Artificial sweeteners are everywhere, marketed as a healthier alternative to sugar, but new research suggests they may not be so harmless.
A team of scientists discovered that aspartame, a common sugar substitute, triggers an insulin surge that contributes to arterial plaque buildup, inflammation, and potentially life-threatening cardiovascular issues.
The Hidden Impact of Artificial Sweeteners
Artificial sweeteners, found in everything from diet soda to zero-sugar ice cream, are often marketed as a guilt-free way to enjoy sweetness. However, new research set to be published today (February 19) in Cell Metabolism suggests that aspartame, one of the most widely used sugar substitutes, may have negative effects on vascular health.
A team of cardiovascular experts and clinicians discovered that aspartame increases insulin levels in animals, which in turn contributes to atherosclerosis — the buildup of fatty plaque in the arteries. Over time, this process can lead to increased inflammation and a higher risk of heart attacks and strokes.
The study was sparked by a casual observation during a project meeting. “One of my students was sipping on this sugar-free drink, and I said, ‘Why don’t you look into that?’” recalls senior author Yihai Cao, who studies chronic diseases related to blood vessel disorders at Karolinska Institute in Sweden.
While past research has associated artificial sweeteners with an increased risk of conditions like cardiovascular disease and diabetes, the biological mechanisms behind these effects were not well understood — until now.
Testing Aspartame’s Effects on Cardiovascular Health
For this study, the researchers fed mice daily doses of food containing 0.15% aspartame for 12 weeks—an amount that corresponds to consuming about three cans of diet soda each day for humans. Compared to mice without a sweetener-infused diet, aspartame-fed mice developed larger and more fatty plaques in their arteries and exhibited higher levels of inflammation, both of which are hallmarks of compromised cardiovascular health.
When the team analyzed the mice’s blood, they found a surge in insulin levels after aspartame entered their system. The team noted that this wasn’t a surprising result, given that our mouths, intestines, and other tissues are lined with sweetness-detecting receptors that help guide insulin release. But aspartame, 200 times sweeter than sugar, seemed to trick the receptors into releasing more insulin.
The Role of CX3CL1 in Arterial Inflammation
The researchers then demonstrated that the mice’s elevated insulin levels fueled the growth of fatty plaques in the mice’s arteries, suggesting that insulin may be the key link between aspartame and cardiovascular health. Next, they investigated how exactly elevated insulin levels lead to arterial plaque buildup and identified an immune signal called CX3CL1 that is especially active under insulin stimulation.
“Because blood flow through the artery is strong and robust, most chemicals would be quickly washed away as the heart pumps,” says Cao. “Surprisingly, not CX3CL1. It stays glued to the surface of the inner lining of blood vessels. There, it acts like a bait, catching immune cells as they pass by.”
Blocking CX3CL1 to Prevent Harmful Effects
Many of these trapped immune cells are known to stoke blood vessel inflammation. However, when researchers eliminated CX3CL1 receptors from one of the immune cells in aspartame-fed mice, the harmful plaque buildup didn’t occur. These results point to CX3CL1’s role in aspartame’s effects on the arteries, says Cao.
Looking ahead, Cao and his team plan to verify their findings in humans. Cao also foresees CX3CL1 as a potential target for chronic conditions beyond cardiovascular disease, given that blood vessel inflammation is involved in stroke, arthritis, and diabetes.
“Artificial sweeteners have penetrated almost all kinds of food, so we have to know the long-term health impact,” says Cao.
Reference: “Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation” by Weijie Wu, Wenhai Sui, Sizhe Chen, Ziheng Guo, Xu Jing, Xiaolu Wang, Qun Wang, Xinshuang Yu, Wenjing Xiong, Jiansong Ji, Libo Yang, Yuan Zhang, Wenjing Jiang, Guohua Yu, Shuzhen Liu, Wei Tao, Chen Zhao, Yun Zhang, Yuguo Chen, Cheng Zhang and Yihai Cao, 19 February 2025, Cell Metabolism.
DOI: 10.1016/j.cmet.2025.01.006
This work was supported by funding from the Swedish Cancer Foundation, the Strategic Research Areas–Stem Cell and Regenerative Medicine Foundation, the Karolinska Institute Foundation, the NOVO Nordisk Foundation, the Swedish Research Council, the Swedish Research Council, the National Natural Science Foundation of China, the Hong Kong Centre for Cerebro-Cardiovascular Health Engineering, the Horizon Europe grant-PERSEUS, Key R&D Program of Shandong Province, the National Natural Science Foundation of China, and State Key R&D Program of China.
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3 Comments
Aspertame – is two amino acids – that humans get in every protein food they eat.
Aspartic acid and Phenylalanine. – Phenylalanine is divided in to Melanine – that you use for your skin color and Tyrosine – which is then turned into your main neurotransmitter – which allows you to think.
Thinking is good –
The sky is not falling –
See when humans hear stuff, they go ahead and believe it is true – and that’s what screws everybody up.
Here’s my advice, which I know you’ve been waiting for me to get around to: Use your own brain. It is as good as anyone else’s – but ya got to use it – and you got to use yourself. Just like lifting weights, you can’t think others will do it for you – brains do not work like that.
I’ve been drinking diet soda 8n large quantities since around age 12 (now 50). Most of had aspartame in it. I also had abnormally great cholesterol (somewhere around 78 bad cholesterol and a crazy 68 good cholesterol with excellent triglycerides. In fact the risk level was soow on the combined formula, I was 3 points from being off the bottom of the risk chart. I had been 3-4 dozen eggs a week on a low carb diet for 5 months I lost 50 pounds in 3 months, but then it stabilized so after 5 months I stopped). The test was nearly a year later so if eggs increased my good cholesterol, the effects lasted. I’ve had great to very good cholesterol ever since. That was like 22 years since that first test.
However, a recent CT scan looking for kidney stones (none found) picked up arteriosclerosis in my aorta area. It wasn’t clear how much by the report and my doctor dismissed it as not even the right test for such things and my blood work was almost perfect despite being overweight and diabetes running on one side of the family. So now I’m wondering about the diet sodas. I hate plain water and virtually ALL flavored drinks that aren’t sugar based (diabetes, insulin spikes and tons of empty calories there instead) have artificial sweeteners.
Now maybe sucralose is better for you than aspartame, but it’s rarely in soda because it doesn’t taste right. They finally have diet sodas that taste very close to the sugar ones (Coke Zero Sugar since the last update a half decade ago tastes almost exactly like Classic Coke, which is now just Coke again (Diet Coke is nasty and it was the basis for Coke’s failed “Coke II” product back in the 1980s that lead to the Classic Coke label for so many years despite the fact Coke II and Coke III had disappeared by the mid 1990s.
So the problem, like most things is the lack of an adequate substitute product. I also can’t possibly know for certain that plaque on the CT Scan is from diet soda. I’ve had trouble with my weight since my mid-20s. My dad’s side has some weird gene where we’re skinny as heck until our 20s or 30s and then it just piles on unless you eat like 1500 calories a day (even at 250 pounds), making it incredibly difficult to keep the weight off because you’re always hungry at that calorie level. I’ve taken to eating once a day (not good I know) just to keep a meal decent while keeping the total calorie count down. That feels less miserable than eating next to nothing and always feeling hungry, but it’s harder on your body too. It’s like the mitochondria just dont work right anymore.
I’ve tried acetylcysteine plus glycine which supposedly helps restore mytochondria but I don’t see any difference in metabolism (my gray hair has been darkening though to dark grey which almost looks normal along with Nisoral shampoo restoring my thinning hair in the front to normal thickness). Sometimes, it pays to read health articles on chemical supplements. Some actually do work.
This article is misleading. The mice work was done in transgenic (mutant) mice that spontaneously develop atherosclerosis, not normal WT mice. These mice are very compromised. Also, they did work in monkeys that is very suspect. We know from multiple human studies that artificial sweeteners do not cause a large insulin spike like sucrose does. And yet they saw exactly equal spikes with the artificial sweeteners and with sugar. IF true, it’s not transferable to humans. But I suspect this is a false result. This whole article is suspect.