Effects of Oral Xylitol on Subsequent Energy Intake

Study Overview
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Brief Summary
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The aim of this project is to investigate the effect of xylitol (given as pre-load), compared to sucrose, Ace-K, and water on energy intake during a subsequent ad libitum test meal in healthy participants. Furthermore, the release of GI hormones, glycemic control, appetite-related sensations, GI tolerance, sweetness and liking in response to the pre-loads will be investigated.

Detailed Description
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The subjects will participate in four study days. The screening will last 60 minutes, the study days about 4.5 hours each. After a simple-carbohydrate standard dinner, the subjects have to do an overnight fast until the next morning. Subjects will receive fixed equisweet doses of sucrose (33.5g), xylitol (33.5g), Ace-K (0.1675g), or water as oral pre-loads in a blinded, randomized (counterbalanced) fashion (t = -15 min). Fifteen minutes after the administration (t = 0 min), a standard solid test meal will be presented and ad libitum energy intake will be measured. The end of the test meal will be after 20 minutes or as soon as the subject stops eating for more than 5 minutes. Blood samples (to measure: glycemic control and GI hormones) will be collected at t = -16, t = -1, t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 min and appetite-related sensation rating will be collected at t = -16, t = -1, t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 min. GI symptoms and nausea are assessed at t = -16, -1, 30, 60, 120 and 180 min. At t = -10 min subjects are asked to rate the perceived sweetness and liking of the pre-load and at t = 180 min the perceived liking of the test meal.

Official Title
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Effects of Oral Xylitol on Subsequent Energy Intake, Gastrointestinal Hormones, Glycemic Control, Appetite-related Sensations, and Gastrointestinal Tolerance

Conditions
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Energy Intake, Gastrointestinal Hormones, Glycemic Control, Appetite, Satiation

Intervention / Treatment
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* Dietary Supplement: Xylitol
* Dietary Supplement: Sucrose
* Dietary Supplement: Acesulfame Potassium
* Dietary Supplement: Water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy normal weight participants (10 male and 10 female) with a body-mass index (BMI) of 19.0-24.9 kg/m2 Age 18-55 years Stable body weight (± 5%) for at least three months Able to give informed consent as documented by signature Exclusion Criteria: Fructose intolerance Pre-existing diet (vegetarian, vegan, sugar free, no breakfast) Pre-existing regular consumption of xylitol and/or Ace-K (> 1/week) Chronic or clinically relevant acute infections/diseases Regular intake of medications, except contraceptives Pregnancy: although no contraindication, pregnancy might influence metabolic state. Substance abuse (more than 1 glass wine/beer per day; consumption of cannabis, cocaine, heroin, etc.) Shift worker Participation in another study with investigational drug within the 30 days preceding and during the present study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Xylitol<br>20 volunteers receive 33.5g xylitol dissolved in 300mL tap water as an oral pre-load. | Dietary Supplement: Xylitol<br>* 33.5g xylitol dissolved in 300mL tap water.<br>* Other names: E967-Xylitol;|
| Active Comparator: Sucrose<br>20 volunteers receive 33.5g sucrose dissolved in 300mL tap water as an oral pre-load. | Dietary Supplement: Sucrose<br>* 33.5g sucrose dissolved in 300mL tap water.<br>* Other names: Saccharose;|
| Active Comparator: Acesulfame Potassium<br>20 volunteers receive 0.1675g Ace-K dissolved in 300mL tap water as an oral pre-load. | Dietary Supplement: Acesulfame Potassium<br>* 0.1675g Ace-K dissolved in 300mL tap water.<br>* Other names: E950-Ace-K;|
| Placebo Comparator: Water<br>20 volunteers receive 300mL tap water as an oral pre-load. | Dietary Supplement: Water<br>* 300mL tap water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of xylitol on energy intake during a subsequent ad libitum test meal | Fifteen minutes after the administration of the pre-loads (t = 0 minutes), a standard solid test meal will be presented and ad libitum energy intake will be measured. | Total energy intake will be measured from t = 0 until t = 20 minutes or as soon as the as the subject stops eating for more than 5 minutes. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects on GI hormone response - GLP-1 | GLP-1 will be quantified using a non-radioactive highly sensitive sandwich ELISA (MSD V-PLEX - #K1503PD) in the presence of a chemiluminescent substrate. | Blood will be drawn at the following time points :t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load). | 
| Effects on GI hormone response - PYY | PYY-3-36 will be quantified using a non-radioactive high sensitive sandwich ELISA (Millipore - # EZHPYYT66K). | Blood will be drawn at the following time points :t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load). | 
| Effects on GI hormone response - CCK | Plasma cholecystokinin (CCK) levels will be measured with a sensitive radioimmunoassay using a highly specific antiserum (No. 92128) | Blood will be drawn at the following time points: t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load). | 
| Effects on GI hormone response - ghrelin | Octanoylated ghrelin will be measured by a radioimmunoassay with 125I [Tyr24] human ghrelin [1-23] as tracer and a rabbit antibody against human ghrelin [1-8] (final dilution 1/100000), which does not cross-react with desoctanoylated ghrelin. | Blood will be drawn at the following time points: t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load). | 
| Effects on glycemic control - plasma glucose | Glucose will be measured by a glucose oxidase method (Rothen Medizinische Laboratorien AG, Basel, Switzerland). | Blood will be drawn at the following time points: t = -16, t = -1 (before administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load). | 
| Effects on glycemic control - plasma insulin | Insulin will be quantified using a chemiluminescent microparticle immunoassay (chemiflex) reagent kit (#8k41; Abbott) and the relative light units detected by the ARCHITECT optical system (model: CI4100; Abbott). | Blood will be drawn at the following time points: t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load). | 
| Effects on glycemic control - plasma c-peptide | C-peptide will be measured with a commercially available sandwich ELISA kit from Millipore (Millipore - # EZHCP-20K). | Blood will be drawn at the following time points: t = -16, t = -1 (before administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load). | 
| Effects on glycemic control - plasma glucagon | Glucagon concentrations in plasma will be measured after extraction of plasma with 70% ethanol (vol/vol, final concentration). The antibody is directed against the C-terminus of the glucagon molecule (antibody code no. 4305) and therefore mainly measures glucagon of pancreatic origin. | Blood will be drawn at the following time points: t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load). | 
| Effects on appetite-related sensations | Appetite perceptions (feelings of: a) hunger, b) satiety) are assessed by visual analogue scale (VAS). Visual analogue scales consist of a horizontal, unstructured, 10-cm line representing the minimum (0.0 points) to the maximum rating (10.0 points). Subjects assign a vertical mark across the line to indicate the magnitude of their subjective sensation at the present time point. The measurement is quantified by the distance from the left end of the line (minimum rating) to the subject's vertical mark. | Visual analogue scales will be recorded at the following time points: t = -16, t = -1 (before the administration of the pre-loads), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-loads). | 
| Effects on GI tolerance | GI symptoms will be assessed by use of a checklist including the following questions: abdominal pain, nausea, vomiting, diarrhea, borborygmic, abdominal distension, eructation and increased flatus. | GI tolerance will be recorded at t = -16, -1 (before the administration of the pre-load), 30, 60, 120 and 180 minutes (after the administration of the pre-load). | 
| Sweetness of pre-load | Sweetness is assessed by gLMS. General Labeled Magnitude Scales consist of an unequal, vertical line, which is marked with quasi-logarithmic verbal anchors describing different intensities (e.g. strongest imaginable, barely detectable). Participants are instructed to place a mark on the line where their perceived intensity of sensation lies. | Sweetness of the pre-load will be recorded at t = -10 minutes. | 
| Liking ot the pre-load | Liking is assessed by gLMS. General Labeled Magnitude Scales consist of an unequal, vertical line, which is marked with quasi-logarithmic verbal anchors describing different intensities (e.g. strongest imaginable, barely detectable). Participants are instructed to place a mark on the line where their perceived intensity of sensation lies. | Liking of the pre-load will be recorded at t = -10 minutes. | 
| Liking of the test meal | Liking is assessed by gLMS. General Labeled Magnitude Scales consist of an unequal, vertical line, which is marked with quasi-logarithmic verbal anchors describing different intensities (e.g. strongest imaginable, barely detectable). Participants are instructed to place a mark on the line where their perceived intensity of sensation lies. | Liking of the test meal will be recorded at t = 180 minutes. |