Artificial sweeteners have long served as healthier alternatives to sugar, but there is growing evidence that they may pose hidden risks. Of these, Aspartame stands out in a newly published study, a possible factor in the cause of atherosclerosis, in which case the arteries become more severe and narrower due to fat deposits called plaques. The study stems from concerns about the health effects of regular consumption of sugar substitutes, especially as they become increasingly common in foods and beverages for people of all ages.
Scientists led by Professor Yihai Cao of the Karolinska Institute conducted the study. Their findings are published in the Science Journal of Cell Metabolism, which covers research on how the body converts food into energy and regulates its internal systems.
The team found that consumption of aspartame caused a significant increase insulin levels in mice and monkeys. This peak in insulin is not caused by sugar or calories, but by stimulation of a part of the nervous system responsible for digestion and relaxation, called the parasympathetic nervous system. Over time, high levels of insulin can lead to insulin resistance – a condition that no longer responds to insulin and cannot effectively manage blood sugar – and encourages growth and attenuation of arterial fat plaques. Even a small amount of aspartame was enough to trigger these effects, and clear plaque buildup was observed in just a few weeks.
When they looked at the process more closely, the researchers identified key pathways involved in proteins, which are like signals that attract immune cells and their matching receptors that are located on the surface of certain immune cells and receive the signal. The number of these molecules was found to be much higher after rising insulin levels and they appeared to be closely related to inflammation and inflammation and worsening arterial damage. Cao’s team took a step and deleted the receptor’s gene in some immune cells. Aspartame no longer has a destructive effect when they do. “Our findings suggest a promising treatment for atherosclerosis-related diseases that affect the heart and brain,” Professor Cao pointed out.
This study highlights that the effect of aspartame is more than just a sweet alternative to sugar. Sweeteners trigger higher insulin levels, which in turn triggers an immune response to the arterial wall. This makes immune cells more likely to stick to these walls, making the plaque worse and making it more likely to break, which can lead to a heart attack or stroke.
These findings are especially important for those who are already at risk of heart disease. The study shows that aspartame can affect the body in a calories or sugar-free way by causing elevated insulin levels and triggering inflammation. This transforms aspartame from being considered a harmless sweetener to a sweetener worthy of a careful examination. Professor Cao explained: “Aspartame worsens atherosclerosis by a process that is dependent on the release of insulin triggered by the vagus signal, which is independent of blood sugar. The vagus nerve is the main communication pathway between the brain and the digestive system, which can help control functions such as heart rate, digestion and insulin release.
In short, CAO’s research challenged Aspartame as a safe alternative to sugar and introduced new ideas for the treatment of arterio-related diseases. The link between proteins and their receptors seems to play a major role in the kind of inflammation that causes arterial damage. In the future, treatments may be designed to stop the process to prevent plaque from becoming worse. As artificial sweeteners continue to appear in more products, this study adds conversations about how they affect the human system in unexpected ways.
Journal Reference
Wu W., Sui W., Chen S. et al. “Inflammation triggered by the sweetener aspartame exacerbates atherosclerosis through insulin.” Cell Metabolism, 2025; 37(5):1075-1088. doi:
About the Author
Professor Yihai Cao is an internationally recognized biomedical researcher known for his pioneering work in the fields of vascular biology and cancer therapy. He serves as a faculty member at the Karolinska Institute in Sweden and has made a significant contribution to understanding the growth and function of blood vessels, especially in the case of cancer, eye diseases and cardiovascular diseases. His research has played a role in identifying new goals for drug development and strategies to shape diseases associated with abnormal vascular growth. Professor CAO is also affiliated with the University of Science and Technology of Macau and has led several collaborative projects that link basic science to clinical applications. Over his decades of career, he has published widely in high-impact journals and is widely regarded as a leader in the field of angiogenesis and inflammation-related diseases. His work continues to impact global efforts to prevent and treat severe chronic diseases.
