Dr Harriet: It's probably safe, so the only downside here is cost if you want to spend your money on collagen supplements, it might help. It might not and it probably isn't going to do you any harm. But if it were me, I'd spend money on SPF 50 and I'd wear SPF 50 all day.
Dr Rupy: Yeah. Which is what I do.
Dr Harriet: As Caroline Hirons says, if it's light enough to to read a book, you should be wearing sunscreen.
Dr Rupy: That's a good advice there. That's my take home message.
Dr Harriet: Welcome to the Doctor's Kitchen podcast. The show about food, lifestyle, medicine and how to improve your health today.
Dr Rupy: I'm Dr Rupy, your host. I'm a medical doctor, I study nutrition and I'm a firm believer in the power of food and lifestyle as medicine. Join me and my expert guests where we discuss the multiple determinants of what allows you to lead your best life. Skin, lifestyle and diet, perhaps some of the commonest things I get asked about by patients and the Doctor's Kitchen community and honestly, one of the least understood at this point. And in today's episode, we dive into acne, a bit about the gut skin axis. We also talk about Dr Harriet's background in science from the lab to the plate or pill, and we talk about our thoughts on collagen. Make sure you listen right to the end because I summarise our thoughts on diet, lifestyle and supplements for healthy skin, so you don't want to miss that. The pod does get a bit technical in places, but don't worry, we will try and explain everything as we go along. It is always a pleasure having Dr Harriet on the pod. Her experience as both a frontline clinician, a scientist and registered nutritionist really shows and I love chatting to her. Dr Harriet Holme is a registered nutritionist and former experienced paediatrician. After studying at Cambridge Uni, she worked as a doctor in the NHS for well over a decade before focusing on nutrition and she also has a PhD in genetics and is a lecturer in nutrition. She's also authored two books that I highly recommend. One is called Eating During Pregnancy that she wrote to provide mums with credible information on pregnancy nutrition, and the other one is Postpartum Nutrition, an expert's guide to eating after a baby. And that was written to support new mums and their journey through motherhood and weaning. Dr Harriet also has a number of virtual courses on nutrition on her website that you can check out at healthyeatingdoctor.com. The links to which are all on the podcast show notes as well that you can find on the doctorskitchen.com. There's also an article to support today's podcast that you can find on my website, which lists some of the references and the evidence base that we use for this episode, and I hope you find that a useful resource. So remember, listen right to the end. I'm going to summarise our thoughts so it's a lot easier for you and also check out the doctorskitchen.com newsletter where I give you something to eat, read, listen or watch every single week that helps you lead a healthier, happier life. Onto the podcast. Okay, cool. So we're going to talk about one of the articles that is on the website that you've you've written. It's all about skin, but we're going to dive into a couple of topics. So we'll talk about acne, atopic skin conditions, psoriasis and obviously collagen, something that we are asked about quite a bit. So why don't we start with with acne itself? What do we mean by acne? I think everyone kind of knows what acne is, but there are a bunch of different types. So how how do we approach acne from a sort of medical perspective first of all?
Dr Harriet: So acne, there are lots of different types, but the main one I'm going to talk about is acne vulgaris and that affects up to 90% of teenagers. And we don't really know quite why it happens, but there are some certainly some pretty decent theories out there. And first of all is that you've got sort of three primary factors that are implicated. So you've got the sebum over secretion, so it's sort of oily, greasiness. And then you've got these cells called keratinocytes, which are part of your normal skin. They act abnormally, so they desquamate and they they obstruct the ducts in the skin. And then you've got superimposed inflammation, which is mediated by a bacteria, and that's either called propionibacterium acne or cutibacterium acne. It's recently changed its name. So it's probably more likely to see it as cutibacterium acne. And it's all thought that those sort of things together cause acne. And obviously it sort of commonly affects those teenagers and that's thought really because at puberty, you've got activation of those sebaceous glands from your hormones, which causes an increase in sebum production. And then actually that changes the microbiota of your skin. So just in the same way that you've got all of those bugs in your gut, you've actually got a whole pile of them on your skin as well. And so that changes the makeup of, changes the conditions and then changes which bacteria have dominance. And so if you've got that that greasy sebum production, it's the cutibacterium acne that end up thrive in those conditions and then cause the inflammation. So that's probably what happens. And it's really interesting that that bacteria has a role in sort of inducing the inflammation and activating probably these other pathways, which I'm sure we'll talk about in a minute, but they are sort of IGF-1, mTOR and NF-kappaB pathways. And that sort of thought to be a sort of mechanistically plausible way that acne happens.
Dr Rupy: Yeah, it seems like the gut and insert organ/axis is sort of being discussed for for everything these days. And and in the article you talk about this gut brain skin axis and and how there's the presence of bacteria all over our body, all over the skin, I should say, in varying amounts and according to different life cycles as well, it can change. Is there something unique during puberty where we can see the differentiation of the different species at that particular time?
Dr Harriet: So if you think you've got, in the skin microbiota, it's actually affected by body sites. You've got moist, sebaceous, like your face, and then dry. So moist is sort of groin areas and armpit, and then you've got sebaceous like your face, and then you've got dry, which is sort of like the rest of your body. And it's really interesting how the microbiota, so the bugs that live in those different places are actually completely different. And during puberty, the your skin on your face changes and becomes sebaceous. And that's why kids aren't really affected with acne because it's effectively a dry area and it's got dry bacteria that live on it. So as it changes and as those hormones during puberty change and you have that drive to increase the sebaceous production, that then creates an area, a sort of conditions that help the the acne bacteria to thrive and that's what causes it. And so it's really interesting then that you've got, you know, if you think of why acne forms on your face, it's because that's the area where it's sebaceous. We think that's where cutibacterium acne is thriving. It's not thriving on other areas because it's not sebaceous. It thrives on your face, your your chest and your back, mainly your face. But for example, you don't get acne on your arms because it's a dry area or you don't get it in your axilla normally or your groin because they are moist and they've got different bacteria. So it's really interesting how it does seem to be really important what your species of bacteria, you know, what bacteria are growing as to how, you know, if you're susceptibility to acne.
Dr Rupy: Yeah, I think most people might be forgiven for thinking of acne as purely an aesthetic problem, something that you grow out of, but this is something that covers, you know, it can create a lot of psychological distress. I mean, certainly when I was a teenager, I had really bad acne, really bad. And to the point where, I can't believe I'm admitting this, but I I would actually put makeup on my on my skin to hide just how bad it was when I went to school because I was so I was just so embarrassed by it. And I know a lot of people go through it and stuff, but for me it was it was particularly bad and I I I've still got ice pick scarring, I think, because I didn't have the confidence to go to my GP at the time and actually speak to them about it and get treatment at the time because I was just, you know, going through all the the changes and stuff and and finding out who I was as a person and all the rest of it. But I've still got like ice pick scarring. And and I I guess, you know, we're going to talk about food and and all the other lifestyle elements, but I wouldn't want to dissuade anyone from from seeing their GP in their first instance to get treatment in the form of pharmaceuticals if they needed to.
Dr Harriet: Absolutely. And I actually spoke to Dr Justine Kluk, a consultant dermatologist who specialises in acne on my podcast. And we were talking exactly that about how much it's associated with, first of all, vanity and people thinking that, oh, it's just some spots, you know, why are you bothered about it or why do you should you get treatment or or coping with it and about how much it really does affect people. And I have, I didn't suffer from acne particularly as a teenager, but I have adult acne occasionally and well, it's going through a quiescent phase at the moment, but it's really miserable and I, you know, totally sympathise. But one thing that's actually really interesting is that acne and anxiety and depression often coexist. And that's possibly not because having acne is so miserable, but because there's actually a an actually a link there between the gut brain skin axis and that the psychological stress, so when you're stressed, actually can can impact the gut bacteria to produce different neurotransmitters. So those are signalling molecules or they trigger nearby enteroendocrine cells to release neuropeptides. And so that may well lead to a change in intestinal permeability and that then means that toxins and bugs and partially digested food can all get into the bloodstream and they then seem to actually be deposited in the skin and cause inflammation and maybe cause acne. So there's actually may well be a link, you know, sort of almost a cyclical thing that, you know, chicken and egg, if you if you're having psychological stress, maybe you're more likely to get acne and then therefore you maybe more likely to be stressed by it because obviously it's pretty unpleasant. And how do you really, how do you unpick that and resolve it? It's it's quite, I think it's quite challenging and I think the more I understand about about the sort of microbiota, both the gut and the skin and the respiratory, I think how complex it is and how it's all interrelated and how just tiny changes can just put you completely out of balance and the wide-ranging impact, you know, just your diet and changes in microbiota can have.
Dr Rupy: Yeah, that that's so wonderfully explained. You know, just thinking about all those different multifactorial processes that could lead to acne or a whole bunch of other conditions, frankly. You mentioned intestinal permeability, sometimes colloquially referred to as leaky gut. If you type in leaky gut into PubMed, you're not going to get anything, but if you type in intestinal permeability or hyperpermeability, you'll you'll probably find a lot more in the way of academic literature on the subject. That for me is quite fascinating because again, it all boils down to anything that impacts inflammation within the gut itself. So how you're nourishing your gut. I'm jumping ahead a bit because I we're going to start talking about foods and prebiotics and probiotics and all and the potential role for them as well. So I'm going to stop myself there. Before we go into some of the the dietary adjuncts, treatment wise, I know from a general practitioner's perspective, we try and look at hygiene initially. Now, a lot of people might be thinking, if you scrub harder, you get rid of that that off bacteria, that's what's going to resolve it. That's not the case, right?
Dr Harriet: No, and absolutely, and acne as well is not caused because you haven't washed your face enough. Absolutely not. Sadly, it would be great if you could just wash your face a bit harder and it all washed away. But actually really interesting that cutibacterium acne actually forms like some other bacteria do, a biofilm. And then they make this sort of self-made matrix of extracellular compounds, so a substance which actually prevents antibacterial agents and, you know, your own anti-inflammatory cells coming in to disturb it. And certainly that's seen on the skin, it's seen with other bacteria in the in the, you know, in the lung pathology. So it's not easy just to get rid of it and certainly scrubbing or, you know, certain agents, you have to overcome that biofilm. But there are anti-inflammatory and antibacterial topical agents like azelaic acid, isotretinoin, and then you've got your antibiotics, which you're aiming to really kill that bacteria and try to get rid of it. There are obviously some problems with with these things, which is why you really need to speak to either your GP or, you know, consultant dermatologist, because one of the sort of downsides of antibiotics is that while you're reducing the the the bacteria that's causing or linked with acne, it does actually increase other species like pseudomonas by quite a significant amount, you know, five to six times. And that's why you can sometimes actually get a sort of associated folliculitis, so that's an infection of your your hair follicles at the same time as having antibiotics. So while you're, you know, killing off or reducing your target bacteria, other bacteria then have a chance to thrive and and they may not always be the ones you want. And and also you've got that sort of challenge of increasingly becoming resistant to certain types of antibiotics, not just in you as an individual, but as you know, a global challenge that we are increasingly seeing antibiotic resistance problems and that is is challenging. So if there was a better way of maybe treating with, you know, certain um sort of immunomodulatory, you know, bacteria or probiotics or changing that skin microbiota in the future, you know, there'd be a really great treatment and and would solve a huge unmet need, I think, but we're we're nowhere near that at the moment, but it would be great.
Dr Rupy: Yeah, definitely. With regard to skin products, I mentioned sort of, you know, what I used to put on my skin and stuff. Is there evidence around the the type of moisturiser particularly you should be using, i.e. one that doesn't block the natural pores that could lead to increased production of sebum leading to acne? Particularly for for teenagers or or even in adulthood as well?
Dr Harriet: Yeah, you should use a non, I think it's called comedogenic, I think it's called. So it's a specific type that doesn't block your pores because greasy skin products that block your pores can increase your risk of, you know, can get the comedones, the blackheads forming more easily and it trapping the the the acne bacteria that you don't want.
Dr Rupy: Yeah, yeah. Brilliant. Okay, let's let's get to dairy in diet because I know I know I'm I'm I everyone always whenever something comes up on on Instagram or or social media, I'll give my response and then somebody in the comments will say, just get rid of dairy. Just get rid of the dairy. That's the issue for a lot of people. And it's not as simple as that, at least not from the research that we currently have. And and as we're anyone who's been listening to the podcast is aware, you know, nutrition research is very, very difficult to draw conclusions from. So, but but there is a potential mechanistic reason as to why dairy might be problematic for certain people. So yeah, so let's tackle dairy.
Dr Harriet: Yeah, so absolutely, I mean, you've you've you've hit the nail on the head there. It is really difficult to unpick this and I think it's quite a nuanced topic, dairy. I should say that the sort of the most comprehensive guidance on diet and acne comes from the 2016 American Academy of Dermatology guidelines and they don't think there's enough evidence to suggest that you should give up dairy. So I think that I'll come with that statement first and then discuss sort of why dairy is important. So really, dairy, when you break it down into amino acids, it promotes insulin secretion. Insulin, we know, drives the glucose into your cells where you can use it. But it also is related to insulin growth factor like one synthesis, so it's IGF-1 synthesis. And IGF-1 has a number of different roles. So it it influences, it induces this other pathway, this other enzyme called FOXO1, which senses cellular nutrition, and that can trigger mTORC1, which is a governor of cell proliferation. So that's how your cells reproduce, how quickly they're turning over. And also it can lead to sebaceous hyperplasia. So by that, the sebaceous glands, those oily, greasy, those oil producing glands on your skin, they can start getting bigger and producing more oil. So that may be one factor. It also IGF-1 stimulates follicular growth and keratinization, all thought to be related to acne, and androgen hormone production, which again related to acne, which is why women with PCOS, so polycystic ovarian syndrome, are at higher risk of acne because they've got higher androgen hormones. And then all of those factors together are a sort of form a mechanistically plausible explanation as to why if you're having anything that's raising your IGF-1, you may well increase your risk of of acne. And there's some studies that support that. So they've shown that in people with polymorphisms of IGF-1, so that means small genetic changes, not mutations, but just small genetic changes in IGF-1 are actually associated with acne. And and they've looked at plasma levels of IGF-1 in a in a small study of just 80 people and they looked and they found that actually the levels of IGF-1 correlated with the severity of acne. So all of that together does sort of form this sort of mechanistically plausible explanation. And and then milk also, not only is sort of the breakdown of the amino acids driving IGF-1 synthesis in your own body, but it also contains bovine IGF-1 and dihydrotestosterone, DHT, which is a precursor of IGF-1 as well. So you can see then that you've got your own endogenous production of IGF-1, the exogenous bovine IGF-1 and it's, you know, the precursor and why therefore, um, it's possible that that dairy does impact it. So there have been a number of studies that have tried to sort of see if that really does happen in the real world. And one of them is a Cochrane review. And Cochrane review being, you know, one of the the highest forms of evidence really, it's a huge meta-analysis looking at lots of randomized control trials, trying to put it all together and work out what the what the outcome is. And they did find that dairy, especially skimmed milk, did increase acne, but a number of the trials really were not very rigorous and and so actually it's quite difficult to draw firm conclusions from it. A number of other studies have found a link with with milk but not with yogurt and cheese. Maybe there's a soluble fat soluble protective factor or maybe it's just that all dairy has a negative effect, it just wasn't picked up on that study. And then there's another meta-analysis that partially overlapped with the Cochrane, so included some of the same studies, and they found that all dairy increased acne. Again, whey powder, part of the building blocks of dairy, has been found to sort of induce truncal acne in bodybuilders. So I think my take-home message from it is that if you have acne, have a trial of dairy-free, you know, for a couple of months and see if it works for you. If it doesn't, it doesn't, and if it does, you know, happy days. And I think, um, it's quite easy to give up dairy now and change over onto a plant-based alternative. I will just say at that point, please don't choose organic plant-based alternative. Choose the ones that are fortified with calcium and iodine. Um, and and you know, have a get your, you know, protein and calcium from from other sources, your iodine from other sources. So it's perfectly easy now, there's lots of products to do that. Um, and I I think it's worth a an individual, you know, a trial at an individual level.
Dr Rupy: Yeah, definitely. It's it's super easy, I I guess these days to get those plant milks, but iodine, like you mentioned, is is super important because even though milk isn't the best source of iodine, it's the most common source of iodine in people's diets, at least in the UK anyway, uh, because of some of the agricultural methods. And certainly touching on the podcast that we did before on fertility, that's super important, um, thinking about iodine, uh, intake, right?
Dr Harriet: Yeah, absolutely. And um, you know, you can get iodine from fish, but if you're vegetarian or vegan, um, you know, it's a bit more challenging.
Dr Rupy: Yeah. Is there a suggestion that the sugars in certain milk products are also exacerbating? I I suppose this touches on the the next point about westernized diets and uh diets that contain a lot of highly refined sugars and and carbohydrates. Is there a suggestion that it's the milk, the the milk sugar specifically that could be activating these pathways or is that a separate?
Dr Harriet: I don't think that anyone knows that. I think it's thought that the amino acid breakdown stimulates the IGF-1, but also, you know, there've been other studies that have looked at, for example, chocolate and jelly beans. And they did a small crossover study with that. And they found that the chocolate did increase the acne, but was that, that was milk chocolate. Was that the milk in it or was that because the the jelly beans didn't increase acne and that's the sugar, right? So, um, what was it in dairy or was it dairy or was it chocolate? So I, you know, I don't think we really understand that yet and I don't, so I I think it's probably not the sugar, it's probably, you know, the IGF-1 production, but, um, but coming back to then westernized diets, you know, they are high fat, uh, high refined carbs, um, and low fibre. And certainly all of those things increase the IGF-1 signalling and also altered retinoid signalling. And you just don't see acne in people with low GI diets. So for example, like Papua New Guinea or somewhere, people don't have acne. And is that related then to, um, the fact that they are eating low processed, uh, you know, raw, whole food, uh, with high fibre, high low GI, that that's what their diet contains. Um, so it's probably that you've got that high fat, high fibre, uh, sorry, high fat, high dairy, low fibre that as well may well be disturbing your microbiota. And we know we've just been talking about how microbiota impacts the skin. So all you need to do is shift your microbiota and then you, um, change your intestinal permeability, you let all of those things in and that get deposited in the skin, which can then lead to inflammation. So it's it's quite a sort of subtle interplay and really quite complicated and it's probably not just one single factor, it's probably all of these factors. And it might be that actually it's not dairy per se, but it's about having a diet that is, you know, low GI, so whole grains and fruit and veg and antioxidants and, you know, fermented food, nurturing your your gut health that allows you to have dairy or allows you to have the occasional, you know, piece of junk food because actually your diet is so good otherwise that your microbiota, your gut health is good, which helps your skin health. So it's difficult to unpick it all at the moment, I think.
Dr Rupy: Yeah, yeah, absolutely. So a low GI diet, high in fibre, lots of roughage, certainly going to be improving your microbiome and you're not going to be having, uh, as many McDonald's or or insert fast food chain, uh, meal. And also you've got omega-3 as well, if you think about it, you know, that sort of the western diet versus like Papua New Guinea, you've got your high omega-6, high low omega-3 in your western diet, which is pro-inflammatory versus a healthier diet would be high omega-3, low omega-6. So and omega-3 actually decreases IGF-1. So you can see how it's involved in possibly involved in the mechanism. But there's just not enough studies to support at the moment whether, I say, taking an omega-3 supplement would help, but um, certainly an interesting thing for the future. And then, um, antioxidants, I think it's fascinating that lower vitamin A and E was found in people with acne. Now, is that chicken or egg? You know, it's really interesting. Um, but topical antioxidants like in green tea have been found in animal studies to actually, um, sort of feed into these pathways. So one of them is one proliferation pathway is mTOR, and so actually did have an impact on mTOR. But, you know, who knows, sort of talking, I know that we've talked a bit before about animal models and things, but, um, so this is if you put, if you're dropping something like green tea, uh, on cells in a petri dish, that's your sort of cellular model of it. It's a very, very long way from a human. And I think, you know, we need to exercise caution in those, but as with any of these things, fruit and vegetables, antioxidants, polyphenols, they're going to, you know, help you.
Dr Rupy: Yeah, actually, I think that's a nice point to do a little sidebar there about how we translate research from a laboratory environment like that where you're literally dropping a solution onto a bunch of cells that you put in a petri dish versus consuming said product, uh, either as a supplement, a nutraceutical or as part of your diet and actually having that effect, uh, you know, on you that's actually clinically relevant. You've done a PhD, you've, uh, you've seen both sides of it and you're a frontline, uh, uh, doctor as well, as as being a nutritionist. So why don't you talk us through like how big a difference that is between the lab and what you put on your plate or what you take in a in a pill?
Dr Harriet: Sure. So I have to say that, um, even though I was an academic clinical fellow, so an academic doctor and I'd done time in the lab and things, it wasn't really until I did my PhD that I actually understood this. And so I think, you know, for the for for most doctors or a lay person, it's actually quite hard understanding all of these different things and why they're used and the pros and cons with them. So if I just sort of break down what the different models are, and I use the word model because, um, it's a sort of a way of testing out a theory. So you're in science, you're always trying to test out that theory, you know, asking a question, um, is your theory right or not? So the easiest way to to look at something, um, is by growing cells in a dish and that's your in vitro method. And, um, it's actually really quite hard to grow cells. If you just, if I took a skin punch biopsy from you and tried to grow your cells in a dish, it's actually really quite hard. And it's only recently that people have got a bit better at it and they're now able to to to do it a bit better. But for a long time, um, and I'll talk a bit more about that in a minute, but for a long time, people have used what's called cell lines. And that's where they're sort of immortalized cells that carry on growing and are happy to grow in plastic. And, uh, one example of those is the famous called HeLa cells. And that's actually from one woman called Henrietta Lacks. And those are her cervical cells. I mean, you know, most cell lines are now contaminated at some point by HeLa. So you've really got to know, um, what you're growing, the fact that it's happy growing on plastic because most cell lines, you put a cell on plastic and it just goes, I'm not growing on that and won't grow. So you've got to make sure that, uh, your cell grows and is is happy growing and you give it the right conditions, so you feed it with some media, you keep it nice and warm and you give it some oxygen. And it's really important that every now and again, you actually check that you know what you're growing because you can't tell down a microscope what it is. It could actually be anything. And as I just said, lots of cell lines get contaminated, you know, it's really easy just to to get a cell in the wrong place. Um, and those, those, that sort of tissue culture it's called, um, is actually really different from from our cells growing in the body because they've they've got totally different growth factors, they're probably, um, they're not used to a 3D environment, there's no extracellular signalling, nothing. And and so what information you can gather from that is actually really quite limited. And that's why people more recently have sort of developed these ways of taking some cells from a primary culture, so going back to your like skin tissue biopsy or something, and they're able to now grow them in the laboratory into these things called organoids. And they're sort of like 3D structures, um, which almost, which are better at mimicking what's actually happening in your in your in your body. But still, you know, there's no blood supply to them, there's no, you know, there are no external factors or hormones or all the rest of it. So it's still is quite limited. And then you've got, um, animal models. And although, you know, I think it's really difficult and challenging to think about testing on animals, it is also, you know, the only way that we can test something is safe before, you know, we we put it first in humans. And drugs aren't always safe. We need to, you know, test that they are first. And, um, and so that's why, you know, animal studies are done for to really forward the field of of of medicine and try to cure people from, you know, all sorts of diseases, cancer included. So if you've got an animal model, you can either, um, induce the disease in the animal, and we'll talk about that in psoriasis later, um, or you can, um, take a bit of, uh, tissue from something else like a human and put it in the animal and test it. Um, you can get a mouse and you can induce cancer, for example, or a model of disease and then test it. The problem with that is that for example, radiation induced osteosarcoma is not the same as a cancer that just spontaneously occurs. It will have different genetics. And and so might not be the best model to test it, but in a, you know, it's if you've got nothing else, then that's going to be your best model. So it does still have its limitations. And then now you can do what's called knock-in, knock-out studies where you can actually specifically edit, uh, even mice and, um, put in a gene of interest, take out a gene of interest and see how that, um, affects, um, growth or a number of different characteristics or how they respond to drugs. And then right at the top of the tree, you've got your human, so in vitro studies and those you're using healthy volunteers, mainly men, and they're testing, um, molecules that have been tested on animals already. So you can see that going from that initial hypothesis, that initial question that you want to to to test and to ask, you've normally gone through cell lines or organoids and then you've put it into a mouse model and then you've got it into a human. And all the way through, you're testing not just, um, does A equals B, but you're testing, well, what about, uh, how can I, can I do it in reverse? Can I do it in an orthogonal, so an alternate alternative method to really be sure that the answer that I'm seeing is correct. So you can see that to get to a human study actually takes years of research, um, to get in all of those other other things lined up first. So it's, um, it's very difficult and expensive to get there. Um, and and also, I think then sort of looking at reading papers, it's really important to know that the difference between a a study that was done in a human versus, um, a topical application of some on a cell line, um, is very different and and that, uh, through all those sort of reasons I've just sort of outlined, I mean, you need to exercise a lot of caution.
Dr Rupy: Yeah, definitely. And I think, you know, for for folks listening or if they see a headline and they click to the paper and then you read the abstract, maybe you don't read the whole paper, you can get an idea of just how far along the down the the chain, uh, the the relevant conclusion is by looking at where they tested this, was this an animal model, was this a cell line, was this in humans, how large a study, and then you get into the nuances of the significance, the number of humans used and all this kind of stuff. Um, so and just to give people an idea, I don't know whether you can actually put a number on this, but let's say you have a positive result in, uh, a cell line, what's the likelihood that that's actually going to, uh, elicit, you know, the creation of a drug or the use of a of a nutraceutical or some sort of some certain supplement? What what's the likelihood that that's actually going to translate into something that's that's going to work?
Dr Harriet: I can't give you a figure for that, but I can tell you that, say for example, um, well, like doing my PhD that, you know, I found lots of positive things or positive things where drug A did, uh, have an effect on our cell line, for example. But the problem is with it is that first of all, if you think, so I, I did my PhD was on osteosarcoma, so it's a rare form of bone cancer, and it's actually really, um, heterogeneous. So the genetics of it are really quite different in different people. Um, and so trying to study a disease like that is really quite difficult. And lots of diseases are like that. Um, you might be able to sort of divide them up into subtype or have a biomarker to sort of delineate groups and things. Um, but actually then, I didn't just use one cell line, I used a panel of 18 cell lines in order to try to to represent the different, you know, a greater depth of the disease. So trying to find one drug then that actually had a significant effect in all of those cell lines, I I did find a couple of those. Um, but then I, I didn't, I think if you're doing rigorous science, you have to then work out quite the mechanism behind it and and test it in an orthogonal way. So that's sort of, you know, coming at it from a different angle. So while you might get an initial hit from your drug screen, then trying to work out either a mechanistically plausible explanation for it or then testing it in a different way, either so I used like siRNA, so that's small inhibitory RNA to knock different genes out. Um, actually then a lot of the hits from your drug screen don't go anywhere. And then from that, then if you actually find something that does work and then you put it into an animal, you're still seeing quite often quite small gains even in the animal. Um, it's quite hard to see an effect. As I said, you've got your, so either your radiation induced osteosarcoma or your you can do what's called, you can actually put some of the cell lines in or you can, um, so you're testing like that into the mouse. Um, so it's quite hard actually then to be sure that even if you do see something in the mouse, that it's actually relevant for the disease in the humans because you're still quite limited to those cell lines and your and the mouse model. So it's really hard at each step, you know, there's a significant drop off and that's why research costs a huge amount of money because there are so many dead ends and, um, it's it's really challenging to find those those, you know, next drugs, um, because, you know, years worth of research has to go into to doing all of the the background before you even see the drug in, you know, with your GP or, you know, whoever's prescribing it. Years and years, you know, 10 plus years normally have gone into that.
Dr Rupy: Absolutely, yeah. And, uh, you know, hopefully that will give people an idea of why it costs billions of pounds to do research into molecules, why there is a a patent, uh, legislation that gives drug companies, I think it's 17 years is the amount of time that they have, um, uh, ownership, uh, of of said product. Um, and it's a really expensive business. And we're going to come back to this actually because there's a bunch of other supplements that are readily available where that kind of rigor hasn't actually been, uh, uh, conducted because there's a way around because they can already sell the product, um, because there's enough hype around it. So, but we'll we'll leave that. I think that's that's really interesting for for people to understand just how molecules are created and and how we, uh, form those into drugs and and the amount of research that goes into that. Let's bring it to atopic, um, uh, psoriasis because this is where sort of your your your experience and research has had an effect. Um, first of all, what is psoriasis for for people at home?
Dr Harriet: Um, psoriasis is a sort of scaly skin condition or sort of a hyperproliferative skin condition. Um, it's actually not that common. You've so hardly any children have it. You see it more in in adults up to 10%. And it's associated with immune activation, but really the sort of mechanism of it is quite unclear. Interestingly, it's actually associated with an increased risk of cardiovascular syndrome and metabolic, uh, cardiovascular disease and metabolic syndrome. And it's now thought that you have altered gut microbiota, um, that might impact and and cause some of this. So they've tested that using imiquimod, um, which is a toll-like seven receptor agonist, and that's to induce a mouse model of this. And the topical IMQ actually then alters gut microbiota in mice and, um, and it increases the marker of inflammation. It also increases the volume of their spleen, which is another sort of surrogate marker of, you know, that there's chronic inflammation going on as well. And it's there thought that it's the gut, um, the gut issues that you've got, the sort of dysbiosis, this altered gut microbiota that then, as we talked about before, then leads to that leakiness and inflammation and then you actually have the deposits of of that leakiness, the stuff that's absorbed, the toxins, the the partially broken down food and things into the skin and that that then, um, is related to, um, psoriasis increase. But it's also that, um, maybe bacteria. Now they don't quite know how this, um, happens, whether it's bacteria from the gut are travelling to the skin or whether it's the change in environment because of the inflammation in the gut leads to a change in inflammation, a change in environment in the skin to then certain bacteria then flourish because staph lentus is one of the bacteria here that's actually been seen in patients with psoriasis and may well be driving some of that. So as part of that sort of study they did in the IMQ treated mice, they have found all of these changes. And interestingly, um, so one of the other things that's quite difficult to explain about KEGG pathways. So KEGG pathways are, it's like this massive database and if you think of in the cell, you've got so many different cellular processes and proteins and trying to work out what on earth does what and how they all interlink and there are so many different pathways. So KEGG have this amazing resource where you can sort of try to to really understand the the molecular biology a bit more because you can see like a sort of metabolic pathway or a cardiovascular disease pathway or a growth pathway and how all of those proteins have linked together in a sequential fashion. Um, and it's at a sort of greater sort of more superficial understanding of sort of high level functioning of of cells really. So they've, um, did this the the people in the study that did this IMQ, uh, model for the mice, they did, um, what's called metagenomics on on the mice. So they sequenced all of the the DNA that they collected from the skin from the psoriatic regions and they actually found there was a difference in KEGG pathways and that actually the cardiovascular risk and metabolic disease pathways were were different, which maybe then explains why psoriasis is linked with cardiovascular disease and metabolic syndrome. So how it all links is actually, I think, incredibly fascinating.
Dr Rupy: Yeah, yeah, definitely. We didn't mention it with, um, with acne, but I I guess it's probably more pertinent here. Would there be a role for probiotics, um, and in in the treatment of psoriasis, other autoimmune conditions and and skin disease?
Dr Harriet: I I think that there probably is a role in the future. I don't think that enough is known about it at the moment. Um, and there aren't the studies to support that, but, um, you know, I think it's it's, you know, may well be something of the future. Be interesting to see whether they're topical probiotics and whether, you know, you're going to be taking gut microbiota, um, or quite, you know, if you think of respiratory conditions as well, I know that's a bit off topic, but will that be nebulized probiotics, you know, it's really prebiotics, would prebiotics work better? Because there's so many, there's so many sort of nuances to it all that, um, it's not just about increasing bacteria or specific strains necessarily, it's about, you know, that, uh, alpha, the diversity and also that, you know, cellular or studies have shown as well that say post antibiotics, taking probiotics can actually prevent recolonization of your own gut. So, so how it, I I just think we we're so in such our infancy in all of this, we just need to know so much more information.
Dr Rupy: Yeah, yeah, that that was actually flying in the face of what I thought would be a pragmatic decision, um, to to take probiotics after having, uh, some form of antibiotic therapy because you want to try and recolonize the gut, but, uh, I I can't remember the the mechanism, whether it's through creating a biofilm that prevents recolonization or something like that.
Dr Harriet: There were two big, two big studies published in Cell, you know, really high impact factor journals that showed that, um, the probiotics either did nothing post antibiotics or in about 30, 40% actually prevented recolonization. I think, you know, it does naturally feel or certainly a lots of clinicians have used them to think, oh well, you know, it must help me, I'm replacing my probiotics, but if I'm replacing my bacteria, but if they are preventing reconstitution, then that's that's certainly a a risk factor that I think that most people don't associate with probiotics or a supplement. You think that supplements are are actually good for you or and the worst they can do is waste your money on, you know, they're maybe expensive, they're not going to harm you. I think that's most people's view of supplements, but then to think actually maybe this could be doing me some harm because it might be preventing my gut from reconstituting is is a bit more of a worry, I think.
Dr Rupy: Yeah, and and like you just mentioned there, you really have to take an orthogonal approach to how we utilize, um, probiotics as a treatment. You know, it's not just about the strain or the type, it's about the formulation, it's how you use it, what the method of delivery is, whether it's nebulized for for folks at home, that's uh when you breathe it in, um, uh, versus topical. You know, I'm already seeing a lot of probiotic preparations in the skin and beauty industry, uh, being sort of, uh, suggested as a way to prevent aging and all the rest of it. Um, I I mean, I haven't come across anything personally. I haven't actually looked, uh, for, uh, skin formulations and whether they're having any benefit. I mean, in the future, maybe, um, but right now, I'm kind of skeptical.
Dr Harriet: Well, I I think it's a really interesting area for development. And I think if you tag, you know, the words probiotic on it, people think, oh, it's must be by science or, you know, oh, it's must be must be good for you. But actually, you know, there's been, well, there's been some mouse studies which have shown that specific strains of bacteria actually, um, prevent UV damage and can actually increase skin health, increase like fur, the shininess and thickness of fur, all, you know, related to skin health. So, maybe in the future, probiotics will be of benefit, but I just think that we don't know enough about what normal skin looks like, what the, you know, what inter-ethnicity, inter-ethnic variation, inter-geographic variation, you know, how does diet and, um, how do all of these other factors link before we can then start modulating stuff? And that to me just feels like we just don't know anywhere near enough. Maybe these are the things of the future, maybe we'll all be, you know, smearing, we won't be using moisturizers anymore, we'll be using our probiotics on our face. Who knows? But I just think we need more information.
Dr Rupy: Talking of aging, uh, so collagen. Uh, collagen is, uh, super hot right now. I feel like I'm Bruno there. Super hot right now. Um, it's it's an interesting one because I I'm getting asked about it a lot. I I said to you last week, I don't know that much about it. I haven't really done much of a deep dive into it, but it's, um, I know obviously it's a it's a factor of skin and and during aging, you lose collagen as well as a whole bunch of elastic fibres, uh, along with the synthesis of hyaluronic acid. I always get that pronunciation wrong, which is why you're, you know, you you see, uh, beauty creams with hyaluronic acid in. Um, from my understanding, the only anti-aging claim you can make, uh, for a product is if it's got, uh, a significant amount of SPF in, um, to qualify for, you know, the UV blocking, um, uh, effects of a of a cream, which has been shown to reduce aging. Uh, but collagen appears to have some potential benefits, I would say. I'm saying that tentatively. Uh, why don't we talk about what what what collagen, uh, preparations there are out there and, uh, and your your perspective on it?
Dr Harriet: So collagen, yeah, I agree. I think it's a really interesting topic because it's actually really nuanced. It's just not clear. Um, so collagen is a large protein. Most of the supplements are, you know, oral, you're taking those collagen supplements by mouth. Um, and so when you ingest a protein, it's digested, so broken down into smaller subunits, and that's your peptides and amino acids before it can be absorbed. So if you're eating that your supplement or you're having a piece of steak, um, all of those proteins will be broken down into amino acids. So, first of all, you have to think that anything you're taking in will be broken down. And then it's quite hard to see then why it would be rebuilt specifically into collagen. Normally, you know, the body knows what it needs and it's synthesizing all sorts of different peptides and, you know, proteins within the liver. Um, why would it specifically reconstitute back into collagen? And even if it did, would it definitely travel to the skin? So that's first of all, the sort of the question behind it, the sort of mechanistic question. But there have been a couple, you know, a few studies that have looked at it. And and actually found that with collagen supplementation, it has improved skin hydration and wrinkle count. Um, but I think they're quite subjective markers and it's quite hard then, you know, to draw conclusions. But possibly one of the more interesting studies actually analyzed skin protein fluids, which I think is a more objective marker. And they did find that procollagen, fibrillin and elastin all actually increased. So I think it's quite difficult then to know what that means. Um, first of all, you don't know what the diet of these people was when they were taking it. There's no record of that at all in these studies. Um, you know, how how high quality was their protein intake. And secondly, just because you've got, um, these proteins that are raised in this in your blood or skin fluid, does that mean that they're having an anti-aging effect? So studies have looked and they've found sort of increased skin plumping and doesn't appear to be associated with side effects. So I think probably what you can, what I take from this is that I don't really understand the mechanism at all because it doesn't make sense to me that it would be broken down, why would it be resynthesized? But maybe it is, maybe this we don't understand that. And if it is, then is it having an effect? I'm not sure. I'm not convinced. Um, I'm not convinced by the subjective element of these, uh, that the outcomes that they've used. They've used small studies, we don't know the diet. Um, but it's probably safe. So if you probably the only downside here is cost if you want to spend your money on collagen supplements, it might help. It might not and it probably isn't going to do you any harm. But if it were me, I'd spend money on SPF 50 and I'd wear SPF 50 all day.
Dr Rupy: Yeah. And that, you know, that sort of comes back to how difficult it is to choose a, what does a high quality supplement look like? It's almost impossible to tell, I think a lot of the time.
Dr Harriet: Yeah, yeah, totally. I I I was laughing to myself because, uh, some of the, um, the output measures, uh, of the studies that I was looking at, I've just I've never come across it before. So there was a changes in visually assessed crow's feet scores, changes in skin wrinkling parameters, skin roughness, uh, uh, what was this? Uh, smoothness depth. Like I I mean, I I don't know like how validated these scores are. I'm sure, you know, maybe there are, but it was just, uh, it just goes to show like how little we know about this. And coming back to our previous discussion about your your PhD and the translation of science from a cell line to a product that you can put into your shelves, there's already enough hype around collagen, longevity molecules that you you'll see being sold on the internet and all the rest of it, such that you don't need to do these rigorous studies because it's available and people will buy it. So this is a multi-billion dollar industry already without having to put any of the research and development behind it. Um, which is quite sad in a way, I guess.
Dr Rupy: It is, because I think we'll we'll actually never know if there's any benefit of collagen because no one will ever fund the study. Um, the one interesting thing about collagen is that it might actually help wound healing. So if you're if you've had an operation, I think that's the one time I'd recommend it, but the rest of the time probably not. But yeah, absolutely. And just to go back to that, so, um, how research is funded in this in the UK is actually mainly due to charities. And that's really often according to which charitable groups have the the loudest, you know, the loudest voice and the the biggest, uh, you know, patient group and patient advocacy. And so lots of the smaller or less well-known diseases are often forgotten in that. Um, but charities make a, you know, have a huge role. And for my, um, my PhD was funded by, um, by Bone Cancer Research Trust and also by Breast Cancer Now. And two charities that do a huge amount of work, you know, people out there running marathons funded my PhD. My PhD cost, you know, at least 250,000 pounds. I don't know the the the final bill. I'm sure there was lots of, you know, extra bits of plastic and tissue and bottles that, you know, maybe didn't quite get onto the final bill. So I'm saying upwards of that. You know, that's a quarter of a million pounds. And while, you know, I sort of pushed pushed forward the world of osteosarcoma a little bit, you know, I didn't find a cure for it. And and, um, you can just see how expensive it is, how difficult it is. And that's three years of, you know, full-time research, you know, really trying to unpick all of those those things and and how difficult it is and and why it takes time and costs lots of money. And if you are supporting charities, please go out there and carry on doing it because you really are the backbone of the research in the UK and it's so important.
Dr Harriet: Absolutely. I'm so glad you mentioned that. Um, and I'm really glad you mentioned, uh, the potential for, uh, collagen research looking at recovery because one thing that I I think probably doesn't get enough attention and I'd love to see people running marathons for it. Maybe maybe I will at some point if I ever do a full marathon. I've only done a half and that was horrible for me. Um, but pressure ulcers. So pressure ulcers and the breakdown of skin that we know happens very commonly, particularly to vulnerable elderly patients in hospital because of prolonged stays, as well as sarcopenia, you know, malnutrition, a big issue. Um, whether collagen supplements could prevent pressure sores that lead to, you know, extended hospital stays as well as infections and all the rest of it. That's what I would be really, really interested in. Um, and there has to be rigorous studies for collagen to be, uh, supplemented in in those vulnerable groups as well. So if you see me running a marathon, it'll probably be for pressure sores. It's not very sexy, I know, but
Dr Rupy: I was just going to talk about then about hospitals and patients and things. I think this is like absolutely incredible how I'm going to stick myself out on a limb here. Having so having worked in hospitals for, you know, well over a decade, I know that the food in many of them is perhaps not quite what you'd like it to be. And that the more and more we know about how the gut health, you know, when was the last time you saw fermented food on a menu in a hospital? You know, I know as a as a, you know, a staff member, the food was, you know, it was pretty fast food a lot of the time. It wasn't, you know, take your own food in. You know, if you're a patient, and also as a a mother of a child who's been in hospital, um, it's it's not great food a lot of the time. And, um, and you think how important food is for gut health and how it has such far-ranging effects on, you know, your skin, your respiratory tract, your mood, your brain, your response to medication, you know, it's just so important. I just think we need to to do better and we need to understand it more and and to to really optimize our gut health because it's the foundation of everything.
Dr Harriet: Yeah, no, I I totally agree. There there is some work. I'm holding my breath for it. Well, I'm not I wouldn't say I'm not holding my breath for it because we've seen a number of hospital reviews in the past, but there's something quite special about this one. So Philip Shelley was the, um, chair of the recent hospital review that started pre-pandemic and obviously it's had a whole bunch of, you know, delays with everything going on. Um, but they have made some really, really interesting suggestions. Uh, something that I'm getting involved in is the NHS chef award of the year. So it's basically to highlight innovation and excellence in NHS catering in in the public sector environment. And so they're showcasing a whole bunch of different chefs from different regions, looking at how they're collaborating across dietitians and nurses as well as patient support groups as well, to deliver safe, uh, delicious food that's actually healthy as well. And I think my sort of contribution is A, trying to prop them up as much as possible, but also feeding them a bit of knowledge about, you know, the gut microbiota, increasing fibre intake, all these different things that the dietitians will be saying as well. But again, just hearing it from a frontline clinician, I think just sticks in a little different way. Um, so there are some things happening, I think. Um, we're probably a little bit further away from like sauerkraut being served on the side of a of a hospital tray, but you know, we can only dream. One day.
Dr Rupy: I hope so. I hope so. Yeah, I hope one day. Definitely, definitely. Well, Dr Harriet, thank you so much for coming back on the pod. This is brilliant. Uh, as always, you're such a fountain of knowledge and, um, uh, I'll have to, I will join your pod. I'm I will definitely come on your podcast, but um, it seems to be doing really well regardless.
Dr Harriet: Well, thank you. No, it's been an absolute pleasure. It's always a pleasure coming and talking. So thank you so much for inviting me.
