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Understanding Gilbert's Syndrome with Maria Allerton (née Shaflender)

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Understanding Gilbert's Syndrome with Maria Allerton (née Shaflender)

Gilbert’s syndrome is a genetic condition that affects the liver’s ability to process bilirubin. Although generally considered harmless, in fact patients with this condition can suffer from fatigue, gastrointestinal issues and fat soluble vitamin deficiencies. 

In this episode, Nutritionist Maria Allerton (née Shaflender) talks to us in depth about Gilbert’s syndrome, speaking both from vast clinical experience and personal perspective. She discusses some of the subtle symptoms of the condition, the connections between Gilbert’s and pyroluria, why patients need to be careful when taking medications, as well as her preferred dietary and supplement interventions.

Covered in this episode

[00:58] Welcoming back Maria Allerton (née Shaflender) 
[01:40] What is Gilbert’s syndrome?
[03:15] Subtle symptoms of Gilbert’s syndrome
[04:17] What else can cause elevated bilirubin?
[05:03] Orthodox treatment of Gilbert’s is lacking
[06:09] Triggers of Gilbert’s syndrome 
[09:07] Connections between Gilbert’s and pyroluria
[11:05] Gilbert’s impairs glucuronidation
[14:36] Oestrogen detoxification
[17:04] Farmers and increased risk
[19:23] Does treatment help?
[20:51] Jaundice in infants - is there a correlation?
[22:20] Pathology
[25:19] Treatment approaches
[27:54] Gilbert’s syndrome and the microbiome
[30:13] Exercise 
[33:35] Dietary recommendations
[37:32] SNPs to be aware of
[39:40] Medication metabolism and alternative options
[44:11] Fat soluble vitamins
[45:34] Safety considerations
[47:31] Getting patients onboard with changes
[49:09] Thanking Maria and closing remarks


Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. Joining us today is Maria Schaflender. She's a clinical nutritionist with a special interest in mental health, children's developmental health, gut health, and genetics, which stem from her own health challenges throughout her childhood and adult life. Maria, especially, is a MINDD Foundation practitioner and an accredited genetic SNP test practitioner. 

Welcome to FX Medicine, Maria. How are you going?

Maria: I'm good. Thank you. Thanks for having me.

Andrew: A pleasure once again, because we've had you on before, speaking about great stuff. So, for our listeners, our watchers out there, please go and look up our previous podcast  with Maria Schaflender. 

Now, I guess to start, today we're talking about Gilbert syndrome or Gilbert's syndrome. So, what is it exactly, Maria?

Maria: So, Gilbert's syndrome, as I tend to call it, is a genetic condition. So, it's a polymorphism in the UGT1A1 enzyme, which is a bit of a mouthful, but essentially it's a SNP. So a variation, like a lot of variations that people probably heard about, things like MTHFR and other genes where essentially the enzyme becomes under-functioning. So, depending on how many variations people have, between 30% to 50% of the enzyme capacity becomes dysfunctional. And it is something that people are born with. 

Essentially, what happens is the bilirubin in the patients, in the person who has Gilbert's syndrome is usually elevated and it's usually elevated pretty consistently on several blood tests. So, not just one. And what happens also is, it becomes pretty tricky to detoxify. 

So, bilirubin and glucuronidation, which is the phase of the liver where the enzyme is functional, is very important for our detoxification. So, things like drugs like paracetamol or non-steroidal anti-inflammatories, but also oestrogens, and pesticides, and a whole bunch of other toxins that we regularly eliminate. So, it's a pretty important enzyme.

Andrew: Yeah, okay. So, we're talking about slightly elevated bilirubin, but it's not to the point of what we'd normally see in hepatitis, the total full jaundice picture. However, people can get a yellowing of the eyes and a yellowing of the skin. So, it's not invisible.

Maria: Absolutely, yeah. I think it really varies. So, in my patient population, there's a whole spectrum. So some people have elevations of between 18 to 20 on their bloods, and some people have 45 and 50 on their bloods. And I find whether they're actually having there's jaundice, obvious symptoms, the yellowing, it really varies on their lifestyle and the liver function in general. 

So, usually, those who have an alcohol habit, or a drug habit, or take a lot of painkillers, they will usually have a worse presentation and those signs will be really obvious, but most of the time they're not really that obvious.

Andrew: Can it be triggered by other things so as well?

Maria: Elevated bilirubin? Yeah. So...

Andrew: Yeah, there will be expression if you like, of it. The evidence.

Maria: The evidence, yeah. Yeah. So liver dysfunction, hepatitis, cirrhosis, you know, all those things need to be ruled out usually before, and they usually are medically ruled out before someone's put into the Gilbert's basket. 

But what I find is people have bloods with elevated bilirubin for years and years and years, and have just always been told, "Don't worry about it. It's benign, nothing to do. All good, carry on." And whilst they're having a whole bunch of psychiatric and gut symptoms, so, it can be really frustrating. I find most people are pretty frustrated. Yeah.

Andrew: Right. So, this is what gets me: you read every single medical textbook, and it's a slightly elevated unconjugated bilirubin, and it's nothing to worry about. It's benign, reassurance is the only treatment given. There’s nothing else to do, walk out. Is this, do you think, because medicine has nothing to offer?

Maria: Yeah, I think also they have nothing to offer because it's not a pathology as such. So it's not a liver pathology. But it's also because I think there's a bit of a laziness around actually digging into the research and digging into the understanding of it. And I think now that we have access to more genetic testing, like we've had in the last few years, these things are becoming more obvious. 

You can actually just order really simple, inexpensive genetic test online and check whether you have the UGT1A1 variation, or one or more of them, and then you know for sure. But yeah, I think it's just not recognised as something that is treatable.

Andrew: Got you. I want to circle back to the symptoms again, forgive me, the triggers again. And it's not just like wholesale use of heavy drugs, or illicit drugs, or anything like that. I mean, even things like dehydration or viral infections that might be affecting your liver, like Epstein-Barr Virus, things like that, is that correct?

Maria: Yeah. Actually…

Andrew: So, as we think of that a bit, does it tend to present or does it tend to be picked up in certain age groups?

Maria: Yes. Yeah, definitely. So, what I'm seeing a lot of is teenagers, teenagers coming in, particularly girls with Gilbert's syndrome, where it's being triggered by puberty. So, a huge hormonal influx goes through the liver, they have the genetic glitch, and then it has this perfect storm. So, too much oestrogen to detoxify, the liver doesn't cope, and the bilirubin starts going up. 

So, that's the most common thing I find. And another one is probably more driven by someone who's been on antidepressants or anxiolytic drugs, which triggers the bilirubin to come up. So, that is another category of people. But yeah, most of the time I find it's more females and presents with teenage puberty, essentially.

Andrew: Okay. So, look, I know this isn't going to be everybody, but I'm wondering if this might answer part of that picture that we see that females tend to be affected more by EBV during that pubertal area, the menarche. Do you find this in clinical practice? Do you find that if... I got to be careful about biasing my picture here. Do you find that, of the women/girls that come to see you who have been diagnosed with EBV and they're really struggling with like HSC, and hormones, and things, do you find a large percentage of those people that come to see you have Gilbert's?

Maria: It's tricky to say because it is a bit of a special interest area for me, I do just tend to see a larger percentage.

Andrew: Right. So you gravitate. You get them.

Maria: So, I think, I just see a lot of people with that and pyroluria, which we can touch on later. But I find, generally, what would be the correlation there is these people tend to be zinc deficient, and they tend to have sub-optimal detox. So, if they're going to be stressed, going through puberty, picking up viral infections in that sort of teenage time, they're on the back foot already with their handling of minerals and their handling of toxins. So they, yeah, definitely going to be more likely to catch something like chronic Epstein-Barr, yeah.

Andrew: Got you. Okay, so, my understanding is, Gilbert's syndrome... I'm going to say Gilbert's syndrome, because it's too hard. I feel like Gilbert’s, like I'm a poser, I know French.

Maria: Yeah.

Andrew: So, with Gilbert's syndrome, I thought that one of the hallmarks was that there was no haemolysis. But you just mentioned pyroluria, that's to do with haemolysis isn't it? With haeme?

Maria: Yeah. Yeah. I think, in every human, we have haeme broken down into bilirubin and pyrroles, and then getting re-metabolised and reused up in the liver. And what I'm finding—and this is anecdotal, I don't think there's been any studies done—but I can probably take a sample of at least 50 or 60 patients who have Gilbert's syndrome and all those signs of pyroluria, and then I'll test them for pyroluria and they usually come up positive. 

Andrew: Right.

Maria: So, my theory is that there's probably been some epigenetic damage done to the liver in the previous generations of these people. So I always, you know, take a whole case history. There's usually somewhere up the family tree, there's usually an alcoholic somewhere, usually on the male line. So, they're either going to be their grandfather who drank too much because he was depressed after the war, or there's usually some sort of, or massive toxicity exposure. So if someone was a farmer. So, oxidative damage to the liver, which then translates through the generations and triggers these things. So, that's what I'm finding, yeah. Just clinically…

Andrew: I tell you what, so there's a research project for somebody listening. I mean…

Maria: I'd love to do that. One day, I'll become a researcher one day and that will be the first thing I'll do.

Andrew: It's really interesting though about pyroluria, or what was colloquially called Mauve Factor, and forgive me, I've just forgotten the...I've gone blank on the actual...

Maria: Kryptopyrrole is the other one. Yeah.

Andrew: No, there was another one, the actual chemical name. Anyway.

Maria: Oh, HPL.

Andrew: That's the one. That's the one. So, to me, it's kind of like the difference between the colloquial term, like leaky gut, and the medical term of bacterial translocation or intestinal hyperpermeability. They're both true. But that one doesn't exist when you're talking to a doctor, and this one does. They're both the same thing, it's just that if a doctor says the word tummy to his patient, is he using the wrong word? No. So, this is what I don't get, this disconnect. 

I also have a question about, do you think maybe the reason it's totally glossed over is because it's already been judged to be benign, therefore, it can't exist, it can't be an issue, so we'll look elsewhere if there might be an issue with you, Mr./Mrs. patient? 

For instance, you mentioned drugs. Now, I picked up, looking at this, I picked up paracetamol toxicity. Surely there's got to be others that have got to do with glucuronidation, correct?

Maria: Yeah, definitely. Yeah. So, it impairs the handling of all those common drugs. So, paracetamol, non-steroidal anti-inflammatories, recreational drugs, all those sort of things. So, aspirin has been cited as well. 
So, I guess the half life of those drugs in that person's body is going to be much longer than average. So the amount, those maximum doses that are on paracetamol packets, they're not going to apply to the Gilbert's person. So, they should be a lot more careful and possibly limiting to half the maximum dose if they need to take those drugs. 

But I think, just to answer your previous point about treatment, medical recognition and treatment. I think medical treatment comes into it when someone has gallstones, when they need to get their gallbladder out, that's usually when that treatment comes in. And I think even most of that time no one goes back to look at whether they've got Gilbert's syndrome, they just, they take the gallbladder out and that's supposed to resolve the problem.

Andrew: And there's been no previous correlative studies on Gilbert's with gallstones?

Maria: Not that I've seen. Not that I've seen. It would be the most obvious thing. And the patients will come in and say, "Oh, I wonder if this is related." But their medical professionals never mentioned anything. So.

Andrew: I mean, it seems to me, there is evidence, albeit case reports at least, that there is increased risk, certainly of paracetamol, which for our United States viewers is acetaminophen. So, there is a real risk, we know this now. It seems that it's been glossed over because it's been already determined, you know, it's just like being left or right handed, or blue or brown eyed, so it can't be the issue. But now we know there's at least some issue, at least with some patients, perhaps we should look further. 

You were also talking about the oestrogens earlier. That's very interesting. So, what about risk of endometriosis or fibrocystic breast disease? What about risks of these other disorders from, I'm not going to say remedial, but certainly a whole range of severities?

Maria: Yeah, yeah. So, the glucuronidation pathway in the liver, which is where the glitch comes in with Gilbert's, is responsible for handling oestrogen detox. It's not the only pathway, you also have methylation and other pathways that handle excess hormones. But glucuronidation is definitely one of the main ones. 

So, whenever that pathway is not functioning to its optimal, you're going to have oestrogen dominance conditions. So, everything ranging from your fibroids, to heavy menses, all the way through to endometriosis, as you said. The way that I explain it to patients is usually, "How big is your bucket? So, what else is in your liver bucket that is stopping your oestrogen from getting detoxified efficiently?" And usually there's histamine issues, and there's alcohol, and there's caffeine, and there's a whole bunch of things that we have in our daily buckets, speaking of caffeine. And those things need to be detoxified.

So, if your glucuronidation is already struggling, plus, if you're taking oral contraceptive or another form of contraception, that's usually when women with Gilbert's syndrome will come in and have a problem. It's usually when they've started taking oral contraceptives and they're not handling it well. So they're having extreme reactions, they're either having mood reactions, or they're having disturbed periods, things that they're not expecting on a contraceptive. So, obviously, their handling of that drug has been impaired because their glucuronidation has been impaired. So, yeah, it's really common one.

Andrew: There's another research topic, the comparison between Gilbert's and non-Gilbert's with the handling or the adverse reactions from whatever else you see. I mean, that would be really interesting to look at. 

You also mentioned farmers before, and you were mentioning the bucket. Now, farmers particularly have a very high...is that coffee?

Maria: This is a Dandy Chai that's supporting my gallbladder and liver right now. Yeah.

Andrew: Sorry, the reason I'm laughing is because of a YouTube video about subtitles, we can't get into that, but anyway. 

But with farmers, we know that their exposure to pesticides is far higher than a lot of other populations. I'm not going to say particularly males, because there's a lot of women farmers out there that really do, they do the hard yakka. So, have you ever looked at this sort of thing and found evidence of high pesticide residues or chemical... Well, residues is the word I guess, in this population?

Maria: Yeah, look, what I usually test for is, and that was our previous podcast topic, is hair mineral analysis. So I do that pretty much with every patient. And what I find is… So I've had a number of female farmers who are clients in rural New South Wales and Victoria. And they both have had a cancer scare, and a predisposition to skin cancers and breast cancers. And what I found with them, so they would have Gilbert's syndrome, and that pathway was completely overwhelmed by the toxicity. So it was both heavy metal toxicity and what we assumed was pesticide and chemical exposure. 

So I don't usually conduct testing for those chemicals, just because the cost of the testing is usually prohibitive. But I think it's pretty much assumed that when someone's in that occupation and they've got a stack of heavy metals like cadmium and mercury on their hair analysis, they also would have accumulated a whole pile of xenoestrogen, pesticide toxins, all those things. So, yeah, they really do struggle. And the liver can only handle so much for so long. And that's usually where the problems come in.

Andrew: Okay. So, I can get the wig in a zigzag a bit, but I need to ask the question now then, and that is that, does treating these people help them?

Maria: Yeah, absolutely. Well, if you're treating the liver, and helping the gut to detoxify, it's extremely helpful. And that's been my own personal experience, I have Gilbert's syndrome, I have pyroluria, and this is why I'm really into these areas, and I've had a lot of heavy metal toxicity as well. And my thinking is that I didn't get blood tests when I was a child because I grew up in Russia, and that's not really a place where they do preventative health care. Well, they probably do now, but they definitely didn't do that in the '70s.

So, based on my childhood symptoms, every time I would have dairy, I would just, you know, it would come straight back up. Any sort of saturated fat, anything like that, I had a lot of issues digesting. So I think I had Gilbert's expressing very early on in life. I was born with jaundice. Both my children were born with jaundice.

So, yeah, I think these things are present, and once you start resolving them, so addressing the gut health, addressing the liver health, replenishing the nutrients that you're missing. Because of the permeability that invariably comes with bilirubin elevation, addressing all those things is really, really fundamental, and supporting it with nutrients that support glucuronidation.

Andrew: You know what? I actually wonder if... You mentioned born with jaundice, and I wonder, because it's not uncommon for babies to have a little bit of icterus, and so they put them in the UV crib for a little while and everything's fine, "See you later. Bye." 

And I just wonder if there was any follow up of this supposedly transient welcome into life. I wonder if there was any follow up where that more Gilbert's syndrome would be picked up and then it would be seen as a condition?

Maria: Yeah. Yeah. I think there's a huge correlation definitely, that's another research study for someone. Not every baby who is born with jaundice will have Gilbert's syndrome. Definitely that's not the case. But I think there's definitely going to be a huge percentage, and how it impacts children, I think. Especially now we have, again, with hair analysis I see a lot of heavy metals on children. Pesticides, glyphosate, all of those things that are in the environment, those kids are definitely going to have a harder time detoxifying. And what you can see is elevated beta-glucuronidase on gut tests. 

So I have seen that quite a few times with kids when I do gut testing, they will have elevated beta-glucuronidase, and they will have Gilbert's syndrome, it's pretty much 100% correlation in the people that I’ve seen.

Andrew: That's interesting. So here we go. You know, look, we've got two tests there, kryptopyrrole or pyroluria, HPL, and you've got functional liver detox, both of which are lambasted by orthodox medicine, and yet which gives the integrated practitioner key clues as to what might help a patient. Particularly when you're thinking — I’m thinking as a nurse here — I'm thinking about medication toxicity. 

But I guess we have to answer the question, if things like stress, and dehydration, and infections trigger the icterus that's seen, the yellowing of the eyes, that sort of thing, and you get re-hydrated, have some rest, get over the infection, and it goes away, does that really mean that it is benign? Because you've still got these potential drug toxicities.

Maria: Yeah. Well, it doesn't really goes away. Yeah. No, look, I find that it doesn't really go away. So, unless you actually treat the issue, so treat the elevated bilirubin, it doesn't necessarily go away by itself on a blood test. So, I found, in terms of...

Andrew: But, I mean, medically it's supposed to be, what is it? Less than... I can't remember the...

Maria: Less than 15 is the…

Andrew: Fifteen, something like that. And that can be chronic, but it's not deemed pathological. It's deemed brown or blue eyes, sort of thing. But when you get things that can trigger a worsening of symptoms, like for instance fatigue, well, that's actually expressing itself now, isn't it?

Maria: Yeah.

Andrew: And you've got now drug toxicity. So, that's now expressing itself into a medical condition.

Maria: Yeah. Yeah, for sure. And I think also other factors like fasting for example, fasting is a really obvious bilirubin elevator.

Andrew: Right.

Maria: So, that's something to be aware of as well, because usually we want people to do fasted bloods. And so, as long as it's consistent, I guess it doesn't matter. But yeah, the bilirubin will be higher on fasted bloods, than not. And especially if someone's exercised before they've taken a blood test. So they've fasted and they've exercised, which is not uncommon, that's going to create a whole bunch of discrepancies on their bloods. 

But I think just viewing it as jaundice, that's just only one very small indicator of the underlying issue. That's when things become really obvious and people start noticing because someone's telling them their eyes look yellow. We can usually intervene 10 steps before that and really address this stuff.

Andrew: Got you. Okay, so, let's talk about treatment. What do you use, apart from that tea that you've got there?

Maria: Yeah. So, look, I mean, lots of liver and gallbladder support. So, I'm not a naturopath, so I don't tend to use herbs. But nutritionally, what I absolutely love is the nutrients that support that glucuronidation pathway in the liver. So, calcium-D-glucarate is the absolute number one star for Gilbert's syndrome. 

And I find that most people do have to be on it ongoing. So, personally, when I slack off and don't take it for a few weeks, sure enough, I'll do my bloods and the bilirubin will be up in the 20s again, and I'll go back on my calcium-D-glucarate and it's going to go all the way back down to 12 or 14. So, it is extremely, extremely helpful. 

Magnesium is a big hero as well. So, one of the nutrients that supports glucuronidation is magnesium. Fish oils…

Andrew: Sorry, can I interject? Do you tend to prefer a certain ligand there?

Maria: Magnesium type?

Andrew: I'm wondering about bile flow here?

Maria: Oh, bile flow. Yeah, usually things that would support bile, so, that would be taurine. Taurine is a really important one for bile flow.

Andrew: Right.

Maria: And again, nutritionally speaking, you know, I'm sure the herbalists will have a whole range of things that can support that as well, globe artichoke and all those fantastic herbs. But yeah, just from a nutritional perspective, taurine is a good one.

Andrew: So, overseas, I know in the states they have magnesium taurate. In Australia, we don't have that, it's not an approved listable ingredient, permissible ingredient, forgive me, by the TGA. So, do you tend to use another ligand of magnesium plus taurine?

Maria: Right. Yes. So I usually will use magnesium citrate, just because it's easily absorbed, well tolerated, all those things. Citrate or bisglycinate, and then usually a separate taurine, yeah. Just because the amount you need is pretty high. I do tend to use pretty high amounts of taurine in between meals. So, yeah, it does help to have a separate one. 

And then, yeah, the other one is fish oils. So, EPA is a really great antioxidant for the glucuronidation pathway. And the other one is bifido probiotics.

Andrew: Ah, of course. Yes.

Maria: Yeah. And I mean, I guess, depending on the microbiome testing, you know, what comes up for the person. But yeah, bifido is a really great enhancer.

Andrew: Now, that would also have an impact on short chain fatty acids, because they're affected by Gilbert's syndrome, aren't they? Is that right?

Maria: Yeah. So, the whole microbiome is affected. And, actually, at least a lot of this learning I have to credit Rachel Arthur, who has done some fantastic research into this area, and has been a great advocate of bringing Gilbert's into the limelight, drawing more attention to it.

Andrew: Yeah.

Maria: And yeah, she has very correctly pointed out that clostridia is a type of bacteria that feeds on bilirubin. And what I find is 100% of the time, I'll do a gut test, and the Gilbert's person will have an overgrowth of clostridia in the gut, and that's based on Rachel's research. I think it's seen as actually, it's an adjustment, like a protective mechanism to chew up some of that bilirubin in the gut.

Andrew: Oh, I mean, there's a can of worms there. How many questions you got? How much time?

Maria: Yeah, it's a big topic though.

Andrew: Well, do you find that there is, I can't say a tie-in, but let's say a worsening of symptomatology in those children that might have neurobehavioural disorders if they also have Gilbert's syndrome? Do they have a worse time of it because they've got high clostridiales?

Maria: Yeah, they would definitely, yeah. And again, look, there just hasn't been enough research. But we do know, anecdotally, and lots of practitioners within the MINDD forum have spoken about this that a lot of kids on the spectrum have pyroluria. 

Andrew: Right.

Maria: So, that's pretty well established, I think, yeah, and a lot of clinicians will find that. So, my guess would be, a lot of them have pyroluria. It's hard to get kids tested for blood. So, we don't know how many of those also have Gilbert's syndrome and elevated bilirubin, but my guess would be a big percentage would have it. And if we were to do routine blood tests on these children, which is really tricky, it would be more obvious. But, yes, absolutely, yeah, so, clostridia is a really big issue in spectrum disorders. Yeah.

Andrew: And one of the other questions floating around my mind is this quandary, this sort of catch-22. You've got issues with oestrogen detoxification. We know that exercise helps to favour the two-series oestrogen, hydroxyoestrogens, which are beneficial, and it decreases the sixteens, helps to get rid of other oestrogens in total. Also helps with enterohepatic recirculation and our microbiota, milieu, diversity, we know that. 

But then you've got fatigue as one of the symptoms of Gilbert's. So, what's this sort of patient populations' exercise tolerance? And how would you go about that? Do you tend to favour different types of exercises maybe, like more strength rather than cardio?

Maria: Yeah, definitely. Yeah, I think there's definitely a fine line between managing fatigue and getting all those benefits from the exercise. So I never tell people to stop exercising unless they're in such chronic fatigue that they can't get out of bed. I think it's more about not over-exercising and not over-exercising on an empty stomach, which is particularly destructive.

Andrew: And dehydration.

Maria: And I do tend to steer people away...and dehydration, exactly, yeah. And I tend to steer people away from the chronic cardio, just that really high cardiovascular demanding, even all those new trendy workouts like CrossFit. I find someone with Gilbert's syndrome, it's just too demanding, it triggers the breakdown of the red blood cells. And it just cascades the whole thing. 

So, there's lots of other ways to do it. You can do your walking or fast walking, you can do weights, weights are fantastic for a whole bunch of reasons. But none of those things are going to trigger these excessive Gilbert's symptoms. So, yeah, it's definitely, it's very individual. But I think, overall, the benefits are amazing from exercise, it's just to not overdo it is just the goal.

Andrew: Right. There seems to be also a changing of the guard with regards to doing cardio first before strength. Some people are swapping that, strength first and then cardio. Do you use that sort of stuff, or…?

Maria: Look, I'm not, you know, because I'm not really an expert in exercise. I tend to send people on to the experts, in terms of training, who are very nutritionally and naturopathically minded. But the general guide I would give to people, I always prioritise weights, because I just find the benefits of that, you know, for mental health, bone health, females. I see it might be a group of patients is usually females 35 to 55. And I just find getting away from that cardio and that overexertion just onto some nice weight training, and walking, and yoga, and things like that is usually what I try and do.

Andrew: Right.

Maria: Yeah, less impact. Yeah.

Andrew: Yeah, I'm a fan of doing my push ups. What I do is I turn the iPhone on its side and I film myself doing push ups against the wall. It's really good.

Maria: Yeah. Makes it look good, yeah.

Andrew: Now, diet. Of course, this is going to be a hallmark. This is going to be the keystone of treatment. So, what dietary recommendations do you use? Do you recommend?

Maria: Yeah. So, usually, what I say to people, and this is probably going to go against the popular trend. The keto diet is probably the absolute worst diet for someone with Gilbert's syndrome. So, loading up on saturated fat is going to be really, really tricky just because the liver and the gallbladder capacity that is not there. So, most of the time, I will get people off things like full fat dairy and full fat coconut products and really high fatty meats. So, burger patties and all that sort of stuff. 

And I just find, when they drop that saturated fat out of their diet and get the leaner versions of the proteins, particularly, everything just functions so much better. They feel better, they digest better, their bowels move better. So, I find that's a really, really tricky area for Gilbert's people. 

And definitely emphasising foods that are plants, vegetables that are great for moving the bile. Fibre, lots of fibre for feeding the microbiome so that the leaky gut is less of an issue. And definitely glutamine foods, because leaky gut is such a problem with Gilbert's syndrome. I love bone broths. Bone broths with the fat skimmed off, so, not with the fat in them. So, all glutamine based foods that can repair the lining. And also high-zinc foods, which I kind of emphasise for every single person because everyone is so...

Andrew: Pepitas, pepitas, pepitas.

Maria: Yeah. And yeah, exactly. Bitters. So, yeah, your rocket, your dandelion, all the bitter greens, everything else, yeah.

Andrew: Just a question about tolerability of high-fat food, which is quite a lump of fat usually, versus fish oils and supplements that are of a fatty acid nature. Do you have any issues with tolerability there? Do you tend to use maybe the phospholipids of krill oil? Or I understand one brand in Australia has a, basically a predigested fish oil out there. Do you tend to favour different ways of getting these good fats into people?

Maria: Yeah, I find that all my non-saturated polyunsaturated fats are usually not a problem for people, it's really just the saturated fat. So, most of the time, they won't struggle with nuts and seeds, or olive oil, or fish, or any of those lighter fats. So, I find, yeah, usually, EPA is being a really supportive nutrient for glucuronidation. Yeah, I'll usually use just a really high quality practitioner brand fish oil. I love hemp oil as well, and the nut oils. Just you want the spectrum of all those polyphenols to get all the antioxidant power. But I don't really find any issues with that. It's usually just the saturated fat.

Andrew: Yeah, and I'm pretty sure you've covered this off, but just to make sure that we are saying it, more plant protein, a little bit less animal protein, would you favour that? Like the nuts and the seed?

Maria: I would take more... Yeah. But also just more lean animal protein. So, not necessarily cutting it out. But like more the traditional paleo way that we used to eat, which is more the game meats, the really lean game meat. So, in Australia, kangaroos are a really excellent protein source for us, or just really lean lamb and beef that are organic grass fed, no pesticides, all that. But yeah, I find usually protein is not, animal protein is not an issue. It's more just getting the really lean varieties.

Andrew: Now, you also do SNP testing. And we've sort of covered off that. But can you just go through what sort of SNPs you look for? Is it a conglomerate, is it a group that you look for, or is there one hallmark that tends to stick out?

Maria: Yeah, with Gilbert's, there's a few different SNPs under the UGT1A1. So it's usually UGT1A1 and there's a few variations of them. So, when I order the testing...and unfortunately, not all panels do the enzymes, so, usually, I will order 23andMe panel from the U.S. and just get that analysed.

Andrew: Everything. Yeah.

Maria: Yeah, that will usually have the UGT SNPs listed in a whole section. So, for example, in my test, I had four homozygous UGT1A1 SNPs in that category. And I'll usually see, with Gilbert's people, I'll usually see at least one or two homozygous, some heterozygous. But yeah, there's usually a whole collection of red in those areas.

Andrew: Right. But this is my pondering about the future, that we won't be concentrating on a SNP, but a group of SNPs, and they may seemingly be not related at first, but when you look at biochemistry — hey, we're a body. Do you ever find that there's tie-ins with, let's say, pimped SNPs with regard to choline, or...

Maria: Choline.

Andrew: Yeah, other things like monoamine oxidase SNPs because of...

Maria: Yeah. I find usually the COMT, yeah, COMT does come out quite a lot with these people. Yeah. So there's a whole oestrogen handling/catecholamine handling issue that comes into it. Yeah. So, quite often, people with Gilbert's who present with anxiety, for example, I'll usually find there's going to be a COMT homozygous in there somewhere.

Andrew: Got you.

Maria: So, yeah. Again, that liver damage. My theory is that intergenerational liver damage. Yeah.

Andrew: Yeah. We've mentioned paracetamol, acetaminophen. Forgive me…

Maria: Non-steroidal inflammatories.

Andrew: I thought I'd done it. We've mentioned several drugs. We've mentioned the oral contraceptive pill, paracetamol or acetaminophen from the U.S. You've mentioned antidepressants as well. Can you elucidate a little bit more on that and also cover off any other drug groups that are of importance, please?

Maria: Yeah. Well, usually I find when someone is on one of those SSRI medications, or anxiolytic drugs, or a lot of the time it because usually that recreational drug use as well. So, every person is affected differently. But yeah, all those drugs have to go through a liver pathway, and glucuronidation does take a big hit in that detox. 

So, yeah, the less of those things a person with Gilbert's can have, the better off they will be. And I do find alcohol, even though it doesn't go through that same pathway, I find that most Gilbert's people do far better with no alcohol or very limited alcohol intake, because it's that bucket, it just fills up the bucket. And obviously cigarette smoke and all the other things will add as well.

Andrew: Yeah. Okay. Of course we haven't covered illicit drugs or recreational drugs. What about them?

Maria: Yeah. Well, that's definitely going to have an impact on that pathway. So, lots of people put that on their questionnaires when they come in and do my intake questionnaire. And yeah, I think any sort of adverse effects, particularly, psychotic effects or episodes, anything like that, it's probably going to be in a person with a glitched, with a pathway of some kind. So, yeah, it's quite likely.

Andrew: Okay. So there's several things going through my mind here with the medications that we've discussed. Paracetamol, ibuprofen, or certain NSAIDs, and you've mentioned illicit drugs, certainly fat-soluble drugs like THC. So, what about people in chronic pain? How do they fare with Gilbert's and what are their options?

Maria: Yeah, look, it's an interesting one. I don't tend to see a lot of those presentations. Chronic pain is probably not my big area of clinical focus. But yeah, I think they'd have to definitely be careful with what they're taking and how they're detoxing it. And looking at their stool, looking at their digestion, watching out for any of those symptoms that might be signalling that they're not detoxifying. And potentially starting with really low doses, if they need to be taking that and increasing really slowly. Yeah, we're just watching for side effects.

Andrew: Have you ever found that if people are required, because of another condition, or their choice, let's say the OCP, that they wish to continue taking the OCP? Have you found that using natural treatments benefits them by taking away those adverse side effects? That's contextual.

Maria: To an extent, yeah. To an extent. My goal is to usually just educate and inform for other options that are non-hormonal, that don't have to be ingested. So, yeah, definitely advocate barrier methods and things like that, but...

Andrew: Perhaps directing them to Lara Briden and the hormonal…

Maria: Yeah, exactly. Yeah, and all sorts of natural tracking of cycles and all of those things. But yeah, I do tend to steer women away from the OCP, just because there's so many other negative effects. But yeah, look, you can manage it, you can give them liver support supplements, and you can improve the glucuronidation and other liver pathways in as many ways as you can. I mean, ultimately, it does add up, so, at some stage in their life, that time that they spent on the OCP always adds up and always goes with copper toxicity, and all the other issues that come with it. So, it's a tricky one. I think women are still choosing that often because it's an easy choice. But it does definitely always carry some baggage.

Andrew: Yep, sure. Okay. So, one last quick note. It's not one last, I have several. But for now, we know that fat-soluble vitamins, certainly vitamin D is a real issue in the eastern seaboard, at least, of Australia. And it's not just Tasmania. We have a real issue in Queensland, southeast Queensland. So, what is the issue with Gilbert's and fat-soluble vitamins. Do you find they're more at risk of not just vitamin D, but let's say vitamin K?

Maria: Yeah, definitely. Yeah. So, the fat-soluble vitamins are getting absorbed through that glucuronidation pathway, so, A, D, E, K, all of those have to be digested and absorbed. So, if someone's coming in and they're having loose stools, light-coloured stools, nausea, all of those sort of fat malabsorption signs, that person, depending on the length of time that they've been having those issues, they're going to have issues with absorbing their vitamin D and A. So their immune system is not going to be working very well. 

Vitamin K, they probably will have calcium absorption issues and bone issues. And Vitamin E, our major antioxidant, so, they're going to have a lot of oxidative stress and possibly thyroid issues as well. So, that's a really common thing I do see and we can definitely try to improve.

Andrew: There's so much more that I have to look at now. Like I've got things going round in my head about what about, are there any case histories out there floating around about warfarin instability and Gilbert's? You know, blah, blah. But that's for me later. 

And I guess for our listeners, I would love your interaction by the way, if you find that you've got any particular interesting cases, or interactions, or concerns, then please let us know at fxmedicine.com.au or via our social medicine platforms. 

But, Maria, any last thoughts? What about caveats, safety issues?

Maria: Safety issues. I guess, yeah, as we mentioned, you know, just being really careful with any medications and being aware of the issues that you have with Gilbert's and liver capacity. And I think the main message would be just to really minimise toxicity as much as possible in your life. So, cutting out the obvious, the cigarettes, the alcohol, the caffeine, the pesticides, eating organic as much as possible. That's a huge area because pesticides do go through glucuronidation pathway. 

And just making sure that you're tracking your bloods and looking at what your bilirubin's doing. Consult with someone who is proficient in understanding this condition. And yeah, using those nutrients like calcium-D-glucarate, magnesium, zinc, all of those things that we mentioned, to just really manage the condition the best way that you can. You can function really well, I'm definitely a testament to that. I do try and look after my liver and not have any of those negative effects from Gilbert's. It's definitely very manageable. It's just having that focus and knowledge of it.

Andrew: So, I've got to add one last question before we go and that is, how do you...you know your stuff, you live and breathe this stuff, you can just see it by looking at you. But when you're talking to patients who come from the other side of the tracks, not having a good diet, too high saturated fat, not enough, I'm going to say Australian grown, Australian made olive oil, but all of the bad things in life, and they don't have a good lifestyle nor diet. Tell us a little bit about the challenges that you face and how you overcome those.

Maria: Yeah. So I think it all comes down to education and just explaining to them what is happening in their liver. And I do spend a lot of time drawing little pictures of buckets, and the buckets being emptied, and leaking buckets, all of those sorts of things. It's, yeah, just educating them and understanding like how important this organ is, and linking the symptoms that they're having directly to their lifestyle. 
And usually I find, I can convince people to try it out for at least a month quite easily. You don't have to tell them that this is a forever change, even though some of these things should be. Just get them to start doing these things for a month, and that's enough time for them to feel dramatically better and improve their digestion, improve the way that their skin looks, the way that they feel, their energy, all those things when digestion improves everything. 

So, yeah, just getting them to commit to small changes for a short amount of time usually is enough for them to then go, "Right. Okay, this is how good I can feel. Okay, let's do this." So, yeah.

Andrew: Yeah. It's actually it's obviously a boon for your patients that you've unfortunately have this condition. I'm not saying it's necessarily a bad thing. But it's good to speak with a clinician that's actually got this personal experience. And you've overcome it, you've managed it, and now you can actually teach that, not just for your patients, but indeed for your peers on FX Medicine. 
It's an absolute pleasure to have you on today, discussing Gilbert's syndrome. Thanks so much.

Maria: Likewise. Thanks so much, Andrew, and great to talk to you as always.

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


Other episodes with Maria include


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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.