Auto-transcribed and lightly edited for readability; speaker labels added by LIV3. Timestamps follow the Acast player above. 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.

01:10 Welcome and introductions

01:10Lucas:Hello, ladies and gentlemen, and welcome back to the Boost Your Biology podcast. My name is Lucas Aoun. I'm the host of this podcast and I'm super excited because we have a very special guest joining me in the studio. And specifically today, we're going to be covering all things metabolic health and we're actually going to be covering one of my favorite compounds, which is a very interesting molecule called Luteolin and beyond. So joining me on the podcast today, we have Christopher Mearns. Chris, welcome to the podcast.

01:46Chris:Thanks so much. Looking forward to it.

01:48Lucas:Awesome, Chris. So we connected a few months back. I mean, you presented to me a very interesting perspective on human metabolism and chronic disease. So let's get the ball rolling. I mean, is there a common root of metabolic illness?

02:07 Is there a common root of metabolic illness?

02:13Chris:That's it. Yeah, that's a big question. So really, what I'm hoping to do with this podcast is introduce basically a unifying model of metabolism. And it's a new idea. And really, it shows why all the other models, they totally do make sense, but they all connect through fructose. So we'll get into that. So like, is there a common root of metabolic illness? I do believe so. And I think you probably are well aware a lot of people are talking about insulin resistance and stuff like that. And I do think that is part of it. But I don't believe that's the actual root. So if you look at metabolic illness, there is there's a common signature that occurs.

02:59Chris:Basically, insulin resistance is one of the warning lights, but there are others. Mitochondrial dysfunction happens. Oxidative stress occurs. There's an elevation, uric acid. There becomes an imbalance in lipids. We start even having effects like brain fog, stuff like that. And those things are common across so many metabolic illnesses. So it's almost like there is something happening underneath. And that's why I kind of like I like using an analogy here where we're thinking about like a car. Because we've had all these ideas of metabolic health and illness and dysfunction, stuff like that. And they explain part of the story, but not the whole thing.

03:44Chris:For example, like the calories in, calories out model that kind of argues that there's a problem with our fuel system. So you think about it as the car. It's like, OK, is the problem that I'm pulling a fuel tank as a little car? Possibly, but that doesn't really sound like it sounds like an easy fix rather than like a root problem. Or like you might say, OK, is the problem hormonal? Is it is it insulin resistance? That's more of a signaling issue. So it's like it's like saying I'm hitting the gas on my car and nothing's happening and blaming the gas pedal. That's almost doesn't sound that doesn't really sound logical either as like a root cause.

04:29Chris:It's like, OK, that's that's probably significant in what you should be looking at. But is it the root cause? So really, the question that becomes from that perspective, if in a car your performance is failing, which is what's happening in our bodies, we don't blame the fuel tank. We don't blame the gas pedal. But we did. We popped the hood. Right. And so that's really what this is about. So what do you think? Do you think that there could be a common like cause of metabolic illness?

05:03Lucas:I mean, the more the more that I study at Chris, the more I'm realizing there's multiple factors at play. When it comes to like some of the chronic issues that people face, high blood pressure, high blood sugar, high cholesterol. I've always been under the impression that it's an energy imbalance issue. And what's driving that energy imbalance could be a lack of energy output and or too much energy input through excess calories. But what you're saying is there's something

05:37Chris:I think you've totally nailed it. So like it's an interesting thing because all of us, regardless of our background, you'd be a biohacker or whatever. We have this like innate thought that like my metabolism is can be influenced and I can speed it up because I feel like it's slowing down. And so it's like, where does that come from? Like we have this like concept, even though no one's really telling us that. And so this does follow that because you're right. It's like if we're not again with the car analogy, if you're not getting enough output performance from your car, then you feel like there's something crippling it like something's going wrong.

06:22Chris:And so and so like from the insulin resistance perspective, I actually believe that's in an adaptation that's gone wrong. And there is some science behind that as well. There's been some thoughts behind it for a long time. And that kind of follows what our bodies do almost across the board, where it's like initially the reaction that our bodies giving is trying to help us. But you leave that on too long and something starts to become problematic. I think insulin resistance is just another example of that. For example, like we might ask the question of like, what is insulin resistance trying to protect you of? And again, with the car analogy, if insulin is delivering fuel to our cells, then it's like it's trying to stop delivering fuel to your cells.

07:14Chris:What would happen if it did? And in a car, if you deliver too much fuel to your engine, the engine will flood. Again, now, if you deliver too much glucose to a cell that can't process it, then you're actually going to elevate your oxidative stress. It's like flooding your engine. It's like you can't use all of that. So it's actually trying to protect your cells from additional stress. And then again, you have to look deeper. It's like, OK, if that's true, then what's happening inside my cells? Why can't process as much glucose as I need to? Why can't I? I'm not producing enough energy, enough ATP. Well, the question that I often get asked, and I'm sure you do as well, is around the different forms of carbohydrates that exist in our diet.

07:48 Is fructose bad for me?

08:04Chris:And obviously, there's, you know, your simple sugars, your complex carbohydrates. But there's one that there's a lot of mystery around and I still get asked today, is fructose bad for me? So did you want to sort of elaborate on that? Sure, absolutely. So, yeah, too. Fructose is an interesting sugar because it's been right there in front of us forever and we haven't really paid attention to it. Like most people, they hear fructose and they think high fructose corn syrup. Or they might think about fruit, which is another topic. Maybe we'll get to that later. But fructose is still so high fructose corn syrup is like maybe 55 percent of sugar in or sorry, of high fructose corn syrup.

08:50Chris:So it's like it's a liquid form of it, which is a little bit more bioavailable, but it's really only 50, 55 percent. Maybe around there. Whereas sucrose, just your regular old table sugar is still 50 percent fructose. So people are still. I think a lot of people forget that. Like forget that.

09:10Lucas:Yeah. You said sucrose is partially fructose. So you're saying half. Half fructose, regular table sugar is half fructose is what you say.

09:20Chris:Exactly. Which is and you're right. It's like we forget that or we don't we don't really we're not really aware of it. And that's that's where we're getting a significant load. And it's funny that we have so much attention on glucose, the other half, because I mean, we all know glucose is super important. Like our bodies run on it. It is our it is our primary fuel system. And so, again, the car analogy, we're blaming the fuel as the problem with our car, which sounds nuts. We go to the we go to the gas station all the time. We eat food all the time really to get fuel. There's other things involved, but it's productive. But yes, we need we need fuel.

10:10Chris:So then what is this other half that's doing like is it doing anything? And that's where the science has gotten super interesting in the last couple of years, because fructose has a very profound influence. A not on it's not it's not fuel in the same way. It doesn't it does raise insulin, but not that much like it's not. And I think that's probably why we've ignored it. It's like, OK, this like this sort of inert half of sugar. But the way it works is super interesting. So basically, what it does is it regulates how glucose is used by your cells. So really quickly, it is it is it is basically metabolized by a particular enzyme that consumes ATP and rapidly degrades ATP.

11:01Chris:So you're available energy in your cell and that converts it eventually into uric acid. And uric acid in your cell then causes stress, which reduces the performance of your mitochondria. Mitochondria are what make energy. It's like the kind of like the engine itself. Almost it converts the fuel into the energy. So then those now stressed don't create as much ATP. So then you end up with a very slow cell. So you've basically reduced the capacity of your engine to a significant degree. And that's really why I think the implications are so important here, because basically. When we have that system starting to fail on a very small level, when you're when your cells don't have enough energy, then that becomes a problem.

11:56Chris:They become fragile. They don't work as well. And so like on a very small scale, like a micro scale, like a single cell, that's that's that's a problematic thing. Basically, you have a cell that has trouble signaling hormones. You have a cell that becomes stressed and inflammatory. You have a cell that is low energy and not really doing its job anymore. And then because it has low energy, it becomes very hungry and it triggers us to basically try to have an emergency state where we need to repair that. And so it basically tells the body, I'm starving. And then we become we end up in like in a in a feedback loop where suddenly we're we're always hungry and always craving and trying to repair this system.

12:52 Uric acid: what the lab test does and doesn't show

12:50Chris:We don't really realize is broken.

12:52Lucas:So let's let's expand upon that, Chris. I mean, uric acid, as I was saying just before we started recording, uric acid is pretty commonly assessed in blood work, or at least from what I've seen with patients when I'm doing consulting, uric acid is oftentimes mentioned a lot of the time. It's often just overlooked. But, you know, in terms of what significance do you think it plays in terms of our overall like, how can we assess someone's health based upon their uric acid score on a blood test?

13:28Chris:It's a very interesting question. And unfortunately, most of the blood tests don't really answer it well enough because what uric acid is testing when you go to the lab is serum uric acid. So it's the free flowing uric acid in your blood. And yeah, purines play a part in that. And but so does the system. It's like it's when that when that degradation happens, like those uric acid is generated sort of through the same system. But it's not just from your food. It's from sugar or from specifically fructose. So unfortunately, what is what is really happening with what we're talking about is intracellular uric acid. And I have a hypothesis that basically the majority of our uric acid is coming from within the cell.

14:18Chris:And then what we're testing is kind of the spillover when it's already become a problem. And it makes sense because that like when people complain about gout and stuff like that, it's kind of quite well along that they've got metabolic issues. And you even look back through history and it was like it was like gout, which was always like the disease of kings and stuff like that. That was it kind of it mirrors our food environment now, where these were the people that had access to sugar because it was very, very rare. They had access to caloric access. They had access. They feasted. They had alcohol, all that kind of thing. And basically, it was like this kind of preview of the state that we're all in now because.

15:09Chris:And yes, they had gout, they had uric acid that was elevated and it spilled over. So unfortunately, to answer your question, I don't really think that the labs are as helpful as we want them to be. I think that uric acid is somewhat of an every one problem because of our food state right now.

15:29 Interventions, eco mode, and lessons from nature

15:29Lucas:So therefore, what you're saying, Chris, is it could actually be a later stage byproduct of like metabolic maladaptation. And so in terms of interventions like what do we use at this point in time? Like are there anti diabetic drugs that actually target uric acid? Is it a pathway we've considered before?

15:59Chris:Well, I think allopurinol is the big one and it's excellent, excellent tool there. But I do think that the real trick is not. I think the problem that we've had for many decades is not knowing the target and the target being fructose itself. So supplements in general. They typically add to this. They try to add something into your metabolic system to boost it. But the problem is really relieving a burden rather than adding to the system. And we've known for a long time that sugar is not good for us. You can ask any kid and they'll be like, yeah, I'm not supposed to eat that much sugar. And it's funny that like in spite of that, we struggle with this because reducing sugar doesn't alone fix the problem.

16:55Chris:It is part of the equation. And that's I think that's why that's why we've not really had this full picture all along. And I think so part of it is that I don't want to villainize fructose. I actually think it is a very powerful system that we don't need to villainize. We need to appreciate because basically, if you think of it this way, back to that analogy of a car. So really what it's trying what it's trying to perform in your body is energy conservation. It is reducing the output of your cells to keep it at a low state, which then encourages your body to obtain more fuel. So basically on the input side and the output side, it's conserving fuel in a really efficient manner.

17:50Chris:And in almost all other cases, whether it's nature or even in a car itself, energy conservation is a valuable tool to have. We call it like we use the eco mode button on our car. We hit it and we because we appreciate having fuel like conserved, it's going to get us a little bit further down the road. The problem is if you drive in that state with that button pushed for a long, long time, then you start to wonder if your car just doesn't perform. It's like if you forget that button exists and you hit the gas and your RPMs go to like maybe 2500, 3000. And it's like, why does it go all the way to 6000? It's like, I've never done that before.

18:41Chris:And really, that's sort of like to this what we were talking about earlier. We have this innate feeling that I have a higher performance level that I'm not hitting. And so essentially, if you look at nature outside our very windows, we have so many different animals that use this system to an amazing effect. Like we have bears, the natural one, who gorge on fructose fruit, like very high in fructose. They wait until that fruit gets super ripe and they just binge on it. They eat like 100,000 Oregon grape berries in a day kind of a thing. And it gives them this huge flood of fructose that allows them to binge and pack on as much weight as possible because we know they've got six months of hibernation that they're trying to survive.

19:40Chris:Right. Or you've got many other animals like birds will kind of do similar when they pack on weight before their migration. There's other crazy examples like naked mole rats. They live under the ground. This is a really wacky one, but I love it. They live under the ground and they have less access to oxygen. And when your cells reduce energy like that, they switch away from using oxygen as a part of their fuel system with ATP and they start running on a non-oxygen dependent fuel system. So fructose actually enables them. So their bodies create it so that they can basically survive underground on low oxygen environments. And we have that all built into us as well.

20:33Chris:So it's like another one, hummingbirds. Hummingbirds binge on sugar every single day. They basically eat nectar all day. They induce a diabetic state because they've exploded their body weight in the course of the day. And then that enables them to survive night. So because their metabolism runs so fast, they induce diabetes, reverse it by morning so that they can go and do it all over again. I thought you were about to say that they hum their way to insulin sensitivity. Right. Yeah. So it's wild to me. Like we have all of these amazing examples of this at work right outside our window where it's another one. Lizards. Lizards don't really use fructose in the same way, but they don't urinate in the same way we do.

21:31Chris:They just excrete uric acid, which is interesting because it shows that there's, again, using this system just in a different way. It's like uric acid seems to be part of this fuel regulation system. And so really looking at humans, the problem is that we've kind of not been aware of how this works. And so in our amazing ability to modify our environment, we just are enjoying food. It's like we've now we've got as much access to sugar as we could ever want. And we kind of just didn't realize what it was doing to our bodies. And because it's a feedback loop, because it's a self-perpetuating system, it's like, it's hard to get off of it once we are.

22:23 How the food environment changed

22:23Lucas:Interesting. Chris, what about in terms of, I mean, the food environment, how that's sort of shifted and evolved over the years? Talk us through that.

22:33Chris:Okay. So I love this little, this is interesting. So we talked about gout, right? How like in the past, it's been around for hundreds and hundreds of years, but in these tiny little microsystems of like, like, wealth, let's say. So, so even it's interesting. So like you go back far enough and you start to see that there were like these little previews of metabolic dysfunction. But it even like blended into like the East India Trading Company, where they, they were harvesting sugar in awful ways. And they had this monopoly where it was very, very tightly controlled with tariffs and stuff like that, where only the wealthy could afford sugar. And that all sort of broke down with a really interesting timeline that, that, that is now, it compares to how our, how our health started to fall apart.

23:31Chris:So basically in the 1850s, there were some, there was some regulations that happened in England where those tariffs were removed. And then there was a London World Fair and like some like 1850 or something where suddenly sugar was like, hey, this is for everybody. Now we can, now it's cheap and everybody can have it. And that almost, you can see over the next number of years, the global intake of sugar just started climbing and climbing and climbing and climbing. And it looks like a leading indicator of like obesity and metabolic dysfunction. Like it's, it's crazy how tightly it fits. It's like just a few decades later, like a few years later and everything starts to follow.

24:20Chris:And then of course our food system started to change in other ways. Instead of like the little grocer that, or the little butcher or whatever, now we're starting to use supermarkets where suddenly you can basically buy whatever you want. And then those supermarkets started changing where now we have more and more processed food and we're pushing all the whole foods to the corners. And those, those processed foods were the channel of now delivering something that they invented of high fructose corn syrup, which, and they had more sodium in it. And like, it was like our entire food environment just rapidly shifted and it does really follow how our metabolic health has kind of deteriorated over like the last hundred years.

25:12Chris:And so really in all of those little moves, what we were doing is just introducing more and more fructose into our diet so that it went from like the, close to a wild diet where it's like you had fruit as your only source of fructose. And it was only when it was basically seasonal to now having it every single day, multiple times a day, often for breakfast. Like it's, it's crazy how much, how much it's been reintroduced into our diet.

25:44 When eco mode won't switch off

25:44Lucas:So Chris, in terms of the, I mean, before you mentioned, I really liked the example where you sort of mentioned the eco mode. You mentioned sort of like, I guess what would actually happen when that eco mode won't switch off?

26:01Chris:Yeah, so that, as I mentioned, it starts as an adaptation that helps us, but the problem is leaving it on too long. So if you think about, it's essentially activating a fuel management system where it's trying to conserve that fuel, conserve the output as much as possible. And in doing so, it actually triggers a response in your brain. So that emergency signal that you're starving is beneficial because it actually kind of causes it in a similar kind of downregulation of energy. And targeted areas of your brain that allows you to go and kind of forage. Whereas it's also kind of keeping you lazy at the same time. And we kind of understand that very well.

26:46Chris:Like we sit on the couch at the end of the night and it's like, I'm sort of like, lazing around, watching Netflix, whatever. But for some reason, I'm really motivated to go and rummage the cupboards for snacks. It's like, and that kind of concept is actually very beneficial if you're thinking about trying to pack on weight as a wild animal. It's like you're going to take a little bit more risk when it comes to finding food. It kind of shortens your short term memory, but at the same time, you're quite sluggish otherwise. So we're very familiar with that. But you can see how long term that becomes maladaptive if you just leave that on too long.

27:31Chris:You've got this underperforming cell. You've got low ATP. Your oxidative stress is rising. You're getting inflammation. And then what happens is those individual cells, they're all part of systems and you have a fragile cell that becomes part of a fragile system. And that's where the problems start happening. So we might think of it like back to that engine analogy. If the engine that is having trouble is like the mail truck and that one mail truck is a problem, that's fine. They'll adapt. But if the entire mail truck fleet starts to have the same engine problems, you might not get your mail anymore. So and that's basically what happens in our bodies is like these systems then start collapsing because the hormone signaling isn't happening.

28:22Chris:There's inflammation, stuff like that. And really, there's even like gene expression that starts falling apart. Your DNA methylation starts occurring. You impair your fat burning. Aging starts accelerating. And then basically, you start having system failures. And the crazy thing is it could be anything because you're talking such a low level system that it's like at that point, it's whatever my own weakness might be. So if I am prone to hypertension, then my and my endothelial cells start collapsing because they are not getting enough. They don't have enough energy, then they start tightening and you start getting hypertension. Or if you're if it's targeting your liver, you're getting liver fat, stuff like that.

29:13Chris:Diabetes. And basically, it shows a route of almost all illness. And that's kind of the crazy part where it's like we are is a good thing that we're targeting all of these things that we're treating them. We have so we've had decades of great research that is giving us medications for all of these things. And this doesn't change any of that. But it's saying, what if the floor is the problem? What if we're like not supporting that environment well enough? Then it almost makes sense why you never get off those medications. You know what I mean? Like it's like.

29:52 GLP-1 drugs through this lens

29:52Lucas:Yeah, I mean, speaking of speaking of medications, I guess one class of drugs that are like really popular at the moment, all over the TV, all over social media are these GLP-1 drugs. Right. So we were looking at semaglutide, you know, tirzepatide, retatrutide, cagrilintide, the different those GLP-1 related drugs. How does this actually shift our understanding of these GLP-1 drugs?

30:22Chris:I think those are amazing. I think that GLP-1s are fantastic. But I think I think a good way that you can consider them is back to that same analogy. So your GLP-1s are really great at influencing your glucose. And so back to that analogy, your glucose is your fuel. So you can imagine you've got this eco mode little economy car where the gas pedal is not working well because you have insulin resistance. And it's unfortunately also hooked up to a fuel trailer because we're overweight. And so if you're targeting the fuel system and saying, OK, you've got too much fuel, it's sort of like GLP-1s are just helping you unhook that fuel trailer.

31:15Chris:It's relieving a burden on a very weak system. So is it going to help? Absolutely. That is so critical. It is a big piece of this puzzle because that is adding so much more stress onto a system that's already burdened. But it also makes sense why when you go off GLP-1s that burden comes back because you're still dealing with a little car that has a fragile engine that's on eco mode. It's still not performing. And so it's still hungry for more fuel because of that. So it's like basically at the same point, whereas it GLP-1s are supporting, but it is not a route intervention. The route really is within the engines itself.

32:08Chris:It's our mitochondria. It's how it's happening within the cell. That's the problem. It's not the fuel itself. So that's why that's why fructose is so important because fructose is actually influencing how those engines run. So if you can open that up, then that's going to make a big difference.

32:33 The hidden switch: your body makes fructose

32:33Lucas:What you're saying there, Chris, is that fructose itself, the molecule, is controlling how glucose is used and stored in the body. That's like the main because people will that's an interesting concept because we've never been really taught this in nutrition school. Like, I mean, I studied naturopathy and we were never taught that fructose is like the mediator, the governor of how glucose is used and handled and the fate of glucose. So the big question sort of really becomes if people don't actually eat a lot of sugar, then why do they still struggle so much?

33:24Chris:That is the big question. And the reason why this hasn't been taught is this is the part that we only started understanding recently and the part that really makes the whole puzzle connect. So you're right. Like fructose is the hidden switch that puts your cells into eco mode, which makes you conserve energy. It drives cravings and it slowly breaks our metabolism. But that is something we've only really understood in the very short amount of time, like in the last 10 years where fructose is actually having an intracellular influence on ATP, on uric acid and that kind of thing. The other half of the story, though, is that the body makes fructose.

34:13Chris:So we make glucose, but we also make fructose. And that's why this is so amazing because not only does this mean that sugar is a problem and it's probably where everything went wrong because we intro we modified our diet so much. But just off the top of your head, what are the other suspected causes of weight gain? What can you think of?

34:39Lucas:I would think of things like excess cortisol, sluggish thyroid, like hypothyroidism, maybe even some mineral like critical B vitamin deficiencies.

34:53Chris:Okay. Yeah, that's good. That's okay. So you got some hormone stuff in there. But as far as like food systems go, because most of us kind of stay in that realm, we think, okay, I don't get enough exercise. I have too much salt in my diet. I eat too many carbohydrates. I probably should cut back on my alcohol. And the wacky thing is that all of those connect to fructose. So and that's why this becomes unifying where it's like there is a part there is a pathway in our body called the polyol pathway that we've known about for a long time, but we thought only applied to diabetics. And what that does is it is a path where glucose is converted into sorbitol, which is then converted into fructose.

35:42Chris:So glucose becomes fructose. And the environment in which that happens is when we have high blood glucose levels. So we thought it was only for diabetics that had that. But basically, it's any time our glucose spikes, then we have a path then to creating fructose in our body. So essentially, the triggers are high glycemic carbs, alcohol, that's another it's almost like a perfect mirror of fructose. It also creates uric acid. It is it's almost identical. So we've got high glycemic carbs, we've got alcohol, salt is another one. It boosts that system enables

36:22 Salt, dehydration, and hypoxia

36:22Lucas:a fruity cocktail would be a terrible, terrible combination.

36:36Chris:It could be right. Another crazy one. So salt, we've got salt and dehydration are the same thing. And you can see how it pairs up into like a survival function at the root of it too, right? It's like, why doesn't have enough water? So what is it going to do? It's going to try to conserve as much glucose as it can, because they hold three grams of water to every gram of glucose. So it's like it, it kind of it. It's a survival system again. Another one is a different kinds of stress. So dehydration is a stress, but also hypoxia is a stress. And so it's interesting, because it makes sense as to why this starts cascading as our health deteriorates by start packing on weight, then that then my then my blood glucose levels are going to raise, which means that my body is going to start making more and more fructose.

37:29Chris:And then at a certain point, maybe I'll start getting like sleep apnea, which is then a pretty significant stress on the body as a as it makes you hypoxic. So your body makes more fructose again. So it's like you get locked into this state of just becoming a self perpetuating fructose machine where your body is just locked into this, which it sounds bad. And it is, but it's great. It explains why we've missed it for decades, because it's like we've got all these different ideas of what gains what helps us gain weight. And they're all true. But we miss that fructose is actually the connector behind all of them.

38:09 Fructose and the brain

38:09Lucas:What's what's really fascinating, Chris, is like I think it was around the concept that you sort of and I've sort of looked into this as well. The concept around how fructose is more tightly linked to dementia than sugar intake is alone. How is that the case?

38:31Chris:That's a good one. So the body makes fructose. You're right. So what's interesting is that our brain runs on glucose. We know that fructose does not cross the blood brain barrier. So then it's like, could fructose be a problem in the brain? But when we just start talking about what we just did about the polyol pathway, how in energy sensitive tissues, glucose can be converted into fructose. And that does apply to the brain. And so that's why I think this is a really fascinating like we've been trying to figure out this blood brain axis connection for a long, long, long time. What it why is what I'm eating causing me issues cognitively. And it connects back to that signaling that happened when our cells are slow.

39:26Chris:Our brain is influenced by this because it tries to. So when glucose levels are raised in the brain, then fructose can be generated when that happens. And the same effects happen where you've got like neurons now that have lowered their energy output. And it seems to happen just like just like the liver is particularly targeted by the system. The brains, certain areas also seem to be particularly targeted by the system. So it almost became some. There's some researchers that suggest that it creates a behavioral template almost where, as I said, we start foraging and we kind of create that little habit. But it's interesting because the certain areas of the brain, the lower it makes you more impulsive, it makes you take more risks.

40:23Chris:But it also protects your different systems. So because it's trying to adapt for you. So if you if you in your in your intention of foraging lost your eyesight, then that would completely ruin the intent, the natural intent. And so it's interesting that it protects those certain critical systems in favor of reducing others. And that's why there is this pattern that emerges. And what's really interesting is that like. It mirrors what's happening with Alzheimer's disease just as a very end state issue here. So in survival mode, the brain creates its fructose. You get this short term memory loss. You start wandering. You start reducing your activity.

41:13Chris:You preserve your vision. You preserve your mobility. And they actually found that these areas of the brain exactly or very closely match what we see in Alzheimer's disease. So in rodents, they gave rodents high sugar diets and they cause brain and brain insulin resistance in these rodents in about two weeks. Didn't take very long. And then keeping them on that diet, it progressed to basically Alzheimer's disease with amyloid plaques by about 18 weeks. And it mirrored exactly the same areas of the brain that we're seeing targeted here. So like there are some there are some researchers that actually said this is the source of Alzheimer's disease.

42:03Chris:And it's and specifically it's not just sugar here because sugar like fructose doesn't make it into the brain, but it's high glycemic carbs. It's like French fries and salty carbs, especially because it kind of it boosts all of that entire process. So then it's crazy, crazy to think about like the downstream effects of high blood sugar leading to production of fructose. The body then endogenously produces fructose.

42:34 The target: fructokinase (KHK-C)

42:34Lucas:What can we then do, Chris, in terms of interventions? Like, how can we potentially block the synthesis of fructose? What can we do about it?

42:47Chris:So for my own little journey, like I've been looking at this for about five years or so. And I found this stuff super fascinating. It's like this unifies everything like this is super important. But then I kind of fell away from it because I didn't think that there was anything you could do about it besides like supplementation, like to boost your mitochondria and maybe reduce some uric acid. So like I think I took tart cherry to reduce uric acid. I tried taking vitamin C. I took green tea extract to kind of EGCG helps your mitochondria recover, things like that. And it was like, OK, that's something. But it's not targeting the problem because fructose is really the source of all of the stress.

43:45Chris:And so I found some research that identified that the there is one particular enzyme that this entire system hinges on. It's called fructose kinase and specifically ketohexokinase type C. So this enzyme, KHK-C phosphorylates fructose into fructose one phosphate. And then that reaction consumes ATP, which eventually generates into uric acid. So that's what's tipping that oxidative stress and leaving the mitochondria underpowered. So basically, that one enzyme, KHK-C or fructose kinase, is sort of the linchpin on this entire system. And the reason it works that way is because it then targets not just dietary fructose, but also endogenous fructose.

44:39Lucas:Wow.

44:39Chris:And so there's there was a genetic clue that was found here because there is a small amount of our population that has a genetic defect called essential fructosuria. It's like a benign genetic condition where basically no one knows that they have it until a doctor says it showed up in your lab work. And it's identified by having sweet urine, fructosuria. It's like part of the name. So they're excreting fructose. They're peeing fructose out because their body is not even using it. And what's interesting about these people is that they stay super healthy. There is basically very little, if any, that cases of metabolic syndrome in people with this condition.

45:26Chris:So which is nice to know because the body does have other means of ridding this fructose from your body. It doesn't just depend on this one enzyme. So it doesn't build up in your system. It can the body can eliminate it, which is nice. It's not like we know that, OK, it's not a it becomes a disposable enzyme which we can target. So that basically identifies the target. So if we target KHK-C, maybe we can stop fructose.

45:56 Luteolin: the research and the bioavailability problem

45:56Lucas:Well, that's where it gets really interesting, Chris, I guess, in terms of interventions to actually target the as a natural KHK inhibitor that particular enzyme you mentioned. What exists in nature? Like are there compounds that you came across where you're like, OK, this is like a miracle molecule in your eyes. This is something worthwhile investigating whether or not it translates from animal studies into human studies. That's that's the big question, right? Because a lot of these natural compounds lack bioavailability, things like that. So what did you find?

46:36Chris:So that was the interesting part. So I kind of shelved this whole thing. And then, like a couple of years later, is reading more research papers. I came across a study that identified luteolin as a KHK-C inhibitor. And I was like, wait a second. That's crazy. So like you said, you've been taking it for years. You love it. So luteolin is very, very closely related to quercetin. So which many people are more aware of because luteolin is fairly unknown still. It's and there's a reason for that. Like it's basically a favorite in the laboratory, as far as I can tell. But so few people as consumers have heard of it. And so there was a.

47:21Chris:Essentially, you're right, there is there is it has poor bioavailability. And that's really, I think, why there's not been too much in the way of clinical trial work on it. It's just but there's piles of animal studies. Like to be honest with you, like I've kind of challenged myself a few times. It's like, I want to see if luteolin can help with Hodgkin's disease or whatever, like some like obscure metabolic issue that few people have. And it was like, could there be a connection there? And almost inevitably, there's research on it. Because it is one of those few molecules that seems to.

48:03Lucas:Sorry. Yeah, I was going to say just before we did up before we prepared the podcast, I actually checked on PubMed. And if you search luteolin on PubMed, there's like seven thousand nine hundred results, which for anyone listening in, if we're looking at like most supplements in a supplement store, they'll be lucky to get maybe like two or three thousand. Luteolin has seven thousand nine hundred clinically cited PubMed studies, which is absolutely insane.

48:37Chris:It's wild because it seems to have a strong influence on basically every metabolic condition. And it makes sense like that. That makes sense when we talk when we think about everything we just talked about. Like if it's that if it's like actually changing the floor, changing the foundation, then it makes sense that you support those fragile cells, you protect them from their key source of stress, then it's going to have a benefit. I guess not saying like, hey, it's going to cure this disease, but it will probably give your body like you. How is it? How we put supplements are always supporting healthy metabolism, right? That is their role because we can't actually say they treat disease.

49:23Chris:But is anything going to support a healthy metabolism really more than something that supports the foundation protects you from the like the root cause? So I think it's super exciting. So there was there was there was there have been a few clinical trials on it and I was super happy to find these. So as an example, there was a six month clinical trial on a luteolin-rich artichoke extract, which I think is the one you use. You are use it in artichoke extract, right?

49:53Lucas:Yeah, yeah. I've actually been singing praises of artichoke extract for so many years. Just a quick side tangent. The reason why I was obsessed with artichoke about four, four years ago was because whenever I went to a Chinese medicine specialist, a traditional TCM practitioner, almost every single one of them said that I have something called liver qi stagnation, which is like the energy flow of the liver is basically their way of putting it is you've got a toxic liver, which is like the Western terminology. Then I'm like, okay, what herbal extracts exist that I'm happy to use with minimal side effects based upon traditional Chinese medicine.

50:38Lucas:And they say that artichoke extract basically has no contraindications. So I was like, you know what, I'm going to select artichoke and that's going to be my liver herb for the rest of my life.

50:52Chris:That's pretty cool. You were on to something that's pretty neat. So yeah, this is so this is wild because this is like that on steroids. This is this is this is taking artichoke extract and like isolating the thing that could sort of change everything. So in this clinical trial, well, okay, to put that in perspective, I'm pretty sure that most artichoke extracts have to the range of like maybe three milligrams of luteolin small, a very small percentage. I think it's like, is it less than 5% luteolin typically,

51:32Lucas:it's even probably even lower.

51:32Chris:Yeah, so it's not to say it's not good, because there's actions. There's another, there's another study. So there was a population study done where there was a dose dependent effect on dietary sources of luteolin. So things like parsley and chamomile and thyme and artichokes, yes, and celery leaves and whatever it might happen to be. And they did a big population study like thousands of people and they actually found for chronic kidney disease, and I think for heart disease, they found that all cause mortality dropped by like 27% or something like that. It was wild, like I quite a significant number for a study that was like, I don't put a whole lot of weight in that because dietary kind of like monitoring is difficult, especially in big populations.

52:34Chris:But it was interesting, like, because that was not a small number. So back to this clinical trial on luteolin itself, there was a there's a proprietary formulation that I think includes chlorogenic acid in this artichoke extract, and they found a 43% drop in HOMA IR, so insulin resistance, which to me was just huge, because now you're saying, okay, I can actually insert more energy into my crushed cells. They also found a 22% drop in liver fat, 22% drop in triglycerides. They had a significant number of weight BMI and waist circumference drops. So it changed it, like you were able to essentially use more of your fuel to burn as energy and it's like it's like that volume control on your metabolism, like we talked about, started to be modified.

53:36Chris:So I think that the most the form, if you're going to be trying to monitor this stuff, as to the influence of fructose, I think the most important things to measure are HOMA IR, uric acid, as you said, although it's not intracellular, so I wish it was deeper, but it will it will be measurable, I would say, triglycerides and your liver enzymes, your ALT, AST. I think those ones are really the key measures of like how fructose is influencing you, and then everything almost cascades from there. Like they're like the next level of separation. So in that, just to kind of give you an idea, we talked about, so the luteolin you're getting is probably in the range of two to three milligrams, I would say.

54:34Chris:This clinical study was in the range of, I think, 60 milligrams, but luteolin is very poor. It has very poor bioavailability. Which I'm pretty sure is why we don't see it outside of the lab very much. So they love it in the laboratory. It's like this does everything, and they're trying to find ways of turning it into a proprietary drug because of that, of course. But in the meantime, it's like we've got all this new stuff where we can actually improve bioavailability now. And the big one really seems to be liposomes. So there's research showing that specifically by using liposomes with luteolin, it then becomes a candidate for cancer treatment because it has all these incredible effects on energy metabolism.

55:32Chris:I don't know if you want to go down this road, but we talked about earlier how when your cells don't make energy, then in naked mole rats, they turn to fructose. They turn to a non-oxygen dependent fuel system because our cells are amazingly adaptive. By that argument, naked mole rats should be riddled in cancer, but they're not because they have special adaptations that protect them. We don't have those. So when our cells move away from healthy energy systems, then we start having cells that can degrade. They're more fragile. DNA methylation happens. You start having this fragility where mutations are less controlled. And really it explains what pops up is the Warburg effect.

56:28Chris:Have you heard of that?

56:30Lucas:Yeah, I have, but I can't exactly remember it. It was like some sort of energy rule.

56:38Chris:Exactly. So the reason that cancer is so difficult is because it is so unique. Every different permutation of it is so unique. And so unless you've got custom immunotherapies that are almost tuned to you and to your particular cancer, then it's really hard to target it once it's metastasized. But what is common across all cancers is the energy signature. So decades ago, they discovered that the Warburg effect, which is basically this modification of the cancer modification of how these cancer cells are using energy, is the one consistent thing across all cancers. So it's like your energy collapses within the cell, it gets fragile, and then it makes sense as to like, okay, things start going awry.

57:36Chris:So luteolin, or specifically inhibiting fructose, protects that energy process in your cell. And so it's pretty incredible how luteolin is being looked at as a target for cancer treatment, because it essentially protects that entire system. Like it targets the root of how those, so it helps with tumors, it helps with blood flow to those tumors. The research on it is pretty incredible. And there's been even reviews consolidating a number of different findings on it. So I don't know how we got into that path, I'm sorry, but it's pretty incredible how it kind of protects our cells there.

58:25 Real-world observations with liposomal luteolin

58:25Lucas:Yeah, that sort of leads me to my next question, Chris, which is around the implications and the effects in real life, applying this liposomal or liposomal formulation of luteolin. Now you guys have actually piloted this in the real world. What did you guys actually identify?

58:50Chris:Yeah, so my little path there was basically as a nerd, I read this stuff, found that luteolin is great. And it was around the same time I realized that liposomes are going to help there. So that was kind of an easy puzzle piece to figure out. And I started sourcing my own and trying it out and self experimentation, because even the reviews I was reading, I was like, hey, this seems like nobody's paying attention to and it seems really powerful. So I started taking it, and my wife started taking it and my in-laws started taking it and stuff like that. And it made a huge difference. Like it was pretty wild. So my own personal effects were that basically by about two to three weeks, I remember we were sitting on the couch and it was like our little, our daughter had gone to bed and it was kind of one of those moments where I was like, should we make a cocktail or something like that?

59:51Chris:And both of us kind of looked at each other and said, I don't really feel like it. And that was weird for us because it's not like we had a dependency or anything like that, but it was like this perfect moment where it was like, you know how food and drink is like just this natural part of enjoying life. And it suddenly was like we had agency over it. There was like, there was no, it became optional. And we noticed over the next few weeks that the same thing held true to basically all food where it was like, we didn't crave carbs anymore. It wasn't like we didn't like them. Like sure, of course, but it was like, we just didn't need it. It was like, it was like that little switch turned off.

60:40Chris:And I started, I actually found that there are people that, that I'm part of a community that on Reddit that tries to hardline sugar restriction. And it was really interesting because they report the same thing. So if they are brutal about protecting their diet from fructose, the same thing happens. Like three weeks in from, for most people, everyone's different obviously, because you're like, you're basically putting, you're supporting the floor in the system. So when, when cell energy starts recovering, it's like those cravings shut off and inflammation goes down. That's one of the first things. And then weight starts dropping because your, and your energy kind of skyrockets.

61:27Chris:I remember I, I woke up one morning and it felt like almost euphoric. And it was like, this is cool. Like, I didn't realize this could happen because I've never felt this in my life. But like, I woke up with like a spring in my step and was like, this is pretty cool. So there's like all these great effects that happen from, from really hard lining your diet to protect yourself from this. But Luteolin also does the same thing. So basically what we saw, I ended up sourcing some and doing, doing, doing, doing like basically a very little gig out of my garage, like so my family, friends and family could get some too. And we've been running that for about two years now.

62:14Chris:And, but now we've kind of upgraded since then because we realized that more people need to see this. And so far, no one else is doing it. So basically we asked the question with that little pilot, for lack of a better word of this little product, could this actually have a measurable impact on health? Like, what would this look like? And we've seen about 80% of people self-report that their energy has gone way up. We've had about 40% of people self-report that their cravings are, are way down. Lots have said they have less digestive discomfort, like the bloating feeling and all that is gone. Lots have lost weight, I think about 20% of self. So when I say self-report, I'm like, this is just their own little testimony.

63:04Chris:Like that we're not asking this question, like, did you lose weight? But 20% said yes, they did. And many of them were like, I lost like 25 pounds. It was like, wow, that's really cool. Good for you. My own father-in-law, as he reported, he's been on it a little while now. And he told me last month that he finally went off of Ozempic and we're like, are you okay? He's like, yeah, I stopped it like two months ago and I'm still losing weight. I'm like, okay, good for you. That's incredible. Our dad, like want to make sure he's okay. But yeah, he's, he's loving it. So for me, I lost about 20 pounds in about four months, I think. So it's just, this is only to say that like, as a proof of concept, blocking KHKC, which was the intent, or like the hope that what would happen here, it seems to work in practice.

64:00Chris:Like, it seems the research indicates that's what this does is one of its effects. And protecting ourselves from fructose seems to make a significant difference. And so like, we've got the research stating this, we've got like these, we've got clinical evidence that shows that this is actually a viable mechanism to target. And we've got now people like you and me saying like, yeah, this is making a massive difference. So to me, and then if you've got all this other evidence of like going back into history and socio economics and like our grocery stores and bears and all this, it's like, I feel like I'm drowning in evidence. And that's why I really wanted this message to get out there.

64:48Chris:Because I feel like this is a really significant thing that we need to be looking at. Like, whether we say it's proven or not, like to me, I'm like 99% there. But the rest of the world needs to kind of make that case for themselves too, I would say.

65:05 SugarShield and closing thoughts

65:05Lucas:And that's what you guys have, I mean, you guys have now pioneered and, you know, pushed this particular concept and applied it into a product, which I believe is called SugarShield.

65:22Chris:Yeah, yeah, that's right. liv3health.com.

65:22Lucas:Massive hats off to you for even like making that, you know, a reality because you know, you've gone from reading clinical trials, seeing what people are saying on websites, on forums, trialing it yourself, running a pilot study with just close friends and family. And now you guys have, you know, encapsulated use the liposomal technology for luteolin. Yeah, can you tell us more about where people can learn more about that?

65:56Chris:Yeah, for sure. So our little product, SugarShield, just to give you an idea, like you said that you were taking like an artichoke extract, like three milligrams, the, that other clinical trial I referenced was like in the realm of like 60 milligrams, that when we add liposomes to that with even a higher dose, we're expecting this is roughly in the range of like 50 times even what was in that clinical trial, as far as potency. And we also combine it with tart cherry extract, because it's shown it's proven to basically help with uric acid. So we're trying to target the, the fructose side of it as, as like stopping that from entering your cell while also relieving the existing burden of uric acid.

66:48Chris:And, and it seems to be working great. And as far as I know, I don't know of any other companies that are doing a liposomal luteolin because, or at least, or at least not anything reputable, like there's, there's some stuff that I am very suspect of that comes from overseas that doesn't have the quality control. And fortunately with liposomes, sometimes people say, okay, they just apply like a blank standard to it and say, this is 1000 milligrams when, because they're assuming that liposomes are doing that, even though the reality is like a fraction of that. So yeah, we're, we're, we're trying to kind of make a, we're bringing a product that to the market that no one knows about.

67:39Chris:And that's why we're trying to get the word out there, because it's not, it's not the product that matters. It's the science that matters. Because if this really is so root, then we need to be talking about it. So yeah, our website is, is liv3health.com. So liv3health.com.

68:00Lucas:Incredible, incredible. Well, I'm actually really proud to be like, one of the first podcasts where you're discussing the science, you know, the theories, the mechanisms. Because that's what, that's why people, you know, subscribe to my YouTube channel, they follow my podcasts, because yeah, I go deep onto the deep into the science, they want to understand mechanisms. And you've done an incredible job at breaking it down, explaining the mechanisms, exploring like hypothesis that, you know, and you've also pioneered something new, like you're bringing forward a liposomal luteolin formulation that doesn't really, there's not many other companies from what we know is that are selling it.

68:44Lucas:So hats off to you, man. Like this is, this is an incredible journey.

68:48Chris:I'm just a, I'm just a learner like you, but your enthusiasm is palpable. And I love it. And I, I know you do good work with a lot of people. And, and I take no credit for this. There are some phenomenal scientists behind this stuff. And honestly, I'm just in awe of it as a natural system, because this has been at work in biology forever. And we just didn't know it. And I feel like it, if it really acts as this amazing lever on our health, that I think it is, then it's just, it's just cool to be part of that journey. Because everyone needs this, like, to me, like, there, there isn't a single one of us where we don't have a family member that's affected by this.

69:36Chris:And if we can move that needle, even the tiniest little amount, that's, that's huge. Because like, it's not just chronic disease, it's like decades of feeling unwell that precede it. So we need something to make that difference.

69:53Lucas:Well, put it put it this way, Chris, I build protocols and stacks and formulations for people. And, you know, anytime I see somebody with a high HbA1c or a high fasting insulin or a high triglyceride, or high AST ALT enzymes, I'm definitely going to be considering your product as part of a stack, maybe with like, you know, your dihydroberberine with your inositol, maybe even some chromium. I can see some incredible synergies there. And I'm confident that it will move the needle, so to speak. But thank you so much for coming on the podcast, Chris, who is an absolute pleasure chatting. I was actually really looking forward to this one, because I've got a deep interest in artichoke extract and, and novel flavonoids, as we're both huge nerds in that front, in that regard.

70:47Lucas:But for anyone listening to this podcast, do check out liv3health.com. If you guys actually want to check it out. I'll also leave it linked in the podcast show notes. And as always, guys, if you did enjoy today's podcast, please do leave it a five star review. It really does help with the algorithm. And please share it around. This is incredibly useful health information that can not only benefit yourself, but also your family and friends. So that's it for me today, guys. Thank you for tuning in. I look forward to seeing you on the next episode. Thanks, Chris.