Blood Erythritol, Blood p-Selectin, Blood Xylitol, Body Composition, Gastrointestinal Tolerance, Glucose Tolerance, Insulin Resistance, Thrombocyte Aggregation
Conditions
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.
Interventions
DIETARY_SUPPLEMENTEryhtritol
Eryhtritol-sweetened beverages twice a day (36g erythritol/day) with main meals during 5 weeks EryClot-Pilot: Erythritol 50g dissolved in 300mL water administered once per visit EryClot: Erythritol 50g dissolved in 300mL water administered once per visit
DIETARY_SUPPLEMENTSucrose
Sucrose-sweetened beverages twice a day (25g sucrose/day) with main meals during 5 weeks
DIETARY_SUPPLEMENTGlucose
Glucose 75g dissolved in 300mL water administered once per visit
DIETARY_SUPPLEMENTFructose
Fructose 25g dissolved in 300mL water administered once per visit
DIETARY_SUPPLEMENTXylitol
Xylitol 33.5g dissolved in 300mL water administered once per visit
DIETARY_SUPPLEMENTWater
300mL water administered once per visit
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
EryClot-Pilot: This trial is a randomized, double-blind, crossover trial. The project set-up is single-center, national. In total, 3 volunteers will be enrolled. There will be 3 study arms. EryClot This trial is a randomized single-blind, crossover trial. The project setup is single-center national. In total 10 volunteers will be enrolled. There will be 3 study arms. EryClot in vitro This trial is an in vitro trial using human blood samples. The project setup is single-center national. In total blood samples from 12 volunteers will be collected.
Eligibility
Sex/Gender
ALL
Age
14 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
EryAdo: 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: C-Peptide | Change from baseline to 5 weeks after polyol/sucrose intake | C-peptide levels during OGTT |
| Glucose tolerance: Glucagon | Change from baseline to 5 weeks after polyol/sucrose intake | Glucagon levels during OGTT |
| Glucose tolerance: Fructosamin | Change from baseline to 5 weeks after polyol/sucrose intake | Fructosamin levels |
| Glucose tolerance: HbA1C | Change from baseline to 5 weeks after polyol/sucrose intake | HbA1C levels |
| Glucose tolerance: Continuous glucose monitoring average | Change from baseline to 5 weeks after polyol/sucrose intake | Continuous glucose monitoring for average glucose levels |
| 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 |
| 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). |
| 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: GLP-1 | Change from baseline to 5 weeks after polyol/sucrose intake | Secretion of GLP-1 during OGTT |
| Gastrointestinal hormones secretion: PYY | Change from baseline to 5 weeks after polyol/sucrose intake | Secretion of PYY during OGTT |
| 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 |
| 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 |
| 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-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-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 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 |
| 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 |
| 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 |
| 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 |
Countries
Switzerland
Contacts
PRINCIPAL_INVESTIGATORBettina K. Wölnerhanssen, PD. MD
St. Clara Research Ltd.
Outcome results
None listed