The Popular Sugar Substitute Xylitol Could Have Some Major Heart-Health Risks

Losing weight is one the best ways to lower your risk of heart disease, and cutting back on sugar can contribute to that. But sweeteners that mimic the taste of sugar with fewer—or no—calories could be increasing, rather than decreasing, the risk of some heart events.

In a study published Thursday in the European Heart Journal, an international group of researchers led by a team at the Cleveland Clinic report that higher levels of xylitol, a sugar substitute found in candy and even toothpaste, are linked to a higher risk of heart attack, stroke, and death.

The study included more than 3,000 people in the U.S. and Europe, about half of whom had a History of heart disease, and almost all of whom had at least a few risk factors for heart disease. They were followed for several years. The researchers measured levels of xylitol in participants' blood after an overnight fast, and found that those with the highest levels had a two-fold greater risk of having a heart attack, stroke, or dying over three years compared to those with the lowest levels.

To further understand the connection between xylitol and heart events, the scientists then injected xylitol in mice and analyzed what effect the chemical had on the Animals’ cardiovascular system. Xylitol increased clotting in the blood by triggering the activation of platelets. The researchers confirmed this mechanism by giving people both a xylitol-based and a glucose-based beverage to drink, and they found that xylitol levels jumped 1000 fold in the plasma immediately after they drank the xylitol beverage, along with levels of clotting factors, but not after they consumed the glucose beverage.

Read More: Why Heart Disease Research Still Favors Men

“Even in people who did not have a History of heart disease, xylitol levels still predicted future cardiac events,” says Dr. Stanley Hazen, chairman of cardiovascular and metabolic Sciences at the Cleveland Clinic and senior author of the paper.

Hazen says xylitol should be considered similar to cholesterol when it comes to heart disease. Like cholesterol, it's made in the body, and people have varying levels of the chemical in their blood. But consuming more xylitol as a sugar substitute in food or drinks could be increasing any baseline risk people already have for clotting in the blood. In the study, the levels the team recorded likely reflected baseline levels of xylitol rather than xylitol from the diet, since the chemical clears the body in four to six hours, and the volunteers had fasted overnight.

“The whole purpose of this research is to find pathways that contribute to heart disease beyond the traditional risk factors like cholesterol, high blood pressure, and diabetes,” says Hazen. “And xylitol is one of them.”

This is the second potential new risk factor that Hazen and his team identified; last year, the group found similar increased risk among people with higher levels of another sugar substitute, erythritol, in their blood. Xylitol and erythritol are considered polyols, or sugar alcohols, and both occur in nature, unlike some artificial sweeteners—including aspartame, sucralose, and saccharin—that are synthetic. While the American Heart Association doesn't specifically address xylitol, it advises that for heart Health, people avoid sugar and opt for low-calorie or no-calorie options instead, including ones that contain erythritol.

“I think it is much more prudent to avoid those and be more judicious about the amount of sugar you use,” says Hazen. “The very people who are most at risk—those who are diabetic, obese or have metabolic syndrome—are the ones who are inadvertently reaching for an unhealthy option. I am absolutely convinced that sugar alcohols are a risk for cardiovascular disease based on all of the clinical and mechanistic data we are seeing.”

Read More: What It Means if You Have Borderline High Cholesterol—And What to Do About It

Hazen is particularly concerned because in his studies, the increased risk is larger than that associated with high cholesterol levels. The U.S. Food and Drug Administration considers artificial sweeteners to be safe in food and beverages, but the latest results suggest more research is needed to better understand the way they affect heart disease. Hazen hopes this early work will seed additional studies that could eventually lead to a test for xylitol and erythritol levels, and even a drug treatment similar to the statins that address cholesterol.