The Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation

NCT05967741 | Recruiting

• 1 other identifier: 2030510
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose is to conduct a dietary intervention study in which human participants will consume beverages sweetened with erythritol or aspartame, each for 2 weeks, in a randomized crossover design

Conditions

Platelet Aggregation, Spontaneous; Vascular Thrombosis

Keywords

platelet activation; vascular inflammation; erythritol; aspartame; dietary intervention

Outcome Measures

Primary Outcomes (10)

• P-selectin, a platelet surface marker, assessed as median fluorescence intensity

  Change in median fluorescence intensity of P-selectin, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

• P-selectin, a platelet surface marker, assessed as percentage of P-selectin positive cells

  Change in percentage of P-selectin positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

• PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as median fluorescence intensity

  Change in median fluorescence intensity of PAC-1, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

• PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as percentage of PAC-1 positive cells

  Change in percentage of PAC-1 positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

• Annexin V, a platelet surface marker, assessed as median fluorescence intensity

  Change in median fluorescence intensity of annexin V, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

• Annexin V, a platelet surface marker, assessed as percentage of annexin V positive cells

  Change in percentage of annexin V positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

• Platelet reactivity to physiologic agonist, assessed as change in median fluorescence intensity

  The change in median fluorescence intensity induced by physiologic agonists, an index of platelet reactivity, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

• Platelet aggregation in response to physiologic agonist, assessed as aggregation/min

  The change in aggregation/min induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

• Platelet aggregation in response to physiologic agonist, assessed as percent of maximum aggregation

  The change in % maximum aggregation induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

• Platelet-leukocyte interaction, assessed as platelet/leukocyte aggregate size by fluorescence mean intensity

  Change in platelet/leukocyte aggregate size, an index of platelet-leukocyte interaction, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks

  6 weeks

Secondary Outcomes (9)

• Plasma concentration of E-Selectin

  6 weeks

• Plasma concentration of sVCAM1

  6 weeks

• Plasma concentration of sICAM1

  6 weeks

• Plasma concentration of D-dimer

  6 weeks

• Plasma concentration of Platelet factor 4

  6 weeks

Other Outcomes (8)

• Plasma concentration of glucose

  6 weeks

• Plasma concentration of triglyceride

  6 weeks

• Plasma concentration of cholesterol

  6 weeks

Study Arms (2)

Erythritol-sweetened beverage

EXPERIMENTAL

1-gram erythritol/kg body weight/day, divided into three beverage servings and fruit-flavored with Kool-Aid® unsweetened drink mix.

Other: Erythritol

Aspartame-sweetened beverage

PLACEBO COMPARATOR

Control beverages will be made from a noncaloric aspartame-sweetened, fruit-flavored drink mix at the concentration needed to match the sweetness (\~3 mg aspartame/kg/day) and flavoring of the erythritol beverages on a per volume basis.

Other: Aspartame

Interventions

Erythritol OTHER

Erythritol is a naturally occurring and non-nutritive sugar alcohol that is classified as generally recognized as safe (GRAS)

Also known as: Noncaloric sugar alcohol

Erythritol-sweetened beverage

Aspartame OTHER

Aspartame consists of two amino acids, phenylalanine and aspartic acid, and a methyl group. It does not have metabolic effects and has served as the blinded control beverage in the investigators' completed NIH-funded clinical trials.

Also known as: Noncaloric sweetener

Aspartame-sweetened beverage

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI ≥ 27 kg/m2

You may not qualify if:

• History of blood clot, transient ischemic attack (TIA), stroke, angina, heart attack, or peripheral vascular disease, or current cancer diagnosis.
• Pregnant or lactating women
• Current, prior (within 12 months), or anticipated use of medications for treatment of hyperlipidemia, high blood pressure or diabetes, or any medication that in the opinion of the investigators will confound results.
• Unwilling to forego the use of anti-inflammatory medication during study.
• Unwilling to forego the use of marijuana during the study.
• Use of tobacco.
• Strenuous exerciser (\>4 hours/week at a level more vigorous than walking).
• Surgery or medication for weight loss.

Sponsors & Collaborators

• University of California, Davis: lead

Study Sites (1)

Ragle Human Nutrition Research Center, University of California, Davis

Davis, California, 95616, United States

RECRUITING

Related Publications (1)

• Witkowski M, Nemet I, Alamri H, Wilcox J, Gupta N, Nimer N, Haghikia A, Li XS, Wu Y, Saha PP, Demuth I, Konig M, Steinhagen-Thiessen E, Cajka T, Fiehn O, Landmesser U, Tang WHW, Hazen SL. The artificial sweetener erythritol and cardiovascular event risk. Nat Med. 2023 Mar;29(3):710-718. doi: 10.1038/s41591-023-02223-9. Epub 2023 Feb 27.

  PMID: 36849732 BACKGROUND

MeSH Terms

Conditions

Platelet Aggregation, Spontaneous; Thrombosis

Interventions

Erythritol; Ethanol; Aspartame

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Kimber L. Stanhope, Ph.D.

CONTACT

5302190914; klstanhope@ucdavis.edu

Marinelle Nunez, B.S.

CONTACT

530-752-2146; mvnunez@ucdavis.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Experimental and control beverage are formulated to be similar color, taste and volume.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized crossover study with 2-week washout

Study Record Dates

• First Submitted: June 6, 2023
• First Posted: August 1, 2023
• Study Start: July 20, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)