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

Abstract

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, crossover study, 18 participants (5 men) with a mean ± SD BMI (in kg/m2) of 21.9 ± 1.7 and aged 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 6 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 with 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 with 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.

Keywords: D-allulose; appetite-related sensations; erythritol; gastric emptying; gastrointestinal satiation hormones; gut sweet taste receptor; lactisole.

FIGURE 1

CONSORT flow diagram.

FIGURE 2

(A) CCK, (B) GLP-1, and (C) PYY release after intragastric administration of solutions containing 25 g D-allulose, 25 g D-allulose + 450 ppm lactisole, 50 g erythritol, 50 g erythritol + 450 ppm lactisole, tap water, and tap water + 450 ppm lactisole to 18 healthy adults. Data are expressed as mean ± SEM; absolute values are reported. N = 18 (5 men, 13 women). Statistical tests: linear mixed-effects modeling followed by planned contrasts with Holm correction for multiple testing. The increase of CCK, GLP-1, and PYY was greater for D-allulose and erythritol compared with tap water (comparisons of the changes from baseline, all P_Holm < 0.0001, d_z >1), with no significant difference for D-allulose + lactisole and erythritol + lactisole compared with the test solutions without lactisole (all P_Holm > 0.1). CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; ppm, parts per million; PYY, peptide tyrosine tyrosine.

FIGURE 3

Gastric emptying after intragastric administration of solutions containing 25 g D-allulose, 25 g D-allulose + 450 ppm lactisole, 50 g erythritol, 50 g erythritol + 450 ppm lactisole, tap water, and tap water + 450 ppm lactisole to 18 healthy adults. Data are expressed as mean ± SEM. Change from baseline values is reported. N = 18 (5 men and 13 women). Statistical tests: linear mixed-effects modeling followed by planned contrasts with Holm correction for multiple testing. Gastric emptying was retarded for erythritol compared with tap water but not for D-allulose compared with tap water (comparisons of the changes from baseline, P_Holm = 0.0002, d_z = –1.05 and P_Holm = 1, respectively), with no significant difference for D-allulose + lactisole and erythritol + lactisole compared with the test solutions without lactisole (all P_Holm = 1). CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; ppm, parts per million; PYY, peptide tyrosine tyrosine.

FIGURE 4

(A) Hunger, (B) Pfc, (C) satiety, and (D) fullness after intragastric administration of solutions containing 25 g D-allulose, 25 g D-allulose + 450 ppm lactisole, 50 g erythritol, 50 g erythritol + 450 ppm lactisole, tap water, and tap water + 450 ppm lactisole to 18 healthy adults. Data are expressed as mean ± SEM; absolute values are reported. N = 18 (5 men and 13 women). Statistical tests: linear mixed-effects modeling followed by planned contrasts with Holm correction for multiple testing. Pfc was lower for erythritol compared with tap water but not for D-allulose compared with tap water (comparisons of the changes from baseline, P_Holm = 0.0442, d_z = –0.60 and P_Holm = 0.6811, respectively), with no significant difference for D-allulose + lactisole and erythritol + lactisole compared with the test solutions without lactisole (both P_Holm = 1). Fullness was greater for erythritol compared with tap water but not for D-allulose compared with tap water (comparisons of the changes from baseline, P_Holm = 0.0190, d_z = 0.69 and P_Holm = 0.8714, respectively), with no significant difference for D-allulose + lactisole, and erythritol + lactisole compared with the test solutions without lactisole (P_Holm = 0.9814 and P_Holm = 0.2071, respectively). No significant results for hunger and satiety. Pfc, prospective food consumption; ppm, parts per million.