Common sugar substitute linked to increased risk of heart attack and stroke

The safety of sugar substitutes is once again being called into question.

Researchers led by the Cleveland Clinic linked the low-calorie sugar substitute xylitol to an increased risk of heart attack, stroke or cardiovascular-related deaths, according to a study published today in the European Heart Journal.

Xylitol is a sugar alcohol that is found in small amounts in fruit and vegetables, and the human body also produces it. As an additive, it looks and tastes like sugar but has 40% fewer calories. It is used, at much higher concentrations than found in nature, in sugar-free gum, candies, toothpaste and baked goods. It can also be found in products labeled “keto-friendly,” particularly in Europe.

The same research team found a similar association last year to the popular sugar substitute erythritol. The use of sugar substitutes has increased significantly over the past decade as concerns about rising obesity rates mount.

“We’re throwing this stuff into our food pyramid, and the very people who are most likely to be consuming it are the ones who are most likely to be at risk” of heart attack and stroke, such as people with diabetes, said lead author Dr. Stanely Hazen, chair of cardiovascular and metabolic sciences at Cleveland Clinic’s Lerner Research Institute.

Many heart attacks and strokes occur in people who do not have known risk factors, like diabetes, high blood pressure or elevated cholesterol levels. The research team began studying sugar alcohols found naturally in the human body to see if the compounds might predict cardiovascular risk in these people.

In the study, the investigators measured the level of naturally occurring xylitol in the blood of more than 3,000 participants after overnight fasting. They found that people whose xylitol levels put them in the top 25% of the study group had approximately double the risk for heart attack, stroke or death over the next three years compared to people in the bottom quarter.

The researchers also wanted to understand the mechanism at work, so they fed xylitol to mice, added it to blood and plasma in a lab and gave a xylitol-containing drink to 10 healthy volunteers. In all these cases, xylitol seemed to activate platelets, which are the blood component that controls clotting, said Hazen. Blood clots are the leading cause of heart attack and stroke.

 “All it takes is xylitol to interact with platelets alone for a very brief period of time, a matter of minutes, and the platelet becomes supercharged and much more prone to clot,” Hazen said.

The next question is what causes naturally-occurring xylitol to be elevated in some people and how do you lower it, said Dr. Sadiya Khan, a cardiologist at Northwestern Medicine Bluhm Cardiovascular Institute and a professor of cardiovascular epidemiology at Northwestern Feinberg School of Medicine who was not involved in the new study.

Much more research needs to be done, said Hazen. In the meantime, he is telling patients to avoid eating xylitol and other sugar alcohols, whose spelling all end in ‘itol.’ Instead, he recommends using modest amounts of sugar, honey or fruit to sweeten food, adding that toothpaste and one stick of gum are probably not a problem because so little xylitol is ingested.

The report had key limitations. 

First, the study of naturally occurring xylitol in people’s blood was observational and can show only an association between the sugar alcohol and heart risk. It does not show that xylitol caused the higher incidence of heart attack, stroke or death.

Nevertheless, given the totality of the evidence presented in the paper, “it’s probably reasonable to limit intake of artificial sweeteners,” said Khan. “Perhaps the answer isn’t replacing sugar with artificial sweeteners but thinking about more high quality dietary components, like vegetables and fruits, as natural sugars.”

Artificial sweeteners shouldn’t be difficult to avoid, said Joanne Slavin, PhD, RDN, a professor of food science and nutrition at the University of Minnesota-Twin Cities. They are listed on the ingredient list of packaged goods.

“Would I say never eat xylitol?” asked Slavin, who had no connection to the study. For some people who struggle to reduce sugar in their diet, sugar substitutes are one tool, and it comes down to personal choice, she said. 

While Slavin found the study interesting and cause for some concern, she noted that sugar alcohols are expensive and are generally used in very small amounts in gum and sugar-free candies.

Another limitation of the study is that the participants whose xylitol levels in the blood were measured were at high risk for or had documented heart disease, and so the results may not apply to healthy individuals.

Still, many people in the general public share the characteristics of the study participants, said Hazen. 

“In middle-aged or older America, it’s common to have obesity and diabetes or high cholesterol or high blood pressure,” he said.