Consumption of Oral Artificial Sweeteners on Platelet Aggregation and Polyol Excretion (COSETTE)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Risk Factor
• Intervention / Treatment: Dietary supplement: xylitol, 30g; Dietary supplement: erythritol, 30g; Dietary supplement: xylitol, 5g; Dietary supplement: glucose, 30g

Detailed Description

The purpose of this study is to examine if drinking a single beverage that contains an artificial sweetener can perceptibly alter the activity of platelets in the body. Platelets are a component of blood that are primarily responsible for helping to stop bleeding and repair damaged blood vessels by grouping together, a process known as aggregation, to form clots.

Artificial sweeteners are popular because they have a lower calorie content than table sugar while still making food and beverages sweet. Their use as a sugar substitute is especially attractive for people with heart disease or diabetes, or for people who are trying to lose weight.

Two popular artificial sweeteners are erythritol and xylitol. Erythritol and xylitol are both naturally occurring polyols, also called sugar alcohols, found in fruits and vegetables. They are potent artificial sweeteners with a higher sweetening intensity and lower calorie content than table sugar.This makes them attractive for the use as sugar substitutes or alternatives, particularly for patients with type 2 diabetes.

Up to now, there is no prospective data available about polyols with respect to their impact on event outcomes in cardiovascular patients, despite their extensive use in the food industry. Moreover, little is known about plasma levels and metabolic changes following food intake of artificial sweeteners, in particular polyols.

The investigators have previously measured fasting levels of various polyols in a large clinical cohort of cardiovascular patients and found that some candidate polyols are related to a higher risk of cardiovascular complications and death. In vitro data using human platelets revealed that the polyols xylitol and erythritol at the levels observed in fasting patients induce platelet aggregation potential. The investigator's data shows that erythritol and xylitol impact platelet function and may, therefore, contribute to cardiovascular mortality.

In preliminary studies the investigators found that when ingesting either erythritol or xylitol, the levels of these sweeteners in the plasma rise within the first hour after consumption. With this study the investigators wish to examine whether the postprandial levels are capable of altering platelet function in vitro. The investigators hypothesize that postprandial polyol concentrations following ingestion increase platelet aggregation in the blood.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Timothy Engelman, LPN; Phone Number: 216-636-6153; Email: engelmt@ccf.org
• Study Contact Backup: Name: Jennifer Wilcox, BA; Phone Number: 216-636-6153; Email: kirsopj@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Cohort 1 Inclusion Criteria:

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

Cohort 1 Exclusion Criteria:

• 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.

Cohort 2 Inclusion Criteria:

• Men and women age 18 years or above.
• Able to provide informed consent and comply with study protocol.
• Diabetes Mellitus Type II

Cohort 2 Exclusion Criteria:

• 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.
• Past history of bariatric procedures or surgeries (e.g. gastric banding or bypass).
• Pregnancy.
• Any condition that, in the judgment of the Investigator, would place a subject at undue risk by being enrolled in the trial or cause inability to comply with the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xylitol, 30g; oral xylitol, a potent artificial sweetener	Dietary supplement: xylitol, 30g; Intervention is a drink consisting of 300mL of water containing 30g of xylitol as a single oral dose.
Experimental: Erythritol, 30g; oral erythritol, a potent artificial sweetener	Dietary supplement: erythritol, 30g; Intervention is a drink consisting of 300mL of water containing 30g of erythritol as a single oral dose.
Experimental: Xylitol, 5g; oral xylitol, a potent artificial sweetener	Dietary supplement: xylitol, 5g; Intervention is a drink consisting of 300mL of water containing 5g of xylitol as a single oral dose.
Active Comparator: Glucose, 30g; oral glucose, delivered as dextrose	Dietary supplement: glucose, 30g; Intervention is a drink consisting of 300mL of water containing 30g of glucose (dextrose) as a single oral dose.; Other Names: dextrose, 30g

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet Aggregation After Polyol Ingestion	Measuring platelet function 30 minutes after polyol ingestion, using established in vitro platelet assays.	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.	Baseline and 30 minutes post ingestion of polyol intervention
Plasma Polyol Levels After Polyol Ingestion	Measuring plasma levels of polyols 30 minutes after xylitol or erythritol ingestion, using established techniques by mass spectrometry.	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.	Baseline and 30 minutes post ingestion of polyol intervention
Urinary Polyol levels After Polyol Ingestion	Measuring the plasma levels of polyols 30 minutes after xylitol or erythritol ingestion, using established techniques by mass spectrometry.	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.	Baseline and 30 minutes post ingestion of polyol intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Plasma Lipid Profile at 30 minutes Post Polyol Ingestion	Measuring changes in lipid levels as markers of changes in metabolism before versus after xylitol or erythritol ingestion.	Baseline and 30 minutes post ingestion of polyol intervention

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Wilson Tang, MD, The Cleveland Clinic

Publications and helpful links

General Publications

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

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2021
• Primary Completion (Actual): August 30, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: xylitol; erythritol
• Additional Relevant MeSH Terms: Vasodilator Agents; Erythritol
• Other Study ID Numbers: 21-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No