Acute Effects of the Two Alternative Sweeteners D-allulose and Erythritol on Gastrointestinal Hormone Secretion and Glycemic Control
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 18
- Locations
- 2
- Primary Endpoint
- Effects on GI hormone response - GLP-1
Study Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Outcomes
Primary Outcomes
Effects on GI hormone response - GLP-1
Time Frame: 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).
Plasma GLP-1 will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA).
Effects on GI hormone response - motilin
Time Frame: 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).
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).
Effects on GI hormone response - ghrelin
Time Frame: 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).
Plasma ghrelin will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA).
Effects on GI hormone response - CCK
Time Frame: 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).
Plasma cholecystokinin (CCK) levels will be measured with a sensitive radioimmunoassay using a highly specific antiserum.
Effects on GI hormone response - PYY
Time Frame: 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).
Plasma PYY, and ghrelin will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA).
Secondary Outcomes
- Effects on glycemic control - plasma glucagon(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 blood lipids(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 glycemic control - plasma glucose(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(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(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 hsCRP (high sensitive c-reactive protein)(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 glycemic control - plasma c-peptide(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 uric acid(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(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).)