Temporal Check-All-That-Apply (TCATA) is a rapid method where attributes are actively checked and unchecked to track sensations over time, so that the checked words fully describe the sample in any given moment. Here, we characterize the temporal profiles of sweeteners using TCATA. In two experiments, sweeteners were tested in water at concentrations known to elicit weak to moderate sweetness. Before evaluating the sweeteners, participants (n= ~125 per experiment) were familiarized with the TCATA method with a guided example using imaginary samples of Kool-Aid. Participants then received 10 ml of each sweetener solution and were instructed to click “start” after he or she finished swallowing the sample. Incidence of 6 attributes obtained from prior literature – sweet, bitter, metallic, licorice, cooling, and drying – was obtained for 60s. We observed similarities across temporal profiles of various sweeteners: sweet and bitter occurred first (~10s), then metallic and cooling (~10–25s), followed by drying much later (30–50s depending on the stimulus). The presence of side tastes influenced how often ‘sweet’ was endorsed: stimuli with fewer endorsements of side tastes showed more prominent sweetness. Finally, unfamiliar side tastes may lead to a smearing bias where participants check every attribute in an attempt to characterize those unfamiliar sensations.

The chemical senses and pharmaceuticals fundamentally depend on similar biological processes, but novel molecule discovery has classically been approached from vastly different vantage points. From the perspective of ingredient and flavor companies, there are countless ingredients that act via largely unknown mechanisms, whereas the pharmaceutical industry has numerous mechanisms in search of novel compounds. Mixtures of agonists can result in synergistic (superadditive) responses, which can be quantified via isobole analysis, a well-proven clinical approach in pharmacology. For the food and beverage industries, bulk (caloric) sweeteners like sugars are a key ingredient in sweetened foods and beverages, but consumers also desire products with fewer calories, which has led to the development of sweet enhancers and sweetener blends intended to achieve synergy or superadditivity. Synergistic mixtures are highly attractive targets commercially as they enable lower usage levels and enhanced efficacy. Although the psychophysical literature contains numerous prior reports of sweetener synergy, others have also noted that classical additive models fail to account for nonlinear dose-response functions. To address this shortcoming, here we systematically apply the isobole method from pharmacology to quantify the presence or absence of psychophysical synergy for binary pairs of sweeteners in a series of 15 separate experiments, each with ~100 adult volunteers (total n = 1576). Generally, these data support the hypothesis that structurally similar sweeteners acting as agonists will not synergize, whereas structurally dissimilar sweeteners binding to overlapping or distal sites can act as allosteric agonists or agonist-antagonists, respectively.