Xylitol Sugar Substitute Linked to Higher Risk of Heart Attack, Stroke, and Cardiovascular Deaths, Study Says

The safety of sugar substitutes is once again under scrutiny.

Research circulated today in the European Heart Journal by researchers from the Cleveland Clinic links the low-calorie sugar substitute xylitol to a higher risk of heart attack, stroke, and cardiovascular-related deaths.

Study Shows Xylitol Possess Higher Risk to Humans

Xylitol, a sugar alcohol found in small amounts in fruits and vegetables and produced by the human body, looks and tastes like sugar but contains 40% fewer calories.

It is used in high concentrations in sugar-free gum, candies, toothpaste, baked goods, and products labeled "keto-friendly," particularly in Europe.

Last year, the same team found a similar connection with the popular sugar substitute erythritol. The use of sugar substitutes has risen essentially over the past decade due to issues about rising obesity rates.

"We're incorporating these substances into our diets, and those most likely to consume them are at increased risk," said lead author Dr. Stanely Hazen, chair of cardiovascular and metabolic sciences at Cleveland Clinic's Lerner Research Institute.

Heart attacks and strokes regularly happen in people without known risk factors like diabetes, high blood pressure, or raised cholesterol levels.

The research team inspected sugar alcohols discovered naturally in the human body to identify if these compounds might cause cardiovascular danger in these people.

In the study, the researchers measured naturally occurring xylitol levels in the blood of over 3,000 participants after overnight fasting.

They found that people with xylitol levels in the top 25% of the study group had roughly double the risk of heart attack, stroke, or death over the next three years compared to those in the bottom quarter.

To recognize the fundamental mechanism, the researchers administered experiments by feeding xylitol to mice, adding it to blood and plasma in the lab, and giving a xylitol-containing drink to 10 healthy volunteers.

In all cases, xylitol appeared to activate platelets, the blood components responsible for clotting. Blood clots are the primary cause of heart attacks and strokes, said Hazen.

"It only takes a brief interaction with xylitol to make platelets much more prone to clot," Hazen explained.

The next question is why naturally occurring xylitol levels are elevated in some people and how to reduce them, said Dr. Sadiya Khan, a cardiologist at Northwestern Medicine Bluhm Cardiovascular Institute and a professor at Northwestern Feinberg School of Medicine, who was not involved in the study.

Much more research is needed, said Hazen. In the meantime, he suggests patients refrain from xylitol and other sugar alcohols, which typically end in 'itol.'

Instead, he advises using modest amounts of sugar, honey, or fruit to sweeten food, noting that toothpaste and one stick of gum are possibly safe due to the lesser amount of xylitol consumed. The report did have key limitations.

Xylitol Levels in Blood Linked to Heart Risk

Firstly, the observational study of naturally occurring xylitol in blood can only show an association with heart risk, not causation.

Despite this, given the overall evidence, "it's probably reasonable to limit intake of artificial sweeteners," said Khan. "Perhaps the solution is not replacing sugar with artificial sweeteners but considering higher quality dietary components, like vegetables and fruits, as natural sources of sugar."

Avoiding artificial sweeteners shouldn't be difficult, according to 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 was not connected to the study. For some people, sugar substitutes are a tool to reduce sugar intake, and it comes down to personal choice, she said.

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

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

However, many people in the general public share characteristics with the study participants, said Hazen.

"In middle-aged or older America, it's common to have obesity, diabetes, high cholesterol, or high blood pressure," he said.