(CNN) — A low-calorie sweetener called xylitol used in many reduced-sugar foods and consumer products such as gum and toothpaste may be linked to nearly twice the risk of heart attacks, stroke and death in people who consume the highest levels of the sweetener, a new study found.

“We gave healthy volunteers a typical drink with xylitol to see how high the levels would get and they went up 1,000-fold,” said senior study author Dr. Stanley Hazen, director of the Center for Cardiovascular Diagnostics and Prevention at the Cleveland Clinic Lerner Research Institute.

“When you eat sugar, your glucose level may go up 10% or 20% but it doesn’t go up a 1,000-fold,” said Hazen, who also directs the Cleveland Clinic’s Center for Microbiome and Human Health.

“Humankind has not experienced levels of xylitol this high except within the last couple of decades when we began ingesting completely contrived and sugar-substituted processed foods,” he added.


Worrisome blood clots occur

In 2023, the same researchers found similar results for another low-calorie sweetener called erythritol, which is used as a bulking sugar in stevia, monkfruit and keto reduced-sugar products.

Additional lab and animal research presented in both papers revealed erythritol and xylitol may cause blood platelets to clot more readily. Clots can break off and travel to the heart, triggering a heart attack, or to the brain, triggering a stroke.

In the new study  on xylitol, “differences in platelet behavior were seen even after a person consumed a modest quantity of xylitol in a drink typical of a portion consumed in real life,” said Dr. Matthew Tomey, a cardiologist at Mount Sinai Fuster Heart Hospital in New York City, who was not involved in the study.

“These experiments are interesting but alone do not prove that platelet abnormalities are to account for a linkage between xylitol and clinical events,” said Tomey, who is also an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai.

Some 61% of American adults will have cardiovascular disease by 2050, according to a recent prediction by the American Heart Association. Reducing clotting activity is a key treatment used by cardiologists, so any additional clotting in platelets is a bad sign, said Dr. Andrew Freeman, director of cardiovascular prevention and wellness at National Jewish Health in Denver.

“When someone has a heart attack, we give them aspirin or drugs like clopidogrel, or Plavix, to counter platelet activity.  These sugar alcohols appear to be enhancing platelet activity, which is concerning,” said Freeman, who was not associated with the new research.

“This is another warning we ought to switch to water, with a close second being unsweetened tea or coffee,” he said.

Carla Saunders, president of the Calorie Control Council, an industry association, told CNN that the study results “are contrary to decades of scientific evidence substantiating the safety and efficacy of low-calorie sweeteners such as xylitol by global health and regulatory ‎agencies. These findings are a disservice to those who rely on alternative sweeteners as a tool to improve their health.”


What is xylitol?

As sweet as sugar with less than half the calories, xylitol is often used in sugarless gum, breath mints, toothpaste, mouthwash, cough syrup and chewable vitamins. It is frequently added in larger quantities to candy, baked goods, cake mixes, barbecue sauces, ketchup, peanut butter, puddings, pancake syrup and more.

Xylitol is a sugar alcohol, a carbohydrate found naturally in foods such as cauliflower, eggplant, lettuce, mushrooms, spinach, plums, raspberries and strawberries. However, the amount of xylitol found in such natural sources is tiny, Hazen said.

“If you actually do the calculation, it literally takes a tonnage of fruit to be equivalent to one diabetic cookie that can have like nine grams of xylitol, which is a typical label amount,” he said. “It would be like eating salt at the level of a salt lick.”

For commercial use, however, xylitol is made from corncobs, birch trees or genetically engineered bacteria.

“It’s sold as a so-called natural sweetener, and because xylitol doesn’t spike blood sugar levels, it’s also marketed as low carb and keto friendly,” Hazen said.

Many professional associations also recommend xylitol as a sugar substitute for patients with obesity, diabetes or prediabetes to improve glycemic control, he added.

“Yet people at risk for diabetes are among the most vulnerable for clotting events,” he said. “We’re targeting the wrong people.”

Exposure has increased over the last two decades, Hazen said, because the US Food and Drug Administration recognizes sugar alcohols as GRAS, or “generally recognized as safe.”

“Xylitol is cheaper to make than cane sugar and so more and more keeps getting incorporated as a sugar substitute into food. Some 12-ounce drinks that use xylitol as a major artificial sweetener can contain 30 grams or more,” he said. “You can even buy it in bulk at the grocery store where you’re told to use as a one-to-one substitute for sugar in home cooking.”

Research has shown some artificial sweeteners may create a backlash in the metabolic system, triggering the body to expect more calories, thus making weight loss more difficult.


Only two of many alcohol sugars

The study, published Thursday in the European Heart Journal, began as a way of finding unknown chemicals or compounds in a person’s blood that might predict the risk for a heart attack, stroke or death within the next three years.

To do so, Hazen and his team analyzed 1,157 blood samples from people who were undergoing assessment for heart disease that had been collected between 2004 and 2011. They also examined another batch of blood samples from more than 2,100 people who may also have had high risk for heart disease.

They found a number of alcohol sugars that appeared to have an impact on cardiovascular function, including xylitol and erythritol. Erythritol is the predominant ingredient by weight in many stevia and monkfruit products.

The February 2023 erythritol in study found the risk of heart attack and stroke nearly doubled within three years when people had the highest levels of erythritol in their blood.

For the new study on xylitol, the results were basically the same — people with the highest levels of xylitol compared to those with the lowest levels had nearly twice the risk of heart attack, stroke and death, Hazen said.

“There’s a receptor on our platelets, which we as yet don’t understand, that is recognizing this molecule and signaling to the platelet to be more prone to clot,” he said. “Our tastebuds can’t tell the difference in the structures between sugar and these other sweeteners, but clearly our platelets can.”

The World Health Organization warned consumers in 2023 to avoid artificial sweeteners for weight loss, and has called for additional research on the long-term toxicity of low- and no-calorie sweeteners, the study said.

“Through their work, the investigators have shined a light on the safety of sugar substitutes. There is more to learn,” Mount Sinai’s Tomey said. “In the meantime, it is worth remembering that sugar substitutes are no substitute for a sincere commitment to the several elements of a healthy diet and lifestyle.”