Consumption of Oral Artificial Sweeteners on Platelet Aggregation and Polyol Excretion

NCT04731363 | Active Not Recruiting Results

• 1 other identifier: 21-005
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The principal goal for the study is to examine whether ingestion of a beverage containing artificial sweeteners alters in vitro platelet aggregation. Because of the increasing number of cardiometabolic diseases, such as diabetes mellitus, in the population, the use of artificial sweeteners to replace free sugars has been gaining popularity. Two popular artificial sweeteners are erythritol and xylitol. Erythritol and xylitol are both naturally occurring polyols found in fruits and vegetables. They are potent artificial sweeteners with a higher sweetening intensity and lower calorie content than table sugar. Previous research has shown that the higher levels of sugar alcohols, like those used as artificial sweeteners, in the blood are related to a higher risk of cardiovascular complications, like heart attacks and strokes, and death. This may be because higher levels of sugar alcohols in one's blood may increase the activity of platelets, which would then increase the risk of heart attack and stroke. The investigators therefore want to find if consuming a single beverage that contains an artificial sweetener can raise the levels of sugar alcohols in the blood and if it can alter platelet function or aggregation.

Conditions

Cardiovascular Risk Factor

Keywords

xylitol; erythritol

Outcome Measures

Primary Outcomes (6)

• Platelet Aggregation After Polyol Ingestion

  Measuring platelet function 30 minutes after polyol ingestion, using established in vitro platelet assays. Platelet aggregation responses, based on changes in light transmission after adding different concentrations of the agonists ADP and TRAP6 are reported. A higher percentage of light transmission indicates an increased aggregation response, with maximum amplitude (100%) indicating total aggregation.

  30 minutes

• Change From Baseline in Platelet Aggregation at 30 Minutes Post Polyol Ingestion

  Measuring changes in platelet function before versus after xylitol or erythritol ingestion, using established in vitro platelet assays. Platelet aggregation responses, based on changes in light transmission after adding different concentrations of the agonists ADP and TRAP6 are reported. A higher percentage of light transmission indicates an increased aggregation response, with maximum amplitude (100%) indicating total aggregation.

  Baseline and 30 minutes post ingestion of polyol intervention

• Plasma Polyol Levels After Polyol Ingestion

  Measuring plasma levels (uM) of polyols (xylitol or erythritol) 30 minutes after xylitol or erythritol ingestion, using established techniques by mass spectrometry. Xylitol was measured, and is reported below, in the two xylitol intervention arms and erythritol was measured, and is reported below, in the erythritol and glucose intervention arms.

  30 minutes

• Change From Baseline in Plasma Polyol Levels at 30 Minutes Post Polyol Ingestion

  Measuring changes in levels of plasma polyols before versus after xylitol or erythritol ingestion, using established techniques by mass spectrometry. Xylitol concentrations are reported in the two xylitol intervention arms. Erythritol concentrations are reported in the erythritol and glucose intervention arms.

  Baseline and 30 minutes post ingestion of polyol intervention

• Urinary Polyol Levels After Polyol Ingestion

  Measuring the urinary levels of polyols (xylitol or erythritol) 30 minutes after xylitol or erythritol ingestion, using established techniques by mass spectrometry. Xylitol was measured, and is reported below, in the two xylitol intervention arms and erythritol was measured, and is reported below, in the erythritol and glucose intervention arms.

  30 minutes

• Change From Baseline in Urinary Polyol Levels at 30 Minutes Post Polyol Ingestion

  Measuring changes in levels of urinary polyols before versus after xylitol or erythritol ingestion, using established techniques by mass spectrometry. Xylitol was measured, and is reported below, in the two xylitol intervention arms and erythritol was measured, and is reported below, in the erythritol and glucose intervention arms.

  Baseline and 30 minutes post ingestion of polyol intervention

Secondary Outcomes (1)

• Change From Baseline in Plasma Lipid Profile at 1 Day Post Polyol Ingestion

  Baseline and 1 day post ingestion of polyol intervention

Study Arms (4)

Xylitol, 30g

EXPERIMENTAL

oral xylitol, a potent artificial sweetener

Dietary Supplement: xylitol, 30g

Erythritol, 30g

EXPERIMENTAL

oral erythritol, a potent artificial sweetener

Dietary Supplement: erythritol, 30g

Xylitol, 5g

EXPERIMENTAL

oral xylitol, a potent artificial sweetener

Dietary Supplement: xylitol, 5g

Glucose, 30g

ACTIVE COMPARATOR

oral glucose, delivered as dextrose

Dietary Supplement: glucose, 30g

Interventions

xylitol, 5g DIETARY_SUPPLEMENT

Intervention is a drink consisting of 300mL of water containing 5g of xylitol as a single oral dose.

Xylitol, 5g

glucose, 30g DIETARY_SUPPLEMENT

Intervention is a drink consisting of 300mL of water containing 30g of glucose (dextrose) as a single oral dose.

Also known as: dextrose, 30g

Glucose, 30g

xylitol, 30g DIETARY_SUPPLEMENT

Intervention is a drink consisting of 300mL of water containing 30g of xylitol as a single oral dose.

Xylitol, 30g

erythritol, 30g DIETARY_SUPPLEMENT

Intervention is a drink consisting of 300mL of water containing 30g of erythritol as a single oral dose.

Erythritol, 30g

Eligibility Criteria

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

You may qualify if:

• Age 18 years or above.
• Willing and able to sign the consent form.

You may not qualify if:

• Use of anti-platelet medications within 14 days of study enrollment.
• Active infection or received antibiotics within 1 month of study enrollment.
• Use of over-the-counter probiotic within 1 month of study enrollment.
• Diabetes mellitus
• Ulcerative colitis, Crohn's disease, or other chronic gastrointestinal disorder.
• Past history of bariatric procedures or surgeries (e.g. gastric banding or bypass).
• Pregnancy.
• Significant chronic illness.
• Men and women age 18 years or above.
• Able to provide informed consent and comply with study protocol.
• Diabetes Mellitus Type II
• Use of anti-platelet medications within 14 days of study enrollment.
• Active infection or received antibiotics within 1 month of study enrollment.
• Use of over-the-counter probiotic within 1 month of study enrollment.
• Ulcerative colitis, Crohn's disease, or other chronic gastrointestinal disorder.

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (5)

• Makinen KK. Gastrointestinal Disturbances Associated with the Consumption of Sugar Alcohols with Special Consideration of Xylitol: Scientific Review and Instructions for Dentists and Other Health-Care Professionals. Int J Dent. 2016;2016:5967907. doi: 10.1155/2016/5967907. Epub 2016 Oct 20.

  PMID: 27840639 BACKGROUND

• Oku T, Okazaki M. Laxative threshold of sugar alcohol erythritol in human subjects. Nutrition Research. 1996;16(4):577-89.

  BACKGROUND

• 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 RESULT

• Witkowski M, Nemet I, Li XS, Wilcox J, Ferrell M, Alamri H, Gupta N, Wang Z, Tang WHW, Hazen SL. Xylitol is prothrombotic and associated with cardiovascular risk. Eur Heart J. 2024 Jul 12;45(27):2439-2452. doi: 10.1093/eurheartj/ehae244.

  PMID: 38842092 RESULT

• Witkowski M, Wilcox J, Province V, Wang Z, Nemet I, Tang WHW, Hazen SL. Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report. Arterioscler Thromb Vasc Biol. 2024 Sep;44(9):2136-2141. doi: 10.1161/ATVBAHA.124.321019. Epub 2024 Aug 8.

  PMID: 39114916 RESULT

MeSH Terms

Interventions

Xylitol; Erythritol; Glucose

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Hexoses; Monosaccharides; Sugars

Results Point of Contact

• Title: Dr. Stanley Hazen, MD
• Organization: Cleveland Clinic Foundation

hazens@ccf.org

216-444-9426

Study Officials

• Wilson Tang, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff, Cellular and Molecular Medicine & Cardiovascular Medicine, Section of Heart Failure

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: February 1, 2021
• Study Start: March 10, 2021
• Primary Completion: August 30, 2023
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 22, 2026
• Results First Posted: June 11, 2025

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)