52: Lipedema with Dr. Ben Bikman

The metabolic classroom. I am Professor Ben Bickman, biomedical scientist and professor of cell biology. Thank you for joining me today. This is a topic that has been a long time coming, especially for a fat scientist like me to say that again. A scientist that studies fat tissue and adipose tissue, which is lipedema. That's the topic of the day. Lipedema. This is one that I have been probably more than any other singular topic over the past few years been asked to discuss. And it took a little for me to learn enough to really speak about it. Hopefully that's going to be helpful information. Today's episode is sponsored by Health Code Complete Meal. You've heard me talk about insulin resistance, of course, for years. It is the focus of my career and you need to address insulin resistance by addressing your diet. The problem is we of course get very busy, we get stressed, we're tired, we have the best of intentions to eat well, but those fly out the window. 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When you think about adipose tissue very commonly and indeed the only thing you've really heard me talk about is the fat cell itself. But the actual adipose tissue is composed of a lot of other things. So I want to first start out as we basically cover the more foundational information of fat tissue by talking about adipocyte structure. So each fat cell, each adipocyte adipose tissue made up of little adipocytes or fat tissue made up of little fat cells primarily consists of a large cell, a fat cell that is basically one big lipid droplet or one big fatty bubble and Then any other parts of the cell like the nucleus or the mitochondria are. There's so little of it, but it's all just kind of pushed up to the edge. I mean, literally pushed up against the edge of the cell. So when you look at the fat cell under a microscope, like we're doing all the time in my lab, you just see this big, like, blank space. It looks just like a big bubble. Now, fat cells are. You would, despite me saying bubble, although that's not a bad analogy for reasons I'll get onto in a moment. But when you think of a bubble, you think about just, just this big spherical, round ball like shape. But in reality, if you were to take bubbles and start stacking them together, you would see that they then begin to form some angles. So fat cells are referred to as having a polyhedral shape formation. So when fat cells start to aggregate and come together like they do in fat tissue, they're packed together in a, in a structure. And this polyhedral or angular shape, lots of little straight edges, arises because the cells deform slightly. They get pressed in a little bit as they're packed in together, kind of like a honeycomb arrangement, although they're not in neat little hexagrams. But it is that sort of view. And now again, let's go back to the idea of the bubble. If we're packing bubbles together, where the bubbles meet, the sphere doesn't continue to go around. It becomes a straight line where they're packed in. So imagine a bubble that has a bunch of other bubbles around. Now, as you're looking at it down from the top, you would say it has a polyhedral shape. So that's the overall shape of it. Now, how does it get organized? In part, how does it maintain that structure? The polyhedral adipocytes are embedded or are, are shoved within this network of collagen fibers. Now, collagen is going to be a very important part of this story as we get into lipedema. So collagen. In fact, we'll, we'll define and discuss collagen more in just a moment. But collagen fibers are wrapping around the fat cells to give them structure. And it also is supported, the adipose structure, by blood vessels that are feeding the tissue and pulling away waste. But also they're fed by lymph tissue. And that's another important part of lipedema, the lymph flow. Now, I hadn't planned on doing this, but now that I mention it, I think maybe I ought to. Briefly, what is Lymph. Lymph is the fluid that is surrounding cells. There's water and stuff or fluid outside of cells, and it's slowly getting pulled away. There's. It's always slowly getting pulled away. And it. That is what will then come into a lymph vessel. So lymph is the fluid that's coming away from tissues separate from blood flow. Now, I'd mentioned how that collagen is helping create this framework or structure around all each individual fat cell. Of course, that's a lot. I mean, you think about fat tissue, how many fat cells there are, there's collagen weaving around all of those fat cells. Where does the collagen come from? The fat cells aren't making it. The collagen is being produced from fibroblasts. So fibroblasts are a different cell type entirely. Share an origin with the fat cells. You know, there's. They. They share a common ancestor. And so within the fat tissue, we have a lot of fat cells, but we also have a fair amount of fibroblasts. And fibroblasts in adipose tissue play a crucial role in producing and organizing what's called the extracellular matrix. Now, I'm dropping on you guys a lot of words. The extracellular matrix is basically just the term for all of the framework round cells, including collagen. Collagen, indeed, is the main part of the extracellular matrix in adipose tissue. Fibroblasts contribute to the tissue's ability to expand and contract, which is, of course, essential for fat storage and mobilization. But it also, the fibroblasts also play a very critical part in healing and remodeling within the tissue. So if someone's gaining weight, you need to remodel some things. If they're losing weight, you need to remodel some things. If there has been damage, some impact, some tr. You need to remodel and recover, you need to build the structure back, you need to repair the blood vessels, et cetera. So that is all the role of the fibroblasts, this other cell type that lives within the neighborhood of the adipose tissue. Whereas the primary residents are the fat cells, adipocytes, there is the secondary. In fact, there are many, many more cell types, too. Fibroblasts is a very important one, particularly in this story of lipedema. All right, so that is all the PR with regards to fat storage and fat tissue. Some aspects you probably didn't know, but what I want you to take away from it is that fat cells are all surrounded by collagen which are being produced, which is being produced by fibroblasts, which are just resident little cells tucked within, you know, randomly throughout all of the fat cells. All right, so let's move on to it now. Now that we've laid down the groundwork for understanding how fat tissue works, let's now move into the subtopics, or lipedema. But then I want to cover lipedema by going through an order of a series of questions. First one being how is collagen affected in lipedema? So now that you understand that collagen is an essential part of the structure of fat tissue, how is it affected in lipedema? So, firstly, one thing to establish is that there's too much collagen. In fact, let me just take a step out of this for just a second and confess to you that when I first heard of lipedema, I thought that it was just a fat cell problem. You know, lipedema is this distort. This, this altered storage of fat tissue where an individual, overwhelmingly a female. Although we're going to get more into the specifics of lipedema in a moment, they're storing fat in. In a way that is really painful. It's a very uncomfortable and very hard, rigid type of fat. Whereas normally, particularly in women who have more subcutaneous fat, something we've discussed previously, but fat stored just beneath the skin, usually it's very squishy. You can pinch it and jiggle it. This is fat that is also stored beneath the skin, but it gets very rigid and hard, and it's very painful for the person. All right, but my point only in bringing all of this up. I used to consider lipedema to be a problem of fat cells. I don't anymore. Particularly doing my homework in preparation for this discussion, I've concluded that, and I don't mind if anyone disagrees with me, that lipedema is a problem of connective tissue like collagen. All right, now, so let's get back into lipedema. How is collagen affected or altered in lipedema? First and foremost, there's too much. In lipedema, there is often an overproduction of collagen by the fibroblasts. This increase can lead to excessive collagen deposition in the adipose tissue. So what should be a very thin, little malleable wall of collagen around a fat cell becomes thicker and harder. And this is something that can be evidenced with fat biopsies in people with lipedema. If they do a fat Biopsy even in the same person in an area where they have lipedema, and then do another fat biopsy in an area where they don't. So maybe they do a biops the thigh of the woman, and then they do a biopsy in her triceps or upper arm. They will in the lower limbs having lipedema, but the upper arm's not. They will detect that there's a much thicker layer of the extracellular matrix, which, as you'll recall, is primarily collagen. So it gets really, really thick. And so again, what should have been a very malleable, pliable surrounding or sac of collagen becomes this thick kind of brick wall which starts to physically press on the fatso. Now, independent of the amount, there's changes in the collagen structure. The collagen and lipedema can become more fibrotic, which just means it's kind of redundant a little bit to what I just said, which becomes thicker and more rigid. So independent of the overall amount, the nature of the collagen starts to change. And this is a known phenomenon within collagen. The human body and all animals have various types of collagen, but it essentially is now behaving like a different type of collagen, a more rigid type. Just by way of interest, subcutaneous fat normally has a type of collagen that is softer, whereas visceral fat typically has a type of collagen that is more rigid. And this almost appears as if the subcutaneous fat is taking on the characteristics of the collagen within the visceral fat, a more rigid, stronger, less pliable type of collagen, and adding to that, where it's getting thicker and thicker. And that just compounds the issue, of course, now, all of this, of course, still speaking about collagen and how it's changed in lipedema, can change the functionality of the adipose tissue. The altered collagen structure can lead to reduced tissue elasticity and increased rigidity. So the loss of elasticity, as the name suggests, just means it's not quite as bouncy, it's less elastic and less compliant. Those are kind of terms of physics. So it can't stretch out as well and it can't rebound as well. But this makes the adipose tissue ultimately, as I've said, just much more rigid, which can very much contribute to the pain and tenderness and then leading to compromised lymph drainage and fluid retention. So that's where the kind of edema part comes from. Edema is another term of biology. And it refers to too much fluid outside the cell, like accumulating in a. In a space, usually a limb. But as a result of that, there's swelling. All right, now, I've kind of segued into this a little bit already, having gotten a little bit ahead of myself in these subtopics. But let's go to another question, which is why is the collagen a problem? So I've. We've now made it clear what collagen is. We've now hopefully made it clear how collagen is misbehaving in lipedema, that there's too much of it and it's too hard. But why is that a problem? Let's go through a few reasons here. Again, answering the question, why is the collagen a problem? So here's how. Fibrosis, which is when there's more production of the. Of the collagen, can affect the function within the adipose tissue in the limbs, usually, again, usually lower limbs, but it can also happen in the upper arms. So, first of all, and I've mentioned this somewhat, but the first is increased tissue stiffness. As collagen accumulates and becomes more fibrotic or rigid and thicker, the adipose tissue becomes stiffer and less flexible. And this increased rigidity can exert some pressure on the fat cells and importantly, nearby nerves and nerves is something we're going to revisit more in a moment. But as the nerve can become. Well, we'll come back to that in a second. But we've introduced nerves for the first time. But that can, of course, lead to discomfort and pain. Remember, all pain is going to be sensed centrally in the brain by nerves. So whatever the problem is, it has to somehow be conducted the sign that there's a problem to the brain, and then the brain senses this as pain or discomfort. All right, number two, in answering the question of why is this collagen a problem? So what if we have more? But number two is impaired blood flow and lymphatic flow. Now, again, just by way of reminder, the lymph circulation system is kind of a parallel system to the blood vessels. And whereas the blood vessels are a pretty closed group, you know, what is in the blood? The fluid is generally staying in the blood, and it's just circulating. Lymph is very different where lymph is constantly just pulling any excess fluid around cells and bringing it back in, ultimately depositing it back into the bloodstream, but. But through its own vessels. But if you have compromised lymph flow, you will have lymph for 10 or water retention or lymph retention. And lymph itself is just a watery mix of. Of stuff. Mostly water, some proteins, some cells, but again, mostly water. And so if you can't lymph circulation is compromised, then you're getting the lymph or the fluid hanging out. And this is just. It happens more readily in limbs like legs especially, and arms, where gravity wants to pull all that water down, making it even harder for it to return. So anyway, back to fat tissue and lipedema. The rigidity within this collagen matrix around fat cells can compress the blood vessels and the lymph channels or the lymph vessels, which can impair circulation. The red blood flow can lead to ischemia, which is basically a. The cells start to suffocate, they are not getting enough oxygen, which itself can cause pain. But also the impaired lymph drainage can cause lymphedema, which is just a classic word for just. You have fluid in your limbs. You know your limbs are swollen and, and that will lead to swelling, of course, and inflammation, which as we'll get to in a moment when we talk more explicitly about the pain, but that will lead to pain. Inflammation can enhan sensitivity to pain signals. Now, I've mentioned the nerve compression a moment ago, and let's just revisit it that now the fibrotic and stiffened fat tissue can compress and even entrap nerves within the adipose tissue. And that nerve compression, literally a nerve coming through. It used to be a very squishy, pliable space. Now it's rigid. So if there's a movement, it can start to pinch off, but that can result in pain which can very readily become chronic and and significantly affect quality of life. Another part about why the collagen is a problem is the inflammatory responses. The altered tissue environment within this fibrotic tissue with impaired dynamics of. Of the fluid with blood or circulation in the blood system and in the lymph system, it can foster inflammatory responses. And chronic inflammation can be a source of pain, not only because some of the inflammatory mediators directly stimul stimulate pain on nerve endings, but also, as I mentioned, it enhances the sensitivity to pain signals. And so this is very much playing into how why the. The often the woman or the individual experiencing lipedema, why it hurts so much and why it does affect their quality of life so much. And then lastly, why is the collagen a problem? As you have started to wall off a cell and compromise blood flow and Lymph drainage and also just created this rigid structure. The mechanical stress exerted on the adipocyte by surrounding. By. By the surrounding rigid, toughened collagen can lead to not only cell dysfunction, but also outright death. And so it's not uncommon for there to be a much higher level of fat cell apoptosis occurring within lipedema fat tissue. All right, now, throughout this discussion, I have been mentioning women more than men. Let's talk about that for just a moment. Well, for a few moments, actually. Why do women suffer? So the next question then, as we move through the topics, is why do women suffer from lipedema so much more often than men do? There are some estimates, just by way of statistics, that lipedema affects almost a little over 10% of all women. And in men the number is unknown to the point of. Of negligible. It is so uncommon. And this is. So lipedema is nearly exclusively reported in women and can begin or worsen. And this is very important, and we're going to move on to this as the next topic. It can begin or worsen at times of substantial hormonal change. Three in particular. Puberty, pregnancy, and then lesser than those ones, Menopause. Mostly it's puberty and pregnancy. Menopause sometimes, but it's much less common there. There's also, of course, a genetic or familial component to it. I should say familial, to be clearer. The genetic component is based on sex, and then the familial component is just a natural variation that we see across individuals, which is some people tend to have things that happen within a familial line without a clear genetics to explain it. All right, now let's. Having said all this, it's easy then to conclude that there must be some difference within the sex hormones. That is a rational conclusion and indeed the likely one. Why is it that women experience lipedema so much more than men? Likely because of the vastly higher levels of estrogens. Remember, there is no individual hormone called estrogen. There are the estrogens, the prototypical female sex hormones. Now, men have estrogens, but much, much lower levels than females. All right, so let's move on. What is the relevance of estrogen in lipedema? Well, let's really get specific because I've been sort of framing this up through the lens of fibroblasts making too much bad collagen, which starts to choke off the fat cells. And the fat cells themselves are just innocent bystanders. Lipedema is not a Disorder of the fat. It is a disorder of the connective tissue. So this is interesting. Within the family of fibroblast, there is something called a myofibroblast, which is basically this. They're specialized cells that are derived from fibroblasts. So fibroblasts can turn into myofibroblasts. And the difference among a few other things is that they are much more aggressive in their production of collagen and thus really contribute to a tissue that becomes fibrotic or sometimes we would say scarred. So where there's a lot more fibrosis occurring, this, this much heavier production and thicker collagen, usually myofibroblasts are responsible for that. Well, wouldn't you know it, estrogen can influence and increase the differentiation or the activation of converting fibroblasts into myofibroblasts. And so in those who have this familial predisposition, when the young woman starts to go through puberty and she has this substantial increase in estrogens, it's no surprise that now things start to happen. Basically, then, the estrogens are stimulating this conversion of benign and content fibroblasts, producing a benign and normal amount of collagen into much more, in this case, I, I mean aggressive, but in this case more sinister myofibroblasts producing a much more aggressive, in this case sinister form of collagen and amount of collagen. And this, this conversion from happy fibroblast to aggressive myofibroblast with the change in collagen production is generally thought to be mediated through this particular pathway that estrogens activate, namely tgf beta, tissue growth factor beta. And this is a potential area of therapy then, although TGF beta is involved in a lot of processes, but there are some trials exploring the regulation of tgf beta as a therapy for lipedema. So, again, just to wrap that thought up, estrogens induce the activation or the conversion from fibroblasts into myofibroblasts. Also, just a little more on that. Estrogens. The effect on fibroblasts and myofibroblast activity can really vary depending on the tissue. But this explains some of why this can happen at all. But for example, in reproductive tissues like the uterus, estrogen's effects are very pronounced in regulating fibroblast function. It's just including, like, stimulating the growth of fibroids, which is a lot of collagen, too much extracellular matrix. So that's where the estrogens are playing its part. Well, normally, you know, stimulating fibroblast activity in a tissue like the uterus, but there is an influence in non reproductive tissues like skin and lungs. Estrogens also play a role there. But and again, in the case of the fat tissue in lipo, in lipedema, it's simply something that's gone too far. Now to complicate things even a little more and to introduce a bit why men can experience this despite having fantastically lower levels of estrogens, it is, is now a problem potentially within the fat cell itself. So we have discussed before how fat cells express an enzyme called aromatase. And aromatase is responsible for the conversion of androgens like testosterone into estrogens like the ones we've been talking about. And so in this instance where a woman, if you measure her circulating levels of estrogens, they may be normal, but if you were to look and you know, drill down or that's a kind of gruesome way of saying it, take a biopsy of her lipedema fat tissue, it could be that her fat cells have a much, much higher level of aromatase. So as androgens like testosterone are flowing through, the fat cells pull it in and release it as estrogens. But it's only having a local effect. This is something within the realm of endocrinology called a paracrine effect. So if you have, has more fat tissue that is over expressing or expressing an, an unusually high amount of aromatase, it could be that her fat tissue is making too much estrogens which don't get into general circulation but are sufficient to activate the fibroblast, which is right next door. That's where the paracrine phenomenon comes into play. So you have one fat cell making a lot of estrogens and it's releasing the estrogens and it just goes next door and stimulates the fibroblast, converting it into a myofibroblast and telling it just to continue to pump out thicker collagen, contributing ultimately of course to lipedema. So I believe that's a relevant part of this that disconnects blood estrogen levels from lipedema, but increases, but still keeps the focus on estrogens, but now right at the only at the level of the fat tissue, where the fat tissue itself is making a lot of estrogens, but it's kind of staying within the neighborhood and it's stimulating other cells within the neighborhood, namely in this case the fibroblasts. Now independent of estrogen levels, it could be a difference In. In expression of estrogen receptors. So this is another potential area. It is an area of research in lipedema and even a potential area of therapy where it's. It's thought that rather than the actual amount of estrogens, there's just too much sensitivity to it. So maybe the fibroblasts have too much of the estrogen receptors, which is a small hormone of a, sorry, a small class of receptors. So it's one thing for the hormone to come to a cell, but if the cell doesn't have a receptor for that hormone, it's. There's no door for the hormone to knock on, if you will. So the cell ignores it. In this case, however, the cell is expressing estrogen receptors. And in the case of lipedema, the fibroblasts may be expressing too much estrogen receptor, so they're too sensitive to the estrogens and reacting too strongly to the estrogens, ultimately contributing to a fibroblast that is simply too active, becoming a myofibroblast and aggressively producing a thicker collagen. All right, now to kind of wrap some of these thoughts up before we move on to the next couple subtopics before we wrap up. This helps you, I hope, understand why lipedema is sometimes referred to as an adipofacial disorder. Adipofacial, that is this combination of words for you, of course, adipose, meaning fat tissue, and then fascia. Fascia, just referring to connective tissue. So the research does suggest that fibroblasts, which are cells responsible for produc and maintaining connective tissue, particularly through the production of lipedema, through. Sorry, through the production of collagen, may play a role in the. The pathophysiology or the origins of lipedema. All right, now let's move on to the next final two topics with this next one being why does it hurt so much? Now, this is not something I. I speak about this with almost some reverence because it's just based on reports that I've heard from people with lipidemia that they will note that it is painful, whereas someone else storing an equal amount of fat without lipedema, it doesn't hurt them. It might be difficult to move around just based on the amount of fat they have, but it doesn't hurt. With lipedema, it is a painful thing. And this is generally both the mechanical and a biochemical phenomenon that there is this mechanical restriction that is. That is literally aggravating the nerves. Then there's this biochemical effect where there's Signals that are activating the nerves, which are then sending the signal to the brain that, hey, we're sensing pain right now. So there can be a couple. There's two things I wanted to mention here. The first one is just the simple physics of it, which is the pressure and the tension, the fibrosis and the excess. And the fat kind of pushing against its restraints can create a physical pressure on the tissue near in that area, including nerves that are innervating. We have nerves everywhere. Of course, the nerves are kind of caught between these two hard rocks, if you will. And the pressure can directly stimulate the nerve fibers. This would be this pressure induced stimulus. That's one of the ways to activate a nerve and that will be sensed, that will be relayed back to the brain as a pain sensation. So again, that is the tension and the pressure because it's like we are continuing to try to blow air into the bubble, but now the bubble is reaching its constraints and so it's pressing against this brick wall of collagen. And then the next point, the last one here just with regards to pain, is the inflammation. And I've alluded to this already, but lipedema is associated with chronic inflammation. This is largely coming from the fat cells themselves and other nearby cells like fibroblasts, like macrophages, which is another cell type in the fat tissue that I've not invoked at all. But inflammatory cells, inflammatory cells within the kind of constrained, tense fat tissue is released. They're releasing cytokines and other chemical mediators, one like substance P and prostacyclines. And these not only can directly stimulate the sensation of pain, but it also enhances the sensitivity to the signal. So it's one thing to say, hey, here's a pain signal. It's a pain signal that should be sensed at a five, but then there are other signals that amplify that up. And then it turns what should have been a 5 pain signal up to an 8 or 9 out of 10 then. So those are some of the main reasons again to just, I, I like to look at that as a mechanical sources of pain with the pressure and the tension and biochemical pathways activating pain through the inflammation and similar mediators. All right, now the last part of this is, what can you do about it? This is of course, where what anyone with lipidemia wants to know. I, I really hope that my paradigm has been helpful to shift the view away from a fat centric paradigm, which is not, I'm not happy doing. So I like to just talk about fat tissue or fat cells. But we don't have to leave the fat tissue to understand lipedema, but it's rather connective tissue and collagen and a different cell type entirely, namely fibroblasts. So the kind of conventional therapies are. And anyone with lipedema, you know, would be laughing at me for discussing these so readily because they know how maybe short lived the, the alleviation of pain is. But the first one is compression therapy. This is basically just a way to try to do anything you can to help help the fluid get out of the limb. As the lymph drainage and circulation becomes compromised, as the collagen becomes ever more rigid and fibrotic, if you can keep it compressed, you just make it easier for the fluid to return. So this would be the same thing like these compression socks, these sleeves down the leg that you would use with just normal edema, you know, the accumulation of fluid. Next, another intervention is manual lymphatic drainage. This is basically just massage, but of course that can be really painful. Just the physical touching of the limb can be very, very painful. So I don't state this lightly, but it is a therapy where it is this massage with an elevated limb, just trying to get the lymph to return and reduce some of the swelling in that area. And then in physical therapy just to improve mobility and to open up flow with drainage and blood flow. Vibration therapy is one that has been used before, or it's thought to. So this would be, this could be something as benign as like standing on a vibration plate. But vibration is thought to stimulate the muscle to, to contract and relax, of course. And that helps activate this, this process of helping remove fluid from a limb, particularly the legs, of course, Ultrasound therapy, particularly low intensity pulse ultrasound. Liposuction, that's a type of ultrasound therapy that uses acoustic, acoustic waves. So a vibration. And this is thought to possibly help with lipedema by softening up the tissue. What is a hard, rigid wall of collagen, this fibrotic sac around of fat cells. The ultrasound is thought to loosen it up a bit, which can, which can improve not only the physical sensation and restriction on nerves, but also improve the return flow from blood and lymph. Now this one's a little controversial. Controversial and indeed the results are conflicted. Namely liposuction. You've heard me talk about liposuction before and I generally talk about it in negative terms because if someone's doing it for vanity reasons, the fat tissue will simply just grow back on the body somewhere else in the case of lipedema. Well, you could make a stronger case that liposuction has been shown to be an effective method for reducing limb volume. Volume and alleviating pain associated with lipedema. One of the, and improving quality of life, at least temporarily. One of the concerns that I have about liposuction is that you can damage lymph vessels and lymph nodes, these kind of way stations for lymph return. And that of course would exacerbate or make worse edema. And so there's a, there's a trade off there. There are different types of, are different interventions with liposuction that are designed to spare lymph a little better than others. And so that would just be of course, a strong, strong consideration. Again, just to really make sure that you can leave the lymph structures, the lymph vessels intact. Now, what I haven't mentioned is weight loss. Of course, anyone with lipedema. I'm ready for you to roll your eyes at me because you would be so tired of hearing that. Right? But I want to of course, show my own view on that. Naturally, if there's something you can do to shrink the fat cells, you are easing up the pressure at least somewhat. But of course, weight loss is not easy and the fat cells in lipedema appear to be a little more stubborn than normal fat cells. And that could be a result of the altered blood flow. Frankly, they're just not getting as much of the signal to break down, down. So here when it comes to the dietary interventions, classically of course, everyone would just say eat less, exercise more. That's purely thermodynamics. And just cut your calories. Well, yes, calorie cutting can work. Or to say that another way. Long term starvation can work, but it's always short lived, which is why I never advocate that style. But just to show you that not all calories are created equal, I want to share with you a paper that was just published a few weeks ago as we record this in March, is that right? No, April. April of 2024, a paper was just published. The name of this, the title of it is Effect of a Low Carbohydrate Diet on Pain and Quality of Life in Female Patients with Lipedema. A randomized controlled trial, that's very important. This is the last name of the first author is Londain L U N D A N E S in the journal Obesity in 2024. So they took 70 women with confirmed lipedema. Average age was 47 years old. Average BMI 37, so high. So these were very overweight women and they put them both on low calorie diets, but one was very low carb and the other one was higher carb, lower fat. Interesting. So if all calories were equal, there should be no difference between them. Right. And that was not the case. The low carb diet had almost three times more fat loss over the eight weeks of this study, over three times greater loss. And they had an almost four times greater reduction in pain as measured through a host of surveys. And they did a bunch of quality of life surveys and in every instance the low fat version underperformed compared to the low carb diet with all of these other quality of life surveys that they did, including just overt sensation of pain. Now interestingly, they found that it was not just a consequence of the fat loss or the weight loss that the reduction in pain actually didn't perfectly track it, but it was still four times stronger. So there was some other effect due to the low, the low carb diet, which of course is going to be increasing ketones. And this is where I can speculate a little because the authors of this paper did not. But there is some work being done, sponsored by this company called American Ketone that is finding that just even exogenous ketones are helpful in women with lipedema. And I would encourage anyone to look up the work of Siobhan Huggins. She's really been pioneering this. But it could be a result of the anti inflammatory effect of ketones. Ketones are known to have an anti inflammatory signal and insofar as inflammation is not only initiating the sensation of pain, but also heightening the sensitivity to the signal. If you can block that inflammation, it stands to reason that you are mitigating pain a little better. But even still, there was three times greater fat loss here, which is pretty significant. So that's one study. Another paper was published in 2024. Sorry, 2023. This is the. The first author, last name is Jeezioric. That's quite the name. J E Z I O R E K jeziork we'll say 2023. But they found that once again a low carb diet significantly reduced body fat, fat mass and leg volume volume in women with lipedema and also also notably with a notable reduction in pain levels. So I would say this is a ray of hope here that as much as a person with lipedema has been trying diet in the past, I would strongly, based on these reports and more suggest that perhaps not all calories need to be cut that there's going to be a bigger bang for the buck, a bigger benefit when it comes to selectively reducing carbohydrates over, say, fat. All right, I hope this has been helpful. Once again, just reminding you of my own paradigm shift here. Looking at lipedema not as a fat cell problem, but as a collagen fibroblast problem and the relevance of estrogens in increasing the activity of the fibroblasts, resulting in a frenetic production and a hyperactive production of collagen, which begins to choke off not only the fat cells but also nerves, resulting in subst substantial pain, choking off the lymph vessel return, resulting in swelling which is further contributing to the pain. This mechanical and biochemical the the mechanical and biochemical contributions to this discomfort. Hopefully this has been helpful. If it has been, please share it with a friend. And if you're watching this live, thank you so much for being a member of the insulin IQ community. I look forward to switching over and answering your questions in just a moment. If you're watching this later on the YouTube channel channel thank you for tuning in. Please be sure to subscribe until next time. The more you learn, the healthier you'll be. See you then.