HQ Team
February 21, 2025: Artificial sweeteners, long used as low-calorie alternatives to sugar, are known to cause a number of health conditions, including gastrointestinal problems, neurological symptoms, diabetes, and cardiovascular disease (CVD). So much so that the World Health Organization has recommended not to use the products to control body weight or cut the risk of non-communicable diseases in adults or children.
Confiming the risks associated with artificial sweeteners, a new mice study has found that aspartame may contribute to CVD risk. The study found that aspartame triggered spikes in the release of insulin— the hormone that controls blood glucose — leading to the build-up of fatty plaques, or atherosclerosis
For the study, the researchers fed mice food containing 0.15% aspartame daily — the equivalent of a person drinking three cans of diet soda a day — for 12 weeks. Another group was fed food minus aspartame, and another group was fed a diet containing 15% sugar (sucrose).
Insulin spike
The mice fed aspartame-laced food showed a spike in insulin levels within 30 minutes of consumption. There are receptors lining the mouths and guts of mice and people that detect sugar levels and guide the release of insulin post-sugar intake. It was noticed that as aspartame is 200 times sweeter than sugar, the receptors were tricked into releasing higher levels of insulin.
The insulin levels remained high for a long time, suggesting that long-term consumption of this artificial sweetener may lead to insulin resistance, which greatly increases the risk of type 2 diabetes.
After 4 weeks of the aspartame diet, the mice started to develop atherosclerotic plaques in their arteries. In mice fed sucrose, the plaques did not develop until the 12-week point, although these mice did gain weight and fat.
CX3CL1 immune signal
Insulin acts on the different types of cells in the body, including muscle cells, adipose (fatty) tissue, liver, brain, and endothelial cells lining the blood vessels. There is research to show that insulin resistance can lead to the malfunctioning of these endothelial cells, which this study seems to further endorse.
Artificial sweeteners, particularly aspartame, trigger insulin spikes via parasympathetic activation, leading to chronic hyperinsulinemia. This affects CX3CL1, an immune signal that promotes arterial plaque formation
Senior author Yihai Cao, from the Karolinska Institute in Sweden, said that the discovery of CX3CL1 was unexpected, but might help the development of more effective drugs:
“Because [CX3CL1] is transmembrane protein, it will be locked on the endothelial cells lining in the inner layer of blood vessels. In this way, it can trap moving inflammatory cells in the blood.”
“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.”
Yi explained why replacing sugar with artificial sweeteners might not decrease the risk of metabolic disorders: “This mechanism could explain why diet soda drinkers, despite avoiding sugar, still show a heightened risk for metabolic diseases. Chronic insulin elevation is a well-known risk factor for insulin resistance and type 2 diabetes, and the inflammatory response triggered by CX3CL1 may contribute to long-term cardiovascular damage.”
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.
The team plans to conduct human trials in the future. The team says that further research can look into CX3CL1’s role in other chronic conditions such as stroke, arthritis, and diabetes.
There is already research that indicates that artificial sweeteners can kill off antibiotic-resistant bacteria. These additives also reduce the bacteria’s resistance to commonly used antibiotics. Another artificial sweetener, sucralose, is “genotoxic” as it breaks up the DNA and causes damage to the gut lining, resulting in a ‘leaky gut,’ a study revealed.
The full study can be accessed in the journal, Cell Metabolism.
