CCC Statement in Response to Xylitol is Prothrombotic and Associated with Cardiovascular Risk

A new study entitled, “Xylitol is prothrombotic and associated with cardiovascular risk“, was recently published in the European Heart Journal. 

The investigators conducted four separate studies. They began with untargeted metabolomics analyses in a discovery cohort and report circulating levels of a polyol tentatively assigned as xylitol, were associated with incident (3-year) risk for major adverse cardiovascular events ( or “MACE” (includes death or nonfatal myocardial infarction or stroke). The investigators then conducted a second clinical study utilizing stable isotope dilution LC-MS/MS analyses in a validated cohort comprised of subjects enrolled in GeneBank (includes DNA DataBank of Japan (DDBJ), the European Nucleotide Archive (ENA), and GenBank at NCBI). The authors report that higher plasma levels of xylitol were again observed among subjects who experienced MACE, and Kaplan– Meier analysis similarly revealed higher levels of circulating xylitol were associated with poorer event-free survival over the follow-up period. In further analyses, elevated xylitol levels (T3 vs. T1) were also associated with incident thrombotic event risks [aHR 1.80 (1.05–3.08), P = .03] and significant association between xylitol levels with incident MACE risk was observed amongst subjects on anti-platelet drugs and, in general, amongst all subgroups examined where subjects were stratified by multiple different platelet functional metrics.    Overall, it was concluded that xylitol is associated with incident MACE risk and enhanced platelet reactivity and thrombosis potential in vivo. The authors note that further studies examining the cardiovascular safety of xylitol are warranted.

In response to this study, the Calorie Control Council has issued the following statement:

“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. While the authors used multiple methods, it should be noted that the findings are limited in their ability to establish association only. Further, one phase of the study included individuals who were already at increased risk for adverse cardiovascular events.‎ These findings are a disservice to those who rely on alternative sweeteners as a tool to improve their health,” said Carla Saunders, President, ‎Calorie Control Council.‎ “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 is naturally occurring in foods such as strawberries, lettuce, and oats.”

Some additional factors to consider:

• While the current study utilized various methodologies, it should be noted that the findings are limited in their ability to establish causality, their application to real-world consumption, and extrapolation to the general public.
• Due to the observational design, both the untargeted and targeted metabolomic analyses included individuals who were already at increased risk for adverse cardiovascular events.
• Though convenient, in-vitro studies cannot mimic the complex physiological environment of the human body. 
• The xylitol dose used in the study (30 g of xylitol dissolved in 300 ml water within 2 minutes) does not reflect a typical real-world serving.