Clinical trial NCT04731363: Consumption of Oral Artificial Sweeteners on Platelet Aggregation and Polyol Excretion
Official title: Consumption of Oral Artificial Sweeteners on Platelet Aggregation and Polyol Excretion
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Cardiovascular Risk Factor
Keywords: xylitol
erythritol
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2021-02-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Platelet Aggregation After Polyol Ingestion
timeFrame: 30 minutes
measure: Change From Baseline in Platelet Aggregation at 30 Minutes Post Polyol Ingestion
timeFrame: Baseline and 30 minutes post ingestion of polyol intervention
measure: Plasma Polyol Levels After Polyol Ingestion
timeFrame: 30 minutes
measure: Change From Baseline in Plasma Polyol Levels at 30 Minutes Post Polyol Ingestion
timeFrame: Baseline and 30 minutes post ingestion of polyol intervention
measure: Urinary Polyol Levels After Polyol Ingestion
timeFrame: 30 minutes
measure: Change From Baseline in Urinary Polyol Levels at 30 Minutes Post Polyol Ingestion
timeFrame: Baseline and 30 minutes post ingestion of polyol intervention
Secondary outcomes:
measure: Change From Baseline in Plasma Lipid Profile at 1 Day Post Polyol Ingestion
timeFrame: Baseline and 1 day post ingestion of polyol intervention
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Wilson Tang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Oku T, Okazaki M. Laxative threshold of sugar alcohol erythritol in human subjects. Nutrition Research. 1996;16(4):577-89.
citation: 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.
citation: 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.
citation: 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.