Neural and metabolic factors in carbohydrate reward: Rationale, design, and methods for a flavor-nutrient learning paradigm in humans

Overconsumption of ultra-processed foods (UPFs), which are linked with adverse health outcomes, is a growing public health concern. UPFs deliver highly bioavailable calories rapidly, which may contribute to their reinforcing potential and drive overconsumption. Our primary aim is to test the role of speed of nutrient availability on reward learning. We hypothesize that brain activity in reward related areas and behavioral preferences will be greater to a flavored drink predicting rapidly available calories (CS + Fast) compared with a flavored drink predicting more slowly available (CS + Slow) or no (CS-) calories. Participants (n = 64, aged 18–45 years, will consume 3 novel flavored, isosweet beverages containing 110 kcal of sucrose (CS + Fast), 110 kcal of maltodextrin (CS + Slow), or 0-kcal sucralose (CS-) 6 times in randomized, crossover order. Blood metabolites and indirect calorimetry measures, including metabolic rate and carbohydrate oxidation, will be assessed before and for 1 h after beverage consumption. Behavioral preference for beverages will be assessed in a pre- and post-test. Brain response to each flavor without calories will be assessed via functional magnetic resonance imaging in a post-test. Findings from this study will contribute to the understanding of basic mechanisms that may drive overconsumption of UPFs. Trial registration:clinicaltrials.gov registration #NCT06053294