The researchers noted that while xylitol is not as commonly used in keto or sugar-free food products in the United States, it is prevalent in other countries. “We were trying to discover the next cholesterol, another pathway that contributes to heart disease that’s naturally occurring in our bodies,” said Hazen, also the chair of cardiovascular and metabolic sciences at the Cleveland Clinic’s Lerner Research Institute. “And we think that’s what we have, is that erythritol or xylitol, these sugar alcohols, are linked to causing heart disease, or at least they’re linked to being associated with future development of cardiac events.”
The same research team found a similar link between erythritol and cardiovascular risk last year.
Use of sugar substitutes is rising
The findings come as use of sugar alcohols such as xylitol is trending upward, as keto and low-carb diet trends are generating growth in alternative sweeteners billed as “natural.” Some $1.19 billion in xylitol products were sold in 2021, and that market is expected to grow to about $1.48 billion by 2030, according to the research firm Custom Market Insights.
“There’s this unusual situation in the last one or two decades where people are experiencing levels of xylitol that has never been experienced in our evolution before,” Hazen said.
The results challenge the popular understanding of sugar alcohols such as xylitol and erythritol as healthy, natural sugar alternatives. People view them as natural because our bodies produce them as part of our energy metabolism; however, our cells produce them at much lower levels. When these sugar alcohols are manufactured, they are industrially prepared, using bacteria or yeast that’s put through brewing and fermentation processes to create a chemical that tricks our taste buds, Hazen said.
“Even though it is a natural compound, it’s used in a very unnatural way, at a level that is massively, massively higher than could ever appear under normal conditions” in our bodies, Hazen said.
Researchers also found that an elevated xylitol level may be worse for your heart than cholesterol. By eating a high-cholesterol diet, we might increase our blood cholesterol levels by 10 to 30 percent, Hazen said.
By eating a product high in xylitol, researchers found, the chemical levels in the blood went up 1,000-fold — or 100,000 percent — and remained elevated for four to six hours.
Another way of putting it is that, among the thousands of people Hazen sees in his preventive cardiology clinic, those whose cholesterol levels are in the top 25 percent have a 30 percent increase in the risk of a cardiovascular disease event compared with those whose cholesterol levels are in the bottom 25 percent. But those whose blood xylitol level is in the top 25 percent had a 200 percent higher risk of having a cardiovascular disease event compared with those whose xylitol levels were in the bottom 25 percent.
The Calorie Control Council, which represents manufacturers and suppliers of low- and reduced-calorie foods and beverages, rejected the study’s findings.
“The results of this study 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,” Carla Saunders, the council’s president, said in a statement.
“Xylitol has been trusted as a great tasting low-calorie sweetener for over 60 years. It has proven dental benefits, including preventing plaque build-up and tooth decay, and is naturally occurring in foods such as strawberries, lettuce, and oats,” she said.
“This study adds to a growing body of literature on the potential physiological problems caused by artificial sweeteners,” Marion Nestle, emeritus professor of nutrition at New York University, wrote in an email. “Researchers are finding problems with one after another, now xylitol.”
While she believes the study needs repeating, it suggests that xylitol may not be benign. The benefits of artificial sweeteners in general are uncertain, she wrote.
“It’s beginning to look more and more that they pose risks,” she wrote. “My preference is to avoid them, but I don’t like the way they taste anyway.”
Rob van Dam, a professor of exercise and nutrition sciences at George Washington University, said that while the paper’s findings are compelling and add to existing research on the risks of artificial sweeteners, scientists may not have been able to properly test the link between consumed xylitol and cardiac risk, given that they used blood from people who had been fasting, which means the blood probably contained xylitol produced in the body itself, metabolically.
“So the question then is, are these elevated xylitol levels really reflecting that dietary intake of xylitol is bad?” van Dam asked. “Or does it just mean that something is wrong in people’s metabolism that leads to higher xylitol levels?”
The researchers acknowledge this issue and performed a follow-up experiment, where they gave 10 people xylitol and water to see what happened with their blood platelets, and they observed that the platelets did seem to aggregate more.
“I think, by itself, it wouldn’t be very alarming, but there’s this accumulating evidence that some of these artificial sweeteners may not be as innocuous as we may have thought,” van Dam said. “If it would just be about something that people don’t consume much, nobody would really care that much. But the context is, this is something that hundreds of millions of people are exposed to, sometimes every day, so every piece of evidence that raises some concern is quite relevant for public health.”
Given that the medical community is widely recommending the use of sugar substitutes instead of sugar as an option for those who are obese or trying to lose weight, or for diabetics or those with metabolic syndrome, this study should be a red flag, Hazen said.
“I hope this is a call for coming to arms, for fellow researchers to start studying this, because this is a huge public health concern, given how much of this stuff we are pumping into our food pyramid, thinking that it’s a safe thing,” Hazen said.