The artificial sweeteners in your diet soda or zero-sugar desserts may not be the guilt-free sweets they've been promoted to be. Aspartame, one of the most common sugar substitutes, has been found to trigger increased insulin levels, something that contributes to atherosclerosis, the build-up of fatty plaques in the arteries. The result? Higher levels of inflammation and an increased risk of heart attacks and stroke over time.

Previous studies have noted this connection — that consumption of sugar substitutes leads to increased chronic disorders like cardiovascular disease and diabetes. The new work, done in mice, shows the reason why this happens.

Most chemicals would be quickly washed away as the heart pumps, but CX3CL1 stays glued to the inner lining of blood vessels.

Researchers at the Karolinska Institute in Sweden fed mice food containing 0.15 percent aspartame daily for 12 weeks, an amount roughly equivalent to that of a human consuming about three cans of diet soda each day.

The aspartame-fed mice developed larger and more fatty plaques in their arteries and had higher levels of inflammation than mice not fed an artificial sweetener-infused diet. Both the plaques and inflammation are signs of compromised cardiovascular health.

When the team analyzed the blood of the mice fed aspartame, they found insulin levels surged after aspartame entered their system. This in itself was not a surprise. Our mouths, intestines and other tissues are lined with receptors that trigger insulin release when they detect sugar. What did surprise the researchers was that aspartame, 200 times sweeter than sugar, seemed to trick the receptors into releasing even more insulin.

The sharp rise in nsulin levels fueled the growth of fatty plaques in the mice's arteries, which suggested that insulin may be the key link between aspartame and cardiovascular health. When they looked into exactly how elevated insulin levels led to arterial plaque buildup, the researchers zeroed in on a small protein that plays a role in immune cell signaling, CX3CL1. It became especially active when stimulated by insulin.

CX3CL1 stuck to the lining of blood vessels. “Because blood flow through the artery is strong and robust, most chemicals would be quickly washed away as the heart pumps,” said the study's senior author, Yihai Cao, a researcher in chronic diseases related to blood vessel disorders at Karolinska Institute. “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.”

Artificial sweeteners are in so many of the foods we eat, and so many of us seek them out as calorie-free alternatives to sugar-sweetened beverages and foods, that they could end up having a surprising and outsize negative effect on our health.

Many of these trapped immune cells are known to increase blood vessel inflammation. And sure enough, when researchers eliminated CX3CL1 receptors from one of the immune cells in aspartame-fed mice, the harmful plaque buildup didn't occur, more evidence for CX3CL1's role in aspartame's effects on the arteries, Cao explained.

In addition, given that blood vessel inflammation is involved in stroke, arthritis and diabetes, CX3CL1 may be a potential target for chronic conditions beyond cardiovascular disease. The team hopes to study these possibilities in future research.

Artificial sweeteners are in so many of the foods we eat, and so many of us seek them out as calorie-free alternatives to sugar-sweetened beverages and foods, that they could end up having a surprising and outsize negative effect on our health. As Cao says, “Artificial sweeteners have penetrated almost all kinds of food, so we have to know the long-term health impact.”

The study is published in Cell Metabolism.