In Dalenberg et al.(2020), we showed that consumption of the low-calorie sweetener (LCS) sucralose in the presence of a carbohydrate rapidly impairs glucose metabolism and results in longer-term decreases in brain, but not perceptual sensitivity to sweet taste, suggesting dysregulation of gut-brain control of glucose metabolism. Kahn and Sievenpiper offer a critique of these results, centered around our choice of carbohydrate comparators (maltodextrin and sucrose) making it difficult to disentangle the effect of the LCS (sucralose) from that of the carbohydrates or their combination. Their argument is based on the assumption that only a small portion of fructose is converted to glucose (< 25%), rendering sucrose an unsuitable comparator for maltodextrin. In contrast to this assertion, a definitive article in Cell Metabolism showed that the small intestine metabolizes most (> 90%) dietary fructose into glucose (Jang et al., 2018) when provided in doses that are in the range of what we used in our study. Thus, differences in conversion to glucose are not an issue. We also point out that the goal of the original study was to test the uncoupling hypothesis that predicts that repeated consumption of a sweet taste without (sucralose), but not with, calories (sucrose) will impair neural, perceptual, and metabolic response to sugar. Since sweet taste was a key variable of interest, we sought to create equally sweet experimental beverages. Here sucrose was included as a comparator for sucralose because equally sweet but differentially caloric beverages could be created. Maltodextrin, which produces minimal oral sensation (ie, it is not sweet) was added to sucralose to create a third similarly sweet beverage that included the LCS coupled with calories as a control to compare to the sucralose alone (ie, uncoupled) condition. Thus, it was not the case, as indicated by Kahn and Sievenpiper, that we included sucrose as a comparator for maltodextrin. However, and unexpectedly, we observed changes in neural and metabolic response to sugar after habitual consumption of sucralose with, but not without, maltodextrin. As pointed out by Kahn and Sievenpiper, we could not rule out the possibility that maltodextrin, rather than the combination, accounted for the observed changes. For this reason, we performed a new, modified study in which we asked volunteers to consume maltodextrin alone, using a similar exposure schedule as the first study. No differences were observed. Kahn and Sievenpiper criticize this analysis and re-analyzed the data by combining data from two separate experiments so that they could directly contrast the effects of maltodextrin+ sucralose versus maltodextrin alone. They reproduce our finding that daily consumption of maltodextrin alone does NOT change insulin sensitivity but note no significant difference between the post-analysis insulin levels for maltodextrin alone versus maltodextrin+ sucralose. First, the argument that the lack of a significant difference between groups implies that there is no difference is logically flawed; absence of evidence is not evidence of absence—Martin Rees. Rather, inspection of their figure shows, as originally reported, a clear difference between the combo group compared to both sucralose alone (p= 0.002 at 30 min and p= 0.003 at 120 min) and sucrose alone groups (p= 0.004 at 30 min and p= 0.03 at 120 min), whereas no difference is observed between the maltodextrin alone group with either the sucralose group or sucrose group at 120 min and only a marginal effect is seen with only the sucrose group at 30 min (p= 0.05). Second, their analysis is not appropriate for the following reasons:(1) the maltodextrin alone …