune conditions that exist in the literature. And a whopping 5% of Australians have an autoimmune disease, and that could possibly be higher because a lot of people don't know they actually have one.

Daniel: Yes.

Lisa: So I think we all know as practitioners what autoimmune disease is, but the recognition that individuals could have multiple autoimmune conditions at one time is relatively new. And the term ‘multiple autoimmune syndrome’ was only described in 1988, and basically describes the association of at least 3 autoimmune diseases in the same patient. So the research suggests that approximately 25% of patients with autoimmune diseases have a tendency to develop another autoimmune condition. So that's like a quarter of all people. 

But there's very little education around this. So I know that autoimmune is your speciality, so very excited to chat with you today about this. So can we start off... Can you tell us what are the main autoimmune conditions that you see in your clinic?

Daniel: Yeah, sure. So, Hashimoto's thyroiditis is probably the main condition that pops up in clinic. I almost feel like, at the moment, there's not one person that comes through that doesn't have autoimmunity of some type.

Lisa: Yeah.

Daniel: Obviously, I tend to lend myself and market myself to that group of patients. Hashimoto's is probably the biggest, I'd say, Lisa. And there's also a lot of patients that I see in screening them, and doing sort of more advanced blood work as you kind of do, that you detect thyroid antibodies. And these people might not necessarily have been diagnosed with Hashimoto's or Graves’ disease at that given point in time, or might not even be aware that their current symptoms is sort of linked to that pathology. But that group of clientèle is quite large too, I would say, where we say, "Oh, you know what? There's actually an autoimmune process going on against your thyroid." And they typically freak out a bit, as you'd expect.

But yeah, there's a lot of people in that camp, I find, kind of walking around with a disconnected sort of array of symptoms or seemingly disconnected. And that could be anything from fatigue to brain fog to dry skin to weight gains or low libido, etc., etc. So yeah, I mean, to answer the question, it's definitely Hashimoto's, but there's probably a large group of clientèle that have that low-level autoimmunity, but a preclinical.

Lisa: Yeah. And how frequently are you seeing patients that have multiple autoimmune conditions? So say, for example, they have the Hashi's, but do they have coeliac as well?

Daniel: Yeah. More and more frequently, as my practice grows, I would say. And it's sometimes - not to take the credit - but it's sometimes myself that happens to find the second or the third and say, "You know what, unfortunately, the autoimmune is in this sort of area of your body as well." And that could be connected tissue or joints in the case of rheumatoid, or whatever it might be. 

But I think we're just in such a good position, Lisa, as CAM practitioners to kind of go, "Well, okay, this is happening, but let's get back to the drivers here, and let's remember that it's an immune condition. Not to get pinned down on the fact that it's targeting your joints or it's targeting the brain, like in MS, or whatever it might be, but that it's a condition of the immune system." And bringing that homeostasis and balance back to the immune system is something that I'm super, super fascinated.

Lisa: Yeah. I think that's so important because definitely within allopathic medicine, there is this focus on just, say for example, if it's Hashimoto's, just the thyroid, or if it's rheumatoid arthritis, just the musculoskeletal system. But what we know is that the major problem is really with the immune system, and that's kind of where I think, as holistic practitioners, we really shine, and that's where we really need to focus. 

So how aware, then, are your clients when they come in to see you, and they've got one autoimmune disease, for example, that they could be predisposed to getting another one, or another two, or three, or four, essentially multiple autoimmune syndrome?

Daniel: Yeah. I would say quite unaware. I find a lot of people stick to their primary diagnosis, and touch wood, not everyone goes on to develop MAS, but in the folks that do, I would say that a lot of them are unaware that their lingering symptoms, even if the primary condition is sort of in remission or under control, are related back to that rogue inflammatory process. And as I mentioned earlier, for someone that can be just sore joints in the morning, headaches, fatigue, very, very vague and disconnected symptoms, but it's just in doing those more advanced sort of pathologies and running additional panels that you can say, "Okay, well, there's still a lot of inflammation." Then the question is what's triggering that? What antigens are still triggering the immune system to keep that polarisation going on with those Th17 cytokines? Which I'm sure we'll talk all about.

But that's where we play detective, and I think we're just in such a fortunate space to be able to use a combination of ancient remedies and the modern functional testing in the pathologies, and so forth, and combine the best of the two. And it's not uncommon for patients to seek a naturopathic approach with their autoimmunity, and you get into taking their story, and they say, "No one's ever asked me any of these questions before. I'm sitting here telling you this whole journey of how it unfolded, and it's only now that I'm actually realising it myself, how it's un unfolded." We're just really blessed to be in that position.

Lisa: Yeah. I think so too. I think it's really, really such a privilege to sit down with someone and be able to listen, first of all, because I think that's a really underestimated kind of tool in terms of that healing process for the client just feeling heard.

But also just getting to kind of put the whole timeline together because we know that autoimmune conditions, generally, it's not something that just happened in a week or two. They often have like a long kind of timeline where it's been initiated and kind of simmered for a while.

So, you know how we were talking about clients coming in and being predisposed to multiple autoimmune syndrome? Is that something that you educate your clients on when they come in, and they've been diagnosed with just one? Do you actually talk to them about the fact that, "Well, 25% of people actually get another, and this is kind of what we need to do to reduce," or do you just not say anything?

Daniel: To be honest, I try not to, if I'm being really honest, and that's because often they're coming in and so kind of overwhelmed with the whole concept of just having the first one. And it's not that I avoid talking about that in particular. And often, it does come in in subsequent sort of consults, particularly if there is that sort of pathology where it's still really playing out, and you can tell that the autoimmunity is very much at play. But I try and avoid the stats, so to speak, that there is a very, very high likelihood that you are going to continue to develop them.

My hunch is though, Lisa, is that if you can get to the drivers, that perhaps we can halt that process despite genetic predisposition and so forth. And obviously, as a naturopath, throwing everything at it to keep it that way. But unless it's very much warranted and they're probing, and they're very interested and asking about it, I'll usually keep that one to myself.

Lisa: So, I actually do. I do tell them. I tell my clients, I don't necessarily say it's 25%, but I do kind of give the bit of information that we know that when you have one autoimmune condition, you're much more likely to get another, but only if those underlying drivers aren't dealt with. 

Daniel: Yes.

Lisa: And I think you hit the nail on the head there, that if we kind of manage those underlying drivers, and we'll talk about what those are in a sec, then it's unlikely, hopefully, that they will get another and another. It's just generally where they're not dealing with those, I think, that we run into problems there.

Daniel: Exactly.

Lisa: So when we look at multiple autoimmune syndrome, the research suggests that we can actually group and kind of categorise certain autoimmune conditions into families, right?

Daniel: Yes. So there's three types that are brought up in the literature, I think, dating back to the '80s. And it's kind of like of the three groupings, the type two, you'd probably agree, happens to be the one that's most prominent, but I'll just spell them out. 

So type one is essentially the combination of myasthenia gravis, thymoma polymyositis, and giant cell myocarditis. So these are the ones that are probably rarer to see clinically, and we don't see a whole heap of. Whereas type two, that's anything from Sjogren's syndrome, RA, primary biliary cirrhosis, scleroderma, and autoimmune thyroid disease. So we see type two most commonly. I think a lot of practitioners hearing this would agree too. And the third type is the autoimmune thyroid disease, the myasthenia, Sjogren's, pernicious anemia, thrombocytopenia, Addison's, type one diabetes, vitiligo, and so forth. So, type two and three, I'd say, are the ones that we see the most crossover with.

Lisa: Yeah, definitely. I definitely see two and three in my clinic. So, do you think there is much recognition by Western medical science on these types?

Daniel: Despite that sort of research grouping, I don't, because I feel like the allopathic approach is very much still based on the symptom control, and that global immune suppression kind of model. I've had many conversations with different GPs and patients as well when you take their stories, where they'll sit there in front of their specialists or their GP, and say, "What about these thyroid antibodies?" And it's like, don't worry about them. It's always sort of a dead-end road. We don't know why they're there, they are there, don't get stressed about it. Just kind of disregard it.

And again, naturopathically, we're kind of looking at that going, "Well, hopefully, we can intervene." There's obviously a process happening here. We don't want to wait till it gets to that point to where you're suddenly fulfilling 8 of the 11 criteria to get a diagnosis, and then respond and react. No, we want to get at it whilst it's in its infancy and halt that. And yeah, as I said, I'm sure we'll drill into the nuts and bolts of what can drive that. But that's where I get really excited because there's just so many tools that we've got available as CAM practitioners.

Lisa: Yeah. I get excited, too, very.

So are there any tests...I mean, when you are looking at blood tests, are there things, if someone's tested positive with thyroid antibodies, for example, or rheumatoid factor, are there things on the bloods that kind of alert you to the fact, "Well, there could be more than one autoimmune condition going on here."

Daniel: Yeah, and this is where it can get a little bit tricky because often, it's a case where patients, even if they want to explore those avenues, they are often told, "Hey, there's just not any chance of that happening because I'm not bulk billing that,” and Medicare really clamping down with the GPs at the minute, which makes it sort of even more difficult. And then, the other option is that the patient pays for it themselves, which some are very, very happy to do, and others, understandably, it's not cheap either, it can be quite expensive.

So within reason, we do sort of go looking, but it's usually the ANAs and the ENAs that kind of allude the practitioner to the fact that, “Hey, there might be something above and beyond that initial diagnosis happening here.” And I've had plenty of patients where they might test positive to an ANA and then get the ENA, extractable nuclear antigen antibodies run as well. And all of those, six to eight or whatever there are, there might be two that are positive, and that you're like, "Oh, this is not looking good." But again, the specialist or the GP are kind of saying, "You're not fulfilling a criteria yet, so off you go and come back in 12 months, and we'll reassess," which is frustrating.

Lisa: Yeah. But I think what's beautiful about what we do is that we don't tend to be necessarily like condition-focused when it comes to autoimmunity. I think that's the real beauty is that we're looking at just modulating the immune system as a whole, as you said earlier. So, no matter what's come up, it's kind of the same sort of protocol. 

I often see things like for me when I'm looking at patients' blood tests, low neutrophils, low platelets, sometimes with the Grave’s picture. And for me, I've had patients that have had Grave’s disease, quite a few, that actually have those low levels of platelets, and I've kind of said, "Oh, what's going on there?" And they've been told, "Oh, well, that's just your normal," but actually, that's another autoimmune condition whereby the immune system's actually attacking those platelets causing that. And so they don't even realise, "Oh, I've got Grave’s, but I've also got this second condition going on here." Similarly, with, I think, thyroid, you might see vitiligo or alopecia, and they all just kind of go together.

So my next question, I guess, is, and I think you've kind of alluded to this already, but where do you see the place of naturopathic medicine in the management of client with multiple autoimmune syndrome?

Daniel: Yeah. So I think it's meeting the patient where they're at. That's what I always try to keep in mind when we start, in any case, with an autoimmune patient. And sometimes, it is a kind of red flag with screaming inflammation, and you just have to get the symptoms under control to bring some clarity to their health picture. And a lot of what I do is education. And I've said it on other podcasts, too, I still stick to my four patients every day. And I do that to give them that time and super, super, invested in the education side of it because I really feel like once the underlying mechanisms are explained, not on a clinical level, but a basic level to where the patient understands what's going on, then the solutions can become a lot more obvious, and they can become solutions-focused. And like you said, getting them out of the thought of, "Why is my body attacking me," and back to the basics of, "I've got immune dysfunction, and my immune system is being aggravated by usually a combination of these factors," and explore those pathologies with the patients. 

And I think that helps a whole heap, getting them out of that kind of helpless personality where it's just like, "I have no control over this. Why me? Life's over. I'll never be able to enjoy da, da, da." And instead, filling them with accounts of remission stories that's been shown in the literature to be so, so pivotal in just a patient's outlook not with only autoimmunity, but different cancers and stuff like that too.

So yeah, meeting them where they're at is very crucial, at least to start with. And then once you get some sort of balance, and you've cleaned up the diet, and you've modulated the immune system to some degree, that's where I usually go digging with the pathologies. And that that can look anything from as simple as a full blood count to a full T-cell blood work as well as underlying microbiome drivers and looking at the gut level, is there dysbiosis, is their gut permeability still driving this? What dietary antigens could there be in there that are still keeping that immune system really aggravated and so forth. 
Probably an area I didn't mention as well in the initial goings is the importance of just stress and sleep.

Lisa: Oh, favourite.

Daniel: I feel like that is just too important not to overlook. I find myself constantly going back to patients, sometimes in the third, fifths, and beyond consults beyond that saying, "What's the sleep quality like now, as opposed to what it was three or four months ago? Has it slipped? Have you been too hyper-focused on the herbs and this part of it, and sleep's really slipped again? Okay. Well, we've got to deal with that because if you're not sleeping, you're not getting on top of your inflammation."

Lisa: Yeah. I feel like sleep is really underestimated when it comes...or underutilised as a tool when it comes to managing autoimmune conditions. And we know from the research that the immune system and the T-cells, in particular, do different things at different points in the night.

Daniel: That’s right.

Lisa: Like the T-cells actually have their own circadian rhythms. So not only is getting enough sleep important but getting enough at the right times. And often with autoimmune patients, we find that they can be burning the candle at both ends and staying up past midnight, and that really does impact the state of their immune system. So we see that lack of sleep is associated with a higher risk of autoimmune diseases. We see that in shift workers as an example. So yes, sleep's a really big one. And I think coming back to what you were saying that yes, we can be doing the herbs and all that sort of stuff, but if we don't get those foundations right, then we're kind of missing the point, aren't we?

Daniel: Absolutely. The nature time, the sleep, the basics, and that can be stripping away from city life for one person, or getting away from a toxic relationship for another, getting out of the mouldy building for another. So reducing the inflammatory insults. And then once you've got them at that kind of ground level, that's where I really feel like the stage is set for the healing. And I always tell patients, "Hey, this has been possibly accruing for 25 years. It's not going to get better in a month. It could take us two years just to get things really under control, but you need to stick with it. The worst thing you can do is give up on yourself, and bounce between different therapies. You really, really have to stick with it and be diligent."

Lisa: Yeah. Consistency, I think, is really where it's at with the management of autoimmune conditions, especially multiple autoimmune conditions. It's something that's taken a long time to get to there, and it's not something that generally just goes away in a month or two. You've kind of got to be in it for the long haul. But patients that are, they are the ones that are able to kind of reduce their medication requirements and modulate their immune system where it's just that slugging away, and just being consistent. 

So can we go back to… I know you just said that you see four patients a day, right? Just so that you have adequate time for that education, which I just think is so great, and I think a lot of our listeners will really love to hear that you're spending quality time educating, which I just think is so important for this patient group.

Daniel: Yes, exactly. And I've refined it over the years in clinical practice, but I allow myself that time, not only for the consult, but it's the good half an hour, 40 minutes after that where I'm putting together notes for them. Because you can say a million and one things in the consult and it can make sense to the patient at the time. If they've got nothing to reflect upon when they go home to drive home, those really crucial points, I feel like it's kind of lost or they might only retain a portion of that. So that follow-up, I feel like is really important for them. And again, just to bring them back to the what's happening, why we think it might be happening, what we're doing about it, and this is kind of the long haul approach here.

Lisa: Love it. So let's talk about some of those underlying drivers of multiple autoimmune syndrome. Let's start with stealth infections because it's not something I focus much on at all in my clinic, but I know…

Daniel: They certainly were the impetus for my own autoimmunity amongst other things. Of course, there's never just one thing on its own. But no, it's one of those scenarios where you take a patient's case and a lot of the time, not always, they're saying sort of, "It sort of was around this time when I was super stressed, and I was working really long hours, and I got this really gnarly infection when I went overseas," or “I got diagnosed with glandular fever. And I've never been well since." Or we had like, I said earlier, mouldy apartment complex, and then you're thinking mycotoxins. So how that relates to autoimmunity is they're looking at it with research with the whole molecular mimicry model or cross reactivity.

So I'll just explain that quickly. That's this concept whereby the immune system has lost tolerance to know what's friend and foe, so it can no longer distinguish between self and non-self. But that pathogens, and there's been a number of them confirmed in the research now linked to certain conditions which are going to share similar sort of peptide sequences in their DNA. And the immune system is kind of surveilling them, and sampling that, but cross-reacting with our own tissue because it looks almost identical to the same sequence. And so, for the case of thyroid disease, for example, H. pylori is one that's very well known. Yersinia enterocolitica, that's a gut bug, that’s another one that's quite linked in addition to the good old Epstein-Barr virus. And that research with EBV, in particular, goes back decades now with that cross reactivity model.

And I'm sure there's heaps out there that haven't been looked at that we also are encountering. At the end of the day, though, it does come back to why does the immune system become dysfunctional though? 

Lisa: Yes.

Daniel: Because we know with EBV in particular, 90% of the world's population has that, but not 90% then go on to develop autoimmunity. So there's obviously nuances underneath that, such as the thymus, for example, which I'll talk about, and how the integrity of that interplays with how pronounced that person's immune response is or how weak it is. What are the genetic levels, are there SNPs and different polymorphisms in the way these people respond to certain pathogen antigens, and so forth.

So that's a big part of it, that cross-reactivity. And we see that carry over also to dietary antigens. So again, that same concept where protein sequences from, say, casein from dairy, or gluten from wheat and oat and barley, have that cross-reactivity with different tissue organs. And coeliac disease is the most well-known with being an established link between gluten and autoimmunity, and that being the very much prominent trigger there. But I do see the dietary aspect being kind of an encourager for those people that are predisposed, and that's via that sort of pathway with gut permeability. 

So if people have the genetics for autoimmunity, and all of the things are aligning to encourage this disease process, and they're eating a lot of gluten and dairy with a leaky gut or an impaired gut barrier, do these things encourage the autoimmunity to eventually develop through that loss of tolerance? And therefore the immune system's starting to attack things that it shouldn't.

Lisa: Yeah, definitely. So many people feel, obviously, coeliacs have got to take it out, but there's research with Hashi's, there's research with type one diabetes reducing that autoimmune response when they remove gluten. 

You’ve talked a little bit about stress. What about stress and hormones and things like that? How much of an importance do you place on those in your clinic? 

Daniel: Yeah. Huge. Absolutely huge. And that's where you've got to play detective, Lisa. So if you've taken out the dietary antigens and the autoantibodies are still quite high, and it's been a considerable amount of time, you've tested with gut permeability and it's come back clear, you can kind of rule that out and say, "All right, well, perhaps in your case, your individual case, gluten or the dietary antigens aren't such a prominent trigger, we have to move over and look into other areas such as stealth infections." Or yeah, like you said, psychological stress. Vagus nerve dysregulation is a huge one and one that I'm getting more appreciation for over time.

Lisa: Can you tell us a little bit more about the vagus nerve dysregulation?

Daniel: Yeah, sure. So the good old sort of link between the gut and the brain, that access being a two-way highway, as they say. So signals coming from the gut microbiome up through those nerves to the brain, and communicating what's happening down there and vice versa. And the regulation, I suppose, I think you kind of relate to it like a muscle, and if it's got good tone, and good posture, and good communication, then we shouldn't see symptoms develop. 

If the vagus nerve, for whatever reason, whether it's infections or prolonged stress, or whatever it might be, start to lead to a dysregulated vagus nerve, then we've impaired that communication between the gut and the brain. And typically, that can lead to constipation because the nerve just becomes too relaxed, essentially. But I have a feeling that it probably does play a role in the opposite end of the spectrum with diarrhoea and those sort of IBS-D presentations as well. So, I think bringing it back to regulation is the key there. And there's good research on different devices that they've used to simulate the vagus nerve to strengthen it, as well as at-home exercises like gargling, singing, and humming, and so forth.

Lisa: Oh, yes. Humming. I've done that before. 

Okay. So it seems like we need to really focus, we know, on modulating the immune system as a whole in someone that has multiple autoimmune conditions, rather than just focusing on one system. What are your favourite ways to modulate the immune system?

Daniel: Great question. Probably just starting by defining what it is, and obviously, a lot of the listeners will know already, but those compounds, whether it be herbal, or probiotic, or peptide, or whatever it might be, that have the ability to raise the immune system where it's kind of defective and exhausted, and to reduce it where it's overexaggerated such as the case in allergy or autoimmunity. So, herbals are probably my favourite, to answer your question. And there's lots that I'm sure you and I kind of both would share, do a great job of that, feverfew, hemidesmus, curcumin, all the basics. Medicinal mushrooms. I've always been a big fan of cordyceps in particular.
But I am looking at more novel therapies at the minute, and peptides are sort of an area that I've done some self-experimentation with my own autoimmunity, and Guinea pigs myself there. But peptides, I feel like at that kind of bridge between naturopathic medicine and pharmaceutical, they're somewhere in between. A lot of them are scheduled and not available to us here in Australia. Overseas, however, they're sort of initially discovered in Europe, and there's a lot of European research sort of dating back to the '70s and '80s where they were initially very popular with different conditions.

But in terms of the immunomodulator realm with peptides, we're really looking at the thymus peptides. And if I back up a little bit, just to explain the thymus is that sort of glimpse, it's behind the breast, and after the age of 10 to 15, just sort of atrophies over time very, very slowly, and correlates with age essentially. So, I guess you could sort of argue with centenarians and folks that do live to a very long age that they probably do have less of an accelerated thymus atrophy or thymus involution. So as a Naturopath I'm really fascinated by that, and I'm looking at anything as in terms of what compounds can delay that process, or bring back some strength to that thymus because that's the one that makes T-cells.

Lisa: That's what I was thinking. Yeah. That's the gland that spits out the T-cells.

Daniel: Exactly. So, anything that I guess affects that, whether that be self-infections, stress, trauma, and so forth, all the things we've kind of talked about, toxins, anything that's stressed that thymus and accelerated that thymus atrophy, theoretically raises the risk of autoimmunity, and maybe some other conditions too related to the immune system. But coming back to the peptides, the thymus that's a kind of...

Lisa: Peptides.

Daniel: My brain's sort of going in eight directions at the minute. But yeah, they're the class of peptides that I think are very specific in the conversation of autoimmunity. So there's thymosin alpha-1, thymosin beta-4 or TB500, and these are peptides that are either administered sort of orally or injected subcutaneously. There's not a whole heap of research, but the research that there is in animal models and human models is really promising. So I'm sure we'll see in the next decade or two that area really explode and functional medicine in the States at the moment, because there's a lot of areas where peptide use is cleared by the FDA is showing some really promising results in the fields of autoimmunity, but as well as in things like stealth infections and chronic inflammatory response syndrome, and immune suppression.

So I think anything that sort of interplays with that thymus may have a really promising outlook on how that lends to autoimmunity because if those regulatory T-cells become dysfunctional, which they do, we know that happens in autoimmunity, then we do set the scene for autoimmunity because there's a loss of that tolerance, and there's no troops and T-cells, the regulatory cells, they're the kind of troops that say, "Hey, everyone, calm down and chill out, and let's get balanced, and stop responding over there, and prevent that hyper-polarisation.” So if there does become peptides available for us to bring that clarity and balance back to the immune system, then that's really promising for autoimmunity.

Lisa: Yeah. I think we will see something along those lines because I was watching a video actually of a researcher from UTS, the University of Technology in Sydney, and she's researching a specific peptide, actually derived from the liver fluke, so a helminth, and they were giving it to animals who had multiple sclerosis, which, you know, has an autoimmune component to it.

Daniel: Yes. I do remember hearing that. Yeah.

Lisa: Yeah. So they actually modulated the immune system in the animals with MS, and the researchers were actually looking for funding to then do some studies in humans. So I think peptides probably will become more of a thing here in Australia once we've got that human research to back it up.

Daniel: Yeah, 100%. And that's super, super promising. And there's a lot at the minute that aren't sort of scheduled that are, I'd say, available, and they're more of the oral sort of class of peptides, more gut-specific such as BPC-157, which is body protective complex 157. And a more novel one, which has got me quite excited, called the larazotide acetate. And that one, they call it the coeliac peptide. I believe that one's upon its way to being approved by the FDA just as a commonplace sort of treatment once a coeliac disease diagnosis has been made. And the way it works is via antagonising zonulin. So zonulin is that protein that opens up the tight junctions and the velcro, that line of the gut. So preventing that from happening, I suppose you could argue it is more allopathic, but hey, why not combine the best of both of those worlds?

Lisa: Oh, look, I think that's really, really important too. It doesn't have to be one or the other. It can be both.

Daniel: No.

Lisa: So I think it's really important for us to be supporting our patients with both where it's required, and I think sometimes, or quite a lot of the time, that results in better patient outcomes.

Any other therapies? So, we've talked a bit about the herbss, we've talked about the peptides. What about nutrients? I don't know if you're still a fan of vitamin D. Tell me, are you? It's controversial.

Daniel: Vitamin D is controversial. Yeah. No, the long story short, I sort of rarely prescribe vitamin D in unison anymore. But that does not sort of mean that I don't recognise the amazing literature we have on how it interplays with the immune system. But what I often do with patients is educate them that it's not all about vitamin D, and that vitamin D has to act in concert and synergy with vitamin A or retinol, which is the animal form. And it's all about the ratio. So to activate 1 unit of vitamin D, you need 10 units of retinol for that to work. And that's mediated by that sort of RXR receptor. And the vitamin D receptor itself actually needs retinol to work also. So it's a symphony of those nutrients. 

I'm a big fan of cod liver oil because it is that 10-to-1 ratio of retinol to D, and you get the beneficial omega-3 fatty acid compounds in there too, which helps support the inflammatory response. So a lot of my autoimmune patients are getting cod liver oil. And A and D, those fat-soluble nutrients, are very well researched with restoring T regulatory cell function. So you get a lot out of that one sort of source or medicine. 

But apart from that, beta-glucans from medicinal mushroom extracts, great. If you've got that autoimmune case where there is still underlying stealth infections, or even really overt infections. I think it's important to say you can have autoimmunity going on as well as someone who has a really poor immune response, and gets a lot of those recurrent infections. 

In addition to that glutathione, I'm huge, huge fan of, and there's probably not one patient these days that doesn't get glutathione at some stage in their journey with me, because it's just such a strong T1, T2, T17 modulator.

Lisa: Oh, my gosh.

Daniel: And you also get a lot of the toxin release and movement of toxins, and bile, and liver support through that pathway too.

Lisa: Can I ask what sort of dose you do there?

Daniel: Yeah. So, I usually start with 5 mills per day. Once they're at a certain stage, mind you, I never go in with something like glutathione or anything too detoxy, straight out of the gates. And I've had some patients, particularly if they feel like they're coming down with something, or they're about to have a flare go up to sort of 20 mill day in divided doses with good results.

Lisa: I've never, never used it for autoimmunity. Okay. Awesome. Excellent.

Daniel: Apart from that, I'm a big fan of, as I mentioned earlier, the herbals, so astragalus, rehmannia, feverfew, the herbals are super, super key. And again, all my patients get a herbal tonic. That doesn't look identical. I’ll always customise it to the patient. And the beauty of that is you can throw the nervines in there if there is a lot of stress or whatever it might be. 

And the probiotics as well. So L. paracasei LP33, and lactobacillus rhamnosus GG have quite good literature on their ability to expand Treg cell function and downregulate TH17 pathways. And then there's more sort of compounds from the dietary aspects which I try and really push as well. So, EGCG from green tea, for example, great inhibitor of reactive oxygen species and silicon 17.

And I'm using a lot of berberine at the minute because there's a particular phytosime or phytosome constituent, I suppose you call it, that does get into areas above and beyond just the gut. So this is great for your patient whose autoimmune but also might have a lot of insulin resistance, and those sort of infections that you're suspecting that are hiding in different nooks and crannies in the body. I think that any medicine that we can get into those areas where we deeply know it's not just going through the gut are really promising, too. And there's good anti-EBV literature with berberine in particular as well.

Lisa: Oh, great. Excellent. Okay. So there's loads of good tips there with regards to therapeutics. Now, what about lifestyle? Because definitely, the more I'm in practice, the more clients I see with autoimmune kind of stuff going on, the more emphasis I'm placing on lifestyle strategies and mindset changes. 

So how important do you think...like, I place a lot of importance with regards to that in my clinic, but how important do you find those factors with assisting with modulating the immune system in your clients?

Daniel: Put it this way, I think if someone was still working under fluorescent lights in a super stressful job, and having that major deficit disorder, that MDD, I don't think you'd get anywhere with any of these compounds, as amazing as they all are. And if you stack them all up, if the patient was still not exercising, the healthy circadian rhythm, grounding, sunlight, nature time, separation from people, and getting their own time, and putting all those things into place, I don't think they'd get far with it. 

So it's heavily, heavily crucial. And there was an article done, a literature article that came out about just what it is from nature that has those immune modulatory effects. And I can't remember how they did it exactly, but they essentially took people with a lot of known, diagnosed inflammatory disorders and exposed them to different compounds in nature and so forth, and studied their immune system and their immune response.

And what they saw was that a lot of the anti-inflammatory pathways kicked in, and a lot of the anti-inflammatory genes kicked in, and a lot of the pro-inflammatory mediators were sort of attenuated, and they put a lot of it down to what's inhaled, and as well as what's touched. So they were talking about the phenolic acids from different plant compounds, and essential oils that are sort of inhaled through, just like a nature walk, for example. They also talked about the contact with the soil and what's happening at the microbial level with the gut microbiome. And again, we've known that for a long time with that disconnected microbiome which happens from a variety of different methods, and how much that impacts things like allergies, and heightens the risk for autoimmunity later on in life and things like that.

So I suppose it's a bit of a no-brainer that there's definitely something to the nature exposure, and the more we get away from that as a civilised society, perhaps the higher the chances, unfortunately, that we will see more autoimmune syndromes present. But in getting back to nature, conversely, do we then see, hopefully, that sort of reversal and that remittance from all that. So yeah, it's really exciting.

Lisa: Yeah. I've seen in Canada, they have a thing called park prescriptions where going out in green space is actually part of the prescriptive advice. 

One last thing with regards to connection and fun. How important do you think that is? Because I think when someone's diagnosed with an autoimmune condition or multiple, there's this real focus, I mean, as you said, they're overwhelmed, they're scared, but also there's this real focus on, “Okay, we've got to take out the gluten, and we've got to do this, and we've got to do that.” And I think you can really kind of put people into this sympathetic overdrive that they're kind of already in. 

How important is that fun and connection? Because I think it's something people with autoimmune conditions often kind of miss.

Daniel: Well, put it this way. When I got away from all that, everything that I anticipated happening was quite the opposite. I went my way backwards. Why? Because I got disconnected from all the things that previously brought me joy and balance to life. And yeah, as I said earlier, I was experimenting with a lot of things that on paper looked amazing, but the lifestyle, the connection, the social connections, the activities, and the hobbies that bring you joy, that separate you from all this, it's really good to know about all this, but you have to get away from it as well. And you have to feel like you are not living this alienated, excluded life.

And for me personally, with the coeliac disease being diagnosed, that's exactly what I then suddenly sort of felt and went from being someone who never experienced anything like that in my life to then having all this alienation and social disconnection. And that, I think, only drives that inflammation and that sympathetic nervous system response, like you say. 

So it's not only something that you should do, it's vital as part of the prescription. So I recommend patients 20 to 25 minutes per day. It's part of the prescription. It's like, take your herbs, do the diet, take this at this time, and insert in that prescription 20 to 25 minutes a day of a nature walk, or getting to the ocean, or whatever it might be. It's crucial, non-negotiable.

Lisa: Oh, lovely, lovely, lovely. Okay. Thank you so much for joining us. I feel like you've provided us with so much excellent information to implement.

Daniel: Thank you.

Lisa: Oh, pleasure. Key points that I have taken away from today would be a lot of therapeutics. I love the idea of the cod liver oil, the D in combination with the vitamin A for that T-cell regulatory function, but probably also for the gut. It would have that effect there too. The peptides, I think are really exciting, emerging area of research for us to kind of know more about. And then the glutathione, I think is very, very exciting for modulating the immune system of particularly those T1, T2, and T17 cells. Love, love, love all of that. Thank you.

Daniel: Pleasure. Thank you, Lisa. It's been fun.

Lisa: Thank you, everyone, for listening today. Don't forget that you can find all the show notes, transcripts, and other resources from today's episode on the FX Medicine website. I'm Lisa Costa-Bir, and thanks for joining us. We'll see you next time.


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