Auto-transcribed and lightly edited for readability; speaker labels added by LIV3. Timestamps follow the published episode. The views expressed are the speakers' own. Individual experiences described in the conversation are anecdotal, are not typical results, and have not been evaluated by the FDA.

00:00 Welcome and introduction

00:00Matty:This is episode 492. Could this conversation give you a natural alternative to Ozempic or any GLP modifier or weight loss drug? Quite possibly. And that's not just a cheesy hook to get you listening. Trust me, you'll want to listen to this whole conversation. It's fascinating. So what if the reason you're tired, inflamed, gaining weight, got diabetes, what if that has nothing to do with calories and everything to do with one enzyme that hijacks your mitochondria every time you eat fruit or sugar of any kind, or even when you're dehydrated or stressed?

00:34Matty:Today's guest is a metabolism researcher and expert that introduces us to the fructose model of disease, showing how this could be the root cause of all the big diseases, and most certainly why restrictive diets continually fail for weight loss for so many people, and why managing sugar cravings is always and perpetually so damn challenging. He's here to blow up basically everything you thought you knew about metabolism. And for me as a scientist, I definitely feel like this makes a lot of sense in pulling a lot of big ideas in the world of disease and medicine together. And I'm super excited to share it with my clients and with you today. So let's get into it.

01:16Matty:Even as a scientist and nutritionist, I was secretly trapped in binge eating and hooked on sugar. And let's be real, the so-called solutions can feel overwhelming: calorie counting, restrictive diets, weight loss pills, surgery, and even injections. I'm Matty Lansdown, and the truth is, more nutrition facts aren't the answer. It's understanding why we eat the way we do. And you don't need to be perfect to achieve great health either. That shift changed everything for me. And now I share it here as the host of the Real Weight Loss Coach podcast, where it's my mission to help one million people break free from the yo-yo diet cycle for good by bringing you the conversations that really matter in nutrition, health, and psychology. And I'm not afraid to challenge mainstream health advice when it doesn't stack up. Are you ready? Let's begin.

02:11Matty:What's up my healthy friends? Today's episode is maybe surprisingly not just another sugar-is-bad chat. In fact, we're going to go much deeper, hopefully all the way to the cellular level with a bit of a metabolic breakdown. So here with me today is Chris Mearns, and shout out to the homie Lucas Aoun at Boost Your Biology for connecting us. Chris is the founder of some incredible products, which you're going to hear a little bit about today, but it's off the back of what he's dubbed the fructose model of disease, and particularly metabolic disease, which could be the answer for millions and millions of people to getting well again. So this is absolutely worth listening to today, because it might challenge a paradigm that's been in place for a long time and be a voice of hope that you haven't heard before. So Chris, welcome to the show.

02:53Chris:Thank you so much for having me, Matty. I'm excited to be here. Looking forward to it.

03:13 Fructose is a stressor, not a fuel

02:58Matty:As I mentioned before we hit record, I've been deep in your world without you really knowing, which sounds a bit creepy. But all week I've just been diving into this, because after our first chat I jumped on and thought, who's Chris? What's he all about? And by the end of it I was like, oh my God, this is amazing. And I've been fascinated and talking about it ever since. So maybe a good place for us to start is with what some would dub the most radical claim: that fructose isn't a fuel, it's a stressor. Let's paint the picture for people of what your idea of fructose is, what it actually is, and how you're flipping things on its head a bit.

03:35Chris:Totally. So it seems like most of the research for many, many decades really kind of put fructose aside because it looked at glucose, the other side of sugar, and it basically said, okay, glucose raises insulin, it's our primary fuel system, we've got too much glycogen around, so it's a problem. This doesn't take away from any of that, but it's saying let's look closer at fructose, because maybe it's not inert. What the latest research shows is that it doesn't just result in a little bit of new fat creation, de novo lipogenesis, but it actually starts to create a scenario where that is the end result. It's like a progressive stressor where inside the cell, fructose metabolism itself causes inflammation, causes reactive oxygen species, and generates uric acid, so that the mitochondria start crushing down as if they're a rate limiter almost, where suddenly their capacity for the input of fuel and the output of energy is reduced. It seems very intentional, where suddenly you basically end up with a stressed, very tired cell, and because it's in conservation mode, the entire body starts having a reaction. It's a deep thing. It goes way past just the digestion of fructose. It's a very deep level.

05:09Matty:Yeah, it's so incredibly fascinating, because we often hear about natural food, whole real food, fruit existing in nature. And a lot of people, that then brings up like, oh, but fruit and fructose are a thing, and we encourage babies to have pureed fruit with lots of glucose and fructose in there. So it's often a challenging idea. I can imagine it would be a challenging idea for people to be like, so hang on, if fructose is in fruit and fructose is in all of these different foods, then fruit's healthy? Yeah. And fruit's healthy. So it's definitely challenging.

05:48 Why whole fruit still counts as healthy

05:48Chris:And that's a major issue, because we're talking biochemistry here. Fruit is a very complex food. It's not just glucose and fructose. It is heavy in fructose, yes, but it's packed full of polyphenols, minerals, fiber, and water, and basically all of that seems to buffer the effects of fructose. So when we're talking about fructose, we're taking literally the chemical out and talking about how that behaves in the body. And I'm not villainizing fructose, I actually think it's a powerful tool. Especially when you look back through history, in the wild, animals would use fruit. Bears before hibernation will literally binge on fruit, and in doing so they seem to be able to activate this underlying mechanism of fructose so that they can pack on weight really heavily and so that they can hibernate. Or hummingbirds: they live on sugar, they eat sugar all day, and their metabolic rate is so crazy that basically that sugar allows them to more or less induce a diabetic state by dusk, and then that allows them to survive night, where by morning they're back to zero and they go crazy on sugar again. So the point is, this is not a bad thing. This is a survival mechanism. We just are flooding our bodies with it and using it improperly.

07:41Chris:And so fruit remains healthy, because most of the time it's buffered. The fiber makes it slow down in your gut, so it doesn't really pass through the liver very quickly. And if we're eating whole fruit, there's not that much of it, realistically. If we start drying it, then we eat like 15 apricots in the course of 10 minutes, or we juice it, and suddenly we get rid of all the fiber that buffers that out. There's literally research that shows you are more likely to end up with metabolic problems if you don't eat your fruit whole.

08:19Matty:So yeah, totally. The thing that I'd love to draw out, or get you to speak in a more detailed way about, that I think really helped me understand what was going on, is: why does fructose act as a rate-limiting step, a reduction in production? Why does it reduce the energy output of the mitochondria, and what are the side effects or the consequences of that reduction?

08:49 The enzyme that rate-limits mitochondrial output

08:49Chris:Perfect. Okay, so the first step in fructose metabolism is an enzyme called fructokinase, or KHK, ketohexokinase C typically. What that does is it converts fructose into fructose-1-phosphate, and that basically starts to deplete your ATP. ATP gets degraded into ADP, into AMP, into IMP, and finally this ends up as uric acid. So we're talking within the cell here, intracellular uric acid. And what that ends up doing is it causes a little bit of stress. Effectively, it's like a waste product in the cell, so we end up with reactive oxygen species, a little bit of inflammation that appears because it's inducing that stress, and basically it blunts a little bit of that mitochondrial performance.

09:42Chris:Most of the time you might look at it and say, okay, it's the rapid depletion of ATP that's the problem, which it is, you get that sugar low in a way, you have the high very briefly with the glucose, and then you hit the crash with the fructose. That's that little drop in ATP. But it's this kind of slow drip, persistent problem with the mitochondrial stress that makes it progressive.

10:08 From one stressed cell to system-wide disease

10:08Chris:If I'm eating too much fructose, or I have too much exposure to it as a child, through my teens, through my twenties, at a certain point that little drip of a problem on my mitochondria is going to induce cellular fragility, which then scales into system fragility. A cell that is not performing well is a problem, but it's not the biggest problem, the body can compensate. But when the entire organ starts to have the same kind of low energy fragility, then it makes a lot of sense that pathology starts coming out, and we start seeing actual chronic disease emerge. Because this low energy, stressed, inflammatory, and ultimately insulin resistant cell state, it doesn't matter where in the body it is: your vascular system, your liver, your brain with endogenous fructose. It kind of becomes the common foundational state of chronic disease, from what I can see. It's the first domino to fall. And then later, when we start actually diagnosing things, we see, yeah, that must have happened long ago, but not enough people are paying attention to that fact.

14:18 The 1850s sugar tariffs and the modern food supply

14:14Matty:I don't know if you want to go here, but even looking back through history at the development of how we modified our diet, it fits in lockstep of everything that kind of changed.

14:14Chris:Yeah, I'm happy to go anywhere.

14:18Matty:By the way, we can talk about the most controversial things you ever want to speak about. I love this one because it's so weird.

14:23Chris:So no one expects us to go here. The East India Trading Company had a monopoly on sugar for ages. Essentially, in the 1850s, that kind of collapsed with some tariffs on sugar and the introduction of sugar to the world at the London World Fair in around 1851. From that moment, if you look at a chart of the world's consumption of sugar, specifically fructose, it's flat, like people couldn't afford it. Prior to that, we heard of gout, but it was in the very wealthy, the elite class that could eat anything they wanted. Then suddenly, when that changed in 1851, it absolutely spikes. As we started eating more and more sugar per year, metabolic decline followed, maybe with a 10 to 15 year lag, and then it's crazy, because from then on, and that was 175 years ago now, we started radicalizing our diet with everything we could possibly eat, because trade improved and everything else.

15:41Chris:So then we invented supermarkets, in the early 1900s, I think the Piggly Wiggly was the first one, where suddenly, instead of going to different artisans, you'd go to a little supermarket and buy everything you want. And then processed foods started getting introduced. Of course, we know high fructose corn syrup started in the late 1960s or so. And basically, it became the point where instead of sugar being for the wealthy, now it's the poor who survive on cheap, processed, sugary foods. So even looking at demographics, like minority groups seemingly being more prone to metabolic problems, because they simply don't have as much advantage, it's crazy how everything kind of just fits. Of course there are other things, and I do believe fructose is just the amplifier, but it fits where we tipped our mitochondria into a state of dysfunction by adding this extra stress. Before, maybe it was just genetic and I could deal with it, but now when I'm eating sugar every single day, it's tipping that little bit of mitochondrial stress past the limit, where all of a sudden disease emerges.

17:35 Eating for winter, and never getting there

17:09Matty:It's something I think about, a little bit of what we spoke about last time, which is this idea, and the bears are a perfect example, that they binge eat fruit, massive volumes of sugar and fructose into their system. And in the Western world we're doing this with junk food and a lot of things that are in a box or a can. And so the idea that made sense for me, the little phrase that kind of wraps it up, and you can correct me if I'm wrong, is that we rate limit the mitochondrial output because the warmer weather produces fructose-rich food. We binge eat the fructose-rich food to store excess body fat to survive a dark cold winter where food is less accessible. So it's kind of like we're all eating for winter, but nobody ever experiences winter. Is that an accurate summation?

18:06Chris:That is bang on, that is bang on. If you look at how fructose is accessed as a food source, it's typically late in summer, right before the scarcity of winter, when food is the most abundant, and you want to eat as much of that as you can, because fat is going to help you survive the winter. So it's this little bit of a fat storage aid, a conservation signal to your body that says, I want to conserve as much as possible. And if you flip that, it's not just abundance that makes this switch turn on, it's also scarcity. In winter, you don't have access to water as well, you don't have access to food as well, and so there will also be a switch that happens, because the stresses the body faces and the endogenous ways the body makes fructose kind of flip it the other way: because times are scarce, we're going to conserve so we don't waste so much. That's the other side of this picture, and that's probably where people trip up a lot, because we've only known this very briefly, that fructose is not just from sugar or from fruit.

19:25Chris:The body produces it through a pathway called the polyol pathway, where glucose is converted into sorbitol and then sorbitol is converted into fructose. What's the function of that pathway, why does that happen? Well, if you think about it, the trigger is a high blood glucose level. If your mitochondria can't access that stuff because they're maxed out, then the body is likely to try to store that for later, so it gets converted into fat. But it also makes sense that it would signal the body to say, we're in conservation mode, we've got more than we need, so let's rate limit that mitochondrial signal again, so we can push more and more of that abundance into fat for later. So basically, the process is the same, because the glucose gets shuttled into fructose, and then it gets metabolized so that the mitochondria get down regulated again.

20:44 The leptin and ghrelin loop behind cravings

20:39Matty:So I've got a question off the back of that. The polyol pathway you're just describing, is that mechanism, is that pathway triggered as a result of leptin signaling?

20:44Chris:I'm not sure, to be honest with you. I don't recall reading that there's a connection there. But if we're talking about cravings and stuff like that, I think the part I didn't mention is that if you have a low energy cell, then it makes sense that the body will signal that there's a starvation problem, because it's basically running on fumes. There is documentation that says leptin and ghrelin are influenced by that state, where basically we eat that sugar, we down regulate our cellular energy, and then it triggers cravings, so that we go and eat more fructose, and the whole thing becomes a loop.

21:41Chris:There is very much a reason so many of the foods we like to eat trace back to this, because it's almost like that was the purpose: of course, biologically, we will want to eat the foods that give us the best chance of survival, and that's where our taste develops. Sweet is of course fructose, but also carbs, so high glycemic carbs, and salty foods, because the high osmolality, basically the saltiness of our blood, is a signal to activate the polyol pathway to generate more fructose. Umami foods are high in uric acid, so they kind of bypass that whole process and feed the entire system by causing that cellular stress with high uric acid directly.

22:47Chris:And then alcohol as well. When we take a piece of fruit that's unripe, it's really high in fiber, it has very little fructose at that point, it's dull in color, it's not attractive, and we can hardly digest it. But as it ripens, all those signals fall off, because the plant wants to distribute its seeds and wants you, the animal, to eat it, so it brightens the colors, makes it sweeter, and reduces those protective fibers. If you take that to the extreme end, you end up with fermentation, and you end up with ethanol, and then it makes sense why alcohol would also stimulate the same pathway: if you drink alcohol, you're going to simulate the same pathway as eating that half-rotten fruit. Just yesterday there was a paper published that properly mapped out that alcohol causes endogenous production of fructose, mechanistically, primarily because of osmolality: it causes dehydration, and because of that, your body is stimulated to create fructose. So all of these different things, everything we like to eat, everything that feels like a cheat, maps back to fructose.

24:31Matty:It really is crazy. But we mentioned before, like the first domino to fall being that rate-limiting step in the mitochondria as a result of fructose signaling. My next question is whether it's the second domino or third: you mentioned insulin resistance. Often when people are talking about obesity, weight gain, blood sugar issues, they start with blood sugar, and then even some people with plenty of body fat discover they've actually got stable blood sugar but insulin dysregulation and resistance. So which domino is the insulin resistance, and how does that play a part in this story?

25:14Chris:That's a great question. We all know that inflammation is good until it becomes a problem, and reactive oxygen is only temporarily a problem. A lot of this stuff starts as an adaptation, then becomes maladaptive because we left it on too long, and I believe insulin resistance is the same thing. If your cells are resisting the delivery of fuel, then why? It makes sense if you think of the mitochondria as the bottleneck: it literally can't process it. If I delivered glucose successfully to that cell, it would create too much substrate and cause more oxidative stress, so it makes sense that it slams the door shut and says, I can't use any more fuel, and starts pushing back a little.

26:19Matty:Yeah, that makes sense to me. I feel like it also begins to explain overeating.

26:24Chris:Yes, exactly. If the mitochondria is a bottleneck, we've got too much fuel piling up on one side and only a drip of energy coming out, then that emergency signal just keeps telling you to fuel up as much as you can because we're starving. As long as that is pinched, that signal keeps happening, so we end up overfeeding, and we can overfeed because we've influenced our satiety with leptin, and it becomes that self-reinforcing problem.

27:08Matty:Yeah, a little phrase is coming to mind: we're overfed but undernourished.

27:14Chris:Yes. And that's the paradox at the heart of this: why am I chronically fatigued and yet always hungry and overweight? If food is fuel, then what is going on, there's something wrong. It makes sense on the very smallest level that the engine itself should be the problem. I've used this metaphor of a car before: we blame too much glucose, and in a car that would be akin to saying my fuel tank is too full, which sounds crazy, that shouldn't really be the problem. Or we blame insulin resistance, saying the gas pedal isn't working because I'm signaling that I want to put fuel into my engine and it's resisting it, so there's something wrong with my gas pedal. But really, even if we know nothing about cars, the logical thing is that there's something wrong with the engine if it's not performing well. And that's what the mitochondria's role is: they are our little tiny engines.

28:18Matty:I'm curious, and this might be a side tangent, but how does that map onto the conversation around diabetes? Because we mentioned insulin. If we look at people that are just given more insulin to cope with the volume of sugar they're putting in, my sense is that those interventions could essentially backfire, and I say that from experience, because I work with heaps of people who use insulin and haven't solved their problems yet.

28:53Chris:Yeah, and I think that's really the thing: unless you solve the engine problem, you're kind of band-aiding it. I think GLP-1s, not to change the subject, but I think GLP-1s are fantastic, they're amazing progress. But I'm honestly not surprised at all by all the off-label stuff happening, because from this model, it's like saying, okay, I have too much weight, I need to lose weight, so I'm going to decouple that fuel tank that my little tiny eco car is trying to drag around. It's cutting, it's like forced starvation almost, because it's influencing your satiety to the point where you just can't eat anymore. Which is great, it's taking the load off. But is it solving the real problem under the hood? No. And that's really what we're seeing: people go off it, and they still see those metabolic problems, and they don't feel great. It's not like it makes you feel amazing for the rest of your life, most of the time. But that said, I am super excited, because it is helping millions and millions of people.

30:13 Fructans, FODMAPs, and the gluten intolerance mix-up

30:13Chris:You know, what's interesting about this is that one of the fructokinase inhibitors we were looking at, to help this whole process, I've only recently realized. I thought I was always focused on the liver and downstream after digestion. But it turns out there's been some confusion when it comes to gluten intolerance: apparently 80% of people who think they're gluten intolerant are not, and what's actually happening is FODMAPs, fermentation in the gut that the body can't handle. So then what are FODMAPs? Most of them, when it comes to wheat, are fructans, little chains of fructose. As the gut breaks those down, it's metabolized within your gut lining, and it causes the same mitochondrial stress, so your gut lining gets more fragile, and it can't handle the pressure of all those fermented foods starting to ferment in your gut. And what's really interesting, I just learned yesterday, is that this also influences the body's ability to secrete GLP-1 in your gut, so your own natural GLP-1 is blunted by the fact that we're eating too much of these stresses in our gut. It all connects.

31:53Matty:Yeah, it really does. And it also, as you described, I think for the, you know, there are also people who take GLP-1s and don't see a result, many people who don't feel great like you described, and I think that leans into a little bit of that conversation of overfed and undernourished, because if it's forced starvation, and your mitochondria isn't supplying the energy the system needs, and now you're putting yourself in a state of starvation without fixing the energy, the rate-limiting step of the mitochondria, then now you're just even further undernourished.

32:32 Why hardline sugar restriction backfires for most people

32:32Chris:Totally. I'm on some communities online, and it's interesting, there's a community that goes hardline sugar, saying, I'm not going to eat it, they completely cut it out of their diet, and half of them can't make it three days. What happens there, if you think of it, is that sugar is both fuel and fuel regulator. So if, in an effort to get rid of that fuel-blunting mitochondrial problem, we get rid of the fuel, then suddenly we're increasing the starvation problem in the short term before we get the chance to recover from it. Those mitochondria can't improve fast enough with that lack of glucose. So when people say, okay, I'm going to cut sugar out, but then they add more complex carbohydrates, it gets much easier. When they add a little bit of MCT oil to deliver ketones to those starving cells, that helps as a break-glass thing, where it's like, okay, I'm okay, now I can handle this. So restriction is a really hard way to handle this problem. It's an important thing, but it's not a world-changing solution, because if alcohol, high glycemic carbs, savory umami foods, and salty foods are all the problem, and everything we like to eat maps to this, then what does a restrictive diet even look like? It's messy.

34:10Chris:And not only that, but hypoxia, dehydration, and high cortisol, stresses on the body, also trigger the body to create fructose. So if someone becomes obese, they may have chronic dehydration, because their glycogen stores are pulling water out of the body, and as that weight starts crushing on their chest, they don't sleep as well, they start getting sleep apnea, and that is now hypoxia. So even if you don't change anything about diet, you become a self-reinforcing kind of problem, where your body's always making fructose and making the problem worse.

37:08Matty:Yeah, I mean, for anybody that listens to this show, they've either been trying to lose weight for a very long time, or at least know several people that have got weight challenges. And the restriction model, I've been revolting against the restriction model of dieting for a long time, because I'm yet to meet many people, less than 1%, probably a random statistic, who can actually do white-knuckle willpower forever, for the rest of ever, because it's essentially like working, and you're heroes, good for you, but the rest of us wish we could be like them. I've been revolting against that for a long time, because either our psychology is manipulated by advertising and marketing, or we're simply in a high sugar state. And I guess the reason I bring that up is because I'm curious, with those other factors, the dehydration, the salt, the stress on the nervous system, what do you feel is the reason for the fructose production? If we're reducing the energy of the mitochondria due to those high stress states, shouldn't we actually need more energy to recover from that stress state?

38:14Chris:From the perspective of it being a fuel management system, maybe not. For example, with dehydration, that's a signal that, if we go into the wild, there isn't enough water. If glycogen stores three grams of water for every gram of glucose, it makes sense that we'd want to try to up regulate as much of that water weight as possible, give the body the ability to store more fat and more glycogen, both of which hold water, so we can survive that little bit of dehydration. And in hypoxia, if you look at it from the perspective of a high altitude environment, or under the ground, naked mole rats are an interesting topic here, because they live under the ground, and because they have low access to oxygen, they trigger fructose endogenously, and that enables their cells to continue working without relying on too much oxygen. If you look closely enough, they all map to a survival mechanism at the root.

39:44 Nitric oxide, blood pressure, and the survival logic

39:25Chris:It even makes sense why hypertension fits into that. If by osmolality you've got salty blood, and I didn't even talk about this, but nitric oxide is also crippled within the cell during that whole process. When fructose is metabolized and uric acid is the end product, nitric oxide is also downregulated, and that's important for endothelial cells to remain flexible. So when that comes down, it makes sense why, if your blood is thick, you'd want to tighten those walls up so that you can maintain blood flow. Again, adaptive short term, but maladaptive long term.

40:04Matty:And this is so fantastic. I'm loving how, even being in the weight loss world, or the gut health world, or the natural health world for a long time, most of my adult life basically, I'm having these moments, a couple of times we've talked, listening to you, just being like, it all makes sense. Oh my God.

40:43Chris:I know, right? And that's the thing, it feels like, and that's what I love about this, it doesn't change anything we already know. We need to get exercise, we need to get sleep, we should be eating whole foods, we should be reducing our sugar, we shouldn't drink too much, pick any one of the strategies we've been experimenting with for decades, they all map onto this. But all this does is it zooms out, and it says that a lot of what's happening here is that they're all mapping to fructose, fructose is stressing your cell, basically working as the dial on your metabolism. So if you turn your metabolism way down, of course you're going to start gaining weight, of course you're going to start eating more, because you're not getting as much of that fuel that you need, your body is performing in a slow state, and if you continue on that road, disease is going to start emerging out of it. It maps out.

41:44 A question about genetics, tropical climates, and fructose tolerance

41:36Matty:Before we dive into talking about luteolin and the work you've done to help people solve this problem, I have a question that actually comes from my partner Yali. When I first met Yali, she'd been a vegetarian for a long time, she ate a lot of fruit. She asked, so she's of Sri Lankan origin, what about people from tropical islands, or tropical locations, where winter doesn't come, where winter actually doesn't happen? If we go along this idea that we're all eating for winter, but winter doesn't come because we manufactured our lives that way, what about those people? She's also got fantastic genetics, she can eat anything and remain tall and stick thin. So is there a genetic difference in people who are more closely aligned to the center of the globe, whether it be the Caribbean or Sri Lanka? She loves fruit, craves it, and even though whole real food fruit isn't tons of fructose, she can eat all sorts of terrible food and still nothing changes for her.

43:08Chris:That's a really good question, and I don't think there's been any research done on demographics there to see if we've got differences. This is pretty early, really. We think, why do these different blue zones have higher longevity? It sort of makes sense that some of these places eat local, locavore, whatever grows, and have less access to processed food, so that kind of maps out. But the interesting part is that I've noticed certain demographics that seem to remain very thin but also start showing signs of metabolic dysfunction, and I worry about that. It's like the skinny-fat phenomenon: super thin still, but no strong muscle tone, and actually a fatty liver, with problems there. I believe this model explains that too, though I'm not suggesting that's what's happening with Yali specifically.

44:20Chris:If your mitochondria are crushed, you're probably sending a signal of starvation, but what happens if you don't listen to that, if you remain caloric restricted even though you're getting this self-reinforcing thing? If your diet is restricted in calories but still not of a really excellent origin, you're still going to end up with that kind of weak mitochondrial cell. You may still end up with lipogenesis happening from the fructose, but it may be localized, just in the liver where this starts cascading, rather than in subcutaneous fat. So the visceral fat might still be there, but not the rest. Some of the research shows this quite specifically: fructose itself drives all of the signals of metabolic syndrome, with or without obesity. It explains why obesity develops if you allow it to, but it doesn't necessarily require it.

45:41Chris:In a way, the Lansdowne men, including myself, we don't really gain body fat, and over the years people have said, oh, lucky you. But in a way it's not good, because we have no signs of deterioration until something horrific, or at least if the body responded to the terrible diet I'd think, I should make some changes. Instead, we get way too far down the garden path. My grandfather, my uncle, and my dad have all had experiences with that. I'm fortunate that I got into this world at a much younger age. But the skinny-fat thing is maybe a bit of a curse sometimes too.

46:22Matty:Yeah, because you don't know what's happening.

46:25Chris:For sure, no indicators.

46:25Matty:So how do we fix this? Talk about luteolin, talk about what you've been doing, the background behind that, and how you came to create what you've created.

46:36 Finding luteolin: a natural fructokinase inhibitor

46:36Chris:Sure. This was all kind of simmering in the background. I did a bunch of research a few years ago, and it was like, wow, that's really interesting, I have no idea what to do about this. I could take a few things to try to stimulate my mitochondria, try to reduce my intake of fructose, but it felt like a losing battle, it was challenging. Vitamin C is fantastic, I was taking EGCG for a while to see if I could stimulate mitochondrial function a little bit. But I knew there was an enzyme that was the control mechanism, I just didn't know if anything could touch it. Until a few years later, I came across some research showing that there are polyphenols that actually work to inhibit fructose kinase. What that means is that wherever that fructose is coming from, whether from food or endogenously produced, if you don't have fructose kinase, you cannot create that cascade that ends up in uric acid and mitochondrial stress. It's this great little linchpin that sits exactly where you want it to.

47:53Chris:What's really amazing is that there's also a natural experiment where humans are born without that enzyme, and they live very happy, healthy lives and do not develop metabolic syndrome. They have no idea they have this genetic mutation until it shows up on a test. So it kind of proves that this is a targetable mechanism, and if we down-regulate it somehow, we protect ourselves from the effects of fructose so that our cells can start naturally rebuilding themselves, as they always will. All the rebuilding things we do, taking supplement after supplement trying to add to a system because there's a deficiency, we're never getting rid of the source of the issue if fructose really is the big elephant in the room. So all that rebuilding work is going to work so much better once you've cut out the fructose. That's where this got really amazing, because we identified that there are polyphenols that start to influence fructose kinase.

49:19Matty:Yeah, that's so incredible. I'm curious, when you say influence the fructose kinase, whether the fructose is going into the system from food or being endogenously produced, what's the downstream impact of stopping it or blocking it? Because I always think drugs have side effects, supplements have effects in other directions, and because it's currently operating as a survival function, based on what we've talked about, people might hear that and think, if we're removing a survival function, is that a risk, isn't that a bad thing?

49:38 The Pfizer trial that worked "too well"

49:55Chris:Yeah, exactly, good question. So Pfizer, around 2019, I believe they ran a trial on a fructose kinase inhibitor, and it had great results, everyone dropped in the range of about 22% liver fat. It moved the needle, and I couldn't figure out why they didn't bring it to phase three for a long time, it looked great, and they made it sound like a business decision. But more recently I discovered it worked too well: it started limiting a different enzyme, I forget the name off the top of my head, and effectively broke the backup system for how the body gets rid of fructose. They hit it too hard, and glycogen started becoming almost a runaway, where they started adding too much glycogen into the body. They said it was safe, but looking closer, it probably wasn't as effective as they were hoping.

51:08Chris:As far as I can tell, luteolin has no evidence of that. It blocks fructose kinase, but your body uses these other sub-systems to just clear out the waste, and that's why that benign genetic condition is called essential fructosuria: they were peeing out fructose, they had fructose in their urine, and that's how it was identified. It's a positive signal that your body can get rid of it even when you don't have this enzyme, and all the problems are taken away upstream.

51:48Matty:Yeah, I mean, a drug or compound that works too well for a company like Pfizer probably is a business decision, who knows. But my random theories aside, the other thing I'm wondering is, this luteolin you're talking about, it's not a drug, where does it come from, where do we find it, what's it in?

52:10 Where luteolin comes from, and its bioavailability problem

52:18Chris:It's in so many of the foods we eat, just in small doses. It's in thyme, parsley, celery leaves, wild artichokes, and others I can't remember. It's not in high doses, just a tiny trace amount. And what's interesting is the body doesn't get it through to your cells very easily either, it has a low bioavailability. So even though there are thousands of studies on it in medical journals, it's something most consumers have never heard of, and it's sad, I'd love to see that change, because it sounds like a really cool strategy for targeting the effects of fructose.

53:03 Liposomes and the bioavailability jump behind SugarShield

53:03Chris:So liposomes change this. Liposomes are when you add a little tiny pocket of fat around the molecule so it can survive the digestive system and make it to your bloodstream, to your cells. They found that raw luteolin is in the range of about 7% bioavailable, even when paired with things like rutin, which binds to it and slows how your digestive system handles it, but doesn't actually change the bioavailability in your cell, it just stretches out its effect. But when you add liposomes, you can hit as high as 80%, so suddenly you have a very strong influence on what's happening inside your cell.

54:01Matty:Yeah, amazing. The liposome technology has transformed the supplement industry in many ways.

54:09Chris:Yeah, it's exciting.

54:24 SugarShield: what people notice, and how to use it

54:10Matty:And I guess the question, people are obviously listening to this conversation and thinking, oh my God, I need to get my hands on this kind of stuff, and I've got one here to show people on camera as well, which you've sent over. Where can people find them?

54:24Chris:Our company is LIV3 Health, so liv3health.com. This is our only product right now, because we kind of think everything maps to this. We're trying to make it as effective and easy as possible to make a part of your life. Given the half-life, it's something you probably want to take with meals, because that's going to be the biggest trigger of fructose, along with hypoxia and sleeping. If you can interrupt that fructose signal, you can begin to recover.

55:02Chris:What we're seeing anecdotally is that sometimes people say they feel great after a couple of days, but most people, in the range of about three weeks or so, start to notice their cravings drop significantly, where that food noise starts to disappear. Around that same time, they start feeling much more energy, and those effects cascade over the next number of months. It's really interesting because these reports mirror what people describe when they successfully cut sugar out of their life through hardline restriction: the inflammation reportedly goes down, the skin gets less blotchy, the puffiness around the middle goes, all of it's similar. So it's a sign that it seems to be pulling on the same lever.

56:36Matty:Yeah, absolutely. I'm curious as well, do you think it's a temporary solution, or is it something that needs to be taken every day forever?

56:48Chris:That's a good question. Someone like Dr. Lustig will suggest that we need to do all these regulations to change our food system, that we have too much sugar and need to litigate and get rid of it. I don't think that's ever going to happen. I think we're stuck with the food system we have, because we wanted it, we have sweet foods because we could make them and eat them. Biology is driving all of this, there's no cabal of evil people trying to fill us full of sugar, it's more likely our grandma who just wants to bake us a cake because she loves us. I don't think our food system is going to change that radically. But if we can turn off the food noise, maybe we'll just be less inclined toward it.

57:51Chris:After a few months, my taste changed, fruit is phenomenal, it tastes like you'd hope it would. A lot of the time, if I go and eat something like cake, the sweet gets too sweet. There's a subtle shift where you're not as interested in sugar as you once were, it's not even just an agency thing where you choose not to have it, it just doesn't have the appeal. Just to answer your question, I do think it's probably something we're stuck with, because our food system is something we're stuck with. But my personal opinion is that a lot of the cascading problems we see may stop being so much of a problem. If chronic disease emerges out of this poorly functioning cell, then theoretically, if you restore the function of that cell and treat the disease with all the tools we already have, maybe that treatment can end, because you've restored the original function. For that reason, maybe a GLP-1 is something you can stop taking once your cells are working again. My own father-in-law stopped taking Ozempic recently because he's still losing weight, it's crazy.

59:27Chris:I think it's exciting to hypothesize where this could go. I don't think this is something we'll want to stop taking, but I'm hoping some of the more major treatments are things we will eventually see that we don't need anymore.

59:43Matty:Fantastic. I'll put a link down in the show notes below for people to get their hands on this. I too am about to dive into experimenting with this. By the time this episode is live, I might be way skinnier. Not that I need to lose much weight.

60:01Chris:You don't need it. Hopefully you feel good.

60:01Matty:Yes, exactly, that's the bit I'm interested in for myself really. Yali will probably run an experiment too. It's just that mitochondrial function returning, I'm excited about that, because I think I've heard you talk about it before, people feel like they've got another gear they could switch into but just can't get there, and I totally relate to that. Although we do have a baby in the house, and that's significantly hampering my sleep.

60:31 Real talk: a quickfire round with Chris

60:31Matty:Okay, so before we wrap up, I would love to do our little real talk segment with you, if you're up for that, I've got a handful of questions, we're going to go back and forth quite quickly and see what happens.

60:38Chris:Sure, amazing.

60:38Matty:All right, question one: what's something you believed 10 years ago that now makes you laugh?

60:51Chris:I think the Atkins diet was something I thought was ridiculous 10 years ago, because I remember an old grandma I know who was only eating steak, eggs, and butter and everything else, and I thought, oh my goodness, she's going to have a heart attack. And now, understanding the role of proteins and carbs, and seeing how the carnivore diet can help people, though I'm not suggesting that for everybody, I get it now. It's crazy how, as we dig deeper into this and understand the real functions, the veil lifts a lot.

61:32Matty:Next one, what's one habit you'd be embarrassed to admit you still have?

61:37Chris:That I still eat sugar, probably. Knowing that fructose is quite possibly the amplifier of all chronic disease, I am not afraid of it anymore, I feel good, and I know I've experimented enough to know my body is actually controlling it. I don't fear it anymore, I moderate it naturally, and it's a great place to be, my diet is fairly even, I feel good.

62:16Matty:What's one supplement habit or wellness trend that you think is overhyped?

62:23Chris:This might sound funny, but I think all of them, and I'll explain. Now that I've zoomed out and see the map, every one of them is important, but they pull a tiny lever. You keep pulling all those levers, you'll be at it for a hundred years trying to hit every little thing, whether it's every little source of fructose, or good sleep, or exercise, all of those things are important, and the supplements do add to a system. But nothing comes close to relieving the source of the problem. I like this metaphor: why do you spend all this time mopping your floor when you don't take off your muddy boots every time you come in the door? We have to get rid of the source of the stress, and then all that other stuff becomes much more interesting and valuable.

62:55Matty:What's a rabbit hole topic that you think more people should explore?

63:24Chris:Oh, fructose metabolism, straight up. We could have talked for 10 hours here, because this maps to Alzheimer's disease with endogenous fructose in the brain, there's a complete pathology of why it would develop and how. In mice, they've mapped it out where fructose will induce Alzheimer's by 18 weeks. Or it's cancer with the Warburg effect, because our cells can't handle proper energy metabolism, and by repairing that energy metabolism, which is the only target for metastatic cancer, it will theoretically apply there too. Every single different kind of health thing tracks back to this, and it's such a cool rabbit hole to dig into, especially when you realize you don't have to be afraid of it, it's actually there with purpose, we just have to understand it.

64:28Matty:Yeah, I can relate to that, and I'm only one week in. All right, the next one is, in 20 years from now, what do you want to be known for?

64:40Chris:I'm just happy to be part of this conversation, but I would love to shine a light on this map, because I feel like it's a very exciting map of all of metabolic health. It reframes everything, and it doesn't invalidate anything in the process, it just validates those theories, whether it's caloric, insulin, whatever it may happen to be, and shows where they fail, where they worked to a point and then didn't get any further. So I'd love to be part of shining a light on the map.

65:14Matty:And finally, if everything you've ever said was deleted, what's one sentence you'd want to leave people with?

65:29Chris:Fructose metabolism is very likely the amplifier of chronic disease that has tipped us into the metabolic epidemic, and we need to change our perspective there and dig much deeper into it and do way more research on it, so that we can either invalidate this whole thesis or solve metabolic health.

66:04 Closing thoughts and where to learn more

66:04Matty:Mic drop. Boom. Thanks for being here, Chris, that was awesome, man.

66:09Chris:Thank you, thank you. I'm excited to get this episode out to people.

66:14Matty:I think people's brains are going to melt, and they're going to be very excited to try SugarShield, and I think you're doing great work. Let's do 10 hours worth of podcasting over 10 episodes though.

66:28Chris:Yeah, I'm happy to come back if it's helpful, I love this stuff. It's funny, I've been nerding out for like four years on this stuff, and every day, like last night I was up at three in the morning with a little moment of restlessness, and I picked up my phone and there was a new study about alcohol, and I was like, oh my goodness, now I'm up all night. That's the crazy thing, day after day there are confirmation signals that come through, even when they don't know it, everything maps to this so seamlessly, it's just exciting to be part of it.

67:06Matty:So amazing, thanks for being on the show, we'll catch up really soon.

67:11Chris:Yeah, for sure, thank you so much, it was great.

67:20Matty:So welcome. Hey, thanks for listening to the show. If you enjoyed this episode or learnt anything at all, the gift of your five star rating would be incredibly helpful. And what's even more powerful is if you write a review, you can do it below each episode on Spotify every time an episode comes out, and inside Apple Podcasts, simply find the main page of the show with all the episodes on it, scroll to the bottom, hit write a review, share your amazing feedback and then hit send. It helps this show grow tremendously and allows me to successfully invite bigger and more famous guests each time we do the show. Thank you for helping us climb the charts, climb the algorithm, and help more people.

67:52 Disclaimer

67:52Matty:Oh, and by the way, I have a short disclaimer as well. I just wanted to quickly remind you that the information provided on this podcast is for general informational purposes only. While we strive to bring you accurate and up to date content, it's important to note that a lot of this is mixed with opinions, stories, and ideas not supported by mainstream science or medicine. Any advice or suggestions should not be considered a substitute for professional medical advice, diagnosis, or treatment. Always consult a healthcare provider before making any decisions about the health and wellness of you and your family. Remember too that what works for one person may not work for another, and each person is responsible for their own health decisions. Thank you for tuning in to The Real Weight Loss Coach podcast.