Evaluation of Sweetener Synergy in Humans by Isobole Analyses.

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.

Human biology of taste.

Taste or gustation is one of the 5 traditional senses including hearing, sight, touch, and smell. The sense of taste has classically been limited to the 5 basic taste qualities: sweet, salty, sour, bitter, and umami or savory. Advances from the Human Genome Project and others have allowed the identification and determination of many of the genes and molecular mechanisms involved in taste biology. The ubiquitous G protein-coupled receptors (GPCRs) make up the sweet, umami, and bitter receptors. Although less clear in humans, transient receptor potential ion channels are thought to mediate salty and sour taste; however, other targets have been identified. Furthermore, taste receptors have been located throughout the body and appear to be involved in many regulatory processes. An emerging interplay is revealed between chemical sensing in the periphery, cortical processing, performance, and physiology and likely the pathophysiology of diseases such as diabetes.