#601: Gallstones & Gallbladder Conditions: Impact of Diet – Angela Madden, PhD RD

Hello, and welcome to Sigma Nutrition Radio. My name is Danny Lennon. You are listening to episode 601 of the podcast. You are very welcome. And a very special thank you to everyone who listened into our milestone, episode 600 of the podcast last week and had very pleasant things to say about it. Thank you for that. And thank you for being a listener for however long it's been for you, whether that's for many years and for the 12 years that this podcast had been going or maybe you're a relatively new listener regardless, thank you so much for listening in and hopefully you enjoy another evidence-based discussion here today. We're gonna be getting into some clinical nutrition and diatetics today and specifically taking a look at gallstone formation related to other gallbladder conditions and some of the dietary management around that for people who are symptomatic and suffering with gallstones or the related consequences of that. And then also we may be touch on situations post gallbladder removal as well. And this actually comes off the back of a question that I got quite a while back from one of our premium subscribers, Katarina. And so thank you so much, Katarina, for the suggestion for this as a topic and some of the questions around this. And indeed one of the things we do inside of Sigma Nutrition Premium is have a place where our premium subscribers can suggest either questions or topics like this that they would like to see covered at some point on the podcast. And those are used to generate some of the podcast episodes. Some of those are premium exclusive episodes. Others like this are conversations with experts. And so some of the discussion that comes up around dietary fat intake in particular and how that relates to either someone that is symptomatic with a gallbladder condition or post surgery and has had their gallbladder removed some of the recommendations there was a question that Katarina had put forward on the basis that it's a commonly discussed issue. There's connection with dietary fat intake and maybe the use of a low fat diet. But do actually have good evidence for such interventions. And so to discuss this topic, I'm very lucky and honored to be talking to Dr. Angela Madden about this who is a clinical researcher in nutrition and dietetics currently based at the University of Hertfordshire in the UK. And she's been embedded within nutrition and dietetics research for decades now across a range of different issues, one of which that she has looked at in detail and indeed was the lead author of a Cochrane review on the topic relates to the very thing we want to investigate today. And that is dietary fat and gallstones. And so this is what we're going to hopefully work our way through. Take a look at what evidence there is, why this even comes up as a question, some of the plausibility behind it, and then all importantly, based on the excellent work that Dr. Madden has done along with our colleagues, see what we can tell from the current evidence. And then where does that leave us in actual practice for those of you who are dietitians or maybe you are patients or a family member of someone who may be suffering with this? Where does that leave us in terms of practical things that we can actually do? And so that's our aim for today. If you are a Sigma nutrition premium subscriber in addition to be able to make recommendations for topics like this, remember you also get your detailed study notes that are linked in the description box here or over on sigmanutrition.com. If you're listening on the free public feed of the podcast and you're interested in getting these extra materials like our study notes for each episode or our edited transcripts, or indeed the key idea segment that will play after the interview is over, then check all that out in the description box where you're currently listening to right now or all of that information is again on sigmanutrition.com. See if it's something that might be useful to you and maybe give it a try. See if it actually helps you get more out of your podcast listening, retain more of the information and understand it more deeply. That is certainly our goal. And all of that is what keeps it podcast running. So thank you very much for your support. Those of you who are premium subscribers or maybe who are considering doing so. So with that, I would of the way, let's dive into this discussion between myself and Dr. Anja Madden. (upbeat music) (upbeat music) - A very big welcome to the podcast to Dr. Anja Madden. Thank you so much for taking the time to join me on the show. - Thank you, Danny. Thanks for the opportunity to talk. - I'm really looking forward to this. There's gonna be a topic that I don't think we've really got into in-depth and actually has been asked by a few of our regular listeners who are looking for more guidance in this area. And so given your background as I'm sure we'll discuss in a moment and some of the reading I've done based on things that you've put out, I think you're in an excellent place to hopefully provide some nuance and some understanding of what evidence we have in this area. But before getting into any of the details, maybe just to open us up and start into the conversation, can you maybe give people an idea of a bit about your background, your work and your interests and anything that might relate to the topic we'll discuss today? - Yes, of course. So I'm a dietician. I qualified from the University of Surrey over 40 years ago. So quite a long time, walking in the NHS in the UK for the first 10 years of my work. During that time, I started working cynically in liver disease. So not specifically bladders, but I did cover a ward where gallbladder surgery was undertaken. And I carried on walking in liver disease, went into research and did my PhD there. But it was actually the gallbladder that got me started in research in the first place because I became aware that I wasn't able to base my advice on any useful information. So after doing my PhD in liver, I then did a bit of research as a postdoc and then I started working as an academic lecturing, finishing off my most recent job and where I still am based, University of Harvardshire, where I led the dietic undergraduate programme. Five years ago, I stood down from my full-time job and continued to work part-time in research. And all during that, during that time, the gallbladder keeps coming back to haunt me every now and again. We've completed a Cochrane review, which was published in 2024, so that was the most recent piece of work on it. And it's, of course, one of the things that has got my attention trying to look for some of the evidence in this area and try to see what evidence base we do have. And so your work has been very instructive in the area and I'm sure we'll walk through some of that. Before getting to some of the details and some of those, the specific issues that can crop up here, maybe the most simple question to help us set the scene is, what exactly does the gallbladder do for those who are unaware? - Yes. So it plays a role in the digestion of our food. So just a briefie outline is, structure is a small sack. It has musculoskeletal walls. It's about somewhere between six and 12 centimeters long in the abdomen and tucked under the liver. And it's connected to the liver through the bile ducts and also connected to the gastrointestinal tract through the bile ducts. And that sort of location is really key to its function. So it's a really unknown function is to store bile that's being produced in the liver and then to release the bile into the GI tract when it's required to act as in the multiplier for dietary fat. So the food that's already come through the stomach and it's in the lumen of the GI tract. So it's playing the important role in digestion, but it's not actually part of the GI tract itself is connected to it. - Of course, one of our goals today is to give people a better understanding of generally gallbladder disorders or issues that can crop up. And then some of the specific things you've written about in relation to nutrition. But if we think of that that kind of phrasing I've just used of a gallbladder issue or a gallbladder disorder, this is obviously quite a vague umbrella term that can encapsulate a number of different things. What is maybe a good way to start categorizing the different things that can arise clinically that are related to the gallbladder? What kind of buckets we can come into come up with? And then what are some examples to give people an idea about? - Yes, the main conditions affecting the gallbladder, particularly in Western type diets and lifestyle are our gallstones. It's a worldwide problem. So it does exist even where people are not having Western type diets and lifestyles. But by far the biggest prevalence of disease relates to two gallstones. The gallstones themselves can be divided into two types. The ones that we more commonly see in countries like the UK and Ireland are gallstones made of cholesterol. So deposits of cholesterol that become hardened and calcified. The other type which we occasionally see but are much less common here are stones that predominantly made of pigment. So most of the conversation today is going to focus around cholesterol type gallstones. But some of the conversation is applicable to bile pigment stones as well. I'll try and differentiate between the two. But those by far the most common conditions. Do you want me to mention perhaps some how that affects people or how it presents or do you want me to perhaps mention some of the less common conditions? - Yeah, I think maybe a good starting point is if we stick with those gallstones that you've outlined some of that kind of clinical presentation. So people might have an idea. - G gallstones are very, very common and in a lot of people. they are asymptomatic. So often cause silent gallstones where people may not know they have them and they're only identified if someone has a scan for another purpose or perhaps a post-mortem after death but they've never caused any trouble. People with gallstones are small proportionals and do start to develop symptoms and some of those then develop complications and the symptoms tend to be abdominal pain. People call it biliriconic at times and this can be relatively mild in some people but can also be extremely severe and incapacitating nausea and vomiting are often associated with that as well. The complications that arise as well as the pain is more related to the pain is that the gallbladder itself becomes very inflamed and infection may set in and that's referred to as cohesistitis and the condition itself can be acute or chronic so acute cohesistitis coming on very rapidly being extremely severe may need hospitalisation whereas for people with chronic cohesistitis it may be something that rumbles on for a period of time flares up but then settles down again. You've already mentioned a bit around the prevalence and given that we can have a whole range here from something that may be asymptomatic and not causing people any problems all the way up to things that can end up if not treated becoming quite severe. Within that range what do we know about how common this is within the general population and what kind of way that distributes among mild, severe and so on? Do we have any data that gives us any idea about that? Yes we do. It is quite hard to get good figures. There was a paper that came out last year that looked at global studies and I think they identified approximately 6% of the population overall have stones that was looking at a variety of publications and pulling out the data. It varies hugely. I think most populations would probably be somewhere between say 3 and 15% but there are some sections of the world populations where it's even much higher than that. I think the most common highest prevalence is in the Pima Indians in North America where maybe it's highest 60% of women have gallstones but just as caveat those prevalence figures it really does depend on how you're assessing it because as I say if they're if they're silent asymptomatic they're only identifiable either on scans or post-mortem and if you're looking at identifying through symptoms that's a much smaller proportion. I think the thing to be aware of is prevalence is changing it's actually increasing with the obesity problem that we have worldwide. It's not just obesity but it's populations that are taking becoming a more taking on using a more Western style diet and I'm I'm meaning they're tending to be higher in fat and refined sugars lower fiber less fruit and vegetables and also a more sedentary lifestyle. Finally the last thing gallstones when I was working tunically decades ago were almost unheard of in children but now gallstones and coastectomy surgery to remove gallstones is becoming quite a regular thing that is seen in children. I think you've already alluded to a couple of these things so I think it's worth expanding on that you've already suggested that we're seeing this increasing prevalence that may be tied to things like increasing obesity rates but also the general dietary pattern we have. Of course we'll talk a bit more about diet later on but yeah if you could get into some of those other related risk factors that seem to be main things that are contributing to these. Yes so I think in all populations the prevalence is higher in women than in men and prevalence tends to increase as people get older it's also more prevalence in people who are overweight in people who are more sedentary and then for the dietary factors that come into it as well. There's something I haven't touched on at the moment when we talked about function I was saying about the gallbladder releases bile into the GI tract and it does that by contracting the muscles of the wall of the gallbladder squeezing the bile out and there's a much higher prevalence of gallstones in in people where that emptying doesn't happen either because they've got a gallbladder that's not functioning well maybe the structure is slightly abnormal or it may be that they are not eating normally and I'm thinking here of people who perhaps are having total parental nutrition so completely IV feeding where they're not eating nothing or very little's going into the GI tract so bile isn't really needed to do the digestion that it would in healthy people and therefore the bile remains in the gallbladder and it's allowed to stay there without coming out as often as it normally would do in someone who's eating normally and I'm hoping I'm triggering some sorts here these are actually very unusual situations but I'm just picking out some unusual cases because I think it does help us a little bit with the understanding of perhaps how things work but also how we can optimize through what we're eating. Yeah absolutely and it's something that I do want to get into detail and have a lot of questions that relate to for example one of the big topics that's discussed often with I think within diatetics is around things like dietary fat intake which I'll get to in a moment you've already alluded to that overall dietary patterns contribute to risk here but we also have these other factors like you mentioned at sex, age, level of physical activity, level of avatoposte and so on that may contribute to risk and you've just talked a bit about some of that pathophysiology and that development of gallstones and so maybe just to reiterate some of that to make it clear for people what is it that is happening during let's say the formation of those gallstones or the development of that condition and it getting worse that connects to these different risk factors we've said why are they why is there a connection between some of these things we've mentioned and the actual development of gallstones? Yes so the stones arise through the precipitation of substances that can harden and form into first of all crystals or sludge in the gallbladder and then they can actually fall together into a stone. Stones vary a little bit sometimes they're in little round stones sometimes they're they have more shape not quite like a dice but you know this let me have edges to them the size vary sometimes they're huge but much more often that they're much smaller than that and the smaller ones can pass out through the bile duct if they're small enough but they can get stuck if they their size is not able in them to flow through the bile duct so basically it's when the bile has something in solution that reaches a concentration where it precipitates out so the two main groups I've mentioned are cholesterol and pigment bile pigments and both of those are capable of the concentration is high enough of precipitating out to form the small crystals and did you ever grow crystals as a child a little science experiment school or something where you's great to see them as a form into shapes but if you stir the water or keep moving the water the solution rather they don't have time to settle they they can't make the crystals and it's the same with the bile if you if the bile is continually moving through the gallbladder then it's much more difficult for a precipitation to happen I mentioned about the concentration rising in the bile and we really then have to think where that comes from and I'm going to focus only on cholesterol now so if the cholesterol levels in the bile are high they're usually high because they're reflecting the cholesterol levels in blood and I feel one of the one of the things that triggered a lot of interest in the last century so I'm thinking that 70s 80s where quite sophisticated research was done but nothing on the level that we are able to do today they're very interested in cholesterol intake, dietary cholesterol intake and the impact on bile and on what's going on in the gallbladder so that's the logic to it but problem with that we know now is not really a relevant thing is that our dietary cholesterol doesn't have as much control or influence on blood cholesterol levels as saturated fat and some other dietary components okay because we basically make cholesterol the liver makes cholesterol so we have a lot of endogenous cholesterol and don't need to be that focused on the pure cholesterol content of food so there is this relationship between the blood cholesterol and bile cholesterol and therefore risk of precipitation is not specifically relating to cholesterol in food but there are other components of the diet that may have an impact on blood lipids and looking more holistically then at aspects of the diet may be more helpful in trying to reduce the risk of gallstone formation in the first place and then managing it when they've actually been formed and I suppose that's another thing that I just wanted to separate out is we've got these two things going on we've got the formations of gallstones and then we've got the management of the symptoms in people who already have gallstones so if we take that first part and again if I try and recap some of the things you've just mentioned and feel free to correct me if any of this is incorrect but you've alluded to this importance of during that formation of that that role of cholesterol and you said how that connects most directly to blood levels of cholesterol and so from there when we start thinking about well what are some of the factors at at least from a dietary perspective that could be playing a role here rather than necessarily being dietary cholesterol although we can maybe talk a bit about that later on and some of the impact. But more so we're thinking about what can be driving blood levels of cholesterol. And so therefore we we look at the evidence around things like the total amount of saturated fat perhaps in the diet. There's other components that we know then can be related to lipids either going up or down from a diet that we might discuss. But we're seeing that really one of the key things here is what is someone's blood level of cholesterol as maybe even more specifically I don't know if we then can narrow that down to LDL cholesterol as opposed to total cholesterol and what kind of relationships we see here. But we're starting to see this picture form of the blood levels of cholesterol are something that is going to be relating to this risk. And so can we modify that risk by changing blood levels of cholesterol on one way to potentially do that is through the dietary changes. Is that a relatively accurate picture or is there anything you want to clear up with that? No it's a it's a good summary. I don't think we've got the answer to all of it. And interesting blood cholesterol is good because it's much easier to take a blood sample. It's quite bothersome and hard for the person involved to take a sample of bile. You can imagine how the complexities of going down into the beyond the stomach to retrieve bile is just not something that can be done easily unlike blood cholesterol. And also you touched on it there thinking about the different types of blood cholesterol. Now I may be wrong and have missed this but I'm not aware that a lot of work has been done in tracking blood with bile. In fact when I was writing something you have to look quite hard to find where there is where the people report evidence of a connection between the two but I haven't actually seen it broken down into the different sub fractions of cholesterol. And I think that's perhaps what needs to be done. This is maybe one of the things that at least originally there was this interest. First you noted in people looking at dietary cholesterol over time that's now being more refined to understand what are some of these factors impacting blood cholesterol. And then there's historically also been an interest in low fat diets for that for that reason as well potentially that if we have less dietary fat maybe that is contributing here. When it comes to that can you give us a picture of not only the what we currently know from a general overview level of the relationship with that total level of dietary fat influencing some of this potential stone formation but then also the let's see types of dietary fats and then what how that is relating to some of these risks that we just discussed. Maybe if I think just perhaps suggest why I think it has become concern about fat intake relating to gallstones I think there's two aspects there is one because of the role that little gallbladder has in fat digestion and it makes off your sense there if you are having a problem with your gallbladder that if its role is in fat digestion if you reduce your fat intake then that might help the problem. I'm not sure that that's been very clearly articulated but that's had to become in practice what has been advocated for a long time restricting fat because if you've got gallstones or gallbladder problem that's a problem. I think also because the dietary fat provokes a gallbladder response so dietary fat provokes the release of cohesors to kind in gut hormones that then trigger gallbladder contraction. It's thought the gallbladder contraction the muscle contraction is related to the pain that people experience when they've got cohesors stitus and as I said that can be very severe and very traumatizing for them not everybody but in those that are affected so if there's a suggestion that what you eat what you eat and if there's fat in it is going to provoke your pain then that's quite a good stimulant not eating those particular foods so that's my thoughts of the reasons apart from we've already talked about the cholesterol in terms of the formation of but I think that's also being part of the the concept of why dietary fat should be avoided and if you're thinking back nutrition and dietetics is a science is actually quite young and a lot of the practice that has been undertaken for quite a long period of time is based on customer practice and a lot of it has not been evaluated so really scrutinize is this beneficial so I'm sure you're all aware of things like diets for ulcers that's always quoted to something you know people will have to keep off fruit and vegetable anything with sharp and acidic because that would make a gastric stomach also worse and that's be identified for a long time that's really not helpful because the stomach acid is much more acidic than fruit and vegetables and you need your vitamin C and all your other micronutrients for fruits from veg to help healing anyway but that's I think an example why the logic of thinking we should do something and then if you don't actually explore it tested out it doesn't necessarily lead to the optimum optimum managed management I think the other thing a lot and Danny pulled me back if I'm going off in a wrong direction I think another reason why there hasn't been a lot of interest in investigation into the dietary effects is because we have some very effective ways managing cohesestitis a surgical removal of the gallbladder is very efficient has a very low mortality rate and most of the ones were certainly undertaken in the UK I would guess probably Ireland is very similar for United States but it's through keyhole surgery so not an open abdominal incision and people recover very quickly from it and this process I think there's about I don't know about Ireland but there's about 70,000 cohesestectomy is done in the UK each year there's over a million of them done each year in the USA so it's the more you do something the better you get at doing it so it's a really good treatment but it doesn't necessarily look at the what other potential inputs could be there in terms of perhaps dietary advice either to prevent or to manage either before surgery or while someone is waiting for surgery there's quite a lot that I think it is really useful there I'd love us to walk through first to maybe fine tune something that I said earlier based on what you just said is that really we can think of this in a couple of ways and the point you made earlier about one is thinking about maybe some of these dietary aspects that could relate to risk over time and so that would fall into this category of if we're pushing out blood levels of cholesterol that could relate to risk but then the other aspects that you've highlighted is in the situation where someone does have gallstones and that's how they we have symptoms and as being diagnosis there's some degree of dietary management that comes in and some ideas that have been around within dietetics for periods of time have related to some of these hypotheses that mechanistically might make some sense for example we know the gallbladder's role here in fat digestion and so maybe having a lower dietary fat intake could be hypothesized to to be useful or we don't want to cause any degree of aggravation so we might change some of these dietary factors including dietary fat and as is often the case sometimes we have to have hypotheses based on those mechanisms and practice that comes before we maybe have some of the best evidence which is where some of your work that we're going to discuss comes in to hopefully try and get these answers but the point being for people is that we've had certain hypotheses put forward as to why maybe moderating fat intake in situations where people do have gallstones could have been useful or why it was maybe used in practice but again that is maybe distinct from the question of what is the quality of the evidence we have for some of these interventions which will discuss now in a moment and so with that and knowing that we have these ideas and maybe they've been used as you noted there's maybe this next step of going and seeing can we get some good quality evidence or can we kind of scrutinize some of these ideas and you were part of the group that we're doing that and the publication that you mentioned earlier the Cochrane review was one of those publications can we start talking about that movement from those hypotheses that you just mentioned earlier into trying getting better quality answers around this dietary management for those with gallstones yes of course okay well just a little caveat here is a big disappointment because basically we looked for the evidence and didn't find it so we were very I'm sure people know what a Cochrane review is ours were set up so we were only going to look at randomised control trials we wanted to make sure that it was the best quality intervention studies that were included and it had to be in people who had a confirmed diet diagnosis of gallstones not just clinically on a scan or other sort of visual presentation and we were looking at outcomes that related to the person's wellbeing so important things like mortality, hospital read missions, quality of life, pain, bleeding infection, things like that and I think we actually identified just over 500 papers and of going through them there were five papers that could be included all but one came from the last century and I'm talking from the 70s and 80s so there was one from published in the last 15 years and only one of them had looked at the outcomes that we were interested in but nothing was reported in a way where we could say there was good quality evidence so then to recap so this was looking at to see whether modifying fat intake, originally I was interested in the low fat diet but this would modify dietary fat intake in anyway, whether that was the different type of fat, saturated fat, monopoly, et cetera. And there was nothing, there was nothing there. Now, maybe if we had a broader protocol looking at other types of studies, so rather than including only randomized control trials, we may have been able to identify some kind of evidence, but the difficulty is that the quality of that evidence is not good. And I think what we really need to be aware of is that if people are changing their fat intake on the basis that it's going to be helpful, then I think we need to be a little bit more confident that it actually is helpful. And I just want to suggest a couple of things where not only do we know that it's not helpful, but there may be some evidence that perhaps it isn't helpful. Can I go off in that direction? Please do. I mentioned a few minutes ago that fat is a potent stimulator of the gallbladder, so through Colisistokinin, the gut hormone, it causes the gallbladder to contract. But we also know the gallbladder contract see response to other things. A Dutch team, a late 80s, early 90s, did quite a lot of work. Look, he had lots of different things. It looked at protein, it looked at medium trade chain triglysteroids, so type of fat that's chomyphonic coconut oil, but it's used therapeutically, but it's not actually the most common part of the diet, but they looked at different elements. And they found that the gallbladder contracted in response to a whole range of different dietary components. They also identified that if a sham feeding procedure was undertaken, so by that, I mean, you get someone to eat something, but they don't swallow it. So you're not getting the stimulation from inside the gut. You're getting just the chophonic, but just the brain stimulation from the pleasure of what's in the mouth, et cetera. And they also found that the gallbladder contracted in response to that. So I suppose a bit like a pavloving response, but rather than just salivation, this is the gallbladder contracting in response. So if we've got these contractions happening in relation to other parts of the diet, and I can't tell you the sort of degree of contraction, but there is contraction going on in relation to all of these, it seems not logical to cut back on one aspect if all of these others may be problematic. Now if I could put that to the side for a moment and think, well, actually, maybe there's something positive about contractions in that we do want the gallbladder to empty. Because if we think about how the mechanism of how the gallstones develop, it's a bile that's sitting in the gallbladder for a long time between contractions before, between the bile being released. A stagnant is not a very nice word to think about in your gut, but if the bile is stagnant, it's much more likely to have gallstones develop. So if we can help by having the gallbladder emptying on a regular basis, it may then be actually helpful, both in terms of preventing formation of gallstones at all or further formation, and bearing in mind once you've got them, they can become larger. That might be useful. And there've been just a few papers that have looked at this sum from lab tests where they've done actual observations of bile. And they suggest that you should have at least 10 grams fat per day to ensure that the bile, there is some contractions there that help. You'd get some contractions from eating anything. But I think that's almost like the other side of the coin. So we want to call some contractions. And if we cut out fat completely, then that might be problematic. Can I just say a 10 gram fat diet is very, very low. So even someone who's having a nice healthy diet would be probably having considerably more than 10 grams of fat per day. But it's this idea that cutting out all fat is just not the right thing to do. It's not, it's not optimum for health. So I'm certainly not advocating a high fat diet, but thinking about having some fat, thinking about other aspects of the food as well. One of the difficulties, I'm sure from a nutritional perspective, you feel the same, is that when we start looking at one component of the diet, we can forget all the other bits that are going on. And if you're tend to reduce your fat intake, low fat intake, people usually increase their carbohydrate and/or protein, but mainly carbohydrates to maintain calorie intake. We know that unrefined carbohydrate is not associated with increased risk of gallstones, but a high refined carbohydrate intake. So including sucrose and fructose, we know that increases risk as well. If that evidence is stronger than looking at the fat intake, this might be mediated via cholesterol root. So we might be thinking of the effect of high sugars on triglycerides, but that's a clear, prognostic risk factor than fats. How I've been very muddled there because I was really. Not at all. Fascinating and really interesting is triggered off a number of things I'm thinking about. And certainly when we think of that typical recommendation that say to use a low fat diet as has become a kind of a conventional thing to have been done for some of the hypotheses that we mentioned earlier. But as you've noted, this real lack of good quality evidence that just isn't existing when we're going to look for good quality evidence for this intervention leaves us almost with at least the way I'm seeing it from what you said, almost these three different layers we can think of. First, if someone is going to use that intervention, what we need to accept is that that is not based on good quality evidence. But we can't point to good quality evidence showing that this intervention is doing what we hope that it's doing. So that's one thing, but we can take it then a couple of steps further. One is that in a pragmatic sense, given that's the case, it could actually be unnecessary to do that at all. And if that is the case that it is unnecessary to have this fat restriction, those particular circumstances, that could lead to some unintended consequences, some of which are just pragmatic and some actually could actually be physiologically as you've outlined, could be having a problem. Again, we don't know if that's the case, but as you've put forward, if we are thinking about the stimulation of the gallbladder and having some degree of dietary fat can be useful to do that, maybe we're having this unintended negative consequence by having a complete restriction. And even beyond that, for a more practical level, trying to get to the levels of absolute fat restriction, someone might conclude they should be doing, if they're worried about their gallbladder, that could lead them to make dietary choices that could actually be worse overall for their dietary pattern, that they're leaving out certain types of foods that could be beneficial, or just trying to stick to that level of dietary fat being so low, unless you're doing something that is just only whole plants. Beyond that, you are going to run the risk for most people in the general population of trying to stick to that type of dietary pattern is not only very difficult, but might lead them to make poorer food choices, or these we could hypothesize. So we have these different layers of unintended consequences, but at the very basis we can say we don't have this strong or really any evidence to point to for such an intervention. And so just to pull back on something that you did mention around that, Angela, when it comes to why we don't have evidence to point to here, why do you think that is, is that there's been just a lack of interest in this from a research perspective given that success you mentioned of surgery, for example, or is there other things going on that relate to why we don't have a robust evidence base, or at least some answers to this research question that we would ideally like to have. That is a good question. I think there is a lack of interest, perhaps in the research population. I think if we could tag this on to the whole metabolic disease. So the interest we have now with diabetes, cardiovascular disease, I see this is probably just a similar another branch of that. There's certainly a lot of interest from a patient public perspective that the nice guidelines are probably familiar with the National Institute of Clinical and Health have produced the guidelines in the UK. They're 2014 guidelines. They have members of the public patients on those, the guideline panels and they were saying, you know, this is what we want to know about it. But there, there wasn't evidence that could be included but it just to flag up evidence is needed. So that's now 12, 12, nearly 12 years ago. I think it's because only cystitis so when there's inflammation, it sits under a surgical speciality and it's one of those very quick surgical things where for the vast majority of people they come in, they're assessed, they're diagnosed, they're prepped, they have their surgery, they might have to wait a little bit but then hopefully they feel a lot better after. So the vast majority of people do, some people have some problems after it's but vast majority of people feel better afterwards. So I think it may be from a clinician's point of view is there doesn't seem to be a need and I think I think there's just so much potential here. If there's any surgeons out there and I would call to surgeons because I think they're the people who are managing this group for taking the referrals and managing them. I think they would be in a really good place to organise future trials, ideally randomised controlled trials but I would suggest that looking more broadly at fat would be fantastic. To eat their lunch and then reduce their need for surgery. But if it did, I think everybody would be happy. Patients and also resources would be better served too. And to clarify because earlier you mentioned that really important distinction between, let's say someone that has symptomatic gallstones but maybe has yet to have any surgery and some of the potential dietary recommendations they're given. And then there's a separate population for people that after, let's say, a gallbladder removal are also given some type of recommendations, or at least they might have logically jumped to things with this idea, oh, because now I don't have my gallbladder and because of its role within fat digestion, therefore a long term or lifelong low fat diet is required. Presumably, the kind of scan evidence applies to both of those situations. It does. I mean, from a clinical perspective, people after had their gallbladder removed surgically, typically don't need any dietary restrictions or any dietary advice. Some people take a little bit longer to get back to recovery and eating again, but they're in a small minority. I think there is evidence that people tend to have higher fecal fat output. So normally in a healthy person, you wouldn't expect to find a lot of fat in the feces, but it is higher in people after gallbladder removal. There's also tendency for them to gain weight, which might be a reflection that they're feeling so much better, so perhaps there are appetite increases that I don't know. But I would say from how I can interpret the evidence that there, that's there are from most people following a typical healthy diet would not only help manage their health in relation to gallstones even after gallbladder removal, but also their risk of other things of diabetes, cardiovascular disease, etc. So I'm thinking here, so in Ireland, I believe you have the food here amid the five shelves of food. Does that sound familiar? Yes, I've certainly seen them. Yes. I hope I've got it right, because I'm not that familiar with it myself, but basically that you do keep intake of refined carbohydrates and fats to a low level, but your biggest intake comes from fruit and vegetables, and then from unrefined high fiber carbohydrates, your bread's pastas, rice, potatoes, etc. And it's the same or similar in the UK, we just have the eat well guide, which is in a circuit format, but the concept is still the same. It's a healthy diet, nothing extreme. And if you'll allow me, I would also like to break out from thinking about the diet in terms of what and introduce when the diet and when people eat, and also other things like health-rated things, is that okay, Danny, can I move on? Yes, please do. I'd love to hear. Thank you. So you're really brilliant. You keep referring to evidence, and that is so important, and I have to say I don't have evidence for this, but it seems to be logical, and it needs to be tested, so I don't think we're in a position to say this to what people should do, but this is, I think, potentially a great interest, is if we want to encourage gallbladder emptying to reduce the chance of bile stagnating and forming gallstones or forming more or larger gallstones, then eating regularly, rather than having very long periods of time between food intake would logically be helpful, but we need evidence to confirm that, and I'm thinking we know that bile that's produced overnight tends to have a higher cholesterol concentration, so that's just part of the normal circadian rhythms. So overnight bile is more lithogenic, more like deformed stones, so if someone has breakfast, whatever that breakfast might be, then hopefully the gallbladder would contract, and that lithogenic bile would then be released into the GI tract, and it's gone. I mean, this is based on the evidence of people who are not eating or people who are fasting for long periods of time, having a higher risk. So that's one thing, so I think he's not just what, but it's when or how often people eat. There's some quite interesting studies that are being published in the last couple of years, where they've analysed very large, either a large data set, a meta-analysis or so-of-large population studies, where they found that people who aren't taking more physical activity have a lower risk of gallstones, and there's also recently been one related to sleep, so people who have quite a low average sleep number of hours sleep over a week have a higher risk than those who sleep more, and they think again that's related to what happens to cholesterol when people are sleeping. I think what it's all pointing to is healthy diet eating, regularly exercising, regularly getting enough sleep, to have really good evidence, we clearly need more studies, but I think we could pull things together to say these are the things that are definitely worth testing. And I mean, that's the whole issue that often comes up for dietitians and nutrition professionals that in situations where we don't have an evidence base that we would IDD like, we're kind of left to put together recommendations that are still based in some degree of evidence, or at least we can point to some degree of reasoning and some evidence for that, that make some degree of sense. So I think everything you've said is completely reasonable, and we've before talked about some of those metabolic responses that occur, let's say, at eating during the biological night, where you do see these really exaggerated free fatty acid levels in the blood, and that post-prandial response is much greater than it would be other times. And so, foreseeably, that is relating to some of this risk that you just outlined here as well, given what we talked about with blood lipids and the potential connection there. And so, given that, for maybe people who are in dietetic practice and are going to be coming across people that no doubt have some degree of gallstone issue, from your perspective, given that we've already given that caveat that there are some clear gaps in the evidence that we would like to see answers to. For right now, what do you think we can summarize some of those dietary aspects or dietary recommendations that you would consider at least to be best practice or a good starting point? Okay, thank you. So I would suggest people follow a healthy diet. So following either the food pyramid or the eat well guide, that they try and eat regularly, particularly eating breakfast, that they watch their weight. So if they are currently overweight, or gaining weight to try and control that, that is so hard. We know that's a real challenge for people, but I think that would be important. And then to pay attention to our things like their lifestyle in terms of activity and sleep. I'd also tell them that we don't have absolutely good evidence that this is definitely going to help you, but it's worth a try and it will definitely have beneficial effects on other aspects of your well-being, so cardiovascular risks, etc. And I would also say to them, if they are experiencing pain after abdominal pain, that they think might be related to their gallstones after eating something specific is just to keep a diary a bit. And if they're noticing a pattern to try and avoid that. And I think just to take it from there, so I think that's probably my summary. But it's really important to be honest with people. You can't say you've got to do this. That's not how we work now. It has to be much more collaborative and trying to find out what's fitting with their lifestyle as well. And again, a number of those things that you mentioned, even if we need some more evidence on them for this particular outcome, there's a number of those steps that someone could take that are going to have beneficial impacts on other aspects of their life anyway, and other risk factors, whether that relates to their overall dietary fiber intake or the meal pattern that you mentioned or some of these aspects related to lower levels of saturated fat, and so on. There's lots of counseling that can be done, it seems, from this perspective. So Dr. Rada, I know you've mentioned some of the gaps we have in research, and I don't want you to necessarily rehash that over again, but maybe as a nice way to tie all this together, if there is a particular research question you would love to see answered in this area in the coming years, what would that be? I guess to try it out and to have an investigation that tries out these suggestions and really can then give us some indication whether they are helpful. If they're not, they should be chucked out, but if they are helpful then we need to know that so that we can ensure that's the practice that we are encouraging everybody to do. So before I get to my final question, for maybe people who are interested in learning a bit more about your group and the work you've done or any of your other publications, is there any places you would like to send their attention towards online or anything that you would suggest for them to look into? So my research papers are up on my university research page, so just by googling my name, Angela Madden at the University of Hartfordshire, the publications are there, and I think that we have, they should all be open access, so hopefully they can find them if not, my email address is there, people are welcome to email me. Great, and I'll put links to all of that, as well as any of the research that we've mentioned to today in the show notes for people listening, so please do go and read through all of that. With that, Dr Madden, that brings us to the final question that I always end the podcast on, and this can be to do with anything even outside of our topic of discussion today, and it's simply, if you could advise people to do one thing each day that might have a positive impact on any area of their life, what might that one thing be? Oh, that is a fantastic question, Danny. Okay, I think it would probably be to go outside, preferably into a garden if you can, but even if it's a street that's got a tree on it or something like that. And just to breathe, just breathe in outside, I'm currently living in Phelix, Dawn the East Coast of Suffolk in England, and it's lovely to be by the sea, but I found, I'm spending much more time just being outside, even briefly, going to the washing line and doing domestic things. It's just such a break from work. And I think, from a well-being perspective, I'd encourage people to do that, even if it's looking down, it's sometimes in the gutter you find these little plants that have escaped, maybe not in January, but the little plants that are growing there, so resilient. And it's a great encouragement when sometimes the world and politics and what not is looking quite discouraging and worrying. It's just a step back from that. As you mentioned, it's certainly something that we need at this current time. So very much appreciate that advice. It's something I'm going to take myself. And with that, Dr. Anjan Madden, thank you so much for giving up your time today, for coming and sharing this great information. And more so for the work you've done that's been, as I mentioned, very instructive to me and I'm sure to other people. So thank you so much for doing this. Thank you for the opportunity. It's been a pleasure and thank you for your well-informed questions as well. Thank you, Danny. Thanks so much for listening into today's episode. Before you go, I just wanted to remind you about Sigma Nutrition Premium, our subscription for those of you podcast listeners who want to significantly deepen your understanding of nutrition science and become truly confident in your knowledge. So what's the idea of this subscription? 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