{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:09:07Z","timestamp":1759190947560,"version":"3.44.0"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"USDA National Institute of Food and Agriculture Hatch Project","award":["600-122"],"award-info":[{"award-number":["600-122"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government","award":["RS-2024-00466703"],"award-info":[{"award-number":["RS-2024-00466703"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Sweet taste adaptation, the decline in perceived sweetness with repeated exposure, may influence dietary behavior and differs across sweeteners. Low-calorie sweeteners (LCSs) such as sucralose strongly activate the T1R2+T1R3 receptor and are generally associated with greater adaptation than sugars, although this effect can be reduced with sweetener blends. Aim: We investigated whether habitual LCS consumption affects sweet taste perception and whether blending sucralose with small amounts of sugars attenuates adaptation using sensory tests in humans and in vivo calcium imaging in a rodent model. Methods: In study 1, habitual (HC; n = 39) and non-habitual (NHC; n = 42) LCS consumers rate sweetness of sucralose (0.6 mM), glucose (800 mM), fructose (475 mM), and blends with low glucose (111 mM) or fructose (45 mM) across repeated trials (1\u201310) using a generalized labeled magnitude scale. In study 2, a microfluidic-based intravital tongue imaging system was used to assess in vivo responses to sweet adaptation in genetically modified C57BL\/6 mice (n = 8) expressing a calcium indicator in type II\/III cells of taste buds. Results: Habitual LCS use was not associated with differences in sweetness perception or adaptation (all p-values &gt; 0.6). Sucralose alone produced stronger adaptation than when blended with sugars in both humans (p-values &lt; 0.002) and mice (p &lt; 0.001). Glucose and fructose alone showed adaptation (relative decrease reached on final trial compared to the first trial: \u221227% \u00b1 4% for glucose, \u221238% \u00b1 5% for fructose, both p-values &lt; 0.002) but to a lower degree compared with sucralose (\u221266% \u00b1 5%). Conclusions: Sweetener composition, rather than habitual LCS use, drives sweet taste adaptation. Blending sucralose with small amounts of sugars reduces adaptation at both perceptual and cellular levels, providing mechanistic insights relevant to the formulation of LCS products.<\/jats:p>","DOI":"10.3390\/nu17193075","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:40:52Z","timestamp":1759146052000},"page":"3075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sweet Taste Adaptation to Sugars, Sucralose, and Their Blends: A Human and Rodent Perspective"],"prefix":"10.3390","volume":"17","author":[{"given":"Stephanie I.","family":"Okoye","sequence":"first","affiliation":[{"name":"Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minjae","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea"},{"name":"The Institute of Molecular Biology and Genetics, Seoul 08826, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Petty","sequence":"additional","affiliation":[{"name":"Food Science and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4235-7003","authenticated-orcid":false,"given":"Myunghwan","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea"},{"name":"The Institute of Molecular Biology and Genetics, Seoul 08826, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2381-1095","authenticated-orcid":false,"given":"Marta Yanina","family":"Pepino","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Food Science and Human Nutrition, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Carle Illinois College of Medicine, Urbana, IL 61801, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1016\/j.cell.2025.04.021","article-title":"The Structure of Human Sweetness","volume":"88","author":"Juen","year":"2025","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1016\/j.cub.2005.09.037","article-title":"Distinct Contributions of T1R2 and T1R3 Taste Receptor Subunits to the Detection of Sweet Stimuli","volume":"15","author":"Nie","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s42004-024-01324-x","article-title":"Steviol Rebaudiosides Bind to Four Different Sites of the Human Sweet Taste Receptor (T1R2\/T1R3) Complex Explaining Confusing Experiments","volume":"7","author":"Hao","year":"2024","journal-title":"Commun. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4746","DOI":"10.1073\/pnas.0911670107","article-title":"Positive Allosteric Modulators of the Human Sweet Taste Receptor Enhance Sweet Taste","volume":"107","author":"Servant","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kawasaki, M., Kidera, Y., Goda, R., Taketani, C., Ide, M., Fujii, W., Nakagita, T., and Misaka, T. (2025). Distinct Potency of Compounds Targeting the T1R3 Subunit in Modulating the Response of Human Sweet and Umami Taste Receptors. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-11636-0"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.conb.2007.07.001","article-title":"Sensory Adaptation","volume":"17","author":"Wark","year":"2007","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3431","DOI":"10.3390\/nu6093431","article-title":"The Role of Sweet Taste in Satiation and Satiety","volume":"6","author":"Low","year":"2014","journal-title":"Nutrients"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/chemse\/4.3.177","article-title":"Note: Individual Differences in Taste Adaptation","volume":"4","author":"Dubose","year":"1979","journal-title":"Chem. Senses"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"607","DOI":"10.3758\/BF03212112","article-title":"Method of Stimulation, Mouth Movements, Concentration, and Viscosity: Effects on the Degree of Taste Adaptation","volume":"62","author":"Theunissen","year":"2000","journal-title":"Percept. Psychophys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/chemse\/bjv021","article-title":"Temperature Affects Human Sweet Taste via At Least Two Mechanisms","volume":"40","author":"Green","year":"2015","journal-title":"Chem. Senses"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hewson, L., and Tarrega, A. (2017). Sensory Adaptation. Time-Dependent Measures of Perception in Sensory Evaluation, Wiley.","DOI":"10.1002\/9781118991640.ch4"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/0091-3057(81)90266-5","article-title":"Multiple Receptor Sites Mediate Sweetness: Evidence from Cross Adaptation","volume":"15","author":"Schiffman","year":"1981","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9860","DOI":"10.1523\/JNEUROSCI.1444-21.2021","article-title":"\u201cTripartite Synapses\u201d in Taste Buds: A Role for Type I Glial-like Taste Cells","volume":"41","author":"Rodriguez","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.cell.2024.10.041","article-title":"Glia-like Taste Cells Mediate an Intercellular Mode of Peripheral Sweet Adaptation","volume":"188","author":"Park","year":"2025","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0361-9230(95)00062-J","article-title":"Investigation of Synergism in Binary Mixtures of Sweeteners","volume":"38","author":"Schiffman","year":"1995","journal-title":"Brain Res. Bull."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/chemse\/28.3.219","article-title":"Effect of Repeated Presentation on Sweetness Intensity of Binary and Ternary Mixtures of Sweeteners","volume":"28","author":"Schiffman","year":"2003","journal-title":"Chem. Senses"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.foodqual.2006.04.007","article-title":"Time to Maximum Sweetness Intensity of Binary and Ternary Blends of Sweeteners","volume":"18","author":"Schiffman","year":"2007","journal-title":"Food Qual. Prefer."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/j.1365-2621.1993.tb04332.x","article-title":"Sweetness Adaptation of Some Carbohydrate and High Potency Sweeteners","volume":"58","author":"Bornstein","year":"1993","journal-title":"J. Food Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Myers, E.A., Passaro, E.M., and Hedrick, V.E. (2018). The Reproducibility and Comparative Validity of a Non-Nutritive Sweetener Food Frequency Questionnaire. Nutrients, 10.","DOI":"10.3390\/nu10030334"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1111\/j.1530-0277.2007.00519.x","article-title":"Effects of Cigarette Smoking and Family History of Alcoholism on Sweet Taste Perception and Food Cravings in Women","volume":"31","author":"Pepino","year":"2007","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_21","first-page":"E13","article-title":"Changes in Taste Perception and Eating Behavior after Bariatric Surgery-Induced Weight Loss in Women","volume":"22","author":"Pepino","year":"2014","journal-title":"Obesity"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wasalathanthri, S., Hettiarachchi, P., and Prathapan, S. (2014). Sweet Taste Sensitivity in Pre-Diabetics, Diabetics and Normoglycemic Controls: A Comparative Cross Sectional Study. BMC Endocr. Disord., 14.","DOI":"10.1186\/1472-6823-14-67"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/0031-9384(84)90269-5","article-title":"Development of the University of Pennsylvania Smell Identification Test: A Standardized Microencapsulated Test of Olfactory Function","volume":"32","author":"Doty","year":"1984","journal-title":"Physiol. Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.physbeh.2004.02.033","article-title":"Valid Across-Group Comparisons with Labeled Scales: The GLMS versus Magnitude Matching","volume":"82","author":"Bartoshuk","year":"2004","journal-title":"Physiol. Behav."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/ajcn\/nqy152","article-title":"Sucralose Decreases Insulin Sensitivity in Healthy Subjects: A Randomized Controlled Trial","volume":"108","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3758\/BF03203030","article-title":"Taste Interaction between Glucose and Fructose Assessed by Functional Measurement","volume":"41","author":"Frijters","year":"1987","journal-title":"Percept. Psychophys."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3758\/BF03206809","article-title":"Monogeusia for Fructose, Glucose, Sucrose, and Maltose","volume":"58","author":"Breslin","year":"1996","journal-title":"Percept. Psychophys."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Han, J., and Choi, M. (2018). Comprehensive Functional Screening of Taste Sensation in Vivo. bioRxiv.","DOI":"10.1101\/371682"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jneumeth.2017.07.031","article-title":"NoRMCorre: An Online Algorithm for Piecewise Rigid Motion Correction of Calcium Imaging Data","volume":"291","author":"Pnevmatikakis","year":"2017","journal-title":"J. Neurosci. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1364\/OL.33.000156","article-title":"Efficient Subpixel Image Registration Algorithms","volume":"33","author":"Thurman","year":"2008","journal-title":"Opt. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Breslin, P.A.S., Izumi, A., Tharp, A., Ohkuri, T., Yokoo, Y., Flammer, L.J., Rawson, N.E., and Margolskee, R.F. (2021). Evidence That Human Oral Glucose Detection Involves a Sweet Taste Pathway and a Glucose Transporter Pathway. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0256989"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"von Molitor, E., Riedel, K., Krohn, M., Hafner, M., Rudolf, R., and Cesetti, T. (2021). Sweet Taste Is Complex: Signaling Cascades and Circuits Involved in Sweet Sensation. Front. Hum. Neurosci., 15.","DOI":"10.3389\/fnhum.2021.667709"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/chemse\/17.3.245","article-title":"Quantitative and Qualitative Evaluation of High-Intensity Sweeteners and Sweetener Mixtures","volume":"17","author":"Ayya","year":"1992","journal-title":"Chem. Senses"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.foodres.2019.03.019","article-title":"Temporal Sweetness and Side Tastes Profiles of 16 Sweeteners Using Temporal Check-All-That-Apply (TCATA)","volume":"121","author":"Tan","year":"2019","journal-title":"Food Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, C., Liu, Y., Zhao, X., and Liu, B. (2022). Current Advances and Future Aspects of Sweetener Synergy: Properties, Evaluation Methods and Molecular Mechanisms. Appl. Sci., 12.","DOI":"10.3390\/app12105096"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1111\/1750-3841.16610","article-title":"Sensory Profiling of Natural Sweeteners and Sucrose\u2013Sweetener Binary Mixtures","volume":"88","author":"Mora","year":"2023","journal-title":"J. Food Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/oby.2010.255","article-title":"Sugar Content of Popular Sweetened Beverages Based on Objective Laboratory Analysis: Focus on Fructose Content","volume":"19","author":"Ventura","year":"2011","journal-title":"Obesity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/0031-9384(94)90116-3","article-title":"Adaptation of Sweeteners in Water and in Tannic Acid Solutions","volume":"55","author":"Schiffman","year":"1994","journal-title":"Physiol. Behav."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3758\/BF03206254","article-title":"Gustatory Cross Adaptation between Sweet-Tasting Compounds","volume":"11","author":"Mcburney","year":"1972","journal-title":"Percept. Psychophys."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.physbeh.2016.03.030","article-title":"Trends in the Consumption of Low-Calorie Sweeteners","volume":"164","author":"Sylvetsky","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.euroneuro.2023.08.496","article-title":"Sucrose Preference Test: A Systematic Review of Protocols for the Assessment of Anhedonia in Rodents","volume":"77","author":"Primo","year":"2023","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1038\/s41467-023-38028-0","article-title":"A Computational Analysis of Mouse Behavior in the Sucrose Preference Test","volume":"14","author":"Verharen","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8171","DOI":"10.1038\/ncomms9171","article-title":"Breadth of Tuning in Taste Afferent Neurons Varies with Stimulus Strength","volume":"6","author":"Wu","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/chemse\/bjm034","article-title":"Taste Solution Preferences of C57BL\/6J and 129X1\/SvJ Mice: Influence of Age, Sex, and Diet","volume":"32","author":"Tordoff","year":"2007","journal-title":"Chem. Senses"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature13873","article-title":"The Neural Representation of Taste Quality at the Periphery","volume":"517","author":"Barretto","year":"2015","journal-title":"Nature"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/19\/3075\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:45:40Z","timestamp":1759146340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/19\/3075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,27]]},"references-count":46,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["nu17193075"],"URL":"https:\/\/doi.org\/10.3390\/nu17193075","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,27]]}}}