Pour Decisions: Why I Won't Touch This Common Ingredient

Aspartame may cause heart disease? This could be bad news for Diet Coke lovers. Let's dig into it. A groundbreaking new study reveals that even at low doses, aspartame may contribute to heart disease. So if you're serious about your health, it's worth considering alternatives. Now, I realize this is a big, big claim, so let's break it down in more detail. But first, for background, studies have already linked artificial sweeteners to cardiovascular disease. However, epidemiological studies have limitations and cannot establish a cause-effect relationship. And conducting longer-term human randomized control trials to track heart disease progression, it's just not feasible. You can't do that 20-odd year study. So research turns to animal models to better understand how aspartame, this sweetener in Diet Coke, and many other foods may contribute to or even cause heart disease. In this study, the researchers examined both mice and monkeys. And to strike this topic on the head because I know it will be a big question, what about dose? How much aspartame was actually used in this study? The primary dose used in the study was 0.15% aspartame, which is the rough equivalent of consuming 3 Diet Cokes per day as a human. And if you want the math on this, you can check the video notes where I go through the math. Now, before I move on to the data, let me say upfront, I know these data are going to provoke emotions. A lot of people love Diet Coke. But hear me out, because while the thrust of this video is about aspartame, there are deeper lessons about metabolism and science that we will unravel through looking at this fascinating mechanism. With that, On to the data. The researchers first showed that aspartame causes cardiovascular disease in susceptible mice. Yeah, I know, people are commenting, but mice weren't designed to drink Diet Coke. Newsflash: neither were humans. Anyway, let me rub that chip off my shoulder and show you the results. Here they are. You can see a clear dose-dependent increase in atherosclerotic plaque formation in mice given the aspartame. And inside the atherosclerotic plaques, there were also more inflammatory cells called macrophages, which we'll get into in more detail in a little bit. But you can see that indicated here by the green stain. More green stain means more macrophages in the plaque. And if you're interested, the aspartame did not actually change total or LDL cholesterol levels. So that's not super relevant here. So based on these first results, we can see clearly aspartame increased plaque development and inflammatory cell invasion, at least in mice. We then ask, how? Enter insulin and insulin resistance. The researchers found that aspartame increased insulin levels in a dose-dependent manner, so more more aspartame, more insulin, and increased insulin resistance as measured by glucose tolerance tests and insulin tolerance tests. Remarkably, the effects of aspartame on insulin resistance, at least in mice, were even greater than those of sucrose, table sugar. And similar results were observed in monkeys, where aspartame consumption led to a significant spike in insulin levels, suggesting these effects could generalize to primates. And of course, humans are primates. And I know you're wondering about the direct human data. Hold on to your diabetic horses, we will get there, but first let me finish this data story. The mechanism by which aspartame increases insulin is by stimulating the vagus nerve, the 10th cranial nerve, the wandering nerve. Which contains numerous sweet receptors, including associated with its neuropod cells. And I do a deeper dive on these neuropod cells in this video. So if you want that deep dive, check out this video. Now, if we agree that aspartame can induce acute and/or chronic increases in insulin by actions on the nervous system, the vagus nerve, and that this contributes to plaque development and inflammatory cell invasion, at least in animal models, we should next ask how. How does aspartame-induced insulin resistance lead to plaque development? What's the connection there? First, it's important to understand that atherosclerotic plaque formation involves the interaction between immune cells and the endothelial cells lining arteries, lining blood vessels. These interactions rely on something called adhesion molecules, which are proteins that act kind of like molecular baseball gloves catching passing immune cells, which in this analogy are the baseballs. And the researchers found that insulin, including insulin spikes triggered by aspartame, can increase levels of a key adhesion molecule called CX3C1. CL1, and this leads to immune cell invasion and inflammation in the artery wall. Thus, summarizing at a high level, the proposed mechanism is as follows: aspartame increases insulin and insulin resistance. This raises CX3CL1 adhesion molecule levels, which enables immune cells to invade the artery wall, accelerating plaque formation. Sounds interesting, kinda scary, and maybe even compelling, right? But how do you know if these data really matter to you in all your Homo sapiens glory? Well, we could ask the question a few ways. First, leaning into the mechanism. Does aspartame increase insulin acutely in humans? Generally, the data actually say no. This certainly diverges from the mouse and even the monkey results in this study and should perhaps offer some reassurance to diet Coke lovers out there. See, not all doom and gloom. However, there are a couple catches. First, the methods and data broadly are mixed, making the cumulative results in the literature fuzzy to interpret. What was the dose given? And in what context? A small dose of aspartame given in the context of a 60% carb meal may have an effect, but one that's subsumed by the other stimuli. So a teaspoon of sugar, by analogy, in a bowl of pasta may not create a detectable change in blood sugar doesn't mean the teaspoon of sugar doesn't actually have any effect on blood sugar. So you get the idea, there can be a signal-to-noise issue for one point. Furthermore, metabolic context might really matter. Is a person lean and fit or living with diabetes and obesity? But to me, the more pertinent question has to do with chronic use. Of aspartame. Since if Diet Coke and similar foods are going to harm you, it's not going to be from a single Diet Coke per week, it's going to be from routine use. And with respect to this chronic use, there are more data suggesting harm in humans, including increased insulin resistance in epidemiological studies, which of course have their limitations, especially in people with diabetes, and speaking more broadly, insulin resistance caused by artificial sweeteners through longer-term changes, including in the microbiome. The landmark study that actually is coming to mind focused on saccharin primarily, but the point remains the same. There were clearly some responders to artificial sweeteners and non-responders. In other words, there were those who had a marked increase in insulin resistance, as measured by things like an oral glucose tolerance test, with artificial sweetener use. And those who did not. And this effect took about a week to manifest. Again, at a high level now, zooming out, my impression of the human data are that they are a bit murky. They're concerning to me, but not conclusive, given a diversity of methods and results. Therefore, I will not claim to be certain that these data I just shared from this new paper translate to humans. But unless you personally are getting a set of serial post-aspartame insulin levels acutely and chronically, which I don't suspect you are, I'd say you're still rolling the dice when you have Diet Coke. At the end of the day though, you do you. I don't think a Diet Coke per week will clog your arteries, and I personally don't give a flying fructose what you eat. Slam fried Oreos and crazy bagels daily for all I care. You're an adult. Your choices are your own. But to make the informed choice, the best choice for you, you need data. So here are the new data. This study provides experimental evidence that even at low to moderate doses, aspartame can contribute to heart disease, insulin resistance, and inflammation through vagus nerve activation and increased Cx3Cl1 levels, at least in animal models, which comes with its caveats. These findings do align with previous human epidemiological studies linking artificial sweeteners to cardiovascular disease, and there may be other mechanisms at play as well. Again, do we know for certain the mechanism described in this video and in this paper apply to humans? No. At the end of the day, you make your own choices. If a weekly Diet Coke is your guilty pleasure, fine. But if you're guzzling the stuff every day, you have to ask yourself, is the risk worth it? What's the actual upside of drinking this? What's the risk-to-reward ratio? And could I simply swap it for something better? For me personally, the answer is easy. Water works just fine. But I'm not you. So, in conclusion, if you found this video helpful, hit that like button and subscribe for more deep dives into the science of nutrition and metabolism. I'm not here to judge you, I'm just here to share data. I really love doing so, and I hope that comes through. And let me know in the comments, will this research change how you feel about aspartame? Or are you sticking with Diet Coke? Stay curious, stay nuanced. Hope you enjoyed this video.