Brain and physiological responses to flavored waters with different sweeteners: a randomized crossover study in healthy young adults.

Overview

1. Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
2. Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
3. German Center for Diabetes Research (DZD), Tübingen, Germany
4. Wageningen Food and Biobased Research, Wageningen University & Research, Wageningen, Netherlands
5. Tate & Lyle PLC, London, UK
6. Internal Medicine IV, Department of Diabetology, Endocrinology and Nephrology, University Hospital Tübingen, Tübingen, Germany
7. Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany

Abstract

Background: Drinks with low-no-calorie sweeteners (LNCSs) do not contribute to energy intake but still provide a hedonic experience through sweetness. LNCS can have differential effects on brain areas involved in food intake and reward compared with sugars.

Objectives: This study determined changes in brain activity and the effect on physiological markers following the ingestion of flavored waters sweetened with the sugar sucrose or LNCS.

Methods: Thirty healthy individuals participated in a randomized crossover study with 6 treatments. Participants were scanned after an overnight fast using magnetic resonance imaging, including arterial spin labeling to measure cerebral blood flow (CBF), before and after ingestion of 500-mL drinks: water, or equisweet flavored waters with 25 g sucrose, sucralose, stevia extract, allulose+stevia extract, or monk fruit extract. CBF was measured at baseline and 5 and 30 min; gastric content volume was measured at baseline and 25 and 45 min. Serum insulin and glucose were measured, and participants rated their appetite and thirst throughout each visit. Data were analyzed with linear mixed models.

Results: Primary: Hypothalamus CBF was not differentially affected by any of the drinks. In the ventral tegmental area (midbrain), treatment effects differed, with lower ΔCBF after sucrose than water, sucralose and monk fruit drink ingestion at 30 min (difference: ∼8% ± 3%; all PFDR < 0.05). Exploratory whole-brain analyses showed increased CBF after consumption for allulose+stevia (amygdala) and stevia (putamen) compared with sucrose (PFWE < 0.05). Despite its low energy content, allulose+stevia delayed gastric emptying similar to sucrose, whereas only sucrose increased glucose and insulin concentrations.

Conclusions: Although flavored waters with LNCS mostly elicit similar neural and gastrointestinal 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.

This study was registered at clinicaltrials.gov as NCT05575687 (https://clinicaltrials.gov/study/NCT05575687).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data described in the manuscript and analytic code will be made available for research use upon reasonable request to the corresponding author.

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Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 8 keywords, 17 MeSH terms, 1 funder, 62 references.

Cite

This paper

Smeets, P. A., Veit, R., Oosterink, E., Meijboom, S., Risso, D., Preissl, H., & Kullmann, S. (2026). Brain and physiological responses to flavored waters with different sweeteners: a randomized crossover study in healthy young adults. The American journal of clinical nutrition, 124(2), 101401. https://doi.org/10.1016/j.ajcnut.2026.101401

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