MUNICH — A large German study presented at the European Society of Cardiology (ESC) Congress 2026 showed that high blood levels of xylitol — a widely used natural sweetener also known as “birch sugar” — were associated with an increased long-term risk for major adverse cardiovascular events in the general population.

In a study published in 2024, Marco Witkowski, MD, PhD, from the Charité University Hospital in Berlin, Germany, and his team had already shown that in 1157 stable patients with a history of cardiovascular disease, high blood concentrations of xylitol were associated with a significantly higher rate of serious cardiovascular events over the following 3 years. The finding was replicated in a second cohort of 2149 patients.

Furthermore, in a small study involving 10 healthy volunteers, Witkowski and his colleagues found that consumption of a xylitol-sweetened beverage led to increased blood markers consistent with greater platelet reactivity.

A 30-Year Follow-Up in the General Population

In this new study, data from 17,710 participants from two prospective observational cohorts were analyzed: the Canadian Longitudinal Study on Aging (CLSA) and the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort.

Individuals with xylitol levels in the top quartile had a significantly higher risk for major adverse cardiovascular events — defined as death, myocardial infarction, or stroke — than those with xylitol levels in the bottom quartile.

Over a 6-year follow-up period, the risk for a major adverse cardiovascular event was 57% higher among individuals with the highest levels compared with those with the lowest levels in the CLSA cohort, after adjusting for established cardiovascular risk factors (including age, sex, smoking, lipid levels, diabetes, and hypertension).

Over a 30-year follow-up period, the risk for major cardiovascular events was 18% higher among individuals with the highest levels than among those with the lowest levels in the EPIC-Norfolk cohort.

Taken together with the intermediate quartiles, findings from both cohorts suggested a dose-response relationship: The higher the blood xylitol level, the higher was the rate of cardiovascular events. The association was also consistent across subgroups and did not appear to vary according to baseline characteristics such as age or sex.

Witkowski also emphasized that the association was independent of factors such as BMI, hypertension, diabetes, and lipid levels, which could predispose some individuals to consume low-calorie products.

“Our long-term results, obtained from the general population, underscore how limited our knowledge of xylitol’s cardiovascular safety remains and suggest that further studies are needed, especially as the amount of xylitol in consumer products continues to increase,” he concluded.

Commenting on the findings, Dan Atar, MD, a member of the ESC Communications Committee, said: “Sweeteners are widely used in modern society, and their safety profiles have generally been regarded as acceptable by regulatory authorities. In this observational study, however, xylitol appears to be associated with a long-term adverse effect on cardiovascular events in the general population. As with all observational research, causal inferences cannot be made, but these findings clearly support the need for further study in an area of major public health importance.”

Sweeteners have long been considered safe by health authorities. However, some — though not all — cohort studies have linked the consumption of artificially sweetened products to cardiometabolic disease. In 2023, in particular, researchers reported similarly concerning findings for another sweetener, erythritol.

Since May 2023, the World Health Organization has advised against using nonsugar sweeteners for weight loss or for the prevention of noncommunicable diseases.

What Should Clinicians Tell Patients?

Asked by Medscape’s French edition about the likely implications of the new findings for clinical practice, Boris Hansel, MD, PhD, endocrinologist and nutrition specialist at Bichat Hospital in Paris, France, said the results were important and consistent with previous findings on erythritol.

He cautioned, however, that “in nutrition, we always need to think comparatively. Between sugar and sweeteners, which is worse? We must not give the public the impression that sugar is no more harmful than sweeteners. A finding suggesting risk should not be isolated and turned into a marketing or communication message that pushes people toward an even less healthy diet.”

Hansel also warned against messages emphasizing the supposed benefits of natural sweeteners. “We need to stop claiming that natural sweeteners are better than artificial sweeteners such as aspartame. Based on current scientific knowledge, I consider them to be in the same category. They are not health products, but they do have a place as substitutes for sugary foods,” he said.

The study was funded by the Canada First Research Excellence Fund, a Fonds de recherche du Québec grant awarded to McGill University’s D2R initiative, the Corona Foundation (S0199/10098/2023), and the Advanced Clinician-Researcher Program at the Berlin Institute of Health. Witkowski and Hansel reported no relevant financial relationships. 

This story was translated from Medscape’s French edition.