Background/Objectives: Xylitol, a natural low-caloric bulk sweetener, is increasingly used as a sugar alternative due to its low-glycemic and low-insulinemic properties. The aim was to investigate the effect of orally administered xylitol, sucrose, and acesulfame potassium (ace-K) on energy intake during a subsequent ad libitum test meal. Methods: In this randomized, controlled, double-blind, crossover trial (ClinicalTrials.gov NCT05671965, 20 December 2022), we included 20 healthy participants with normal body weight. Over four study visits, participants consumed an oral preload containing 33.5 g xylitol, 33.5 g sucrose, or 0.1675 g ace-K dissolved in 300 mL water, or 300 mL pure water as control. Participants were provided with an ad libitum test meal 15 min after the preload consumption, and both energy intake and total energy intake (= preload + ad libitum test meal) were assessed. Blood samples were collected to quantify cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), glucose, and insulin concentrations. Results: Total energy intake was lower in response to xylitol and ace-K compared to sucrose (p_Tukey < 0.03), with no differences between xylitol and ace-K or water. Plasma CCK concentrations were higher in response to xylitol compared to sucrose, ace-K, and water (p_Holm < 0.01), whereas GLP-1 concentrations did not differ between the preloads. Plasma glucose and insulin concentrations were lower in response to xylitol compared to sucrose (p_Holm < 0.01), but xylitol led to an increase in insulin compared to ace-K and water (p_Holm < 0.01). Conclusions: The consumption of oral preloads sweetened with xylitol or ace-K prior to an ad libitum test meal result in a lower total energy intake compared to a preload with sucrose.

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 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.

The sugar alcohol erythritol occurs naturally in fruits and fermented foods, is used as a sweetener, and is also endogenously synthesized via the pentose-phosphate pathway and metabolized into erythronate. Untargeted metabolomic studies have associated elevated plasma erythritol and erythronate concentrations with metabolic disorders, while weight loss has been linked to decreased plasma erythritol concentrations. In this trial, two complementary analyses were performed to identify predictors of fasting erythritol and erythronate concentrations across different populations and to assess changes in these metabolites following bariatric surgery-induced weight loss. Fasting plasma samples from 30 lean adolescents, 50 lean adults, and 138 adults with obesity (including 15 who had undergone bariatric surgery) were analyzed to measure erythritol, erythronate, glucose, and insulin concentrations. Across all populations, age but not body mass index (BMI), glucose, or insulin, was a significant predictor of fasting erythritol concentrations. Fasting erythronate concentrations were associated with both age and BMI. Post-surgery, change in BMI but not fasting glucose or insulin was a predictor of changes in fasting erythritol concentrations, while time was the only predictor of changes in fasting erythronate concentrations. Although the metabolic processes regulating the endogenous erythritol and erythronate production remain unclear, our findings suggest that age-related physiological changes may influence fasting concentrations of both erythritol and erythronate.