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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Self-citationThe macronutrients, appetite, and energy intake
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“…2011; Rudenga and Small 2012; Oberndorfer et al. 2013; Rudenga and Small 2013; Gagnon et al. 2015) " (Francis et al. 1999; Chambers et al. 2009) NA " (Frank et al. 2008; Oberndorfer et al. 2013) " (Chambers et al. 2009; Green and Murphy 2012) " (Faurion et al. 1999) (CerfDucastel et al. 2001) !”
BackgroundInfluentialInvolvement of Endogenous Enkephalins and β-Endorphin in Feeding and Diet-Induced Obesity
Mendez, I. A., Ostlund, S. B., Maidment, N. T., & Murphy, N. P. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.67 · Cited by 55
Stamataki, N. S., Crooks, B. J., Ahmed, A., & McLaughlin, J. T. (2020) · Nutrients · doi:10.3390/nu12103049 · Cited by 57
“However, during NNS tasting the reward centres remained unresponsive [51,52].”
BackgroundBMI Modulates Calorie-Dependent Dopamine Changes in Accumbens from Glucose Intake
Wang, G., Tomasi, D. G., Convit, A. J., Logan, J., Wong, C., Shumay, E., Fowler, J. S., & Volkow, N. D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101585 · Cited by 55
“Moreover in humans neuroimaging studies have shown that sucrose solution but not a non-caloric sweet solution activates the midbrain, which is where DA neurons are located [7].”
BackgroundSchiano, C., Grimaldi, V., Scognamiglio, M., Costa, D., Soricelli, A., Nicoletti, G. F., & Claudio Napoli, A. (2021) · Food Research International · doi:10.1016/j.foodres.2021.110220 · Cited by 60
Le, T. M., Liao, D., Ide, J. S., Zhang, S., Zhornitsky, S., Wang, W., & Li, C.-S. R. (2019) · International Journal of Obesity · doi:10.1038/s41366-019-0496-8 · Cited by 47
Griffioen-Roose, S., Smeets, P. A. M., Weijzen, P. L. G., van Rijn, I., van den Bosch, I., & de Graaf, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081924 · Cited by 47
“Several fMRI studies have shown that the brain can differentiate between sugar and sweeteners in several reward areas [9,10].”
BackgroundMethodJeukendrup, A. E. (2013) · Current Sports Medicine Reports · doi:10.1249/jsr.0b013e31829a6caa · Cited by 45
“The fact that many of these higher brain regions have been reported to be activated by oral carbohydrates and not nonnutritive sweeteners (12,20,22) may provide a mechanistic explanation for the positive effects of a carbohydrate mouth rinse on exercise performance.”
BackgroundHunger and BMI modulate neural responses to sweet stimuli: fMRI meta-analysis
Chen, E. Y., & Zeffiro, T. A. (2020) · International Journal of Obesity · doi:10.1038/s41366-020-0608-5 · Cited by 48
Yunker, A. G., Alves, J. M., LUO, S. H., ANGELO, B. C., DEFENDIS, A. W., Pickering, T. A., Monterosso, J. R., & Page, K. A. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.26313 · Cited by 46
Roberts, C. A., Giesbrecht, T., Fallon, N., Thomas, A. C., Mela, D., & Kirkham, T. (2020) · Journal of NutriLife · doi:10.1093/jn/nxaa071 · Cited by 42
“0202 1336 Frontal operculum R 4 (16, 30, 31, 44) 26.”
BackgroundEl-Terras, A. A., Soliman, M. M., Alkhedaide, A. Q., ATTIA, H. F., Alharthy, A., & Banaja, A. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.4903 · Cited by 44
Ispoglou, T., O'Kelly, D., Angelopoulou, A., Bargh, M. J., O'Hara, J. P., & Duckworth, L. C. (2015) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000000882 · Cited by 43
“Indeed, this seems to be the case because more brain regions are activated in response to sucrose when consumed after fasting (19), and these are the regions reported to be responsible for the central effect in response to CHO in the mouth (11,15,19).”
BackgroundNon-nutritive sweeteners and their impacts on the gut microbiome and host physiology
Richardson, I., & Frese, S. A. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.988144 · Cited by 49
Murray, S. M., Tulloch, A. J., Criscitelli, K., & Avena, N. M. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.04.004 · Cited by 47
“Research does show that the human brain is capable of dissociating sweet taste from calories [56, 57].”
Effect of Carbonation on Brain Processing of Sweet Stimuli in Humans
Salle, F. D., Cantone, E., Savarese, M. F., Aragri, A., Prinster, A., Nicolai, E., Sarnelli, G., Iengo, M., Buyckx, M. E., & Cuomo, R. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.05.041 · Cited by 41
Differences in brain responses between lean and obese women to a sweetened drink
Connolly, L., Coveleskie, K., Kilpatrick, L. A., Labus, J. S., Ebrat, B., Stains, J., Jiang, Z., Tillisch, K., Raybould, H. E., & Mayer, E. A. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12125 · Cited by 38
Yunker, A. G., Patel, R., & Page, K. A. (2020) · Current Nutrition Reports · doi:10.1007/s13668-020-00323-3 · Cited by 38
Risdon, S., Battault, S., Romo-Romo, A., Roustit, M., Briand, L. V., Meyer, G., Almeda‐Valdés, P., & Walther, G. (2021) · Advances in Nutrition · doi:10.1093/advances/nmaa185 · Cited by 41
“Consistent with this, clinical brain imaging data also indicate that sucrose and sucralose both activate taste-reward circuits, but responses to sucrose appear to be greater in intensity and involve additional brain areas related to pleasure (67).”
ResultShum, B. J., & Georgia, S. K. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.625415 · Cited by 40
Tasting calories differentially affects brain activation during hunger and satiety
van Rijn, I., de Graaf, C., & Smeets, P. A. M. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.11.019 · Cited by 37
CARBOHYDRATE MOUTH RINSE: PERFORMANCE EFFECTS AND MECHANISMS
Jeukendrup, A. E., Rollo, I., & Carter, J. M. (2013) · Cited by 35
Crézé, C., Candal, L., Cros, J., Knebel, J., Seyssel, K., Stefanoni, N., Schneiter, P., Murray, M. M., Tappy, L., & Toepel, U. (2018) · Nutrients · doi:10.3390/nu10050615 · Cited by 38
“Furthermore, other studies have found increased insular activity subsequent to PYY infusion mimicking satiety [45], to mouth rinsing with a glucose drink mimicking food intake anticipation [46], but also in response to calorie ingestion as such [20,47].”
BackgroundHartley, C., Carr, A., Bowe, S. J., Bredie, W. L. P., & Keast, R. S. J. (2022) · Sports Medicine · doi:10.1007/s40279-022-01658-3 · Cited by 34
“Furthermore, these regions have been found to be activated by oral exposure to carbohydrates but not by non-nutritive sweeteners [19, 26, 27], which may assist in explaining the positive effects of carbohydrate rinsing on exercise performance.”
BackgroundAguayo-Guerrero, J. A., Méndez-García, L. A., Solleiro-Villavicencio, H., Viurcos-Sanabria, R., & Escobedo, G. (2024) · Life · doi:10.3390/life14030323 · Cited by 34
“For example, Temizkan et al. reported contradictory effects in healthy subjects and patients with newly diagnosed T2DM, suggesting that measuring the acute effect of sucralose may not reflect its long-term outcomes [51].”
BackgroundEny, K. M., Corey, P., & El‐Sohemy, A. (2009) · Lifestyle Genomics · doi:10.1159/000276991 · Cited by 34
“Sugars such as sucrose given orally and glucose infused intravenously stimulate dopaminergic regions of the brain [”
BackgroundNoncaloric Sweeteners in Children: A Controversial Theme
Durán‐Agüero, S., Angarita, L., Contreras, M. C. E., Rojas-Gómez, D. M., & Costa, J. D. A. (2018) · BioMed Research International · doi:10.1155/2018/4806534 · Cited by 34
“The consumption of sugary beverages shows a positive effect on adiposity [39].”
BackgroundTzieropoulos, H., Rytz, A., Hudry, J., & le Coutre, J. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00036 · Cited by 34
“Another study (Frank et al., 2008) similarly showed that sucrose elicited higher responses in anterior insula, frontal operculum, striatum, and ACC than sucralose and also that only sucrose activated dopaminergic midbrain areas (VTA, substrantia nigra).”
ResultThe Influence of Adding Spices to Reduced Sugar Foods on Overall Liking
Peters, J. C., Marker, R. J., Pan, Z., Breen, J. A., & Hill, J. O. (2018) · Journal of Food Science · doi:10.1111/1750-3841.14069 · Cited by 32
“In addition, some consumers do not like the taste profile of these compounds when used in foods and beverages (Frank et al., 2008; Kamerud & Delwiche, 2007).”
BackgroundDe novo artistic activity following insular–SII ischemia
Thomas-Antérion, C., Créac’h, C., Dionet, E., Borg, C., Extier, C., Faillenot, I., & Peyron, R. (2010) · Pain · doi:10.1016/j.pain.2010.04.010 · Cited by 32
“It is remarkable that the insular cortex is involved in multiple processes including pleasantness/unpleasantness [6,21] and emotions [11], but also, interestingly, in discrimination for warm, heat, cold and painful stimuli [4,7,20,23].”
BackgroundThe “sweet” effect: Comparative assessments of dietary sugars on cognitive performance
Ginieis, R., Franz, E. A., Oey, I., & Peng, M. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.12.010 · Cited by 31
“This deduction is in line with recent neuroimaging data, which suggest that caloric and noncaloric sweeteners could activate different brain regions, despite having equip-sweetness [30,31].”
Why can't we control our food intake? The downside of dietary variety on learned satiety responses
Martin, A. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.04.010 · Cited by 30
Enhancing sweetness using double emulsion technology to reduce sugar content in food formulations
Buyukkestelli, H. I., & El, S. N. (2021) · Innovative Food Science & Emerging Technologies · doi:10.1016/j.ifset.2021.102809 · Cited by 29
Casperson, S. L., Johnson, L. K., & Roemmich, J. N. (2017) · Appetite · doi:10.1016/j.appet.2017.01.028 · Cited by 28
“Researchers using fMRI have shown that even though sugar stimulates more regions in the brain related to food reward compared to NNS (sucralose); the connectivity within the food reward pathways is stronger with NNS consumption (Frank et al., 2008).”
An Exploration of the Role of Sugar-Sweetened Beverage in Promoting Obesity and Health Disparities
Sigala, D. M., & Stanhope, K. L. (2021) · Current Obesity Reports · doi:10.1007/s13679-020-00421-x · Cited by 28
Forbush, K. T., & Hunt, T. K. (2014) · Physiology and Behavior · doi:10.1016/j.physbeh.2014.02.045 · Cited by 26
“Notably, artificial sweetener and diet soda intake stimulates the taste reward circuitry, but at lower magnitudes than sucrose [33], such that individuals with eating disordersmay need to consume higher amounts of artificial sweeteners to satisfy their desire for sweet tastes.”
BackgroundChakravartti, S. P., Jann, K., Veit, R., Liu, H., Yunker, A. G., ANGELO, B. C., Monterosso, J. R., Xiang, A. H., Kullmann, S., & Page, K. A. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01227-8 · Cited by 26
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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