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

Not Applicable

Recruiting

• Conditions: Blood Xylitol; Thrombocyte Aggregation; Blood p-Selectin; Blood Erythritol; Insulin Resistance; Glucose Tolerance; Body Composition; Gastrointestinal Tolerance

• Registration Number: NCT04966299
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

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.

EryClot-Pilot:

Erythritol is also produced by the human body and possibly elevated erythritol levels in the blood are an indication of an increased risk of cardiovascular disease, obesity or diabetes in the future.

In a recently published study, a possible effect of erythritol on blood clotting function was described. In this in vitro experiment, increased blood clotting was observed when erythritol was added to clotting cells (platelets) in the test tube. Studies in humans on blood coagulation after administration of erythritol are missing so far.

With a pilot study, the investigators study whether erythritol is detectable in the blood after administration of glucose and fructose. Furthermore, the erythritol level in the blood and a possible effect on the blood coagulation function after administration of erythritol will be investigated.

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

The preliminary results of the EryClot_Pilot study indicate that there appears to be no measurable effect of erythritol on thrombocyte aggregation. This implicates 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 administration on more parameters of blood coagulation as well as in more subjects.

Due to a study published in June 2024, there appears the need to investigate the effects of xylitol on blood clotting function as well.

EryClot in vitro:

In addition to the human EryClot study, we will conduct in vitro experiments (aggregometry assay after addition of erythritol or xylitol in human platelet rich plasma).

Detailed Description

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.

EryClot-Pilot:

The aim of this pilot study is to investigate whether erythritol is detectable in the blood after administration of glucose and fructose. Furthermore, the erythritol level in the blood and a possible effect on the blood clotting function after administration of erythritol will be investigated.

EryClot:

The aim of this study is to investigate the erythritol level in blood after administration of erythritol and a possible effect on blood clotting function. Additionally, a possible effect of xylitol on blood clotting function will be investigated.

EryClot in vitro:

The aim of this study is to investigate the platelet responsiveness in vitro in human plasma after addition of erythritol and xylitol.

Study Timeline

• Study First Submitted: 2021-05-25
• Study First Submitted QC: 2021-07-06
• Study First Posted: 2021-07-19
• Study Start: 2021-08-18
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-28
• Last Update Posted: 2025-01-31
• Primary Completion: 2025-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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.)

EryClot-Pilot:

3 participants

Inclusion criteria:

• Healthy participants 18-55 years upon inclusion
• Normal weight (BMI between 19.0-24.9 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 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

EryClot:

Inclusion criteria:

• Healthy participants 18-55 years upon inclusion
• Normal weight (BMI between 19.0-24.9 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 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 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.))

EryClot in vitro

Inclusion criteria:

• Healthy participants 18-55 years upon inclusion
• 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.
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Insulin resistance	Change from baseline to 5 weeks after polyol/sucrose intake	Insulin resistance as measured by the HOMA Index.
EryClot-Pilot Thrombocyte aggregation	Blood samples at timepoint t= 0, 30, 60, 120, 180 minutes	Thrombocyte aggregation after consumption of test solution measured with a blood sample
EryClot Thrombocyte aggregation	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes	Thrombocyte aggregation after consumption of test solution measured with a blood sample
EryClot in vitro: Platelet responsiveness in human platelet rich plasma	One single fasting blood sample at timepoint t = -10 minutes	Aggregometry assay after addition of erythritol or xylitol in human platelet rich plasma

Secondary Outcome Measures

Name	Time	Method
Body composition: fat free mass	Change from baseline to 5 weeks after polyol/sucrose intake	Body composition assessed by mean of bioimpedance analysis: fat free mass in kg
EryClot blood sVCAM1 concentrations	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours	Blood sVCAM1 concentrations after consumption of test solution
Glucose tolerance: C-Peptide	Change from baseline to 5 weeks after polyol/sucrose intake	C-peptide levels during OGTT
Body composition: fat mass	Change from baseline to 5 weeks after polyol/sucrose intake	Body composition assessed by mean of bioimpedance analysis: fat mass in kg
Glucose tolerance: Continuous glucose monitoring glucose variability	Change from baseline to 5 weeks after polyol/sucrose intake	Continuous glucose monitoring for glucose variability
Glucose tolerance: Continuous glucose monitoring time within range	Change from baseline to 5 weeks after polyol/sucrose intake	Continuous glucose monitoring for time within range
Gut microbiota composition	Change from baseline to 5 weeks after polyol/sucrose intake	The taxonomic and functional profiles of the gut microbiota (stool samples) assessed by metagenomic shotgun sequencing.
Gastrointestinal hormones secretion: PYY	Change from baseline to 5 weeks after polyol/sucrose intake	Secretion of PYY during OGTT
Glucose tolerance: Insulin	Change from baseline to 5 weeks after polyol/sucrose intake	Insulin levels during OGTT
Glucose tolerance: Glucose	Change from baseline to 5 weeks after polyol/sucrose intake	Glucose levels during OGTT
Glucose tolerance: Fructosamin	Change from baseline to 5 weeks after polyol/sucrose intake	Fructosamin levels
Glucose tolerance: Continuous glucose monitoring average	Change from baseline to 5 weeks after polyol/sucrose intake	Continuous glucose monitoring for average glucose levels
Gastrointestinal hormones secretion: GLP-1	Change from baseline to 5 weeks after polyol/sucrose intake	Secretion of GLP-1 during OGTT
EryClot blood p-selectin concentrations	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours	Blood p-Selectin concentrations after consumption of test solution
Glucose tolerance: Glucagon	Change from baseline to 5 weeks after polyol/sucrose intake	Glucagon levels during OGTT
Glucose tolerance: HbA1C	Change from baseline to 5 weeks after polyol/sucrose intake	HbA1C levels
Glucose absorption	Change from baseline to 5 weeks after polyol/sucrose intake	Glucose absorption measured by 3-OMG concetrations during OGTT
Metabolomics	Change from baseline to 5 weeks after polyol/sucrose intake	Metabolomics in plasma, urine and stool samples, measured by 1H-NMR and Liquid Chromatography-Mass Spectrometry (LC-MS).
Gastrointestinal hormones secretion: Ghrelin	Change from baseline to 5 weeks after polyol/sucrose intake	Secretion of Ghrelin during OGTT
Gastrointestinal hormones secretion: CCK	Change from baseline to 5 weeks after polyol/sucrose intake	Secretion of CCK during OGTT
Food intake	Change from baseline to 5 weeks after polyol/sucrose intake	Food intake assessed with self-reported food records
Gastrointestinal tolerance	Change from baseline to 3 and 5 weeks after polyol/sucrose intake	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
EryClot-Pilot Blood Erythritol concentrations	Blood samples at timepoint t= 0, 30, 60, 120, 180 minutes and 24, 48 hours	Blood Erythritol concentrations after consumption of test solution
EryClot-Pilot Blood p-Selectin concentrations	Blood samples at timepoint t= 0, 30, 60, 120, 180 minutes and 24, 48 hours	Blood p-Selectin concentrations after consumption of test solution
EryClot blood Erythritol concentrations	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours	Blood erythritol concentrations after consumption of test solution
EryClot blood Xylitol concentrations	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours	Blood xylitol concentrations after consumption of test solution
EryClot blood PF4 concentrations	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours	Blood PF4 concentrations after consumption of test solution
EryClot blood D-Dimers concentrations	Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours	Blood D-Dimers concentrations after consumption of test solution

Trial Locations

Locations (1)

St. Claraspital; 🇨🇭 Basel, Basel-Stadt, Switzerland