Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The artificial sweetener erythritol and cardiovascular event risk

Abstract

Artificial sweeteners are widely used sugar substitutes, but little is known about their long-term effects on cardiometabolic disease risks. Here we examined the commonly used sugar substitute erythritol and atherothrombotic disease risk. In initial untargeted metabolomics studies in patients undergoing cardiac risk assessment (n = 1,157; discovery cohort, NCT00590200), circulating levels of multiple polyol sweeteners, especially erythritol, were associated with incident (3 year) risk for major adverse cardiovascular events (MACE; includes death or nonfatal myocardial infarction or stroke). Subsequent targeted metabolomics analyses in independent US (n = 2,149, NCT00590200) and European (n = 833, DRKS00020915) validation cohorts of stable patients undergoing elective cardiac evaluation confirmed this association (fourth versus first quartile adjusted hazard ratio (95% confidence interval), 1.80 (1.18–2.77) and 2.21 (1.20–4.07), respectively). At physiological levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo. Finally, in a prospective pilot intervention study (NCT04731363), erythritol ingestion in healthy volunteers (n = 8) induced marked and sustained (>2 d) increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies. Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of erythritol are warranted.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Kaplan–Meier estimates and forest plots indicating the risks of MACE, according to erythritol quartile level.
Fig. 2: Long-term risk of MACE among patient subgroups.
Fig. 3: Erythritol enhances platelet responsiveness.
Fig. 4: Erythritol enhances in vivo thrombosis formation.
Fig. 5: Effects of an erythritol challenge on mean plasma levels.

Data availability

There are restrictions to the availability of some of the clinical data generated in the present study (Figs. 1 and 2), because we do not have permission in our informed consent from research subjects to share data outside our institution without their authorization. Where permissible, the datasets generated and/or analyzed during the present studies are available from the corresponding author Stanley L. Hazen (hazens@ccf.org) on request. An answer can be expected within 14 d.

Code availability

Custom R codes used in this manuscript are available at ‘https://doi.org/10.5281/zenodo.6780497’. The BinBase database is accessible using the following link ‘https://bitbucket.org/fiehnlab/binbase/src/master/?’.

References

  1. Abarca-Gómez, L. et al. Worldwide trends in body-mass index, underweight, overweight and obesity from 1975 to 2016: a pooled analysis of 2,416 population-based measurement studies in 128.9 million children, adolescents and adults. Lancet 390, 2627–2642 (2017).

    Article  Google Scholar 

  2. Sylvetsky, A. C. & Rother, K. I. Trends in the consumption of low-calorie sweeteners. Physiol. Behav. 164, 446–450 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Buerge, I. J., Buser, H. R., Kahle, M., Müller, M. D. & Poiger, T. Ubiquitous occurrence of the artificial sweetener acesulfame in the aquatic environment: an ideal chemical marker of domestic wastewater in groundwater. Environ. Sci. Technol. 43, 4381–4385 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Roberts, A. The safety and regulatory process for low calorie sweeteners in the United States. Physiol. Behav. 164, 439–444 (2016).

    Article  CAS  PubMed  Google Scholar 

  5. Mortensen, A. Sweeteners permitted in the European Union: safety aspects. Scand. J. Food Nutr. 50, 104–116 (2006).

    Article  Google Scholar 

  6. Gardner, C. et al. Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation 126, 509–519 (2012).

    Article  PubMed  Google Scholar 

  7. British Dietetic Association. Policy statement—the use of artificial sweeteners. https://www.bda.uk.com/uploads/assets/11ea5867-96eb-43df-b61f2cbe9673530d/policystatementsweetners.pdf (2016).

  8. Markovic, T. P. et al. The Australian obesity management algorithm: a simple tool to guide the management of obesity in primary care. Obes. Res. Clin. Pract. 16, 353–363 (2022).

    Article  PubMed  Google Scholar 

  9. Ruanpeng, D., Thongprayoon, C., Cheungpasitporn, W. & Harindhanavudhi, T. Sugar and artificially sweetened beverages linked to obesity: a systematic review and meta-analysis. QJM 110, 513–520 (2017).

    Article  CAS  PubMed  Google Scholar 

  10. Romo-Romo, A., Aguilar-Salinas, C. A., Brito-Córdova, G. X., Gómez-Díaz, R. A. & Almeda-Valdes, P. Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial. Am. J. Clin. Nutr. 108, 485–491 (2018).

    Article  PubMed  Google Scholar 

  11. Imamura, F. et al. Consumption of sugar sweetened beverages, artificially sweetened beverages and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis and estimation of population attributable fraction. Br. Med. J. 351, h3576 (2015).

    Article  Google Scholar 

  12. Mossavar-Rahmani, Y. et al. Artificially sweetened beverages and stroke, coronary heart disease and all-cause mortality in the Women’s Health Initiative. Stroke 50, 555–562 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Malik, V. S. et al. Long-term consumption of sugar-sweetened and artificially sweetened beverages and risk of mortality in US adults. Circulation 139, 2113–2125 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mullee, A. et al. Association between soft drink consumption and mortality in ten European countries. JAMA Intern. Med. 179, 1479–1490 (2019).

    Article  PubMed  Google Scholar 

  15. Lohner, S., Toews, I. & Meerpohl, J. J. Health outcomes of non-nutritive sweeteners: analysis of the research landscape. Nutr. J. 16, 55 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mitchell, H. (ed.) Sweeteners and Sugar Alternatives in Food Technology (Blackwell Publishing, 2006).

  17. European Food Safety Authority. Statement in relation to the safety of erythritol (E 968) in light of new data, including a new paediatric study on the gastrointestinal tolerability of erythritol. EFSA J. 8, 1650 (2010).

    Article  Google Scholar 

  18. Food and Drug Administration. GRAS notice (GRN) No. 789. https://www.fda.gov/media/132946/download (2018).

  19. Bornet, F. R., Blayo, A., Dauchy, F. & Slama, G. Plasma and urine kinetics of erythritol after oral ingestion by healthy humans. Regul. Toxicol. Pharm. 24, S280–S285 (1996).

    Article  CAS  Google Scholar 

  20. Hootman, K. C. et al. Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults. Proc. Natl Acad. Sci. USA 114, 4233–4240 (2017).

    Article  Google Scholar 

  21. Global erythritol market research report 2020. https://www.360researchreports.com/global-erythritol-market-15041957 (2020).

  22. Yokozawa, T., Kim, H. Y. & Cho, E. J. Erythritol attenuates the diabetic oxidative stress through modulating glucose metabolism and lipid peroxidation in streptozotocin-induced diabetic rats. J. Agric. Food Chem. 50, 5485–5489 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. Flint, N. et al. Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study. Acta Diabetol. 51, 513–516 (2014).

    CAS  PubMed  Google Scholar 

  24. Rebholz, C. M. et al. Serum metabolomic profile of incident diabetes. Diabetologia 61, 1046–1054 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Selvin, E. et al. Association of 1,5-anhydroglucitol with cardiovascular disease and mortality. Diabetes 65, 201–208 (2016).

    Article  CAS  PubMed  Google Scholar 

  26. Zhu, W. et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 165, 111–124 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Schlicker, L. et al. Unexpected roles for ADH1 and SORD in catalyzing the final step of erythritol biosynthesis. J. Biol. Chem. 294, 16095–16108 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Regnat, K., Mach, R. L. & Mach-Aigner, A. R. Erythritol as sweetener-wherefrom and whereto? Appl. Microbiol. Biotechnol. 102, 587–595 (2018).

    Article  CAS  PubMed  Google Scholar 

  29. Tetzloff, W., Dauchy, F., Medimagh, S., Carr, D. & Bär, A. Tolerance to subchronic, high-dose ingestion of erythritol in human volunteers. Regul. Toxicol. Pharm. 24, S286–S295 (1996).

    Article  CAS  Google Scholar 

  30. Bornet, F. R., Blayo, A., Dauchy, F. & Slama, G. Gastrointestinal response and plasma and urine determinations in human subjects given erythritol. Regul. Toxicol. Pharm. 24, S296–S302 (1996).

    Article  CAS  Google Scholar 

  31. Munro, I. C. et al. Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data. Food Chem. Toxicol. 36, 1139–1174 (1998).

    Article  CAS  PubMed  Google Scholar 

  32. Gardener, H. et al. Diet soft drink consumption is associated with an increased risk of vascular events in the Northern Manhattan Study. J. Gen. Intern. Med. 27, 1120–1126 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Narain, A., Kwok, C. S. & Mamas, M. A. Soft drinks and sweetened beverages and the risk of cardiovascular disease and mortality: a systematic review and meta-analysis. Int. J. Clin. Pract. 70, 791–805 (2016).

    Article  CAS  PubMed  Google Scholar 

  34. Vyas, A. et al. Diet drink consumption and the risk of cardiovascular events: a report from the Women’s Health Initiative. J. Gen. Intern. Med. 30, 462–468 (2015).

    Article  PubMed  Google Scholar 

  35. Lin, J. & Curhan, G. C. Associations of sugar and artificially sweetened soda with albuminuria and kidney function decline in women. Clin. J. Am. Soc. Nephrol. 6, 160–166 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. de Koning, L. et al. Sweetened beverage consumption, incident coronary heart disease and biomarkers of risk in men. Circulation 125, 1735–1741 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  37. de Koning, L., Malik, V. S., Rimm, E. B., Willett, W. C. & Hu, F. B. Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men. Am. J. Clin. Nutr. 93, 1321–1327 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Suez, J. et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell 185, 3307–3328 (2022).

    Article  CAS  PubMed  Google Scholar 

  39. Debras, C. et al. Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. Br. Med. J. 378, e071204 (2022).

    Article  Google Scholar 

  40. Toews, I., Lohner, S., Küllenberg de Gaudry, D., Sommer, H. & Meerpohl, J. J. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and nonrandomized controlled trials and observational studies. Br. Med. J. 364, k4718 (2019).

    Article  Google Scholar 

  41. Azad, M. B. et al. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. Can. Med. Assoc. J. 189, 929–939 (2017).

    Article  Google Scholar 

  42. Miller, P. E. & Perez, V. Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. Am. J. Clin. Nutr. 100, 765–777 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. McGlynn, N. D. et al. Association of low- and no-calorie sweetened beverages as a replacement for sugar-sweetened beverages with body weight and cardiometabolic risk: a systematic review and meta-analysis. JAMA Netw. Open 5, e222092 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Sylvetsky, A. C., Blau, J. E. & Rother, K. I. Understanding the metabolic and health effects of low-calorie sweeteners: methodological considerations and implications for future research. Rev. Endocr. Metab. Disord. 17, 187–194 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wang, Z. et al. Metabolomic pattern predicts incident coronary heart disease. Arterioscler. Thromb. Vasc. Biol. 39, 1475–1482 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tang, W. H. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575–1584 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57–63 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Stevens, L. A. et al. Comparative performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) study equations for estimating GFR levels above 60 ml min−1/1.73 m2. Am. J. Kidney Dis. 56, 486–495 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  49. König, M. et al. Cohort profile: role of lipoproteins in cardiovascular disease-the LipidCardio study. Br. Med. J. Open 9, e030097 (2019).

    Google Scholar 

  50. STROBE Statement—checklist of items that should be included in reports of observational studies1 (STROBE Initiative). https://www.equator-network.org/wp-content/uploads/2015/10/STROBE_checklist_v4_combined.pdf (2008).

  51. Nemet, I. et al. A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors. Cell 180, 862–877 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gupta, N., Li, W. & McIntyre, T. M. Deubiquitinases modulate platelet proteome ubiquitination, aggregation and thrombosis. Arterioscler. Thromb. Vasc. Biol. 35, 2657–2666 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Scavone, M. et al. Platelet adhesion and thrombus formation in microchannels: the effect of assay-dependent variables. Int. J. Mol. Sci. 21, 750 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Witkowski, M. et al. Vascular endothelial tissue factor contributes to trimethylamine N-oxide-enhanced arterial thrombosis. Cardiovasc. Res. 118, 2367–2384 (2021).

    Article  PubMed Central  Google Scholar 

  55. Ludäscher, B. & Raschid, L. (eds.) Data Integration in the Life Sciences (Springer, 2005).

  56. Wilson, P. W. et al. Prediction of coronary heart disease using risk factor categories. Circulation 97, 1837–1847 (1998).

    Article  CAS  PubMed  Google Scholar 

  57. SCORE2 Working Group and ESC Cardiovascular Risk Collaboration. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur. Heart J. 42, 2439–2454 (2021).

    Article  Google Scholar 

Download references

Acknowledgements

This work is supported by grants from the NIH and Office of Dietary Supplements P01 HL147823, R01 HL103866 (S.L.H.), the Leducq Foundation 17CVD01 (S.L.H. and U.L.) and the Deutsche Forschungsgemeinschaft WI 5229/1-1 (M.W.). A.H. is a participant in the BIH-Charité Advanced Clinician Scientist Program funded by the Charité—Universitätsmedizin Berlin and the Berlin Institute of Health. The LipidCardio Study was partially funded by the Sanofi-Aventis Deutschland GmbH (I.D. and U.L.). P.P.S. was supported in part by an AHA postdoctoral grant 20POST35210937. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank G. Deshpande (Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic) for technical support during whole blood in vitro thrombosis studies. We also thank M. Ferrell for assistance in data analysis and T. Weeks (both at the Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic) for editing the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

M.W. participated in the design of all in vitro and in vivo studies, performed experiments and statistical analysis and drafted the manuscript. M.W. and I.N. wrote the manuscript with input from all authors. I.N. and H.A. developed and performed the mass spectrometry analysis in human and mouse samples. N.N. helped with mass spectrometry analysis. J.W. and M.W. coordinated the Cosette study. N.G. performed whole blood in vitro thrombosis assays. P.P.S. helped with calcium studies. T.C. and O.F. performed untargeted metabolic analysis. Y.W. and X.S.L. analyzed data. A.H., I.D., M.K., E.S.-T. and U.L. contributed clinical study samples and assisted with data analysis from the European validation cohort. W.H.W.T. coordinated the Cosette study and provided critical scientific input and discussions. S.L.H. conceived, designed and supervised all experiments and participated in the drafting and editing of the article. All authors contributed to the critical review of the manuscript.

Corresponding author

Correspondence to Stanley L. Hazen.

Ethics declarations

Competing interests

Hazen reports being named as co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, being a paid consultant formerly for Procter and Gamble and currently with Zehna Therapeutics. He also reports having received research funds from Procter and Gamble, Zehna Therapeutics and Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, a wholly owned subsidiary of Quest Diagnostics, Procter and Gamble and Zehna therapeutics. Tang reports being a consultant for Sequana Medical A.G., Owkin Inc., Relypsa Inc. and PreCardiac Inc., having received an honorarium from Springer Nature for authorship/editorship and American Board of Internal Medicine for exam writing committee participation—all unrelated to the subject and contents of this paper. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Peer review

Peer review information

Nature Medicine thanks Andrew Gray, Steffen Massberg and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Ming Yang, in collaboration with the Nature Medicine team.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Polyol metabolites and major adverse cardiovascular events (MACE) in untargeted metabolomics analyses of the discovery cohort.

Shown are boxplots with relative levels for the indicated polyol (defined as compounds with two or more hydroxyl groups) area in both patients with (red) and without (blue) incident (3 yr) MACE ranked by Mann Whitney P values. Compound relative areas are shown as log of fold change (no MACE vs. MACE) to facilitate comparison. Boxes represent interquartile ranges (IQR) with the notch indicating the median. Lower whiskers represent smallest observation (≥25% quantile -1.5×IQR) and upper whiskers largest observation (≤75% quantile +1.5×IQR). Two-sided P values were calculated by Mann–Whitney U-test. N for no MACE = 1041, n for MACE = 116. False discovery rate corrected two-sided P values (Benjamini-Hochberg method) are indicated as follows: ****P<0.0001, ***P < 0.001, **P < 0.01, *P < 0.05.

Extended Data Fig. 2 Chromatographic separation of erythritol from its structural isomer threitol.

After exhaustive acetylation with acetic acid anhydride, the polyols erythritol and its structural isomer, threitol, were baseline resolved by the HPLC method developed. Shown are the chromatograms generated by multiple reaction monitoring transitions (MRM) for the derivatized plasma analytes (m/z 308; [M+NH4]+) and synthetic isotopically labeled erythritol internal standard (D6-Erythritol; m/z 314; [M+NH4]+). With the column matrix and mobile phase /gradient employed, coupled with the characteristic parent [M+NH4+] —> daughter ion transition used (for both erythritol and threitol), baseline chromatographic resolution of the two structural isomers was achieved.

Extended Data Fig. 3 Plasma levels of erythritol are elevated in patients with major adverse cardiovascular events (MACE) and coronary artery disease (CAD) in both US and European validation cohorts.

Erythritol levels in patients stratified by presence of (3 year) MACE or CAD. Data are shown as log of plasma Erythritol. Plotted are individual values as dots. Boxes represent interquartile ranges (IQR) with the notch indicating the median. Lower whiskers represent smallest observation (≥25% quantile - 1.5×IQR) and upper whiskers largest observation (≤75% quantile + 1.5×IQR). Two-sided P values were calculated by Mann–Whitney U-test. Numbers of subjects within each group are indicated.

Extended Data Fig. 4 Erythritol increases platelet aggregation responses to submaximal concentrations of agonists.

ADP-stimulated and Thrombin receptor-activating peptide(TRAP)6-stimulated platelet aggregometry responses of human platelet-rich plasma with fixed concentration of erythritol (45 or 90 μM, red) versus normal saline (vehicle, blue). Data in bar graphs are represented as means (±s.d.), and two-sided P values were calculated by Mann Whitney Test (bar graphs) and by 2-way analysis of variance (overall P value is shown for erythritol effect) with Sidák’s post hoc test. Sidák’s adjusted P values for Erythritol 45 μM vs. vehicle: for ADP 2 μM P = 0.01, ADP 3 μM P = 0.005, for erythritol 90 μM vs. vehicle: TRAP6 5 μM: P = 0.0002. Numbers of independent biological replicates (n) are indicated. *P < 0.05, ** P < 0.01, ***P < 0.001.

Extended Data Fig. 5 Impact of glucose on platelet aggregation.

ADP-stimulated (left panel) and Thrombin receptor-activating peptide (TRAP) 6-stimulated (right panel) platelet aggregometry responses in human platelet-rich plasma incubated with glucose (270 μM, green) versus vehicle (saline, blue). Data in bar graphs are represented as means (±s.d.). Two-sided P values were calculated using Mann–Whitney U-test. Numbers of independent biological replicates (n) are indicated.

Extended Data Fig. 6 Impact of 1,5-Anhydroglucitol (AHG) on platelet aggregation and calcium release.

Panel A ADP-stimulated and Thrombin receptor-activating peptide (TRAP)6-stimulated platelet aggregometry responses in human platelet-rich plasma incubated with 1,5-AHG (green) versus vehicle (saline, blue). Two-sided P values were calculated by Mann Whitney Test. For ADP and TRAP6 stimulated platelet-rich plasma n = 7. Panel B shows thrombin-induced (0.02 U ml−1) changes in intracellular calcium concentration in Fura 2-filled washed human platelets incubated with 1,5-AHG (green) or vehicle (saline, blue). Data represent mean (±s.d.). Two-sided P values were calculated by Wilcoxon matched-pairs signed rank test. Numbers of independent biological replicates (n) are indicated.

Extended Data Fig. 7 Impact of 1,5-Anhydroglucitol (AHG) and glucose on platelet activation.

ADP-induced changes in GP IIb/IIIa (PAC-1 antibody staining) and P-selectin surface expression in washed human platelets pre-incubated with vehicle (saline, blue) or the indicated concentrations of either 1,5-AHG (green, panel A) or glucose (green, panel B). Bars represent means (±s.d.), Two-sided P values were calculated by Kruskal–Wallis test with Dunn’s post hoc test for multiple-group comparisons. Numbers of independent biological replicates (n) are indicated.

Extended Data Fig. 8 Impact of erythritol at different physiological concentrations on platelet aggregation responses.

Human platelet-rich plasma was incubated with erythritol (red) at low levels observed in fasting patients (18 μM) and higher concentrations observed after erythritol ingestions (6 mM) versus vehicle (saline, blue). Shown are thrombin receptor-activating peptide(TRAP)6-stimulated (panel A) and ADP-stimulated (panel B) platelet aggregometry responses. Data in bar graphs are represented as means (±s.d.). Two-sided P values were calculated by Mann Whitney Test. Numbers of independent biological replicates (n) are indicated.

Supplementary information

Supplementary Information

Supplementary Fig. 1 and Supplementary Tables 1–14.

Reporting Summary

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Witkowski, M., Nemet, I., Alamri, H. et al. The artificial sweetener erythritol and cardiovascular event risk. Nat Med 29, 710–718 (2023). https://doi.org/10.1038/s41591-023-02223-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41591-023-02223-9

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing