Higher Circulating Xylitol Levels Associated With Increased Cardiovascular Event Risk in 2 Prospective Cohorts
September 22, 2026
Key Points
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Higher circulating concentrations of xylitol were associated with an increased risk of major adverse cardiovascular events (MACE) in 2 large population-based cohorts.
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The association persisted after adjustment for several established cardiovascular risk factors, including age, body mass index, blood pressure, diabetes, and lipid concentrations.
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The observational findings support an association between circulating xylitol and cardiovascular risk but do not establish that xylitol consumption causes cardiovascular events.
Background
Xylitol is a 5-carbon sugar alcohol commonly used as a low-calorie sweetener in foods and other products. According to Marco Witkowski, MD, PhD, of Charitรฉ University Hospital in Berlin, xylitol can also be produced endogenously in relatively small amounts.
โXylitol is a 5-carbon sugar alcohol sweetener [that] can be endogenously produced to a small extent, but itโs also highly enriched and added to artificially sweetened processed foods.โ
Previous research cited by the investigators has linked circulating xylitol concentrations with cardiovascular event risk, particularly in populations with a high prevalence of cardiovascular risk factors. Experimental studies have also suggested a potential mechanism involving platelet activation and thrombosis.
Witkowski noted:
โWe also know from mechanistic studies that xylitol can enhance platelet reactivity, and it also leads to an acceleration of in vivo thrombosis in animal models.โ
The investigators therefore examined whether circulating xylitol concentrations were associated with cardiovascular events in the general population.
Study Design and Population
Researchers analyzed metabolomic and longitudinal clinical data from 17,710 participants enrolled in 2 large observational cohorts:
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Canadian Longitudinal Study on Aging (CLSA)
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European Prospective Investigation into Cancer (EPIC)-Norfolk
The cohorts differed substantially in their follow-up periods, providing an opportunity to examine the association over both intermediate and longer periods.
Characteristics of the Study Cohorts
| Characteristic | CLSA | EPIC-Norfolk |
|---|---|---|
| Mean age | 62 years | 59 years |
| Men | 47% | 44% |
| Follow-up | 6 years | 30 years |
| Study type | Longitudinal population cohort | Longitudinal population cohort |
| Xylitol measurement | Metabolomics | Metabolomics |
| Cardiovascular outcomes | Major adverse cardiovascular events | Major adverse cardiovascular events |
The investigators had measurements of circulating xylitol concentrations for participants as well as longitudinal information regarding cardiovascular outcomes.
โWe had access to metabolomics data that quantified xylitol in all samples and longitudinal data with major adverse cardiac events during follow-up.โ
Higher Xylitol Levels Associated With Cardiovascular Events
In analyses that did not account for other cardiovascular risk factors, participants with higher xylitol concentrations had lower event-free survival than those with lower concentrations.
This pattern was observed in both cohorts, with the difference in event-free survival statistically significant at P < .0001.
After adjustment for traditional cardiovascular risk factors, participants in the highest quartile of xylitol concentration continued to demonstrate a higher risk of MACE compared with those in the lowest quartile.
Association Between Xylitol Level and MACE
| Cohort | Comparison | Adjusted HR | 95% CI |
|---|---|---|---|
| CLSA | Highest vs lowest xylitol quartile | 1.57 | 1.22-2.01 |
| EPIC-Norfolk | Highest vs lowest xylitol quartile | 1.18 | 1.09-1.27 |
Thus, compared with participants in the lowest xylitol category, those in the highest category had an approximately 57% higher relative hazard of MACE in CLSA and an approximately 18% higher relative hazard in EPIC-Norfolk, after adjustment for reported cardiovascular risk factors.
Importantly, these are relative hazard estimates, and the study information provided does not establish the absolute increase in cardiovascular events attributable to xylitol.
Association Persisted Across Multiple Subgroups
The researchers reported that the association between xylitol concentration and cardiovascular risk was consistent across several clinically relevant subgroups.
Subgroups Examined
| Variable | Association reportedly consistent? |
|---|---|
| Age | Yes |
| Sex | Yes |
| Body mass index | Yes |
| Hypertension status | Yes |
| Diabetes status | Yes |
| HDL cholesterol | Yes |
| LDL cholesterol | Yes |
| Triglycerides | Yes |
These findings suggest that the observed association was not obviously restricted to a particular demographic or cardiovascular-risk subgroup.
However, subgroup consistency in an observational analysis does not eliminate the possibility of residual confounding or other sources of bias.
Possible Biological Mechanism
The investigators discussed a potential prothrombotic mechanism to explain the association.
Previous mechanistic work has suggested that xylitol may increase platelet reactivity. Experimental animal data have also reportedly demonstrated accelerated thrombosis after exposure to xylitol.
Witkowski characterized the potential interpretation as follows:
โIn the general population, we have shown that xylitol levels in the blood are associated with event risk, and based on the known prothrombotic properties of xylitol, we can assume or speculate that even without overt cardiovascular disease, xylitol portends risk in the general population.โ
The wording is important: the speaker described this as an assumption or speculation based on mechanistic evidence, rather than demonstrating that xylitol causes thrombosis or cardiovascular events in humans.
Clinical Interpretation
The study raises questions about the cardiovascular implications of elevated circulating xylitol concentrations, particularly because xylitol is increasingly used as a sugar substitute in processed foods.
However, several distinctions are important:
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The study was observational, so it demonstrates an association rather than causation.
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Circulating xylitol concentrations do not necessarily correspond directly to a personโs dietary xylitol intake.
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Xylitol can be endogenously produced, meaning blood concentrations may reflect more than consumption of xylitol-containing products.
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The reported associations persisted after adjustment for several conventional cardiovascular risk factors, but residual or unmeasured confounding cannot be excluded.
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The mechanistic evidence involving platelet reactivity and thrombosis provides a biologically plausible hypothesis, but does not prove that this mechanism accounts for the clinical associations observed.
Consequently, these findings should not by themselves be interpreted as evidence that consuming xylitol causes cardiovascular disease.
What the Study Adds
The analysis extends previous observations linking circulating xylitol concentrations with cardiovascular events by examining individuals from the general population rather than focusing exclusively on populations with substantial cardiovascular disease burden.
The consistency of the association across 2 large cohorts, including one with approximately 30 years of follow-up, strengthens the rationale for further investigation.
Future research would need to determine whether xylitol itself contributes causally to cardiovascular events and whether reducing dietary exposure changes cardiovascular outcomes. Randomized clinical trials or other studies specifically designed to address causality would be particularly important.
Study at a Glance
| Feature | Details |
|---|---|
| Study question | Whether circulating xylitol levels are associated with cardiovascular events in the general population |
| Participants | 17,710 |
| Cohorts | CLSA and EPIC-Norfolk |
| CLSA mean age | 62 years |
| EPIC-Norfolk mean age | 59 years |
| CLSA follow-up | 6 years |
| EPIC-Norfolk follow-up | 30 years |
| Exposure | Circulating xylitol concentration |
| Outcome | Major adverse cardiovascular events |
| Highest vs lowest quartile, CLSA | aHR, 1.57 (95% CI, 1.22-2.01) |
| Highest vs lowest quartile, EPIC-Norfolk | aHR, 1.18 (95% CI, 1.09-1.27) |
| Unadjusted event-free survival | Lower with higher xylitol levels in both cohorts |
| Statistical significance of unadjusted comparison | P < .0001 for both cohorts |
| Reported subgroup consistency | Age, sex, BMI, hypertension, diabetes, HDL, LDL, triglycerides |
Conclusion
In an analysis of 17,710 participants from 2 large longitudinal cohorts, higher circulating xylitol concentrations were associated with a greater risk of major adverse cardiovascular events. The association remained after adjustment for several traditional cardiovascular risk factors and was reportedly consistent across multiple clinical subgroups.
The findings are biologically plausible given experimental evidence suggesting effects of xylitol on platelet reactivity and thrombosis. Nevertheless, the observational design prevents a conclusion that xylitol causes cardiovascular events. Further research is needed to distinguish endogenous xylitol metabolism from dietary exposure and to determine whether modifying xylitol intake affects cardiovascular outcomes.
Source: Witkowski M. Hungry heart: Nutrient deficiencies and cardiovascular disease. Presented at the European Society of Cardiology Congress, August 28-31, 2026, Munich. Disclosure: Witkowski reported no relevant financial disclosures.
