Artificial sweeteners are widely used as alternatives to dietary sugar. Xylitol is a sugar alcohol that occurs naturally in the body as a byproduct of glucose metabolism and is also found in some natural foods, although in very small amounts.

Xylitol is also added to foods, beverages and oral care products, often in quantities more than 1,000 times higher than naturally occurring levels.

Despite its growing use, the long-term impact of xylitol on cardiovascular health has not been widely studied.

"In previous studies, we showed that xylitol can enhance the ability of platelets to form clots," said study presenter Dr Marco Witkowski of Charité University Hospital, Berlin, Germany.

"We also found that high blood levels of xylitol were linked to cardiovascular events in high-risk individuals over a three-year period. Here, we studied if xylitol increases cardiovascular events in a larger sample of the general population over much longer follow-up," he said.

The research team analysed data from 17,710 participants in two prospective observational cohorts — the Canadian Longitudinal Study on Aging (CLSA) and the European Prospective Investigation into Cancer (EPIC)-Norfolk.

Participants with xylitol levels in the highest quartile were found to have a substantially higher risk of major adverse cardiovascular events — defined as death, myocardial infarction or stroke — compared with those with levels in the lowest quartile.

Over a six-year follow-up period, the risk of a major adverse cardiovascular event was 57 per cent higher among participants with the highest xylitol levels compared with those with the lowest levels in the CLSA cohort, after adjusting for known cardiovascular risk factors, including age, sex, smoking status, lipid levels, diabetes and hypertension.

Over a 30-year follow-up period, the risk of major adverse cardiovascular events was 18 per cent higher among participants with the highest xylitol levels compared with those with the lowest levels in the EPIC-Norfolk cohort.

When data from the middle quartiles were also considered, the findings from both cohorts suggested a dose-dependent relationship, with higher blood xylitol levels associated with higher cardiovascular event rates.

The researchers also reported a consistent increase in cardiovascular events associated with xylitol levels irrespective of baseline characteristics such as age and sex.

Dr Witkowski said the association was independent of underlying factors including body mass index, hypertension, diabetes and lipid levels, which could otherwise predispose people to consuming low-calorie products.

"Artificial sweeteners are consumed by people who think they are healthier than sugar and they are generally regarded as safe by regulatory agencies," Witkowski said.

"Our long-term findings in the general population highlight how little we know about the cardiovascular safety of xylitol and indicate that further studies are warranted, especially as the amount of xylitol in products continues to increase," he added.

Commenting on the findings, Professor Dan Atar, a member of the ESC Communication Committee, said artificial sweeteners were widely used in modern society and had generally received favourable safety assessments from regulatory authorities.

"In this observational work, however, it appears that xylitol has a negative long-term effect on cardiovascular events in the general population," Atar said.

"As with all observational studies, causality is difficult to infer, but this work shows that further studies are warranted into this societally important topic," he added.