Xylitol is a “sugar alcohol” made from xylose, a plant-based sugar. Its sweet taste and lower glycemic index have led to its use as an artificial sweetener. A recent paper from authors at the Cleveland Clinic has linked the ingredient to an increased risk of heart attack, stroke or cardiovascular-related deaths, reigniting debate about the overall safety of artificial sweeteners.
What are sugar alcohols?
Sugar alcohols can occur naturally in food but are more likely to be consumed from synthetic sources added to processed food. Despite the name, there is no ethanol in sugar alcohols. The class includes products like erythritol, maltitol, mannitol, sorbitol and xylitol. Because they’re lower in calories (0-2 calories per gram, vs 4 calories/gram with sugar) and do not cause cavities, they are used in “sugar-free” products, especially gum and mouthwashes, but also food products. These products are not absorbed by the body well (hence their lower calorie count), so side effects can include gas and diarrhea. See these reviews of sugar-free Haribo Gummy Bears to get some idea of the side effects of eating an immoderate amount of sugar alcohols.
Moderate amounts of sugar alcohols in the diet appear safe, and xylitol and erythritol are approved food additives in the United States. There have been some concerns that processed foods that contain sugar alcohols in large amounts may have health hazards.
Safety signals with consumption
In research published in Nature Medicine in February 2023, Marco Witkowski and colleagues examined the artificial sweetener erythritol and thrombotic heart disease risk, building on other studies that have tried to understand if a causal relationship exists. This study looked at patients undergoing cardiac risk assessments (i.e., this was not a healthy population). They found that high circulating levels of multiple sweeteners, especially erythritol, were associated an elevated risk for major adverse cardiovascular events (MACE; includes death or nonfatal myocardial infarction or stroke), even after controlling for multiple risk factors, over three years. Those with the highest erythritol levels (top 25%) were approximately 2x as likely to have cardiovascular events over three years of follow-up as those with the lowest (bottom 25%) levels. Subsequent analyses in other populations confirmed this association.
Finally the authors did a prospective pilot evaluation of erythritol in eight volunteers and found that ingestion of a large single dose (30g) led to plasma levels (for at least two days) that were associated with (in vitro and in vivo) studies showing effects on platelet reactivity and thrombosis. The authors concluded that erythritol is increasing cardiovascular risk and recommended further safety studies.
It’s important to note that dietary intake was not captured in this study – this was simply a measurement of levels. As erythritol is produced by the body, we do not know if the elevated levels were attributable to diet, or to natural (endogenous) levels. Causation attributable to diet is not clear, as the authors note that most participants were enrolled before erythritol became popular as a dietary ingredient in food products. Given fasting blood levels were being drawn, there is the possibility that the higher levels were endogenous (i.e., produced by the body) and not due to dietary consumption.
Like many other products, the dose makes the poison, and correlation is not causation. Because this was not an otherwise healthy population, and the pilot with dosing was only in 8 people, the findings have been criticized – is it possible that plasma erythritol is raised because of a different cause (e.g., chronic disease) and only correlates with cardiovascular disease? Yes.
In research published in July 2024 in the European Heart Journal, the same group of researchers studied xylitol levels and platelet function in a manner similar to their 2023 analysis. Blood samples from 10 healthy people before and after drinking a xylitol-sweetened beverage were examined (a dose that would be comparable to a serving of xylitol-sweetened ice cream). Not surprisingly, xylitol levels shot up in the blood and decreased over 4-6 hours. Blood xylitol levels increased 1,000-fold within 30 minutes of drinking and returned to baseline after 4 to 6 hours. Platelets were more sensitive to clotting signals when xylitol levels were high. Again, no direct causation of harm was shown.
Overall this research suggests that blood levels of erythritol and xylitol may correlate with cardiovascular disease. I personally am not one to panic based on observational data that could be confounded (and I don’t consume sugar-free foods except Coke Zero) but I would like to see more research exploring this relationship, and if there is causality. Until then, the advice to use sugar alcohol sweeteners in moderation and minimize consumption of all processed foods (sweetened with sugar alcohols or not) remains reasonable.