ArticleEuropean heart journal2024
Xylitol is prothrombotic and associated with cardiovascular risk.
Article in European heart journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04731363 (Consumption of Oral Artificial Sweeteners on Platelet Aggregation and Polyol Excretion), which is not on this map. Cited by 26 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Consumption of Oral Artificial Sweeteners on Platelet Aggregation and Polyol Excretion
Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Specific effects of xylitol chewing gum on mutans streptococci levels, plaque accumulation and caries occurrence: a systematic review.BMC oral health · 2025Pooled it
- Beneficial Effects of Xylitol Chewing Gum and Candies on Oral Health in Older People and Individuals With Disabilities: A Systematic Review.Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric DentistryPooled it
- Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2024Trial
- Declines in plasma erythritol levels and improvements in insulin sensitivity and glucose metabolism: POUNDS lost trial.International journal of obesity (2005) · 2026Article
- Xylitol, Mitochondrial Plasticity, the Warburg Effect, and Oral Pathobiont-Associated Immune Evasion in Cancer Hypothesis.International journal of molecular sciences · 2026Review
- Reply: Nonnutritive Sweeteners and Cardiovascular Risk: Correlation Is Not Causation.JACC. Advances · 2026Article
- Special Issue "New Insights into the Effects of Microbiome-Derived Metabolites on Health and Disease".International journal of molecular sciences · 2026Article
- Metabolomic Atlas of Cardiovascular Diseases: Mapping Shared and Specific Signatures.JACC. Advances · 2026Article
- [Nutrition recommendations for people with diabetes (Update 2026)].Wiener klinische Wochenschrift · 2026Review
- In Vitro Inhibition of Pathogens by Polyols: Optical Density-Based Screening and Implications for the Oral-Systemic Axis.Microorganisms · 2026Article
- Article
- Potential Effects of Low-Calorie Sweeteners on Human Health.Nutrients · 2025Review
- Sweeteners: erythritol, xylitol and cardiovascular risk-friend or foe?Cardiovascular research · 2025Review
- Erythritol and xylitol and cardiovascular disease risk: a growing concern.European heart journal · 2025Article
- Threitol, a Novel Functional Sugar Alcohol Biosynthesized by EngineeredFoods (Basel, Switzerland) · 2025Article
- The denitrosylase SCoR2 controls cardioprotective metabolic reprogramming.bioRxiv : the preprint server for biology · 2025Article
- Oral health benefits and safety of xylitol and potential cardiovascular risk: questioning the validity of the model of Witkowski et al.European heart journal · 2025Article
- Xylitol and cardiovascular risks.European heart journal · 2025Article
- Deep learning to assess erythritol in zebrafish development, circadian rhythm, and cardiovascular disease risk.NPJ science of food · 2025Article
- Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
BACKGROUND AND
aimsThe pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute.
methodsUntargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10).
resultsIn initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12-2.21), P < .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects.
conclusionsXylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.