Neural responses to oral administration of erythritol vs. sucrose and sucralose explain differences in subjective liking ratings.

INTRODUCTION: High sugar intake is associated with many chronic diseases. However, non-caloric sweeteners (NCSs) might fail to successfully replace sucrose due to the mismatch between their rewarding sweet taste and lack of caloric content. The natural NCS erythritol has been proposed as a sugar substitute due to its satiating properties despite being non-caloric. We aimed to compare brain responses to erythritol vs. sucrose and the artificial NCS sucralose in a priori taste, homeostatic, and reward brain regions of interest (ROIs). METHODS: We performed a within-subject, single-blind, counterbalanced fMRI study in 30 healthy men (mean ± SEM age:24.3 ± 0.8 years, BMI:22.3 ± 0.3 kg/m2). Before scanning, we individually matched the concentrations of both NCSs to the perceived sweetness intensity of a 10% sucrose solution. During scanning, participants received 1 mL sips of the individually titrated equisweet solutions of sucrose, erythritol, and sucralose, as well as water. After each sip, they rated subjective sweetness liking. RESULTS: Liking ratings were significantly higher for sucrose and sucralose vs. erythritol (both pHolm = 0.0037); water ratings were neutral. General Linear Model (GLM) analyses of brain blood oxygen level-depended (BOLD) responses at qFDR<0.05 showed no differences between any of the sweeteners in a priori ROIs, but distinct differences were found between the individual sweeteners and water. These results were confirmed by Bayesian GLM and machine learning-based models. However, several brain response patterns mediating the differences in liking ratings between the sweeteners were found in whole-brain multivariate mediation analyses. Both subjective and neural responses showed large inter-subject variability. CONCLUSION: We found lower liking ratings in response to oral administration of erythritol vs. sucrose and sucralose, but no differences in neural responses between any of the sweeteners in a priori ROIs. However, differences in liking ratings between erythritol vs. sucrose or sucralose are mediated by multiple whole-brain response patterns.

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, 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.

Metabolic Effects and Safety Aspects of Acute D-allulose and Erythritol Administration in Healthy Subjects.

The rapid increase in sugar consumption is associated with various negative metabolic and inflammatory effects; therefore, alternative sweeteners become of interest. The aim of this study was to investigate the metabolic effects and safety aspects of acute D-allulose and erythritol on glucose, insulin, ghrelin, blood lipids, uric acid, and high-sensitive C-reactive protein (hsCRP). In three study visits, 18 healthy subjects received an intragastric administration of 25 g D-allulose or 50 g erythritol, or 300 mL tap water (placebo) in a randomized, double-blind and crossover order. To measure the aforementioned parameters, blood samples were drawn at fixed time intervals. Glucose and insulin concentrations were lower after D-allulose compared to tap water (p = 0.001, dz = 0.91 and p = 0.005, dz = 0.58, respectively); however, Bayesian models show no difference for insulin in response to D-allulose compared to tap water, and there was no effect after erythritol. An exploratory analysis showed that ghrelin concentrations were reduced after erythritol compared to tap water (p = 0.026, dz = 0.59), with no effect after D-allulose; in addition, both sweeteners had no effect on blood lipids, uric acid and hsCRP. This combination of properties identifies both sweeteners as excellent candidates for effective and safe sugar alternatives.

Oral Erythritol Reduces Energy Intake during a Subsequent ad libitum Test Meal: A Randomized, Controlled, Crossover Trial in Healthy Humans.

The impact of oral erythritol on subsequent energy intake is unknown. The aim was to assess the effect of oral erythritol compared to sucrose, sucralose, or tap water on energy intake during a subsequent ad libitum test meal and to examine the release of cholecystokinin (CCK) in response to these substances. In this randomized, crossover trial, 20 healthy volunteers received 50 g erythritol, 33.5 g sucrose, or 0.0558 g sucralose dissolved in tap water, or tap water as an oral preload in four different sessions. Fifteen minutes later, a test meal was served and energy intake was assessed. At set time points, blood samples were collected to quantify CCK concentrations. The energy intake (ad libitum test meal) was significantly lower after erythritol compared to sucrose, sucralose, or tap water (p < 0.05). Before the start of the ad libitum test meal, erythritol led to a significant increase in CCK compared to sucrose, sucralose, or tap water (p < 0.001). Oral erythritol given alone induced the release of CCK before the start of the ad libitum test meal and reduced subsequent energy intake compared to sucrose, sucralose, or tap water. These properties make erythritol a useful sugar alternative.