A Low-Calorie Rebaudioside D–Glucose–Sodium Sweetener Matches Sucrose in Palatability and Neural Responses in a Functional MRI Study of Healthy Adults

Background/Objectives: Non-nutritive sweeteners (NNSs) often taste less palatable than glucose-containing sugars, potentially because they differentially engage sweet taste pathways. We developed a low-calorie rebaudioside D–glucose–sodium (RebD mix) sweetener designed to engage T1R2/T1R3 and sodium–glucose cotransporter 1 (SGLT1) pathways. We tested whether the RebD mix matches sucrose in palatability and neural responses. Methods: A within-subject fMRI study was performed on 28 healthy adults. Participants received three gustatory conditions: sucrose, RebD mix, and RebD mix without sodium (Na+), which is known to enhance SGLT1 activation. Liking and wanting ratings for gustatory stimuli were obtained at scanning. The imaging analyses focused on the orbitofrontal cortex (OFC), which is associated with palatability. Results: Liking and wanting did not differ across the three conditions. OFC response to the RebD mix did not differ from sucrose, whereas the RebD without Na+ condition showed greater OFC–postcentral gyrus connectivity than the other two conditions. Across participants, OFC–postcentral connectivity in the RebD without Na+ condition was negatively associated with fullness measured at the scan. Conclusion: The RebD mix matched sucrose in subjective palatability and OFC responses, while removal of Na+ altered OFC– postcentral connectivity linked to satiety. These findings suggest that oral SGLT1–linked signaling may contribute to satiety-related aspects of sweet taste, and that the RebD mix can provide sucrose-comparable palatability with reduced calories.