Monday, May 19, 2025
5/19/2025
Artificial sweeteners and cardiovascular disease - Project Summary This application is entitled “Artificial sweeteners and cardiovascular disease”. The proposed studies investigate whether low calorie, non-nutritive sweeteners (NNS’s), and commonly employed artificial sweeteners, contribute to the development of cardiovascular disease (CVD) through enhanced vascular inflammation, atherosclerosis and platelet reactivity and thrombosis potential. Our overall studies are based on a combination of both clinical observations, and mechanistic cellular and animal model studies. Using untargeted mass spectrometry as an initial discovery platform, we identified circulating levels of the endogenous metabolites erythritol, xylitol and other polyols as being associated with incident (3yr) risk for major adverse cardiovascular events (MACE = myocardial infarction (MI), stroke or death). Subsequent preliminary studies (with erythritol and xylitol) confirm these initial clinical associations, and a variety of animal model and other investigations suggest a role for these polyols in directly promoting vascular inflammation and thrombosis potential in animal models of disease. It is notable that a growing body of epidemiological data questions whether artificial sweetener use provides the presumed added benefits (weigh reduction, improved diabetes control). And the present studies significantly add to the growing concern about artificial sweeteners and cardiometabolic diseases. Erythritol, xylitol and other polyol NNS have more recently been widely adopted by the food industry as artificial sweeteners. Consequently, supra-high physiological levels are now routinely experienced by consumers of foods where these agents are abundant components (e.g. keto-friendly foods, low-carb foods, and zero-calorie foods), amplifying the urgency of the proposed studies. We propose to investigate whether low calorie NNS like erythritol, xylitol, their numerous structural isomers also being explored as commercial artificial sweeteners, and commonly employed/consumed artificial sweeteners, might inadvertently be contributing to heightened CVD risks in the very subjects most vulnerable to CVD. Our proposed studies are multidisciplinary. They are based on human clinical observational studies, from which numerous mechanistic investigations involving cell-based assays and preclinical models of vascular inflammation, vascular injury, atherosclerosis and thrombosis are proposed. Successful completion of the proposed studies will further advance our knowledge of how polyols, artificial sweeteners and other NNS’s may impact vascular health.
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