The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Sucrose activates human taste pathways differently from artificial sweetener
Abstract
Animal models suggest that sucrose activates taste afferents differently than non-caloric sweeteners. Little information exists how artificial sweeteners engage central taste pathways in the human brain. We assessed sucrose and sucralose taste pleasantness across a concentration gradient in 12 healthy control women and applied 10% sucrose and matched sucralose during functional magnet resonance imaging. The results indicate that (1) both sucrose and sucralose activate functionally connected primary taste pathways; (2) taste pleasantness predicts left insula response; (3) sucrose elicits a stronger brain response in the anterior insula, frontal operculum, striatum and anterior cingulate, compared to sucralose; (4) only sucrose, but not sucralose, stimulation engages dopaminergic midbrain areas in relation to the behavioral pleasantness response. Thus, brain response distinguishes the caloric from the non-caloric sweetener, although the conscious mind could not. This could have important implications on how effective artificial sweeteners are in their ability to substitute sugar intake.
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In the citing paper
“Human imaging studies have shown that tasting palatable foods activated the insula and midbrain areas (143,144).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [144]
In the citing paper
“For example, when normal-weight women tasted a sweetener with calories (sucrose), both the insula and dopaminergic midbrain areas became activated, whereas tasting a calorie-free sweetener (sucralose) only activated the insula (144).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [144]
In the citing paper
“For example, when normal weight women tasted a sweetener with calories (sucrose), both the insula and DA midbrain areas became activated, whereas tasting a calorie-free sweetener (sucralose) only activated the insula (103).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [103]
In the citing paper
“Indeed, in humans, tasting palatable foods activated the insula and midbrain areas (102,103).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [103]
In the citing paper
“Human imaging studies have shown that tasting palatable foods activated the insula and midbrain areas (DelParigi et al 2005;Frank et al 2008).”
From Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction (2011) · cites this paper as Frank et al 2008
In the citing paper
“However, the DA signaling may also be necessary for sensing the calorie content of food.For example, when normal weight women tasted a sweetener with calories (sucrose), both the insula and dopaminergic midbrain areas became activated, whereas tasting a calorie-free sweetener (sucralose) only activated the insula (Frank et al 2008).”
From Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction (2011) · cites this paper as Frank et al 2008
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Type of sweet flavour carrier affects thyroid axis activity in male rats
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“Results in animal models suggest that certain NCSs can promote the release of GLP-1 or gastroinhibitory peptide, which modify intestinal movement.(43,44) In vivo and in vitro studies(44,45) have shown that sucralose, aspartame, and acesulfame-K cause enteroendocrine cell stimulation, increasing the release of GLP-1, C…”
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Multiple Dimensions of Sweet Taste Perception Altered after Sleep Curtailment
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“Sucralose runs used a sucralose solution individually matched to sweet taste perception of the sucrose solution (detailed description see Frank et al., 2008; Oberndorfer et al., 2013).”
MethodSelf-citationThe Neural Correlates of Cued Reward Omission
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“Previous neurobiological studies have found that sucralose, an artificial sweetener often used in diet soda, stimulates the same taste reward circuitry as sucrose but at a lower magnitude (Frank et al., 2008).”
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“Recently, the presence of calories in the mouth has also been associated with activation in several brain regions including the amygdala, striatum, ACC and insula and overlying frontal operculum (Chambers et al. 2009; Frank et al. 2008; Griffioen-Roose et al. 2013; Smeets et al. 2011; van Rijn et al. 2015; van Rijn et…”
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Effects of carbohydrate mouth rinse and caffeine on high-intensity interval running in a fed state
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“While we did find that the vegetables sweetened with NNS were sweeter than those sweetened with sucrose, the effect was not as robust as previous studies (Frank et al. 2008; Fitch and Keim 2012) would suggest: the vegetables sweetened with NNS were on average 1.”
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“…neural activity in different brain regions, and that caloric compounds tend to more strongly activate classic dopaminergic midbrain areas, relative to artificial sweeteners (Chambers, Bridge, & Jones, 2009; Frank et al., 2008; Smeets, Weijzen, de Graaf, & Viergever, 2011; Tellez et al., 2016).”
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“A functional magnetic resonance imaging (fMRI) investigation confirmed that rinsing a CHO solution as well as an artificial sweetened placebo solution activated the various taste pathways such as frontal operculum/anterior insula, with higher activation to the region of dopaminergic neurons within the brain (Frank et…”
BackgroundRelative Sweetness and Sweetness Quality of Low Calorie Sweeteners in Milk and Coffee Model System
Choi, J.-H., Kim, K.-P., & Chung, S. (2013) · Korean Journal of Food Science and Technology · doi:10.9721/kjfst.2013.45.6.754 · Cited by 9
“다른 감미료에 비해 단맛발현 시간이 빠른 것 이 이 소재의 장점 중 하나이다(6).”
Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity
van Rijn, I., Griffioen-Roose, S., de Graaf, C., & Smeets, P. A. M. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00371 · Cited by 9
“Many fMRI papers with a tasting-paradigm have used a comparable sample size and have shown significant results, for example: Bender et al. (2009) ( n = 19), Frank et al. (2008) ( n =”
From Sweetness to Mouthfeel: A Review on Overcoming Sensory Barriers in Sugar‐Free Beverages
Ramsey, I., Liu, J., Swiegers, J. H., & Oladokun, O. (2025) · International Journal of Food Science · doi:10.1155/ijfo/2345722 · Cited by 9
Artificial Sweeteners Consumption among Alexandria University Students, Egypt
Tayel, D. I., Khamis, N., & Darwish, O. A. (2017) · Journal of High Institute of Public Health · doi:10.21608/jhiph.2017.19971 · Cited by 8
“(5,25) There may be an association between acute oral exposure to a non-energy containing palatable stimulus and augmented appetite.”
BackgroundKeesing, C., Mills, B., Rapsey, C. M., Haszard, J. J., & Venn, B. J. (2019) · Nutrients · doi:10.3390/nu11112647 · Cited by 8
“Sucralose has been found to activate taste pathways in the brain differently from sucrose [32].”
BackgroundSensory disruption and sensory inequities in the Anthropocene
Hoover, K. C. (2021) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.21882 · Cited by 9
Machen, B., Miller, S. N., Xin, A. W., Lampert, C., Assaf, L., Tucker, J., Herrell, S., Pereira, F., Loewinger, G. C., & Beas, B. S. (2025) · iScience · doi:10.1016/j.isci.2025.114390 · Cited by 11
“42 However, despite their wide use, relatively little is known about the effects of non-caloric sweeteners in the brain.”
Le goût sucré, de l’enfance… à la dépendance ?
Nicklaus, S., & Divert, C. (2013) · Cahiers de Nutrition et de Diététique · doi:10.1016/j.cnd.2013.06.002 · Cited by 7
“[4] Frank GK, Oberndorfer TA, Simmons AN, Paulus MP, Fudge”
BackgroundInfluentialBrown, D., Cappozzo, F., Roeck, D. D., Zariwala, M. G., & Deb, S. K. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.678105 · Cited by 7
“, glucose or maltodextrin) in the buccal cavity, for example, are reported to activate the central reward systems of the brain, such as the anterior cingulate cortex and ventral striatum, that are believed to mediate positive emotional, cognitive and behavioural responses to this stimuli (35, 36).”
BackgroundHogenkamp, P. S. (2017) · Wiley eBooks · doi:10.1002/9781119044970.ch4 · Cited by 7
How Attention Changes in Response to Carbohydrate Mouth Rinsing
Hosang, T. J., Laborde, S., Löw, A., Sprengel, M., Baum, N., & Jacobsen, T. (2023) · Nutrients · doi:10.3390/nu15133053 · Cited by 6
“In our recent study [15], we used the EEG-ERP method to investigate whether CHO mouth rinsing affects mental processing through reward circuits [7,8,21].”
BackgroundMethodLong, T., Milbourn, C. C., Smith, A., Khin, K. L. S., Page, A. J., IDRIS, I. R., Yang, Q., Young, R. L., & Eldeghaidy, S. (2025) · Life · doi:10.3390/life15071075 · Cited by 6
von Atzingen, G. V., Arteaga, H., da Silva, A. R., Ortega, N. F., Costa, E. J. X., & Silva, A. C. D. S. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.901333 · Cited by 8
“(5) observed that only sucrose, but not sucralose, stimulation engages dopaminergic”
BackgroundResultInfluentialEtxebarria, N., Clark, B., ROSS, M. L. R., Hui, T., Goecke, R., Rattray, B., & Burke, L. M. (2020) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2020-0265 · Cited by 6
Low-Calorie Sweeteners and Reproductive Health: Evidence and Debates
Atalay, E. Ç., Demirhan, B. E., & Celep, G. S. (2024) · Current Nutrition & Food Science · doi:10.2174/0115734013315621240802055207 · Cited by 8
Artificial Sweetened Beverages and Pediatric Obesity: The Controversy Continues
Freswick, P. (2014) · Children · doi:10.3390/children1010031 · Cited by 5
Delogu, F., Huddas, C., Steven, K., Hachem, S., Lodhia, L., Fernandez, R., & Logerstedt, M. (2016) · Frontiers in Psychology · doi:10.3389/fpsyg.2016.00036 · Cited by 6
“Such preference is likely to be associated with striatal dopamine release and the consequent rewarding effect after consuming sugar, which are absent in noncaloric sweeteners (Frank et al., 2008; Ren et al., 2010; Smeets et al., 2011).”
BackgroundYılmaz, H. Ö., Meriç, Ç. S., & Ayhan, N. Y. (2023) · Applied Neuropsychology Adult · doi:10.1080/23279095.2023.2232911 · Cited by 5
“This deduction is in line with recent neuroimaging data, which suggests that caloric and noncaloric sweeteners could activate different brain regions, despite having equal sweetness (Frank et al., 2008; Smeets et al., 2011).”
Carbohydrate Oral Rinsing, Cycling Performance and Individual Complex Carbohydrate Taste Sensitivity
Hartley, C., Carr, A. J., Roberts, S., Bredie, W. L. P., & Keast, R. (2024) · Nutrients · doi:10.3390/nu16030459 · Cited by 5
In Search of a Role for Carbonation: Is This a Good or Bad Taste?
Sternini, C. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.07.018 · Cited by 5
“5% per patient-year)(2,3) than those with high-grade dysplasia (6%–19% per patient-year).(4) However, given the uncertainty of predisposing risk factors in progression to EAC, most current medical society guidelines recommend surveillance endoscopy in all patients diagnosed with Barrett’s esophagus.”
BackgroundCaloric labels do not influence taste pleasantness and neural responses to erythritol and sucrose
Budzinska, A., Byl, L., Teysseire, F., Flad, E., Dupont, P. J., Wölnerhanssen, B. K., Meyer‐Gerspach, A. C., Oudenhove, L. V., & Weltens, N. (2025) · NeuroImage · doi:10.1016/j.neuroimage.2025.121061 · Cited by 4
Ko, H.-K., Shi, J., Eidenberger, T., Shi, W., & McCabe, C. (2025) · NeuroImage · doi:10.1016/j.neuroimage.2025.121552 · Cited by 4
Sucralose uses reward pathways to promote acute caloric intake
Wang, Q., Li, A., Wang, B., Zhao, X., Li, S., Herzog, H., & Neely, G. G. (2025) · Neuropeptides · doi:10.1016/j.npep.2025.102502 · Cited by 4
The Cerebral Cortex and Complex Cerebral Functions
ten Donkelaar, H. J., Catani, M., van Domburg, P., Eling, P., Küsters, B., & Hori, A. (2020) · Springer eBooks · doi:10.1007/978-3-030-41878-6_15 · Cited by 4
Ampel, B. C., O'Malley, E. E., & Muraven, M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801850-7.00007-x · Cited by 5
Zheng, Y., Gao, H., Wang, H., Zhu, B., Shi, B., Zhong, K., Sun, P., Zhang, L., & Zhao, L. (2021) · Journal of Sensory Studies · doi:10.1111/joss.12699 · Cited by 4
Taim, B. C., Suppiah, H. T., Wee, J., Lee, M., LEE, J. K. W., & Chia, M. (2021) · Nutrients · doi:10.3390/nu13124197 · Cited by 4
Multisensory Sweetness Enhancement: Comparing Olfaction and Vision
Spence, C. J. (2024) · Springer eBooks · doi:10.1007/978-3-031-41375-9_2 · Cited by 4
Nummenmaa, L., & van Dillen, L. F. (2021) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2021.02.026 · Cited by 6
Ingesting a Bitter Solution: The Sweet Touch to Increasing Short-Term Cycling Performance
Etxebarria, N., ROSS, M. L. R., Clark, B., & Burke, L. M. (2018) · International Journal of Sports Physiology and Performance · doi:10.1123/ijspp.2018-0554 · Cited by 4
Interoception in Eating Disorders
Choquette, E. M., & Khalsa, S. S. (2025) · Oxford University Press eBooks · doi:10.1093/9780197675212.003.0009 · Cited by 4
Ko, H.-K., Shi, J., Eidenberger, T., Shi, W., & McCabe, C. (2025) · Nutritional Neuroscience · doi:10.1080/1028415x.2025.2508772 · Cited by 4
“Further we examined the caudate as this was a striatal region found previously different between sucrose and sucralose [16] however with an anatomical ROI for the caudate we found no Department of Physiology, Anatomy and Genetics, linking neuronal responses to visual perception and decision-making…”
InfluentialHighly Palatable Foods Are Addictive
Wilcox, C. E., & Farrar, D. C. (2021) · Springer eBooks · doi:10.1007/978-3-030-83078-6_11 · Cited by 4
Metadata
- Authors
- Frank, G. K. W., Oberndorfer, T. A., Simmons, A. N., Paulus, M. P., Fudge, J. L., Yang, T. T., & Kaye, W. H.
- Affiliations
- Children's Hospital Colorado (US)
- University of California San Diego (US)
- University of Rochester Medicine (US)
- University of Pittsburgh (US)
- Corresponding author
- Kaye, Walter H.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 39
- Issue
- 4
- Pages
- 1559-1569
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2083215956
- Cited by
- 274
- References
- 59
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 10 · 2023: 10 · 2022: 15 · 2021: 23 · 2020: 20 · 2019: 15 · 2018: 20 · 2017: 23 · 2016: 20 · 2015: 10 · 2014: 20 · 2013: 22 · 2012: 7
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000005)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- sucrose, sucralose, artificial sweeteners, taste pleasantness, anterior insula, frontal operculum, striatum, anterior cingulate cortex, dopaminergic midbrain, functional connectivity, sugar substitution
- MeSH terms
- Adult, Afferent Pathways, Brain, Cerebral Cortex, Dopamine, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Reward, Sucrose, Sweetening Agents, Taste, Taste Buds
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