Human leukocyte antigens (HLAs) can be found on the surface of most cells of the body. They are a method of categorising one's 'tissue type' and they play a role in determining a person's immune response to foreign substances. Most notably, they are used to establish donor matching for organ transplants.
Today, Dr Mark Donohoe takes us through some of the emerging ways HLAs can reveal a person's predisposition to certain adverse health outcomes, such as mould toxicity, thyroiditis, type 1 diabetes, psoriasis and other autoimmune issues.
Covered in this episode
[00:54] Welcome back Mark Donohoe
[01:26] What is Human Leukocyte Antigen (HLA)
[05:34] The changing clinical significance of HLA
[08:36] Immunology and reproduction
[10:22] Genetic diversity
[13:21] HLA subtypes: mould and mycotoxins
[18:50] HLA inheritance
[20:50] Clinical value in screening
[40:32] Diseases/Disorders relevant to HLA
[46:34] Medicine interfering in evolution
[49:56] HLA and thyroid disorders
[54:36] Psoriasis and delayed drug reactions
[1:01:14] Determining when to screen for HLA?
[1:03:45] Final summary and resources
Andrew: This is FX Medicine, and I'm Andrew Whitfield-Cook. Joining me once again in the studio today, is Dr. Mark Donohoe, an integrative GP of great renown, and somebody who I'm very proud to call a friend of mine. Today, we're going to be discussing something quite technical and something that's of great interest to me although I'm on the very low stages of a steep learning curve, and that's human leukocyte antigen typing, HLA.
So welcome, Mark Donohoe, to FX Medicine.
Mark: My pleasure to be here as usual.
Mark: HLA is just a fancy way of saying tissue typing. We have different tissue types, and people know it primarily from the area of organ transplants. That you match the HLAs, and the tighter the match of the HLA characteristics, the better the likelihood that your organ transplantation is going to take effect. And these are little markers that cells put out around the body, on the surface of the cells, and they’re largely to say, "Hey, I'm me. Normal. Let me alone." And it's a marker in part to the immune system to say, "Don't hurt me, I'm friend." It's one of the ways that our body differentiates invaders from what we grow ourselves, what we get from our own DNA.
Andrew: Are they on all cells?
Mark: They're not expressed as much as I understand it on the red cells, but the reason that we use the leukocytes, the white cells is they're easily available, they're standard cells. You can get them from a blood test harvest them, and get a good look at them. But they are expressed on the surface of all cells because as the immune system wanders around the place it needs to see these HLA markers to say, "No, leave you alone. Don't touch there. Leave this alone." And so they have a tight interaction with our immunology, and when it comes to organ transplant that's critical.
You put the organ of an entirely mismatched donor in, then your life is miserable because the body will say, "That's a foreign cellular material. That looks like not me," and the fight goes on. And that's why we use Prednisone, immunosuppressants for kidney transplants, for any kind of a transplant. The best outcome is an identical twin, where you can transplant the organs..., I mean, it's not at a whim because you've got to have one of the others as a donor, but it does leave open identical twins giving a donor kidney, for example, if one has a problem.
But for everybody else there's typically a mismatch, and that mismatch of the HLAs is what we understand with organ rejection and how hard we've got to work to get around that.
At a deeper level though, the HLAs also have got signalling that allows us to say, "Well, epidemiologically, people with say an HLA-B27 have a much, much higher risk of ankylosing spondylitis." And so as doctors there's a practical value there. That we see a person with lower back pain, bit of destruction of the sacrum and the lumbar area of the spine. And the question is, "Could this be a disease called ankylosing spondylitis?" And the vast majority have a very specific HLA-B27 positive.
Now, it's important to say HLA-B27 doesn't cause ankylosing spondylitis. But if you don't have that gene, it's very unlikely to be ankylosing spondylitis. And so the way of thinking about these is a bit the way we think about autoimmunity. Lots of these HLA types predispose to a potential something. It can be good or it can bad, heightened immune defences, depressed immune defences. There are a whole range of these HLAs being decoded as we speak. They're neither good nor bad. The reason I say that is evolution has preserved these and so the variety of the different HLAs provides a diversity at a level which allows us to defend ourselves well, leave ourselves alone, not get autoimmune disease. But what we do pick up is these different HLAs, the DQ, the DRB1s that predispose to say, autoimmune disease.
Andrew: So first off before we start and go any further, I know that later on in this podcast, you're going be mentioning Bramley apples.
Mark: I am. I am.
Andrew: And I’m going be talking about the Hadza tribe.
Mark: The genes that move us towards stewed apples.
Andrew: But it's something that really interests me because my first knowledge of human leukocyte antigen was, as you say, with transplant rejection and rheumatoid arthritis.
Andrew: As you say, it's not in and of itself, but when it reacts to something, and that's where, particularly with ankylosing spondylitis there's a few others, that we seem to be reacting to bugs.
Mark: Yep. And so the bugs don't make the HLA. So, if you like...
Mark: ...the tissue typing is defined by our genetics, and the expression otherwise of those genes. So the HLA, the DQ group, the DR group. These are ways of looking for activation markers. So when we do, for example, we do flow cytometry, we're looking at the activity of the immune system. The DR marker is an activation marker. So it allows us to distinguish okay, those that express a high percentage of DR-positive cells, those are the ones that have got a job to do, they are out doing something. So we have a practical use for determining the expression of immune cells by the expression of the DR activations. So DR-positive cells have got a job to do. The DR-negative cells haven't yet got a job to do.
Most B lymphocytes are out there because they've got a job to do, but most of the T lymphocytes are inert just waiting for activity to happen. So there are practical ways in which the expression of these tissue types allows us to make an assessment of the activity. What we're more interested in though, I think now is as we're breaking down what subtypes of the DRB1, for example, and DQ genes. We know the DQ genes has, you know, Alessio Fasano talked to us about the DQ2 and the DQ8, are basically the sub-groups of the population who have the potential to react and cause coeliac disease. That's why those kind of tissue markers became of great significance.
Now, of all the people that carry the DQ2 or DQ8 genes, only 10% get coeliac disease.
Andrew: Yeah, so this is the...
Mark: Yeah. So it's a predisposition, but most people still don't get coeliac disease. However, here's the trick. Of the people who carry those DQ2 or DQ8 genes and eat gluten, an enormous proportion, probably greater than 50% get thyroiditis. Or they get some other...polycystic ovarian syndrome, Type 2 diabetes. There is a DQ2 and DQ8 pre-disposition to see gluten, or to see at least the prolamines of wheat, rye and barley especially, to see those as an activating agent. And what happens is the immune system starts to scatter-gun. It picks a fight with the glutens at a very, very low level, but because we eat the stuff day in, day out, year in, year out. Eventually, it shows up as activating an autoimmune-type of response.
So we do know coeliac disease was thought to be a little bit like you put gluten in and it just, like gravel, just tears the gut apart. It's not that. It's an autoimmune disease of the gastro-intestinal tract. The gluten hits, the immune system's activated, the destruction of the microvilli there is the outcome.
Andrew: And it seems that of a lot of this is... Obviously, it's a leukocyte antigen. But it seems like a lot of the diseases that HLA is associated with, have got to do with the immune system, with sort of, you know infections or autoimmunity, graft rejection.
So if I would go through a list, it's like infectious disease, graft rejection, autoimmunity, cancer, again there's an immune hypothesis with that. The one that didn't gel with me with the immune system unless it was, I guess, to do with infertility, was mate selection. But it's an interesting thing, I've never heard of that before.
Mark: Well, mate selection is arguably the most important thing, choosing diversity of genetics. The ability to sniff out your mate, or select on some basis, the expression of the HLA is an important component. The wider that diversity, the more resilience you get in the offspring of a population.
So you can say biology's primary interest is always the next generation. It really doesn't give a shit about your thyroid, or my adrenal glands, or anything else. If we get to mating age, and we choose mates wisely, the diversity of the sperm and ovum and the genetic interaction, creates a broader diversity for the next generation and the prolongation of the duration of that species hanging around.
So you can almost make the argument, immunology serves fertility. You can, if you like, make the argument that everything serves fertility. If you do not procreate, you're not around to have your HLAs measured. And so there is an evolutionary biology component to this. But as in all experiments of nature, nature values diversity even if it's not good for the individual, but if it's good for the group...
Andrew: Population, yeah.
Mark: ...the species, or the population. And so you do run into problems. And so a very specific one at the moment we could say is omega-3s. There was roughly 1:1, 3:1 ratio in the past, and the genetics of those people who can metabolise the omega-3s produce better brains, diminish inflammation, repair after inflammation. People with that propensity tended to do fine when the omega-3s were available for those purposes. As the omega-6, omega-3 ratio has changed, now it's 10:1 or 20:1 in favour of omega-6, life now favours those that can manage the inflammation.
And if you go back in history what I'm saying is doctors in the past wanted people to fight infections. Now, what we want them to do is stop fighting themselves, stop the arthritis, stop the autoimmune disease, stop the Alzheimer's. So we've moved from a profession that within 100 years has gone from not really a problem with autoimmunity and inflammation, getting rid of infections was the job. We kind of won a battle against that. Primarily, you know, nutrition, lifestyle and the like, now what we've gotta do is turn off the inflammatory predisposition so now the people that could fight well are the survivors.
What we now have to do is say, "Well, we've got a consequence of that” and that is arthritis, neuro-degenerative disease, these other diseases, and the tools that won the infection battle are not the tools that are gonna win this next battle. So we've done a bit of selection. The survivors who... - we metabolise lactose on the whole pretty well. Most of the world does not.
Andrew: Caucasians, yeah.
Mark: Yeah. And so Caucasians, because they were able to metabolise lactose, didn't get diarrhoea when they drank milk. They survived winters better than they would have otherwise survived. So selection is cruel. It's not that we developed lactase. It's that the people who didn't have lactase didn't make it through the harsh winters. They didn't make it through because they had diarrhoea.
Andrew: When they immigrated out of the temperate zone, yeah
Mark: Yeah. And so they then ended up with a different kind of selection process. We are selected fairly highly for our ability to clear lactose. And the races that don't do that, did not even need to have that process going on.
So look, this is a long way of coming back to evolution selects. For breadth and width and diversity. HLA is part of that selection of diversity. We do know that in a good world mates select each other to maximise genetic diversity, and that's a good thing. Part of that selection process is HLA expression, and it may go all the way down to neurological selection. A woman smelling out a male, as long as there's no perfume, there's no after-shaves, no Brute 33s or any of those things in the way.
Andrew: What's wrong with Brute 33?
Mark: Nothing's particularly wrong with it, except it covers up all the other smells. And so the ability to smell out a mate, I'm pretty sure that's disappeared in the past. I think that perfumes are probably a way of getting mate selection under entirely different circumstances.
Having said all of that, we now have a problem that some of the HLA subgroups are particularly vicious in fighting certain things. And in that fight, turning-up as an autoimmune or other chronic inflammatory process. And this is the work done by Ritchie Shoemaker. I think spectacularly good, early work, still what I would say is not really ready for prime time because there's still a lot of work to be done.
What he and his group have done in the past decade is take a look at those HLA-DRB1, which is one particular subgroup, and the DQ, and have a look at the variations and say, "What do these... Or how are these attached to susceptibility?" It arose through the mould mycotoxin that the turning-up of a very specific set of subgroups of the HLA had people who were in mould-affected buildings, incredibly sick. Whereas others in that building without those same predispositions, without that same HLA-DRB1 typing, not so sick.
This comes down to medicine's difficulty in dealing with outliers. If we don't have a concept of it, the disease doesn't exist. Allergy didn't exist until we knew IgE, mast cells, the release of histamine, once it all made sense, allergy became a ‘thing’ and medicine owned the term. And we can say we can now go after allergy.
What we have is these other conditions like mould reactivity, Lyme disease, chronic infections, chronic staphylococcal disease. And the problem is only a small proportion of people get it. We in medicine have a tendency to say, "If it's not like most people, there's a guy called a psychiatrist over here who will help you out of your problem."
And so we've had a psychiatric management of people who have unusual presentations that's considered more a fearful response. Now we're putting the pieces together to say, "No, no, no. That's genetic diversity coming back to identify situations which are hazardous to that host's health and life." What does the body do? It mounts its defences, it gives a negative sensation, people get away from it, and you can make a case that the mould sensitive people in a community were good at getting people out of caves where there was toxic moulds that would injure people.
That these sensitivities are not negatives as far as a community or survival of a species goes. These are just like early warning radar systems. There are some with built-in, very intense radars for one thing, that individual gets sick, maybe their children get sick, but the community paying attention to it learns to keep away from those problems.
Andrew: As with any one question that I ask you, I've now got five...
Andrew: ...at least.
Mark: This is like nuclear fiction. We're developing news.
Andrew: So firstly, what you mentioned about the work with Ritchie Shoemaker and the DRQ, DRB...
Mark: DRB1 to DQ.
Andrew: DRB1 to DQ. Sure. So I think Nicole Bijlsma alluded to this in her podcast with toxic building syndrome. You also mentioned about histamine and the sort of allergic type reactions with IgE. And HLA is part of the major histocompatibility complex, the MHC. Is that right?
Mark: That's correct.
Andrew: So HLA is part of that, but it's more to do with autoimmunity in general, and that's a very general... Or reacting against self, how's that? Rather than reacting against something foreign?
Mark: No, I don't think that's right. I think the...
Andrew: No, I think not.
Mark: I think that the HLA part is receptors for hazard. And that there is a... you know, certain people differ greatly in their ability to identify hazard. And so if you like, it's an in-built radar to say, "These are the potential hazards." A person with an HLA-DRB1, DQ combination that's terrible for moulds. Staying in a mould-infested environment is going to work out very badly for them. And part of the reason it works out badly is what Ritchie Shoemaker has termed the CIRS, or chronic inflammatory response system. That it's in fact, an over responsiveness of an immune system to a threat that really shouldn't be all that great to our health, but where the person is finally tuned to that particular toxin, the mycotoxins being a good example.
The other classic group at the moment is being debated vigorously here in Australia is the Lyme disease group. Not everybody exposed to Borrelia is going to develop Lyme disease in the classic sense, and certainly not the neuroborreliosis or the chronic Lyme disease. But subgroups of those particular...
Andrew: And Lyme is borrelia burgdorferi.
Andrew: We might have a different species of that, which is not Lyme, it's Lyme-like-ish.
Mark: Yeah, well we do have one identified now which is a Borrelia close species from the echidna.
Andrew: Echidna, yeah.
Mark: There's not enough echidnas to make sense.
Andrew: And yet it doesn't exist, which I think is hilarious.
Andrew: It doesn't exist but it does.
Mark: I mean, we go back to my problem that I have the binary world of it's everywhere, it's nowhere. Neither side is right there. But there is definitely groups of bacterial organisms that can trigger these responses. And what Ritchie Shoemaker, who was a Lyme doctor, along the way, his broadening out was, you know, moulds, Lyme disease, staphylococci. There's a whole range of different insults out there that should not cause the damage we see in some individuals. People with this DRB1 and DQ combinations are showing up to have real problems. What is the problem?
Andrew: So it's when they have the combinations.
Andrew: Not just one or the other.
Mark: No. So it typically is a match of DRB1 of a particular type. So you have a kind of one column and then you have a look-up table...
Andrew: allele, yeah.
Mark: ...which is here's your DRB1 matched with an innocuous DQ gene, that's not a problem. However, you mate with somebody else who's got a DQ gene which is a mismatch. And suddenly those children are highly mould reactive or have the potential to become that. So it's a combination of...
Andrew: And this is why not everybody in the house gets sick.
Mark: That's right.
Mark: That's right. And, you know...
Andrew: Is it always the children then?
Mark: No, it's not always the children. So it also dilutes out that way. One parent typically, you know, when I see them, a mother or a father is particularly sick in a mould affected home, and I'm thinking of hundreds of examples of this. Tree falls on the house, there's water ingress, and the mother becomes exceptionally sick, and the father doesn't even know that there's a problem. As far as anyone's concerned, it's just a bit of a mouldy smell in the background. The children have a high variability of the combination of those two parents, and so the matching up of the genes it's very rarely that you get all the inheritance on the DRB1, DQ from the one parent.
So it can dilute out on the next generation. But you can also have two parents that both feel fine, but the mismatch, that one of them combines one allele of the DRB1 and the other one provides the mismatched other, and suddenly the child is exceptionally sick. And those children present differently. They may present as say, autistic or learning disabilities. They tend to get more neurological issues early on in life. Auto-immunity is largely time, plus inflammation leads to something which is obvious in that inflammatory response, and kids you know, there are exceptions, the juvenile rheumatoids and things do happen early, but kids, it plays out much more in the brain. The developing nervous system is highly susceptible there.
Andrew: So I have to ask like, when they're dealing with a lot of the disorders - diseases, whether it be cutaneous, whether it be one of the arthralgias…. graft rejections going to be something totally and utterly medical. What types of human leukocyte antigen are going to be relevant for natural health practitioners? And, is there a use of screening for this, or is it just after the fact we find out, "Oh, yes. That's why."
Mark: Well, taking the last question first. Screening is useful especially where parents who have been unwell are having kids and you identify for the parent after the event. So you tend to only test, in fact, Medicare in Australia as you know, pays for disease. It does not pay for prevention. It will not do these tests, and so you're on your own if you want to look for these. But after a parent has say, swollen joints, and you find that there is a mismatch and the mouldy work environment or home environment is the cause, then it is really worthwhile having a look at the kids. It's a very, very simple test. And the kids that have the highest...
Andrew: Cheap or expensive?
Mark: Well, it's paid for on Medicare in one sense because these are tests which are done for purposes to look at inflammation. So a doctor can organise these tests with the particular laboratories and Medicare covers the bill, but it does not cover prevention.
Andrew: Screening, no.
Mark: So it is really important to differentiate that...
Andrew: You've got to have a clinical suspicion.
Mark: ...the test done for the mom or the dad who is sick is a relevant test because it would change clinical outcomes. Prevention screening is on our own. We haven't...
Andrew: Yeah. And natural health practitioners aren't covered by Medicare with this regard.
Mark: That's true.
Andrew: So...? Cost for them?
Mark: Yeah, they may as well order the test, but the test cost is in the order of around about $80 to $100.
Mark: So you can do that part of the Shoemaker CIRS categorising, the look-up table is fairly straightforward. And a lot of the time, as you would expect, we're on the wrong path. It's not to do with the genetics of mould exposure, it's the fact that it's fusarium or it's a highly toxic mould, and it just is poisonous and it's poisonous for everyone in the family. So it's not that this is the universal answer. It's that this allows us to understand heightened susceptibilities a little bit the same as when doctors do IgE testing, allergy testing, they're looking for an antibody.
If it's over 100 we say, "Well, that's probably allergy that's going to be significant," and if it's 10 we say, "That's probably not allergy." So the same with the CIRS, the DRB1 and DQ genes, the little look-up table just says, "You're in a category which places you at high risk of an abnormal exposure to mould mycotoxin, to Borrelia, to staphylococci. And so you would pay much more attention for that individual's minimising of that particular risk to themselves. It's like a trigger, you know, the gun is loaded with the HLA. It does not mean the gun fires, but the trigger is the exposure to the mould, to the staph, to the gluten. And those triggers are really, really important. You stop pulling the trigger the gun goes off less and less and less, and then people get a chance to recover.
So the value of it in my practice is, and I was skeptical, when Ritchie came over it was only a year-and-a-bit ago. I was skeptical because I thought, "No, that's too simplistic." But it's not simplistic, it's just saying, "Here are these...a framework for thinking about susceptibilities." It's not, you know, you get rheumatoid if you have rheumatoid factor. It's nothing like that. Most people with rheumatoid factor never get rheumatoid disease. There are other factors, but this identifies, okay, look for moulds in this kind of person. Look for chronic bacterial infections in this kind of person. Swab the nose for a particular type of staphylococcus in this group. And so that way of thinking about it, I think is utterly valuable now.
I've only done this for a year-and-a-bit, and over and over, the mysterious "Why would you get sick?" to a person comes back as, "Oh, that's why you get sick. What we've got to do is now remove that."
Andrew: So again, it seems like it's after-the-fact. What's interesting to me about, is the reaction with bugs. And I know that we're going to get back into this, I get it, right? But something spurred my interest when I heard Professor Alan Ebringer talk from UK, a lovely, lovely, gentleman. And his calling, if you like, is the cross-reactivity with Klebsiella and HLA-B27 causing ankylosing spondylitis. Likewise, there seems to be, or he professes that there's a cross-reactivity with Proteus species and rheumatoid arthritis, which I thought was really interesting.
Now, when I looked into it, it seems to be more than...there's more bugs that are attributed to rheumatoid arthritis than just Klebsiella...than just Proteus, forgive me. And I haven't really looked into what bugs might be associated with ankylosing spondylitis. But I thought it's really interesting that there seems to be this bug required for a...and I'm gonna over-simplify this I know, but a self versus danger reactivity. My question here is, is this another one of these hygiene diseases?
Mark: Yeah. Good question.
Andrew: Is it because we've cleaned up so much that we don't have parasites because we don't like them because they're quote, unquote, "bad." We want to eradicate them wherever we can. I mean, even Helicobacter pylori has interested me. But, you know, these bugs are bad so therefore we kill them off. And then we wonder why are we’re getting all of these other weird diseases. Like, just recently, I was looking at Helicobacter and I know that it's a class 1 carcinogen, I get that. And I know that with 10% of the people who... Of the 30 odd percent in Australia who are infected with it, 10% of those will get symptoms of dyspepsia, gastritis, blah, blah, blah. Of those, 10% will go on to get gastric cancer.
But that doesn't cover most of the people infected with Helicobacter pylori, you know?
Mark: Here’s the nexus here is anything that triggers inflammation. So if we go back, Bruce Ames whole thing is mutagen plus mitogen equals cancer, basically. Something that mutates and something that gets cells to grow. The classic thing getting cells to grow is inflammation in an adult. So if you put anything with chronic inflammation, if you pick the one point in your face, cancer is more likely to occur there because one of those two factors is already in place. The mitogen stimulating cell growth is going on. The mutagen is something damaging the DNA, or opening in the expression of DNA, or turning off one of the growth inhibitors.
So it's not unusual that you would say Helicobacter causes cancer, but Helicobacter does not cause cancer. Helicobacter causes inflammation in some people. The inflammation runs up the risk of cancer if you put nitrosamines or if you put...
Andrew: Barry Marshall will counter that. Helicobacter pylori causes inflammation in all of those infected with it, but whether they progressed... This is what he professes on his site. But not all of those who get the infection will progress to symptomatology. So that therefore springs something in my bone. So well what's holding it in check? Is it a species? Is it a gene?
Mark: Well, Barry was right but he's also wrong. There is a level of inflammation which is under control which will not cause a clinical problem. So he may be right at the academic level that you can say, "Here's a foreign protein of a foreign bug that should not be there." But we are starting to see...
Andrew: It's not a foreign bug.
Mark: I know. We are starting to see Helicobacter as having two aspects of it. One of them is the inflammatory aspect that can lead to breakdown, can lead to ulceration, and ultimately, that inflammation leads to cancer in a proportion of people. But the nexus is, why do some people get the inflammation which goes on to pathology? And others have an immune system which keeps it in check, doesn't let it get out of control, but sees it as just another part of those stresses in life. There are now I think enough people moving down that same conceptual pathway. There's something about predispositions that we have not really paid attention to.
There are then bugs or environmental agents. Many of the carcinogens are only carcinogens for a certain subgroup of the population. They only trigger inflammation, mercury being one of those. But you have to have susceptibilities in place and that is the population at risk. Why do we wanna know that in medicine? What we'd ideally like to know is lots of people expose to the one thing. Where would we put our resources to focus on really working with the person to not do that, to not have that exposure, to get them away from mouldy environments, to get the Helicobacter killed off?
The magic of the tissue typing, the HLA, the type of inflammatory markers that we've got. The day is not that far off where we should be able to say to people, "With that gene pattern your nemesis are among the following." These are the things you would pay attention to, whereas for you being bitten by a tick not that big an issue. You are probably gonna deal with that okay. Or catching colds, flus, getting a sinus infection, it's not that big a deal. So the separation of the people who are at risk from the whole population. You do not wanna treat 30% of the population for anything. If you've got 30% then...
Andrew: It's a big expense.
Mark: ...it's a commensal type of organism. It is not...
Andrew: But it's a big expense as well if you start to treat that way.
Mark: It is, plus the adverse effects of treatment are really, really significant. And so medical intervention where it's not necessary, medicine will invade every aspect of our life if we're not careful. One of the risks that you have with the CIRS testing, the DRB1, DQ. Is that you may get into the feeling that, "Hey, if we just murder all of your foes you'll be fine," and not pay attention to the fact that this is a host response. Which is largely, "If I escape from those foes, if I do what I need with my diet, with my, you know, where I live, the house that i'm in, the work that i'm in”, most of these things are environmental, nutritional or exposure to a pathogen of some type, that we can do something about without medical intervention. We can be away from those.
There are certain bugs that once you've caught them are highly persistent, and that you've got to really do something about it or you pay the consequence, or you pay the price. And there are consequences for chronic infection of any type. But I think the exciting part of Shoemaker's CIRS conceptual framework is it's step one of saying, "Here's a bunch of patents. Only if it's a smallish minority of the population, but for those people, life is hell when they run into their nemesis, and here's the reason why." And the intervention as a prevention for the next generation becomes possible because the HLA tendencies tend to be inherited. So you get a chance to say to kids, "You should not be in a school where there is high mould exposure, where there's damp floors. You should not be exposed to agents like mercury. Your tolerance for these things is a lot lower." Otherwise, inflammation gets set up and the consequences of that are chronic ill health.
So the excitement that I think is, his published pattern of recognition of the subtypes and the specifics of reactivity explain a lot of what has otherwise been mysterious in my own medical practice. Testing it out as a cynic for the first six months after I heard his talk was eye-opening for me because these odd patterns in the people who were the sickest, in a home, or a building or workplace, kept on coming up with, "Oh, yeah. That's the high risk of mould exposure."
Andrew: But are you seeing a biased sample like...
Mark: Of course I am.
Andrew: Yeah, I mean, like, you know, they also had two legs. If you test for two legs and hey, they've all got it. So how do you tease that apart for a negative, you know, somebody who isn't sick but does have the gene, or likewise, somebody who is sick but doesn't have the gene?
Mark: All the clinician is able to do is say, 'Does a new categorisation system give me a head start to understand a process?" It's not just, "Here's the gene. Oh, by the way. Here's it is." It's, "How does that gene affect say, inflammation control, fatty acid management?" There is a pattern. The gene isn’t a magic, "Hey, you will be sick with moulds." The gene is a pattern which says, "When the inflammatory response starts it's to this type of antigen." The normal approach from a person who is sickened by it would be to get away from that environment, that food, that - whatever it is.
What we don't have the capacity to do with our modern homes, with our modern diet is to in any way escape from the things which keep triggering those genes to form inflammatory responses. So when I come from a clinician's perspective, hundreds of people have said, "Oh, I've got a new categorising system that makes sense of why people have chronic fatigue syndrome, chemical sensitivities, chronic infections." And the way that a doctor tests it is, I’ll do your test on the people that are sick. If the pattern is holding up then that's a useful thing for me to understand more about. If it is randomly distributed, or if you know, the incidence of HLA-DRB1 subtype and DQ subtype is 3% of the population, but only 3% of my patients have it, then it's irrelevant.
Andrew: Yeah, yeah
Mark: But if that subtype is 3% of the population and 75% of my patients have it, that's really interesting. It does not prove it. You're next step is to do exactly what Shoemaker is proposing. You take the trials forward, you identify people who are well with those early on in life...
Andrew: See the future. Yeah.
Mark: ...and you follow them through. And the problem is a little, that when you have a drug trial you have one item you control all variables. The difficulty for nutritional, integrative medicine, lifestyle medicine, or anything is once you identify the person they go about their life. You're not about to put them in sterile environments. You can't do what you can do with rats. So they go out and they live in their mouldy homes and all you can do is keep track of them at 5, 10 years, do the lifestyle inventory, see how they've gone.
That is, by definition, a 30 to 40 year trial before you can make any sense of it. Coming back to the other thing you talked about, the interaction between the pathogens, that is fascinating. So for example, the DQ2 and DQ8 people, there's strong evidence now that a Yersinia type of parasite in the gut is an essential co-factor before the thyroiditis starts. We have to explain a few things there.
I've been to my own IM conferences and people basically say, "Oh, gluten equals thyroiditis," right? If you have gluten intolerance then you're going to get thyroiditis. There's some truth to it because the DQ group that will react to the gluten you put a pathogen like Yersinia in there and it makes its home in the gut. Now the immune system’s got a turn-on from the gluten, and a bug which has, at the antigenic level, a similarity to the thyroid. And you see people in their thirties to forties getting thyroiditis really, really reliably. As in more than half of them end up with a thyroiditis. Of the males, only about 5% to 10% get thyroiditis.
Way/how do we understand that? What's the sex difference? It could be as simple as, females have a much more powerful immune system than males do. They're built to last. Males are built to, not last but, you know, kill their dinosaurs and kill their mammoths and drop dead as quickly as possible. So there's an investment in immunology for a female and that may pay off by keeping women alive longer and seeing their kids through adolescence. But the cost of it seems to be autoimmunity. Women have a far higher rate of autoimmune disease than do males.
So when the immune system is activated, when you get this chronic inflammatory response, the risk is those with predispositions, those predispositions become real. And what we call autoimmune disease, I think we will look back and say, "There are a like four components here. Some environmental, some dietary, some infection, some parasitic." The most interesting question is, "Why did these not show up at a time when we were dirtier, filthier? If it is all of these things interacting together what was it that was protection in the past?"
I have a predisposition to believe that it was variety of foods in season. That you ate your food in season and so there was no perpetual antigenic stimulant. The reason that we're so keen on getting people off gluten is gluten's an identifiable, immunoreactive protein that is very difficult to digest, and is associated with specific types of autoimmunity.
So if we vary our diet, take one component and just varied our diet for foods in season, half of those people may never get what is otherwise their fate. If you could get more parasites competing with Yersinia, you probably would find that there would be no final thyroiditis. The immune system when it's got jobs to do that are keeping it busy in all kinds of different areas. At host protection, gastrointestinal wall, inflammatory responses, coming back to why stewed apples do their good, those...
Andrew: I knew. I knew you...
Mark: I was always going get it in there, and why probiotics can make a difference in the way that they do. It may not be that, you know, we just need basic diversity. It may be that we've got to get dirtier. This is going to be a challenge for us. If dirt and the, you know, the old friends in the dirt...
Andrew: This is the old friends theory. Yeah.
Mark: ...and the root vegetables, those things...
Andrew: The hygiene hypothesis, yeah.
Mark: That's right. If those things are real, we have a challenge. We have, you know, basically food laws and we like to keep things sterile. We like to believe that us separated from microbes is overall a good thing, because we're so fearful of our infectious past. When people came to cities, when you know, plagues hit, when things like that...that sits on our cultural memory. But we have to get over it. We're educated. We can now make our choices of living foods and we can move back to something that is protective.
Andrew: I foresee an issue with our black and white mentality with modern day, westernised man and that is that we want to get back to that, so therefore we'll just put it in. And I just think, "No, it doesn't work." I'm not going to mention the guy.
Mark: Oh, dear.
Andrew: …..That went to live with a certain tribe. I won't mention him. But we have this "I want, so therefore I'll get." Something twigged my interest though when you mentioned Yersinia. And again, that's a genus. You've got heaps of species.
Mark: I know.
Andrew: Like, you know, you can talk about the plague with Yersinia pestis...
Mark: That's right.
Andrew: But you've also got Yersinia... What is it, enterocolitica or something. So that could well be a commensal type organism and we have to then look at the virulence of the organism. You know, for instance...
Mark: What keeps it in check?
Andrew: Yeah, what keeps it in check? And indeed how powerful or how poisonous is that organism in smaller amounts, you know? When does it cause an infection? When does it cause a problem? When does it just reside there as a little bit of a sort of, "I'm waiting….?”
Mark: Well, one argument is, the bugs construct humans to have a good life, be fed, keep in a nice dark moist environment, and at the end of life they're just there to clean this up. They mop us up and move on.
Andrew: Let's talk about some of the other diseases or disorders that are relevant for HLA. Things like psoriasis, lupus and diabetes Type 1. They really interest me, when there's this cross-reactivity. What are the relevant HLAs, and should we be testing for HLA and just going, "Yeah, no worries," or is it something that you just notice afterwards? Like when you see an association maybe with one disease with another.
Mark: It's observational days still, in my view at the moment. The idea would be you can test theories but you have to have a coherent theory. And the Shoemaker version of this coherent theory is not going to be the dominant one. There will be a whole range of theories. I know plenty of people, immunologists, gastroenterologists and others, and each of them has their own passionately held view of what autoimmune disease means.
To a gastroenterologist, coeliac disease is just gluten. You don't have any other factors. You ask why is it only 10% of people with a high genetic risk and the other 90% are lucky, you know, it strikes randomly.
That obviously is not true. There are reasons that one person will proceed onto a potentially fatal or seriously life-threatening disease, and coeliac disease is a really tough one to get hold of because there's no way that a coeliac is going to procreate and have next generations at the same rate as another person when it happens early. But it only happens in people in gluten populations. Out in the world we've got one apparently beautiful experiment going on which I did not know of.
But the north of China relies primarily on wheat, the south of China primarily on rice. You've got a country divided by the dominant grain. One of them are prolamine glutens that are highly reactive and the other one, the glutens of rice are very minimally, if non-reactive at all. And so you do see the separation of autoimmune type disorders, as far as we know, without there being much of a difference in the bugs that are in the people's gut. But you can't say that because the climate that makes for the wheat growing is not the same as the climate that makes for the rice growing. The soil is utterly different between those two climates.
So we look at the final product, "Oh, it's rice," but it's rice with the microbes of a much richer soil, with a kind of runoff from the mountains that are nearby, and a climate which is utterly different. If you want my view is, come 10 years from now, we'll have a concept of, let's have a look at your susceptibilities. What are the things that you may run into in your life? What are the signals of things going wrong which are inflammatory markers? It may be as simple as doing C-reactive proteins, and seeing those underwhelmed with the C-reactive protein probably not having an inflamed...
Andrew: CRP or high sensitivity CRP?
Mark: Well, high sensitivity CRP if you're going to go down there. But we do have a cutoff where you say less than three for C-reactive protein. There are doctors that say, "I don't pay attention to CRP until it's 25." But at 25 you have you have a...
Andrew: You have a problem.
Mark: ...a chronic inflammatory process. Yes, you get values of 90 and 100 when you get the severe flu, but it's gone a week later. People with CRPs that are running around about 10, 12, 15, I see lots of those people, and the question is, "What is triggering that pathway?" Fascinatingly for me, after many years, the C-reactive protein settles down, they've sorted in themselves into another state of chronic disability and inflammation. But the C-reactive protein's no longer a marker. So the body has ways internally of taking inflammation of the classic acute short term, and turning it into an adapted state where there are clearly sick people, but they don't show the markers of inflammation in the same way.
Andrew: I’ve got a question there with regards to cancer progression. If you talk about the model of silent inflammation, should alarm bells ring when we see what has been a higher CRP that's gone on for many months, years, whatever, and we see that settling down, should we then be starting to be alert and say, "Hang on. What's happening here?" If they're still unwell, should we perhaps be looking to other areas of inflammation?
Mark: Well, that's an area right outside my area of expertise. I see very few cancer patients and so I see people who've merged into chronic, low grade, apparently inflammatory states where every doctor who sees him says, "Well, I see CRP and ESR are ok, so it can't be bad." And that's where the psychiatric referrals start. So there are probably many ways of getting around the acute inflammatory response and getting back to a baseline where you don't die of it, but you also don't get better from it.
I worry sometimes that what's happening is the person plays their best shots, and hit after hit after hit doesn't work and that the body falls back into a lower metabolic state, a lower inflammatory state. It's a kind of, "I give up. We'll live with this and let's get on with life and do the best we can." And I keep saying chronic fatigue syndrome is my model, but we don't have a model for cats. So a tired cat is just a cat. The tired dog just sleeps all day. You don't know what their aspirations, their hopes and everything were. So it's hard to get a model. We do the model on rats where we deplete their energy reserves and they do less, but that's not a good model for chronic fatigue syndrome. That's a complicated thing of diet, lifestyle, environment in the home, environment...
Andrew: All of them in a controlled environment, yeah.
Mark: ...in the workplace. Yeah. And the individual response is not well adapted or the the cost of adaptation is just too high for them. Still I come back to the, it's nice to have a model and a framework to think of. The DRB1, the DQ are the first little baby steps along a path of saying, "What are our susceptibilities? What's the world for each human?"
There is a risk to this as you probably know, you know. We regard evolution as the best description of biology. Medicine is anti-evolutionary. It's survival of the richest not survival of the fittest. We regard every loss of a baby's life as an anomaly that must be fixed, whereas nature in evolutionary terms is very vigorous on selections of things that don't adapt to the...
Andrew: Very hard.
Mark: ...rest of the world. So we have that mismatch that, in medicine we want to keep everything and everyone alive and everyone procreates at the same rate. We have to manage the cost of that and that is...
Andrew: It's such a hard line...
Mark: I know.
Mark: I know.
Andrew: ...and making line in the...
Mark: But truthfully, no one has got a better idea about how biology works than evolution. Natural selection, survival of the fittest meaning the fittest to procreate, left to themselves in their environment. It’s still going on in Africa. It's still going on in a lot of places where medicine doesn't stick its nose in, but what we're finding is, to defy evolution it can be done by the brainpower. But the costs escalate and escalate and escalate and now we're going to the second and third generations of kids that in the past, would have tragically died, but would not have bred to have children that are also susceptible in the ways that make them quite sick and costly for us as a community.
So there still comes a point where you have to decide prevention is going to be our best way. What other factors that say, Shoemaker and others have identified, which pick out the individuals, line them up for chronic ill health, pull those factors out of the way and watch a generation and see can we be specific enough that personalised medicine means, "I know the trajectory you're likely to be on. I will work with you with diet, lifestyle, housing, stressors." The stress response is another one which is really powerful in that area of susceptibility to bad outcomes.
Is there a new medicine which looks at that predisposition? Can't be done within Medicare. Our country's gonna fall behind in that way because prevention is not funded. Health is costly and disease is free here, and that mismatch means that people wait till they get sick see us then we do the testing after the event. When I say to people, "Look, your family should be tested," there are families that say, "I just cannot afford to know what my children may be running into." Plenty of families do but some of them can't, and that's the tragedy.
To me, armed with that knowledge of family and I as their doctor can make sensible decisions. Do you move house? Really important one, a mould affected house that's making two or three members of the family sick. It's stressful to move but if you know that they’re in their hell hole, this is their nemesis and they're not going to run into good health until they escape, it makes the decision to move home and to find a safer place better. If you know that they're gluten reactive or likely to be from their genetics, it's worthwhile to be off gluten. Being off gluten in your diet is a pain in the bum, but doing it transforms the health of more families, even than the stewed apple.
So I'm a big fan of knowing ahead, not saying it's cause and effect. Saying there are other factors and we'll put those jigsaw puzzle pieces together as time goes by, but take the susceptibility issue and make sensible decisions on that. And as new features arise we may be able to do very specific things.
Mark: It is.
Andrew: Certainly more common than when I was first nursing, thyroid issues. And they seem to be a lot more insidious as well. The biggest factor that I see I've got to say is stress. But when would a practitioner say, "I wanna test you for HLA because I see a possible link between your thyroid condition and your wheat consumption"?
Mark: Good question.
Andrew: ...you know, like, do you just do a trial of avoidance of wheat and see if their thyroid settles down and measure it, prove it?
Mark: I think that the common approach that lots of integrative doctors take is, the thyroid is a problem for people in whom gluten is a problem. That there is such a powerful association between gluten reactivity and ultimately thyroiditis. And the complicating factor is a damaged thyroid with thyroiditis, can be underactive or overactive, it goes through a couple of stages, without the TSH reflecting what's going on...
Andrew: It's an efficient pump.
Mark: Yeah, and so... Well, also, you remember TSH is a combined decision by the hypothalamus, the brain, the pituitary, saying, "Give me more thyroid hormone." A damaged thyroid, the brain may have said, "Give me more thyroid hormone," and the damage just gets worse, because it becomes more blood supply, more everything. And the brain turns off that response. It says, "Okay, you know, that's not good for me either."
So the thyroid is often, normal TSH but low metabolic activity. The thyroid is not doing much and it's certainly not doing enough to get a person out of trouble, but the TSH which is the common marker that people use, they say, "If the TSH is normal the thyroid is fine." If the TSH is normal the brain's saying, "I don't want that thyroid to do any more." That can be true, but it may not want it to do any more for the same reason that we don't jog on a sprained ankle.
The brain is good at figuring out there's damage there, asking it to do more is stupid. And you do find that when you are able to do the Free T3 and the Free T4, the TSH is normal, but the Free T3 and Free T4 are very low. Or the conversion of T4 to T3, the less active to the more active form of the hormone is very, very poor. And so in those circumstances, doing something to aid the thyroid, stop the inflammation, that's a really useful thing to do.
I would say you don't need to do the whole chronic inflammatory response assessment. You need to know if that person is gluten reactive. The simplest answer is you come off gluten, really, really come off gluten for a month of your life and tell me how you feel. And the people will say, "I've been on gluten free." "How gluten free?" "Oh, pretty well, you know, a couple of biscuits, a bit of bread. I kept the pasta in obviously, because you can't go without pasta.”
Andrew: It's a Mediterranean diet, yeah.
Mark: That's right. And so those things you have to be vigorous for at least a month, and possibly two. And the number of people will come back and say, "Wow," you know, "My energy is back. I'm actually waking up feeling less tired in the morning." And you do the Free T3 and the Free T4 and they've come back up, within a couple of months even after years of thyroid inflammation, the antibody levels drop. And that's the other thing. I mean, I would put this in.
The endocrinologist and the rheumatologist say, once you've got thyroiditis, you'll leave it, you'll replace the thyroid at the end .You give thyroid replacement, cut it out. There's nothing you can do.
If you do get gluten out and it is gluten reactive thyroiditis, the antibodies drop progressively. And I've seeing this on hundreds of patients. They go from, in fact, one of my patients this week, a very well-known thyroid specialist said, "You are gonna have to have that thyroid out. There is no way that that thyroid is going to recover." And that thyroid is now functioning perfectly, and it's only two years after that event. Their antibodies have dropped from very high to almost nothing.
Her sister had Grave's disease. Her mom had Hashimoto's. There's a kind of history there where you know that that's the pattern that's going to happen. And so for that family she knows that for her kids one or more of those children is likely to have a similar effect. There's a value of being relatively gluten free at that time. Those are more the markers, I think that the clinician is good at juggling lots of subtle inputs, and when we know more about say, the parasites in the gut, and we know more about the specific organisms, we may get far trickier and trendier about that. But at the moment simple stuff like gluten restriction and watch the outcome, I think is a clinician's best friend.
Andrew: Two quick points. Firstly on psoriasis which can be an absolute pig of a disease to try and treat. The second one which really interested me was drug issues with HLA. Things like allopurinol, for instance. So, you know, you go and get treated with your gout and you've got this cross-reactivity with HLA.
Mark: Well, what I was saying about chronic inflammatory response is there's a lot of poisons that are not poisons for most people.
Andrew: Forgive me, sorry. I should qualify what I said then. When I'm talking about drug issues it's delayed drug sensitivity, delayed drug hypersensitivity.
Mark: The delayed drug reactions, there are plenty of well-known drugs that can trigger autoimmune-like processes, and doctors know them. You know, there's a whole list of them and you look out for that. Psoriasis, probably the majority is associated with an autoimmune process. So psoriasis is very different from eczema. Eczema is typically an allergic type reactivity and mainly from the gastrointestinal tract. So you see the skin reactions, most people who've had infantile eczema will have eczema later on in life, and that's allergic, true medical allergy.
But psoriasis, strongly associated with autoimmune disease, and if you see arthritis and psoriasis in the one person. If there is joint pain along with the psoriasis it gives you a lot more confidence that this is an autoimmune process which you should have a look at dietary and inflammatory factors for. Psoriasis is not one of the things that Shoemaker's focused on particularly, nor is a specific name of any autoimmune disease. It's more, what are the environmental, infectious and other factors that are going to trigger responses in susceptible people? And for many people psoriasis in the scalp is just one of those tiny little signs that you see, where it hasn't bothered them enough. It's abnormal cell growth there. It is autoimmune in nature and that gives us a bit of a hint to go down that line of looking for environmental and nutritional factors for triggers.
The drugs, all you can really say is when you get those delayed type drug-reactions...
Andrew: You'll hardly ever know beforehand.
Mark: No, you don't. And what's worse is stopping the drug often doesn't have all that much of a benefit. It's almost like there is a trigger pulled by something that you would not have suspected, and people can go on for years.
Andrew: So it's gotta be medically treated anyway. I mean, that's gonna be a severe reaction.
Andrew: Delayed, but severe….
Mark: It could go on for years afterwards and it may end up becoming a permanent problem. And those kind of reactions to drugs are tragic because if we had a better way of pre-assessing people, if we said, "Okay, this is the group that we should be ultra-cautious," we wouldn't be thinking of these as it's only going to 0.1%. We'd be saying it's 10% of this particular subgroup. So we pay attention to them and that gives you a bit of a free-pass in other areas where there is no susceptibility.
Andrew: So from my memory like allopurinol was one, carbamazepine was another, and there was a third one which I can't remember. Which was a more common, you know... but I don't know the extent of delayed drug reaction.
Mark: Some of the antibiotics that we used for tuberculosis also fit into that category. So there is a broader range of drugs that when you go back and you have a look at what are the drugs that trigger autoimmune, psoriatic, and other type of reactions, there is a broader range of those drugs. There's nothing particularly that links them together as, you know, commonly a polyphenol group or anything along those lines. So it is almost like ‘lock and key’. Some of these drugs they are the key, but if you don't have any lock for that to open, then you're home free.
And this is very different from, you know, sulfa reactions. People get skin reactions, rashes, you know, all kinds of terrible outcomes from sulfa drugs, that's the component...
Andrew: Can we just point out that they're sulfa, S-U-L-F-A?
Mark: Yeah, sure.
Andrew: Not sulphur, S-U-L-P-H-U-R.
Mark: Ask the Americans. Those two words are exactly the same word, it's just a misspelling. But the organosulfas and the sulphur, S-U-L-P-H-U-R, there are whole variabilities which have nothing further...
Andrew: But sulphur holds your insulin together?
Mark: I know. You can't be...
Andrew: ..makes your hair curly…
Mark: ...adversely affected by sulphur. It is also your detoxification system. There are primary things of sulphur. People do say, "I reacted to Bactrim when I was young, so I could never have sulphur." So the MSMs and these types of...
Andrew: As they're eating their egg sandwich, but...
Mark: Yeah, those types of things and the foods that they have don't induce any fear. There is a paradox of course, that is, fear is one of the things that will escalate any type of a minor response and make it a major response. So a person anticipating a bad reaction from say, an anaesthetic, is far more likely to have a bad reaction than one who is unaware that they were even having an anaesthetic.
It is complicated. Life and humans are complicated. We're categorising them. We're putting them into smallish groups and saying, "This is a smallish group, but a high risk of X. This is a smallish group and a high risk of Y."
What that does is provide sign posts for a doctor of the immediate future, the next 5 years, 10 years, to say, "Let's see if you're part of that group and maybe before you run into your problems, we'll just categorise you."
You may remember the drug companies a decade or more back, or bit over a decade back, came out with the idea that, "Hey, we can do drug CYP testing to find out who needs what dose of a drug." There was this idea and unfortunately, the press release went out as, "Sixty percent of people were on the wrong dose of the drug and we have testing which can now identify whether you're one of that 60%."
The poop that hit the fan after that was so great that they just withdrew the claim. And so what we did was say, "No, no. It's all good. Everyone relax. There's no 60% that are on the wrong dose," because the concept of everybody not being the same was antithetical to medicine. So it is true, most of us need...when we have a drug, a different dose to the one we're given. Just no easy way of determining it. I think everyone says the medicine of the future will be, that we know our susceptibilities and that dosage is adjusted per person.
At the moment, we've got doctors trying to adjust the dose after the event has happened, trying to adjust inflammation after the event has happened. All we're talking about is sign posts that allow us to get a little bit smarter and make that not happen in the first place.
Andrew: The drug issue lends itself more to the CYP SNPs, doesn't it?
Mark: It does.
Andrew: But be that as it may, psoriasis. I guess the whole thing is I think we've already covered off. It's not something that you should screen for. You might see a reason to test for it should you see a high or a highly correlative disease like gluten and thyroid. But when would you bother with things like diabetes Type 1 or Lupus or psoriasis? Would you indeed, bother going, "Oh, I'm gonna check your HLA?"
Mark: I don't think that's what you can do now. I think there are different things. If we get a little better about Type 1 diabetes. So even vitamin D, you know, your vitamin D levels are critical to the expression of the insulin itself.
Andrew: What I mean casein? I mean, there’s...
Mark: There are too many variables, and so the chronic inflammatory response syndrome, the CRIS of Shoemaker is baby step one to say, "Here's a certain set of groups. Here's the things that you'll see from that. Get smart about those ones." Now, what are the other co-factors? Most of the people who have those genetics do not develop the disease. If you have mould susceptibility but you're never in a mouldy house, no problem whatsoever.
Andrew: No problem.Yeah.
Mark: And I think the same will go for Type 1 diabetes. That we do have lots of factors. Low vitamin D seems to be a risk factor. Same for multiple sclerosis. Not everyone with low vitamin D gets either of those conditions. You can have exceptionally low vitamin D levels and have no risk of those conditions at all. So I am thinking of this more as pieces still to be put in place, and then the framework is, there is genetics, there's environment, there's diet, there's pests of various types, be they fungi or bacteria or parasites or whatever, viruses, you know we've got a whole world of pain.
Andrew: Yeah, lets not go there
Mark: The bag of hurt...
Andrew: Don’t start….
Mark: ...of trying to figure out where they fit in. But these are the pieces to be constructed. The microbiome project is one important part of that because that is an area of a fermentation that, where large numbers become really, really apparent and in direct contact with our immune system. So I see this as the exciting time. We are putting together pieces that make sense of individual susceptibilities, and that trans-generationally are going to be an enormous improvement. That knowing the kids and their susceptibilities before they get sick is going to be far more powerful than the people who've gone to thyroiditis and they're 44 years of age and the damage has largely already occurred.
The power of this to me is not what can we make sense of right now, but why did you get sick? What is a predisposition that we could go and sensibly look at in your family, relatives, your mother, father or anyone else, the number of people that I see that go out to their family and say, "I have methylation issues," "I have DQ," and "I have gluten reactivity." Other people in the family are motivated to try it, they get themselves better with no doctors. And I think that's the power of this style of medicine. That we have susceptibilities which are not rocket science in one way. You can do basic things which get you a trial, and then on the other end, health propagates through a family that's had a history of chronic illness that made no sense in the past.
Andrew: Given this isn't a concrete subject, I think what we're going to have to do is put a lot of information up on our website, www.fxmedicine.com.au. And from varying areas like for instance, you know I'll put up Alan Ebringer's KickAs.org. I call it kick-ass because I'm an Australian, kick A-S. But also Martin Blaser, really interesting researcher with microbes and he's got a very interesting paper that basically talks about the issue of evolutionary companionship with Helicobacter pylori. I would like to point out that I do not think that it is relevant therefore, to just ignore Helicobacter pylori. It can be dangerous. It is a group 1 carcinogen, and should be treated as thus in the absence of, you know, a firm demonstration of a commensal relationship.
But I think it's interesting that it's just not always... It's not an exceptionally high correlation with devastating disease. But that disease is devastating. So that's my caution on Helicobacter pylori, but also I'll put up some things with regards to psoriasis and HLA, Ankylosing spondylitis as I said, with Alan Erbringer. And I've gotta say we need to get Ritchie Shoemaker on FX Medicine. Absolutely.
Mark: I think he's an...
Andrew: To discuss this...
Mark: a) he's an excellent clinician, and observationally, he's... He's observed stuff, published it, written it, and aggregated others to get the work done. But even he would say, this is the small step, the big steps are yet to come. It's as much of an issue, in fact a much bigger issue than even say a microbiome. The genetics of humans was very powerful. The genome study was very costly, very big, and we realised how small a contribution that makes now, in the context of environment, diet, stress, humans living their lives in houses, different countries, what they eat, the Hadza tribes, these things...
Andrew: I didn't say it?
Mark: No. But these things... The TGA will never approve eating goat colons full of poo. They just won’t. But we need to get used to the fact that we are biological citizens of this planet. And that our health and the planet's health and our tendency to eat meat instead of plants... I still love David Katz's quote. It's from the "New York Times".
"What do we know about diet? Eat food, not too much, mainly plants."
That's it. Like you do that, around about half the problems in the world of human health gets solved by just those seven words. I'm now becoming a big fan of that. I went from my practice….
Andrew: Can you just repeat that please for our listeners?
Mark: David Katz has been over here recently, Australian Lifestyle Medicine Society and A5M. And the simple line from the "New York Times" was seven words about diet, "Eat food, not too much, mainly plants."
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