Acute Effects of the Two Alternative Sweeteners D-allulose and Erythritol on Metabolism

Acute Effects of the Two Alternative Sweeteners D-allulose and Erythritol on Gastrointestinal Hormone Secretion and Glycemic Control

The aim of this project is to investigate the effect of intragastric (ig) D-allulose on metabolic parameters in general and to investigate the effect of sweet taste receptor blockade on GI hormone responses, glycemic control, gastric emptying (GE) rates and appetite-related sensations to ig administration of erythritol and D-allulose.

Study Overview

• Status: Completed
• Conditions: Physiological Satiation Mechanisms
• Intervention / Treatment: Dietary supplement: Erythritol; Dietary supplement: Erythritol + lactisole; Dietary supplement: D-allulose; Dietary supplement: D-allulose + lactisole; Dietary supplement: Tap water; Dietary supplement: Tap water + lactisole

Detailed Description

Erythritol (natural non-caloric sweetener) could be an ideal candidate substitute for sugar as it may reduce caloric intake without compensatory overeating or earlier return of hunger. Moreover, it may serve as a physiological tool to disentangle the effects of gastrointestinal (GI) sweet taste receptor stimulation, (an)orexigenic hormone secretion, and glucose metabolism/caloric content on food intake regulation in vivo in humans. However, its effects on appetite, satiation, and satiety have not been studied systematically. Moreover, the mechanisms underlying erythritol-induced anorexigenic GI hormone release have not been investigated so far.

D-allulose is a sugar substitute with almost zero calories and is naturally occurring in small quantities. Apart from its use as sugar replacement, D-allulose seems to favorably affect glycemic control and metabolism as could be shown in animal trials and in a few human trials. However, to date the effects of D-allulose on GI hormone secretion, appetite-related sensations and glycemic control, are not or insufficiently studied in humans.

The aim of this project is therefore to investigate the effect of intragastric (ig) D-allulose on metabolic parameters in general and to investigate the effect of sweet taste receptor blockade on GI hormone responses, glycemic control, gastric emptying (GE) rates and appetite-related sensations to ig administration of erythritol and D-allulose.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4002
    • St. Claraspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy normal weight subjects with a body-mass index of 19.0-24.9
• Normal eating habits (no diets; no dietary changes)
• Age 18-55 years
• Stable body weight for at least three months
• Informed Consent as documented by signature (Appendix Informed Consent Form)

Exclusion Criteria:

• Pre-existing consumption of erythritol or D-allulose on a regular basis (usage of erythritol or D-allulose as sugar replacement; in contrast, erythritol-containing toothpaste is allowed)
• Substance abuse
• Regular intake of medications, except anticonceptives
• Chronic or clinically relevant acute infections
• Pregnancy: although no contraindication, pregnancy might influence metabolic state. Women 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.
• Participation in another study with investigational drug within the 30 days preceding and during the present study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Erythritol; 18 volunteers receive 50g erythritol dissolved in 300mL tap water via a nasogastric tube	Dietary supplement: Erythritol; 50g erythritol dissolved in 300mL tap water; Other Names: E968-Erythritol
Active Comparator: Erythritol + lactisole; 18 volunteers receive 50g erythritol with lactisol (450ppm) dissolved in 300mL tap water via a nasogastric tube	Dietary supplement: Erythritol + lactisole; 50g erythritol + lactisole (450ppm) dissolved in 300mL tap water; Other Names: E968-Erythritol
Active Comparator: D-allulose; 18 volunteers receive 25g D-allulose dissolved in 300mL tap water via a nasogastric tube	Dietary supplement: D-allulose; 25g D-allulose dissolved in 300mL tap water
Active Comparator: D-allulose + lactisole; 18 volunteers receive 25g D-allulose with lactisole (450ppm) dissolved in 300mL tap water via a nasogastric tube	Dietary supplement: D-allulose + lactisole; 25g D-allulose + lactisole (450ppm) dissolved in 300mL tap water
Placebo Comparator: Tap water; 18 volunteers receive 300mL tap water via a nasogastric tube	Dietary supplement: Tap water; 300mL tap water
Placebo Comparator: Tap water + lactisole; 18 volunteers receive 300mL tap water + lactisole (450ppm) via a nasogastric tube	Dietary supplement: Tap water + lactisole; 300mL tap water + lactisole (450ppm)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects on GI hormone response - GLP-1	Plasma GLP-1 will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA).	Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on GI hormone response - PYY	Plasma PYY, and ghrelin will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA).	Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on GI hormone response - ghrelin	Plasma ghrelin will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA).	Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on GI hormone response - CCK	Plasma cholecystokinin (CCK) levels will be measured with a sensitive radioimmunoassay using a highly specific antiserum.	Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on GI hormone response - motilin	Plasma motilin levels will be measured with a sensitive radioimmunoassay as previously described using 125I [Nle13] human motilin as tracer and rabbit anti-human Nle13 motilin antibody (final dilution 1/12000).	Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects on glycemic control - plasma glucose	Blood glucose concentrations will be measured by a commercial hexokinase-glucose-6-phosphate-dehydrogenase method (Roche, Basel, Switzerland). Insulin, c-peptide and glucagon will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). The lowest level of insulin that can be detected by this assay is 87 pg/mL when using a 25 µL sample. The lowest level of c-peptide that can be detected by this assay is 9.5 pg/mL when using a 25 µL sample. The lowest level of glucagon that can be detected by this assay is 13 pg/mL when using a 25 µL sample. The intra-assay coefficient of variation for all peptides (insulin, c-peptide and glucagon) is below 10%, whereas the inter-assay coefficient of variation is below 15%.	Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on glycemic control - plasma insulin	Insulin will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). The lowest level of insulin that can be detected by this assay is 87 pg/mL when using a 25 µL sample. The intra-assay coefficient of variation for insulin is below 10%, whereas the inter-assay coefficient of variation is below 15%.	Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on glycemic control - plasma c-peptide	C-peptide will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). The lowest level of c-peptide that can be detected by this assay is 9.5 pg/mL when using a 25 µL sample. The intra-assay coefficient of variation for c-peptide is below 10%, whereas the inter-assay coefficient of variation is below 15%.	Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on glycemic control - plasma glucagon	Glucagon will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). The lowest level of glucagon that can be detected by this assay is 13 pg/mL when using a 25 µL sample. The intra-assay coefficient of variation for glucagon is below 10%, whereas the inter-assay coefficient of variation is below 15%.	Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Effects on gastric emptying rate	Gastric emptying rate will be determined using a 13C-sodium acetate breath test.	Changes from baseline to four hours after treatment. Breath samples will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180 and 240minutes (after administration).
Effects on blood lipids	Analyses of blood lipids are carried out in the hospital laboratory.	Changes from baseline to two hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, and 120minutes (after administration).
Effects on uric acid	Analyses of uric acid are carried out in the hospital laboratory.	Changes from baseline to two hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, and 120minutes (after administration).
Effects on hsCRP (high sensitive c-reactive protein)	Analyses of hsCRP are carried out in the hospital laboratory.	Changes from baseline to two hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, and 120minutes (after administration).
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.	Changes from baseline to four hours after treatment. Visual analogue scales will be recorded at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180 and 240minutes (after administration).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects on GI tolerance	GI symptoms will be assessed by use of a checklist including the following questions: abdominal pain, nausea, vomiting, diarrhoea, borborygmi, abdominal distension, eructation and increased flatus.	Changes from baseline to four hours after treatment. GI tolerance will be recorded at time=-10, time=30, time=60, time=90, time=120, time=150, time=180, and time=240minutes.

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 17, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2020
• Last Update Submitted That Met QC Criteria: September 28, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vasodilator Agents; Erythritol
• Other Study ID Numbers: PolyAlluLac

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