The Role of D-allulose and Erythritol on the Activity of the Gut Sweet Taste Receptor and Gastrointestinal Satiation Hormone Release in Humans: A Randomized, Controlled Trial

BACKGROUND: Glucose induces the release of gastrointestinal (GI) satiation hormones, such as glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine (PYY) in part via the activation of the gut sweet taste receptor (T1R2/T1R3). OBJECTIVES: The primary objective was to investigate the importance of T1R2/T1R3 for the release of cholecystokinin (CCK), GLP-1 and PYY in response to D-allulose and erythritol by assessing the effect of the T1R2/T1R3 antagonist lactisole on these responses and as secondary objectives to study the effect of the T1R2/T1R3 blockade on gastric emptying, appetite-related sensations and GI symptoms. METHODS: In this randomized, controlled, double-blind, cross-over study, 18 participants (five men, mean ± SD BMI: 21.9 ± 1.7 kg/m2, age: 24 ± 4 y) received an intragastric administration of 25 g D-allulose, 50 g erythritol, or tap water, with or without 450 parts per million (ppm) lactisole, respectively, in six different sessions. 13C-sodium acetate was added to all solutions to determine gastric emptying. At fixed time intervals, blood and breath samples were collected, and appetite-related sensations and GI symptoms were assessed. Data were analyzed with linear mixed model analysis. RESULTS: D-allulose and erythritol induced a significant release of CCK, GLP-1 and PYY compared to tap water (all PHolm < 0.0001, dz > 1). Lactisole did not affect the D-allulose- and erythritol-induced release of CCK, GLP-1, and PYY (all PHolm > 0.1). Erythritol significantly delayed gastric emptying, increased fullness and decreased prospective food consumption compared to tap water (PHolm = 0.0002, dz = -1.05, PHolm = 0.0190, dz = 0.69 and PHolm = 0.0442, dz = -0.62, respectively). CONCLUSIONS: D-allulose and erythritol stimulate the secretion of GI satiation hormones in humans. Lactisole had no effect on CCK, GLP-1, and PYY release, indicating that D-allulose- and erythritol-induced GI satiation hormone release is not mediated via T1R2/T1R3 in the gut. Clinical Trial Registry number and website: Number: NCT04027283, Website: https://clinicaltrials.gov/ct2/show/NCT04027283?term=NCT04027283&draw=2&rank=1.