No Evidence for Increased Platelet Reactivity with Xylitol or Erythritol Sweeteners in Healthy Humans
Year: 2026
Type: preprint
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Background Erythritol and xylitol, naturally present in fruits and vegetables, are widely used as alternative sweeteners with minimal glycemic and insulinemic effects. Both are also produced endogenously, with elevated plasma concentrations reported in metabolic disorders and cardiovascular disease. Recently, two interventional studies reported enhanced platelet aggregation after acute oral intake of erythritol or xylitol, raising concerns about potential prothrombotic effects. We investigated whether acute exposure to erythritol or xylitol increases platelet reactivity in healthy individuals. Methods We conducted a randomized, single-blind, crossover study in 14 healthy participants who received erythritol (50 g), xylitol (33.5 g), or water. Platelet aggregation was assessed ex vivo , together with circulating markers of platelet activation (P-selectin), endothelial activation (sVCAM-1), and coagulation (D-dimer), as well as plasma erythritol and xylitol concentrations. Complementary in vitro experiments were performed using platelet-rich plasma from 11 healthy participants exposed to increasing concentrations of erythritol or xylitol, followed by assessment of platelet aggregation. Results Despite substantial increases in circulating erythritol and xylitol concentrations following oral intake, neither erythritol nor xylitol increased ex vivo platelet aggregation compared with water. Consistently, no relevant changes were observed in P-selectin, sVCAM-1, or D-dimer concentrations. Direct in vitro exposure of platelet-rich plasma to increasing concentrations of erythritol or xylitol likewise did not enhance platelet aggregation. Conclusions In healthy individuals, acute oral intake of erythritol or xylitol did not increase platelet aggregation or circulating markers of platelet activation, endothelial activation, or coagulation. These findings were supported by in vitro experiments showing no direct effect of erythritol or xylitol on platelet aggregation. Our results do not support an acute platelet-activating effect of erythritol or xylitol under the conditions studied. Registration URL: https://clinicaltrials.gov/study/NCT04966299 ; Unique identifier: NCT04966299 . Graphical Abstract Effect of erythritol and xylitol versus water (control) on platelet reactivity. TRAP-6, thrombin receptor-activating peptide; ADP, adenosine diphosphate; PRP, platelet-rich plasma. What Are the Clinical Implications? Recent human intervention studies have raised concerns that acute erythritol or xylitol intake may enhance platelet reactivity and promote a prothrombotic state. In the present randomized crossover study of healthy adults, neither erythritol nor xylitol increased platelet aggregation or circulating markers of platelet activation, endothelial activation, or coagulation. These findings do not support an acute prothrombotic effect of erythritol or xylitol under the conditions studied and provide reassurance regarding their immediate effects on platelet function in healthy individuals. However, they do not establish long-term cardiovascular safety. Larger, longer-term studies, particularly in individuals at increased cardiovascular risk, are needed to determine the clinical relevance of chronic erythritol and xylitol exposure.
Source: medRxiv
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7214785262