Mechanisms of bitterness reduction by sweeteners - PROJECT SUMMARY This project addresses a critical issue in health care and nutrition: the bitter taste of many liquid medications, bioactive compounds in numerous health-promoting fruits and vegetables, and psychoactive substances in beverages (e.g., caffeine in coffee and tea) often leads to poor compliance with medication, avoidance of healthy foods, and excessive sugar consumption to mask bitterness. While non-sugar sweeteners are widely used to replace sugars, their ability to reduce bitterness is inconsistent, and their underlying mechanisms remain poorly understood. This limits our ability to predict which sweeteners effectively suppress bitterness or are the most potent options. Bitter suppression by sweeteners can occur in the brain (central cognitive suppression), on the tongue (peripheral suppression), or a combination of both, which may provide an additive effect. However, no sweetener has yet been identified as having these dual properties, largely due to a lack of systematic study, in both human participants and cell lines. This innovative application aims to fill this gap by combining two research strategies: (1) a human sensory panel to determine peripheral/central mechanisms of bitter suppression by seven common sweeteners paired with two distinct bitter compounds, and (2) cellular receptor-based assays to test these sweeteners against eight human bitter taste receptors (TAS2Rs) activated by one or both bitter compounds. In Aim 1, using the established split-tongue paradigm, a classic approach in human psychophysics, 60 healthy adult participants will be administered sweet and bitter solutions either separately on two sides of the tongue (sweet on one side, bitter on the other) or together on the same side of the tongue (vs. water on the other). Because signals from the two sides are not joined until central processing, this allows a comprehensive investigation of taste processing at both peripheral and central levels. Because peripheral suppression may involve blocking TAS2Rs, a process widely studied using cell lines expressing human TAS2Rs, Aim 2 will use heterologous human embryonic kidney 293 cells, transfected with one of eight specific TAS2R constructs, to test the efficacy and potency of inhibition for each bitter compound, alone and in the presence of each sweetener, using real-time cell calcium assays. Ultimately, this research will advance our understanding of how sweeteners suppress bitterness, thereby helping identify sweeteners most effective in reducing bitterness and guiding development of palatable foods and medicines while reducing consumption of sugars and non-sugar sweeteners. By integrating multidisciplinary approaches, this research has the potential to enhance patient compliance and improve overall public health outcomes while providing data to support my future application for an R01 award.
