# Effects of Allulose vs Aspartame Consumption on Postprandial Glucagon-Like Peptide-1 Profiles and Metabolic Health: Protocol for a Randomized, Crossover, Double-Blind, Placebo-Controlled Trial

## TL;DR

This study compares how allulose and aspartame affect GLP-1 hormone levels and metabolic health in healthy adults.

## Contribution

It introduces a novel crossover trial protocol to assess acute and subacute effects of allulose on GLP-1 and metabolic parameters.

## Key findings

- Allulose may stimulate GLP-1 secretion compared to aspartame.
- Multiomic data will explore metabolic and gut health effects of allulose.
- Results could support allulose as a sugar substitute with potential health benefits.

## Abstract

Excessive sugar consumption is a public health concern. Allulose, a low-calorie sugar with similar functional properties to sucrose, offers potential metabolic benefits. Animal and limited human studies suggest it may stimulate glucagon-like peptide-1 (GLP-1) secretion, improve glucose regulation, and support weight management. However, evidence to substantiate these effects in humans remains scarce.

The primary aim of this study, the low-calorie sweetener intervention study allulose (LisA), was to assess differences in the postprandial GLP-1 profile (primary outcome) between an acute intake of allulose and aspartame interventions in healthy adults. Secondary goals included exploratively assessing potential subacute adaptation effects over a 4-week consumption period and evaluating a comprehensive set of parameters as hypothesis-generating findings for future large-scale research.

We conducted a randomized, double-blind, placebo-controlled, crossover trial in healthy adults. Participants daily consumed either 3 allulose-sweetened or aspartame-sweetened beverages for 4 weeks in crossover, with a washout in between. Standardized inpatient procedures were conducted at the study baseline and at the beginning and end of each intervention phase. The primary outcome is the postprandial profile of GLP-1. Secondary outcomes include further parameters of gut hormone secretion, insulin sensitivity (Matsuda Index), body composition (body impedance analysis), subjective satiety (visual analog scales), and gastrointestinal tolerance. We also assess multiomic endpoints, including sugaromics and gut microbiome composition. The primary outcome will be analyzed using the incremental area under the curve with a 2-tailed paired t test. All further outcomes (including peak and total area under the curve for GLP-1) will be assessed using linear mixed models.

A total of 10 participants (4 female and 6 male; mean age 31.2, SD 6.8 years; BMI 25.1, SD 2.6 kg/m2) completed all study procedures. The sample collection phase was successfully concluded in November 2023. Data processing and statistical analysis for the primary outcome are expected to be completed by June 2026.

The comprehensive study protocol, integrating a rigorous crossover design with multiomic analysis, is poised to provide confirmatory evidence for the acute GLP-1 effects of allulose and generate valuable mechanistic hypotheses regarding its subacute metabolic and gut health effects. The findings will contribute to the evidence base required for evaluating allulose’s potential role in public health sugar reduction strategies.

German Clinical Trials Register DRKS00028521; https://drks.de/search/en/trial/DRKS00028521

DERR1-10.2196/81857