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Brain and physiological responses to flavored waters with different sweeteners: a randomized cross-over study in healthy young adults

Smeets, P. A. M.; Veit, R.; Oosterink, E.; Meijboom, S.; Risso, D.; Preissl, H.; Kullmann, S.

2025-12-09 nutrition
10.64898/2025.12.08.25341825 medRxiv
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BackgroundDrinks with low-no-calorie sweeteners (LNCS) do not contribute to energy intake while still providing a hedonic experience through sweetness. LNCS can have differential effects on brain areas involved in food intake and reward compared to sugars. ObjectiveTo determine changes in brain activity and the effect on physiological markers following the ingestion of flavored waters sweetened with the sugar sucrose or LNCS. Methods30 healthy individuals participated in a randomized crossover study with six treatments. Participants were scanned after an overnight fast using magnetic resonance imaging, including arterial spin labelling to measure cerebral blood flow (CBF), before and after ingestion of 500-ml drinks: Water, or equi-sweet flavored waters with 25 g sucrose, sucralose, stevia extract, allulose+stevia extract or monk fruit extract. CBF was measured at baseline, 5 and 30 min; gastric content volume at baseline, 25 and 45 min. Serum insulin and glucose were measured and participants rated their appetite and thirst throughout each visit. ResultsHypothalamus CBF was not differentially affected by any of the drinks. In the ventral tegmental area (midbrain), treatment effects differed, with lower CBF after sucrose compared to water, sucralose and monk fruit drink ingestion at 30 min. Exploratory whole-brain analyses showed differential CBF changes for the allulose+stevia (amygdala) and stevia (putamen) drinks compared to sucrose. Despite its low energy content, the allulose+stevia drink delayed gastric emptying similar to the sucrose drink, while only sucrose increased glucose and insulin levels. ConclusionsAlthough flavored waters with LNCS mostly elicit similar neural and gastrointenstinal responses as water, they have some distinct effects on the brain compared with 25 g of sucrose, particularly in reward-related brain areas. Further exploration of the neural and physiological effects of allulose and stevia and dose-dependent investigations are warranted.

Published in The American Journal of Clinical Nutrition (predicted rank #23) · training set

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