Artificial sweeteners have long been marketed as healthier alternatives to sugar, but growing evidence suggests that they may carry hidden risks. Among them, aspartame stands out in a newly published study as a possible contributor to atherosclerosis, a condition where arteries become harder and narrower because of fatty deposits called plaques. The research arose from concerns about the health effects of regularly consuming sugar substitutes, especially as they become more common in foods and drinks for people of all ages.
Scientists led by Professor Yihai Cao from the Karolinska Institute, conducted the study. Their findings were published in the scientific journal Cell Metabolism, which covers studies on how the body turns food into energy and regulates its internal systems.
The research team discovered that aspartame consumption caused a significant increase in insulin levels in both mice and monkeys. This spike in insulin was not due to sugar or calories but was caused by stimulation of a part of the nervous system responsible for digestion and relaxation, known as the parasympathetic nervous system. Over time, high levels of insulin led to insulin resistance—a condition where the body no longer responds well to insulin and cannot manage blood sugar effectively—and encouraged the growth and weakening of fatty plaques in the arteries. Even small amounts of aspartame were enough to trigger these effects, with clear plaque buildup observed after just a few weeks.
When they looked more closely at the process, the researchers identified a key pathway involving a protein, which acts like a signal that attracts immune cells, and its matching receptor, which sits on the surface of certain immune cells and receives that signal. These molecules were found in much higher amounts after insulin levels rose, and they appeared to be closely linked to the inflammation and worsening artery damage seen in animals given aspartame. Professor Cao’ team went a step further and removed the gene for this receptor in certain immune cells. When they did, aspartame no longer had the damaging effect. “Our findings suggest a promising therapeutic approach for treating atherosclerosis-associated diseases affecting the heart and brain,” Professor Cao noted.
This study highlights that aspartame’s effects go beyond just being a sweet replacement for sugar. The sweetener triggered higher insulin levels, which in turn sparked an immune response in the artery walls. This made it easier for immune cells to stick to and enter these walls, worsening the plaque and making it more likely to break apart—something that can cause heart attacks or strokes.
The findings are especially important for people who are already at risk for heart disease. The study revealed that aspartame can affect the body in ways not related to calories or sugar by causing insulin levels to rise and triggering inflammation. This shifts aspartame from being seen as a harmless sweetener to one that deserves closer examination. “Aspartame worsens atherosclerosis through a process that does not depend on blood sugar but instead relies on insulin release triggered by signals from the vagus nerve,” Professor Cao explained. The vagus nerve is a major communication pathway between the brain and the digestive system that helps control functions like heart rate, digestion, and insulin release.
In conclusion, Professor Cao’s research challenges the common view that aspartame is a safe alternative to sugar and introduces new ideas for treating artery-related diseases. The connection between the protein and its receptor appears to play a major role in the kind of inflammation that leads to artery damage. In the future, treatments may aim to block this process to stop plaques from getting worse. As artificial sweeteners continue to appear in more products, this study adds to the conversation about how they might affect the body’s systems in unexpected ways.
Journal Reference
Wu W., Sui W., Chen S., et al. “Sweetener aspartame aggravates atherosclerosis through insulin-triggered inflammation.” Cell Metabolism, 2025; 37(5): 1075-1088. DOI: https://doi.org/10.1016/j.cmet.2025.01.006
About the Author
Professor Yihai Cao is an internationally recognized biomedical researcher known for his pioneering work in vascular biology and cancer therapeutics. He holds a faculty position at the Karolinska Institute in Sweden and has made substantial contributions to understanding how blood vessels grow and function, particularly in the context of cancer, eye diseases, and cardiovascular conditions. His research has been instrumental in identifying new targets for drug development and in shaping strategies for treating disorders linked to abnormal blood vessel growth. Professor Cao is also affiliated with the Macau University of Science and Technology and leads several collaborative projects that bridge basic science with clinical applications. With a career spanning decades, he has published extensively in high-impact journals and is widely regarded as a leader in the fields of angiogenesis and inflammation-related diseases. His work continues to influence global efforts in the prevention and treatment of serious chronic illnesses.
