New Study: Aspartame Causes Heart Disease – Bad News for Diet Coke

A groundbreaking new study reveals that even low doses of aspartame may contribute to heart disease. If you’re serious about your health, you'll read this brief letter...

A groundbreaking new study, published 2 days ago in Cell Metabolism, reveals that even low doses of aspartame may contribute to heart disease. If you’re serious about your health, it’s worth considering alternatives. I realize this is a big claim—so let’s break it down.

Background

Studies have already linked artificial sweeteners to cardiovascular disease. However, epidemiological studies have limitations and cannot establish a cause-effect relationship. Conducting a long-term human trial to track heart disease progression isn’t feasible, so researchers turned to animal models to better understand how aspartame may contribute to heart disease. This study examined both mice and monkeys.

Dose: A common question: how much aspartame was used? The primary dose in this study was 0.15% aspartame, roughly equivalent to consuming ~3 Diet Cokes per day in humans.

Aspartame Causes Cardiovascular Disease in Mice

Feeding mice aspartame caused a dose-dependent acceleration of atherosclerotic plaque development.

There was also a higher number of inflammatory cells in the plaques.

This occurred without an increase in total or LDL cholesterol.

Aspartame Increases Insulin and Causes Insulin Resistance

Researchers found that aspartame increased insulin levels in a dose-dependent manner (A) and caused insulin resistance, as measured by glucose and insulin tolerance tests (B-C). Remarkably, the effects of aspartame on insulin resistance were even greater than those of sucrose (table sugar, red vs blue bars).

Similar results were observed in monkeys (D-E), where aspartame consumption led to a significant spike in insulin levels, suggesting these effects generalize to primates.

Aspartame Increases Insulin by Stimulating the Vagus Nerve

Researchers found that aspartame triggers insulin release by stimulating the vagus nerve, which contains numerous sweet receptors. Interestingly, severing the vagus nerve completely protected against aspartame-induced plaque development.

Aspartame, Insulin, and CX3CL1

But HOW does aspartame-induced insulin resistance lead to plaque development?

First, it's important to understand that plaque formation involves interactions between immune cells and the endothelial cells lining the arteries. These interactions rely on adhesion molecules—proteins that act like molecular baseball gloves, catching passing immune cells.

Researchers found that insulin, including insulin spikes triggered by aspartame, increases levels of a key adhesion molecule called CX3CL1.

Thus, the proposed mechanism is as follows: Aspartame increases insulin and insulin resistance → this raises CX3CL1 levels → which enables immune cells to invade the artery walls, accelerating plaque formation.

Does This Apply to Humans?

Sounds 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 say, “no.”

This certainly diverges from the mouse and even monkey results and should, perhaps, offer some reassurance.

However, there are a couple catches.

The methods and data are mixed, making the cumulative results ‘fuzzy’ to interpret. What was the dose given, and in what context? A small dose given in the context of a 60% carb meal may have an effect, but one that’s subsumed by other stimuli.

A teaspoon of sugar in a bowl of pasta may not create a detectable change in blood sugar. A rock thrown into stormy waters may not create visible ripples. You get the idea. There can be a signal-to-noise issue.

Furthermore, metabolic context might 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 – since, if Diet Coke is going to harm you, it’s going to be from routine use… not a single Diet Coke a week.

With respect to this question, of chronic use, there are more data suggesting harm in humans, including increased insulin resistance in studies in persons with diabetes and – speaking more broadly – insulin resistance caused by artificial sweeteners through longer-term changes in the microbiome. The landmark study that comes to mind actually looked at saccharine; but the point remains the same: there were clearly some responders (red) and non-responders (black), i.e. there were those who had marked increasing insulin resistance, as measured by impaired performance on an oral glucose tolerance test (OGTT), with sweetener use and those who did not. And this effect took about a week to manifest.

At a high-level, my impression of the human data are they are a bit murky.

They’re concerning, but not conclusive given a diversity of methods and results. Therefore, I will not claim to be certain these data translate to humans. But unless you personally are getting a set of serial post-aspartame insulin levels, acutely and chronically, I’d say you’re still rolling the dice.

Conclusion: You Do You

At the end of the day, you do you. I do not 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. Your choices are your own. But to make the informed choice you need the data.

So, here are the new data: This study provides experimental evidence that even low doses of aspartame can contribute to heart disease, insulin resistance, and inflammation through vagus nerve activation and increased CX3CL1, at least in animal models. These findings align with previous epidemiological studies linking artificial sweeteners to cardiovascular disease.

Do we know for certain this mechanism applies in humans? No. So, ask yourself, what’s Diet Coke worth to you? How does the risk/reward ratio balance in your life. In mine, water is just dandy. But I’m not you.

The Aspartame Math (*Updated*)

For context, upon publication of this manuscript in Cell Metabolism, several sources were reporting the human dose equivalent of the 0.15% aspartame dose used in this study was three diet sodas.

From: NY Post

From: Medical News Today

However, these sources did not show their math. For this letter, I wanted to verify this conversion independently. Unfortunately, this seems to have created more confusion and distraction than I anticipated, as there are different ways to do this calculation given assumptions about daily water intake, adjustments for body surface area vs body mass, or even attempts to adjust for metabolic rate. As far as I’ve seen, most calculations produce figures in a 3-11 Diet Coke ‘range’ for the 0.15% aspartame dose. Of course, there was a biological effect for the 0.05% dose too, which would bring the ‘11’ figure down to 3 and two-thirds. And, there was an effect in the acute study in which mice were given 200 uL of aspartame solution. Given the diversity of calculations and the distraction this seems to have caused, suffice to to say, there is potential harm of doses that humans can and do consume. And, of course, the cost of eliminating aspartame from your life is zero, metabolically speaking. So, as I said, take these data from what they are and make your own choice.