Determining Cardiovascular Risks Resulting from Xylitol Use with LC-MS/MS

Researchers from the Lerner Research Institute at the Cleveland Clinic (Cleveland, Ohio) are using isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if the sugar substitute xylitol has an association with incidents of major adverse cardiovascular event (MACE) risk, according to a study published in the European Heart Journal (1).

Marco Witkowski, M.D., and associates performed untargeted metabolomics studies on overnight fasting plasma samples in a discovery cohort of 1157 sequential stable patients undergoing elective diagnostic cardiac evaluations. Subsequent isotope dilution LC-MS/MS analyses were performed on an independent validation cohort comprising 2149 participants. The effect of xylitol on platelet responsiveness and thrombus formation in vivo was examined in complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies. Finally, the effects of xylitol consumption were examined on platelet function in 10 healthy volunteers (1).

The researchers found that circulating levels of a polyol tentatively assigned as xylitol were associated with incident MACE risk in the initial untargeted metabolomics study. The association of xylitol with incident MACE risk was confirmed in stable isotope dilution LC-MS/MS analyses (third versus first tertile adjusted hazard ratio, 1.57). Xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma were seen in complementary mechanistic studies. Xylitol-sweetened drinks markedly raised plasma levels in interventional studies and enhanced multiple functional measures of platelet responsiveness in all individuals (1).

“Our studies suggest that xylitol will likely confer heightened thrombosis potential in the same vulnerable patients that it is marketed towards and intended to protect,” the authors wrote (2).

Xylitol, according to Web MD (3), is a natural sugar alcohol found in plants, including many fruits and vegetables. Xylitol tastes sweet but, unlike sugar, it does not cause tooth decay. Widely used in “sugar-free” chewing gums, mints, and other candies, xylitol reduces levels of decay-causing bacteria in saliva, and additionally acts against some bacteria that cause ear infections. In the United States, while products that contain xylitol are allowed to state that they reduce the risk for cavities, people also use it to prevent tooth plaque, dry mouth, and many other conditions; however, there is no good scientific evidence to support most of these uses. The xylitol market is rapidly growing, having reached $701.3 million in 2023; annual growth is expected to be greater than 4% due to it being considered “natural,” as well as the long list of reported positive effects (4).

An editorial published in European Heart Journal in conjunction with the article (4) said that the data and the questions generated collectively call for a closer examination by the authorities and researchers alike at sugar alcohol sweeteners as a cardiovascular hazard. Confirmatory studies, longer exposure analyses, and elucidations of mechanisms will have to confirm these “not-so-clear skies” for the widespread use of sugar alcohols.

Several authors of the original study disclosed ties to the biopharmaceutical industry. In addition, several authors are named coinventors on pending and issued patents relating to cardiovascular diagnostics and therapeutics.

References

1. Witkowski, M.; Nemet, I.; Li, X. S.; Wilcox, J.; Ferrell, M.; Alamri, H.; Gupta, N.; Wang, Z.; Tang, W. H. W.; Hazen, S. L. Xylitol is Prothrombotic and Associated with Cardiovascular Risk, Eur. Heart J. 2024, ehae244. https://doi.org/10.1093/eurheartj/ehae244 (accessed 2024-06-18)

2. Xylitol Linked to Incident Major Adverse Cardiovascular Event Risk. Physician's Weekly website. https://www.physiciansweekly.com/xylitol-linked-to-incident-major-adverse-cardiovascular-event-risk/ (accessed 2024-06-18)

3. Xylitol. Web MD website. https://www.webmd.com/vitamins/ai/ingredientmono-996/xylitol (accessed 2024-06-18)

4. Beer, J. H.; Allemann, M. Xylitol: Bitter Cardiovascular Data for a Successful Sweetener, Eur. Heart . 2024, ehae252, https://doi.org/10.1093/eurheartj/ehae252

Xylitol: © mnimage - stock.adobe.com