Fatty Liver Expert: Your Liver Could Be In Trouble | Dr. Vishal Patel

0:00Dr Karan: One in three adults have fatty liver disease and many don't even know it. But protecting your liver health is vital and cleaning your teeth could be one part of the solution. Dr. Vishal Patel is here to tell us how to improve liver health and why your mouth, gut and liver are more connected than we realized. We know that people who've got liver disease tend to also have poor oral health, dental decay, teeth missing, poor dentition, all these factors. What we see is that the more advanced liver disease someone has, the more overlap there is between the mouth and the gut in terms of the type of bugs you have, number one.

0:31Dr Karan: I'm Dr. Curran, and in this podcast, I speak to the world's foremost experts in science and medicine to cut through the BS of modern health advice. Thanks as always to Throne Science, the world's first continuous, hands-free, smart toilet platform that can track your gut health with every flush for sponsoring the show, as well as Loam Science, the world's first invisible fiber blend that's also clinically backed. Vishal Patel, thank you so much for joining me. Pleasure to be here. Now, you're an expert in hepatology, a study of liver, liver disease, and specifically looking at the role of our gut bacteria and the microbiome and its impact on liver disease, but also specifically fatty liver.

1:10Dr Karan: People don't really understand the impact that liver disease has on the world. There's 1.5 billion people in the world living with chronic liver disease. You know, that is a significant chunk of the world. What do people need to understand about their liver health? I mean, the liver is so important in general, right? So every organism, and as a hepatologist, I'm naturally going to be more biased towards your liver health than perhaps the cardiologist when you think about heart. But actually, liver health is a really good barometer in terms of your overall metabolic health. And as you mentioned, fatty liver disease, you know, as an epidemic is exploding.

1:42You know, years ago when I was training to become a hepatologist, you know, it was other causes liver disease which are very much on the radar, particularly viral hepatitis, as well as alkaline to liver disease. And whilst those are both still significant causes for people becoming sick with chronic liver disease, whether cirrhosis and scarring the liver, fatty liver disease is very much now, you know, the thing that we are really concerned about because it's affecting all swathes of people from all backgrounds, ethnicities, and the sort of knock-on effects of developing this at an early stage mean that people often living with the sequelae of those problems for years and years and years.

2:17And as I mentioned, it's really a barometer for your overall metabolic health and risk. So when we find someone detected to have fatty liver disease, and there's different stages and gradings which we can get into, the biggest concern there is actually what does this mean for the rest of them, their health in terms of the risk of diabetes and cholesterol, risk of heart attacks, risk of strokes, and even risk of cancer. So it's a huge concern at the moment. but there are definitely ways to sort of manage it if you're diagnosed with it but you know my biggest motto with these sort of things is very much prevention prevention is absolutely key in the earlier we can get that message out to people a prevent the disease in the first place but if you've got it what can you then do to actually start to halt that process but also then start to reverse it and regress it ideally to get yourself back to sort of what we'd hope would

3:04Dr Karan: be a normal liver so yeah the liver itself is such an underrated organ because it has over 500 functions which is what the medical tech that we know yeah typically site I guess and a lot of people maybe think about it as a excretory filtration organ but it's producing things producing cholesterol processing cholesterol sex hormones so many things so you know it does connect to the gut to the brain to the bloodstream why does it have such an impact on our health beyond just being that filtration organ yeah so I mean you're absolutely right So the typical way we think of liver is very much as a filter.

3:40And that's generally thought of as a filter for whatever's coming out your gut. So your gut is, you know, obviously it's long tube. They're responsible for, you know, digestion of nutrients, absorption nutrients, and also filtering of bacteria and their products, which some of which you do, you don't want them in the human body. And all of the blood that comes out of your gut, you know, liters and liters of it is then filtered through the liver through a vessel called a portal vein. And that is an absolutely critical vessel because everything that's coming out in terms of digestive stuff from your gut is ending up in your liver.

4:10And your liver is very much a secondary firewall. So, you know, your gut's the primary firewall, which kind of prevents some of these toxins, particularly from the gut bacteria, which are potentially harmful from leaking out. But your liver is very much there to try and then stop those toxins if they do get out. If your liver is unwell for whatever reason, and particularly if you have kind of end stage cirrhosis where you've got scarring, so there's less liver cells to do the job of the liver. and obviously that's replaced by scar tissue essentially you get less of that filtration happening and that's very much a kind of one-way system between the gut and the liver what we sometimes have kind of poor understanding and explaining is actually the liver to gut sort of relationship is also equally important so you know your liver is responsible for producing bile and bile is essentially a chemical that contains digestive enzymes and that's very much that's really important in terms of fat and vitamins of absorption so the liver produces bile ends up in in the in the gut through the bit of small bowel called the judenum but that's the sort of biodextual relationship between the gut and the liver um obviously the liver does as you say you know we think at least 500 different things but actually probably far more than we recognize and we're still learning all the time and ultimately it's the reason where if you have liver failure there is no liver dialysis machine that you have with kidneys you know in the worst case scenario we potentially need to replace someone's liver by way of transplantation um so everything we're now trying to do is trying to prevent people from getting to that stage ideally because the liver is so pivotal to your kind of you know your health and life full stop no specifically i mean we there's

5:39Dr Karan: so many tangents we could go down with regards to liver health one thing i want to focus on because it's personal to me and something which is should be personal to a lot of people because one in three people worldwide have fatty liver disease and the problem is that usually the common sign is that it's no symptoms it's asymptomatic it's often pinked incidentally as it was for me uh slightly targeted but one in three people have fatty liver disease what is the full spectrum of fatty liver disease and why is that a growing huge wave of a problem that you know in years to come that's actually going to be significantly bad for you know population health yeah so i mean you've touched on already so the problem with this disease is like many liver diseases it's silent and people can have actually quite advanced liver disease with fatty liver disease without having any symptoms whatsoever and it's picked up incidentally sometimes because they are having a direct to kind of liver health check which is much more unusual so that's for example through kind of health screening that you may be accessing to your general practitioner in the hospital or through sort of you know private insurance but the other main issue is when you've got other kind of metabolic risk factors so people who've got for example high cholesterol diabetes overweight with obesity these are people who've got metabolic risk by definition because of those different risk factors and that's often something that also drives people getting fatty liver disease the other slightly unusual group is people who have almost no risk factors to all of us they'll look fairly healthy they'll be going to the gym pretty active eating a reasonable diet and those individuals may still have fatal disease sometimes due to an inborn kind of error of metabolism based on how they process lipids and how lipids and fats end up in the liver so that's this kind of why do they get it um a huge problem now is very much around the way we eat the lack of exercise we don't sleep well and i kind of call it self-sabotage it's it's not deliberate but you know everyone's very busy a lot of people that i see in my kind of clinical practice are very much sort of day-to-day sensible doing their thing not necessarily overindulging but because of a combination of you know poor diet um let's say not exercising not being very active sleep definitely has an impact on us so we know the circadian kind of rhythms and dysfunction around that is really important so those combinations and then you put metabolic risk factors on top that you may or may not know about mean that you then potentially months or years later have a problem which becomes quite significant and serious you talked about stages so you know the stages are as i say very subtle initially so this is very much about how fat ends up in the liver it starts to irritate the liver causing inflammation in the liver and inflammation in the body anywhere is a problem but in the liver it's a particular issue because it irritates the cells it causes the immune cells in that area to sort of start to overreact and essentially you get a bunch of chemicals spilling out particularly cytokines chemokines which essentially then can injure the cells and the liver is really complicated in the sense that you've got kind of two lots of blood flow into liver artery and vein you've also got outflow into the kind of rest of the body but then you've also got the bile ducts and you've got the liver cells themselves so it's a complex kind of anatomical system which is doing these kind of fiber and old functions and when you get inflammation area the blood vessels get irritated the cells get irritated and so on that inflammation and and fat in the liver over time can then need to sort of very kind of minimal scarring which we call fibrosis and now different stages of fibrosis kind of f123 but essentially as you progress and this can happen of months and generally years the worst case scenario is during cirrhosis and that's where essentially the liver as mentioned earlier is the kind of functioning cells are replaced by scar tissue and if you don't have enough functioning cells in terms of critical mass to do those different functions you then start to develop a liver failure symptoms and we get a lot of people refer to our practice for liver transplantation you know with fatty liver disease maybe 50s and 60s perhaps even earlier who are you know essentially who've had this kind of hidden disease for years and years and years that they probably could have done something about, but didn't know.

9:41And now got to a point where they've got a scar.

9:43Dr Karan: Well, I think there's a couple of things to unpack there. I guess, number one, the stigma of liver disease. People often make the psychological association between liver and alcohol. So if someone has liver problems, it's because they're an alcoholic. That's, you know, a pervasive myth that's been there. So I guess the initial terminology, non-alcoholic fatty liver disease was, that's why it was changed to muscle, Yes, but secondly, also, given I've personally gone through fatty liver disease, albeit very early stage, I picked it up early. You know, my mom told me to go and get a liver scan because of my high cholesterol.

10:17Dr Karan: Always listen to mom. Always listen to mom, especially if your mom is an Asian parent. You definitely have to listen early stage, mild stage one fatty liver disease, beginnings of fibrosis and the scarring that we were talking about. And for me, it was linked to high cholesterol. And when I changed my lifestyle factors in my diet and increasing exercise, losing weight, that had the halo effect of reversing the fatty liver disease, albeit over a couple of years of slow, steady work. And I still get to this day, get repeat annual ultrasound scans to make sure I don't have a recurrence of that. And it was a long process.

10:51Dr Karan: So for me, it was linked to that. But, you know, fatty liver disease in itself, how long is that timeline of progression to someone who's having no symptoms? They have metabolic syndrome, insulin resistance, high cholesterol, all these sort of obesity worsening. What is the timeline from getting the initial deposition to then progressing potentially in the worst case scenario to chronic liver disease and then liver failure? yeah so in general the timeline from start to kind of cirrhosis and or developing symptoms of what we call liver decompensation where you then get you know the kind of really horrific complications um that end up meaning you're hospitalized uh and potentially very sick is generally years okay so that's usually the paradigm there will be people who will progress more rapidly because when you have a combination of risk factors for example insulin resistance or full-blown diabetes hypercholesteroidemia overweight and they drink excessively from alcohol point of view you know these things kind of work synergistically so on their own it's not one plus one equals two when you have these things as one plus one equals seven in terms of impact on your liver right so it is generally years and what we have now in our kind of armamentarium to sort of diagnose is not just the ultrasound scans which are okay in terms of saying there's some fat in the liver or lots of fat or whatever that's a sort of semi-quantitative way based on the person doing the scan we've now got access to you know machines called fiber scans where we are able to essentially put a wave an ultrasound wave through the liver but very different to the ultrasound scan what it does it gives us two readings one is it gives us a fat content reading and then also gives us what we call the liver stiffness reading and the fan content reading is really helpful because it kind of quantifies with a number this is the amount of fat in your liver and so if you have sequential scans over time you can see which way the fat content is going ideally you want it to be going you know in in kind of the southern direction but the other one which is the kind of liver stiffness reading is super important because that's the one that's telling you whether or not you're developing fibrosis and or heading towards cirrhosis and they have certain cutoffs and thresholds where you say this liver is a happy healthy liver whereas you know fibrosis stage x y and z kind of marries up with those sort of liver stiffness scores but essentially a soft liver yeah is a happy liver yes do not want to have a stiff liver ultimately so in my case with my mild fibrosis and early stage fatty deposition.

13:13Dr Karan: It was easy to reverse with lowering my cholesterol, losing weight, exercising, cutting saturated fat. What is the final stage at which a person still has control over lifestyle factors and maybe medications for certain metabolic problems that they can still reverse over several years their fatty liver? And when is it too late? I guess the way I would always kind of address that is it's never too late to do something about your liver health right so even for our patients that come in with fat liver disease you know and they've ended up getting cirrhosis and or complications you know which land them in hospital and potentially needing a transplant it's still never too late at that stage to put into place measures which address all the things we've been talking about becomes much harder when you've got end-stage liberties to do those things because you are more lethargic you have less muscle you know there's all sorts of symptoms which symptom burn which kind of hits your ability to exercise etc etc so it's ideal to get in before you got to that end stage and to really go hard on all the things we're talking about so absolutely diet and diet you know is multifactorial right we all eat differently we're exposed increasingly to carb-lating ultra-processed sugary foods that's oversimplifying but you know what i mean um and it's harder to make healthy choices depending on what kind of lifestyle you lead you know so there's there's that aspect but it's it is possible but it takes a bit of planning and it takes a little bit of and i don't like the word discipline because i suggest that your lack of discipline means that you've developed a disease it's more because environmental facts are kicking in and making it harder for us to eat well so that's number one number two is around the exercise so you know you mentioned being overweight and you obviously put the hard work in and you got your weight down now you know if we look at the kind of guidelines just from a general perspective we should be exercising 30 to 40 minutes a week um 30 to 40 minutes sessions three to four times a week that's the aim and the aim there is to be raising heart rate sufficiently so that you are sweating um we will all have different kind of heart rate zones which which you know based on age and fitness but that's really the minimum so when people talk about i've done 8 000 steps or 10 000 steps that's sort of a measure of activity which is great it's better than doing 5 000 steps or no thousand steps but 10 000 steps and not raising your heart rate isn't going to touch the sides there so it's really important for us to all realize that your cardiovascular health is you know absolutely linked to your liver health and actually the more active you are and the more kind of consistent cardiovascular exercise you're doing super important the other bit of exercise is not just kind of you know running or cross training or swimming which is great for that kind of heart rate issue we need to be all doing lots more resistance work as well because ultimately muscle is what essentially burns calories uh and the more muscle you have the better you are going to be it's in terms of managing kind of carbohydrate loads and so on that's one bit the but the other bit is that's you know and especially as i'm as i approach my 50s i'm much more aware of the fact that you know once you hit 40 you lose one percent of muscle mass every year just naturally so you know if i did nothing to to sort of help myself by the time i'm 60 i've lost 20 of my muscle mass so from a kind of you know living well perspective let alone how do we manage our sort of cardiovascular health and our liver health um you know a really big part is resistance training and making sure that's better than, you know, as effectively as possible.

16:25Dr Karan: Yeah. It's interesting. The last guest we had on, he was actually a muscle protein expert. And we were speaking about the gut muscle liver access, especially the muscle liver access as well. Muscle, especially resistance training, producing myokines, other neurochemicals, providing anti-inflammatory effects, which obviously will no doubt help to reverse any low grade inflammation that's produced by the fatty liver deposition. But I guess also to your point that exercise independently, but also in addition to weight loss, based on all the studies, it looks like weight loss, whether it's five to 5 % of your body weight or 10 % of your body weight is the biggest, most evidence-based lever for reversing and preventing the negative sequelae of chronic liver problems, right?

17:11Dr Karan: Like in biopsies, they've actually shown reversal of fibrosis with just weight loss. Correct. So a lot of the clinical trials that have been done in the fatty liver disease space will historically and even even more recently have required our trial participants who are patients with fatty liver disease to have a kind of a biopsy when they go into the trial whatever that trial is and then they would tend to have a second biopsy you know six twelve months late depending what the trial protocol looks like and what the agent is even in those people where they haven't had a response to the newer therapy what they found is that when people lose weight and it's usually the kind of the magic number is around five seven percent after that you're winning but that's the minimum amount you need to be losing to see an effect that's where you start to see reversal osteotosis and sometimes reversal fibrosis as well so this kind of old adage of when you get scarring liver not necessarily end-stage cirrhosis scarring but sort of early fibrosis similar to what you had or even medium-stage fibrosis that is absolutely reversible so this kind of concept of oh i've got liver disease and i've got some scarring and i can't do anything about it is utter nonsense you can and the earlier start and the more aggressive one is in getting into that, the better, because it just means you're not kind of developing that risk and that sort of damage moving forward, essentially.

18:23Dr Karan: Quick one before we continue, and something I've been genuinely nerding out on in my chief of science role at Throne Science is poop and pee. You see, most of us are completely blind to what's happening in our guts and urinary health day to day. We often wait until something is wrong, but your body's actually constantly churning out data in your urine, in your bowel habits, in those patterns that most people never track. I'm proud to say that at Throne Science, we're building technology that captures exactly that. Passive, consistent biomarker monitoring of your gut health, your hydration status, your prostate health markers, without you even having to think about it.

18:58Dr Karan: From a clinical standpoint, the shift from reactive to continuous monitoring is really important because that is where the early signal detection happens and that's when you can change your habits and hopefully outcomes as well. I've been deeply involved from the science side because I think the research here is serious. And with rising rates of colon cancer, poop talk is no laughing matter. So if you're curious about what that data could tell you, the links in the show notes. Now looking maybe more on the diet, we touched on it off air, we're talking about fibers, fermentable fibers. You know, again, for me personally, there are so many factors obviously leading to fatty liver, genetic factors, obesity, diet is a huge component.

19:36Dr Karan: Mine was, I guess, twofold. The fact that I was consuming or under consuming fiber, which we know is a beneficial for liver health in general from producing short chain fatty acids, but also just, you know, helping the liver to increase LDL receptor activity, clearing liver, you know, binding it, excreting it in the stool, but also cutting down saturated fats. For me, I was consuming a lot of saturated fat, which was harmful for me. What is it about diet? Is it a combination of fermentable fibers, polyphenols, antioxidants, plant food, in addition to just moderating animal protein intake if you can?

20:15It's essentially what you just described, but probably some nuances around that. So animal protein, by definition, will come with a significant saturated fat because of the nature of it. There are obviously animal proteins which are better for you. So if you're eating, for example, lean chicken breast, you know, that's correct. you know those are the kind of meats and i guess you know sort of non-plant um proteins that we want people to have because they come with benefits particularly you know the fatty fishes and omega-3s and that kind of thing um obviously you know rich meats for example pork or beef and so on you know as a treat that's fine but not as a kind of everyday for sure i talked earlier about ultra processed foods and i'll come back to that you know we inadvertently consume a lot of these without realizing it yes supermarkets are better now sort of labeling stuff but you know generally when we're doing our shopping if you've got young kids it's very easy to pick these things up and then not quite realize actually what you're eating is essentially garbage but it tastes great and it's and it's and fundamentally actually it's because it's also you know much easier to access in terms of opening eat it be done with it you don't have to sort of necessarily cook and so on so that's a big thing to avoid and we need to be much more conscious about that looking at sort of plant-based stuff so you know really the fiber bit is super important yes and we don't talk enough about this I think in health it's underrated but certainly when you start to hit diseases which are metabolic in nature for example you know your diabetes cholesterol fat liver disease cardiovascular disease related issues you know yeah that's what you're putting in is very much what comes out and very much what makes you and I know that's an old adage but it's really important and we are not getting enough fiber as a general population most people are getting 10 to 12 grams they're lucky you know 30 is the minimum and if you look around the world and you look at those those kind of groups of indigenous people that have done well you know I grew up in Africa Zambia's home and if I look at what people eating there you know it's it's a much simpler kind of diet it's much a subsistence base yeah but you know there's a reason why some of these disease that we're seeing the Western world don't just don't exist in part these parts of these world sadly they are coming through because of westernization of the summer populations um but fiber is a huge thing there right and it's it's kind of this fermentable non-fermentable different types and so on but we're not getting enough um let's say in health and certainly in liver disease it's impossible that a better amount of fiber is not going to be better better for your liver health in general have we got the data it's coming through slowly you know a lot of my work is around the microbiome not just the gut but the mouth as well

22:43Dr Karan: and all of these things obviously interrelated i think you know the one sort of problem i have with the recommendations about fiber intake is that, you know, number one, it's based on Western populations and number two, it's decades old. So we continue to put this message of 30 grams of fiber a day. And I think that misses out some of the data that they see within those epidemiological studies where they don't show the full dose response curves that we know. Sure, You get most of the benefits of fiber at 25 to 35 grams a day. You get reductions in all cause mortality, gut benefits, cancerous reductions around that, you know, the most of it.

23:24Dr Karan: But actually you get additional yield beyond that, which they never talk about in these studies. And to your point, I briefly lived in Africa for a year when I was three in Nairobi. But I always talk about the Hadza tribe in Tanzania, right? eating a diversity, wet season, dry season, different types of fiber, which again, we don't get enough diversity of fibers. And they're eating over a hundred grams a day. And even if you're looking at their microbiome compared to other African cohorts in more sort of, you know, who are eating processed diets and maybe Malawi versus Hadza, Italian populations, US populations.

23:58Dr Karan: There was that fascinating study done where they've got these unique bacterial species, which are almost extinct in other populations. and that alone is nothing to kind of write home about. But when you combine that with the fact that they also have these lifestyle factors, also have a low burden of chronic disease, it starts to make sense that you should eat more fiber, definitely, maybe not 100 grams a day because it takes a while to get there, but also the diversity as well, you know? And maybe it's as simple as next time you go shopping, instead of just buying some more carrots, buy some beans, buy an aubergine, something different to your routine, right?

24:34Dr Karan: That diversity. Yeah. I mean, when you're looking at sort of population based health, right. And you're looking at the studies, particularly nutritionally driven. A lot of the endpoints are often disease related. So what the sort of focus is often, you know, are we preventing an endpoint which is unhealthy, essentially. To your point around sort of, you know, what happens if you you're above that 30 grams kind of threshold, 40, 50 or whatever that looks like. we're not necessarily good at designing studies we're looking at sort of health benefits and i think that needs to be weaved in a much more around how we design our trials and that kind of thing and that will come with time um but that's the reason i think why this space needs a lot more sort of evolving and a lot more thought in terms of how we do our clinical trials something um you know that when i was diagnosed with fatty liver disease i was looking at everything which could accelerate my you know move away from fatty liver you mentioned already Fibers are a big component of that, soluble, fermentable fibers, but also coffee.

25:32Dr Karan: You know, to this day, I actually don't enjoy coffee. I don't hate it. I don't enjoy, I don't love it. I have one to two cups of just black coffee a day. And because of the abundance of data, it's pretty good evidence base that you can actually, I use it as a supplement. I take black coffee every day as a supplement. I don't like it. It's just something that I'll swallow every day because I know that it's reducing my risk of developing chronic liver disease. it's you know good for the gut as well and i just have it as a ritual every single morning and so to that point what else is there from maybe a supplement point of view that has any evidence for that beyond coffee and beyond soluble prebiotic fibers people talk about milk thistle and all these random things which don't really seem to have the evidence yeah so it's the million dollar question and it's one that we get asked very regularly with patients and i'm often alarmed by the concoctions that that people come in with uh particularly quite advanced liver disease and actually some of these concoctions actually contain chemicals and herbs uh which potentially can do quite a lot of damage to the liver and inadvertently can actually trigger inflammation and trigger in the worst case scenarios liver failures we we you know we do see people um not not commonly it's a kind of rare issue but you know they will come in they've had some sort of ayurvedic or sort of chinese herbal kind of homeopathic you know whatever and and it's really frightening to see how they and it's an idiosyncratic reaction it's not something that you'd expect because lots of people on these but it's just how that individual has kind of reacted to that particular supplement so my motto with the supplements is take the stuff which is makes sense that there's evidence based around omega-3s in general from a cardiovascular point of view plenty out there coffees you mentioned i mean you at the moment you can't open a journal without seeing a big study you know in thousands of people where there's there's there's clearly some benefit um depending on the endpoints so they're measuring but i i think one of the and it's very much a sort of you know a here and now issues that people are looking for a shortcut right so the hard yards which is eat well sleep well exercise look after yourself these things are hard to do so there's this kind of wanting to reach out for a pill or to or something that you can you can swallow and then it sort of you know does some good for you in reality for liver disease that just doesn't exist and so the hard yards which you know once you bed in once you get that routine it actually becomes much easier to kind of to go to kind of maintain that's really the direction of travel and you know as time goes on we'll get more data on certain so you know i have a substance stack that i use whether or not it all kind of does me good i'm not sure the main thing is i want to make sure it doesn't do any harm yes um but you know omega-3s are in there vitamin d is in there because you mentioned earlier you know a lot of us particularly with darker skin are vitamin d deficient and actually that's a really easy fix in terms of just feeling better right so these are things that we want to be taking um and also look at where your supplements are made because some of the stuff is being imported in you've got to be careful you know it's also laced with chemicals which you really don't want in your body yeah i think it's it's a good idea from you mentioning that all these patients are coming in yeah likely in desperation that they want quick fixes in addition to medical therapeutics and pharmaceuticals that can help them, right?

28:44Dr Karan: There's this sort of naturalistic fallacy that they go down that natural is better, but actually those natural compounds are still powerful chemical modulators and even things which seem that they would be good, like turmeric, for example. If you're using turmeric and the curcumin, which is found in turmeric, it's obviously a potent anti-inflammatory compound, which if you're making a curry, great. It's a great addition. It can help with your microbiome diversity. But then if you're taking a turmeric supplement, which is likely to be potent high dose, that has proven evidence for liver injury and hepatotoxicity.

29:18Dr Karan: Same with green tea, probably great anti-inflammatory in a single green tea that you brew at home. But then the actual compound EGCG that you find in green tea, someone puts it in a capsule at 2000 milligrams. Again, that could be hepatotoxic and cause injury. And that is obviously the concern you're probably facing. What is the burden that you see in clinics or your colleagues see where patients are coming in with liver injury because of these compounds and botanicals? Yeah, so the truth is that we don't see a huge amount as a result of those kind of compounds. But what we are seeing, and I don't think it's necessarily on the rise, but there's definitely a kind of background sort of bit of noise around sports supplements.

30:01So there are lots of sports supplements out there and there's probably 20 or 30 different types of chemicals if you really go for it where you can be stacking. You know, creatine probably is the safest and the most well understood of these things. but there's a whole bunch of other things where people will be taking them for perceived health benefit but actually will come to quite a lot of harm and obviously anabolic steroids are kind of the most extreme end but we do see people who've got quite severe liver injuries and even liver failure because of that kind of idiosyncratic reaction and or a reaction over years because of abuse i think to your point it's it's about trying to access these compounds for example turmeric through kind of natural sources you know through your cooking and through your food as opposed to being sort of super dosed in a capsule yeah i when people ask about liver supplements or

30:51Dr Karan: any supplements at all especially when it's got these kind of fancy herbal things i always direct them towards tox base and i just say you know there's a lot of these things which are popular now like you know red yeast rice black cohosh you know random things like that look up tox base and look at the burden of kind of liver injuries that have been associated with that and if you see that, probably stay away from that sort of thing. And I guess, you know, to last touch on the liver sort of thing, we mentioned often it's asymptomatic, fatty liver disease specifically. So number one, why isn't national liver screening, at least as a one-off, a thing, given the serious consequences it can go down, is it just the ROI isn't there for cost-benefit ratio?

31:36Dr Karan: and second because you know it does lead to serious metabolic problems and you know cancer risk as well so does it just not you know save money in the end and secondly what is something that someone can do to just look for signs of their liver health going you know down the wrong path yeah so i'll take your first question first so there are calls for a form of a national screening program and the more work we do the more kind of community-based screening that's happening often with for example a fiber scanning machine going out in a van into the community and literally scanning people who we would consider to be at high risk because they have certain risk factors you know there is obviously a pickup rate there but ultimately it is exactly that is the resource required to put a screening program into place going to give the benefit in terms of not just health return but you know ultimately financial return as well you're preventing enough to justify the outlay um i think this is an area that's going to then expand and i think there will be some form of screening coming through you know there are tools that we're using already based on the sort of ratio between liver enzymes and and other sort of non-invasive biomarkers which can be done in primary care by your gp and you know those will very much trigger a referral to kind of for a kind of dedicated liver scan if you reach that special saying you're high risk of fatty liver disease and or fibrosis of your liver so there are these kind of programs in place um but you know it's it's not necessarily as consistent we'd like to be nationally if you think about the uk kind of pipeline but i think this will come particularly as newer therapies come on board because one of the issues around screening is if you're screening and then your advice is oh you need to do these various lifestyle things without necessarily a therapeutic attached to it you know it becomes harder than as a cell particularly from a patient motivation point of view so you know there's there's that bit but again as new treatments coming coming online and there are now one or two which will be licensed in the uk uh dedicated for fatty liver disease you know this will be in a time when actually being able to detect disease at an early stage because you can actually start to get treatment in to prevent it from progressing knowing that progression potentially leads to liver failure and the need for transplantation the worst case scenario you know that you can see how the sums add up and it would be bonkers to not get a screening program in place that's the first thing in terms of sort of you know an individual's liver health and how can they tell whether or not they're going to be potentially at risk or developing liver disease you know we really don't want people to be kind of turning up at the front door you know with jaundice where they've gone yellow that's usually the first sign or they've got complications of cirrhosis and decompensation of the disease where they've for example had catatrophic bleeding from varicose veins in their gullet they've got fluid in their tummy because of something called ascites and and and that's you know awful and very very debilitating they're losing muscle mass and they start to get bruising for example if you start to develop those symptoms then of course you are at risk you may well have had already developed chronic liver disease and you need to get medical attention like today okay those things are happening sadly we are still diagnosing a significant portion of people chronic disease due to fatal disease at the front door in emergency department up and down the country that's the first time that they are aware that they've got liver disease so it is very much then what can you do as an individual to say well if this is a silent disease is there a way for me to get some screening done you are offered health checks in primary care which will take a blood test and do those things to look at certain biomarkers and like i said the ratio of enzymes which will then push you towards needing a scan but it's what we started off with do you have potential risk factors which are putting you at risk for fat losing if you've got one risk factor that's a concern if you've got multiple risk factors insulin resistance diabetes cholesterol uh being overweight drinking excessively and and you know we've not really talked too much about alcohol but actually the amount of alcohol that we need to consume to harm our livers varies from person to person so there are people that can drink significant quantities and never come to medical attention and it will be something else that kills them and there are a lot of people who can drink very minimal amounts and because of the way that you know we're all different how we process alcohol how our livers and handle alcohol and how livers are affected by alcohol those individuals can come to significant harm with actually drinking quite moderate amounts and what we find in those individuals that they often have other what we call co-factors for liver disease so there's other metabolic conditions etc which come together to then drive that liver disease more rapidly more aggressively so it's what can you do as an individual to sort of mitigate those factors be aware of the risk factors and then to start to really kind of address them i think you know the liver obviously has this remarkable ability to not only do so many things but regenerate as well and people take that as almost like a challenge that they can really throw anything at their liver and it will bounce back.

36:21Dr Karan: And maybe they don't fully understand just the limits of that as well. And, you know, there's something that I got wrong a while ago, even as a, you know, educated doctor. It was regards to the liver and its ability to process cholesterol. And there's a myth that was also wrong where people think that you're, you know, eating eggs is bad because, you know, the cholesterol on eggs can raise your cholesterol, which is, you know, that absolute is wrong. but also thinking that you can completely ignore the impact of dietary cholesterol on blood cholesterol is also wrong because the premise is that your liver has the ability to process and then down regulate its own production of cholesterol.

37:07Dr Karan: If you eat cholesterol, you know, but that's a threshold effect, not an absolute effect, right? So you can't eat 10 eggs a day and expect to get away with it because your liver will only compensate up to a point. and you know to your point earlier if people are hyper responders or you know respond different ways they may have an impact and actually i think there's enough data to suggest out there that actually you do need to care about your dietary cholesterol even disregarding the fact that eggs are high cholesterol but low in saturated fats you still need to be mindful somewhat of the dietary cholesterol you consume up to a point what you've described there is very much everything in balance right so if you if you are exceeding for example egg intake okay and you're having five six seven a day that's going to catch up with you no matter what state of health you're in anything in excess to that degree is going to harm you so i think a lot of this comes back to sort of how do we go back to first principles around diet and how do we make sure from a nutritional point of view we're eating the right things in the right quantities with a degree of balance but we talked about this earlier about sort of you know maybe when you go to your supermarket and you're not doing a carrot getting aubergine instead how do we introduce variety as well because the other thing that becomes very very easy is you sort of get into habits of eating things you either like or you get used to and lacking that variety is is you know it's a real issue from a microbiome health point we know that the bugs really need to have that variety in terms of intake of nutrients and exposure to the different fibers and again it's just being more mindful about what you're consuming in terms of the day-to-day.

38:42Dr Karan: I want to talk about something that's quite personal to me and about some medical conditions that I suffered from. I used to have high cholesterol and fatty liver disease and that primarily stemmed from a severe lack of fiber in my diet. And on my quest for finding the perfect fiber supplement over the last few years that could help me add more fiber into my diet, I couldn't find one. That ticked all the boxes that I wanted and the high bar that I set for myself. So I built Loam Science. What I'm most proud of is not the product. I know that's great, but it's the fact that we've run two clinical trials on it, two randomized controlled trials, which is far more than the vast majority of supplements on the market will ever do.

39:17Dr Karan: And we've got even more coming because I'm a doctor first and foremost, and a scientist, and I wanted to build something that I could actually stand behind with data and not just rely on good branding. So if you want to understand what's inside Loam Science and why, the science is all on the website and the link is in the show notes. Most people won't really see the link between these three things, but you've obviously studied it in depth and you mentioned it earlier. The mouth and the oral microbiome, the gut microbiome and liver, especially it's in relation to liver disease like cirrhosis. What is the link between that three triangulation points?

39:53Yeah. So I started my work looking at the gut-liver axis when I was doing my PhD many years ago. actually interesting it was a time when you know many of my colleagues and living units said look you know this this is a waste of time if you want to do kind of gut related stuff and you're going to you're going to chase patients for poo samples all day you might want to become a gastroenterologist and i'm glad i ignored them because you know years and years on actually that link between the gut livers we talked about earlier but with the gut being the kind of primary firewall uh response kind of you know absorption nutrients um certain degree digestion and so on and then the liver sort of being the secondary firewall stopping some of those harmful products that can escape from the from the gut into the liver and further field you know absolutely critical and obviously how the biolacin kind of from the from the liver to the gut works we've over years understood that the gut obviously isn't just what's in the stomach and then down to your bottom end but it starts in the mouth right and actually it's a long tube lots of different segments anatomically and functionally which are important but a lot of work we've done more recently where we've collected for example saliva samples from our patients paired with stool samples sequenced in terms of looking at what's there from a dna and microbial point of view and then functionally trying to interrogate what's going on has been absolutely fascinating and what we see is that the more advanced liver disease someone has and i'm talking about people with cirrhosis and then various forms of cirrhosis the more overlap there is between the mouth and the gut in terms of the type of bugs you have number one but also how much more pathogenic the bacteria are So there's a switch between more healthy bugs to more sort of harmful bugs, the sicker people are.

41:30And essentially where it's led us to is that we are now thinking that aside from therapies to sort of target the bowel, and we're looking at things like fecal transplantation, you know, as the most extreme form, we're talking about probiotics, prebiotics, fiber-type supplementation, other nutritional interventions, whole bunch of things which are more gut targeting. we're also now looking at the mouth as a potential therapeutic target because we know that people who've got liver disease tend to also have poor oral health various forms of periodontitis you know dental decay teeth missing poor dentition all these factors and when you look at actually for example people's ability to get through a liver transplant if they go into a liver transplant with a mouth that has a lot of disease their risk of losing their graft the new liver that's been implanted is significantly higher to the point where the guidelines say that we should be ensuring that people's mouths are really well looked after and if they are a mess then you essentially remove all the teeth before you're transplanted to reduce that risk we've known that for years so why are we not doing more work in the space and that's exactly where the research group by lead and other people are now driving we're working much more close with our dental colleagues which is really good fun because there's that kind of interdisciplinary you know educational kind of piece there as well

42:44Dr Karan: So I guess that's a bidirectional relationship between the mouth and the gut and the liver. And can we extrapolate some of the learnings that you've made from disease cohorts to like a normal healthy population who have maybe early signs of gum disease, halitosis because of some dysbiosis and bacteria imbalances in the mouth and how generally we can provide some actionables from that disease cohort to improve our mouth, to improve liver health ultimately. Yeah, I'm really excited by two aspects. One is around what you just touched on, which is what can you translate from disease to health? But the other bit is what can you translate from essentially what is a chronic inflammatory condition, which is what liver disease, particularly an end stage is, to other inflammatory conditions, whether it's metabolic, diabetes, for example, or rheumatological.

43:33and so a lot of these changes that we're seeing in the mouth in those people liver disease appears to be very liver specific but there's no doubts that some of those biological processes around inflammation changes in the composition of the bacteria therefore their function the virulence factors they carry which is the ability for kind of harmful bacteria survive and thrive where there shouldn't be antimicrobial resistance which is a huge issue for us in liver disease because of risk of infections and the amount of antimicrobials people are getting as a result of that you know there'll be a huge amount to learn from that and how we then sort of look after other people with other conditions but absolutely there are some paradigms there where if you've got oral disease which is often something that you know we ignore so for example you're brushing your teeth and you find some blood when you're spitting out and i'm not a dentist so this is my kind of this is my sort of naughty version of that you know people tend to ignore that whereas if you found blood from other parts of you uh particularly went to the toilet you found blood in the toilet you'd be much more alarmed and probably be much more on the front foot to do something about it so you know oral disease is very common and there's no doubt that actually there's there's significant impacts not just in your liver potentially through this kind of oral gut liver access which i've talked about but also you know between other kind of axes between the mouth and the brain for example or the mouth and the heart so there's lots of you know well well published quite large case series where they've looked at changes in the mouth and how that impacts on sort of end points affecting other parts of the body so the mouth is really critical And it's because of the fact that you've got all these mucosal surfaces in your mouth, which can be disrupted.

45:05And that's a really easy way then for not only bacteria, but their products, which can be sort of toxic to then access other parts of the body and sort of have kind of systemic and more harmful effects on those organs.

45:17Dr Karan: Yeah, I don't think it's top of mind for anyone to think of their mouth as like a seeding ground for disease in the gut and the liver, especially the liver. So I think that's fascinating. And I know earlier off air, we were sort of, you know, geeking out about fiber and the potential for a lot of research opportunities. So definitely we'll be, you know, chatting to that as well. But, Sharl, thank you so much for joining me, because I think this is a huge, you know, burden that people are not really aware of with regards to their liver health, but also fatty liver. So, yeah, thank you for joining me and, you know, shedding a light on this very important topic.

45:51Dr Karan: No, it's been an absolute pleasure. Thanks for having me.