Sweet Taste Adaptation to Sugars, Sucralose, and Their Blends: A Human and Rodent Perspective

<b>Background:</b> Sweet taste adaptation, the decline in perceived sweetness with repeated exposure, may influence dietary behavior and differs across sweeteners. Low-calorie sweeteners (LCSs) such as sucralose strongly activate the T1R2+T1R3 receptor and are generally associated with greater adaptation than sugars, although this effect can be reduced with sweetener blends. <b>Aim:</b> We investigated whether habitual LCS consumption affects sweet taste perception and whether blending sucralose with small amounts of sugars attenuates adaptation using sensory tests in humans and in vivo calcium imaging in a rodent model. <b>Methods:</b> In study 1, habitual (HC; <i>n</i> = 39) and non-habitual (NHC; <i>n</i> = 42) LCS consumers rate sweetness of sucralose (0.6 mM), glucose (800 mM), fructose (475 mM), and blends with low glucose (111 mM) or fructose (45 mM) across repeated trials (1-10) using a generalized labeled magnitude scale. In study 2, a microfluidic-based intravital tongue imaging system was used to assess in vivo responses to sweet adaptation in genetically modified C57BL/6 mice (<i>n</i> = 8) expressing a calcium indicator in type II/III cells of taste buds. <b>Results:</b> Habitual LCS use was not associated with differences in sweetness perception or adaptation (all <i>p</i>-values > 0.6). Sucralose alone produced stronger adaptation than when blended with sugars in both humans (<i>p</i>-values < 0.002) and mice (<i>p</i> < 0.001). Glucose and fructose alone showed adaptation (relative decrease reached on final trial compared to the first trial: -27% ± 4% for glucose, -38% ± 5% for fructose, both <i>p</i>-values < 0.002) but to a lower degree compared with sucralose (-66% ± 5%). <b>Conclusions:</b> Sweetener composition, rather than habitual LCS use, drives sweet taste adaptation. Blending sucralose with small amounts of sugars reduces adaptation at both perceptual and cellular levels, providing mechanistic insights relevant to the formulation of LCS products.