Parsing the impact of calories versus sweet taste on beverage brand conditioning: a randomized controlled trial

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Monell Chemical Senses Center $828,937 on August 1, 2026, to conduct a randomized controlled trial investigating how calories and sweet taste condition beverage brand preference and neural response.

The project, titled "Parsing the Impact of Calories Versus Sweet Taste on Beverage Brand Conditioning," addresses a gap in understanding the mechanisms linking orosensory and metabolic signaling to real-world drivers of food intake such as branding and advertising. The research design tests competing theories about whether gut-brain caloric signaling operates independently of sweet taste cues or whether orosensory sweetness and gut-caloric signals integrate such that non-nutritive sweetener consumption—by uncoupling sweetness from calories—disrupts metabolic predictions and satiation signaling. The award funds a large human neuroimaging experiment to directly connect metabolic and neural mechanisms of sweetness and calories to branding sensitization and intake regulation.

The funding is provided under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), which supports basic and clinical biomedical research on mechanisms underlying disease and improved prevention, diagnosis, and treatment of diabetes, digestive, and kidney diseases.

Performance occurs in Philadelphia, Pennsylvania. The period of performance runs from August 1, 2026, through May 31, 2031.

Abstract

Despite decades of research on non-nutritive sweeteners (NNS) and sugar-sweetened beverages (SSB), critical gaps in understanding their role in eating behavior remain. Food-reinforcement theories of obesity have focused on different possible mechanisms, such as sensitization of food advertisements and branding or metabolic endpoints from orosensory and GUT signaling. In support of the former, we completed a randomized controlled trial to investigate the sensitization mechanisms of a SSB brand. We observed that daily SSB consumption over a 3-week period increased implicit approach motivation toward the SSB brand (which was encoded in ventral striatum response) relative to consumption of an unsweetened, non-caloric control beverage. There are conflicting theories about the roles of orosensory and GUT signaling. One theory suggests that subconscious GUT-brain caloric signaling pathways are processed independently of explicit orosensory cues (e.g., sweetness). Another suggests that orosensory sweet taste and GUT-caloric signals are integrated and when a NNS is repeatedly consumed, the uncoupling of orosensory sweetness and calories reduces the accuracy of metabolic sweet→calorie predictions, which disrupts satiation signaling and compromises food intake regulation. Despite evidence supporting both theories, they have not been directly tested against one another, nor has previous work assessed their role in the sensitization of external food cues. This is a critical GAP-without directly connecting metabolic and neural mechanisms of sweetness and calories to real-world drivers of intake such as branding and advertising, the field lacks the translational evidence needed to inform mechanistic understanding and public health interventions. The proposed project addresses this GAP through a large, rigorously designed human neuroimaging experiment. This study provides the first direct comparison of sweetness versus calories on CUE conditioning and motivation and applies cutting-edge neuroimaging tools to interrogate dopamine and vagal-brain pathways that guide behavior. In aim 1, we seek to understand the impact of real-world behavior through daily consumption of a SSB or NNS 'diet' beverage. In aim 2, we focus on the sensitization mechanisms of sweet VS. Calories in both short- and long-term conditioning settings. In aim 3, we test whether individual differences in key aspects of eating regulation physiology moderate the ability of SSB and NNS consumption to sensitize the beverage brands. This work has the potential to establish a translational bridge between preclinical studies and human consumption patterns, advance the understanding of key mechanisms that govern eating behavior, identify undiscovered risk-factors for overeating, and provide information about soft drinks and advertisements that is directly applicable to dietary recommendations and food-related policy-level decisions.