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Exploring Autoimmunity with Belinda Reynolds

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Exploring Autoimmunity with Belinda Reynolds

There are over 80 different autoimmune disorders. So what is the aetiology and what are the commonalities?

What is happening to people's immune systems and what are some of the simple nutritional interventions we need to be addressing?

We welcome back dietician, Belinda Reynolds, who has a gift for putting complex biochemical processes into easy-to-digest terms, and today is no exception.

Belinda takes us through immune imbalances, inflammatory processes, dietary considerations, toxin and infectious triggers, nutritional deficiencies and even the role of the thyroid in autoimmunity.

Belinda has a passion for keeping abreast of the research in this field, and has some valuable insights into how approach these conditions.

Covered in this episode:

[00:54] Welcoming back Belinda Reynolds
[01:56] What is autoimmunity, anyway?
[04:05] Emerging evidence for complementary medicines
[08:30] Triggering genetics for autoimmune illness
[10:53] The gut plays a diverse role in immunity
[16:40] Addressing deficiencies
[20:57] Boosting Secretory IgA
[26:20] The value of Zinc - not to be overlooked
[30:06] The role of hormones in autoimmunity
[37:33] Toxicity and autoimmune risk
[41:32] Look to thyroid health
[48:43] Final summary and wrap up

Andrew: This is FX Medicine, and I'm Andrew Whitfield-Cook. Joining me in the studio today is Belinda Reynolds, who’s a dietician with over fifteen years of experience in the integrative medicine industry. She's an acclaimed Senior Educator with BioCeuticals who regularly presents to audiences throughout Australia and New Zealand. And she's known for her practical and easy style, bringing complex biochemical processes into an easily-digestible format with practical clinical applications. 

Now, today we're gonna discussing some concepts around autoimmunity. But I'd like to welcome Belinda back to FX Medicine, How are you, Belinda?

Belinda: I'm great, thank you Andrew, thank you for having me.

Andrew: Now, autoimmunity; complex, horrible presentation in some instances, devastating to the patients. And I've got to say that medicine really doesn't have the gold answers that we'd like. It’s frustrating to these immune specialists if you like, the rheumatologists and so forth, who deal with the sort of diseases. 

So let's discuss the premise of autoimmunity, what really are we talking about here?

Belinda: So generally with autoimmune diseases, there's over 80 different types of diseases which are currently classed as having an autoimmune component. And generally, what would classify something as an autoimmune disease is the presence of autoantibodies in the circulation. So, and generally, if you look at the immune profile of an individual presenting with autoimmune disease, they tend to have a high expression of Th17 as opposed to say Th1 or Th2. Which are commonly associated with the inflammation and allergic diseases respectively. But I should say that there often is elevated levels of Th1, as well.

Andrew: Yeah, they can be co-morbid, these things.. it used to be thought that it was was a see-saw. It’s not. It’s more swings and roundabouts.

Belinda: Yeah, That’s right. 

The Th17 what it does is then; see an increase in the release of certain cytokines such as Interleukin 17 and 22. And ultimately we see tissue destruction, and as a result of that we get the initiation of inflammation, the release of NFkB which is a variety of different downstream effects, which can contribute to worsening of symptoms and the progression of the disease state. 

So, what you tend to also see is a suppression in regulatory T cells. And they generally considered to assist the body in maintaining immune tolerance. So, in the absence of healthy levels of regulatory T cells that's when the immune system can I guess, go ‘a little bit crazy’ and lead to all of the symptoms which tend to be associated with these illnesses.

Andrew: But the converse of this is that, there are patients with rheumatoid factor out there that don't have, for instance, rheumatoid arthritis. 

So that to me says that there's got be other coinciding if you like, factors. Even if you say the word ‘entourage’ that then says, “you're going to get an autoimmune disease.”

Belinda: It's very complicated and I should start by saying that we definitely don't have all the answers and I'm not suggesting that I have all the answers at all….

Andrew: I don’t think anybody does.

Belinda: …No, it's some…but what we are going to look at today is more just understanding a little bit about some of the research that's being done behind the scenes to understand the numerous different factors that can be potentially contributing to the increased risk of autoimmune disease development. And therefore, what we might consider in terms of interventions whether it be dietary, lifestyle, or nutritional supplementation. In order to assist in rebalancing the imbalances in T cells and cytokines which have been observed in these patients. 

So a lot of the research is still in that in-vitro and in animal sort of stages. There's not a great deal on big numbers of humans in terms of the research.

Andrew: Which is weird and sadly needed.

Belinda: It is definitely just to sort of help to get a better understanding of how effective these things can be. 

But at the same time understanding how complex the development of autoimmune diseases can be, I don't think these ever going to be one magic bullet. So yes, there is some really promising research in humans with multiple sclerosis using high doses of Alpha-lipoic acid for improving the cytokine profiles in these patients. But understanding how complex and how many different factors can potentially be contributing to the MS development and the worsening of the symptoms and the disease progression. You need to be addressing all of those factors and it will vary from person to person. So I think it's definitely got to be a functional medicine and personalised approach rather than thinking that there will be one magic answer.

Andrew: I think that's the key to integrated medicine is that, if you're looking at population medicine, then orthodox medicine has the answer for that because you're dealing with large groups of people. What about those people, who present to the doctor and saying, “it didn't work, I'm still sick.” These are the people who need more different approaches. 

Now, you know orthodox medicine only has certain black boxes if you like, it quite rigid guidelines for what it does and doesn't do. And that's with the personalised medicine comes in to say, “What's happening with you Mrs. Jones?” That to me is the beauty of a natural medicine approach.

Belinda: I agree. You know some people do achieve some benefit and good benefit from the pharmaceutical medications they have been prescribed. And what's actually great is, when you look at some of the research that's being done using certain nutritional interventions like lipoic acid and selenium for patients with the multiple sclerosis or autoimmune thyroiditis. A lot of these studies are done administering the nutrient in conjunction with the standard therapy. So it's good to know that we are not necessarily saying that this needs to be an alternative to what their using it can be something that can be safely prescribed together with the standard treatment.

Andrew: And that to me is one of the biggest travesties of medicine when they blame this, they have this ignorant, and it is ignorant, where they judge natural medicine as being alternative, as if people are rejecting orthodox approaches. That to me is not the way, certainly with more serious diseases, it's irresponsible to do that. 

And to me the beauty is, as you say, it's when the marriage happens. I just wish that there would be this, “this is as far as I can do,” let's see if we can improve it by using some of these non-proven, you know, theoretical-perhaps or at least with a smaller amount of evidence; Let's see if we can you know crawl a little bit further up the hill to wellness.

Belinda: I agree it definitely should be a complimentary and integrated approach not necessarily an alternative one. 

In saying that though, some people do choose to go down the alternative path if they've experienced any say, negative side effects and little-to-no-benefit from the interventions they have been prescribed, but that’s up to the patient. It's not what I’d encourage necessarily. 

But I think the important thing to is to understand that yes, there’s generally always the genetic factor. When it comes to autoimmune disease risk there is definitely a genetic factor, but that on its own is not enough to explain why an autoimmune disease develops in a person. They needs to generally be some sort of trigger. So, that it's that whole “the genetics load the gun, environment pulls the trigger.” And what science is still trying to do at the moment is understand what those triggers are? And there’s a couple of autoimmune-like diseases where we very clearly understand what the trigger is. So celiac disease is often used as an example of that. It may not necessarily be a true autoimmune disease but it certainly has an autoimmune-like profile.

Andrew: And this is interesting, I’ll let you go, sorry…

Belinda: Yeah. So with celiac disease, we know the trigger is gluten. Remove gluten from the diet and the symptoms subside. 

So I guess what we are trying to understand with all of the other autoimmune diseases is what is the trigger for these. And when you start looking at the research, there's a number of different theories and they all could be correct for different individuals. 

So for example, we know that a Vitamin D deficiency is associated with the increased risk of developing the autoimmune disease. But having Vitamin D deficiency doesn't mean you develop one, and having an autoimmune disease doesn't necessarily mean you are Vitamin D deficient. So that's why we need to treat the patient, assess for a Vitamin D deficiency, and correct that Vitamin D status if it is, if that person is deficient. 

What research has also found is that, in women of childbearing age they looked at levels of mercury in the body, and associated that with the risk of having autoantibodies. And they found that at doses, even that which is considered ‘safe’, of methyl mercury, in the body there was a significantly increase risk. And it stood out, as the major risk factor for developing autoantibodies. And so, we know that heavy metal toxicity is likely to play a role. 

But there is also evidence suggesting that certain infection types can potentially be a trigger or a contributing factor to the development of certain autoimmune diseases as well. So there is Epstein-Barr virus or EBV, H pyroli, candidiasis, Chlamydia, hepatitis C, herpes simplex, there’s klebsiella, there's a huge range of infections that are thought to trigger the autoimmune process.

Andrew: Which is interesting to me it's not one bug. 

Belinda: No.

Andrew: You know there's some work done by Professor Alan Ebringer, and he was talking about cross-reactivity with a certain one bug. And I think it was klebsiella, with ankylosing spondylitis, and proteus species with rheumatoid arthritis. But it's much wider than that. What's interesting to me is that it's an immune-mediated response. That is aberrant. That is triggering something wrong. And that to me is very interesting, it's like where does it go wrong? I couldn't help, when you’re talking about Interleukin 17, I'm champing at the bit here going, “segmented filamentous bacteria.”

Belinda: Yeah.

Andrew: I mean I'm just so interested in that work by Dan Littman and Avalyo Ivanov, as a primer. But again as you say it needs something else. And that ‘something else’ is when you wipe out good bugs and so here we get back to the gut.

Belinda: And the gut definitely plays a huge role, I mean just understanding the fact that 80 to 90% of our total immune tissue exists within the mucosal associated lymphoid tissue of the gut. 

And what we understand now too, is that when there is hyperpermeability or leakiness of the intestinal tract. We get an increased passage of macromolecules and that can include endotoxins such as lipopolysaccharides or LPS, that exist on this so wall of gram-negative bacteria and that can elicit an immune response. And generally, the gut cells open and close to allow things through all the time. It's when they sort of sit open for an unusually long period of time that there is that constant initiation of an immune response. And what's interesting is the type of immune response which is initiated by the LPS is a Th17-driven one. So Th17 tends to respond to extracellular infections. I think that's where the concept of intermitted fasting comes from as well for individuals with autoimmune and inflammatory illnesses, is that, if you can minimise the periods through which you're consuming food…

Andrew: Antigenic load?

Belinda: Yes, so every time you eat you're basically bombarding your body with potentially harmful things and pro-inflammatory products. And there is that opening and closing of the tight junctions which are allowing passage of things through the gut wall. So, and when certain people with the certain genetic predisposition, consume gluten, the opening of those tight junctions persists for a much longer period of time. 

I think it’s, don't quote me, but I but it was around half an hour for most individuals, but for those that have the increased zonulin expression due to gluten consumption, based on their genetics, the gut wall can stay open for about four hours. And so if someone's regularly consuming gluten throughout the day their gut is open and leaky, for much of the day, every day, and as a result, you're getting that mild passage of the LPS into the body, and over time that becomes a chronic initiation of a stress response which leads to inflammation. Which then cause oxidative stress. Which initiates NFkB release and then a downstream inflammatory response as a result of that. 

And so it's really important when we have a patients presenting with an autoimmune illness. We need to look at Vitamin D status. Yes. We also need to consider if there is a heavy metal toxicity which is contributing to the oxidative stress and inflammation, and I guess, mitochondrial dysfunction and things. But we also need to consider the presence of leaky gut because that could certainly be, one of the drivers, of the disease development. So it may not necessarily have been what set it off in the first place, but it could certainly be contributing to their symptoms and by healing up the gut, and potentially removing gluten if it's indicated, that could really help to minimise the symptoms and slow disease progression.

Andrew: A paper that comes to mind when you're talking about the man who I had a bromance with at the 2016 [BioCeuticals] Symposium and that's Dr. Alessio Fasano

Belinda: Yes.

Andrew: So this is in Current Opinion in Gastroenterology, it's a bit of an older paper now 2006. But it's Systemic Autoimmune Disorders in Celiac Disease. So its talking about the association of other co-morbid autoimmune disorders alongside the immune-mediated disorder of coeliac disease. Which I used to think, it was an autoimmune disease. I just used to classify it as that. It just seems that we’re teasing apart these sort of differences now. You know those are few other disorders that were in there, but anyway, very interesting paper. 

One thing that just twigged my interest then is that you spoke about Vitamin D a little bit earlier and I just wondered about the point of Vitamin A as well. As the sort of Ying and Yang with immune regulation of the gut. And you know on a population basis we'd say, “oh but we don't have Vitamin A deficiency in Australia.” That's true. In normal people. But what if you've got malabsorption syndrome? What if you've got excessive devastation or destruction of the villi and the microvilli of the gut so that you can't absorb that soluble vitamins, there goes your inflammatory regulation.

Belinda: And I think too, definitely a lot of the carotenoids act as pro-Vitamin A and can be converted to Vitamin A. However, it's not done very efficiently in the body and particularly if you have concurrent deficiencies such as zinc. Zinc deficiency is known to negatively impact the carotenoid to Vitamin A conversion. And if someone has leaky gut that tends to be associated with zinc deficiency as well. So Vitamin A definitely needs to be considered. I think we all are very familiar with Vitamin D playing that role in immune modulation, but Vitamin A seems to be under appreciated.

Andrew: It's the paranoid vitamin.

Belinda: Yes, well we’re all fearful of it because of its teratogenic…..

Andrew: Even in men. It had this name for causing birth defects. I searched the literature years ago in Australia like the actual warnings and there was one. And that was not with Vitamin A. It was with freeze-dried liver extract, on the TGA website. I have it. 2005? So not withstanding that higher doses may-well be teratogenic, the World Health Organisation….

Belinda: Too high doses of anything is not recommended really.

Andrew: True, they are, I’m sorry, not ‘may-well’ - they are teratogenic. 

But I note that the international Vitamin A consultation group of World Health Organisation so IVAG. They state on their Vitamin A paper, that a pregnant woman who, at any stage of pregnancy, regardless of existing status can have 10000 IU quite safely. Now that's IU, not retinol equivalents, so you divide that by 3.3.

Belinda: It's about 3000.

Andrew: Yeah, 3300. But I think we've got to look at responsible use and required use, reasonable use, but without being flippant in the dosages.

Belinda: And even dietary intake as well. There was an interesting paper which looked at how we can, through dietary means enhance carotenoid uptake and then also enhance the conversion to Vitamin A. And it found that the consumption of avocado together with carrot significantly increased the uptake of the carotenoids from the carrot and also significantly increased the conversion of those carotenoids to Vitamin A. 

So it was 6.6 times the increase of carotenoids were achieved through concurrent consumption with the avocado and then it was a 12.6-fold increase in the conversion of that carotenoid to Vitamin A. And it was measured by retinol esters.

Andrew: So smashed avo, with grated carrot on top?

Belinda: Yeah! Well, I even use, just mash-up avocado and use it as a dip, like with carrot sticks and you know that's a way to achieve, improved Vitamin A status, but also understanding all the other benefits that particularly avocado has for health. Particularly with provisions of the essential fatty acids, also the fibre, it can be very beneficial. So, it's always good to look at the ways that you can improve that nutritional status through the diet.

Andrew: And you do it at 12 PM, so that you're getting enough Vitamin D on your skin.

Belinda: Sit down in the sun and eat it.

Andrew: Just for five mins, eating your avocado with carrot sticks.

Belinda: But yeah with Vitamin A just to sort of clarify the roles that it plays; It's essential for secretory IgA release. And secretory IgA is really important at the gut level, not only because of it playing a role in the first line of defence and protection against mucosal-related infections. But it also by protecting the underlying immune cells, like the dendritic cells for the example, from exposure to a lot of antigens, it can help with reducing unnecessary or inappropriate activation of the immune response. So it helps to assist in maintaining a more tolerogenic type of immune system. 

So via that mechanism the Vitamin A can assist in providing immune modulation benefits. But it's also been shown to help with bringing down Th1 and Th17, but also increasing the release of regulatory T cells as well. So it definitely provides those benefits that we are looking for in terms of improving that, that immune profile.

Andrew: So we're looking at obviously gut-immune response mechanisms, and the secretory IgA is the hero. So most natural health practitioners would immediately think about probiotics and fibres and things like that.

Belinda: Yes, Definitely.

Andrew: Can you take our listeners through a few of those that you might use as interventions, at least to you know, to hopefully dampen down that immune response.

Belinda: So first of all the saccharomyces boulardii is one of the key beneficial microorganisms which are known to stimulate an increased secretory IgA production. So it can definitely be one of the first things that you can be utilised, and I guess taking to account what else might be going on. 

So if there is persistent candidiasis which is potentially initiating an inappropriate-type, or persistent immune response. The saccharomyces boulardii can also be useful in assisting in addressing that infection too. It works very competitively against the adherence of Candida to the intestinal wall. Also through its increased production of secretory IgA that stimulates, it can help the body and more effectively addressing any potential infection at the gut level. 

So the interesting thing with saccharomyces boulardii as well, is that it also has trophic effects to which help with improving intestinal integrity but, also via its ability to improve the health of the brush-border and reducing local inflammation it enhances the disaccharide enzyme release too. So that assists in alleviating certain food-type intolerances such as mild lactose intolerance, that could be secondary to gut inflammation.

Andrew: Oh absolutely.

Belinda: So, it would be one of the first things I’d think about. But then, it's also very important to recolonise the gut with beneficial microorganisms. 

With the saccharomyces boulardii, it’s a yeast that's non-commensal. So it will move on through and out. In the research that they did with patients taking saccharomyces boulardii within three to five days of ceasing supplementation it was gone. So it moves through, provides its benefits and passes out. So what we also need to do is, look to recolonise following that. And so, really high doses of lots of different types of beneficial microorganisms can assist in restoring that microbial diversity which is so essential for healthy digestive function. And the provision of prebiotics is essential as well. 

So currently we're limited to what different strains we’re able to produce in a commercial way, to being encapsulated and to be sold as a supplement. So, although what we have is incredibly beneficial in terms of probiotic supplements, we still are limited. So it's very important to provide prebiotics which assist in feeding all of those other microorganisms in the gut, that are essential or very beneficial for our health. And that then too assist us in increasing the benefit we can get from the probiotics. Because it's via their fermentation of prebiotic fibres that the probiotics will provide a lot of their benefits. And that's through particularly the production of certain short chain fatty acids. Butyrate for example, is particularly beneficial for supporting gut integrity, it's one of the primary fuel sources used by the colonocytes. So it's very good for supporting gut healing. Glutamine of course too, is very important for the small intestines.

Andrew: You’ve got to use a lot of glutamine, though right?

Belinda: Pretty high dosage of so, gram-doses is really important. And the other short-chain fatty acids that are produced by the probiotics too. They all help to maintain an environment that is ideal for the growth of beneficial of organisms and helps to deter some of those potentially pathogenic-type organisms as well.

Andrew: Traditionally, you know, you mentioned zinc before, and you know, in a gut-mediated inflammatory disorder, I would very often start with like, a liquid zinc, we use to make it in the pharmacy where I use to work. But now there are these forms of zinc on the Australian market that have much better sort of absorption, particularly to inflamed sites like zinc carnosine. And it greatly interests me, this. 

And you know it's, I think its hallmark use is in things like, as an adjunct to helicobacter treatment, but also with gastroesophageal reflux to settle down the inflammation. But I haven't look at any of its use in potentially lower gastrointestinal disorders, ever heard of anything at all?

Belinda: What I've seen is similar to what you've seen in terms of the H. pylori, the dyspepsia, ulceration. That's mostly what I've seen, a lot of the evidence around the zinc improving the functioning of tight junction proteins has generally looked at other forms of zinc. But I would imagine that considering the antioxidant and anti-inflammatory benefit of that zinc-carnosine complex, I would expect that you’d also achieve good results there.

Andrew: I just be very interested like, I think I've got this right, in that the carnosine appears to anchor it?

Belinda: Yes, it remains there.

Andrew: Anchor the complex, so that the zinc can be used to heal an inflamed site. Sort it’d be interesting to see, what its utility would be in you know, lower bowel disorders.

Belinda: It definitely does seem to hang around there longer. 

And what's interesting to even, skipping across to pyrroles, where they suggest that with elevations in pyrroles. Where there’s often a zinc and Vitamin B6 deficiency, due to the increased losses through the urine and the resultant increase in gut permeability. And then the greater passage of the pyrroles into the body, the greater then, the loss of zinc. 

One hypothesised beneficial way of supplementing with zinc is to give a poorly absorbed form of zinc, so that it is used locally. But I guess too even if you do have zinc that is well absorbed, the blood that the zinc is in still feeds the gut.

Andrew: Well your body compartmentalises zinc. This is the whole issue with measurement. You know, you measure it in the serum, it doesn't tell you how much in your toe. So maybe?

Belinda: Yeah, it’d be interesting.

Andrew: I think the whole thing is, there may not be level A1 evidence on this, but it's something where your patient is in dire need of help. And you try something that might work.

Belinda: Yes, and that the good thing is that these things, as long as they are prescribed responsibly and the practitioner always considers the potential interactions with any drugs the patient might be on. 

As long as those things are addressed, these don't do any harm. So and they're generally quite cost effective as well.

Andrew: Yeah, zinc’s very cheap.

Belinda: Yes, so I think it definitely doesn't hurt to try because if it doesn't work you've lost nothing, but if it does, well, fantastic.

Andrew: Oh you've got to be quite silly, anybody has to be really silly, chronically, with the zinc, for it to cause long time ill-effects like you know, copper deficiency and cardiomyopathy. You've got to take 150 milligram plus per month.

Belinda: Yes, and it will often cause nausea before you can go too high.

Andrew: Yeah, like I challenge many people to take that much for that long. 150mg if you look at the research, that's a lot.

Belinda: That is a lot, yes.

Andrew: I've gone up to 100mg, but short term, you know two months maybe, maybe? But I think it's very interesting… 

You mentioned something just before, regarding B6 and zinc and obviously, these two nutrients are involved in many, many enzymes systems. Zinc, B6, magnesium. And particularly those which govern hormone control, synthesis, even detoxification, bio-transformation. So can you take us through the relevance of hormones in autoimmune disease or I might even say, autoimmune-like disease. 

Because it's really interesting that diseases that I was brought up on, “that is an autoimmune” - then coeliac disease? They're now saying it's an immune mediated autoimmune-like disease.

Belinda: And it's same, cardiovascular disease, PCOS even. They’re even suggesting that there’s an autoimmune-type driver there, but don't necessarily fit into the classical definition.

Andrew: Yeah, like rheumatoid arthritis appears to be a classic autoimmune disease. MS is still classified as an autoimmune disease, yes?

Belinda: Yes.

Andrew: Right.

Belinda: And even Hashimoto’s and Graves. Because there's clear presence of certain antibodies in there.

Andrew: Right. That's interesting, see I thought Hashimoto’s was an inflammatory thing, that had autoimmune-like. There is this confusion I don't get it. I think there is so much to be done.

Belinda: I'm sure we'd find evidence to say that you're right, and I’m right too.

Andrew: And vice versa I can tell you that. The research that you do. 

So let's go into hormones because you know, let's speak on oestrogen. It’s the proliferative hormone, that its job. But when it's, let's say, mismanaged by the body or given the opportunity to do aberrant actions. It can have deleterious effects on health. So, can you take us through some of these drivers and where I guess hormones, various hormones not just oestrogen, are implicated in autoimmune disease?

Belinda: Sure, so it's definitely found that women have a greater risk of autoimmune disease development. And so they has been a lot of research conducted into trying to identify what it is that make women more susceptible to the development of these diseases. 

And so, there's a few interesting hypothesis out there that haven't necessarily been proven, but there differently interesting to consider. One of them is the Foetal microchimerism. Where, during pregnancy the foetus shares its cells with the mother and vice versa. To sort of say, “look this is me, don't let your immune system attack me.” 

However, those cells persist long after birth. And so with each subsequent pregnancy, a woman has an increasing number of, I guess, foreign DNA within her tissues.

Andrew: The foetal stuff in her…? right?

Belinda: Yes. So, for example in one situation I think that were conducting autopsies on boys who had Type 1 diabetes. And they, were looking at their pancreas. And they found that, they found XX chromosomes, within some of the cells in the pancreas. And there was the hypothesis that it was the body, due to some sort of trigger, the immune system's checks and balances I guess, became insufficient to prevent the immune system from attacking that foreign, I guess as you would say, DNA within their tissues.

Andrew: So could this be why they were looking at milk as a possible trigger? If I think about the intake of beta casein from non-jersey cow milk. That it could then have a dysregulatory effect of T helper cells in the gut. Inflammatory cytokines being produced. Which then react with the chimeric chromosomes in the pancreas. There’s a long shot… so Andrew’s hypothesis, haha!

Belinda: It's definitely with considering. 

I mean, looking deeper into the research that was around, it's definitely not something that's proven and that they've confirmed to be a definite contribution. I think there was even some evidence that's suggested that no, it's not the immune system targeting that DNA but it's an interesting thing to consider.

Andrew: Andrew's hypothesis out the window.

Belinda: And the other thing is, I guess, the hormonal balances, or imbalances, that can occur within women. So there's some interesting research around looking at hyperprolactinemia, as a potential trigger for autoimmune attacks or periods of worsening in the systems. 

Andrew: Exacerbation, yeah.

Belinda: And that is because prolactin is considered to be more stimulatory for the immune system and more pro-inflammatory. But it's interesting because there is also evidence to the contrary which suggests prolactin could be beneficial for MS. Animal studies have been done on that. 

So I guess what you’d probably need to do is take a step back and look at well, what is it that would have being contributing to the hyperprolactinemia? So maybe it's that, it's a bystander that there's that association but not necessarily causation of that high prolactin.

Andrew: Just quickly thinking about that, I just note that, prolactin inhibiting hormone the other name for that, is dopamine. And so one would automatically assume that you know, lack of dopamine equals stress, equals high prolactin. But if you’re looking at this stuff, giving prolactin in animals who are not otherwise stressed they maybe that cytokines milieu isn't there. Maybe it's just one of the branches, one of the keys, not the key. And this is the problem with research when you're looking at one thing isn’t it?

Belinda: Yes, that's right and I think understanding what else happens with hyperprolactinemia often, you tend to have an imbalance with progesterone and oestrogen in that situation as well. Like you said stress generally is a big contributing factor to that, but also what tends to happen when you have elevations in prolactin? One of the consequences can be that there is a compromised health of the corpus luteum. Or the quality of the corpus luteum is compromised during imbalances in FSH and LH. And as a result, because the corpus luteum is normally responsible for pumping up progesterone during the luteal phase to maintain that lining that's being developed to facilitate conception and implantation. What you tend to get is an insufficient release of progesterone, and that can contribute to a shortened luteal phase or break-through bleeding that also can compromise conception. But knowing that progesterone is considered to be anti-inflammatory and in a sense, immunosuppressive. It could be that the stress and the progesterone depletion that is contributing more-so to the worsening effects or the worsened symptoms of autoimmune diseases as opposed to that high prolactin itself. 

And what's interesting too is that understanding the role toxicity plays in causing or contributing to autoimmune disease risk. Progesterone when depleted, whether that be due to high prolactin, chronic stress? Progesterone is essential for the functioning of the pregnane x receptor which is involved in detecting the presence of toxins and stimulating the expression of a certain other proteins such as Nrf2. Which when activated, initiates a number of the cellular antioxidant and detoxification defence mechanisms within a cell. 

So indirectly, depleted progesterone can significantly compromise a healthy detoxification and antioxidants systems within the cell leaving someone more vulnerable to the toxins and things in their environment that they may otherwise been. And then if you combine that with genetic susceptibility, some other nutritional deficiencies, microbial imbalance, leaky gut, an infection that could trigger the immune system, it could be all of those things contributing there.

Andrew: Yeah, the perfect storm.

Belinda: Yes.

Andrew: So apart from medical practitioners being able to prescribe levels of hormones as a band aid and I underline that word to, if you like, to use a hormone as a supplement, a natural hormone, as in the bio-identical hormone. What other natural ways can we support the normal production and indeed the normal detoxification of these hormones?

Belinda: So generally, if you're looking at high prolactin and low progesterone as a result of that; Vitex interestingly has shown some evidence to be beneficial. The actives Vitex combine dopamine receptors helping to bring down those elevations in prolactin, ultimately improving corpus luteum quality. And therefore, assisting healthy progesterone and oestrogen levels during the luteal phase. So there is some early research which is suggesting that to be of benefit. 

Furthermore, supporting the activation of things such as Nrf2 can assist in healthy activation of the detoxification and antioxidant defence mechanisms within a cell. And there is a huge number of different things that have been found to assist in activating Nrf2 and that can include things such as turmeric. Like a lot of the compounds that we consider important anti-inflammatory and antioxidant that seems to be via this Nrf2 activation that they're providing a lot of their benefits. 

So I think cumin, also resveratrol. And interesting the nutrients too such as Alpha-lipoic acid, selenium, even glutathione, sulforaphane, and a number of different antioxidant and natural compounds tend to be quite useful. Intermittent fasting seem to be beneficial for activating that as well. 

So I've considered all those things, and what's interesting too, is that we know the dark leafy vegetables provide beneficial ingredients such as the DIM. And not only is it assisting in healthy metabolism of oestrogen but DIM has also been found to interact with the aryl hydrocarbon receptor at the the gut level. And helping to regulate then, how the body responds to toxins and helping to regulate the inflammatory-immune reaction that the body would have when exposed to certain toxins. So those dark green leafy vegetables are very, very important for assisting not only healthy hormone metabolism but also ensuring protection against the ill effects of toxins in the environment.

Andrew: This is obviously a huge topic and what you've covered today is really, seriously, the tip of the iceberg. There’s so much more to uncover. 

But what other things can you enlighten us with, that just might give us a few more little more little hints and tips with regards to autoimmune type disorders, I mean thyroid? You mentioned that earlier?…

Belinda: Yes, so, looking at thyroid conditions of course, there's Graves’ where you have the hyperthyroidism and Hashimoto's where there’s hypo. But individuals with Hashimoto’s can swing to hyper, as well. 

Interestingly, although they have very different presentations the underlying contributing factors tend to be very similar. And they generally have that same imbalance within their immune profile. With insufficient regulatory T cells, high Th17, Th1, and the inflammation that results. 

And so what is interesting is that one of the key nutrients that have been researched in particularly Graves’ disease is selenium. So at doses of 100mcg twice daily, it's been used to assist with reducing the orbitopathy associated with Graves’ disease where there’s that, increased fat accumulations behind the eye which can lead to the protrusion of the eyes. But it was also shown in those studies to assist with slowing the progression of the disease itself. 

And selenium plays a number of important roles in the body. But one of its key roles is as an important cofactor for glutathione peroxidase. So glutathione really can't provide its antioxidant benefits, if there is insufficient selenium to ensure healthy levels of glutathione peroxidase to allow the reduced glutathione to do its job. So if you have insufficient selenium, that compromises the glutathione - ‘the universal antioxidants’ ability to do its job and as a result, you can get increased oxidative stress and resultant inflammation occurring. You also have compromised detoxification mechanisms as well. 

But what is also interesting too is that selenium is essential for the deiodination enzymes involved in converting T4 to the active thyroid hormone T3. So not only is it indicated in Graves’, but it also can be indicated in under-activity of the thyroid as well, particularly if there’s low T3.

Andrew: I remember a paper being reviewed by Professor Creswell Eastman.  And the paper was by Drutel, D-R-U-T-E-L. et al

Belinda: Sure. Yeah, so I mean, it's quite interesting that the important role selenium status can certainly play in ensuring the health of individuals with thyroid conditions. 

But we also need to consider other factors too. So what's interesting, we were talking about the relationship between certain hormonal imbalances particularly in females in autoimmune disease and there's definitely a close relationship between polycystic ovarian syndrome and Hashimoto's. 

Andrew: Ahh, right.

Belinda: They tend to coexist quite frequently. And looking at the research around that there's some interesting evidence emerging around the use of myoinositol and Alpha-lipoic acid in those situations. 

So not only does the myoinositol act as a second messenger for the thyroid hormone, at the cellular level to improve the functioning of thyroid hormone. But it also does a similar action for assisting healthy insulin functions. So it can improve glycemic control, making it beneficial for thyroid under activity and for PCOS patients presenting with poor glycemic control or hyperinsulinema. And then, with considering the role that the Alpha-lipoic acid plays in assisting insulin function and carbohydrate metabolism. It can be beneficial for the PCOS sufferers but has also shown to be useful in the autoimmune type situations. But also, via its ability to assist with providing antioxidants benefits, it has also been shown to assist with preventing the imbalance between T3 and the reverse T3. 

Because there’s a theory that when the body is in a… there's a lot of inflammation and oxidative stress, the body intentionally produces more reverse T3. 

Andrew: To slow it down?

Belinda: Because it believes that we need to suppress the metabolism to reduce the production of those oxidative stressors or free radicals. And so by addressing that inflammation, particularly in the liver, the lipoic acid is suggested to help with attenuating that increased reverse T3 synthesis which can be working at blocking or attacking as an antagonist at the T3 receptor sites. 

And then looking at autoimmune disease in itself, Alpha-lipoic acid has been shown to assist in reducing that tissue injury that can occur as a result of increased LPS passage and the inflammation that causes. So it's definitely an interesting nutrient to consider for autoimmune type situations. And anything associated with poor glycemic control. 

The other thing I was going to mention too is that Alpha-lipoic acid plays a role in helping to ensure healthy glutathione levels as well. So due to its role in assisting in recycling cysteine, it helps to improve the availability of cysteine for glutathione synthesis. And it also plays a role in regenerating a number of different other antioxidants, so it plays quite a pivotal role in the body and there is some...

Andrew: Under-utilised.

Belinda: Yeah, yeah, and is quite, in terms of looking at the research on MS, they used around 1,200mg and they chose that dose based on the serum levels they had achieved in animals, to achieve the results that they found quite impressive. They then looked at what doses they needed to give a human to achieve the same serum levels. And that came out of 1200mg, and they did administer it with food, to reduce the effect of a gastric upset, as a result of the high doses they were using. But in terms of looking at thyroid type conditions and PCOS, the doses used were around 400mg to 800mg and that was a racemic mix, used in those studies.

Andrew: Yeah, and most of the research is still the R-S lipoic acid, even though there may be some benefits of the R Form, I get it. But the human research is showing that the RS works.

Belinda: Yes.

Andrew: So it's like well, it’s kind of like well… you know we also had pyridoxine hydrochloride. I got to say I feel like to dunce. I've got to say, there's so much to learn.

Belinda: There is.

Andrew: We seriously have only skimmed the skin off the apple with this podcast.

Belinda: Yes, I mean look, we definitely are no where near having all of the answers. But there is definitely a lot of really interesting research that's out there that certainly helps, give us some ideas of where to start, and what we need to investigate further when someone presents. I mean, the importance of personalised medicine can't be emphasised enough. Where we see through the evidence that although yes there's an association with D deficiency or insufficient Vitamin A ingestion. There is definitely some associations there but it doesn't mean that who presents to you is going to have that particular issue. And that's where a good thorough investigation is really important and just keeping all of these factors in mind when treating someone.

Andrew: This is FX Medicine and I'm Andrew Whitfield-Cook.

Additional Resources

Belinda Reynolds
Prof Dan Littman
Prof Alan Ebringer
Prof Ivalyo Ivanov
TGA Vitamin A Warnings
Prof Creswell Eastman

Research explored in this podcast

Fasano A. Systemic autoimmune disorders in celiac disease. Curr Opin Gastroenterol 2006 Nov; 22(6):674-679

Ivanov I, Littman D. Segmented filamentous bacteria take the stage. Mucosal Immunol 2010 May; 3(3):209-212

Rashid T, Ebringer A. Rheumatoid Arthritis is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection. Clin Dev Immunol 2006 Mar;13(1): 41–48.

Ivanov I, Atarashi K, Manel N, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009 Oct 30;139(3):485-98

Drutel A, Archambeaud F, Caron P. Selenium and the thyroid gland: more good news for clinicians. Clin Endocrinol (Oxf). 2013 Feb;78(2):155-64

Other podcasts with Belinda Include:


The information provided on FX Medicine is for educational and informational purposes only. The information provided on this site is not, nor is it intended to be, a substitute for professional advice or care. Please seek the advice of a qualified health care professional in the event something you have read here raises questions or concerns regarding your health.

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FX Medicine Podcast
FX Medicine is at the forefront of ensuring functional and integrative medicine gains the recognition it deserves and ultimately establishes itself as an integral part of standard medical practice. Hosted by Andrew Whitfield-Cook, our podcasts are designed to promote research and evidence-based therapeutic practises, acting as a progressive force for change and improvement in patient health and wellbeing.