Study Finds Link Between Xylitol and Increased Risk of Heart Attack, Stroke

Researchers from Cleveland Clinic have linked xylitol, a common sugar substitute, to increased risk of heart attack and stroke. Their study, published in the European Heart Journal, highlights potential health concerns associated with xylitol and other sugar alcohols in adults. The finding underscores the need for further investigation into the safety of artificial sweeteners and their impact on cardiovascular health.

Sugar alcohols are polyols and hydrogenated carbohydrates that are often labeled as “natural” because they can be extracted from berries. Image Credit: © mnimage - stock.adobe.com

Artificial sweeteners have been largely accepted by the general population, as well as the scientific community, as a beneficial supplement to reduce excess sugar intake. Xylitol is a sugar alcohol widely used as a sugar substitute in sugar-free candy, gums, baked goods, and toothpaste and is a rapidly growing market reaching $701.3 million in profits in 2023.¹

Sugar alcohols are polyols and hydrogenated carbohydrates that are often labeled as “natural” because they can be extracted from berries, oats, corn husk, birch, and sugarcane bagasse. However, xylitol is also produced by the body in very low levels, typically much lower than levels used in food production. Compared with endogenous production of xylitol, ingested xylitol has a shorter plasma half-life, with peak plasma levels occurring after 30 minutes with rapid metabolism of 80% by the liver.¹

Xylitol is similar to sucrose but has fewer calories per gram (2.4 kcal/g or 9 kJ/g vs 4 kcal/g or 17 kJ/g for typical sugars). Various countries and medical organizations tout positive side effects of ingesting xylitol, claiming associations with oral health, fewer respiratory infections, and increased satiety. However, findings by Cleveland Clinic researchers show that ingesting xylitol in a 1000-fold plus quantity can enhance platelet reactivity and thrombosis potential in vivo.^1-3

The study involved more than 3000 patients from the United States and Europe who were divided into 3 cohorts: (1) a discovery cohort consisting of 1157 participants whose fasting plasma samples underwent elective diagnostic cardiac evaluations for untargeted metabolomics study; (2) an independent validation cohort with 2149 participants whose plasma was used for subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses; and (3) an intervention study cohort involving 10 healthy participants to assess the direct effects of xylitol consumption on platelet function.³

The researchers performed complementary experiments using isolated human platelets, platelet-rich plasma, whole blood, and animal models to examine the effects of xylitol consumption on platelet responsiveness and thrombosis in vivo. The results from subsequent stable isotope dilution liquid chromatography with tandem mass spectrometry analyses identified that high levels of circulating xylitol in the body are associated with incident (3-year) major adverse cardiovascular event (MACE) risk (third vs. first tertile adjusted hazard ratio [95% confidence interval], 1.57 [1.12–2.21], P < .01).^1,3

Among the 3000 participants, one-third of patients with the highest plasma levels had an elevated likelihood of experiencing a cardiovascular event. The study authors found that consumption of products containing xylitol compared to glucose significantly raised platelet responsiveness in all participants, which may contribute to thrombosis, heart attack, or stroke.^1,2

Further investigation into the effects of xylitol consumption on cardiovascular health is warranted due to several limitations, including the study’s demonstration of association and not causation. As a result, the study authors recommend referring to a health care professional for advice about healthy eating habits.²

“It does not mean throw out your toothpaste if it has xylitol in it,” Stanley Hazen, MD, PhD, chair of cardiovascular and metabolic sciences at Cleveland Clinic’s Lerner Research Institute, said in a press release, “but we should be aware that consumption of a product containing high levels could increase the risk of blood clot related events.”²

References

1. Beer J, Allemann M. Xylitol: bitter cardiovascular data for a successful sweetener. European Heart Journal, June 6, 2024. https://doi.org/10.1093/eurheartj/ehae252

2. Cleveland clinic-led study links sugar substitute to increased risk of heart attack and stroke. EurekAlert. June 6, 2024. June 10, 2024. https://www.eurekalert.org/news-releases/1046958

3. Witkowski M, Nemet I, Li X, et al. Xylitol is prothrombotic and associated with cardiovascular risk. European Heart Journal, June 6, 2024. https://doi.org/10.1093/eurheartj/ehae244