Consumption of Oral Artificial Sweeteners on Platelet Aggregation and Polyol Excretion

NCT ID: NCT04731363

Last Updated: 2025-06-11

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-10

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cardiovascular Risk Factor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Xylitol, 30g

oral xylitol, a potent artificial sweetener

Group Type EXPERIMENTAL

xylitol, 30g

Intervention Type DIETARY_SUPPLEMENT

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

Erythritol, 30g

oral erythritol, a potent artificial sweetener

Group Type EXPERIMENTAL

erythritol, 30g

Intervention Type DIETARY_SUPPLEMENT

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

Xylitol, 5g

oral xylitol, a potent artificial sweetener

Group Type EXPERIMENTAL

xylitol, 5g

Intervention Type DIETARY_SUPPLEMENT

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

Glucose, 30g

oral glucose, delivered as dextrose

Group Type ACTIVE_COMPARATOR

glucose, 30g

Intervention Type DIETARY_SUPPLEMENT

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

Interventions

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xylitol, 30g

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

Intervention Type DIETARY_SUPPLEMENT

erythritol, 30g

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

Intervention Type DIETARY_SUPPLEMENT

xylitol, 5g

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

Intervention Type DIETARY_SUPPLEMENT

glucose, 30g

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

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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dextrose, 30g

Eligibility Criteria

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Inclusion Criteria

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


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

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.


* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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The Cleveland Clinic

OTHER

Sponsor Role lead

Responsible Party

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Wilson Tang

Staff, Cellular and Molecular Medicine & Cardiovascular Medicine, Section of Heart Failure

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wilson Tang, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 27840639 (View on PubMed)

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

Reference Type 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.

Reference Type RESULT
PMID: 36849732 (View on PubMed)

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.

Reference Type RESULT
PMID: 38842092 (View on PubMed)

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.

Reference Type RESULT
PMID: 39114916 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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21-005

Identifier Type: -

Identifier Source: org_study_id

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