Effect of Daily Erythritol Versus Sucrose Intake Over 5 Weeks on Glucose Tolerance in Adolescents (EryAdo)

Effect of Daily Erythritol Versus Sucrose Intake Over 5 Weeks on Glucose Tolerance in Adolescents: a Pilot Trial

This trial is divided into different parts: Part A the EryAdo trial and Part B the EryClot trial.

Part A EryAdo Trial:

Childhood and adolescence are crucial periods for prevention of obesity, as obese children are five times more likely to be obese at adulthood than lean children. To this purpose, sugar consumption should be reduced. The sugar alcohol erythritol is increasingly popular as sugar substitute in the food industry and is also recommended to diabetic patients. The substance is freely available. Recent acute studies show that erythritol has a positive influence on satiation and gastric emptying without affecting insulin and plasma glucose. In this trial, the investigators aim to assess the effect of a chronic intake of erythritol versus sucrose on insulin resistance in healthy adolescents.

Part B EryClot Trial:

In recently published studies, a prothrombotic effect of erythritol and xylitol was described.

Therefore, within a pilot study the investigators examined whether erythritol is detectable in the blood after administration of erythritol and conventional sweeteners (glucose and fructose). Also the effect on blood clotting was investigated.

These preliminary tests served to clarify the data situation so that further studies can be based on them.

The preliminary results of the pilot study indicated that there appears to be no measurable effect of erythritol on thrombocyte aggregation. This implicated that there is a discrepancy between our results and the results reported in a recent published study. This is why we need to assess the effects of erythritol in more detail (thrombocyte aggregation, and markers of platelet activation, endothelial activation and coagulation) in more subjects.

Due to a study published in 2024 describing similar prothrombotic effects for xylitol, this substance needs to be investigated as well. Thus, the participants will receive erythritol, xylitol, or water in a randomized order.

In addition to the EryClot ex vivo experiments, we will conduct in vitro experiments incubating platelet-rich plasma from healthy donors with increasing concentrations erythritol or xylitol followed by measurement of platelet aggregation by aggreegometry assay.

Study Overview

• Status: Active, not recruiting
• Conditions: Insulin Resistance; Body Composition; Glucose Tolerance; Gastrointestinal Tolerance; Thrombocyte Aggregation; Blood p-Selectin; Blood Erythritol; Blood Xylitol
• Intervention / Treatment: Dietary supplement: Sucrose; Dietary supplement: Erythritol; Dietary supplement: Glucose; Dietary supplement: Fructose; Dietary supplement: Xylitol; Dietary supplement: Water

Detailed Description

Part A EryAdo Trial:

This trial aims to assess the effects of the daily intake of an erythritol-sweetened beverage over 5 weeks on insulin resistance, glucose tolerance and metabolism as well as on gut microbiota. Moreover, this study will also assess the effect of the above-mentioned intervention on food intake, body composition and gastrointestinal tolerance in this population.

Part B EryClot Trial:

The aim of this study is to investigate whether erythritol is detectable in the blood after administration of glucose and fructose, whether there is an effect of erythritol or xylitol on blood clotting and to investigate the platelet responsiveness in vitro in human plasma after addition of erythritol and xylitol.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4002
      • St. Claraspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Part A EryAdo Trial:

Inclusion Criteria:

• Healthy adolescents
• Aged 14-18 years
• Normal weight (BMI between 15th and 85th percentile for age and gender)
• Minimum weight of 45kg
• Regular sugar consumption >25g/d

Exclusion Criteria:

• Severe acute or chronic diseases
• Pregnancy
• Regular intake of prebiotics
• Regular intake of probiotics
• Regular intake of pro-/prebiotic foods
• Antibiotics cure within 3 months preceding the present study
• Substance abuse
• Inability to follow procedures due to psychological disorders or insufficient knowledge of project language (German)
• Participation in another study with investigational drug within the 30 days preceding and during the present study.
• Pre-existing regular consumption (>1/week) of erythritol
• Fructose-intolerance
• Pre-existing diet (vegetarian, vegan, gluten-free, lactose-free, caloric restriction, etc.)

Part B EryClot Trial:

Inclusion criteria:

• Healthy participants 18-55 years upon inclusion
• Normal weight (BMI between 19.0-24.9 kg/m2; for in vitro: BMI < 30 kg/m2)
• Informed consent signed by participant

Exclusion criteria:

• Severe acute or chronic diseases
• Pregnancy: although no contraindication, pregnancy might influence metabolic state. Female adolescents who are pregnant or have the intention to become pregnant during the course of the study are excluded. In female participants a urine pregnancy test is carried out upon screening
• Substance abuse, smoking
• Inability to follow procedures due to psychological disorders
• Participation in another study with investigational drug within the 30 days preceding and during the present study.
• Pre-existing regular consumption (>1/week) of erythritol or xylitol
• Pre-existing impairment of blood coagulation/thrombocyte function (e.g., hereditary, regular intake of anti-coagulant agents (e.g., NSAIDs, heparin, warfarin, etc.))

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EryAdo: Sucrose; Participants receive 25g sucrose per day during 5 weeks	Dietary supplement: Sucrose; Sucrose-sweetened beverages twice a day (25g sucrose/day) with main meals during 5 weeks
Experimental: EryAdo: Erythritol; Participants receive 36g erythritol per day during 5 weeks	Dietary supplement: Erythritol; EryAdo: Erythritol-sweetened beverages twice a day (36g erythritol/day) with main meals during 5 weeks EryClot: Erythritol 50g dissolved in 300mL water administered once per visit; Other Names: E968-Erythritol
Active Comparator: EryClot Glucose; Participants receive 75g glucose dissolved in 300mL water once during the visit (only in the pilot study)	Dietary supplement: Glucose; Glucose 75g dissolved in 300mL water administered once per visit
Active Comparator: EryClot Fructose; Participants receive 25g fructose dissolved in 300mL water once during the visit (only in the pilot study)	Dietary supplement: Fructose; Fructose 25g dissolved in 300mL water administered once per visit
Experimental: EryClot Erythritol; Participants receive 50g erythritol dissolved in 300mL water once during the visit	Dietary supplement: Erythritol; EryAdo: Erythritol-sweetened beverages twice a day (36g erythritol/day) with main meals during 5 weeks EryClot: Erythritol 50g dissolved in 300mL water administered once per visit; Other Names: E968-Erythritol
Experimental: EryClot Xylitol; Participants receive 33.5g xylitol dissolved in 300mL water once during the visit	Dietary supplement: Xylitol; Xylitol 33.5g dissolved in 300mL water administered once per visit; Other Names: E967-Xylitol
Placebo Comparator: EryClot Water; Participants receive 300mL water once during the visit	Dietary supplement: Water; 300mL water administered once per visit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EryAdo: Insulin resistance	Insulin resistance as measured by the HOMA Index.	Change from baseline to 5 weeks after polyol/sucrose intake
EryClot: Platelet Aggregation After Sweetener Ingestion	Measuring ex vivo platelet aggregation turbidimetrically using an optical aggregometer	0 and 60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EryAdo: Glucose tolerance: Insulin	Insulin levels during OGTT	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Glucose tolerance: Glucose	Glucose levels during OGTT	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Glucose tolerance: C-Peptide	C-peptide levels during OGTT	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Glucose tolerance: Glucagon	Glucagon levels during OGTT	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Glucose tolerance: Fructosamin	Fructosamin levels	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Glucose tolerance: HbA1C	HbA1C levels	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Glucose tolerance: Continuous glucose monitoring average	Continuous glucose monitoring for average glucose levels	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Glucose tolerance: Continuous glucose monitoring glucose variability	Continuous glucose monitoring for glucose variability	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Glucose tolerance: Continuous glucose monitoring time within range	Continuous glucose monitoring for time within range	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Glucose absorption	Glucose absorption measured by 3-OMG concetrations during OGTT	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Metabolomics	Metabolomics in plasma, urine and stool samples, measured by 1H-NMR and Liquid Chromatography-Mass Spectrometry (LC-MS).	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Gut microbiota composition	The taxonomic and functional profiles of the gut microbiota (stool samples) assessed by metagenomic shotgun sequencing.	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Gastrointestinal hormones secretion: GLP-1	Secretion of GLP-1 during OGTT	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Gastrointestinal hormones secretion: PYY	Secretion of PYY during OGTT	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Gastrointestinal hormones secretion: Ghrelin	Secretion of Ghrelin during OGTT	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Gastrointestinal hormones secretion: CCK	Secretion of CCK during OGTT	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Food intake	Food intake assessed with self-reported food records	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Gastrointestinal tolerance	Gastrointestinal tolerance recorded by the "Gastrointestinal Symptoms Rating Scale" (GSRS), 15 items rated on 7 Point Likert-Scale, a higher score means a worse outcome. Maximum score: 90, Minimum score: 0	Change from baseline to 3 and 5 weeks after polyol/sucrose intake
EryAdo: Body composition: fat mass	Body composition assessed by mean of bioimpedance analysis: fat mass in kg	Change from baseline to 5 weeks after polyol/sucrose intake
EryAdo: Body composition: fat free mass	Body composition assessed by mean of bioimpedance analysis: fat free mass in kg	Change from baseline to 5 weeks after polyol/sucrose intake
EryClot blood p-selectin concentrations	Blood p-Selectin concentrations after consumption of test solution	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
EryClot blood sVCAM1 concentrations	Blood sVCAM1 concentrations after consumption of test solution	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
EryClot blood PF4 concentrations	Blood PF4 concentrations after consumption of test solution	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
EryClot blood D-Dimer concentrations	Blood D-Dimer concentrations after consumption of test solution	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
EryClot blood Erythritol concentrations	Blood erythritol concentrations after consumption of test solution	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
EryClot blood Xylitol concentrations	Blood xylitol concentrations after consumption of test solution	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Bettina K. Wölnerhanssen, PD. MD, St. Clara Research Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2021
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: July 6, 2021
• First Posted (Actual): July 19, 2021

Study Record Updates

• Last Update Posted (Actual): September 30, 2026
• Last Update Submitted That Met QC Criteria: September 25, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Nutritional and Metabolic Diseases; Insulin Resistance; Organic Chemicals; Carbohydrates; Inorganic Chemicals; Alcohols; Polysaccharides; Anions; Ions; Electrolytes; Hydroxides; Alkalies; Oxides; Oxygen Compounds; Disaccharides; Oligosaccharides; Sugars; Sugar Alcohols; Hexoses; Monosaccharides; Ketoses; Erythritol; Water; Glucose; Xylitol; Sucrose; Fructose
• Other Study ID Numbers: EryAdo

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