In this three‑chapter YouTube presentation, the speaker (Nick Norwitz) first explains why fructose is metabolically harmful: it is phosphorylated by ketohexokinase without negative feedback, depleting cellular ATP, generating uric acid, causing mitochondrial oxidative stress, and driving de novo lipogenesis. He cites mouse studies published in Cell Metabolism that show fructose both increases its own intake via intestinal signaling and promotes metabolic syndrome via hepatic metabolism, creating a vicious two‑step cycle. In the second chapter he introduces allulose, the C3 epimer of fructose, which tastes like fructose but is not a substrate for ketohexokinase, provides no calories, does not raise glucose or insulin, and uniquely stimulates a four‑fold increase in portal GLP‑1, the incretin hormone targeted by weight‑loss drugs such as Ozempic and Wegovy. He frames obesity as a partial GLP‑1 deficiency and argues that boosting endogenous GLP‑1 via allulose could confer similar metabolic benefits. In the third chapter he argues pragmatically that society will not abandon sweetness, so replacing fructose with allulose offers a scalable, affordable alternative to expensive GLP‑1 analogues. He endorses the company RX Sugar, highlighting its leadership (CEO Steve Hanley) and scientific advisors (Dominic D’Agostino, Ben Bikman, Richard Johnson) as aligned with his mission to improve population metabolic health. He concludes with a call to share the information, not to purchase products, emphasizing allulose as a tool for individuals and loved ones seeking healthier sweet options. The video blends biochemical detail, evidence citation, and public‑health advocacy.
Chapters
If you follow me, you know that I'm low carb and keto and love the lifestyle. In fact, I have no desire for sweet whatsoever, intent to think that sugar is detrimental to health. However, could I be wrong? Could a sugar actually be part of the solution to the obesity epidemic? And could a sugar, that same sugar, be a tool that you or a loved one could use to optimize your metabolic health within the confines of practical limitations of life in the year 2024? Maybe? Stick around and I'll answer that question with quite a bit of nuance, and I promise you'll learn something. Welcome to my channel. Stay curious. This video is going to proceed in 3 chapters. First, I'm going to tell you about fructose and why it's metabolically malicious. Second, I'm going to introduce you to fructose's chemical twin. A twin that, whereas fructose is the evil twin, this other twin is the good twin. It mirrors fructose both in chemistry and in virtue. And third, I'm going to tell you about how this twin might actually be a solution to obesity on a population scale and a tool that you as an individual or loved ones could potentially use to improve metabolic health. Chapter 1: Why Fructose is Metabolically Malicious. Well, obviously I don't actually think fructose as a 6-carbon sugar is malicious. It doesn't have any intent. But what I'm trying to communicate through that expression, metabolically malicious, is a contrast to the idea that fructose is just empty calories. I think we tend to think of things like fructose as unhealthy because they don't really provide any nutrition and they have calories and that can make us fat. But this is much more complicated and way cooler than just energy balance, calories in, calories out. No. The biomolecules we ingest into our bodies have unique catabolic metabolic pathways through which they're processed, and those different pathways have different consequences on our biology. And fructose is very, very special. So when fructose gets into the cell, it's processed by an enzyme called ketohexokinase. And this ketohexokinase enzyme is special because, unlike a lot of other enzymes, it doesn't have negative feedback or an off switch. So usually what happens in these sort of pathways is a substrate gets gets acted on by an enzyme, generating a product, and the product can feed back on the enzyme so that the pathway doesn't get out of control. It has a kind of auto-brake set in. This is called negative feedback. But the keto-hexokinase enzyme does not have that negative feedback. It doesn't have the brake. So what ends up happening is you can get the process spinning out of control. And because of what keto-hexokinase does, this can lead to intracellular energy depletion. Specifically, what it's doing is it's taking fructose and it's attaching a phosphate group onto it, taking this functional group called the phosphate, popping it onto fructose. But when it does that, it's actually harvesting a phosphate off of ATP, the energy currency of the cell, and in so doing depletes ATP, depletes intracellular energy. But the story doesn't stop there. No, it gets even more interesting, because when ATP is broken down, it eventually becomes AMP, and then the AMP can be further broken down into an intracellular toxin. Called uric acid. And this has all been demonstrated in the literature. And what uric acid then does is it can cause another enzyme that causes oxidative stress to translocate— move— to mitochondria, the powerhouse of the cell, and actually create oxidative damage at mitochondria. And then as you go down the pathway, what ends up happening is you get buildup of other biomolecules like citrate, which get funneled down alternate pathways and eventually induce de novo lipogenesis, the generation of new fat. So all this in a nutshell: fructose, via its unique metabolism through keto-hexokinase, leads to intracellular energy depletion and eventually damage to mitochondria and de novo lipogenesis, the generation of new fat. So as you can see, this is much, much more complicated than just energy balance. No, fructose has unique metabolic properties that make it metabolically malicious. But not only that, It's been shown in vivo, in living organisms, in particular in mouse models, and you do have to do these experiments in mice because they require, you know, fine-tuned genetic manipulations, but it's been shown in Cell Metabolism, one of my favorite journals, that fructose delivers a one-two punch to metabolism to induce metabolic syndrome. In particular, what they show in this one study is that fructose metabolism in the intestines actually drives intake of more sugar. So eating fructose makes you want to eat more fructose and sucrose, a combination of glucose and fructose, so driving more intake. And separately, fructose metabolism via keto-hexokinase, this enzyme we talked about before, in the liver drives metabolic syndrome. So what you end up with is this vicious cycle whereby fructose, its metabolism in the liver is promoting metabolic syndrome, and its metabolism in the intestine is driving more intake, promoting even more metabolic syndrome, in a terrible vicious cycle. So again, one-two punch, as shown in live organisms, fructose has this unique metabolism that promotes metabolic dysfunction. But now that I've brought you down, I want to lift you back up again, emotionally speaking, and talk to you in Chapter 2 about fructose's good twin, allulose. Technically, allulose is what's called the C3 epimer of fructose. Simply, you can think of it as like kind of if fructose is the left hand, allulose is the right hand. And because the body is very specific to left hand, right hand, it processes allulose very differently. So allulose, it which does taste exactly like fructose to the tongue, but in the body it's not processed by keto-hexokinase, you know, it doesn't really confer calories, and you don't get any of the negative metabolic impacts of fructose. So at absolute minimum, allulose will displace fructose, and so you don't get the negative effects of fructose. But that is only the tip of the iceberg. In addition to displacing fructose in the diet, allulose can have concrete metabolic benefits. On the one hand, at just a very high-level view, it has no glycemic and no insulinogenic response, so it's not spiking your glucose or spiking insulin, which is in contrast to other sweeteners which can actually do so. And here's where things get really interesting: allulose is actually a very potent inducer of the body's incretin hormone GLP-1. And GLP-1, you may have heard that before. You're probably scratching your head thinking now, what Where have I heard of that before, that hormone's name? Well, GLP-1 is the hormone that drugs like Ozempic and Wegovy, those blockbuster weight loss drugs, are now trying to mimic. GLP-1 has certain metabolic benefits, and people, when they take these medications, tend to lose a lot of weight and can have improvements in insulin sensitivity. But pause here and step back and think to yourself, well, what is the rationale for using these medications? Why would we use these medications for obesity?? And to answer that question, I actually want to use the analogy of other hormonal deficient disorders. So if you have hypothyroidism, for example, Hashimoto's, what do you do to treat that? You give back thyroid hormone, you give levothyroxine. Or if you have adrenal insufficiency, what do you do? Your steroids are low, so you give back corticosteroids so you don't have, you know, adrenal crisis and die. Bottom line is, in hormonal deficiencies, you tend to give back hormones. And obesity is a disease in which GLP-1 tends to be deficient. Actually, there are inflammatory cytokines in the gut which damage L-cells, decrease GLP-1 production, and there are T-cells in the gut that can actually sop up GLP-1 in the gut, so it decreases GLP-1 bioavailability to the body in the state of obesity, as has been shown in prior literature. So via these mechanisms, you can actually think of obesity, at least in part, as a GLP-1 deficit. Part of the solution might actually be to give GLP-1 back. I don't think that's the whole solution. I don't think Ozempic is gonna cure the obesity epidemic, but it does make sense from that angle, that if you think of obesity as a GLP-1 deficit, at least in part, and yes, it's more complicated than that, then part of the solution might be augmenting GLP-1 levels, which can be through injection, that's an option, or it can be through promoting the body's own production. Of bioavailable GLP-1. And one way we can do that is through this compound, this molecule, allulose. Allulose, this non-caloric rare sugar, rare natural sugar, is actually a very potent inducer, for whatever reason, of the body's own GLP-1. It can even boost GLP-1 levels in the portal vein after ingestion by fourfold. And, you know, that presumably can have metabolic benefits. Potentially benefits on obesity and metabolic health. Now, it remains to be determined if this translates in large-scale RCTs, which have yet to be conducted, but it stands to reason that it would, right? It just makes sense. I mean, Ozempic works, so why wouldn't boosting your body's own production of the Ozempic hormone do the same? That brings us to Chapter 3: Allulose as a potential solution to the obesity epidemic. And that's a hard thing, honestly, for me to say, 'cause part of me wants to be a purist, but more than that, I'm a pragmatist. So let me lay upon you two hard truths. One is that we aren't going to give up sweet. We as a population are not going to give up sweet anytime soon. It's basically baked in, I could say CRISPR'd into the DNA of our culture to like sweet. So practically, we need to find a way to have our cake and eat it too. To get the refined sugar and the fructose out of our diet and replace it with something, an allulose, seems to make sense. It's a way to reduce the glycemic load of our diet while still having something sweet. So from that angle, I think it's very pragmatic and a potential solution, a potential tool that people can use. And then hard truth 2 to bring back in these weight loss drugs, Ozempic and Wegovy, is whether you're a fan or you're a critic, the reality is, is they're expensive and they're not going to be available to everybody. So even for those who want access to them, if their insurance isn't covering them, then we need other solutions. And I'm not going to say that allulose is as potent as Ozempic, but it does act through the same axis, and it's something that's way more accessible to everyone. If it's in the food supply and displaces fructose, then they have access to it fully based on the foods that they're already consuming. So again, it makes sense from both these pragmatic points of view. With all that said, you know I like to operate on a pretty transparent basis, so what I'm going to do now is plug a particular company, but I'm not plugging this company because I'm going to ask you to buy their product, or even if you did, I'm not going to get any profit from it. So I don't care if you go and— the company is RX Sugar— buy RX Sugar products now or not. That doesn't matter to me. The reason I'm bringing up the company is because I've actually had some time to meet the people behind the company, including the CEO Steve Hanley, and I've been really impressed by the authenticity and the integrity of the company, seeing what they put in to research. And I believe wholeheartedly that Steve and his company are aligned with my mission to make metabolic health mainstream, to improve population health, to get sugar out of the food supply. And they're just coming at it at an orthogonal angle to what I'm doing. I like public education, I'm pursuing medicine, I'm pursuing science, and they're working from an industry angle, which is a complementary angle. As long as our interests are aligned and our interests are squarely focused on improving population health, then we can actually partner. So I think it's worth giving them a plug. And more than that, more than believing in, you know, the business side of the team, I believe in the science team. Steve has done an incredible job putting together a fantastic scientific team. I came on because of the people that were already on: Dominic D'Agostino, Ben Bikman, Professor Richard Johnson. People— these are names you probably know and trust. And they've come together, we've come together as a team because we believe in the mission of getting sugar out of the food supply. In part, this means displacing it with allulose. That is a piece of the puzzle, or at least it can be the piece of the puzzle. With all that, I do want to say this is a company that I think is pretty awesome as an allulose company. I think they're doing innovative things, and I think that they have a high degree of integrity. You don't have to buy their product, but I do think it's worth naming them in order to pick out one big food company among the myriad that is actually finally doing something good and cares about people. And with all that, I want to leave you with a call to action, and again, it's not to buy a product. I'm not asking that of you. What I will ask of you is to share this video, to share information. If you're like me, maybe you don't have any sweet tooth. Maybe you could never have a drop of sweet in the rest of your life and be perfectly happy. That's the way I live. But I think you also know loved ones, family, friends who aren't like that, but who you want to invest in their health. And this can be a foot in the door. Tell them this is a tool, allulose is a tool that they could use to improve their health from where it is, and a tool that they could lean on if they're not gonna get sweet out of their diet, because let's face it, a lot of people aren't. So if you're pro pushing for metabolic health for the population, I think that this is, you know, some content that you should share out there. I think it's content that, you know, if you want sweet in your diet, it can help you, but if not, maybe it can help a loved one. So think about it. Hopefully I dropped some knowledge here that you found interesting, and as always, appreciate feedback.
