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.

The beneficial effects of substituting sugar with non-caloric sweeteners (NCSs) remain uncertain due to the mismatch between their rewarding sweet taste and lack of energy content. Functional magnetic resonance imaging (fMRI) studies indicate an influence of cognitive processes (e.g., beliefs, expectations) on reward system responses to NCSs, thereby changing their rewarding properties. We measured the impact of cognitive influences about the caloric content on brain responses and liking ratings to erythritol, a natural NCS with satiating properties, versus sugar (i.e., sucrose). We performed a within-subject, single-blind, counterbalanced fMRI study in 30 healthy males (mean ± SD: age 23 ± 0.6 years, BMI 22.5 ± 0.3 kg/m²). Concentrations of erythritol were individually titrated to match the perceived sweetness intensity of a 16 % sucrose solution. During the scan, sucrose and equisweet erythritol solutions were delivered as 1 mL sips with either correct or purposefully incorrect "low-calorie" or "high-calorie" labels. After each sip, participants rated sweetness liking. Water with a "water" label was used as the control condition. A 2 × 2 ANOVA revealed lower liking ratings for erythritol than sucrose (p < 0.0001), but no main effect of the label, nor label-by-sweetener interaction. General Linear Model (GLM) analysis of brain responses at FDR q < 0.05 showed no main effect of sweetener nor label, nor a label-by-sweetener interaction. However, several patterns of brain activity mediated the differences in subjective liking ratings between the sweeteners. Moreover, different neural responses were found for sucrose vs. water in parcel-wise, SVM, and ROI-based analyses, whereas for erythritol vs. water, only the latter two showed differences. Lastly, sucrose induced a stronger craving signature response compared to erythritol, driven by the pattern specific to drug craving. Liking ratings were lower for erythritol than sucrose, and they were unaffected by the caloric label. There were no differences in neural responses between the sweeteners and labels, except in comparisons with water.

Background/Objectives: Xylitol, a natural low-caloric bulk sweetener, is increasingly used as a sugar alternative due to its low-glycemic and low-insulinemic properties. The aim was to investigate the effect of orally administered xylitol, sucrose, and acesulfame potassium (ace-K) on energy intake during a subsequent ad libitum test meal. Methods: In this randomized, controlled, double-blind, crossover trial (ClinicalTrials.gov NCT05671965, 20 December 2022), we included 20 healthy participants with normal body weight. Over four study visits, participants consumed an oral preload containing 33.5 g xylitol, 33.5 g sucrose, or 0.1675 g ace-K dissolved in 300 mL water, or 300 mL pure water as control. Participants were provided with an ad libitum test meal 15 min after the preload consumption, and both energy intake and total energy intake (= preload + ad libitum test meal) were assessed. Blood samples were collected to quantify cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), glucose, and insulin concentrations. Results: Total energy intake was lower in response to xylitol and ace-K compared to sucrose (p_Tukey < 0.03), with no differences between xylitol and ace-K or water. Plasma CCK concentrations were higher in response to xylitol compared to sucrose, ace-K, and water (p_Holm < 0.01), whereas GLP-1 concentrations did not differ between the preloads. Plasma glucose and insulin concentrations were lower in response to xylitol compared to sucrose (p_Holm < 0.01), but xylitol led to an increase in insulin compared to ace-K and water (p_Holm < 0.01). Conclusions: The consumption of oral preloads sweetened with xylitol or ace-K prior to an ad libitum test meal result in a lower total energy intake compared to a preload with sucrose.

Utilizing artificial low-caloric sweeteners as sugar alternatives remains controversial, as they provide sweet taste and the associated rewarding responses but fail to stimulate satiation. Erythritol, a non-caloric bulk sweetener, is able to stimulate the release of gastrointestinal (GI) satiation hormones, yet its influence on reward responses is inconclusive. The aim of this study was to investigate reward responses to erythritol, sucrose, and sucralose during and after flavor preference learning, and to explore the potential involvement of GI satiation hormones. In this randomized, double-blind, crossover study, 20 healthy participants (10 women, 10 men; mean ± SD; age: 25.8 ± 7.5 years, BMI: 22.3 ± 1.8 kg/m²) rated the reward responses (explicit wanting and liking) of three novel, neutral flavored beverages before and after pairing with erythritol, sucrose, or sucralose. GI satiation hormones (cholecystokinin, glucagon-like peptide-1) and parameters of glycemic control (glucose, insulin) were measured. After conditioning, explicit wanting and liking ratings increased, with no differences between the sweeteners. The release of GI satiation hormones and changes in glucose and insulin concentrations had no effect on the reward responses, which therefore might not be associated with flavor-nutrient learning (FNL) but rather with flavor-flavor learning (FFL). To conclude, beverages previously paired with erythritol appear to be equally liked as sucrose and sucralose.

The sugar alcohol erythritol occurs naturally in fruits and fermented foods, is used as a sweetener, and is also endogenously synthesized via the pentose-phosphate pathway and metabolized into erythronate. Untargeted metabolomic studies have associated elevated plasma erythritol and erythronate concentrations with metabolic disorders, while weight loss has been linked to decreased plasma erythritol concentrations. In this trial, two complementary analyses were performed to identify predictors of fasting erythritol and erythronate concentrations across different populations and to assess changes in these metabolites following bariatric surgery-induced weight loss. Fasting plasma samples from 30 lean adolescents, 50 lean adults, and 138 adults with obesity (including 15 who had undergone bariatric surgery) were analyzed to measure erythritol, erythronate, glucose, and insulin concentrations. Across all populations, age but not body mass index (BMI), glucose, or insulin, was a significant predictor of fasting erythritol concentrations. Fasting erythronate concentrations were associated with both age and BMI. Post-surgery, change in BMI but not fasting glucose or insulin was a predictor of changes in fasting erythritol concentrations, while time was the only predictor of changes in fasting erythronate concentrations. Although the metabolic processes regulating the endogenous erythritol and erythronate production remain unclear, our findings suggest that age-related physiological changes may influence fasting concentrations of both erythritol and erythronate.