https://www.nature.com/articles/s42255-025-01227-8 Skip to main content Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Advertisement Advertisement Nature Metabolism * View all journals * Search * Log in * Explore content * About the journal * Publish with us * Subscribe * Sign up for alerts * RSS feed 1. nature 2. nature metabolism 3. articles 4. article * Article * Published: 26 March 2025 Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights * Sandhya P. Chakravartti ORCID: orcid.org/0000-0002-7267-6742^1,2 ,3, * Kay Jann ORCID: orcid.org/0000-0003-3574-0538^4, * Ralf Veit ORCID: orcid.org/0000-0001-9860-642X^5, * Hanyang Liu^2,3, * Alexandra G. Yunker^2,3, * Brendan Angelo ORCID: orcid.org/0000-0003-3558-2840^2,3, * John R. Monterosso^1,6, * Anny H. Xiang^7, * Stephanie Kullmann ORCID: orcid.org/0000-0001-9951-923X^5,8,9^ na1 & * ... * Kathleen A. Page ORCID: orcid.org/0000-0002-9083-6615^1,2,3^ na1 Show authors Nature Metabolism volume 7, pages 574-585 (2025)Cite this article * Metrics details Subjects * Hypothalamus * Metabolism * Obesity * Randomized controlled trials Abstract Sucralose, a widely used non-caloric sweetener, provides sweet taste without calories. Some studies suggest that non-caloric sweeteners stimulate appetite, possibly owing to the delivery of a sweet taste without the post-ingestive metabolic signals that normally communicate with the hypothalamus to suppress hunger. In a randomized crossover trial (ClinicalTrials.gov identifier: NCT02945475), 75 young adults (healthy weight, overweight or with obesity) consumed a drink containing sucralose, sweetness-matched sucrose or water. We show that acute consumption of sucralose versus sucrose stimulates hypothalamic blood flow (P < 0.018) and greater hunger responses (P < 0.001). Sucralose versus water also increases hypothalamic blood flow (P < 0.019) but produces no difference in hunger ratings. Sucrose, but not sucralose, increases peripheral glucose levels, which are associated with reductions in medial hypothalamic blood flow (P < 0.007). Sucralose, compared to sucrose and water, results in increased functional connections between the hypothalamus and brain regions involved in motivation and somatosensory processing. These findings suggest that non-caloric sweeteners could affect key mechanisms in the hypothalamus responsible for appetite regulation. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution Access options Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $29.99 / 30 days cancel any time Learn more Subscribe to this journal Receive 12 digital issues and online access to articles $119.00 per year only $9.92 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout Additional access options: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support Fig. 1: Participant enrollment flowchart for the Randomized Crossover Brain Response to Sugar II trial and final analysis. [42255_2025_1227_Fig1_HTML] Fig. 2: Schematic of study design. [42255_2025_1227_Fig2_HTML] Fig. 3: Differential hypothalamic response to drink comparisons. [42255_2025_1227_Fig3_HTML] Fig. 4: Difference in hypothalamic response to drinks by weight status. [42255_2025_1227_Fig4_HTML] Fig. 5: Differential functional connectivity from hypothalamus seed region after sucralose ingestion relative to sucrose and water. [42255_2025_1227_Fig5_HTML] Fig. 6: Visual display of changes in hypothalamic, peripheral glucose, insulin, GLP-1 and hunger responses over time. [42255_2025_1227_Fig6_HTML] Fig. 7: Associations between peripheral glucose, hunger and changes in medial hypothalamic blood flow. [42255_2025_1227_Fig7_HTML] Data availability The datasets generated and analysed during the current study are available from the corresponding author (K.A.P.) on reasonable request, and all brain imaging data are available in the Open Science Framework repository (https://osf.io/tuw93). 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CAS Google Scholar Download references Acknowledgements This work was supported by the National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102794 to K.A.P, F31DK137584 to S.P.C). A Research Electronic Data Capture, REDCap, database was used for this study, which is supported by the Southern California Clinical and Translational Science Institute through NIH grant UL1TR001855. We thank the volunteers who participated in this study and the staff at the Dornsife Cognitive Neuroimaging Center and Diabetes and Obesity Research Institute of the University of Southern California. A. Romero, E. Trigo, R. Maniego, H. Dorton, E. Jahng, B. Ge, L. N. Overholtzer, J. Hislop, M. Erdstein and P. Dave (all from University of Southern California) assisted with study visits and recruiting volunteers. Author information Author notes 1. These authors jointly supervised this work: Stephanie Kullmann, Kathleen A. Page. Authors and Affiliations 1. Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA Sandhya P. Chakravartti, John R. Monterosso & Kathleen A. Page 2. Division of Endocrinology and Diabetes, Department of Medicine & Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Sandhya P. Chakravartti, Hanyang Liu, Alexandra G. Yunker, Brendan Angelo & Kathleen A. Page 3. Diabetes and Obesity Research Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Sandhya P. Chakravartti, Hanyang Liu, Alexandra G. Yunker, Brendan Angelo & Kathleen A. Page 4. Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Kay Jann 5. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tubingen, Tubingen, Germany Ralf Veit & Stephanie Kullmann 6. Department of Psychology, University Southern California, Los Angeles, CA, USA John R. Monterosso 7. Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA Anny H. Xiang 8. Department of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, Eberhard Karls University Tubingen, Tubingen, Germany Stephanie Kullmann 9. German Center for Diabetes Research (DZD), Tubingen, Germany Stephanie Kullmann Authors 1. Sandhya P. Chakravartti View author publications You can also search for this author inPubMed Google Scholar 2. Kay Jann View author publications You can also search for this author inPubMed Google Scholar 3. Ralf Veit View author publications You can also search for this author inPubMed Google Scholar 4. Hanyang Liu View author publications You can also search for this author inPubMed Google Scholar 5. Alexandra G. Yunker View author publications You can also search for this author inPubMed Google Scholar 6. Brendan Angelo View author publications You can also search for this author inPubMed Google Scholar 7. John R. Monterosso View author publications You can also search for this author inPubMed Google Scholar 8. Anny H. Xiang View author publications You can also search for this author inPubMed Google Scholar 9. Stephanie Kullmann View author publications You can also search for this author inPubMed Google Scholar 10. Kathleen A. Page View author publications You can also search for this author inPubMed Google Scholar Contributions K.A.P. conceived and designed the study. All authors were involved with the acquisition, analysis or interpretation of data. S.P.C. and K.A.P. drafted the manuscript; S.P.C., K.A.P., S.K., R.V., K.J., J.R.M., A.H.X. and A.G.Y. critically reviewed the manuscript for important intellectual content. S.P.C. performed statistical analysis. S.P.C., H.L. and B.A. visualized the project. H.L., A.G.Y., B.A., K.J. and R.V. provided administrative, technical or material support. K.A.P. obtained funding and supervised the research. Corresponding author Correspondence to Kathleen A. Page. Ethics declarations Competing interests The authors declare no competing interests. Peer review Peer review information Nature Metabolism thanks the anonymous reviewers for their contribution to the peer review of this work. Primary Handling Editors: Jean Nakhle and Ashley Castellanos-Jankiewicz, in collaboration with the Nature Metabolism team. Additional information Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Extended data Extended Data Fig. 1 Visual Display of Hypothalamic ROI. Hypothalamic Region of interest (ROIs) and corresponding coordinates. (a) Lateral hypothalamus (green), (b) Medial hypothalamus (blue), (c) Neudorfer (yellow). The images are displayed in neurological convention. Supplementary information Supplementary Information Supplementary Tables 1-10; Supplementary File 1, Study Protocol, Statistical Analysis Plan Reporting Summary Source data Source Data Fig. 3 Statistical source data Source Data Fig. 4 Statistical source data Source Data Fig. 6 Statistical source data Source Data Fig. 7 Statistical source data Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Reprints and permissions About this article Check for updates. Verify currency and authenticity via CrossMark Cite this article Chakravartti, S.P., Jann, K., Veit, R. et al. Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights. Nat Metab 7, 574-585 (2025). https://doi.org/10.1038/ s42255-025-01227-8 Download citation * Received: 04 July 2024 * Accepted: 31 January 2025 * Published: 26 March 2025 * Issue Date: March 2025 * DOI: https://doi.org/10.1038/s42255-025-01227-8 Share this article Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. 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